US Quantification of Liver Fat: Past, Present, and Future

David T Fetzer, Theodore T Pierce, Michelle L Robbin, Guy Cloutier, Arjmand Mufti, Timothy J Hall, Anil Chauhan, Reinhard Kubale, An Tang

Radiographics. 2023 Jul;43(7):e220178. doi: 10.1148/rg.220178

Hepatic steatosis is a growing public health problem with crescent clinical impact and associated medical costs and Non-alcoholic fatty liver disease (NAFLD) is now the most common cause of chronic hepatopathy worldwide. [1]

This article focuses on the urgent need to find a method capable of detecting and quantifying liver fat that is reliable, reproducible, non-invasive and accessible to the general population.

US is a widely availability and non-invasive method and manufactures have been working in the devolvement of quantitative software to overcome the subjective evaluation of hepatic steatosis using the classical B-mode. This classic approach is not sensitive enough, especially when liver fat content is less than 20% and in patients with obesity or renal disease. [2,3]

The authors begin by praising the role of MRI proton-density fat fraction as the most accurate non-invasive biomarker of hepatic steatosis. However, MRI is not widely available for screening and surveillance of the general population, which becomes quite limiting taking into account the dimension and prevalence of this pathology. [4]

The article focuses especially on methods that use ultrasound to evaluate hepatic steatosis, emphasizing the limitations and advantages of each technique.

A non-image-guided technique, the Controlled Attenuation Parameter (CAP), is only available in vibration-controlled transient elastography (VCTE) devices and it is widely available. Nevertheless, it is a non-image-guided method and therefore does not allow avoiding masses, vessels and other possible artefacts. Furthermore, it is not a reliable method in the presence of ascites, obesity and in the presence of steatohepatitis and fibrosis.

The qualitative assessment of steatosis by ultrasound has been carried out since 1970 and is based on the assessment of the echogenicity of the liver and the comparison with the echogenicity of the right kidney and pancreas as well as the conspicuity of the portal vessels, gallbladder walls and diaphragm-lung interface. However, this method is subjective and does not allow the severity of the stenosis to be quantified, making it difficult to follow these patients over time.

The hepatorenal index is a semiquantitative method that is calculated by dividing the ROI of the liver parenchyma and the right renal cortex. This method is reproducible and intuitive; nevertheless, it is operator-dependent and there are no established cut-offs. Furthermore, it demands the presence of a normal kidney.

The attenuation coefficient, backscatter coefficient and speed of sound are other recently introduced methods that allow a quantitative assessment of steatosis.

The attenuation coefficient is a relatively intuitive and reproducible method that quantifies the acoustic energy that is lost when crossing the liver parenchyma. [5]

In turn, backscatter coefficient measures ultrasound echoes generated by reflection and scattering, which determine the brightness in the image generated in B-Mode.

Finally, Speed of Sound is influenced by the stiffness and the density of the liver and is inversely correlated with steatosis.

These three methods can be confounded by several factors such as near-field reverberation artefacts, liver heterogeneity or fibrosis.

More recently, a promising technique has emerged - modeling phantom-corrected attenuation and backscatter—which combines the attenuation coefficient and the backscatter coefficient, thus reducing possible sources of variability. This technique has demonstrated a linear correlation with MRI-PDFF. The need for a large ROI (3 cm) might be a limitation of this method, as these measurements may be affected by the presence of liver masses and the non-homogeneous distribution of steatosis. [6]

At the end of the paper, the authors give us a glimpse of what the future holds in this matter, highlighting evolving techniques such as radiofrequency envelope analysis and artificial intelligence–based techniques. They also highlight the role of multiparametric modeling that takes into account the various conditions that can affect the liver, like inflammation and fibrosis, improving the diagnostic performance in this setting.

References:

[1] Giovanna Ferraioli and Livia Beatriz Soares Monteiro. Ultrasound-based techniques for the diagnosis of liver steatosis. World J Gastroenterol. 2019 Oct 28; 25(40):6053-6062. DOI: 10.3748/wjg.v25.i40.6053
[2] Yu-Tian Cao, Liu-Lan Xiang, Fang Qi, Yu-Juan Zhang, et al. Accuracy of controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) for assessing steatosis and fibrosis in non-alcoholic fatty liver disease: A systematic review and meta-analysis. EClinicalMedicine. 2022 Jul 10;51:101547. DOI: 10.1016/j.eclinm.2022.101547
[3] Laurent Castera, Mireen Friedrich-Rust, Rohit Loomba. Noninvasive Assessment of Liver Disease in Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology. 2019 Apr;156(5):1264-1281.e4. DOI: 10.1053/j.gastro.2018.12.036
[4] Jiulian Gu, Shousheng Liu et al. Diagnostic value of MRI-PDFF for hepatic steatosis in patients with non-alcoholic fatty liver disease: a meta-analysis. Eur Radiol. 2019 Jul;29(7):3564-3573. DOI: 10.1007/s00330-019-06072-4
[5] Marco Dioguardi Burgio, Maxime Ronot et al. Quantification of hepatic steatosis with ultrasound: promising role of attenuation imaging coefficient in a biopsy-proven cohort. Eur Radiol. 2020 Apr;30(4):2293-2301. DOI: 10.1007/s00330-019-06480-6
[6] Riccardo De Robertis, Flavio Spoto, et al. Ultrasound-derived fat fraction for detection of hepatic steatosis and quantification of liver fat content. Radiol Med. 2023 Aug 12. DOI: 10.1007/s11547-023-01693-8


Dr. Adriana Silva is a second-year radiology resident at the Centro Hospitalar Universitário do Porto, in Portugal. She has a wide range of interests in diagnostic imaging including abdominal and gastrointestinal radiology.

Comments may be sent to adrianamane360@remove-this.gmail.com 


Crohn’s disease phenotype analysis with iodine density from dual‐energy CT enterography

Dane B, Li X, Goldberg JD, O'Donnell T, Le L, Megibow A

Abdom Radiol (NY). 2023;48(7):2219-2227. doi:10.1007/s00261-023-03923-z

This study investigated the correlation between dual-source dual-energy CT enterography (dsDECTE) iodine density and Crohn's disease phenotypes, providing insights into disease progression and severity.

The Society of Abdominal Radiology and American Gastroenterological Association (SAR-AGA) jointly developed recommendations for interpreting CT enterography in small bowel Crohn's disease [1]. These guidelines introduced a morphological framework to describe the inflammation and progression of Crohn's disease [2, 3]. Transmural inflammation often leads to complications like strictures, sinus tracts, fistulas, and abscesses [4, 5]. Consequently, the consensus statement grouped imaging findings into Crohn's disease patterns or phenotypes, reflecting different stages of disease activity and severity:

  • Crohn’s disease with no imaging signs of active inflammation
  • Active inflammatory small bowel Crohn’s disease without luminal narrowing
  • Active inflammatory small bowel Crohn’s disease with luminal narrowing
  • Stricture without active inflammation
  • Stricture with active inflammation
  • Penetrating Crohn’s disease

CT enterography is the recommended modality to assess and monitor Crohn's disease activity [6]. Spectral CT has the unique advantages over conventional CT to achieve material differentiation, shifting the paradigm from qualitative to quantitative imaging. This holds particularly true for iodine density [7], which correlates with inflammation and disease activity better than Hounsfield Units [8]; however, no previous investigations correlated iodine density with Crohn’s disease phenotypes as defined by the SAR-AGA consensus.           

The initial population consisted of 451 patients with “Crohn’s disease” in the radiology report, scanned from May 2017 to December 2021. After excluding patients with no Crohn’s disease diagnosis based on clinical or endoscopic assessment, no endoscopy within 4 months of CT, and no subsequent ds-DECTE, final patient population included 50 patients (31 males, 19 females).

Each patient underwent dsDECTE on a third-generation dual-energy CT scanner, small bowel distention was obtained by administration of 900 mL of neutral oral contrast medium, while a single acquisition was performed after i.v. contrast medium injection based on patient’s weight.

Two readers, blinded to dual-energy CT iodine density, clinical information, and original radiology report, categorized Crohn's disease as follows:

  • Group 1 - stricture without active inflammation (n= 4)
  • Group 2 - no active inflammation (n= 12)
  • Group 3 - active inflammation without luminal narrowing (n= 2)
  • Group 4 - active inflammation with luminal narrowing (n= 13)
  • Group 5 - stricture with active inflammation (n= 9)
  • Group 6 - penetrating disease (n= 10)

Subsequently, small bowel mural iodine density and mural iodine density normalized to the aorta were semiautomatically determined. Mean iodine density was 2.14 ± 1.1 mg/mL for groups “1 or 2”, 3.54 ± 1.7 mg/mL for groups “3 or 4”, and 5.50 ± 3.3 mg/mL for group 5, and 3.36 ± 1.4 mg/mL for group 6. The differences among the groups were statistically significant (P = 0.001), especially for groups “1 or 2” versus group 5. Iodine density normalized to the aorta was 21.2 ± 6.1% for groups 1 or 2, 39.47 ±9.7% for groups 3 or 4, 40.98 ± 11.7% for group 5, and 35.01 ± 7.6% for group 6. Also the differences were statistically significant (P < 0.001), especially when comparing groups “1 or 2” versus the other groups.

Limitations of the study that may affect the generalizability of the results included: the a single center, retrospective nature of the enrollment, the single-vendor, single-generation dual-energy CT scanner use and the lack of accessible endoscopy for some bowel segments.

These findings were consistent with the disease's varying activity levels and progression, demonstrating both iodine density (mg/mL) and normalized iodine density (I%) potential as markers for disease Crohn’s disease characterization and monitoring.

References:

1.     Dane B, Li X, Goldberg JD, et al (2023) Crohn’s disease phenotype analysis with iodine density from dual-energy CT enterography. Abdom Radiol (NY) 48:2219–2227. doi.org/10.1007/s00261-023-03923-z
2.     Pariente B, Cosnes J, Danese S, et al (2011) Development of the Crohn’s disease digestive damage score, the Lémann score. Inflamm Bowel Dis 17:1415–1422. doi.org/10.1002/ibd.21506
3.     Cosnes J, Cattan S, Blain A, et al (2002) Long-term evolution of disease behavior of Crohn’s disease. Inflamm Bowel Dis 8:244–250. doi.org/10.1097/00054725-200207000-00002
4.     Kelly JK, Preshaw RM (1989) Origin of fistulas in Crohn’s disease. J Clin Gastroenterol 11:193–196. doi.org/10.1097/00004836-198904000-00015
5.     Oberhuber G, Stangl PC, Vogelsang H, et al (2000) Significant association of strictures and internal fistula formation in Crohn’s disease. Virchows Arch 437:293–297. doi.org/10.1007/s004280000226
6.     Guglielmo FF, Anupindi SA, Fletcher JG, et al (2020) Small Bowel Crohn Disease at CT and MR Enterography: Imaging Atlas and Glossary of Terms. Radiographics 40:354–375. doi.org/10.1148/rg.2020190091
7.     McCollough CH, Leng S, Yu L, Fletcher JG (2015) Dual- and Multi-Energy CT: Principles, Technical Approaches, and Clinical Applications. Radiology 276:637–653. doi.org/10.1148/radiol.2015142631
8.     Kim H, Goo JM, Kang CK, et al (2018) Comparison of Iodine Density Measurement Among Dual-Energy Computed Tomography Scanners From 3 Vendors. Invest Radiol 53:321–327. doi.org/10.1097/RLI.0000000000000446


Antonella Del Gaudio is a 29-year-old third-year radiology resident at Sant’Andrea University Hospital, Sapienza University of Rome. She graduated in medicine at the University of Naples Federico II in 2020 and has a wide range of interest in diagnostic imaging. Her main research interest is gastrointestinal imaging, with a special focus on the applications of artificial intelligence in CT imaging. She is currently working as a research fellow at the Department of Radiology of Duke University, Durham, NC, USA. She has given scientific presentations at many international radiology meetings and she has contributed as a co-author in some scientific publications.

Comments may sent to Antonella.delgaudio@remove-this.uniroma1.it


A retrospective preliminary study of intrapancreatic late enhancement as a noteworthy imaging finding in the early stages of pancreatic adenocarcinoma

Yoshihiro Konno, Yasuhiro Sugai, Masafumi Kanoto, Keisuke Suzuki, Toshitada Hiraka, Yuki Toyoguchi & Kazuho Niino

European Radiology 33, 5131–5141 (2023). doi.org/10.1007/s00330-022-09388-w

Pancreatic adenocarcinoma (PAC) represents the most common primary pancreatic malignancy (90%) [1]. Accounting for 2% of all cancer cases, it has the lowest 5-year survival rate of all solid cancers (5-9%) and is the fourth-leading cause of cancer-related death in USA and Canada [1,2]. Due to its aggressive behavior, early diagnosis is critical for appropriate management. Imaging has a central role in this regard as early PAC is often challenging to diagnose clinically [2].

CT and MRI are the cornerstones of PAC detection, staging, treatment response assessment and recurrence diagnosis, with CT often being the test of choice due to its reproducibility and availability [1,3]. The primary imaging finding is a hypo-attenuating/intense pancreatic mass on contrast-enhanced studies [4]. However, up to 27% of tumors <2 cm in size can be isoattenuating at CT [4]. Indirect findings (IFs) include main pancreatic duct abnormalities (MPDA) with dilatation (when associated with common bile duct dilatation = “double duct”
sign), contour distortion, focal pancreatic parenchymal atrophy (FPPA), vascular encasement and loss of pancreatic lobulation [3,4]. The most common focal pancreatic abnormalities noted in pre-diagnostic CT (at least 1 year before the diagnosis of PAC) were FPPA, focal faint parenchymal enhancement and focal MPDA [5].

The aim of this retrospective study was to analyze intrapancreatic late enhancement (ILE) in pre-diagnostic CT studies of patients with pathologically confirmed PAC and its potential significance as an early indirect finding in PAC. The final study population enrolled 32 patients (23 men and 9 women, median age 72 years), with pathologically confirmed PAC (surgically or by biopsy). The main inclusion criterion was a contrast-enhanced CT (CECT) study performed 6 months to 5 years prior to the pathological diagnosis of PAC, without a visible focal pancreatic mass. Exclusion criteria included patients with (a) previous pancreatectomy, (b) difficult distinction from inflammatory changes and (c) carcinoma in situ.

Technically, all CECT exams were obtained using a helical CT (64-320 rows) with 1 or 5 mm thick slices, with either monophasic (late phase 120s after contrast injection) or multiphasic (early and late arterial, portal and late phase at 180s after contrast injection) protocols. ILE was defined as a focal enhancement in the pancreatic parenchyma of any size or shape, with subsequent quantitative evaluation in Hounsfield Units (HU) by calculating the ILE-to-pancreas contrast (HU [region of ILE] – HU [pancreatic parenchyma]). Other IFs were also defined in the study, including FPPA and MPDA, as well as cystic lesions. To verify the potential significance of ILE, two independent experienced radiologists, blind to all clinical data, reviewed representative pre-diagnostic CT images and indicated potential sites where PAC would become apparent in the future. The evaluation was done both before and after the two observers received lectures on the significance of ILE as an IF in PAC, with subsequent comparison between the two assessments in terms of lesion detection and interobserver agreement.

The positive group (with present IFs) included 23 cases (72%), without any significant differences in terms of demographics, preexisting conditions or time interval to diagnosis compared to the negative group (without IFs). Incidental PAC (clinically asymptomatic) was significantly more frequent in the positive group with a tendency for more frequent body/tail lesions, while in the negative group tumor size tended to be larger at diagnosis.

In the positive group, ILE was observed in 14 patients (63%) either alone (35%) or in combination with other IFs like FPPA and MPDA (26%), with a higher proportion of pancreatic head lesions in those with ILE alone. Median long-axis diameter of ILE was 10 (IQR 5-11) mm with a median ILE-to-pancreas contrast value of 24 (IQR 17-33) HU. Interobserver agreement and lesion detection improved after ILE awareness.

Limitations of the study acknowledged by the authors include single-center small sample size, possible overestimation of IFs and ILE and unknown extent of false positives, issues that could be clarified in large-scale multicenter studies.

In conclusion, this study emphasizes the role of ILE as an important imaging feature in the early diagnosis of PAC, either as a standalone finding or associated with other IFs. Lesion detection could be improved by including a late phase (at least 120s after injection) in the CECT study and by training radiologists to be familiar with ILE significance.

References:

1. Morani AC, Hanafy AK, Ramani NS et al. Hereditary and Sporadic Pancreatic Ductal Adenocarcinoma: Current Update on Genetics and Imaging. Radiology: Imaging Cancer, 2(2),e190020 (2020). doi:10.1148/rycan.2020190020
2. LeBlanc M, Kang J, Costa AF. Can we rely on contrast-enhanced CT to identify pancreatic ductal adenocarcinoma? A population-based study in sensitivity and factors associated with false negatives. European Radiology (2023). doi:10.1007/s00330-023-09758-y
3. Haj-Mirzaian A, Kawamoto S, Zaheer A et al. Pitfalls in the MDCT of pancreatic cancer: strategies for minimizing errors. Abdominal Radiology 45, 457–478 (2020). doi:10.1007/s00261-019-02390-9
4. Schima W, Adam EJ, Morgan RA. The Pancreas. In: Adam A, Dixon AK, Gillard JH, Schaefer-Prokop CM, eds. Grainger & Allison’s Diagnostic Radiology. 6th ed. Churchill Livingstone – Elsevier Limited; 2015:803-831.
5. Toshima F, Watanabe R, Inoue D et al. CT Abnormalities of the Pancreas Associated With the Subsequent Diagnosis of Clinical Stage I Pancreatic Ductal Adenocarcinoma More Than 1 Year Later: A Case-Control Study. American Journal of Roentgenology 217, 6, 1353-1364 (2021). doi:10.2214/AJR.21.26014


Andrei Mavroian is a fourth-year radiology resident at Cluj-Napoca County Emergency Hospital. He completed his undergraduate medical degree at “Gr. T. Popa” University of Medicine and Pharmacy in 2019. His field of interest includes neuroradiology, cardiovascular imaging and artificial intelligence, with a focus on abdominal imaging.
Comments may be sent to: andrei.mavroian11@remove-this.gmail.com
 


Understanding Reader Variability: A 25-Radiologist Study on Liver Metastasis Detection at CT

Hsieh SS, Cook DA, Inoue A, Gong H, Sudhir Pillai P, Johnson MP, Leng S, Yu L, Fidler JL, Holmes DR 3rd, Carter RE, McCollough CH, Fletcher JG

Radiology 2023 Feb;306(2):e220266. doi: 10.1148/radiol.220266.

Interreader variability in radiology exists even for routine tasks, such as detection of hepatic metastases at CT. Various factors may contribute to this variability, including reader experience, sub-specialization and patterns of image navigation (1, 2). Lesion characteristics might also affect interreader variability, as they are heterogenous in nature (3). Sources of error in lesion detection can generally be categorized as either visual search or cognitive classification error, i.e. the lesion is missed because the eye never fixates it or because it is not reported after eye fixation (4). These errors can be differentiated by measuring gaze time with eye tracking. While interreader variability can undermine patient care by misdiagnosis, only marginal efforts have been made to address these performance differences among radiologists.

In this prospective observational study, the authors aimed to determine the impact of (a) reader experience, (b) image navigation patterns, and (c) eye gaze time on interreader variability of missed liver metastases in contrast-enhanced abdominal CT.

Twenty-five radiologists from a single academic center were recruited to screen 40 abdominal, portal venous CT studies for hepatic metastases. Raters had different experience and training levels, consisting of 9 abdominal subspecialists, 5 non-abdominal subspecialists and 11 trainees. They reviewed each study on a custom viewing workstation with an integrated eye tracker, while data on image navigation was collected (interpretation time, time in liver window and zoomed images, number of scrolls in axial and coronal stack). Gaze time near metastases was calculated, as well as the number of times a reader gazed at the same metastasis in both axial and coronal plane (correlated view). Blinded readers circumscribed the suspected hepatic metastases and scored their confidence from 0 to 100. Confidence scores of 0 indicated a benign lesion and would be disregarded in later analysis. Thirty-two studies contained 91 hepatic metastases proven by histopathology or progression; the other eight had no metastases.

Diagnostic performance was measured by area under the jackknife alternative free-response receiver operating characteristic (JAFROC) curve and per-metastasis sensitivity.

When comparing reader groups, abdominal specialists showed a significantly higher JAFROC performance as they had greater mean confidence in true-positive circumscriptions. However, there was no significant difference in sensitivity or false-positive findings among groups.

With regards to image navigation patterns, there were significant associations between sensitivity and the following six navigation variables: Interpretation time, time in liver windows, time spent gazing at coronal images, coronal scrolls, number of circumscriptions, and correlating views between axial and coronal images. Interestingly however, the number of false-positive findings also increased with these navigation variables, although not significantly. Therefore, navigation variables were not associated with improved JAFROC.

Eye-tracking data showed that of 377 missed metastases, 71%, 40% and 7 % occurred after a gaze time longer than 0.5, 2.0 and 10.0 seconds, respectively. Prior studies suggest that gaze times of less than 0.5 second represent search errors, and gaze times longer than 2 seconds represent classification errors.

The present study is of interest as it demonstrates the impact of various factors on interreader variability, which might affect our everyday performance. Certain image navigation patterns are associated with higher sensitivity. The majority of missed metastases received at least a brief eye gaze, indicating that visual search was not the dominant source of error.

Limitations of this study include the finite accuracy of the eye tracker, the selective investigation of only difficult-to-detect hepatic metastasis and the observational nature of the study. Therefore, the present findings may not be transferable to other tasks in routine clinical practice and may not fully address the problem of interreader variability as a whole.

Nevertheless, the authors offer novel and comprehensive insights in the challenging field of interreader variability, raising its awareness in abdominal imaging. Future work can integrate these findings into a more effective training program for radiologists. Furthermore, AI algorithms could be developed to reduce search errors for subtle lesions and classification errors for unclear liver lesions.

References:

1.         Tsurusaki M, Numoto I, Oda T, et al.Assessment of liver metastases using CT and MRI scans in patients with pancreatic ductal adenocarcinoma: Effects of observer experience on diagnostic accuracy. Cancers. 2020;12(6):1455.
2.         Marin D, Catalano C, De Filippis G, et al.Detection of hepatocellular carcinoma in patients with cirrhosis: added value of coronal reformations from isotropic voxels with 64-MDCT. American Journal of Roentgenology. 2009;192(1):180-7.
3.         Pillai PS, Hsieh S, Holmes III D, et al. Individualized and generalized learner models for predicting missed hepatic metastases. Medical Imaging 2022: Image Perception, Observer Performance, and Technology Assessment, 2022. SPIE.
4.         Brunyé TT, Drew T, Weaver DL, Elmore JG. A review of eye tracking for understanding and improving diagnostic interpretation. Cognitive research: principles and implications. 2019;4:1-16.


Falko Ensle is a fifth-year radiology resident at the University Hospital Zurich. His interests in imaging cover a wide spectrum with a current focus on the musculoskeletal system, where he is also engaged in research projects.
Comments may be sent to: falko.ensle@remove-this.usz.ch


Factors Associated With Complete Pathologic Necrosis of Hepatocellular Carcinoma on Explant Evaluation After Locoregional Therapy: A National Analysis Using the UNOS Database

Sarwar A, Bonder A, Hassan L, Malik MS, Novack V, Curry M, Ahmed M.

AJR Am J Roentgenol. 2023 May;220(5):727-735. doi: 10.2214/AJR.22.28385. Epub 2022 Dec 7. PMID: 36475810.

Hepatocellular carcinoma (HCC) is one of the most common indications for liver transplant (LT) [1]. Complete pathologic necrosis (CPN) obtained by different types of locoregional therapies (LRTs) before LT is associated to a lower 5-year estimated risk of recurrence and better 5-years recurrence-free and disease-specific survival rates [2].

So far, the most widespread LRT is transarterial chemoembolization (TACE) [3-6], followed by thermal ablation and transarterial radioembolization [TARE]. However, the choice of the most appropriate locoregional therapy varies widely among institutions. Notwithstanding the importance of CPN as a significant predictor of recurrence-free survival and overall survival, The American Association for the Study of Liver Diseases guidelines for treating HCC do not recommend a particular type of LRT over another as a bridge to LT [7] due to the paucity of studies reporting an improved survival.

The current study [8] aims to examine the type of LRT associated with higher rates of CPN on explant evaluation, as well as patients characteristics, HCC and transplant-center features associated.

The final study population consisted of 6265 patients (median age, 62 years [IQR, 58–66 years]; 1505 [23.1%] women, 4760 [76.9%] men) who underwent LT after a single type of LRT for HCC measuring 3 cm or smaller.

From The United Network for Organ Sharing (UNOS) database authors obtained information about the necrosis percentage at the explant evaluation, patient’s clinical and laboratory features, HCC’s characteristics like size and several transplant center’s data (e.g. median waiting time for LT).

Out of the 6265 patients included, 4352 (69.5%) performed TACE, 1217 (19.4%) underwent thermal ablation and 696 (11.1%) were treated by TARE. On explant evaluation, CPN for all HCCs was achieved in 23.5% (1475/6265) of patients.

The CPN rate was 18.5% (805/4352) in patients who underwent TACE, 35.8% (436/1217) in patients who underwent thermal ablation, and 33.6% (234/696) in patients who underwent TARE.

Centers (n = 118) were stratified into tertiles according to the CPN rate; the first tertile comprised 40 centers with a CPN rate of 0.0–17.5%; the second tertile comprised 39 centers with a CPN rate of 17.6–27.6%, and the third tertile comprised 39 centers with a CPN rate of 27.7–50.0%. Centers in the second and third tertiles performed higher number of thermal ablation (23.6% and 25.5%, respectively) than centers in the first tertile (14.4%) (p = .02). A higher number of TAREs were performed in the third tertile (14.7%) than centers in the second tertile (12.3%) and first tertile (5.2%) (p = .03). These data showed a higher CPN rate percentage in centers where TAREs and thermal ablations were  performed more frequently than TACEs.

Considering laboratory findings of patients with CPN and without CPN, authors reported α-fetoprotein level (AFP) at the time of LRT lower in CPN group (6.0 ng/mL vs 7.0 ng/mL, p < .001), as well as model for end-stage liver disease (MELD) score at the time of LRT (10.0 vs 11.0, p < .001). Patients with CPN, were also more likely to have a single HCC (79.7% vs 67.6%, p< .001) and a smaller median size of the largest HCC (1.0 cm vs 1.3 cm, p< .001).Despite several limitations of the study, mainly related to the lack of patients’ information (the reason why a particular type of LRT was selected, the position of HCC within the liver, radiologists experience, technical aspects of LRTs, post procedural complications, survival rate after LT), TARE seems to be superior to TACE and equivalent to thermal ablation in terms of CPN rates.

In conclusion, the overall rate of CPN was low among patients who underwent LT after LRT for HCC measuring 3 cm or less in the United States. The use of thermal ablation or TARE, rather than TACE, showed a significant independent association with an increased likelihood of CPN.

References:

  1. Wang S, Toy M, Hang Pham TT, So S. Causes and trends in liver disease and hepatocellular carcinoma among men and women who received liver transplants in the U.S., 2010-2019. PLoS One. 2020 Sep 18;15(9):e0239393.
  2. Agopian VG, Morshedi MM, McWilliams J, et al. Complete pathologic response to pretransplant locoregional therapy for hepatocellular carcinoma defines cancer cure after liver transplantation: analysis of 501 consecutively treated patients. Ann Surg. 2015 Sep;262(3):536-45; discussion 543-5.
  3. DiNorcia J, Florman SS, Haydel B, et al. Pathologic Response to Pretransplant Locoregional Therapy is Predictive of Patient Outcome After Liver Transplantation for Hepatocellular Carcinoma: Analysis From the US Multicenter HCC Transplant Consortium. Ann Surg. 2020 Apr;271(4):616-624.
  4. Welling TH, Eddinger K, Carrier K, et al. Multicenter Study of Staging and Therapeutic Predictors of Hepatocellular Carcinoma Recurrence Following Transplantation. Liver Transpl. 2018 Sep;24(9):1233-1242.
  5. Manzia TM, Lai Q, Iesari S, et al. Impact of remnant vital tissue after locoregional treatment and liver transplant in hepatocellular cancer patients, a multicentre cohort study. Transpl Int. 2018 Mar 23.
  6. Pommergaard HC, Rostved AA, Adam R, et al; European Liver and Intestine Transplant Association (ELITA). Locoregional treatments before liver transplantation for hepatocellular carcinoma: a study from the European Liver Transplant Registry. Transpl Int. 2018 May;31(5):531-539.
  7. Heimbach JK, Kulik LM, Finn RS, et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology 2018; 67:358–380.
  8. Sarwar A, Bonder A, Hassan L, et al. Factors Associated With Complete Pathologic Necrosis of Hepatocellular Carcinoma on Explant Evaluation After Locoregional Therapy: A National Analysis Using the UNOS Database. AJR Am J Roentgenol. 2023 May;220(5):727-735.
  9. Young S, Golzarian J. Locoregional therapies in the treatment of 3- to 5-cm hepatocellular carcinoma: critical review of the literature. AJR 2020; 215:223–234.

 

Dr. Paola Capodiferro is a second-year radiology resident at “Sapienza, University of Rome”. She completed her undergraduate medical degree at “Sapienza, University of Rome” and she is undertaking training in diagnostic and interventional radiology. Her main fields of interests in the area of diagnostic imaging are abdominal, gastrointestinal and urogenital radiology.  

Comments may be sent to paola.capodiferro@uniroma1.it


Assessment of main pancreatic duct cutoff with dilatation, but without visible pancreatic focal lesion on MDCT: a novel diagnostic approach for malignant stricture using a CT-based nomogram

Chae Young Lim 1Ji Hye Min 2Jeong Ah Hwang 1Seo-Youn Choi 3Seong Eun Ko 1

European Radiology 2022 Dec;32(12):8285-8295. doi: 10.1007/s00330-022-08928-8. Epub 2022 Jun 21.

Pancreatic ductal adenocarcinoma (PDAC) typically manifests as a hypoattenuating mass with upstream main pancreatic duct (MPD) dilatation on contrast-enhanced dynamic CT [1]. However, it is not rare in clinical practice to encounter an isoattenuating PDAC, thereby manifesting only as an isolated MPD dilatation [2, 3]. In this situation, indirect secondary signs other than the interrupted duct sign for suspected hidden pancreatic malignancies gained importance [2, 4, 5].

This is a retrospective study focused on emphasizing useful tools to predict the presence of a hidden pancreatic karyogenetic mass in patients who don’t have a visible focal pancreatic lesion on CT, but present main pancreatic duct abrupt cutoff and dilatation.

The sample size comprised 92 patients from a CT database of a single large academic institution. The inclusion criteria were: abrupt cutoff of MPD associated with upstream dilatation, unidentified focal pancreatic lesion, histopathological confirmation or more than 2 years of stability on imaging surveillance. The exclusion criteria were: suboptimal image quality of CT and history of pancreatic surgery.

The following imaging findings were assessed: MPD cutoff site, parenchymal contour abnormality, maximum diameter of the MPD proximal to the duct cutoff site, presence of distal parenchymal atrophy, associated acute pancreatitis on CT and presence of pancreatic cystic lesions.

The clinical findings including new-onset diabetes mellitus (DM) and unintentional weight loss and laboratory findings including the serum level of carbohydrate antigen 19-9, amylase and lipase were also evaluated. After the histopathologic results or clinical follow-up, the sample was divided in two main groups: malignant (41,3%) and benign (58,7%).

Multivariable logistic regression analysis showed that CA19-9 elevation (odds ratio [OR] 7.5, 95% CI 2.0–28.6; p = 0.003), cutoff site at the head/neck (OR 7.6, 95% CI 1.8–32.3; p = 0.006), parenchymal contour abnormality at the duct cutoff site (OR 13.7, 95% CI 3.3–58.0; p < 0.001), and the presence of pancreatitis (OR 11.5, 95% CI 2.1–62.6; p = 0.005) were significant features for predicting the malignant group.

A combination of any two significant features showed an accuracy of 77.2%, and a combination of any three features exhibited a specificity of 100%. For predicting the probability of the malignant group, a CT-based nomogram was constructed based from the four significant features. This nomogram showed an area under the curve (AUC) of 0.84 (95% confidence interval [CI], 0.77–0.90). Therefore, a patient with three CT imaging features and CA19-9 elevation requires further diagnostic tests with aggressive management.

The authors acknowledge some limitations: its retrospective single-center design with a probable selection bias; the results are limited to the population of patients with MPD cutoff sign; histologic confirmation had only been achieved for seven patients in the benign group; the large portion of CT examinations in this study were not optimized for delineation of pancreatic abnormalities because most CT indications were unrelated to screening for PDAC, which might have lowered the sensitivity of each CT imaging feature; not performing an external analysis using an independent validation set to determine the thresholds for the ratios used to construct the nomogram; therefore, there is a need for further studies involving larger numbers of cases.

In conclusion, the authors have shown that a combination of three CT features (parenchymal contour abnormality, head/neck location of the duct cutoff site, and the presence of pancreatitis) and CA19-9 elevation facilitates the estimation of the probability of hidden pancreatic malignancy in patients with MPD abrupt cutoff and dilatations, but without visible pancreatic focal lesions on CT. This nomogram could contribute to a better selection of candidates for immediate further imaging studies using abdomen MRI with MRCP and/or EUS. Also, they have developed a CT-based nomogram that assesses the probability of the presence of pancreatic malignancy with excellent diagnostic performance (AUC of 0.84).

References:

1. Takeshita K, Kutomi K, Haruyama T et al (2010) Imaging of early pancreatic cancer on multidetector row helical computed tomography. Br J Radiol 83:823–830
2. Kim JH, Park SH, Yu ES et al (2010) Visually isoattenuating pancreatic adenocarcinoma at dynamic-enhanced CT: frequency, clinical and pathologic characteristics, and diagnosis at imaging examinations. Radiology 257:87–96
3. Prokesch RW, Chow LC, Beaulieu CF, Bammer R, Jeffrey RB Jr (2002) Isoattenuating pancreatic adenocarcinoma at multi-detector row CT: secondary signs. Radiology 224:764–768
4. Yoon SH, Lee JM, Cho JY et al (2011) Small (</=20 mm) pancreatic adenocarcinomas: analysis of enhancement patterns and secondary signs with multiphasic multidetector CT. Radiology 259: 442–452
5. Edge MD, Hoteit M, Patel AP, Wang X, Baumgarten DA, Cai Q (2007) Clinical significance of main pancreatic duct dilation on computed tomography: single and double duct dilation. World J Gastroenterol 13:1701–1705

Alexandra Hapca is a fifth-year Radiology Resident at County Emergency Clinical Hospital of Cluj-Napoca, Romania. She completed her undergraduate Μedical Doctor degree at "Iuliu Hatieganu" University of Medicine and Pharmacy in Cluj-Napoca. The abdominal and pelvic radiology is one of her main fields of interests in diagnostic imaging.  

Comments may be sent to dr.alexandrahapca@gmail.com


VICT2 Trait: Prognostic Alternative to Peritumoral Hepatobiliary Phase Hypointensity in HCC

Hanyu Jiang, Hong Wei, Ting Yang, Yun Qin, Yuanan Wu, Weixia Chen, Yujun Shi, Maxime Ronot, Mustafa R. Bashir, Bin Song

Radiology. 2023. DOI: 10.1148/radiol.221835

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, it has been recognized as a leading cause of death among patients with cirrhosis, and its incidence is expected to increase in the future [1].

MRI plays a key role in the management of HCC. To improve long-term survival in patients with HCC, in recent years several studies have been performed to detect imaging features with prognostic value.

Prior studies developed and validated preoperative models based on hepatobiliary (HBP) MRI features for predicting microvascular invasion (MVI) [2], which is one of the main histopathological factors associated with recurrence during the first 2 years after curative treatment [3]. Peritumoral hypointensity on HBP has been identified as the MRI feature most suggestive of MVI [4,5]. However, the assessment of peritumoral HBP hypointensity needs hepatobiliary contrast agent MRI, which is associated to some drawbacks, such as suboptimal arterial phase quality, higher cost, and deteriorated imaging quality in patients with conditions like cirrhosis or biliary obstruction.

To overcome these problems, Jiang and colleagues [6] have recently proposed an accurate non-hepatobiliary-specific imaging alternative to peritumoral HBP hypointensity named the “VICT2 trait”, including four non-hepatobiliary-specific MRI features:

  1. Peritumoral portal venous phase (PVP) hypoenhancement;
  2. Incomplete capsule;
  3. Corona enhancement;
  4. Peritumoral mild-moderate T2 hyperintensity.

By the application of the inclusion and exclusion criteria, this study enrolled 660 patients (551 males with a median age of 53 years) who underwent preoperative extracellular or hepatobiliary contrast-enhanced MRI for HCC assessment between December 2011 and November 2021. In this study, the most common etiology of the chronic liver disease was hepatitis B virus in 610 (92%) patients.

The predictive values of this non-hepatobiliary-specific MRI alternative for MVI and postoperative recurrence-free survival (RFS) were compared with peritumoral HBP hypointensity for patients with a solitary tumor with adequate documentation of the MVI status and follow-up information. The authors involved two liver pathologists who evaluated the margin resections by classifying tumors as positive or negative for MVI but they were aware of the clinical and imaging data. 

The preoperative MRI exams were analyzed retrospectively by two blinded abdominal radiologists which considered the “VICT2 trait” for each patient as positive when peritumoral PVP hypoenhancement was present or if all three other features were present or negative if these features are absent.

Univariate and multivariate logistic regression analysis was employed to determine the association between ECA/EOB features and MVI, and postoperative RFS was estimated by using the Kaplan-Meier curves.

Results demonstrate that both peritumoral HBP hypointensity (OR for MVI = 2.5, P = .02; hazard ratio for RFS = 2.5, P < .001) and the VICT2 trait (OR for MVI = 5.1, P < .001; hazard ratio for RFS = 2.3, P < .001) were significantly correlated to MVI and RFS. These values of the VICT2 trait were confirmed in the extracellular contrast agent group (OR for MVI = 4.0; hazard ratio for RFS = 1.7; both P < .001). Particularly, in the gadoxetate disodium-MRI group, the “VICT2 trait” showed a stronger association with MVI compared to peritumoral hypointensity on HBP. The study clinical impact suggests that “VICT2 trait”, identifying a high-risk area for MVI, could improve the preoperative management of patients with hepatocellular carcinoma for the selection of appropriate medical and/or surgical therapy.

However, the authors acknowledge a few limitations, especially the following:

  • high prevalence of chronic hepatitis B virus infection (92%) in the study cohort;
  • selection bias due to retrospective study design;
  • use of subjective features with suboptimal interobserver agreement;
  • not-blinded assessment of MVI status and uncertain correlations between those imaging and pathologic features.

The “VICT2 trait” could be considered a simple and non-invasive imaging tool useful to identify microvascular invasion and predict postoperative recurrence in patient with HCC treated with curative intent resection with the aim to improve their management by customizing the therapeutic modalities for each patient. These results should be confirmed in multi-center studies with patients without hepatitis B virus who undergo both extracellular and hepatobiliary MRI.

References:

1. Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet. 2018 Mar 31;391(10127):1301-1314. doi: 10.1016/S0140-6736(18)30010-2.
2. Zhang S, Huo L, Zhang J, Feng Y, Liu Y, Wu Y, Jia N, Liu W. A preoperative model based on gadobenate-enhanced MRI for predicting microvascular invasion in hepatocellular carcinomas (≤ 5 cm). Front Oncol. 2022;12:992301. doi: 10.3389/fonc.2022.992301.
3. Baleato-González S, Vilanova JC, Luna A, Menéndez de Llano R, Laguna-Reyes JP, Machado-Pereira DM, Bermúdez-Naveira A, Osorio-Vázquez I, Alcalá-Mata L, García-Figueiras R. Current and Advanced Applications of Gadoxetic Acid-enhanced MRI in Hepatobiliary Disorders. Radiographics. 2023;43:e220087. doi: 10.1148/rg.220087.
4. Hong SB, Choi SH, Kim SY, Shim JH, Lee SS, Byun JH, Park SH, Kim KW, Kim S, Lee NK. MRI Features for Predicting Microvascular Invasion of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis. Liver Cancer. 2021;10:94-106. doi: 10.1159/000513704.
5. Erstad DJ, Tanabe KK. Prognostic and Therapeutic Implications of Microvascular Invasion in Hepatocellular Carcinoma. Ann Surg Oncol. 2019;26:1474-1493. doi: 10.1245/s10434-019-07227-9.
6. Jiang H, Wei H, Yang T, Qin Y, Wu Y, Chen W, Shi Y, Ronot M, Bashir MR, Song B. VICT2 Trait: Prognostic Alternative to Peritumoral Hepatobiliary Phase Hypointensity in HCC. Radiology. 2023;307(2):e221835. doi: 10.1148/radiol.221835.

Dr. Giulia Pilato is a second-year young radiology resident at the University of Palermo (Italy). She graduated in Medicine and Surgery at the University of Palermo in July 2021 with a dissertation on the Outcome of LI-RADS observations identified after anti-HCV therapy with direct-acting antivirals (DAA). Her main interest is abdominal radiology, with focus on hepatobiliary disease.

Comments may be sent to pilato.giulia@remove-this.yahoo.it


Radiologic-Pathologic Correlation of Hepatobiliary Phase Hypointense Nodules without Arterial Phase Hyperenhancement at Gadoxetic Acid–enhanced MRI: A Multicenter Study.

Ijin Joo, So Yeon Kim, Tae Wook Kang, Young Kon Kim, Beom Jin Park, Yoon Jin Lee, Joon-Il Choi, Chang-Hee Lee, Hee Sun Park, Kyoungbun Lee, Haeryoung Kim, Eunsil Yu, Hyo Jeong Kang, Sang Yun Ha, Joo Young Kim, Soomin Ahn, Eun Sun Jung, Baek-Hui Kim, Hye Seung Han, Jeong Min Lee.

Radiology 2020 Aug;296(2):335-345. doi: 10.1148/radiol.2020192275. Epub 2020 Jun 2.

Introduction
Current guidelines for hepatocellular carcinoma (HCC) [1] include gadoxetic acid-enhanced magnetic resonance imaging (MRI) as a first line imaging modality, due to its high sensitivity in the assessment of vascular changes and the possibility to acquire the hepatobiliary phase [2]. 

As already established, HCC develops by a multistep carcinogenesis process from low- to high-grade dysplastic nodules to early and progressed HCC [3]; since the expression of the cellular transporter responsible for the uptake gadoxetic acid in hepatocytes starts to decrease earlier than the arterial changes causing arterial phase hyperenhancement (APHE), hepato-biliary phase (HBP) hypointense nodules without APHE are proposed as HCC precursors as early HCC or high grade dysplastic nodule[3].

As the presence of APHE is a major feature in HCC diagnosis in most guidelines [1, 4], HBP hypointense nodules without APHE are considered as “probably HCC”; in several studies these nodules are associated with hypervascular transformation and poor prognosis after curative treatment for HCC [5, 6].

In view of the different management of HCC and early HCC versus dysplastic premalignant nodules and considering the possibility of non-invasive treatments [7], being able to differentiate these nodules may have an important clinical value.

Discussion
This retrospective multicenter study aimed to evaluate the pathologic diagnosis of HBP hypointense nodules at gadoxetic acid-enhanced MRI without APHE in a large patient cohort from eight institutions, aiming at determining significant imaging and clinical features.

The authors final enrollment sample included 334 nodules in 298 patients with cirrhosis or chronic liver disease with Child Pugh A-B liver function, who underwent gadoxetic acid-enahnced MRI within 3 months from the histologic diagnosis. Included nodules were of 30 mm or smaller in diameter, since early HCCs and non-malignant cirrhosis associated nodules are rarely larger than 30 mm [8] and the size cited is generally a suitable indication for local ablation.

The authors involved ten pathologists who retrospectively evaluated the histologic specimens and gave the final diagnosis of regenerative nodule, low or high grade dysplastic nodule, HCC foci in dysplastic nodule, early or progressed HCC. A consensus was considered if more than five pathologists agreed on one category or after performing a second round of pathologic review to achieve consensus.

The results of the study showed that 44% of HBP hypointense without APHE nodules were progressed HCC, 20.4% were HCC foci in dysplastic nodules or early HCC, 27.5% were high grade dysplastic nodules, and 8.1% were low grade dysplastic or regenerative nodules.

Multivariable analysis found imaging and clinical features associated with progressed HCC that could help distinguish from lower grade nodules, such as well defined margins, hypointensity on T1 weighted images, intermediate signal intensity on T2 weighted images, washout in portal phase, and restricted diffusion(odds ratios 5.5, 3.2, 3.4, 1.9 respectively; P values .03, .001, .001, and .04 respectively)  and a-fetoprotein level > 100 ng/mL (odds ratio 2.7; P value .01).

73.8% of the progressed HCCs and 56% of early HCCs nodules were considered as LR-4 (probably HCC) according to the Liver Imaging Reporting and Data System version 2017 (P < .001); lower grade nodules were less frequently classified  as LR-4.

Contrary to previous publications considering HBP hypointense nodules without APHE as early HCC, in this study a substantial proportion of nodules (44%) was pathologic diagnosed as progressed HCC. Considering that invasive surgery is not routinely performed for HBP hypointense nodules, having a pathologic assessed counterpart to radiologic features of HBP hypointense nodules without APHE in a large number of patients at risk for HCC could be helpful to select patients for biopsy, direct management, and local treatments.

References:

1.         Chernyak, V., et al., Liver Imaging Reporting and Data System (LI-RADS) Version 2018: Imaging of Hepatocellular Carcinoma in At-Risk Patients. Radiology, 2018. 289(3): p. 816-830.
2.         Zech, C.J., et al., Consensus report from the 8th International Forum for Liver Magnetic Resonance Imaging. Eur Radiol, 2020. 30(1): p. 370-382.
3.         Motosugi, U., et al., Recommendation for terminology: Nodules without arterial phase hyperenhancement and with hepatobiliary phase hypointensity in chronic liver disease. J Magn Reson Imaging, 2018. 48(5): p. 1169-1171.
4.         (KLCA), K.L.C.A. and G. National Cancer Center (NCC), K.rea, 2018 Korean Liver Cancer Association-National Cancer Center Korea Practice Guidelines for the Management of Hepatocellular Carcinoma. Korean J Radiol, 2019. 20(7): p. 1042-1113.
5.         Lee, D.H., et al., Non-hypervascular hepatobiliary phase hypointense nodules on gadoxetic acid-enhanced MRI: risk of HCC recurrence after radiofrequency ablation. J Hepatol, 2015. 62(5): p. 1122-30.
6.         Toyoda, H., et al., Non-hypervascular hypointense nodules detected by Gd-EOB-DTPA-enhanced MRI are a risk factor for recurrence of HCC after hepatectomy. J Hepatol, 2013. 58(6): p. 1174-80.
7.         Kim, B.H., Surgical resection versus ablation for early hepatocellular carcinoma: The debate is still open. Clin Mol Hepatol, 2022. 28(2): p. 174-176.
8.         Kondo, F., Histological features of early hepatocellular carcinomas and their developmental process: for daily practical clinical application : Hepatocellular carcinoma. Hepatol Int, 2009. 3(1): p. 283-93.
 

Dr. Benedetta Masci is a radiology resident at Sapienza University of Rome - Sant'Andrea University Hospital , attending the third year of residency. Her main field of interest is abdominal radiology, focusing on hepatic and pelvic magnetic resonance imaging, with a particular interest in pediatric radiology. She has been actively involved in clinical imaging research and  has contributed as a co-author in some publications.

Comments may be sent to benedetta.masci@uniroma1.it


Transient severe motion artifacts on gadoxetic acid–enhanced MRI: risk factor analysis in 2230 patients.

Eun Bee Jang, Dong Wook Kim, Sang Hyun Choi, Seung Baek Hong, Taeyong Park, Yousun Ko, Su Jung Ham.

European Radiology (2022) 32:8629–8638. https://doi.org/10.1007/s00330-022-08885-2

Gadoxetic acid is a contrast agent used in MRI liver imaging. However, the appearance of the transient severe motion artifact (TSM) during the arterial phase may limit its use.

The authors analyzed retrospectively the risk factors involved in the appearance of this artifact and its relationship with gadoxetic acid in a large cohort. After applying the inclusion and exclusion criteria, 2230 patients who underwent a MRI at tertiary centre between January 2017 and June 2017 were selected. 

Inclusion criteria included: age over or equal to 18 years and have a MRI done between January 2017 and June 2017. Exclusion criteria included: absence of laboratory data or anthropometric measurements for at least one month prior to the test. 

The clinical information was obtained from the electronic database: demographic data, laboratory data, underlying disease, ascites and pleural effusion, and previous gadoxetic acid–enhanced MRI studies.

The degree of ascites and pleural effusion was analysed on the MRI examination.

Two board-certified radiologists evaluated TSM artifact on arterial phase images in gadoxetic acid-enhanced MRI using a 5-point grading scale. According to the severity of the artifact, patients were classified into two groups:

1.  non-TSM group, includes artifact grade of 0 to 3:  grade 1 or no artifact, grade 2 or minimal artifact and grade 3 or moderate artifact with some effect on diagnostic quality.

2.  TSM group, includes artifact grade of 4 or 5: grade 4, severe artifact that affects diagnostic quality but still interpretable. Finally grade 5 which consisted of extensive artifact with non-diagnostic images. 

The incidence of TSM using gadoxetic acid enhanced MRI was 5.0% (111/2230 examinations). Univariable and multivariable logistic regression analyses were performed obtaining the following results:

-The risk factors such as old age (≥ 65 years) [OR = 2,01 (1,31–3,07)], High Body Mass Index (BMI ≥ 25 kg/m2) [OR = 1,76 (1,18–2,63)], chronic obstructive pulmonary disease (COPD) [OR = 6,11 (2,32–16,04)], and moderate to severe pleural effusion [OR = 3,55 (1,65–7,65)], were recognized as significant independent risk factors for TSM occurrence.

-Hepatitis B and previous gadoxetic acid–enhanced MRI studies was associated with a lower risk of TSM occurrence, [OR = 0,66 (0,43–0,99)] and [OR = 0,52 (0,33–0,83)], respectively. In this study, hepatitis B was an independent negative risk factor probably because these patients have previous MRI studies and some of them do not have advanced cirrhosis.

Based on risk factors (age > 65 years, BMI > 25 kg/m2, COPD, moderate to severe pleural effusion, no hepatitis B, and no previous experience of gadoxetic acid), the predictive risk of TSM was 0,6% in the absence of risk factors,5,7% if at least one of the significant factors was present, and this percentage increased to 16,3% with at least four risk factors.

In addition to the current study, many of these patients underwent examinations with an extracellular contrast agent within 1 year (138/2230).  This fact allowed the authors of the study to create a subgroup analysis to compare the incidence of TSM with hepatospecific and extracellular contrast agent. The incidence of the TSM was higher with gadoxetic acid-enhanced MRI (McNemar test:  9,5% vs 2,2%, p =0,006).

The authors acknowledge the following limitations: selection bias due to retrospective study design, studies obtained from Korean institutions where the hepatitis B virus is endemic and low incidence (5%) compared with previous meta-analysis (13%).    

However, the authors also acknowledge that this study evaluated a significant number of individuals (2230), as well as it comprehensively evaluated the TSM-related risk factors. Therefore, they consider that this study has sufficient statistical power and a high consistency.

In conclusion, even though some technical methods (multiarterial sequence with parallel and sensing images) might mitigate the problem, knowing the risk factors for TSM artifact on gadoxetic acid–enhanced MRI can be useful for providing diagnostic strategies more tailored to individual patients.

As gadoxetic acid improves the lesion conspicuity and the characterization of the focal liver lesions, and it is increasingly used especially in cirrhosis background, the interest of this papers for abdominal radiologists is to know about the risks factors that might impair the imaging quality and potentially avoid the artifacts that would become the images non-diagnostic.

References:

  1. Kim DW, Choi SH, Park T, Kim SY, Lee SS, Byun JH. Transient Severe Motion Artifact on Arterial Phase in Gadoxetic Acid-Enhanced Liver Magnetic Resonance Imaging: A Systematic Review and Meta-analysis. Invest Radiol. 2022 Jan 1;57(1):62-70. doi:10.1097/RLI.0000000000000806. PMID: 34224484.
  2. Hong S, Choi SH, Hong SB, Kim SY, Lee SS. Clinical usefulness of multiple arterial-phase images in gadoxetate disodium-enhanced magnetic resonance imaging: a systematic review and meta-analysis. Eur Radiol. 2022 Aug;32(8):5413-5423. doi: 10.1007/s00330-022-08620-x. Epub 2022 Feb 22. PMID: 35192009.
  3. Furlan A, Close ON, Borhani AA, Wu YH, Heller MT. Respiratory-motion artefacts in liver MRI following injection of gadoxetate disodium and gadobenate dimeglumine: an intra-individual comparative study in cirrhotic patients. Clin Radiol. 2017 Jan;72(1):93. e1-93. e6. doi: 10.1016/j.crad.2016.08.005. Epub 2016 Sep 12. PMID: 27633725.
  4. Motosugi U, Bannas P, Bookwalter CA, Sano K, Reeder SB. An Investigation of Transient Severe Motion Related to Gadoxetic Acid-enhanced MR Imaging. Radiology. 2016 Apr;279(1):93-102. DOI: 10.1148/radiol.2015150642. PMID: 26473642; PMCID: PMC5562163.
  5. Komatsu N, Motosugi U, Maekawa S, Shindo K, Sakamoto M, Sato M, Tatsumi A, Miura M, Amemiya F, Nakayama Y, Inoue T, Fukasawa M, Uetake T, Ohtaka M, Sato T, Asahina Y, Kurosaki M, Izumi N, Ichikawa T, Araki T, Enomoto N. Hepatocellular carcinoma risk assessment using gadoxetic acid-enhanced hepatocyte phase magnetic resonance imaging. Hepatol Res. 2014 Dec;44(13):1339-46. doi: 10.1111/hepr.12309. Epub 2014 Apr 24. PMID: 24528803.
     

Jose F. Melo Villamarín is an abdominal radiologist at University and Polytechnic La Fe Hospital in Valencia, Spain, the same hospital where he also completed his residency (2020). He completed his undergraduate medical degree at the ELAM in Cuba in 2012.

Comments may be sent to: melo_josvil@remove-this.gva.es


Clinical, Imaging, and Pathologic Features of Conditions with Combined Esophageal and Cutaneous Manifestations.

Matthew H. Lee, MD, Meghan G. Lubner, MD, J. Klint Peebles, MD, Molly A. Hinshaw, MD, Christine O. Menias, MD, Marc S. Levine, MD, Perry J. Pickhardt, MD

RadioGraphics 39:1411–1434. Published Online: Aug 16 2019

The esophagus, consists of squamous epithelial cells, similar to what composes the skin. As a result, these two separate organs are linked through a concomitant affliction by diseases ranging from infections, autoinflammatory and autoimmune conditions to genetic syndromes and paraneoplastic manifestations. Each such disorder may present with characteristic findings on either the skin or/and the esophagus, thus providing a certain diagnostic direction.

The present study seeks to bring those different entities under a converging scope of clinical presentations and imaging observations with the aim to provide the reader with the tools to assert the underlying etiologic factor.

The infectious organisms studied here are HSV, CMV, HIV and Candida albicans. Multiple, lesser-sized esophageal ulcers are typical of HSV, whereas larger lesions are more characteristic of CMV and HIV infections. C. albicans assumes a linear, plaque-like appearance on the esophagography. Regarding the skin, HSV features clustered blisters; CMV exhibits non-distinct traits, C. albicans presents the characteristic white plaques of oral thrush, whereas, HIV-infection, defined by its immunodefective nature and concurrent opportunistic infections can assume any of the aforementioned skin lesions [1], [2], [3].

Moving on to bullous diseases, two categories are described, namely the epidermolysis bullosa  (EB) and the pemphigoid disorders (PD). The former concerns a group of genetic conditions that affect the epidermis and mucosa, weakening their structural integrity, making them susceptible to mechanical damage [4]. The latter targets the subepidermis and mucosa in the form of autoimmunity, can affect any part of the soma and presents as pruritic or painful vesicular lesions. On regard to esophageal involvement, both entities may cause strictures of the esophagus, with EB most commonly affecting its upper anatomic area, whereas PD any part of it [5].

In direct contrast, scleroderma, another autoimmune disease, mostly affects the distal part of the esophagus, reducing its motility, causing it to dilate early on, though also effecting strictures later on the course of the disease. The skin of the extremities seems to be damaged first, becoming rigid and prone to trauma [6].

The autoinflammatory conditions studied here are lichen planus and Crohn’s disease. Lichen planus is allegedly a T-cell oriented disease that causes lilac-coloured papules on the skin, while also involving the nails and hair. The esophagus, mainly its thoracic part, reduces in diameter [7] and can pose a differential bipolar, having a similar esophagographic appearance to eosinophilic esophagitis. The elder of age and female sex predominant on lichen planus in contrast to a younger male patient on eosinophilic esophagitis help differentiate between the two. Crohn’s disease, a primarily bowel disorder, may affect the skin via perianal fissures and fistulas or indirectly via its implications on nutrient absorption. The esophagus is not usually a trademark organ of this disease, but it may manifest with small ulcerative lesions or fistulas to adjacent organs [8].

Cowden syndrome consists a genetic disorder of a defective tumour suppressor gene that results in an increase in hamartomas and malignancy. Related skin conditions are hair follicle-derived hamartomas, fibromas and papules on the acral dorsal parts. The esophagus is infrequently affected, but may present with a nodule-like appearance at the esophagography [9]. Blue Rubber Bleb Nevus Syndrome (BRBNS) is a congenital disorder with a mutated endothelial cell receptor and resulting venous malformations both on the skin and the GI tract, in the form of polyps or even mass-like configurations [10].

Melanoma constitutes a primary malignant tumour of melanocytes, presents as uneven, varicoloured, growing skin lesion that has rarely an impact on the esophagus but can, nonetheless, affect it as a non-obstructive, but lumen-expanding polypoid mass [11]. Acrokeratosis paraneoplastica comprises a paraneoplastic condition, often of an SCC, of the respiratory and/or the GI tract. Its varying skin lesions can direct to a primary neoplastic or secondary disseminated foci. An SCC of the esophagus can assume a plaque or polypoid lesion morphology early on or a mass-like form that causes narrowing of the esophageal lumen at later stages [12].

Finally, neither the skin nor the esophagus could be spared from drug side-effects, such as those caused by doxycycline. Doxycycline can, namely, have phototoxic effects on both the skin and nails and give rise to small ulcerative lesions in the esophagus, particularly at sites of physiologic anatomic compression [13].

References:

[1]Bando, T. et al. (2009) ‘HERPES SIMPLEX ESOPHAGITIS IN THE ELDERLY’, Digestive Endoscopy. John Wiley & Sons, Ltd, 21(3), pp. 205–207. doi: 10.1111/J.1443-1661.2009.00888.X.
[2]Regezi, J. A. et al. (1996) ‘Herpes simplex and cytomegalovirus coinfected oral ulcers in HIV-positive patients’, Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology. Mosby, 81(1), pp. 55–62. doi: 10.1016/S1079-2104(96)80149-1.
[3]Adesiyun, O. A. et al. (2015) ‘Candida esophagitis: Feathery appearance as a new sign on barium esophagogram’, West African Journal of Radiology. Medknow Publications and Media Pvt. Ltd., 22(2), p. 110. doi: 10.4103/1115-3474.162152.
[4]Guerra-Leal, J. D. et al. (2016) ‘The Importance of Esophagography in Patients With Recessive Dystrophic Epidermolysis Bullosa’, dx.doi.org/10.2214/AJR.16.16115. American Roentgen Ray Society , 207(4), pp. 778–781. doi: 10.2214/AJR.16.16115.
[5]Reed, C. C., Dellon, E. S. and Shaheen, N. J. (2022) ‘Miscellaneous diseases of the esophagus: foreign bodies, physical injury, and systemic and dermatological diseases’, Yamada’s Textbook of Gastroenterology. John Wiley & Sons, Ltd, pp. 909–923. doi: 10.1002/9781119600206.CH48.
[6]Katzka, D. A. (2018) ‘A gastroenterologist’s perspective on the role of barium esophagography in gastroesophageal reflux disease’, Abdominal Radiology. Springer New York LLC, 43(6), pp. 1319–1322. doi: 10.1007/S00261-017-1352-8/METRICS.
[7]Rauschecker, A. M. et al. (2016) ‘Esophageal Lichen Planus: Clinical and Radiographic Findings in Eight Patients’, dx.doi.org/10.2214/AJR.16.16793. American Roentgen Ray Society , 208(1), pp. 101–106. doi: 10.2214/AJR.16.16793.
[8]De Felice, K. M., Katzka, D. A. and Raffals, L. E. (2015) ‘Crohn’s Disease of the Esophagus: Clinical Features and Treatment Outcomes in the Biologic Era’, Inflammatory Bowel Diseases. Oxford Academic, 21(9), pp. 2106–2113. doi: 10.1097/MIB.0000000000000469.
[9]Tang, S. J. and Wu, R. (2015) ‘Esophageal introitus (with videos)’, Gastrointestinal Endoscopy. Mosby Inc., 81(2), pp. 270–281. doi: 10.1016/j.gie.2014.09.065.
[10]Tomita, H. et al. (2016) ‘The imaging features of protruding esophageal lesions’, Japanese Journal of Radiology. Springer Tokyo, 34(5), pp. 321–330. doi: 10.1007/S11604-016-0534-6/METRICS.
[11]Tirumani, H. et al. (2015) ‘Imaging of uncommon esophageal malignancies’, Diseases of the Esophagus. Oxford Academic, 28(6), pp. 552–559. doi: 10.1111/DOTE.12208.
[12]Camilleri, M. J. (2021) ‘Cutaneous Diseases of the Esophagus’, The Esophagus. John Wiley & Sons, Ltd, pp. 789–803. doi: 10.1002/9781119599692.CH46.
[13] Katzka, D. A. (2021) ‘Medication-Induced Esophageal Injury’, The Esophagus. John Wiley & Sons, Ltd, pp. 728–735. doi: 10.1002/9781119599692.CH42.
 

Christos Korres is a first-year radiology resident at the Konstantopouleion General Hospital of Athens, Greece. He studied at the Medical School of Athens and concluded a postgraduate program in Linkoping, Sweden with a dissertation on the Olfactory Function of Healthy Participants, explored through fMRI and mathematical models. His interests are still developing, but currently focused on Abdominal Radiology and Neuroradiology.

Comments may be sent to kris.korres@remove-this.gmail.com


Influence of dilution on arterial-phase artifacts and signal intensity on gadoxetic acid–enhanced liver MRI.

Sarah Poetter-Lang, Gregor O. Dovjak, Alina Messner, Raphael Ambros, Stephan H. Polanec, Pascal A. T. Baltzer, Antonia Kristic, Alexander Herold, Jacqueline C. Hodge, Michael Weber, Nina Bastati, Ahmed Ba-Ssalamah

European Radiology, volume 33, pages 523–534 (2023)

MRI with gadoxetic acid is widely and increasingly used to detect and characterize focal liver lesions. (1) However, one of the main limitations of gadoxetic acid is represented by arterial-phase (AP) artifacts: transient severe motion (TSM) and truncation artifacts. Both are due to the acute fleeting peak of gadoxetic acid blood plasma concentration, which causes acute transient dyspnea by activating central chemoreceptors,  and the rapid disappearance of contrast from the imaging field. (2,3). The acute fleeting peak plasma gadoxetic acid concentration during the arterial phase can be prevented by saline dilution of gadoxetic acid at 1:1 and a slow injection rate of 1 ml/s (4), both off-label. The Authors’ aim was to assess the effect of these two strategies on AP artifacts reduction, on quantitative differences in signal intensity (SI), signal-to-norm, and contrast-to-norm, and hence focal lesion conspicuity on MR imaging.

This single-center retrospective study enrolled 112 patients who had undergone at least one non-diluted (ND) and one saline-diluted (D) gadoxetic acid–enhanced MRI at 1 ml/s for known or suspected liver or pancreaticobiliary diseases between December 2010 and July 2017. Patients who had undergone liver transplantation between the two MRIs or who had artifacts in all sequences were excluded.

Arterial-phase imaging was initiated at the individual patient’s t-peak, timed using a test bolus technique. Two blinded radiologists independently graded on a 5-point scale the presence of artifacts in dynamic T1-weighted sequences (unenhanced, arterial, portal venous, transitional, and 20-min HB phases). AP artifacts were defined as a score ≥ 4 in the arterial phase.(2) Then, quantitative signal intensity (SI) measurements were acquired by drawing regions of interest (ROI) at the level of the celiac trunk in five locations: aorta, portal vein, liver parenchyma, focal liver lesion, and paraspinal muscle in all phases in each patient. The SI value was normalized to the SI of the paraspinal muscle to obtain signal-to-norm ratio (SINorm). For focal lesions, the contrast-to-norm ratio (Cnorm) was also calculated.

AP artifacts were significantly reduced with dilution and were present in 35 (31%) of the non-diluted exams compared to 10 of the diluted exams (9%). An artifact severity score of 5 (i.e. nondiagnostic exam) was assigned to 18 exams (16%), 17 of which were in the non-diluted group. The scored severity of the artifacts was significantly higher in the ND compared to the D protocol (p < 0.001).

The mean absolute liver parenchyma SI and mean liver SINorm were significantly higher in the diluted exams in all contrast-enhanced phases. The mean SiNorm of the aorta in the AP and of the portal vein in the portal venous phase was significantly higher in the D exams (p = 0.005 and p = 0.035, respectively). There was no significant difference in the CNorm of all lesions (FNH, metastases, cirrhotic nodules, adenomas, hemangiomas) combined for D versus ND exams (all phases p > 0.05). Evaluation for lesion subtype, when n ≥ 10 (i.e., FNH and metastases), also revealed no significant difference in CNorm between the ND and D exams (all phases p > 0.05).

Arterial-phase artifacts did not have a significant influence on the SI of liver parenchyma on the ND (p=0.627) and on D (p=0.644) exams. The higher SI and SINorm in the diluted exams were attributed to contrast dilution and slower injection rate. In order to assess the effect of artifacts on lesion visibility, the authors also analyzed the detectability of lesions smaller than 1 cm. They were able to detect 5 more lesions and to see 3 lesions better on the diluted vs non-diluted scans. They attributed these findings to TSM artifact reduction as truncation artifacts did not influence the visibility of these lesions.

The high relaxivity of gadoxetic acid explains why the difference in SI and SINorm was largest in the HBP. Also,  during recirculation, on the diluted exams hepatocyte transporters had more time to accumulate gadoxetic acid due to doubling the volume on the diluted exams.

The Authors acknowledge some limitations. First, the retrospective study design, with a relatively small cohort and few comparable lesions, as the majority of the patients with HCC and metastases underwent treatment leading to a change in the appearance of these lesions between ND and D exams. Notwithstanding these limitations, the authors obtained significant results. A prospective study, ideally in a larger cohort, is warranted to confirm the findings of the study. Furthermore, a test bolus injection was used to estimate peak enhancement, which may affect subsequent signal intensity, choosing the same delay. This problem was overcome by the choice of intraindividual comparison for measuring SINorm differences on D versus ND exams. In this way, they also eliminated the influence of factors that can contribute to severe AP artifacts such as gender, weight, and BMI.

In conclusion, the authors demonstrated that 1:1 saline dilution of gadoxetic acid, administered at the slower injection rate of 1 ml/ s via a power injector, reduces significantly arterial phase transient severe motion artifacts, while increasing normalized signal intensity and preserving lesion contrast compared to standard non-diluted images.

References:

  1. Ba-Ssalamah A, Uffmann M, Saini S, Bastati N, Herold C, Schima W (2009) Clinical value of MRI liver-specific contrast agents: a tailored examination for a confident non-invasive diagnosis of focal liver lesions. Eur Radiol 19:342–357
  2. Davenport MS, Bashir MR, Pietryga JA, Weber JT, Khalatbari S, Hussain HK (2014) Dose-toxicity relationship of gadoxetate disodium and transient severe respiratory motion artifact. AJR Am J Roentgenol 203:796–802
  3. Huang SY, Seethamraju RT, Patel P, Hahn PF, Kirsch JE, Guimaraes AR (2015) Body MR imaging: artifacts, k-space, and solutions. Radiographics 35:1439–1460
  4. Kim YK, Lin WC, Sung K et al (2017) Reducing artifacts during arterial phase of gadoxetate disodium-enhanced MR imaging: dilution method versus reduced injection rate. Radiology 283:429–437
  5. Jornada Tda S, Murata CH, Medeiros RB (2016) Influence of partial k-space filling on the quality of magnetic resonance images. Radiol Bras 49:158–164


Giulia Tomelleri  is a third-year radiology resident at the Radiology Department of the University of Verona, Italy. She graduated in 2020 in Medicine and Surgery at the University of Ferrara. Her main field of interest in diagnostic imaging is Abdominal imaging, with focus on gastrointestinal and hepato-pancreato-biliary disease.

Comments may be sent to: giulia.tom94@gmail.com


Liver stiffness measurement by magnetic resonance elastography is not affected by hepatic steatosis.

Jie Chen, Alina M. Allen, Terry M. Therneau, Jun Chen, Jiahui Li, Safa Hoodeshenas, Jingbiao Chen, Xin Lu, Zheng Zhu, Sudhakar K. Venkatesh, Bin Song, Richard L. Ehman, Meng Yin

European Radiology (2022) 32:950–958

Magnetic resonance elastography (MRE) is an excellent tool for the non-invasive detection of liver fibrosis. [1] It quantitatively evaluates liver stiffness (LS) and is increasingly demanded in clinical routine. This diagnostic technique can be performed using additionally hard- and software representing an objective, reliable and reproducible method without significant variability across vendors and magnetic field strengths. [2]

Continuous acoustic waves generated by an active driver induce a tissue stimulation; with a phase contrast sequence the propagating waves are visualized and then automatically converted into quantitative sectional images so-called elastograms. [3] Typical and recommended parameters of either GRE or SE-EPI MRE performed sequences are listed in the regularly updated QIBA profile. [4] Usually four axial slices are taken through the liver in different positions. The image evaluation takes place on the 95% confidence maps, considering the wave and magnitude images. In the liver, partially automatically, an as large as possible or several subcapsular regions of interest (ROIs) are drawn. [5] Finally, the MRE result (specification in kPa, SI unit for pressure/mechanical stress) is an indication of the fibrosis score, from F0 (no fibrosis) to F4 (cirrhosis). [6] The interpretation of MRE results should always consider the clinical context, as MRE assessment of liver fibrosis may be affected by other pathologic changes as inflammation, passive congestion, biliary obstruction, or diffuse infiltrative disorders which may also increase liver stiffness values. [1; 7]

In diffuse liver disease, steatosis is an important entity, representing the most common form of diffuse liver disease. With a worldwide prevalence of 25-45% nonalcoholic fatty liver disease (NAFLD) has become a medical burden. [8] Patients with NAFLD can progress to liver fibrosis or even cirrhosis. It is of great clinical relevance among all NAFLD patients, to non-invasively differentiate those with non-alcoholic steatohepatitis (NASH) and advanced fibrosis, as these have the greatest risk of developing liver-related increased morbidity and mortality.

The authors of the present retrospective study aimed to evaluate the relationship between pathology-assessed hepatic steatosis, MR-measured proton density fat-fraction (PDFF), and MRE-gaged liver stiffness in a large patient cohort with biopsy-proven or high risk of NAFLD.  The study focuses on the impact of hepatic steatosis/liver fat on liver stiffness measurement (LSM).

256 patients with liver biopsy and MRI/MRE examination carried out within one year were included. The MRI protocol was performed on a 1.5T device and consisted of a 2-point or 6-point Dixon to estimate the PDFF and of a 2D MRE to measure the LS. NAFLD was defined by imaging or histology.

The PDFF correlated significantly with steatosis grades. An excellent correlation (r = 0.97, p < 0.001) was found in 87 patients. Age, fibrosis stage and biopsy-based steatosis were significant covariates influencing the LS. Patients without histopathologic steatosis showed significant lower LS as patients with steatosis but no significant difference of LS was found between the different degrees of steatosis severity. Finally, no statistically significant relationship between LS and PDFF could be confirmed.

The results indicate that the severity of hepatic steatosis in patients with NAFLD, as assessed quantitatively with MRI-PDFF methods, does not have a significant effect on MRE-assessed LS. Steatosis is therefore not a relevant variable in the setting of MRE measurements. This observation is consistent with other publications in which no or only little effect of the severity of hepatic steatosis on MRE was found. [9]

The authors further hypothesize that the apparent correlation between LS and hepatic steatosis, that is reported in literature [10], could be linked to other histopathologic processes as inflammation.

This study shows that the severity of hepatic steatosis has no significant effect on MRE-based LSM. It should be considered that adjustment for fibrosis stage and other independent factors is important. The conclusion has an impact to our daily clinical routine. MRE is a valuable tool, but possible confounders, e.g. iron, must be addressed. This problem exists in many quantitative investigations regarding diffuse liver diseases and shows that a multi-parametric access should be chosen. Nevertheless, steatosis in MRE does not appear to have a significant impact on the results, which in turn facilitates clinical application.

References:
1. Venkatesh SK, Wells ML, Miller FH et al (2018) Magnetic resonance elastography: beyond liver fibrosis-a case-based pictorial review. Abdom Radiol (NY) 43:1590-1611
2. Ozturk A, Olson MC, Samir AE, Venkatesh SK (2022) Liver fibrosis assessment: MR and US elastography. Abdom Radiol (NY) 47:3037-3050
3. Pepin KM, Welle CL, Guglielmo FF, Dillman JR, Venkatesh SK (2022) Magnetic resonance elastography of the liver: everything you need to know to get started. Abdom Radiol (NY) 47:94-114
4. QIBA, MR, Biomarker, Committee. MR Elastography of the Liver, Quantitative Imaging Biomarkers Alliance. Profile Stage: Technically Confirmed. February 14, 2022. Available via http://qibawiki.rsna.org/index.php/Profiles
5. Tang A, Cloutier G, Szeverenyi NM, Sirlin CB (2015) Ultrasound Elastography and MR Elastography for Assessing Liver Fibrosis: Part 1, Principles and Techniques. AJR Am J Roentgenol 205:22-32
6. Brunt EM (2016) Nonalcoholic Fatty Liver Disease: Pros and Cons of Histologic Systems of Evaluation. Int J Mol Sci 17
7. Tang A, Cloutier G, Szeverenyi NM, Sirlin CB (2015) Ultrasound Elastography and MR Elastography for Assessing Liver Fibrosis: Part 2, Diagnostic Performance, Confounders, and Future Directions. AJR Am J Roentgenol 205:33-40
8. Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M (2016) Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology 64:73-84
9. Leitao HS, Doblas S, Garteiser P et al (2017) Hepatic Fibrosis, Inflammation, and Steatosis: Influence on the MR Viscoelastic and Diffusion Parameters in Patients with Chronic Liver Disease. Radiology 283:98-107
10. Joshi M, Dillman JR, Singh K et al (2018) Quantitative MRI of fatty liver disease in a large pediatric cohort: correlation between liver fat fraction, stiffness, volume, and patient-specific factors. Abdom Radiol (NY) 43:1168-1179

Dr. Michaela Plaikner is radiologist at the Medical University of Innsbruck. She has a wide range of interests in diagnostic and interventional imaging with focus of the abdomen and the musculoskeletal system. She is actively involved in different areas of clinical research, mainly in the field of MR based diagnosis of diffuse liver disease and is first and co-author in several publications. She also completed her PhD thesis with research focused on the evaluation of different MRI sequences analyzing diffuse liver disease.

Comments may be sent to: michaela.plaikner@i-med.ac.at 


Transjugular intrahepatic portosystemic shunt (TIPS) complications: what diagnostic radiologists should know.

Giuseppe Mamone, Mariapina Milazz, Ambra Di Piazza, Settimo Caruso, Vincenzo Carollo,  Giovanni Gentile, Francesca Crinò, Gianluca Marrone, Gianvincenzo Sparacia, Luigi Maruzzelli, Roberto Miraglia

Abdominal Radiology (2022) doi: 10.1007/s00261-022-03685-0

Transjugular intrahepatic portosystemic shunt (TIPS) is a recognized treatment for the complications of portal hypertension. Morbidity has been shown to be as high as 20% (1) with complications having a 2% fatality rate (2). Early identification of complications have a favorable outcome. The authors provide a review to outline the role of diagnostic radiology in identifying and assessing post-TIPS complications.

CT, MRI and Doppler US all have a role in the pre-procedural evaluation of hepatic and portal vein patency as well as important anatomical variations. Liver morphology, masses and cysts should all be documented as these may interfere with the technical success of the procedure. Obstructed bile ducts should be identified as they require pre procedure decompression.

The authors identify two categories of complications: those related to interventional technique (e.g. hepatic vein thrombosis, haemorrhage, ischaemia, vascular or biliary injury, stent malpositioning or migration) and those associated with TIPS dysfunction and the portosystemic shunting effect.

Correct stent position is of prime importance to achieve adequate function and patency. Stent malpositioning can cause perfusion and shunt outflow stenosis (1). Stent migration can lead to a myriad of cardiovascular complications (1). Covered stents have a higher tendency for migration on comparison to bare metal stents (1). Stent position can be assessed by US, CT and MRI, with the proximal end sited at the confluence of the portal vein and the liver parenchymal tract.

Accidental perforation of the hepatic artery or a branch occurs in 1 to 6% of patients (1, 3). This is usually of low clinical significance (1). Multiphase contrast enhanced CT can be utilized to detect potential complications including pseudoaneurysm, vascular dissection or occlusion and arterioportal fistula haemorrhage. 

Portal vein injury on the other hand, has been considered the riskiest step in a TIPS procedure (4) as it can result in massive haemorrhage. Clear understanding of the vascular anatomy with pre-procedural imaging is of prime importance. This is treated immediately by the interventional radiologist, however post-procedure CT or MRI are useful for visualizing residual perihepatic haemorrhage. Haematoma appears as hyperdense on CT and hyperintense on T1, with no contrast enhancement. (4)

Portal and hepatic vein thrombosis appear as non-enhancing vessels on contrast enhanced CT or MRI, with absence of flow at colour doppler examination. Hepatic vein thrombosis is usually of little clinical consequence (5), however a Budd-Chiari type hepatic ischaemia and acute hepatic failure can result.

Biliary duct puncture is reported in up to 5% of cases (1, 3). The connection between biliary and vascular systems can result in infection and haemobilia (1). TIPS stents can also generate biliary occlusion (6) and rapid hepatic decompensation (7).  Segmental cholestasis, with intrahepatic biliary dilatation can be seen on imaging. MRI and MRCP is the best way to evaluate cholangitis. Classic findings of a hepatic abscess are the double target sign on contrast enhanced CT: caused by a central low attenuation lesion surrounded by an enhancing rim and a low density outer ring (oedema) (8).

The incidence of liver ischaemia is thought to be underestimated imaging is only performed when complications occur. Infarcts are rare due to the dual blood supply. CT show the parenchymal ischaemic injury as a hypodense, non-enhancing area without mass effect which is often peripheral and wedge shaped.

Puncture of non-target organs, most commonly gallbladder (1), is another known complication.

TIPS dysfunction is defined as a reduction in the portal venous decompression due to occlusion or stenosis of the shunt. Follow up with doppler US is the method to identify such complications, with the initial baseline examination performed 7-14 days post-procedure.

Stenosis and occlusion are the most frequent complications, with long term patency of ePTFE covered stents having favorable outcomes on comparison to bare metal stents: dysfunction at 2 years of 20-30% as compared to 60-80% respectively (9).

Gold standard for TIPS evaluation is trans-shunt venography with portosystemic pressure gradient (PSG) measurement. TIPS dysfunction criteria include a PSG greater than 12mmHg or a luminal narrowing greater than 50%. CT can be used to identify filling defects but it does not provide functional information about flow or pressure. MRI is limited in view of a large number of susceptibility artefacts. Overall, doppler US is the best screening tool for identifying early shunt dysfunction, with reversal of flow and abnormal shunt velocities being the key criteria of assessment (2). The authors however identified that few studies have examined how to apply doppler US optimally, in particular to covered stents.

Less than 5% of TIPS result in acute shunt thrombosis (6). Diagnosis is with doppler US: neither colour nor duplex signals are present in the shunt lumen. Contrast enhanced CT or MRI show absence of lumen opacification (10).

Patients with hernias who undergo TIPS for refractory ascites are at increased risk of incarceration (6) due to the resolution of massive ascites changing the intra-abdominal configuration. CT and MRI can be used to evaluate these complications and plan for surgery

The authors conclude that although TIPS is a relatively safe procedure, the understanding of the procedure and the knowledge of potential complications helps the diagnostic radiologist reach a prompt and correct diagnosis. 

References:

  1. Gaba RC, Khiatani VL, Knuttinen MG, Omene BO, Carrillo TC, Bui JT, Owens CA; Comprehensive review of TIPS technical complications and how to avoid them. AJR 2011 March 196 (3): 675-85
  2. Bucher JN, Hollenbach M, Strocka S, Gaebelein G, Moche M, Kaiser T, Bartels M, Hoffmeister A. Segmental intrahepatic cholestasis as a technical complication of the transjugular intrahepatic porto-systemic shunt. World J Gastroenterol. 2019 Nov 21;25(43):6430-6439
  3. Shah RP, Sze DY. Complications During Transjugular Intrahepatic Portosystemic Shunt Creation. Tech Vasc Interv Radiol. 2016 Mar;19(1):61-73
  4. Ripamonti R, Ferral H, Alonzo M, Patel NH. Transjugular intrahepatic portosystemic shunt-related complications and practical solutions. Semin Intervent Radiol. 2006 Jun;23(2):165-76
  5. Bureau C, Otal P, Chabbert V, Peron JM, Rousseau H, Vinel JP. Segmental liver ischemia after TIPS procedure using a new PTFEcovered stent.  Hepatology 2002; 36:155
  6. Suhocki PV, Lungren MP, Kapoor B, Kim CY. Transjugular intrahepatic portosystemic shunt complications: prevention and management. Semin Intervent Radiol. 2015 Jun;32(2):123-32
  7. Duller D, Kniepeiss D, Lackner C, et al. Biliary obstruction as a complication of transjugular intrahepatic portosystemic shunt. Liver Transpl 2009;15(5):556–557
  8. Bachler P, Baladron MJ, Menias C et-al. Multimodality Imaging of Liver Infections: Differential Diagnosis and Potential Pitfalls. Radiographics. 2016;36 (4): 1001–23.
  9. Manatsathit W, Samant H, Panjawatanan P, Braseth A, Suh J, Esmadi M, Wiedel N, Ingviya T. Performance of ultrasound for detection of transjugular intrahepatic portosystemic shunt dysfunction: a meta-analysis. Abdom Radiol (NY). 2019 Jul;44(7):2392-2402.26: 10
  10. Uflacker R, Reichert P, D’Albuquerque LC, de Oliveira e Silva A. Liver anatomy applied to the placement of transjugular intrahepatic portosystemic shunts. Radiology 1994;191:705–712.


This article was prepared by Dr. Stephanie Arrigo from the Mater Dei Hospital in Msida, Malta.  

Comments may be sent to: steffianastasi@gmail.com 


Emerging imaging techniques for acute pancreatitis

Saeed Ghandili, Shahab Shayesteh, Daniel F. Fouladi, Alejandra Blanco, Linda C. Chu

Abdom Radiol (NY). 2020 May;45(5):1299-1307.
doi: 10.1007/s00261-019-02192-z.

Acute pancreatitis (AP) is caused by acute inflammation of the pancreas and adjacent tissue. Current CT and MRI evaluation of AP, included in the revised Atlanta classification of AP, is based on morphologic imaging criteria [1].

Authors suggest that newer MR techniques such as diffusion-weighted imaging (DWI), T1 and T2 mapping can offer quantitative imaging features. DWI is a MR imaging technique that quantifies the diffusion of water molecules within biologic tissues. In AP, pancreatic inflammation and tissue injury restrict diffusion, therefore, the ADC (apparent diffusion coefficient) of AP has been reported to be significantly lower than that of normal pancreas [2,3]. Lower ADC values were also associated with increased severity of AP. DWI is also potentially useful in diagnosing necrotizing pancreatitis, as ADC values have been found to be significantly higher [4]. Finally, DWI has shown incremental value in identifying superimposed infection in pancreatic fluid collections, which have more restricted diffusion and lower ADC values relative to sterile collections [5].

Pancreatic disease states such as edema increase T1 relaxation time and decrease the signal intensity on T1-weighted images. The T1 relaxation time cannot be directly measured on traditional T1-weighted image. On the other hand, T1 mapping directly measures the T1 relaxation time of the region of interest, facilitates comparison of T1 relaxation time of patients with different pancreatic pathologies and allows serial assessment of T1 relaxation time to monitor disease progression and response to treatment, with a single breath hold [6]. Several studies performed at 3T have shown increased T1 relaxation time for patients with chronic pancreatitis (CP) and autoimmune pancreatitis (AIP) compared to normal controls. While there are no currently published reports detailing alterations in T1 relaxation time in patients with AP, based on these preliminary results, one would expect that T1 relaxation time should also be elevated in patients with AP. This needs to be validated in future studies.

Similar to T1 mapping, T2 mapping is a technique that can quantify the transverse relaxation time. Pancreatic edema and inflammatory changes in AP typically account for the observed increased signal intensity on T2-weighted images. T2 mapping offers the potential to quantify the degree of pancreatic edema and inflammatory changes, which may provide diagnostic and prognostic information [7]. A series of preliminary studies, by Vietti Violi et al. etc, showed that T2 mapping may provide quantitative biomarkers indicative of underlying pancreatic disease. These results need to be validated in future studies.

Advances in image post-processing and analytic techniques also offer opportunities for improved disease detection and classification. Both radiomics and artificial neural networks take advantage of the high-dimensional mineable data present in medical images. There is growing evidence that radiomics may provide useful imaging biomarkers for pancreatic tumor detection. A few studies have applied similar radiomics approaches to extract additional diagnostic and prognostic information in patients with AP. Lin et al. reported that contrast-enhanced MRI-based radiomics features were predictive of AP severity in a retrospective study of 259 patients with AP [8]. The results showed that the radiomics model was able to more accurately predict severity of AP in the early stage compared to some of the existing clinical models, as well as, predict complications related to AP, or recurrent episodes of AP.

Another emerging technology that has the potential to improve risk stratification and management in AP is the artificial neural network (ANN). ANNs pass the input values through a number of “hidden layers” of mathematical equations to develop a model that best fits the data. Most of the current literature on ANNs and AP focuses solely on clinical and laboratory data as input, while only one study by Keogan et al. incorporated both radiologic and laboratory data [9]. No published reports have directly used ANNs to extract quantitative imaging features from AP, however, there have been several recent exciting developments in applying ANNs to detect pancreatic ductal adenocarcinoma, which may be translatable to AP.

In conclusion, authors try to underline the significance of recent advances in image acquisition and analysis, which offer the opportunity to go beyond morphologic features. DWI, T1, T2 mapping, radiomics and ANNs, can potentially quantify signal changes reflective of underlying tissue abnormalities for detection and classification of AP, offering the promise of uncovering imaging biomarkers for additional classification and prognostic information.

References:

1. Banks PA, Bollen TL, Dervenis C, Gooszen HG, Johnson CD, Sarr MG, et al. Classification of acute pancreatitis--2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013;62(1):102-11.
2. Shinya S, Sasaki T, Nakagawa Y, Guiquing Z, Yamamoto F, Yamashita Y. The efficacy of diffusion-weighted imaging for the detection and evaluation of acute pancreatitis. Hepato-gastroenterology. 2009;56(94-95):1407-10.
3. Thomas S, Kayhan A, Lakadamyali H, Oto A. Diffusion MRI of acute pancreatitis and comparison with normal individuals using ADC values. Emergency radiology. 2012;19(1):5-9.
4. de Freitas Tertulino F, Schraibman V, Ardengh JC, do Espírito-Santo DC, Ajzen SA, Torrez FR, et al. Diffusion-weighted magnetic resonance imaging indicates the severity of acute pancreatitis. Abdominal imaging. 2015;40(2):265-71.
5. Borens B, Arvanitakis M, Absil J, El Bouchaibi S, Matos C, Eisendrath P, et al. Added value of diffusion-weighted magnetic resonance imaging for the detection of pancreatic fluid collection infection. European radiology. 2017;27(3):1064-73.
6. Tirkes T, Lin C, Fogel EL, Sherman SS, Wang Q, Sandrasegaran K. T(1) mapping for diagnosis of mild chronic pancreatitis. Journal of magnetic resonance imaging : JMRI. 2017;45(4):1171-6.
7. Vietti Violi N, Hilbert T, Bastiaansen JAM, Knebel JF, Ledoux JB, Stemmer A, et al. Patient respiratory-triggered quantitative T(2) mapping in the pancreas. Journal of magnetic resonance imaging : JMRI. 2019;50(2):410-6.
8. Lin Q, Ji YF, Chen Y, Sun H, Yang DD, Chen AL, et al. Radiomics model of contrast-enhanced MRI for early prediction of acute pancreatitis severity. 2020;51(2):397-406.
9. Keogan MT, Lo JY, Freed KS, Raptopoulos V, Blake S, Kamel IR, et al. Outcome analysis of patients with acute pancreatitis by using an artificial neural network. Academic radiology. 2002;9(4):410-9.


Dr. Ioannis Christofilis is a fifth-year Radiology Resident at ‘Konstantopouleion’ General Hospital of Nea Ionia, Athens, Greece. He completed his undergraduate Μedical degree at University of Athens, Medical School. His main fields of interests in the area of diagnostic imaging are Abdominal and Thoracic imaging, Cardiovascular imaging and Ultrasonography.    

Comments may be sent to: ioannis.christofilis@remove-this.gmail.com


Systematic review and meta-analysis of MRI features for differentiating autoimmune pancreatitis from pancreatic adenocarcinoma

Seung Bae Yoon, Tae Yeon Jeon, Sung-Hoon Moon, Sang Min Lee, Myung-Hwan Kim.

European Radiology (2022) 32:6691–6701

Autoimmune pancreatitis (AIP) is a form of chronic pancreatitis that need to be differentiated from other types of pancreatitis such as alcoholic, hereditary or obstructive [1, 2]. Nowadays it is known that this condition has an autoimmune etiology and is not limited to the pancreas alone, but also involves organs such as bile ducts, retroperitoneum, and lymph nodes [3].

Further histological and clinical profiling of AIP revealed 2 distinct types: type 1, histological descripted as lymphoplasmacytic sclerosing pancreatitis (LPSP); and type 2, called idiopathic duct-centric pancreatitis (IDCP). Both share some histopathological features, such as periductal lymphoplasmacytic infiltrate and storiform fibrosis. A characteristic histopathologic finding of IDCP is granulocyte epithelial lesions. Instead, LPSP can lead to venulitis, with lymphocytes and plasmacells, often leading to obliteration of the affected veins, and is associated with either serum IgG4 elevation and with other organ involvement.

Extrapancreatic involvement of IDCP, reported approximately 30% of cases, is with inflammatory bowel disease.

The most frequent presentation of AIP is obstructive jaundice and/or pancreatic mass. Whereas most patients have pancreatic swelling (diffuse or focal), a few patients may show low-density pancreatic masses. The diagnosis of LPSP is made through a combination of imaging, serologic and clinical findings, making histological confirmation not mandatory. Contrarywise, since IDCP patients are seronegative and lack other organ involvement, definitive histological diagnosis is needed [4]. Both conditions respond to steroid therapy and do not need surgery [5].

The differential diagnosis with pancreatic ductal adenocarcinoma (PDAC) is challenging, especially for focal-type AIP, due to de clinical manifestations and radiological features.

A recent systematic review and meta-analysis conducted by Yoon and colleagues aimed to identify MRI features that will aid the differential diagnosis between AIP and PDAC. After an initial screening or 1214 studies, the authors included 12 retrospective studies published between January 2006 and July 2021. After reviewing 92 overlapping descriptors of MRI findings in the included studies, 16 MRI features were selected:

  • Ten favoring AIP: diffuse enlargement, capsule-like rim, multiple main pancreatic duct (MPD) strictures, homogeneous delayed enhancement, low apparent diffusion coefficient value, speckled enhancement, multiples pancreatic masses, tapered narrowing of MPD, penetrating duct sign, and delayed enhancement.
  • Six favoring PDAC: target type enhancement, discrete pancreatic mass, upstream MPD dilatation, peripancreatic fat infiltration, upstream parenchymal atrophy, and vascular involvement.

From these features, the pooled diagnostic accuracy, including the diagnostic odds ratios (DORs) with 95% confidence intervals (CIs), was calculated using a bivariate random effects model. MRI features for AIP tended towards a high specificity but low sensitivity. Among them, diffuse enlargement, capsule-like rim, multiple MPD strictures, and homogeneous delayed enhancement had the highest DORs, and showed a high pooled specificities (90–100%). Diffuse enlargement had the highest DOR; however, diffuse-type AIP can be differentiated from PDAC due to the growing awareness of imaging appearance of AIP [6]. Radiologists must be aware that pancreatic lymphoma, diffuse PDAC, or metastasis to the pancreas can also present with diffuse enlargement of the pancreas [7-8]. The capsule-like rim, representing a continuous halo-like soft tissue lesion surrounding the pancreas can be thin or thick depending on disease activity [9]. Multiple pancreatic masses and MPD strictures without intervening duct dilatation are especially helpful in the differentiation of focal-type AIP from PDAC. Delayed enhancement had low specificity compared to the “homogeneous” delayed enhancement (55% vs. 90%). Due to its desmoplastic nature, PDAC can show delayed enhancement. However, radiologists should consider the presence of homogenous enhancement when evaluating the enhancement pattern of a focal pancreatic mass in the differential diagnosis between AIP and PDAC. Penetrating duct sign has a high sensitivity (81%) and is indicative of AIP.

The Apparent Diffusion Coefficient (ADC) values are lower for AIP than PDAC, and had a relatively high sensitivity (84%) and specificity (86%). However, the cutoffs for the ADC value differed among the studies included by the authors.

On the other hand, for the diagnosis of PDAC, MRI features with the highest pooled DOR were target type enhancement and discrete pancreatic mass. The informative MRI features favoring PDAC had moderate specificity. Whereas upstream MPD dilation and upstream parenchymal atrophy had relatively high specificities (88 and 81%, respectively), with low sensitivities (46-59%, respectively).

The results of the current study are important as they provide informative MRI features with their diagnostic performance that may help the radiologists in the differential diagnosis between AIP and PDAC, which can be particularly challenging in clinical practice.

In conclusion, MRI features summarized in this study may aid in the detection and accurate differentiation of AIP from PDAC, in combination with serologic, extra-pancreatic involvement and clinical features.

References:

  1. Klöppel G, Detlefsen S, et al. Autoimmune pancreatitis: the clinicopathological characteristics of the subtype with granulocytic epithelial lesions. J Gastroenterol. 2010;45:787–793.
  2. Yoshida K, Toki F, et al. Chronic pancreatitis caused by an autoimmune abnormality. Proposal of the concept of autoimmune pancreatitis. Dig Dis Sci. 1995;40:1561–8. 
  3. Fan BG, Andrén-Sandberg A, et al. Autoimmune pancreatitis. N Am J Med Sci. 2009;1:148-51.
  4. Shimosegawa T, Chari TS, et al. International Consensus Diagnostic Criteria for Autoimmune Pancreatitis: Guidelines of the International Association of Pancreatology. Pancreas: April 2011 - Volume 40 - Issue 3 - p 352-358.
  5. Javed AA, Wright MJ, Ding D et al. Autoimmune pancreatitis: a critical analysis of the surgical experience in an era of modern diagnostics. Pancreas. 2021;50:556–563.
  6. Lee S, Kim JH, Kim SY et al. Comparison of diagnostic performance between CT and MRI in differentiating non-diffuse type autoimmune pancreatitis from pancreatic ductal adenocarcinoma. Eur Radiol. 2018;28:5267–5274.
  7. Choi YJ, Byun JH, Kim JY et al. Diffuse pancreatic ductal adenocarcinoma: characteristic imaging features. Eur J Radiol. 2008;67: 321–328.
  8. Ishigami K, Tajima T, Nishie A et al. MRI findings of pancreatic lymphoma and autoimmune pancreatitis: a comparative study. Eur J Radiol 2010:74:e22–e28.
  9. Sahani DV, Sainani NI, Deshpande V, Shaikh MS, Frinkelberg DL, Fernandez-del Castillo C. Autoimmune pancreatitis: disease evolution, staging, response assessment, and CT features that predict response to corticosteroid therapy. Radiology. 2009;250:118–129.


Dr.  Mario Pace is a fourth-year radiology resident at the University of Palermo in Italy. During his student carrier he was at the Department of Cardiology, Nephrology, Gastroenterology and Endocrinology of the “University Medical Center” in Slovenia and at the Department of Gynecology of the “Hospital San Martin” of La Plata  in Argentina. His main interests are abdominal and musculoskeletal radiology, in fact he had a fellowship of 6 month to the IRCCS AOU San Marino in order to improve the knowledge of musculoskeletal and peripheral nerve system.

Comments may be sent to 91mariopace@remove-this.gmail.com


Identifying high-risk colon cancer on CT an a radiomics signature improve radiologist’s performance for T staging?

Eun Kyoung Hong, Zuhir Bodalal, Federica Landolf, Nino Bogveradze, Paula Bos, Sae Jin Park, Jeong Min Lee, Regina Beets-Tan

Abdominal Radiology (2022) 47:2739–2746.

Colon cancer is the third most common malignancy and the fourth most common cause of cancer-related death [1]. Accurate staging and identification of high-risk colon cancer is crucial to avoid overtreatment and unnecessary exposure of low-risk patients to higher morbidity of surgical resection after preoperative treatment [2]. Based on published works, radiomics can provide us with quantitative imaging information to describe the comprehensive morphological features of the tumor, which can help and guide clinicians [1, 2, 3, 4]. Regarding the role of radiomics in colon cancer, most studies have investigated the role in terms of survival, lymph node metastasis, and molecular/genetic subtype prediction. Not much is known about radiomics application in risk stratification for colon cancer [2, 4, 5].

The aim of this retrospective study [2] was, firstly, to assess the additional value of radiomics features that were automatically extracted from pre-operative colon cancer CT in distinguishing high-risk colon cancer patients. Secondly, the purpose was to develop a combined model integrating both radiomic and conventional CT staging features for the prediction of high-risk colon cancer.

The authors used a sample of 292 patients (205 from Seoul National University Hospital and 87 from Netherlands Cancer Institute) with colon cancer (85 patients with ≤ T2 and 207 patients with ≥ T3 primary tumor) who received surgical resection and with pre-operative imaging within 60 days of surgery. Exclusion criteria were: neoadjuvant therapy, inadequate pathologic data, multiple primary tumors, non-visible tumor on CT, and poor quality CT. The radiologists noted the presence of the tumor beyond the muscularis propria layer of tumors (cT3-T4), blinded by all the clinical and histological information. Further, 6048 radiomic features were automatically extracted, and after applying an unsupervised dimensionality reduction technique, orthogonal principal feature analysis, only 29 features were selected and included for further analysis.

Univariate and multivariate logistic regression analysis was performed to determine the significant association between imaging features, CT staging and pathologic staging of colon cancer in differentiating tumor staging ≤ T2 vs.  ≥ T3. Afterwards, using logistic regression, elastic net regularization and 10-fold cross validation, the authors developed different predictive models for each outcome. ROC curve analysis was conducted and area under the curve (AUC) with DeLong confidence interval (CI) was calculated to evaluate the performance of each model.

Results show that radiologist’s performance in CT staging of colon cancer was significantly associated with high pT tumors from both univariate (OR = 6.16, p < 0.001) and multivariate (OR = 1.22, p < 0.001) logistic regression analysis. The AUC value of CT staging was 0.697 (95% CI 0.638-0.756). Moreover, when radiomic features were added to the model, AUC increased to 0.779 (95% CI 0.720-0.839). From the 10-fold cross-validation, CT staging demonstrated AUC of 0.628 (95% CI 0.558-0.689) and increased to 0.727 (95% CI 0.621-0.777) when radiomic features were included.

These results of this study show that CT radiomic features could improve the radiologist’s performance in T staging colon cancer on CT, and using the combined model using both CT staging and radiomic features demonstrated significantly better diagnostic performance [2]. But, the integration of these combined models and radiomic scores in a clinical validation stage would require extensive multicenter prospective studies to prove their generalizability.

Neoadjuvant chemotherapy for locally advanced colon cancer remains an evolving treatment paradigm [6]. The FOxTROT trial, an international randomized controlled trial of 1052 patients evaluating neoadjuvant chemotherapy for colon cancer, used CT as a reliable tool for stratifying high-risk patients. The trial reported that 98% of patients undergoing neoadjuvant chemotherapy underwent surgery compared with 99% of patients who did not have neoadjuvant treatment, a reassuringly similar rate [7].

CT is already a routine part of preoperative staging of colon cancer, but in the context of documenting extracolonic disease [6]. A meta-analysis reported a sensitivity of 90%, and specificity of 69%, in differentiating stage T3 and T4 tumors on CT [8], which currently serves as the major selection criteria for patients with high-risk colon tumors who will receive neoadjuvant chemotherapy [9].

In conclusion, accurate pre-surgical staging of colon cancer is crucial for pre-operative chemotherapy, but the addition of radiomics/artificial intelligence approaches can help to build models that hold significant promise for integrated diagnosis and clinical decision making.

References:

  1. Mármol I, Sánchez-de-Diego C, Pradilla Dieste A, Cerrada E, Rodriguez Yoldi MJ. Colorectal Carcinoma: A General Overview and Future Perspectives in Colorectal Cancer. Int J Mol Sci. 2017 Jan 19;18(1):197. doi: 10.3390/ijms18010197.
  2. Hong EK, Bodalal Z, Landolfi F, Bogveradze N, Bos P, Park SJ, Lee JM, Beets-Tan R. Identifying high-risk colon cancer on CT and a radiomics signature improve radiologist's performance for T staging? Abdom Radiol (NY). 2022 Aug;47(8):2739-2746. doi: 10.1007/s00261-022-03534-0.
  3. Moldovanu CG, Boca B, Lebovici A, Tamas-Szora A, Feier DS, Crisan N, Andras I, Buruian MM. Preoperative Predicting the WHO/ISUP Nuclear Grade of Clear Cell Renal Cell Carcinoma by Computed Tomography-Based Radiomics Features. J Pers Med. 2020 Dec 23;11(1):8. doi: 10.3390/jpm11010008.
  4. Yao X, Sun C, Xiong F, Zhang X, Cheng J, Wang C, Ye Y, Hong N, Wang L, Liu Z, Meng X, Wang Y, Tian J (2020) Radiomic signature-based nomogram to predict disease-free survival in stage II and III colon cancer. Eur J Radiol 131:109205. doi:10.1016/j.ejrad.2020.109205.
  5. Huang YQ, Liang CH, He L, Tian J, Liang CS, Chen X, Ma ZL, Liu ZY (2016) Development and Validation of a Radiomics Nomogram for Preoperative Prediction of Lymph Node Metastasis in Colorectal Cancer. J Clin Oncol 34 (18):2157-2164. doi:10.1200/JCO.2015.65.9128.
  6. Body A, Prenen H, Latham S, Lam M, Tipping-Smith S, Raghunath A, Segelov E. The Role of Neoadjuvant Chemotherapy in Locally Advanced Colon Cancer. Cancer Manag Res. 2021 Mar 17;13:2567-2579. doi: 10.2147/CMAR.S262870.
  7. Seymour M.T., Morton D., on behalf of the International FOxTROT Trial Investigators FOxTROT: An international randomised controlled trial in 1052 patients (pts) evaluating neoadjuvant chemotherapy (NAC) for colon cancer. J. Clin. Oncol. 2019;37:3504. doi: 10.1200/JCO.2019.37.15_suppl.3504.
  8. Nerad E, Lahaye MJ, Maas M, Nelemans P, Bakers FC, Beets GL, Beets-Tan RG (2016) Diagnostic Accuracy of CT for Local Stag-ing of Colon Cancer: A Systematic Review and Meta-Analysis. AJR Am J Roentgenol 207 (5):984-995. doi: 10.2214/AJR.15.15785.
  9. Foxtrot Collaborative G (2012) Feasibility of preoperativechemotherapy for locally advanced, operable colon cancer: the pilot phase of a randomised controlled trial. Lancet Oncol 13(11):1152-1160. doi: 10.1016/S1470-2045(12)70348-0.


Moldovanu Claudia-Gabriela is a young radiologist who has just completed her residency program at Emergency County Clinical Hospital in Cluj-Napoca, Romania. Her main areas of interest are abdominal and urogenital radiology and the use of artificial intelligence in radiology. She has been actively involved in clinical imaging research, contributing as author/co-author to many projects leading to conference presentations, publications and awards. She also recently completed her Ph.D. thesis with research focused on the role of artificial intelligence in medical diagnosis.

Comments may be sent to: moldovanucg@gmail.com

 


MRI follow‑up for pancreatic intraductal papillary mucinous neoplasm: an ultrashort versus long protocol

Johansson K, Mustonen H, Nieminen H, Haglund C, Lehtimäki TE, Seppänen H.

Abdom Radiol (NY). 2022 Feb;47(2):727-737. doi: 10.1007/s00261-021-03382-4.

Intraductal papillary mucinous neoplasms (IPMNs) are mucin-producing tumors that arise from the pancreatic duct and are considered precursor lesions to pancreatic cancer [1]. There are three types of IPMNs differentiated based on morphologic differences.

with different risk profiles for malignant transformation. The Main duct IPMNs (MD-IPMN) are characterized by involvement with the main pancreatic duct (MPD) and identified by a dilated MPD (5 mm) without an associated cyst or other cause for ductal obstruction. Branch duct IPMNs (BD-IPMN) arise from a branch of the MPD and are identified as unilocular or multilocular pancreatic cysts with communication with the MPD, which measures <5 mm. Mixed-type IPMNs (MT-IPMN) meet the criteria for both MD and BD IPMNs [2].

Given that approximately an average of 8% of all pancreatic cancers arise from these lesions, IPMN follow-up offers an opportunity for early cancer detection [3]. Most IPMNs are accidentally detected when abdominal imaging is performed for another indication, as they are mostly asymptomatic. The presence of some clinical symptoms, such as abdominal pain or bloating, has been associated with malignant transformation in patients with IPMNs [4, 5].  Abdominal MR and MR cholangiopancreatography (MRCP) is the investigation of choice for initial characterization and follow-up of IPMN, thanks to its high contrast and spatial resolution and lack of ionizing radiation. However, MR examinations suffer from long acquisition time and, the spreading of MR short and ultra-short protocols is reaching interest also in IPMNs follow-up; however, the possibility to optimize MR protocols for IPMNs follow-up needs to be investigated [6].

The authors of the present study aimed to assess whether an MR ultrashort magnetic protocol (USP) that includes only axial T2-weighted half-Fourier single-shot turbo spin-echo (HASTE) sequences and 3D MRCP sampling perfection with application-optimized contrasts using different flip angle evolution (SPACE) sequences is comparable in terms of diagnostic accuracy with longer protocols in the identification of worrisome features (WF) and high-risk stigmata (HRS) and, in the measurement of the major diameter of the largest cyst and main pancreatic duct (MPD). Reductions in cost and time related to USP were also assessed.

This retrospective study included a final population of 112 surveillance patients evaluated for pancreatic cysts at Helsinki University Hospital who underwent examination with 1.5 Tesla MRI. Three MRI datasets were analyzed including USP as abovementioned then, long protocol (LP) including axial T2-weighted HASTE with and without fat saturation (fs), thin and thick coronal T2-weighted HASTE fs, axial T1-weighted fast low angle shot (FLASH) fs, axial T1-weighted in/opposed phase, T2-weighted 3D MRCP SPACE and maximum intensity projection (MIP) reconstruction, diffusion-weighted imaging (DWI), and T1-weighted fs volumetric interpolated breath-hold (VIBE) before and after the administration of the contrast agent; and, finally short protocol (SP) including axial T2-weighted HASTE, thin and thick coronal T2-weighted HASTE fs, axial T1-weighted FLASH fs,  3D MRCP SPACE, and MIP.

Two radiologists evaluated the three datasets for each patient in a random order to reduce recall bias. The following parameters were evaluated from the datasets: cyst and MPD size, cystic and MPD mural nodules, abrupt change in the MPD caliber, distal parenchymal atrophy, lymph node enlargement, and a solid pancreatic tumor presence. The WF and HRS analysis included cystic and MPD mural nodules, an MPD size of ≥ 5 mm, an abrupt change in the MPD caliber with distal pancreatic atrophy, a cyst of ≥ 3 cm, and/or lymphadenopathy.

Results showed agreement between longer protocols and USP for cystic mural nodules, MPD mural nodules, solid pancreatic tumor, and WF/HRS (94.9%, 99.1%, 99.1%, 92.4% respectively). Non-significant differences were reported in the largest cyst measurement nor in the mean MPD value.  In addition, no significant systematic bias in the difference between methods and the confidence intervals was observed.

Then, all true cases were identified using USP and S-LP, and all three datasets led to identifying true cystic mural nodules. All the measurements performed showed an agreement from moderate to strong between the two readers. 

Regarding time and cost analysis total sequence acquisition time was on average 23 minutes for LP, 13 minutes for SP, and 7 minutes for USP, while USP was estimated, based on Hospital costs, as 77% that of SP and 39% of LP.

Despite the interesting results, this study had some limitations such as the retrospective nature, the lack of complete sampling of IPMN with WS/HRS also due to the conservative approach in an elderly population, lack of analysis performed with 3.0T that might differ from 1.5T,  and the aspect related to the different costs between three protocols that were estimated at the University Hospital of Helsinki, and, therefore, price variations may exist between hospitals and countries.

The study carried out and the results obtained could be very relevant in clinical practice in terms of time and cost saving, without affecting diagnostic assessment. Enabling the use of USP for surveillance of IPMN without  WF/HRS might allow for improving clinical workflow without the risk of missing important diagnostic information.

References:
1. Keane MG, et al. A Review of the Diagnosis and Management of Premalignant Pancreatic Cystic Lesions. J Clin Med. 2021 Mar 19;10(6):1284.

2. Furukawa T, et al. Classification of types of intraductal papillary-mucinous neoplasm of the pancreas: a consensus study. Virchows Arch. 2005 Nov;447(5):794-9.

3. Pergolini I, et al. Long-term Risk of Pancreatic Malignancy in Patients With Branch Duct Intraductal Papillary Mucinous Neoplasm in a Referral Center. Gastroenterology. 2017 Nov;153(5):1284-1294.e1.

4. Fernández-del Castillo C, at al. Incidental pancreatic cysts: clinicopathologic characteristics and comparison with symptomatic patients. Arch Surg. 2003 Apr;138(4):427-3; discussion 433-4.

5. Kim JR, at al. Clinical implication of serum carcinoembryonic antigen and carbohydrate antigen 19-9 for the prediction of malignancy in intraductal papillary mucinous neoplasm of pancreas. J Hepatobiliary Pancreat Sci. 2015 Sep;22(9):699-707.

6. Delaney FT, at al. An abbreviated MRI protocol for surveillance of cystic pancreatic lesions. Abdom Radiol (NY). 2021 Jul;46(7):3253-3259.


Dr. Carlotta Rucci is a radiology resident at "Sapienza" University of Rome - Sant'Andrea University Hospital in Rome, attending the fourth year of residency. Her main fields of interest in the area of diagnostic imaging are Abdominal Oncologic Imaging, Cardiovascular Imaging and, Breast Imaging. She has also been actively involved in clinical imaging research, and she has contributed as a co-author in some publications.

Comments may be sent to carlotta.rucci@remove-this.uniroma1.it


Management and follow‐up of gallbladder polyps: updated joint guidelines between the ESGAR, EAES, EFISDS and ESGE

Kieran G. Foley1 · Max J. Lahaye2 · Ruedi F. Thoeni3 · Marek Soltes4 · Catherine Dewhurst5 · Sorin Traian Barbu6 · Yogesh K. Vashist7 · Søren Rafael Rafaelsen8 · Marianna Arvanitakis9 · Julie Perinel10 · Rebecca Wiles11 · Stuart Ashley Roberts12

European Radiology  volume 32, pages 3358–3368 (2022)

Incidental gallbladder polyps are a common sonographic finding, occurring in approximately 3–6% of the general population [1]. Although most are benign cholesterol polyps or inflammatory polyps, a small percentage of them are true neoplastic polyps. Despite gallbladder cancer being a relatively infrequent diagnosis [2], detection of malignancy at an early stage of disease is critical to improve survival rates because gallbladder cancer is associated with a poor prognosis [3].

The original guidelines for the management of gallbladder polyps were released in 2017. In this paper, the authors updated the European guidelines by incorporating new evidence regarding the management of gallbladder polyps into its recommendations. They made 8 recommendations that we will summarize. Recommendations 1 to 7 have changed from the previous guidance, whereas recommendation 8 is unchanged.

1. Primary investigation of polypoid lesions of the gallbladder should be with abdominal ultrasound. Routine use of other imaging modalities is not recommended presently, but further research is needed. In centers with appropriate expertise and resources, alternative imaging modalities (such as contrast-enhanced and endoscopic ultrasound) may be useful to aid decision-making in difficult cases.
Since the original guidelines, several studies have explored the potential of alternative modalities for detecting gallbladder polyps and differentiating dysplastic malignant from benign polyps. Although some techniques, like high-resolution ultrasound (HRUS), endoscopic ultrasound (EUS), contrast-enhanced ultrasound (CEUS), magnetic resonance imaging (MRI) and positron emission tomography (PET), tried to improve the detection of pre-malignant and malignant lesions, a size greater than 1 cm remained a factor independently associated with a neoplastic polyp [4; 5].

2. Cholecystectomy is recommended in patients with polypoid lesions of the gallbladder measuring 10 mm or more, providing the patient is fit for, and accepts, surgery. Multidisciplinary discussion may be employed to assess perceived individual risk of malignancy.
Several studies have investigated alternative size thresholds at which to intervene, but the overall quality of evidence remains low. In the absence of an alternative size threshold with better evidence, the group chose to leave the 10 mm threshold unchanged. Multidisciplinary team meetings were introduced in this update to discuss the best management of individual patients.

3. Cholecystectomy is suggested if no alternative cause for the patients symptoms is demonstrated and the patient is fit for, and accepts, surgery. The patient should be counseled about the benefit of cholecystectomy versus the risk of persistent symptoms. There was limited and low-quality evidence regarding the value of cholecystectomy, in patients with symptoms potentially attributable to the gallbladder.  One study reported that 61% symptomatic patients reported ongoing pain after their cholecystectomy [6].  So, in this update the group emphasized that symptomatic patients with gallbladder polyps should be counseled about the potential benefits of cholecystectomy versus the risks of persistent pain.

4.If the patient has a 6–9 mm polypoid lesion of the gallbladder and one or more risk factors for malignancy, cholecystectomy is recommended if the patient is fit for, and accepts, surgery.
These risk factors are:

  • Age more than 60 years old;
  • History of primary sclerosing cholangitis (PSC);
  • Asian ethnicity;
  • Sessile polypoid lesion (including focal gallbladder wall thickening > 4 mm).

A systematic review [7], which included 5,482 gallbladder polyps, identified the age threshold of more than 60 years as a significant risk factor for malignancy, resulting in the update of the age threshold (vs 50 years in the 2017 guidelines). In previous recommendations, only Indian ethnicity was considered a risk factor, however more recent reviews [8] suggested that the entire Asian population is at increased risk.

5. If the patient has either:

  • No risk factors for malignancy and a gallbladder polypoid lesion of 6–9 mm
  • Risk factors for malignancy and a gallbladder polypoid lesion 5 mm or less

Follow-up ultrasound of the gallbladder is recommended at 6 months, 1 year and 2 years. Follow-up should be discontinued after 2 years in the absence of growth.
The preview guidelines suggested that follow-up ultrasound is recommended at 6 months, 1 year and then yearly up to 5 years in these cases. In this update, the authors suggested that a limited strategy of one or two follow-up ultrasound investigations in the subsequent 1–2 years is sufficient to provide adequate reassurance for patients and clinicians, emphasizing that monitoring should be reserved for those who are potentially fit for surgery.

6. If the patient has no risk factors for malignancy, and a gallbladder polypoid lesion of 5 mm or less, follow-up is not required.
Previously, it was suggested that these patients were re-evaluated by ultrasound at 1 year, 3 years and 5 years. Although a few cases of gallbladder cancer in polyps measuring 5 mm or less have been reported in the literature to date, the group felt that a pragmatic approach to small gallbladder polyps was necessary, and, as such, do not recommend follow up for gallbladder polyps measuring 5 mm or less. New data reported by Szpakowski and Tucker [9] was considered insufficient justification for follow-up.

7. If during follow-up the gallbladder polypoid lesion reaches 10 mm, then cholecystectomy is advised. If the polypoid lesion grows by 2 mm or more within the 2-year follow-up period, then the current size of the polypoid lesion should be considered along with patient risk factors. Multidisciplinary discussion may be employed to decide whether continuation of monitoring, or cholecystectomy, is necessary.
Szpakowski and Tucker [9] provided the best evidence to date that slow growth is part of the natural history of gallbladder polyps. Their study reported that the cumulative probability of a gall- bladder polyp growing by 2 mm or more at 10 years was small. For this reason, in these guidelines, this recommendation was changed, and cholecystectomy was not advised for all patients with polyp growth.

8. If during follow-up the gallbladder polypoid lesion disappears, then monitoring can be discontinued.
This recommendation is unchanged from the previous guidance.

Conclusion:
Systematic reviews and large observational studies described above have been published since the previous version of the guidelines, in an attempt to discover important answers to these challenging clinical questions.
The substantial knowledge gained over the past several years has shown that aggressive follow-up and treatment of incidentally identified small gallbladder polyps may be unwarranted.
These revised guidelines from the ESGAR, EAES, EFISDS and ESGE are very important because they allow radiologists to stay up to date, optimize the use of resources and to provide the best and most up-to-date care for their patients.

References:
1. Aldouri AQ, Malik HZ, Waytt J, et al. The risk of gallbladder cancer from polyps in a large multiethnic series. Eur J Surg Oncol 2009;35(1):48–51.
2. Sung H, Ferlay J, Siegel RL et al (2021) Global Cancer Statis- tics 2020: GLOBOCAN Estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71(3):209–249
3. Misra MC, Guleria S (2006) Management of cancer gallbladder found as a surprise on a resected gallbladder specimen. J Surg Oncol 93(8):690–698
4. Kim JH, Lee JY, Baek JH et al (2015) High-resolution sonogra- phy for distinguishing neoplastic gallbladder polyps and staging gallbladder cancer. AJR Am J Roentgenol 204(2):W150-159
5. Zhang H-P, Bai M, Gu J-Y, He Y-Q, Qiao X-H, Du L-F (2018) Value of contrast-enhanced ultrasound in the differential diagnosis of gallbladder lesion. World J Gastroenterol 24(6):744–751
6. Aliyazicioglu T, Carilli S, Emre A et al (2017) Contribution of gallbladder polyp surgery to treatment. Eur Surg Acta Chirurgica Austriaca 49(1):23-26
7. Elmasry M, Lindop D, Dunne DFJ, Malik H, Poston GJ, Fenwick SW (2016) The risk of malignancy in ultrasound detected gallbladder polyps: a systematic review. Int J Surg 33(PtA):28-35
8. Babu BI, Dennison AR, Garcea G (2015) Management and diagnosis of gallbladder polyps: a systematic review. Langenbecks Arch Surg 400(4):455-462
9. Szpakowski J-L, Tucker L-Y (2020) Outcomes of gallbladder polyps and their association with gallbladder cancer in a 20-year cohort. JAMA Network Open 3(5):e205143

 

Dr. Pedro Maganinho is a third-year Radiology resident at the Centro Hospitalar Universitário do Porto, in Portugal. He has a wide range of interests in diagnostic imaging including abdominal and gastrointestinal radiology.
Comments may be sent to: pmaganinho@remove-this.gmail.com

 


Imaging of Bowel Ischemia: An Update, From the AJR Special Series on Emergency Radiology

Michael C. Olson, Corrie R. Bach, Michael L. Wells, James C. Andrews, Ashish Khandelwal, Christopher L. Welle and Jeff L. Fidler

American Journal of Roentgenology: -. 10.2214/AJR.22.28140  https://www.ajronline.org/doi/abs/10.2214/AJR.22.28140

 

Intestinal ischemia represents an important pathological entity that still represent a challenging diagnosis for the Emergency Radiologist. This review article describes various common causes of mesenteric ischemia and provides to illustrate the multimodality imaging findings, especially CT that could be considered the first diagnostic tool in acute conditions.

After anatomical description of the mesenteric vasculature, the Authors considered the arterial thromboembolism, the mesenteric vein thrombosis and the nonocclusive mesenteric ischemia. The most common cause of acute mesenteric ischemia is represented by an arterial embolic disease that accounts for up to 50% of cases [1] and often results from underlying cardiovascular disease (e.g., atrial fibrillation or thrombi that form from a preceding myocardial infarction) [2]. The Authors specified that the superior mesenteric artery (SMA) is particularly susceptible to emboli due to its high flow rate and narrow branching angle from the aorta. Emboli often lodge 3-10 cm distal to the SMA origin, near the takeoff of the middle colic artery, which results in sparing of inferior pancreaticoduodenal branches and preservation of inflow to the proximal jejunum [3, 4]. A small proportion (approximately 15%) of emboli occur at the SMA orifice, which, in the absence of robust collateral circulation, may result in catastrophic small bowel ischemia. Thrombotic occlusion could be considered the second-most common cause of acute mesenteric ischemia, responsible for 20-30% of cases [5, 6]. The mesenteric venous thrombosis appears to be responsible of 5-20% of cases of acute mesenteric ischemia and is more frequently encountered in younger patient populations [2, 4]. Risk factors include, among others, some hypercoagulable states, such as those caused by Factor V Leiden mutation or deficiencies in proteins S, protein C, and antithrombin [22]. The superior mesenteric vein (SMV) and portal vein are commonly involved, and symptoms are more likely to develop in patients with thrombosis of peripheral mesenteric venous branches [5].

The review article also considers in a special section other entities such as the ileus, the strangulating bowel obstructions, the reperfusion findings as well as the colonic ischemia. Various imaging technique, from conventional radiograph to CT and CTA are considered, with special notes regarding the Dual Energy technique, protocols and advantages [7]. In conclusion, this review could provide a general critical approach to an important clinical question of mesenteric ischemia for the radiologist.

Distinction between ischemia (that could be a total reversible event) and infarction (irreversible, with death of the involvement intestinal segment) of the small and large intestines have been previously considered and described in literature [8,9]. The sequentiality of the ischemic damage and respective imaging findings (mainly CT) in different phases (from early ischemia to late infarction) and knowledge of the physiologic response of the intestinal wall to the vascular injury could be important to consider when scanning patients with suspected mesenteric ischemia. Whereas the “chronicity” of the ischemic event could be debatable to consider and distinguish, the acute findings related to bowel wall injury from impaired venous drainage or arterial etiology must be well known to avoid mistakes and delay in diagnosis.

CT imaging findings related to ischemia and infarction in patients with intestinal obstruction have been also specifically described in literature [10] and the relevance to be able to distinguish the early ischemic complication is critically important for the referring surgeon to plan the correct time for the surgical therapy.

 

References:

 

  1. Bjorck M, Koelemay M, Acosta S, et al. Editor's Choice - Management of the Diseases of Mesenteric Arteries and Veins: Clinical Practice Guidelines of the European Society of Vascular Surgery (ESVS). Eur J Vasc Endovasc Surg 2017; 53:460-510
  2. Kanasaki S, Furukawa A, Fumoto K, et al. Acute Mesenteric Ischemia: Multidetector CT Findings and Endovascular Management. Radiographics 2018; 38:945-961
  3. Bobadilla JL. Mesenteric ischemia. Surg Clin North Am 2013; 93:925-940, ix
  4. Garzelli L, Nuzzo A, Copin P, et al. Contrast-Enhanced CT for the Diagnosis of Acute Mesenteric Ischemia. AJR Am J Roentgenol2020; 215:29-38
  5. Gnanapandithan K, Feuerstadt P. Review Article: Mesenteric Ischemia. Curr Gastroenterol Rep2020; 22:17
  6. Expert Panels on Vascular I, Gastrointestinal I, Ginsburg M, et al. ACR Appropriateness Criteria R Imaging of Mesenteric Ischemia. J 2018; 15:S332-S340
  7. Olson MC, Lubner MG, Menias CO, et al. Venous Thrombosis and Hypercoagulability in the Abdomen and Pelvis: Causes and Imaging Findings. Radiographics 2020; 40:875-894
  8. Romano S, Niola R, Maglione F, Romano L. Small bowel vascular disorders from arterial etiology and impaired venous drainage. Radiol Clin N Am 2008: 46 891-908
  9. Romano S, Lassandro F, Scaglione M et al. Ischemia and infarction of the small bowel and colon: spectrum of imaging findings. Abdom Imaging 2006: 31(3) 277-292
  10. Romano S, Bartone G, Romano L. Ischemia and infarction of the intestine related to obstruction. Radiol Clin N Am 2008: 46: 925-942

 

Dr. Vlastimil Valek is a third-year radiology resident at the University Hospital Brno, Czech Republic. His main interests include gastro-intestinal (especially imaging of inflammatory bowel diseases), hepato-pancreato-biliary radiology and related non-vascular diagnostic and therapeutic interventions.

Comments may be sent to: Valek.Vlastimil2@remove-this.fnbrno.cz


Diagnostic performance of MRI for staging peritoneal metastases in patients with colorectal cancer after neoadjuvant chemotherapy

Rijsemus CJV, Kok NFM, Aalbers AGJ, Buffart TE, Fijneman RJA, Snaebjornsson P, Engbersen MP, Lambregts DMJ, Beets-Tan RGH, Lahaye MJ

Eur J Radiol. 2022 Apr;149:110225 doi: 10.1016/j.ejrad.2022.110225

 

Peritoneal metastases (PM) affect up to 30% of colorectal cancer (CRC) patients and remain the second leading cause of death after liver metastases (1,2).

The extent of PM is assessed by the peritoneal cancer index (PCI), which provides a measurement of the volume and extent of metastases. The PCI score combines the distribution of peritoneal implants at 13 abdominal and pelvic regions with the tumor size, being the most important and precise quantitative prognostic factor of peritoneal disease (3,4). Patients are eligible to undergo surgical cytoreduction (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) if PCI score is < 21, taking into account their location (5). Unfortunately, computed tomography (CT) underestimates the extent of PM and therefore it is not an accurate method to select patients who may benefit from CRS. With CT, small peritoneal nodules are often indistinguishable from the adjacent surrounding tissues, resulting in reduced sensitivity for peritoneal carcinomatosis (6).

Recent evidence has shown that abdominopelvic magnetic resonance imaging (MRI), including DW-MRI and gadolinium-enhanced MRI, significantly improves the staging and treatment in patients with PM from colorectal cancer (PM-CRC) due to its high accuracy in assessing PCI, compared to CT (7,8). While the diagnostic performance of DW-MRI to assess the PCI in patients with PM-CRC has been evaluated with good results, there are no studies that aimed to investigate PM-CRC after neoadjuvant chemotherapy (NACT).

This single center retrospective study was conducted at the Netherlands Cancer Institute in Amsterdam, a tertiary referral center for peritoneal surface oncology. The aim of this study was to evaluate diagnostic performance of DW-MRI in reassessing the PCI after NACT for patients with PM from colorectal cancer or appendiceal cancer who are potential candidates for CRS-HIPEC. The study included 47 patients from January 2016 until February 2021.

Two abdominal radiologists evaluated the PCI on restaging DW-MRI (mriPCI) and assessed the peritoneal lesions as suspicious if they were identifiable as solid or mucinous lesions on non-enhanced T2-weighted and gadolinium-enhanced T1-weighted images or as an area with diffusion restriction in DW-MRI imaging. The reference standard was PCI at surgery (sPCI). In all patients, sPCI was established by diagnostic laparoscopy, staging laparotomy or CRS-HIPEC. If CRS-HIPEC was performed, resected peritoneal lesions were evaluated and correlated with final pathological PCI (pPCI).

14 out of 47 patients were excluded because they had undergone surgery more than 42 days after the MRI scan; 33 out of 47 patients were eligible for inclusion. 19 out of 33 patients received 2 to 4 cycles of chemotherapy and 14 out of 33 received more than 4 cycles. Both readers correctly detected all 23 patients with resectable disease; however, the unresectable patients were not all correctly identified. The first reader detected 8 out of 10 unresectable patients (sensitivity 100% and specificity 80%) while the second reader identified 4 out of 10 unresectable patients (sensitivity 100% and specificity 40%).

The correlation between sPCI and mriPCI was 0.82 (0.66-0.91) for the reader 1 and 0.67 (0.43-0.82) for the reader 2. Six patients (26.1%) had pPCI of 0, indicating a complete regression of all resected lesions without any vital tumor remnants; five of these patients with complete response had a mriPCI of 3 or less.

Interestingly, this study corroborates in colorectal cancer the results of Jonsdottir et al. in which a group of patients with ovarian cancer underwent NACT before DW-MRI staging in the absence of significant differences between mriPCI and sPCI (7,9). This study shows that DW-MRI is an accurate diagnostic tool in determining the PCI after NACT because it could accurately select those patients in which a CRS-HIPEC was feasible; all patients with resectable disease were detected with MRI.

In conclusion, MRI appears to be a reliable and promising tool for determining the extent of PM in order to improve patient and treatment selection after NACT. The main limitation of the study is the retrospective design and the small sample size; validation with a greater number of patients receiving NACT for PM is therefore necessary.

 

References:

 

  1. Cao C, Yan TD, Black D, Morris DL. A systematic review and meta-analysis of cytoreductive surgery with perioperative intraperitoneal chemotherapy for peritoneal carcinomatosis of colorectal origin. Ann Surg Oncol. 2009;16:2152–65.
  2. Koppe MJ, Boerman OC, Oyen WJ, Bleichrodt RP. Peritoneal carcinomatosis of colorectal origin: incidence and current treatment strategies. Ann Surg. 2006;243:212–22.
  3. Sugarbaker P, Ryan D. Cytoreductive surgery plus HIPEC to treat peritoneal metastases from colorectal cancer: standard of care or an experimental approach? Lancet Oncol. 2012;13:362–9.
  4. Cashin PH, Graf W, Nygren P, Mahetme H. Cytoreductive surgery and intraperitoneal chemotherapy for colorectal peritoneal carcinomatosis: prognosis and treatment of recurrences in a cohort series. Eur J Surg Oncol. 2012;38:509–15.
  5. Chua T, Esquivel J, Pelz J, Morris D. Summary of current therapeutic options for peritoneal metastases from colorectal cancer. J Surg Oncol. 2013;107:566–73.
  6. Koh JL, Tan TD, Glenn D, Morris DL. Evaluation of preoperative computed tomography in estimating peritoneal cancer index in colorectal peritoneal carcinomatosis. Ann Surg Oncol. 2009;16:327–33
  7. van 't Sant, I., et al., Diffusion-weighted MRI assessment of the peritoneal cancer index before cytoreductive surgery. Br J Surg. 2019 Mar;106(4):491-498.
  8. Low, R.N. and R.M. Barone, Combined diffusion-weighted and gadolinium-enhanced MRI can accurately predict the peritoneal cancer index preoperatively in patients being considered for cytoreductive surgical procedures. Ann Surg Oncol, 2012. 19(5): p. 1394-1401.
  9. B. Jonsdottir, M.A. Ripoll, A. Bergman, I. Silins, I.S. Poromaa, H. Ahlstro ̈m, K. Stålberg, Validation of 18F-FDG PET/MRI and diffusion-weighted MRI for estimating the extent of peritoneal carcinomatosis in ovarian and endometrial cancer -a pilot study, Cancer Imag. 21 (1) (2021).

 

Dr. Sergio Ruggiero is a second-year radiology resident at Sapienza University of Rome and an ESGAR member. He has graduated at the University Campus Bio-Medico of Rome with merit in June 2020. He has a wide range of interests in diagnostic imaging and plans to subspecialize in abdominal and gastrointestinal radiology. As a junior resident, he aspires to continuously learn and consolidate his radiological knowledge.

Comments may be sent to: s.ruggiero94@remove-this.gmail.com


Incidence of pancreatic cancer during long‐term follow‐up in patients with incidental pancreatic cysts smaller than 2 cm

Masoud Nakhaei · Mathew Bligh · Victoria Chernyak · Abraham F. Bezuidenhout · Alexander Brook · Olga R. Brook

Eur Radiol 32, 3369–3376 (2022) doi: 10.1007/s00330-021-08428-1

 

Pancreatic cysts are frequent finding in patients undergoing cross-sectional imaging for non-pancreatic reasons, with prevalence ranging from 2.6% (on CT) to 20% (on MRI) [1], [2]. Most of these cysts reveal to be intraductal papillary mucinous neoplasms (IPMN), with low risk of malignant transformation [3]–[5]. Fukuoka guidelines suggest that small (less than 2 cm) cysts without high-risk stigmata, can be followed up with imaging [4], [5]. However, there is no consensus on how to follow up these cysts. The existing guidelines available on this topic propose different follow-up protocols, such as terminating follow-up after a time interval of dimensional stability or stopping follow-up only when the patient is no longer suitable for surgery[6]–[9]. The cause of this lack of consensus is to be referred to the fact that there is no definite data on the incidence of PDAC in patients with pancreatic cysts of these dimensions.

The objective of this study [10] is to evaluate long-term malignancy risk and mortality of small pancreatic cysts in asymptomatic patients with the purpose of optimizing follow-up protocols in this population.

In a retrospective multicenter study, 267 asymptomatic patients from Beth Israel Deaconess Medical Center (Boston, MA) with incidental MRI finding of pancreatic cysts, with diameter ranging from 5 to 20 mm, were enrolled in the “small pancreatic cyst” group. The selected patients had at least two abdominal MRIs at least six months apart. Patients with history of pancreatitis were excluded, as it is considered a risk factor for PDAC. 1459 patients from Montefiore Medical Center (Bronx, NY) with matching age decade, imaging modality (MRI vs. CT) and year of the index date formed the “no cyst” group. Patients with a diagnosis of any pancreatic neoplasm within 5 years before the date of the index study were excluded.

Endpoints of the study included mortality and incidence of pancreatic cancer; in case of pancreatic cancer occurrence, it was noted weather it developed in the same location of the cyst or from a different area.

In the “small pancreatic cyst” cohort, 0.7% of patients developed pancreatic cancer. 0.4% of patients developed low-grade dysplasia. Mortality was 21%, 4% of which was due to pancreatic cancer. In the “no pancreatic cyst” group, 1.2% of patients developed pancreatic cancer; mortality was 26%. The difference between the incidence of PDAC in the two groups did not appear to be statistically significant. During the radiological follow-up (mean 6.1 ± 4.2 years) the yearly growth rate was 0.0003± 1.8 mm/year or 0.7 ± 20.9%/year.

Interestingly, the most clinically relevant result of this study is that none of the PDAC diagnosed during the follow-up originated from the followed cysts.

The importance of this study resides in the fact that not only it evaluates the incidence of PDAC in patients with small pancreatic cysts but compares it with the incidence of PDAC in patients without cysts, proving that the presence of small cysts does not act as an additive risk factor in the general population.

These results are in line with a previously published paper from Chernyak and co-workers [11], where the incidence of PDAC less then 2 cm did not differ significantly from patients without cysts. On the other hand, larger cysts increase the risk by three times.

The retrospective design of the study may have caused some patient selection biases, the limited clinical data mentioned in the indication of the imaging study does not allow to completely rule out risk factors for PDAC, such as pancreatitis. Moreover, the enrolment of patients in the two groups was only based on the report, thus, patients with pancreatic cysts may have been either excluded from the “cyst group” or included in the “no cyst group”.

In conclusion, the results of this study show that the presence of small pancreatic cysts does not represent a risk factor for PDAC, since its incidence over a 6 years follow up period is similar in patients with less than 2 cm pancreatic cysts and patients without pancreatic cysts.

Therefore, the frequency and duration of follow-up proposed by existing guidelines could be reduced, thus decreasing the induced patient anxiety and the burden on healthcare system.

 

References:

 

  1. M.-L. Kromrey et al., “Prospective study on the incidence, prevalence and 5-year pancreatic-related mortality of pancreatic cysts in a population-based study,” Gut, vol. 67, no. 1, pp. 138–145, Jan. 2018, doi: 10.1136/gutjnl-2016-313127.
  2. O. R. Brook et al., “Delayed Growth in Incidental Pancreatic Cysts: Are the Current American College of Radiology Recommendations for Follow-up Appropriate?,” Radiology, vol. 278, no. 3, pp. 752–761, Mar. 2016, doi: 10.1148/radiol.2015140972.
  3. Y. Yamada, H. Mori, S. Matsumoto, N. Kamei, and N. Hongo, “Invasive Carcinomas Derived From Intraductal Papillary Mucinous Neoplasms of the Pancreas,” Journal of Computer Assisted Tomography, vol. 30, no. 6, pp. 885–890, Nov. 2006, doi: 10.1097/01.rct.0000220801.76276.0f.
  4. M. Tanaka et al., “Revisions of international consensus Fukuoka guidelines for the management of IPMN of the pancreas,” Pancreatology, vol. 17, no. 5, pp. 738–753, Sep. 2017, doi: 10.1016/j.pan.2017.07.007.
  5. M. Tanaka et al., “International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas,” Pancreatology, vol. 12, no. 3, pp. 183–197, May 2012, doi: 10.1016/j.pan.2012.04.004.
  6. A. J. Megibow et al., “Management of Incidental Pancreatic Cysts: A White Paper of the ACR Incidental Findings Committee,” Journal of the American College of Radiology, vol. 14, no. 7, pp. 911–923, Jul. 2017, doi: 10.1016/j.jacr.2017.03.010.
  7. S. S. Vege et al., “American Gastroenterological Association Institute Guideline on the Diagnosis and Management of Asymptomatic Neoplastic Pancreatic Cysts,” Gastroenterology, vol. 148, no. 4, pp. 819–822, Apr. 2015, doi: 10.1053/j.gastro.2015.01.015.
  8. G. H. Elta, B. K. Enestvedt, B. G. Sauer, and A. M. Lennon, “ACG Clinical Guideline: Diagnosis and Management of Pancreatic Cysts,” American Journal of Gastroenterology, vol. 113, no. 4, pp. 464–479, Apr. 2018, doi: 10.1038/ajg.2018.14.
  9. “European evidence-based guidelines on pancreatic cystic neoplasms,” Gut, vol. 67, no. 5, pp. 789–804, May 2018, doi: 10.1136/gutjnl-2018-316027.
  10. M. Nakhaei, M. Bligh, V. Chernyak, A. F. Bezuidenhout, A. Brook, and O. R. Brook, “Incidence of pancreatic cancer during long-term follow-up in patients with incidental pancreatic cysts smaller than 2 cm,” European Radiology, vol. 32, no. 5, pp. 3369–3376, May 2022, doi: 10.1007/s00330-021-08428-1.
  11. V. Chernyak, M. Flusberg, L. B. Haramati, A. M. Rozenblit, and E. Bellin, “Incidental Pancreatic Cystic Lesions: Is There a Relationship with the Development of Pancreatic Adenocarcinoma and All-Cause Mortality?,” Radiology, vol. 274, no. 1, pp. 161–169, Jan. 2015, doi: 10.1148/radiol.14140796.

 

Dr. Sara Belcastro is a first-year radiology resident on the “Sapienza, University of Rome” training scheme in Italy. She completed her undergraduate medical degree at “Sapienza, University of Rome” in 2021. She joined the Medical Imaging Department in the same year where she is undertaking training in diagnostic and interventional radiology, with particular interest towards abdominal imaging.

Comments may be sent to: sarabelcastro2@remove-this.gmail.com


Branch-duct intraductal papillary mucinous neoplasm (IPMN): Are cyst volumetry and other novel imaging features able to improve malignancy prediction compared to well-established resection criteria?

Raffaella M. Pozzi Mucelli, Carlos Fernández Moro, Marco Del Chiaro, Roberto Valente, Lennart Blomqvist, Nikolaos Papanikolaou, Johannes-Matthias Löhr, Nikolaos Kartalis

Eur Radiol 32, 5144–5155 (2022). doi.org/10.1007/s00330-022-08650-5

 

Intraductal papillary mucinous neoplasms (IPMN) are epithelial pancreatic cystic tumours of mucin-producing cells that arise from the pancreatic ducts and are usually detected incidentally on cross-sectional imaging. IPMN can be divided into three types according to duct involvement: main duct, branch-duct, and mixed (affecting main and branch ducts) (1). Based on their degree of dysplasia, IPMN range from low-grade dysplasia (LGD) up to high-grade dysplasia and invasive carcinoma (HGD/INV) (1). Current guidelines base their management on several well-established resection criteria (3,4). The cyst size is associated with an increased risk of HGD/INV, but there is not a cut-off size risk established; thus, the size alone is an inappropriate parameter to perform surgery due to its poor predictive positive value for HGD/INV (2).

The aim of this retrospective single-center study was to assess the role of volume, morphology, and other well-established resection criteria in malignancy prediction of patients with branch-duct and mixed-type IPMN.

Patient selection was consecutively done from a prospectively collected database of 345 patients who underwent pancreatic surgery with histologically confirmed IPMN at Karolinska University Hospital from 2008 to 2019.

The inclusion criteria were: a) Preoperative pancreatic MRI with at least one axial and coronal T2W sequence and b) At least one histologically proven BD-IPMN detectable on the T2W images. The exclusion criteria were: a) Main-duct diameter ≥5 mm without a BD-IPMN clearly identifiable at preoperative MRI and b) Solid mass forming pancreatic cancer with or without a main pancreatic duct stricture.

The final study population was 106 patients.

The images of the pancreatic MRI closest to the date of surgery were evaluated by two experienced abdominal radiologists in consensus reading, and one cyst per patient was chosen for the analysis (the largest or the most suspicious for malignancy based on guidelines at the time of surgery). The collected imaging parameters were: maximum cyst diameter on T2WI (axial and coronal), elongation value (a relation between width and length) (5), cyst volume, main pancreatic duct diameter, contrast-enhancing mural nodules, cyst wall thickening (≥2 mm), progress in size during follow-up (≥5 mm/year), solitary/multiple lesions, and cyst location.

Multiple clinical parameters were collected from each patient's electronic record, including: age at surgery, gender, and serum levels of CA 19-9. Also, the grade of dysplasia from each resected IPMN was recorded.

Univariable logistic regression analysis was performed to identify variables associated with HGD/INV. Posteriorly, statistically significant variables were tested with multivariable logistic regression, adjusted for age and gender.

There were no statistically significant differences in cyst volume (OR=1.01, 95% CI: 0.99–1.02 p=0.12) or elongation value (OR=0.38, 95% CI: 0.02–5.93, p=0.49) between patients with LGD and HGD/INV. Also, there was not found an association between HGD/INV and maximum cyst diameter, wall thickness, solitary or multiple lesions, or progress in cyst size (≥5 mm/year). Histological cell subtypes did not correlate with cyst diameter, volume, or elongation value. The results showed that the only variables associated with HGD/INV were also ones that are present in current guidelines (2,3): the presence of contrast-enhancing mural nodules (OR=4.32, 95% CI: 1.18–15.76, p=0.02), the diameter of the main pancreatic duct ≥5 mm (OR=4.2, 95% CI: 1.34–13.1, p=0.01), and elevated serum levels of CA 19-9 (>37 µmol/l) (OR=6.72, 95% CI: 1.89–23.89, p=0.03).

Important limitations of the study were that it was retrospective, the inclusion of only surgically managed IPMN patients (moreover, the indications for surgery varied during the duration of the study), the small patient sample, and the consensual reading of the images by the two radiologists (preventing the assessment of interobserver agreement).

Another important point is that even if the main objective of the study was not demonstrated, the research was published anyway, avoiding publication bias.

In summary, the study shows that neither volumetry nor elongation value can predict malignancy in branch-duct and mixed-type IPMN. And, as known from current guidelines, the dilatation of the main pancreatic duct, contrast-enhancing mural nodules, and elevated serum levels of CA 19-9 are associated with a higher risk of malignancy.

 

References:

 

  1. Ren B, Liu X, Suriawinata AA (2019). Pancreatic ductal adenocarcinoma and its precursor lesions: histopathology, cytopathology, and molecular pathology. Am J Pathol 189:9–21. doi.org 10.1016/j.ajpath.2018.10.004
  2. Maire F, Couvelard A, Palazzo L, et al. (2013). Pancreatic intraepithelial neoplasia in patients with intraductal papillary mucinous neoplasms. Pancreas 42:1262–1266. doi.org/10.1097/ MPA.0b013e3182962723
  3. Tanaka M, Fernandez-Del Castillo C, Kamisawa T, et al. (2017). Revisions of international consensus Fukuoka guidelines for the management of IPMN of the pancreas. Pancreatology 17:738– 753. doi.org/10.1016/j.pan.2017.07.007
  4. The European Study Group on Cystic Tumours of the Pancreas (2018). European evidence-based guidelines on pancreatic cystic neoplasms. Gut 67:789–804. doi.org/10.1136/gutjnl-2018- 316027
  5. Aghaei Lasboo A, Rezai P, Yaghmai V (2010). Morphological analysis of pancreatic cystic masses. Acad Radiol. doi.org/10. 1016/j.acra.2009.09.013

 

Eduardo Bättig Arriagada is a fourth-year radiology resident at Hospital Universitari i Politècnic La Fe in Valencia, Spain. His main fields of interest are chest and abdominal imaging, and the use of artificial intelligence in radiology. He has been actively involved in clinical imaging research and has contributed as a co-author in some publications. Besides radiology, his main interests are playing guitar, yoga, and homemade bakery.

Comments may be sent to: eduardo.baettig@remove-this.gmail.com


Avoiding contrast-enhanced sequences does not compromise the precision of the simplified MaRIA for the assessment of non-penetrating Crohn's disease activity

Agnès Fernàndez-Clotet, Víctor Sapena, Nunzia Capozzi, Sonia Rodríguez, Maria-Carme Masamunt, Elena Ricart, Ingrid Ordás, Julian Panés, Jordi Rimola

Eur Radiol 2022 May;32(5):3334-3345; doi: 10.1007/s00330-021-08392-w. Epub 2022 Jan 15.

 

Magnetic resonance enterography (MRE) has gained a central role in the evaluation of small bowel in patients affected by Crohn’s disease; it is widely accepted as an imaging method with good ability to provide a detailed assessment of small bowel involvement [1]. MRE has been recently proposed as an alternative to ileocolonscopy, which could be often incomplete, and not able to describe transmural involvement and eventual presence of abdominal abscesses [2]. Moreover, MRE has a pivotal role in measuring therapeutic response, representing a noninvasive imaging tool to guide the clinicians in the decision-making process [3]. The use of contrast enhancement is a cornerstone in current MRE protocols, and it is also required for the Magnetic Resonance Index of Activity (MaRIA), one of the major MR grading systems to evaluate the response to therapy in Crohn’s disease [4]. However, MaRIA is a time consuming classification, and the recent evidence of gadolinium deposits in the brain concerns the clinicians, especially in young patients [5]. Then, to overcome these shortcomings and to make the score assessment easier, a novel simplified version of MaRIA (sMaRIA) has been proposed [6].

This study aimed to test the performance, in terms of accuracy, of sMARIA calculated with and without contrast-enhanced sequences, with the goal to assess the biologic therapeutic response in patients affected by Crohn’s disease. Authors prospectively enrolled 46 patients, selected according to the presence of endoscopic ulcerations in at least two intestinal segments, and eligible to be treated with biologic therapy. All patients underwent MRE and ileocolonoscopy within 1 month before starting therapy and they repeated the follow-up examinations (MRE and ileocolonoscopy) at 46 weeks. Ileocolonoscopy was considered the reference standard to assess disease activity by using Simple Endoscopic Score for Crohn’s Disease (SES-CD) [7]. The evaluation of inflammatory changes was conducted on five tracts of colon and terminal ileum. This approach was built to compare in a structured manner the MRE with ileocolonoscopy. Two abdominal radiologists, blinded to clinical and endoscopy results, classified the sMaRIA descriptors in the first round by using the unenhanced sequences (T2-sMaRIA) and in the second round, 1 month later, with all set of sequences (CE-sMaRIA). They calculated the agreement for both T2-sMaRIA and CE-sMaRIA to classify the biologic response in each intestinal tract and per-patient. In per-patient analysis, three different endpoints were evaluated for T2-sMaRIA and CE-sMaRIA: the MRE ability to identify patients with ulcer healing, MRE accuracy in decrease ≥50% of global scores, and MRE performance in identifying endoscopic remission. Overall, in identifying ulcer healing in per-patient analysis the agreement of T2-sMaRIA and CE-sMaRIA was comparable with ileocolonoscopy (sensibility = 80 and 76%; specificity = 95.2 and 95.2%; kappa = 0.74 [0.55-0.93] and 0.70 [0.5-0.9], respectively). Both T2-sMaRIA and CE-sMaRIA identified better the ulceration in the colon in comparison with the ileal segments (Cochran’s Q test <0.001 for both tests). Concerning the therapeutic assessment T2-sMaRIA and CE-sMaRIA were also like ileocolonoscopy for both treatment response (kappa = 0.44 [0.17 - 0.71] and 0.53 [0.28-0.79]) and remission (kappa = 0.43 [0.17-0.69] and 0.48 [0.22-0.73]). The standardized effect size was moderate for both CE-sMaRIA = 0.63 ([0.41-0.85] p < 0.001) and T2-sMaRIA = 0.58 ([0.36-0.80] p < 0.001) when was considered an improvement of at least 0.5 standard deviation in endoscopic evaluation (SES-CD), this cut-off was used as criterion for radiological changes.

Despite the interesting results, limits of the study include the single-institution origin of the radeaders and the possible cohort bias with a few patients with isolated colonic disease, less prone to undergo MRE for treatment assessment during follow-up.

To sum up, sMaRIA calculated with and without contrast-enhanced sequences showed similar performance in classifying the activity, severity, and biologic therapeutic response in patients with Crohn disease. Only few cases of disagreement were observed by the authors to assess therapeutic response, the endpoint with lower accuracy was the assessment of remission. In conclusion, the acceptance and safety of MRE can increase by avoiding the use of contrast medium, without the risk of reducing accuracy.

 

References:

 

  1. Maaser, C., et al., ECCO-ESGAR Guideline for Diagnostic Assessment in IBD Part 1: Initial diagnosis, monitoring of known IBD, detection of complications. J Crohns Colitis, 2019. 13(2): p. 144-164.
  2. Danese, S., et al., Endoscopic, Radiologic, and Histologic Healing With Vedolizumab in Patients With Active Crohn's Disease. Gastroenterology, 2019. 157(4): p. 1007-1018.e7.
  3. Ordás, I., et al., Accuracy of magnetic resonance enterography in assessing response to therapy and mucosal healing in patients with Crohn's disease. Gastroenterology, 2014. 146(2): p. 374-82.e1.
  4. Rimola, J., et al., Magnetic resonance for assessment of disease activity and severity in ileocolonic Crohn's disease. Gut, 2009. 58(8): p. 1113-20.
  5. Media, A.C.o.D.a.C., ACR Manual on Contrast Media. 2021.
  6. Capozzi, N., et al., Validation of the Simplified Magnetic Resonance Index of Activity [sMARIA] Without Gadolinium-enhanced Sequences for Crohn's Disease. J Crohns Colitis, 2020. 14(8): p. 1074-1081.
  7. Daperno, M., et al., Development and validation of a new, simplified endoscopic activity score for Crohn's disease: the SES-CD. Gastrointest Endosc, 2004. 60(4): p. 505-12.

 

Dr. Michela Polici is a radiology resident at "Sapienza" University of Rome - Sant'Andrea University Hospital in Rome, attending the third year of residency. Her main fields of interest are radiomics and diagnostic imaging, with a particular attention to the Gastrointestinal tract Abdominal parenchyma. She has also been actively involved in clinical imaging research, and she has contributed as a co-author in some publications.

Comments may be sent to: michela.polici@remove-this.uniroma1.it


Interobserver Variability in CT-based Morphologic Tumor Response Assessment of Colorectal Liver Metastases

Nina J. Wesdorp, Ruby Kemna, Karen Bolhuis, Jan H. T. M. van Waesberghe, Irene M. G. C. Nota, Femke Struik, Ikrame Oulad Abdennabi, Saffire S. K. S. Phoa, Susan van Dieren, Martinus J. van Amerongen, Thiery Chapelle, Cornelis H. C. Dejong, Marc R. W. Engelbrecht, Michael F. Gerhards, Dirk Grünhagen, Thomas M. van Gulik, John J. Hermans, Koert P. de Jong, Joost M. Klaase, Mike S. L. Liem, Krijn P. van Lienden, I. Quintus Molenaar, Gijs A. Patijn, Arjen M. Rijken, Theo M. Ruers, Cornelis Verhoef, Johannes H. W. de Wilt, Rutger-Jan Swijnenburg, Cornelis J. A. Punt, Joost Huiskens, Jaap Stoker, Geert Kazemier

Radiology: Imaging Cancer   https://doi.org/10.1148/rycan.210105

 

Colorectal cancer is one of the most common malignant neoplasms, ranking 2nd to 4th in terms of incidence globally (1). More than half of patients with colorectal cancer develop colorectal liver metastases (CRLM). Only 20% of these patients are eligible for curative therapy (resection and/or ablation). The remaining patients with CRLM most often receive systemic treatment to suppress the tumour load for secondary local treatment or in a palliative setting. The advent of targeted therapies such as bevacizumab and panitumumab has improved these patients’ outcomes.

Using size-based radiologic parameters, the RECIST 1.1 criteria are widely applied to evaluate tumour response to treatment. However, therapy induces not only size changes but also morphologic modifications.

This study evaluates interobserver variability in morphologic tumour response assessment according to set criteria in participants with CRLM treated with systemic therapy. The relation of morphologic tumour response with RAS/BRAF mutation status and targeted therapy, and the comparison of morphologic tumour response with the RECIST 1.1 measurements were secondary objectives.

The authors used a sample of 369 patients (from the CAIRO5 trial) with initially unresectable colorectal cancer with liver-only metastases. These patients were followed in one of the 54 medical centers included in the trial.

Exclusion criteria were: more than 15 CRLM at baseline or first follow-up CT examination, missing baseline or first follow-up CT, incomplete CT examination, technical error in diagnostic software and the use of MRI or PET with non–contrast-enhanced CT. This resulted in a sample of 156 patients. In addition, three other patients were excluded due to the presence of calcifications or the reduced size of lesions.

All the 153 patients in the final sample did a contrast-enhanced CT scan at baseline and at every two months during systemic therapy. Only the baseline and first follow-up CT scans in the portal venous phase were included in the current study.

Tumour response to systemic therapy was evaluated according to the morphologic criteria formulated by Chun et al (2). Morphology group 3 was characterized by heterogeneous attenuation and ill-defined tumour–liver interface, with or without peripheral rim enhancement. Morphology group 1 was described as homogeneous and low attenuation, with a sharply defined tumour–liver interface and an absence of peripheral rim enhancement. Morphology group 2 tumours could not be assigned to morphology group 1 or group 3 and were described as mixed attenuation, variable tumour–liver interface, and, if initially present, partially resolved rim enhancement. The morphologic response was defined as an optimal response if there was a change from either group 2 or 3 to group 1; a suboptimal response if there was a change from group 3 to 2; and no response if the morphology group did not change or moved to a higher group.

According to those criteria, three radiologists independently assessed tumour response on the baseline and first follow-up CT scans. Two additional radiologists evaluated disagreement cases. Interobserver agreement was calculated using Fleiss k.

Morphologic assessment performed by the three radiologists yielded 86 (56%) agreement cases and 67 (44%) disagreement cases (including four major disagreement cases). Overall interobserver agreement between the panel radiologists on morphology groups and morphologic response categories was moderate (k = 0.53, 95% CI: 0.48, 0.58 and k = 0.54, 95% CI: 0.47, 0.60, respectively). Optimal morphologic response was particularly observed in patients treated with bevacizumab (= 0.001) and in patients with RAS/BRAF mutation (= 0.04). No evidence of a relationship between RECIST 1.1 and morphologic response was found (= 0.61). 

Some limitations should be considered in this study. First, the CT scans were acquired in one of 54 medical centres, in different devices and with different protocols. Besides, the selection of participants with initially unresectable CRLM might have influenced the results. Furthermore, the criteria used for morphologic evaluation are not objective, mainly in group 2. Additionally, evaluating small lesions according to the proposed parameters is difficult. 

There is also a lack of studies evaluating the relationship between morphologic tumour response and histopathologic or survival outcomes.

In conclusion, the morphologic response of liver metastasis to chemotherapy can be clinically relevant, as considering only the size of lesions can underestimate response. Despite that, objective response parameters should be defined to improve the interobserver variability.

 

References:

 

  1. Sawicki, T., Ruszkowska, M., Danielewicz, A., Niedźwiedzka, E., Arłukowicz, T., & Przybyłowicz, K. E. (2021). A Review of Colorectal Cancer in Terms of Epidemiology, Risk Factors, Development, Symptoms and Diagnosis. Cancers, 13(9), 2025. https://doi.org/10.3390/cancers13092025
  2. Chun, Y. S. (2009). Association of Computed Tomography Morphologic Criteria With Pathologic Response and Survival in Patients Treated With Bevacizumab for Colorectal Liver Metastases. JAMA, 302(21), 2338. https://doi.org/10.1001/jama.2009.1755

 

Vasco Ferrão Mendes is a third-year radiology resident at Centro Hospitalar e Universitário de Coimbra, Portugal. From the city of Famalicão, he graduated from the University of Porto in 2018. Vasco has a broad range of interests in diagnostic imaging, including abdominal imaging in various imaging techniques such as CT and ultrasonography. He is a member of various societies such as SPRMN (Sociedade Portuguesa de Radiologia e Medicina Nuclear), RSNA (Radiology Society of North America) and ESR (European Society of Radiology).

Comments may be sent to: vascoferraomendes@remove-this.hotmail.com


Abbreviated non-enhanced magnetic resonance imaging in patients with acute necrotizing pancreatitis

Akash Bansal, Rajath Ramegowda, Pankaj Gupta, Jimil Shah, Jayanta Samanta, Harshal Mandavdhare, Vishal Sharma, Rakesh Kochhar, Manavjit Singh Sandhu

Abdominal Radiology (2022) doi: 10.1007/s00261-022-03531-3 

 

Acute pancreatitis is one of the commonest differentials of acute abdomen which presents to accident and emergency (1). It can be divided into interstitial oedematous pancreatitis and acute necrotizing pancreatitis (1). The Revised Atlanta Classification classifies pancreatic fluid collections according to the presence of necrosis and the interval from pain of onset (2).

CT is the commonest imaging modality used to determine the morphology of pancreatitis and its complications, however the use of MRI is inevitable in some cases. MRI is used in complicated cases as a supplement to CT, and in cases where CT is contra-indicated (such as contrast allergy or acute kidney injury) or when it is advisable to reduce radiation dose (such as in pregnancy or the need for multiple scans) (3). The patients requiring MRI are generally unwell and therefore the long acquisition time often leads to unreliable images of reduced quality.

Bansal et al carried out a retrospective study to assess an abbreviated MRI protocol based on a single axial T2 weighted sequence. They conducted a retrospective analysis of patients with acute necrotizing pancreatitis who underwent MRI between January 2017 and November 2020. Patients with moderately severe or severe acute pancreatitis who underwent MRI within two weeks of admission were included. The exclusion criteria were those with mild or chronic pancreatitis, and those whose MRI was performed later than 2 weeks following admission.

The complete MRI (cMRI) protocol included the following sequences: T2 weighted half Fournier acquisition single shot turbo spin echo (HASTE) axial and coronal, true fast imaging with steady state free precision axial and coronal, T1 weighted gradient echo axial sequence, coronal 2D and 3D MRCP sequences, and DWI with ADC maps. Contrast enhanced axial and coronal T1 weighted sequences using Magnevist were also acquired in some cases. For the abbreviated MRI (AMRI) protocol, only the T2 HASTE axial sequence was evaluated.

Two separate sets of data (AMRI and cMRI) were randomly presented to and independently analyzed by two radiologists who were blinded to the clinical details and to any previous imaging.

The following parameters were assessed: intrapancreatic and extrapancreatic necrosis, percentage of intrapancreatic necrosis (<30% or >30%), presence, site and size of collection, presence of wall, presence and percentage of solid components in the collection, venous thrombosis, presence of ascites, pleural effusion, gallstones, common bile duct stones, main pancreatic duct dilatation and disconnected pancreatic duct.

28 patients were included in the study. Overall, there was no statistical difference in the identification of pancreatic necrosis between AMRI and cMRI, however AMRI under-estimated pancreatic necrosis in one patient. The collections were accurately detected, however the mean size was larger on cMRI compared to AMRI. Disconnected pancreatic duct was seen on cMRI more than AMRI, however this difference was not statistically significant.

Overall acquisition time was 25 seconds for AMRI and 27-32 minutes for cMRI with contrast and 23-27 minutes without contrast. cMRI had some sequences (particularly the MRCP and post-contrast) which were not diagnostic due to respiratory motion artifact.

In conclusion, the authors found that AMRI may be a suitable alternative to cMRI in patients with necrotizing pancreatitis, especially in those with severe disease, as it can be acquired rapidly without the need for contrast injection. The study was limited by the small cohort, therefore further prospective studies with a larger patient cohort should be conducted to support their preliminary observations.

 

References:

 

  1. Banks, P. A., Bollen, T. L., Dervenis, C., Gooszen, H. G., John-son, C. D., Sarr, M. G., Tsiotos, G. G., Vege, S. S., & Acute Pancreatitis Classifcation Working Group (2013). Classifcation of acute pancreatitis--2012: revision of the Atlanta classification and defnitions by international consensus. Gut, 62(1), 102–111.
  2. Foster BR, Jensen KK, Bakis G, Shaaban AM, Coakley FV (2016) Revised Atlanta Classifcation for Acute Pancreatitis: A Pictorial Essay. Radiographics 36(3):675-87.
  3. Shyu, J. Y., Sainani, N. I., Sahni, V. A., Chick, J. F., Chauhan, N. R., Conwell, D. L., Clancy, T. E., Banks, P. A., & Silverman, S. G. (2014). Necrotizing pancreatitis: diagnosis, imaging, and intervention. Radiographics, 34(5), 1218–1239.

 

Dr Stephanie Arrigo is a higher specialist trainee in the Medical Imaging Department of Mater Dei Hospital (Malta) currently preparing for her final exams.  She has a special interest in cross sectional imaging.

Comments may be sent to: steffianastasi@remove-this.gmail.com


The growth pattern of liver metastases on MRI predicts early recurrence in patients with colorectal cancer: a multicenter study

Qian Cai, Yize Mao, Siqi Dai, Feng Gao, Qian Xiao, Wanming Hu, Tao Qin, Qiuxia Yang, Zhaozhou Li, Du Cai, Min-Er Zhong, Kefeng Ding, Xiao-Jian Wu, Rong Zhang

Eur Radiol, 2022 Apr 14. doi.org/10.1007/s00330-022-08774-8

 

The liver represents the main metastatic site of colorectal cancer: approximately 50% to 60% of patients with colorectal cancer develop liver metastases during the course of the disease (1). For patients with isolated liver metastases, locoregional treatments can be curative, as an alternative or in association with systemic chemotherapy: the complete resection of liver metastases can achieve up to 50% 5-year and 20% 10-year survival rates (2,3). Anyway, in up to 60% of patients with colorectal cancer liver metastases (CRCLM) the disease recurs early after treatment. The Authors’ aim was to test the feasibility of a qualitative assessment of hepatic lesions focused on the growth pattern of liver metastases on preoperative MRI, in order to find a useful and simple tool to estimate recurrency risk after surgery.

In this multicentric retrospective study 348 CRCLM patients with 820 metastatic lesions were enrolled from three different Chinese hospitals, between January 2012 and November 2020. All patients underwent a liver MRI within 1 month before surgery and follow-up CT/MRI examinations to monitor recurrence; no enrolled patient was diagnosed with extrahepatic metastases, or other simultaneous malignancies.

Two radiologists in consensus analyzed all contrast enhanced preoperative MRIs and categorized each liver metastasis into four growth patterns based on tumor shape, with reference to the gross classification of HCC (4): rough type, smooth type, focal extranodular protuberant (FEP) type and nodular confluent (NC) type.

The endpoints of the follow-up program included disease-free survival (DFS) and intrahepatic disease free survival (IDFS).

Patients with FEP- and NC-type metastases had shorter DFS and a higher intrahepatic recurrence rate than patients without such metastases in the liver (FEP type: median DFS 5.5 vs. 20.6 months, p = 0.044; 6-month intrahepatic recurrence rate 50.0% vs. 16.0%, p = 0.005; NC type: median DFS, 6.4 vs. 28.0 months, p = 0.007; 6-month intrahepatic recurrence rate, 35.7% vs. 18.6%, p = 0.023). Since no significant differences in DFS or IDFS were observed between patients with rough- and smooth-type metastases and those without such metastases in the liver (p > 0.05), FEP and NC types were classified as high-risk types, while rough and smooth types were classified as low-risk types. Subsequently, patients with high-risk-type liver metastases were renamed as high-risk patients, while patients only with low-risk-type liver metastases were renamed as low-risk patients. High-risk patients had shorter DFS and a higher intrahepatic recurrence rate than low-risk patients (median DFS: 6.4 vs. 28.0 months, p = 0.005; 6-month intrahepatic recurrence rate: 37.5% vs. 13.4%, p = 0.003).

Univariate and multivariate Cox regression analyses proved that high-risk-type liver metastases (hazard ratio [HR]: 2.319, 95% confidence interval [CI]: 1.442– 3.728; p = 0.011) and the number of liver metastases (HR: 1.793, 95% CI: 1.062–3.027; p = 0.029) were independent risk factors for DFS; moreover, high-risk-type liver metastases (HR: 2.169, 95% CI: 1.293–3.639; p = 0.003) were an independent risk factor for IDFS.

A small sample of 53 patients with 177 liver metastases accepted chemotherapy before surgery and had a liver MRI at baseline; in those patients, the Authors analyzed changes in the growth pattern of liver metastases after chemotherapy, and they observed that approximately 79.3% of low-risk types remained low-risk types, while 40.5% of high-risk types were converted to low-risk types. In addition, patients with high-risk types after chemotherapy had shorter DFS and a higher intrahepatic recurrence rate than those with low-risk types (median DFS: 5.9 vs. 33.1 months, p = 0.014; 6-month intrahepatic recurrence rate: 52.4% vs. 9.4%, p = 0.027).

The Authors showed that the DFS of patients with FEP- and/or NC-type liver metastases was shorter than that of patients only with rough- and/or smooth-type liver metastases in three independent centers. Moreover, despite the small sample, the Authors proved that the growth pattern can be converted during chemotherapy.

The main limitation of this study is that a qualitative evaluation was used to determine liver metastases growth pattern, thus prone to inter-observer variability. A quantitative method, such as radiomics, could add clinical value to preoperative growth pattern evaluation.

Assessing the growth pattern of liver metastases on preoperative MRI may be important for surgical planning. Furthermore, the changes in growth patterns of liver metastases on MRI images during chemotherapy may have significance in predicting postoperative recurrence of CRCLM patients, and should be paid attention to in clinical practice.

 

References:

 

  1. Leung U, Gönen M, Allen PJ, Kingham TP, DeMatteo RP, Jarnagin WR, et al. Colorectal Cancer Liver Metastases and Concurrent Extrahepatic Disease Treated With Resection. Ann Surg. 2017 Jan;265(1):158–65.
  2. Creasy JM, Sadot E, Koerkamp BG, Chou JF, Gonen M, Kemeny NE, et al. Actual 10-year survival following hepatic resection of colorectal liver metastases: what factors preclude cure? Surgery. 2018 Jun;163(6):1238–44.
  3. Tomlinson JS, Jarnagin WR, DeMatteo RP, Fong Y, Kornprat P, Gonen M, et al. Actual 10-year survival after resection of colorectal liver metastases defines cure. J Clin Oncol. 2007 Oct 10;25(29):4575–80.
  4. Kanai T, Hirohashi S, Upton MP, Noguchi M, Kishi K, Makuuchi M, et al. Pathology of small hepatocellular carcinoma. A proposal for a new gross classification. Cancer. 1987 Aug 15;60(4):810–9. .

 

Francesca Mambrin is a fourth-year radiology resident at the Medical Imaging Department of the University of Verona, Italy. She graduated in 2017 in Medicine and Surgery at the University of Padua. She is affiliated to the Radiological Society of North America (RSNA) and the European Society of Radiology (ESR). Her interests include upper abdominal imaging, with particular focus on CT and MR assessment of postoperative complications after major pancreatic resections

Comments may be sent to: francesca.mambrin@remove-this.gmail.com


A functional liver imaging score for preoperative prediction of liver failure after hepatocellular carcinoma resection

Ningbin Luo, Xiangyang Huang, Yinan Ji, Guanqiao Jin, Yunying Qin, Bangde Xiang, Danke Su, Weizhong Tang

European Radiology. 2022. DOI: 10.1007/s00330-022-08656-z

Monica Milazzo (radiology resident, University of Palermo, Palermo/IT) and
Roberto Cannella (radiologist and researcher, University of Palermo, Palermo/IT)

 

Hepatocellular carcinoma (HCC) accounts for about 75-85% of all primary liver cancers, representing one of the most important causes of cancer death worldwide [1]. Surgical resection is widely accepted as the most effective treatment option for HCC in patients with preserved liver function. Despite the improvements of post-hepatectomy mortality rates due to the advances in surgical technique and postoperative management, morbidity remains high. The post-hepatectomy liver failure (PHLF) is one of the most severe and challenging complications. It is related to the insufficient residual liver function and it represents a leading cause of hepatectomy-related mortality and increased cost of hospitalization [2, 3]. The incidence of PHLF ranges from 1,2% to 32% according to different definitions, characteristics of study population, and surgical procedures. Several predictors of PHLF have been explored in recent years with inconstant results to improve long-term survival in patients with HCC.

Bastati et al. [4] proposed and validated the functional liver imaging score (FLIS), a visual 6-point score, based on three imaging characteristics on gadoxetic acid-enhancement MRI: 1) liver parenchymal enhancement; 2) biliary contrast excretion; and 3) portal vein sign. The FLIS is calculated on the 20-minutes hepatobiliary phase after the administration of gadoxetic acid by summing semiquantitative assessment of each parameter, scored on an ordinal 0-2 scale. The FLIS reflects the residual hepatic function in patients with advanced chronic liver disease and it turned out to be an independent predictor for mortality in both patient with compensated and decompensated advanced chronic liver disease [5, 6].

A recent study by Luo and colleagues [7] assessed the potential of the FLIS to predict PHLF in patients with HCC in comparison with other routine liver functional parameters. This study included a large cohort of 502 patients (422 men and 80 women), who underwent hepatic resection and had a histologically confirmed HCC. In this cohort, the most common etiology of the chronic liver disease was hepatitis B virus in 425 (84.7%) patients. A total of 90 patients experienced PHLF and this was associated with a higher risk of 30-day and 90-day mortality (OR of 3.4 and 2.6, respectively). The gadoxetic acid-enhanced MRI exams were acquired within 1 month before surgery and they were assessed independently by two abdominal radiologists which assigned the FLIS to each patient.

The main study results demonstrate that PHLF was associated with cirrhosis, ascites, aspartate aminotransferase, platelet count, model for end-stage liver disease (MELD) score, albumin–bilirubin (ALBI) score, FLIS, and major hepatic resection. Interestingly, multivariate analyses revealed that only the FLIS and mayor hepatectomy were independently associated with the risk of PHLF. Particularly, a higher FLIS was associated with a lower risk of PHLF (OR 0.452) [7]. Importantly, the FLIS demonstrated a higher accuracy for the prediction of PHLF compared to other clinical scores including the MELD, ALBI score, and the indocyanine green 15-min retention rate. A FLIS lower than 4 predicted the PHFL with a sensitivity of 61% and a specificity of 79% [7].

The results of this study are relevant for the preoperative management of patients with HCC, as gadoxetic acid-enhanced MRI is often acquired for the preoperative HCC diagnosis and staging. In this setting, the assessment of FLIS on the hepatobiliary phase images can provide an additional functional information for the optimal selection of candidates to surgical resection. Moreover, the FLIS demonstrated an excellent reproducibility between different radiologists, and it may have the advantage to be easily assessed compared to other quantitative liver imaging functional parameters. Indeed, this visual assessment does not require complex equations or specific software for measurement of signal intensity. The main limitations of this retrospective study are the lack of comparison between different grades of PHLF and the low number of patients without viral hepatitis (14,5%), such as nonalcoholic fatty liver disease.

In conclusion, PHLF remains a challenging and life-threatening complication in patients with chronic liver disease. The FLIS score could help the preoperative assessment of patients with HCC at risk of PHLF, improving their management and allowing to select the appropriate surgical strategies. Furthermore, the FLIS is confirmed a simple, noninvasive, and reproducible score. Therefore, it has the potential to be easily implemented in clinical practice and to be used for future applications supported by further studies.

 

References:

 

  1. Sung, H, Ferlay, J, Siegel, RL, Laversanne, M, Soerjomataram, I, Jemal, A, Bray, F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209-249. 
  2. Rahbari NN, Garden OJ, Padbury R, Brooke-Smith M, Crawford M, Adam R, Koch M, Makuuchi M, Dematteo RP, Christophi C, Banting S, Usatoff V, Nagino M, Maddern G, Hugh TJ, Vauthey JN, Greig P, Rees M, Yokoyama Y, Fan ST, Nimura Y, Figueras J, Capussotti L, Büchler MW, Weitz J. Posthepatectomy liver failure: a definition and grading by the International Study Group of Liver Surgery (ISGLS). Surgery. 2011;149:713-724.
  3. Fukushima K, Fukumoto T, Kuramitsu K, Kido M, Takebe A, Tanaka M, Itoh T, Ku Y. Assessment of ISGLS definition of posthepatectomy liver failure and its effect on outcome in patients with hepatocellular carcinoma. J Gastrointest Surg. 2014;18:729-736.
  4. Bastati N, Wibmer A, Tamandl D, Einspieler H, Hodge JC, Poetter-Lang S, Rockenschaub S, Berlakovich GA, Trauner M, Herold C, Ba-Ssalamah A. Assessment of Orthotopic Liver Transplant Graft Survival on Gadoxetic Acid-Enhanced Magnetic Resonance Imaging Using Qualitative and Quantitative Parameters. Invest Radiol. 2016;51:728-734.
  5. Bastati N, Beer L, Mandorfer M, Poetter-Lang S, Tamandl D, Bican Y, Elmer MC, Einspieler H, Semmler G, Simbrunner B, Weber M, Hodge JC, Vernuccio F, Sirlin C, Reiberger T, Ba-Ssalamah A. Does the Functional Liver Imaging Score Derived from Gadoxetic Acid-enhanced MRI Predict Outcomes in Chronic Liver Disease? Radiology. 2020;294:98-107.
  6. Lee HJ, Hong SB, Lee NK, Kim S, Seo HI, Kim DU, Han SY, Choo KS. Validation of functional liver imaging scores (FLIS) derived from gadoxetic acid-enhanced MRI in patients with chronic liver disease and liver cirrhosis: the relationship between Child-Pugh score and FLIS. Eur Radiol. 2021;31:8606-8614.
  7. Luo N, Huang X, Ji Y, Jin G, Qin Y, Xiang B, Su D, Tang W. A functional liver imaging score for preoperative prediction of liver failure after hepatocellular carcinoma resection. Eur Radiol. 2022. doi: 10.1007/s00330-022-08656-z.

 

Dr. Monica Milazzo is a second-year young radiology resident at the University of Palermo (Italy). Dr. Milazzo graduated from the University of Palermo in March 2019. Her main interest is abdominal and gastrointestinal radiology, with particular attention to hepatobiliary disease, and she is currently engaged in a multidisciplinary oncology group.

Comments may be sent to: monicamilazzo92@remove-this.gmail.com


Addedvalue of ancillary imaging features for differentiating hepatocellular carcinoma from intrahepatic massforming cholangiocarcinoma on GdBOPTAenhanced MRI in LIRADS M

Zheng W, Huang H, She D, Xiong M, Chen X, Lin X, Cao D

Abdom Radiol 2022 Mar;47:957-968. doi: 10.1007/s00261-021-03380-6

 

The Liver Imaging Reporting and Data System (1) is an imaging-based diagnostic system applicable in patients at high risk of hepatocellular carcinoma (HCC) (2). In LI-RADS, each liver observation is assigned a category that reflects probability of malignancy (2). LI-RADS M (LR-M) is a category for liver lesions that are definitely or probably malignant, but not specific for hepatocellular carcinoma (HCC) (1, 3). LR-M primarily aims to maintain the high specificity of LR-5 without sacrificing sensitivity to diagnose hepatic malignancies (1). HCC and intrahepatic mass-forming cholangiocarcinoma (IMCC) are the two predominant types in the LR-M group (4).

In this study, the authors aimed to identify reliable imaging features on Gd-BOPTA-enhanced MRI and determine the value of adding ancillary imaging features to distinguish HCC and IMCC in LR-M patients. Data were retrospectively collected from consecutive patients with pathologically proven HCC or IMCC. The inclusion criteria were as follows: a) pathologically proven HCC or IMCC by surgical resection or liver puncture; b) patients underwent Gd-BOPTA-enhanced MRI within three months before surgery or liver puncture; and c) patients were suitable for the LI-RADS categorization system according to the LI-RADS v2018 criteria. Among the remaining potentially eligible patients, only patients with liver lesions classified as LR-M were included, resulting in a final population of 116 patients with HCC (n= 82) and IMCC (n=34).

The LI-RADS imaging features were independently analyzed by two radiologists (with 11 and 5 years of experience in abdominal imaging). If the observations were classified to LR-M, the two readers would evaluate ancillary imaging features simultaneously.

Multivariable logistic regression analysis was performed to identify independent predictors to diagnose HCC among LR-M observations.

HCCs showed significantly more often an enhancing capsule (59.8%), while in IMCCs targetoid appearance on DWI (29.4%) and HBP (73.5%) were more common. Among the ancillary imaging features blood product in mass, fat in mass, mosaic architecture, round margin, intratumoral septa and small-scale central HBP hyperintensity were significantly more frequent in HCC. Peritumoral biliary dilatation and cloud-like enhancement on HBP were significantly more frequent in IMCC.

In the multivariable logistic regression analysis enhancing capsule, intratumoral septa and small-scale central HBP hyperintensity were identified as independent predictors for HCC over IMCC. The model where ancillary imaging features were added demonstrated a significantly superior AUC (0.918 vs. 0.845, p=0.021) and sensitivity (91.5% vs. 79.3%), but lower specificity (79.4% vs. 85.3%) compared to the model without ancillary imaging features for diagnosing HCC.

This study is of interest as it brings light into the wide category of LR-M. Among the large number of ancillary features only two were identified as independent predictors, which may be easily assessed in addition to the major features and LR-M characteristics.

Limitations of this study are the exclusion of other non-HCC malignancies and the rather small study population. Since most patients had hepatitis B viral infection and Child–Pugh class A the results have limited generalizability. Furthermore, the results may not be transferable to Gd-EOB-DTPA enhanced liver MRI.

Nevertheless, ancillary imaging features have shown potential in the differentiation of LI-RADS M lesions in this study. Further studies including a larger study population, other non-HCC malignancies (i.e. combined HCC-ICC), and different contrast agents are needed to prove applicability and eventual incorporation in the LI-RADS classification.

 

References:

 

  1. Tang A, Bashir MR, Corwin MT, et al.Evidence Supporting LI-RADS Major Features for CT- and MR Imaging-based Diagnosis of Hepatocellular Carcinoma: A Systematic Review. Radiology. 2018;286(1):29-48.
  2. Chernyak V, Santillan CS, Papadatos D, Sirlin CB. LI-RADS((R)) algorithm: CT and MRI. Abdom Radiol (NY). 2018;43(1):111-26.
  3. (2018). RAACoR;Pages. Accessed at https://www.acr.org/Clinical-Resources/Reporting-and-Data-Systems/LI-RADS/CT-MRI-LI-RADS-v2018.
  4. Fowler KJ, Potretzke TA, Hope TA, et al.LI-RADS M (LR-M): definite or probable malignancy, not specific for hepatocellular carcinoma. Abdom Radiol (NY). 2018;43(1):149-57.

 

Lisa Jungblut is a fourth-year radiology resident at the University Hospital Zurich. During her residency she has spent 12 months as research scholar and has been involved in several research studies centered on chest imaging.

Comments may be sent to: lisa.jungblut@remove-this.usz.ch


Diagnostic performance of 18F‑fluorodeoxyglucose‑PET/MRI versus MRI alone in the diagnosis of pelvic recurrence of rectal cancer

Verena Plodeck, Ivan Platzek, Johannes Streitzig, Heiner Nebelung, Sophia Blum, Jens‑Peter Kühn, Ralf‑Thorsten Hoffmann, Michael Laniado, Enrico Michler, Sebastian Hoberück, Klaus Zöphel, Jörg Kotzerke, Johannes Fritzmann, Jürgen Weitz, Christoph G. Radosa

Abdominal Radiology (2021) 46:5086–5094 https://doi.org/10.1007/s00261-021-03224-3

 

Colorectal cancer is the third most common cancer worldwide, and is expected that number will increase by around 60% to more than 2.2 million new cases by 2030. Rectal cancer accounts for about 40% of all cases of colorectal cancer (1,2).

Local recurrences rates have decreased significantly after the introduction of total mesorectal excision and neoadjuvant radiotherapy (3). In case of local recurrence, complete surgical resection is the only curative treatment, but due to the challenging method and the potential extent up to pelvic exenteration, accurate preoperative diagnosis is essential (4).

The diagnosis can be difficult, due to pelvic scarring and inflammatory/reactive changes after radiotherapy or anastomotic leaks (5,6). Follow-up of rectal cancer is usually done with CT, which is most commonly used, MRI and PET/CT. These methods have different sensitivities and specificities, with noticeable higher sensitivity in MRI versus CT, but comparable specificity. PET/CT was described to have a relatively low (58%) PPV for FDG-avid presacral lesions, but improved diagnostic performance after adding MRI sequences. A recent study demonstrated good accuracy of PET/MRI (7). The use of PET has been recommended in equivocal cases and prior to extensive resection (8).

The aim of this retrospective study was to compare 18F-FDG-PET/MRI and MRI in the diagnosis of pelvic recurrence of rectal cancer.

They included eligible forty-one PET/MRIs of forty patients, which were reviewed by four groups, in a blinded fashion, with a total of three radiologists and one nuclear medicine physician. To avoid bias, a time gap of 3 months was kept between the readings. Each finding was scored 0-4, depending on probability of recurrence.

MRI criteria for malignancy were:

  • On T2: nodular or irregularly shaped soft tissue masses, inhomogeneous structure, signal intensities equivalent or higher compared to muscle and/or infiltration of adjacent organs.
  • On DWI: high signal on b800 images with corresponding low signal on ADC maps.
  • On CE MRI: inhomogeneous enhancement with suspicious morphology on T2.

PET/MRI criteria considered shape, location and intensity, by visual assessment, of 18F-FDG uptake. Therefore:

  • Increased uptake compared to liver background was suspicious.
  • Lower uptake than liver background in anatomical structures like ovaries or rectal stump, typical uptake in the urinary tract or along bowel loops was considered benign.
  • Photopenic areas with slight uptake of the margins were considered fluid collections.
  • Non focal uptake, less compared to background, was presumed to be due to inflammation, if this corresponded to MRI.

Lesions were considered malignant if they showed intense focal 18F-FDG uptake, as well as suspicious MR findings.

The results showed that PET/MRI leads to less equivocal findings and increases readers’ confidence in diagnosing or excluding local recurrence. Inter-reader agreement, sensitivity, specificity, PPV/NPV and accuracy are comparable for MRI and PET/MRI, with slightly higher values for PET/MRI. Also, PET/MRI showed higher AUC (0.97 versus 0.92), but not statistically significant.

The authors referred to other studies. Comparing MRI results, Molinelli et al. obtained a higher AUC value for T2+CE-T1+DWI (9), but these results can depend on the experience of the readers and types of histology, for example mucinous tumors, included in the reviewed study, that has been shown to cause false negative results on ADC. Regarding PET/MRI results, Plodeck et al. (7) obtained higher specificity and NPV, but comparable sensitivity, PPV and accuracy.

This can be explained by some limitations to this study, because PET/MRI is used almost exclusively as second-line investigation, so a high number of recurrences is found, leading to a selection bias.

In conclusion, this study demonstrates that PET/MRI increases readers’ confidence levels and reduces the number of equivocal findings compared to MRI alone. It can be clinically useful in patients with equivocal findings in other imaging modalities, particularly in a preoperative setting.

 

References:

 

  1. Bray F, Ferlay J, Soerjomataram I, et al (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424. https://doi.org/10.3322/caac.21492 2
  2. Arnold M, Sierra MS, Laversanne M, et al (2017) Global patterns and trends in colorectal cancer incidence and mortality. Gut 66:683–691. https://doi.org/10.1136/gutjnl-2015-310912
  3. van Gijn W, Marijnen CA, Nagtegaal ID, et al (2011) Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial. Lancet Oncol 12:575–582. https://doi.org/10.1016/S1470-2045(11)70097-3
  4. Law WL, Chu KW, Choi HK (2000) Total pelvic exenteration for locally advanced rectal cancer. J Am Coll Surg 190:78–83. https://doi.org/10.1016/S1072-7515(99)00229-X 14
  5. Even-Sapir E, Parag Y, Lerman H, et al (2004) Detection of Recurrence in Patients with Rectal Cancer: PET/CT after Abdominoperineal or Anterior Resection. Radiology 232:815–822. https://doi.org/10.1148/radiol.2323031065 9
  6. de Lange EE, Fechner RE, Wanebo HJ (1989) Suspected recurrent rectosigmoid carcinoma after abdominoperineal resection: MR imaging and histopathologic fndings. Radiology 170:323–328. https://doi.org/10.1148/radiology.170.2.2911656
  7. Plodeck V, Rahbari NN, Weitz J, et al (2019) FDG-PET/MRI in patients with pelvic recurrence of rectal cancer: first clinical experiences. Eur Radiol 29:422–428. https://doi.org/10.1007/s00330-018-5589-6
  8. Georgiou PA, Tekkis PP, Brown G (2011) Pelvic colorectal recurrence: crucial role of radiologists in oncologic and surgical treatment options. Cancer Imaging 11:S103–S111. https://doi.org/10.1102/1470-7330.2011.9025
  9. Molinelli V, Angeretti MG, Duka E, et al (2018) Role of MRI and added value of diffusion-weighted and gadolinium-enhanced MRI for the diagnosis of local recurrence from rectal cancer. Abdom Radiol 43:2903–2912. https://doi.org/10.1007/s00261-018-1518-z

 

Dr. Alexandra Babici is a fifth and final year radiology resident at the County Clinical Emergency Hospital in Cluj-Napoca, Romania. Her main areas of focus include gastrointestinal imaging, as well as oncologic and hybrid imaging. She is also interested in non-vascular interventional radiology, such as image-guided biopsies. She is a fellow of the European Society of Radiology (ESR) and RSNA (Radiological Society of North America) and has participated in many congresses and conferences.


Ablation Difficulty Score: Proposal of a new tool to predict success rate of percutaneous ablation for hepatocarcinoma

Conci S, D'Onofrio M, Bianco A, Campagnaro T, Martone E, De Bellis M, Longo C, Dedoni S, Vittoria D'Addetta M, Ciangherotti A, Pedrazzani C, Dalbeni A, Campagnola P, Mansueto G, Guglielmi A, Ruzzenente A.

Eur J Radiol. 2022 Jan;146:110097. doi: 10.1016/j.ejrad.2021.110097

 

Hepatocellular carcinoma (HCC) accounts for about 90% of primary liver cancer. Its incidence is increasing worldwide, representing the fourth most frequent cause of cancer-related death globally [1]. According to Barcelona Clinic Liver Cancer (BCLC) guidelines, local ablation is one of the curative treatment options available for HCC at the moment [2,3]. Success rates of local ablative techniques (LAT) range from 80% to 98,7% [4, 5, 6], regardless of the high rate of necrosis in the ablated area.

The authors of this study analyzed retrospectively the outcome of 585 nodules treated with radiofrequency ablation in 282 patients from 2010 to 2020, with the objective of developing an ablation difficulty score (ADS) to improve patient selection and treatment allocation. Ablation with microwave device, guided by CT-scan or fusion imaging or performed by laparotomy / laparoscopy were not included. Other exclusion criteria were the presence of macrovascular invasion and patients with follow up imaging not performed in their local radiology department.

Preoperative imaging, either CT or MRI, were used to measure the shortest distance between the edge of the nodule and the liver capsule, and to the major vascular structures. Nodules with distance ≤ 5 mm to vascular structures were defined perivascular, and those with distance ≤ 5 mm to liver surface sub-capsular.

A contrast-enhanced CT 30 days after the procedure was the imaging technique used to assess the ablation success. Incomplete ablation (IA) was defined as residual tumor on the edge of the ablated area. Failure ablation was considered after two consecutive procedures with IA. Ablation success was established as the absence of residual tumor after up to two consecutive procedures.

This study reported an ablation success rate of 85.5%. Univariate and multivariate analysis revealed that nodule’s size > 20 mm, isoechoic nodule appearance, sub-capsular location, perivascular location, and non-cirrhotic liver parenchyma were significantly related to failure ablation. Each one of these factors was awarded 1 point and the ADS was built up with a score from 0 to 5. Three categories of risk were established: low risk (ADS 0), intermediate risk (ADS 1), and high risk (ADS ≥ 2), with an ablation success rate of 93.5%, 85.8%, and 71.3% respectively. The cumulative local tumor progression (LTP) free survival rates at 1-year were 90.2%, 80.6%, and 72.3% for low, intermediate, and high-risk group, respectively. Only nodule size, isoechoic appearance, and perivascular location resulted to be independent factors for LTP free survival rates on univariate and multivariate analysis.

We believe that this study is relevant. On the one hand, LAT remains a widely used curative treatment for HCC thanks to its high success rate, feasibility and low postoperative morbidities [7,8]. On the other hand, the proposed ADS scoring system is a very simple and easy-to-use tool that provides additional and relevant information to guide HCC treatment decisions, reserving LAT in high-risk (ADS ≥2) nodules only for patients not suitable for surgery or liver transplantation.

The study had some limitations. Firstly, a potential risk of selection bias owing to the retrospective single-center design of this study. Secondly, only nodules treated with radiofrequency ablation were considered. Also, ablation with microwave devices or advanced local ablative techniques, such as ablation guided by fusion imaging, CT scan or CEUS, were not included in this study. The latter may explain the lower ablation success rate obtained for those nodules which location or imaging characteristics made it difficult to position the ablation needle.

In conclusion, the establishment of a score to assist in deciding the optimal treatment for HCC is a good step forward to improve patient selection, however, we believe that further studies are needed to address the limitations and to corroborate the results of this study.

 

References:

 

  1. A. Jemal, E.M. Ward, C.J. Johnson, K.A. Cronin, J. Ma, B. Ryerson, et al., Annual report to the nation on the Status of Cancer, 1975-2014, featuring survival, J. Natl. Cancer Inst. 109 (9) (2017).
  2. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J. Hepatol. 69(1) (2018) 182–236. http://doi.org/10.1016/j.jhep.2018.03.019.
  3. A.B. Benson, M.I. D’Angelica, D.E. Abbott, T.A. Abrams, S.R. Alberts, D.A. Anaya, et al., Guidelines Insights: Hepatobiliary Cancers, Version 2.2019, J Natl. Compr. Cancer Netw. 17 (4) (2019) 302–310, https://doi.org/10.6004/jnccn.2019.0019.
  4. M.W. Lee, D. Kang, H.K. Lim, J. Cho, D.H. Sinn, T.W. Kang, et al., Updated 10-years outcomes of percutaneous radiofrequency ablation as first line therapy for single hepatocellular carcinoma <3cm: emphasis on association of local tumor progression and overall survival, Eur. Radiol. 30 (2020) 2391–2400, https://doi.org/10.1007/s00330-019-06575-0.
  5. A. Mukund, P. Vats, A. Jindal, Y. Patidar, S.K. Sarin, Early hepatocellular carcinoma treated by radiofrequency ablation. Mid and long term outcomes, J. Clin. Exp. Hepatol. 10 (6) (2020) 563–573, https://doi.org/10.1016/j.jceh.2020.04.016
  6. M.W. Lee, D. Kang, H.K. Lim, J. Cho, D.H. Sinn, T.W. Kang, et al., Updated 10-years outcomes of percutaneous radiofrequency ablation as first line therapy for single hepatocellular carcinoma <3cm: emphasis on association of local tumor progression and overall survival, Eur. Radiol. 30 (2020) 2391–2400, https://doi.org/10.1007/s00330-019-06575-0.
  7. M.C. Jansen, R. van Hillegersberg, R.A.F.M. Chamuleau, O.M. van Delden, D. J. Gouma, T.M. van Gulik, Outcome of regional and local ablative therapies for hepatocellular carcinoma: a collective review, Eur. J. Surg. Oncol. 31 (4) (2005) 331–347, https://doi.org/10.1016/j.ejso.2004.10.011.
  8. J.C. Nault, O. Sutter, P. Nahon, N. Ganne-Carri´e, O. S´eror, Percutaneous treatment of hepatocellular carcinoma: State of the art and innovations, J. Hepatol. 68 (4) (2018) 783–797, https://doi.org/10.1016/j.jhep.2017.10.004

 

Ali Boukhoubza is a third-year radiology resident at the Hospital Universitari i Politècnic La Fe in Valencia, Spain. He completed his medical degree at University of Granada in 2018. He has a wide range of interests in interventional radiology with a special focus on interventional oncology and liver locoregional therapies.

Comments may be sent to: AliBoukhoubza@remove-this.gmail.com


Conventional-dose CT versus 2-mSv CT for right colonic diverticulitis as an alternate diagnosis of appendicitis: secondary analysis of large pragmatic randomized trial data

Hae Young Kim, Seungjae Lee, Dong Hwan Kim, Yousun Ko, Ji Hoon Park, Ara Ko, Seok Min Jeong, Sung Bin Park, Kyoung Ho Lee and for the LOCAT Group

American Journal of Radiology, November 2021. https://www.ajronline.org/doi/10.2214/AJR.21.25584

 

The adoption of lower dose CT in routine practice in young adults has been slow, partly due to concern regarding missing alternative diagnoses, such as right colonic diverticulitis (RCD), and other more subtle abnormalities.

The purpose of this paper was to retrospectively compare diagnostic performance of 2mSv low dose CT (LD-CT) to conventional dose CT (CD-CT) for the diagnosis of right sided diverticulitis in a relatively young cohort (ages 15-44) with suspected appendicitis.

The original randomized control trial was performed in Korea and involved 3074 patients with suspected appendicitis (1). These patients underwent random assignment for Low dose or conventional dose CT. The imaging findings were compared and it was concluded that the low dose CT was non-inferior for diagnosis of appendicitis. Of note, 37% of the original cases were positive for appendicitis.

This retrospective analysis reviewed all of the previously seen right colonic diverticulitis cases seen in the original trial. End points for the diagnosis of right colonic diverticulitis between the different scan dosage were statistically analysed with different end points. In addition, all of the previously seen right colonic diverticulitis cases were re-reviewed by 4 radiologists (2 consultants and 2 trainees). The radiologists were blinded to the cases with additional alternative pathology cases, totaling 200 LD-CT and 200 CD-CT cases. A proforma was used and review only commented on if right colonic diverticulitis was present, indeterminate or absent.

Results demonstrated that interobserver group differences were minute at 95% confidence intervals. Both Gwet and Kappa coefficients were used to assess interobserver differences. Gwet coeffient was preferable to Kappa in this cohort as the prevalence of diverticulitis was high and this statistic is less vulnerable to disease prevalence compared to other common statistics. Gwet coefficient (2) were high and comparable between the low dose and conventional dose groups.

The paper concluded that 2msv CT is comparable to conventional-dose CT for the diagnosis of right colonic diverticulitis.

There were a number of limitations with this paper which were highlighted by the authors. The patient demographic were Korean patients with a high prevalence of right sided diverticulitis, which is presumably related to diet (7% of the 3074 cases). Although less prevalent in western societies, this study and the randomized control trial still highlight that reduced CT dosage is accurate for alternative diagnoses to appendicitis in an acute setting.

Although blinded there was potential bias for the 4 retrospective reporters. They each read an article on reporting diverticulitis before undertaking the study and there was a high proportion of positive studies with over 50% of the retrospective image reviews having right sided diverticulitis. Gwet coefficients were used to help eliminate this high bias.

Another very important limitation is that the median (IQR) dose received by the individual patients were more than double the target dose in both groups with 4.1 (3.7–4.5) mGy versus a target of 2mSv in the low dose group and 14.4 (12.9–16.2) versus a target of 7mSv in the conventional dose group. This clearly has implications for services considering adopting this technique.

In conclusion although there were several limitations this paper indicates that lower dose CT has comparable accuracy to conventional dose CT in the assessment of patients with right sided abdominal symptoms and a primary diagnosis is acute appendicitis. While a 2mSv dose was not actually achievable in a majority of patients in the trial setting this paper adds further support to the routine use of lower dose CT in younger patients with suspected appendicitis.

 

References:

 

  1. The LOCAT Group, Hyuk Jung Kim, Byeong Geon Jeon, Chong Kun Hong et al. Low-dose CT for the diagnosis of appendicitis in adolescents and young adults (LOCAT): a pragmatic, multicentre, randomised controlled non-inferiority trial. The Lancet Gastroenterology & Hepatology Volume 2, Issue 11, November 2017, Pages 793-804
  2. Charles Zaiontz. 2020. Gwets AC1 and AC2. Real statistics. Viewed 04/12/2021. https://www.real-statistics.com/reliability/interrater-reliability/gwets-ac2/

 

Dr William Hogg is a 4th year Radiology Registrar on the Leeds Radiology Training Scheme, England. He completed his undergraduate medical degree at Leeds Medical School in 2016, during this time he undertook a Radiology elective in Brisbane, Australia where he was involved with a Neuroradiology mechanical thrombectomy project. He stayed locally in Yorkshire for his foundation training and subsequent Radiology post within the Leeds Radiology Academy. After obtaining his FRCR qualification Dr Hogg has started subspecialty GI Radiology training. He is involved in a Crohn’s disease MRI/ultrasound research project which is exploring his interest in intestinal ultrasound and luminal GI work.

Comments may be sent to: william.hogg@remove-this.nhs.net


Abbreviated MRI in patients with suspected acute appendicitis in emergency: a prospective study

Islam, G. M. N., Yadav, T., Khera, P. S., et al.

Abdominal Radiology (2021). doi:10.1007/s00261-021-03222-5

 

Acute appendicitis is one of the most common abdominal emergencies, with a lifetime risk of 7-8% (1). Nowadays, the requirement of appendectomy in patients without complicated appendicitis is being increasingly refuted, since in these selected cases the choice of antibiotic treatment-only avoids the risk postoperative morbidity. The most widely used imaging methods for the radiological diagnosis of acute appendicitis are transabdominal ultrasound (US) and computed tomography (CT).

US is more available than CT, but it has a lower accuracy: with US the visualization of the appendix is highly dependent on the skill of the sonographer, patient habitus, position of the appendix and presence of intestinal gas (sensitivity 44-100%, specificity 47-99%) (2-3).

Previous literature has demonstrated that magnetic resonance imaging (MRI) is superior to US in the diagnosis of appendicitis, and nearly equal to CT (4-5). The main limitations of MRI include its high cost, limited availability, and long examination times.

Therefore, the objective of this prospective study is to determine the feasibility and diagnostic performance of an abbreviated MRI protocol for the diagnosis of appendicitis.

A total of 152 consecutive patients with clinical suspicion of acute appendicitis were referred to the emergency department of radiology. The choice between surgical intervention and medical-only treatment was based on the specific institution’s protocol, based on a clinical-radiological assessment with ultrasound and CT in selected cases only. Of these 152 patients, 67 patients underwent MRI, based on the results of a severity score (Alvarado score ≥ 5) and were subsequently included in this study. The abbreviated MRI protocol was acquired on a 3T MR system (Discovery 750w, GE Healthcare) with patients in the supine position, with axial and coronal T2-Weighted (T2W) sequences and axial Diffusion-weighted Imaging (DWI). No oral or intravenous contrast agents or antiperistaltic agents were used in the study.

MRI images were analyzed by two radiologists, blinded to clinical and other imaging data, on consensus. Features analyzed were: maximum serosa-to-serosa diameter of the appendix, maximum wall thickness, T2 signal intensity in the wall and lumen, presence of diffusion restriction in the wall, fat stranding in the right lower fossa (RIF), presence of appendiculitis, free fluid in the abdomen, and presence of loco-regional mesenteric lymphadenopathy. For the diagnosis of appendicitis, an appendix greater than 6 mm in diameter with signs of inflammation was considered positive (6). T2 hyperintensity and diffusion restriction in the wall of the appendix were used to determine positivity in suspect cases.

Histopathological examinations (HPE) were used as reference standard in surgical cases (n= 39); in non-surgically treated cases, the clinical diagnosis at discharge and 3-months follow-up were used instead (n= 28).

The mean and median duration of acquisition with the abbreviated MRI protocol was 14 and 12.5 min, respectively. The appendix was visualized at MRI in 62/67 patients (92.5%) and a diagnosis of appendicitis obtained in 45/67. Of the remaining 22 cases, an alternative diagnosis was found in 6, and the remaining 16 were considered negative MRI examinations. Of the 39 patients who underwent surgery, HPE determined that 34 had appendicitis, 3 normal appendix, 1 cecal perforation, and 1 appendiceal diverticulum.

The abbreviated MRI protocol had a sensitivity, specificity, PPV, NPV and accuracy of 93.3%, 86.4%, 93.3%, 86.4%, and 91.0%, respectively. The two parameters with best diagnostic accuracy were fat stranding in RIF and diffusion restriction in the wall of the appendix, 86.6% and 83.7%, respectively. The median diameter of the appendix in patients with acute appendicitis was 9.7 mm and 5.9 mm in those without appendicitis. The ROC curve of appendix diameter for the diagnosis of appendicitis had an AUC of 0.843: a cut-off of 8 mm had a sensitivity of 81.8% and specificity of 83.3%. The median appendix wall thickness in patients with acute appendicitis was 3.3 mm and 2.3 mm in those without appendicitis: the ROC curve had an AUC of 0.737. The ADC values in the appendix wall could only be satisfactorily measured in 49 subjects, and no significant difference was found between those with and without appendicitis.

In conclusion, the authors have defined an abbreviated MRI protocol consisting only of T2W and DWI sequences, without contrast or antiperistaltic agents, able to reduce the duration of the examination while maintaining an excellent diagnostic accuracy.

 

References:

 

  1. Stewart B, Khanduri P, McCord C, Ohene-Yeboah M, Uranues S, Vega Rivera F et al (2014) Global disease burden of conditions requiring emergency surgery: Global disease burden of conditions requiring emergency surgery. Br J Surg 101:e9-22.
  2. Terasawa T, Blackmore CC, Bent S, Kohlwes R J (2004) Systematic Review: Computed Tomography and Ultrasonography To Detect Acute Appendicitis in Adults and Adolescents. Ann Intern Med 141:537.
  3. Giljaca V, Nadarevic T, Poropat G, Nadarevic V S, Stimac D (2017) Diagnostic Accuracy of Abdominal Ultrasound for Diagnosis of Acute Appendicitis: Systematic Review and Meta-analysis. World J Surg 41:693-700.
  4. Thieme ME, Leeuwenburgh MM, Valdehueza ZD, Bouman DE, de Bruin IG, Schreurs WH et al (2014) Diagnostic accuracy and patient acceptance of MRI in children with suspected appendicitis. Eur Radiol 24:630-7.
  5. Eng KA , Abadeh A, Ligocki C, Lee YK, Moineddin R, Adams-Webber T et al (2018) Acute Appendicitis: A Meta-Analysis of the Diagnostic Accuracy of US, CT, and MRI as Second-Line Imaging Tests after an Initial US. Radiology 288:717–727.
  6. Moteki T, Horikoshi H (2007) New CT Criterion for Acute Appendicitis: Maximum Depth of Intraluminal Appendiceal Fluid. AJR Am J Roentgenol 188:1313-9.

 

Dr. Alessandro Calabrese is a fourth-year radiology resident at Sapienza University of Rome, Italy. He graduated from Sapienza University in 2017 with a thesis on the role of Intravoxel Incoherent Motion (IVIM) in the evaluation of breast lesions. His main interests include breast and abdominal radiology, with several papers as author/co-author published on these topics in international journals.

Comments may be sent to: alessandro.calabrese@remove-this.uniroma1.it


Assessment of morphological CT imaging features for the prediction of risk stratification, mutations, and prognosis of gastrointestinal stromal tumors

Roberto Cannella, Emanuele Tabone, Giorgia Porrello, Giovanni Cappello, Cecilia Gozzo, Lorena Incorvaia, Giovanni Grignani, Alessandra Merlini, Lorenzo D’Ambrosio, Giuseppe Badalamenti, Daniele Regge, Tommaso Vincenzo Bartolotta

Eur Radiol31, 8554–8564 (2021). https://doi.org/10.1007/s00330-021-07961-3

Dr. Charikleia Triantopoulou, Head of the Radiology Department and Anastasia Doukopoulou, Third-Year Radiology Resident ‘Konstantopouleion’ General Hospital of Nea Ionia, Athens, Greece.

 

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. Most commonly originate from the stomach (50-60%) and small bowel (30-35%) and occasionally are found in colorectum (5%) and esophagus (<1%). Nevertheless, they can arise anywhere along the gastrointestinal tract and rarely even in extra-gastrointestinal locations [1].

In order to achieve the appropriate treatment and patient’s management it is important to ensure an accurate preoperative risk stratification of gastrointestinal stromal tumors. The National Institutes of Health (NIH) consensus classification system is currently used to assess patient prognosis after surgical resection and is based on tumor location, size, mitotic count and rupture [2].

In this retrospective dual-institution study, the authors intended to assess the correlation between CT imaging features of GISTs with risk stratification, prediction of mutation status, and prognosis.

Eighty-eight patients with pathologically proven GISTs were included in the study. All of them had preoperative contrast-enhanced CT performed between 2008 and 2019, received no treatment before imaging and had available pathological analysis. All CT studies were reviewed by two readers with experience in abdominal imaging in a blinded fashion.

Firstly, they evaluated the location of the lesion, as well as the size and the growth (endophytic, exophytic or mixed). Also, the following morphological imaging features of GISTs were assessed: contour, margins, enhancement pattern, enhancement degree, presence of intralesional calcifications, intralesional hemorrhage, surface ulceration, cystic degeneration, tumor necrosis, intratumoral vessels, enlarged feeding vessels or draining veins and direct invasion of adjacent abdominal organs.

The analysis of CT studies revealed that the primary tumor was located in the stomach in 52 cases, and small bowel and colorectum in 32 and 4 cases, respectively. GISTs most commonly presented as large lesions measuring ≥ 5 cm with exophytic growth, well-defined margins, and variable amount of intralesional necrosis. Distant metastases were identified in 14 cases. According to NIH 2008 risk stratification criteria, 3 patients had very low-risk GISTs, 21 low-risk, 19 intermediate risk and 45 high-risk. Mutational analysis presented 50 KIT 11, 11 KIT 9, 14 PDFGRα mutations, and 13 wild-type GISTs.

After statistical analysis, it was shown that there are differences in imaging features according to the risk stratification of GISTs. The percentage of high-risk tumors demonstrating lobulated contour, heterogeneous enhancement, hypoenhancement on portal venous phase, presence of necrosis, severe intralesional necrosis, intratumoral vessels and enlarged feeding vessels was remarkably higher compared to low-to-intermediate risk GISTs. Independent predictors of high-risk GISTs were lesions size ≥ 5 cm and enlarged feeding vessels, whereas in the cases of GISTs without metastases, only lesions size ≥ 5 cm and lobulated contour independently predicting high-risk tumors.

The identification of specific mutations genes has led to more targeted treatments with exceptional increase in survival rates [3]. This study investigates the correlation between tumor enhancement and different mutation genes. As a result, hyperenhancement on portal venous phase was significantly more frequent in PDGFRα-mutated/wild type GISTs compared to GISTs with KIT mutations.

During a median follow-up time of 44.7 months, progression and postoperative recurrence was observed in 25 patients, while 5 patients died due to the GIST. High-risk GISTs had remarkably shorter progression-free survival compared to low-to-intermediate-risk GISTs. Despite that several imaging features were associated with poorer PFS (including size, contour, margins, enhancement pattern, calcifications, necrosis, amount of necrosis, cystic degeneration, intratumoral vessels, enlarged feeding vessels, and direct organ invasion), only ill-defined margins were associated with poorer PFS at multivariate analysis. In addition, ill-defined margins and intralesional hemorrhage were independently associated with poorer overall survival.

In this study, the authors try to indicate that multiple CT imaging features are significantly different between low-to-intermediate-risk and high-risk GISTs and investigate the predictive values of these features for the progression-free survival and overall survival. They also refer to other studies, i.e. Zhou et al [4], with which interestingly share some common results, that tumor size and enlarged vessels feeding or draining the mass are independent predictors of high-risk tumors.

In conclusion, this efficient study may have used a relatively small sample, but it proved that morphologic contrast-enhanced CT features are considerably different depending on the risk status or mutations. These findings may help in the prognostic prediction of GISTs and if supported by further studies with radiologic-pathologic correlations may lead to more appropriate and targeted therapies.

 

References:

 

  1. Imaging of Gastrointestinal Stromal Tumors: From diagnosis to evaluation of therapeutic response. Federica Vernuccio et al. Anticancer Research Jun 2016, 36 (6): 2639-2648
  2. Risk stratification of patients diagnosed with gastrointestinal stromal tumor. Heikki Joensuu et al. Human Pathology 2008, 39: 1411-1419
  3. Gastrointestinal stromal tumours: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up. Casali P.G. et al. Annals of Oncology 2018, 29: iv68–iv78
  4. Predictive features of CT for risk stratifications in patients with primary gastrointestinal stromal tumour. Zhou C. et al. Eur Radiol 2016, 26:3086–3093

 

Dr. Anastasia Doukopoulou is a third-year radiology resident at ‘Konstantopouleion’ General Hospital of Nea Ionia, Athens, Greece. She completed her undergraduate medical degree at Comenius University in Bratislava in 2018 and after that she joined the Medical Imaging Department at General Hospital of Naoussa in Greece. Abdominal imaging is one of the main fields she is interested in.

Comments may be sent to: anas.doukopoulou@remove-this.gmail.com


Predictive value of gadoxetic acid-enhanced MRI for posthepatectomy liver failure: a systematic review

Qiang Wang, Anrong Wang, Ernesto Sparrelid, Jiaxing Zhang, Ying Zhao, Kuansheng Ma & Torkel B. Brismar

European Radiology (2021). doi: 10.1007/s00330-021-08297-8

 

Postpancreatectomy liver failure (PHLF) is a major complication after liver resection and is the leading cause of perioperative morbidity and mortality. The reported incidence is typically around 10%, depending on different PHLF criteria and individual medical centre experience, however a frequency of 43% has also been reported [1,2]. For this reason, there is an urgent need for effective and non-invasive biomarkers to predict and avoid PHLF.

Common investigations and scoring models for the evaluation of liver function include, blood biochemical tests, indocyanine green (ICG) retention test, the LiMAx ® test, Child-Pugh score and the Model for End-Stage Liver Disease (MELD). Whilst these provide information on global liver function, they do not take into consideration the heterogeneous distribution of liver function amongst the different liver segments, which is especially significant in liver fibrosis or cirrhosis patients or after chemotherapy [3].

Gadoxetic acid (Primovist ®) enhanced magnetic resonance imaging (MRI) is used as a routine preoperative workup for the detection of liver lesions and their characterisation. 50% of the contrast medium is taken up by organic anion-transporting polypeptides (OATPs) or sinusoidal membrane of normal hepatocytes, and is then excreted into biliary ducts [4]. Enhancement of liver parenchyma is determined by the equilibrium of this transport mechanism.

Wang et al. carried out a systematic review which aims to evaluate the efficacy of gadoxetic acid-enhanced MRI-derived parameters as an imaging biomarker in preoperative prediction of PHLF. Studies evaluating the incidence of PHLF in patients who underwent preoperative liver function assessment using gadoxetic acid-enhanced MRI were included in a systematic literature search. The Quality In Prognostic Studies (QUIPS) tool was adopted to evaluate the risk of bias. Out of a total of 114 studies found in the systematic research search, 15 studies were considered eligible.

Most studies included were marked as low to moderate risk of bias in each domain of QUIPS. The most commonly used parameter was relative liver enhancement or its related parameters. The reported incidence of PHLF ranged from 3.9 to 40%, and the predictive sensitivity and specificity of gadoxetic acid-enhanced MRI parameters varied from 75 to 100% and from 54 to 93% in ten reported studies. A majority of the studies revealed that the gadoxetic acid-enhanced MRI parameter was a predictor for PHLF.

Risk factors for PHLF may result from patient aspects (namely age, body mass index, chronic diseases), liver quality (cirrhosis, hepatitis, neo-adjuvant chemotherapy), and factors related to the surgery itself (such as intraoperative blood loss, time of in-flow occlusion) [5].

The Authors highlight a number of limitations of this study, with the most significant limitation being the heterogeneity of the studies, both in the variance of MRI liver function parameters as well as in the indication and extent of liver resection. Other limitations include the fact that only less than half the studies had a large sample size, only one was prospectively designed, and just two studies included both a study cohort and a validation cohort.

Overall, this present systematic review provides evidence that quantitative liver function parameters derived from gadoxetic acid-enhanced MRI exhibit encouraging efficacy in the prediction of PHLF. Multicenter, prospective trials with large sample size and reliable, unified liver function parameters are required to validate the efficacy of individual liver function parameters.

 

References:

 

  1. Rahbari NN Garden OJ Padbury R Maddern G Koch M. Posthepatectomy liver failure: a definition and grading by the International Study Group of Liver Surgery (ISGLS) Surgery . 2011;149:713–724.
  2. Mehrabi A, Golriz M, Khajeh E et al (2018) Meta-analysis of the prognostic role of perioperative platelet count in posthepatectomy liver failure and mortality. Br J Surg 105:1254–1261
  3. Guglielmi A, Ruzzenente A, Conci S, Valdegamberi A, Iacono C (2012) How much remnant is enough in liver resection? Dig Surg 29:6–17
  4. Van Beers BE, Pastor CM, Hussain HK (2012) Primovist, Eovist: what to expect? J Hepatol 57:421–429
  5. Guglielmi A, Ruzzenente A, Conci S, Valdegamberi A, Iacono C. How much remnant is enough in liver resection? Dig Surg. 2012;29(1):6-17. doi: 10.1159/000335713. Epub 2012 Mar 15. PMID: 22441614.

 

Dr. Maria Croucher is a first-year radiology resident at Mater Dei Hospital, Malta. She completed her undergraduate medical degree at the University of Malta in 2017 and joined the Medical Imaging Department in 2020 where she is undertaking training in diagnostic and interventional radiology. She is also currently studying for a Master's degree in Clinical Radiology at the University of Malta.

Comments may be sent to: mariacroucher@remove-this.gmail.com


CT angiography of abdomen and pelvis in critically ill COVID-19 patients: imaging findings and correlation with CT chest score

Harsna V. Vadvala, Alam Shan, Elliot K. Fishman, Rakhee S. Gawande

Abdominal Radiology. Published online, 11 June 2021. https://doi.org/10.1007/s00261-021-03164-y

Dr. Charikleia Triantopoulou, Head of the Radiology Department and Paraskevi Vlachou, Consultant Radiologist ‘Konstantopouleion’ General Hospital of Nea Ionia, Athens Greece.

 

The COVID-19 disease is a global pandemic, affecting more than 185 countries worldwide. SARS-COV2 is a highly infectious virus, responsible not only for acute respiratory syndrome, but also encompasses a high possibility for vascular and coagulation disorders, the leading factor for high mortality rates.

COVID-19 disease seems to result in a multi system dysfunction (1) with the involvement of several organs as well as vascular involvement. Endothelial injury and inflammation associated with SARS-COV2, mediate reactions which promote vascular complications.

In this retrospective study, the authors intended to focus on the most common vascular abnormalities seen in COVID-19 patients and combine them with the severity of lung disease.

COVID-19 patients admitted to the hospital underwent CTA chest, abdomen and pelvis or CTA abdomen and pelvis studies. Patients should be >18 years old, with diagnosis of COVID-19 infection. Exclusion criteria for this study were examinations performed prior to diagnosis, or examinations performed later than 3 months from initial COVID diagnosis. All studies were reviewed by two independent experienced radiologists.

Firstly, CT chest score was estimated. The five lung lobes were evaluated individually, on a scale from 0 (no involvement- 1 for <5% involvement, 2 for 5-25%, 3 for 26-50%, 4 for 51-75%) to 5 (for more than 75% involvement). The sum of the scores of all five lobes ranges from 0 to 25 (maximal involvement).

Then, analysis of CTA abdomen and pelvis revealed many vascular disorders. Most common were hematomas (46,7%). Second comes active vascular extravasation (24.4%). 8 patients had vascular occlusion and finally artery occlusion was seen in 3 patients. Arterial pseudoaneurysm was even rarer.

After statistical analysis, it was proven that there is strong association between high incidence of vascular disorders and higher CT chest score. Patients with moderate (11-17) to severe (18-25) scores, had had 6,22 to 21 times more possibilities to develop vascular disorders, compared to those with low CT chest score (2).

Additionally, high CT chest score seems to be associated with other types of injury (non-vascular), as abdomen and pelvis CT reveals. Most common sites of involvement are biliary tree, liver, kidneys and GI tract.

In this study, the authors try to summarize all vascular complications in a very helpful and comprehensive way. They also refer to other studies, i.e. Nadkarni et al (3), which emphasizes the benefits of prophylactic anticoagulation therapy, in comparison to those who did not receive any anticoagulation. A total of 46,7% developed a hematoma and 24,4% of patients had emergency active vascular extravasation.

Despite the bleeding propensity, thrombotic complication rate still remains higher as several studies demonstrated (4). Thus, the literature suggests that prophylactic anticoagulation is crucial, for less mortality and less intubation rates, nonetheless underlines the necessity for caution and strict compliance with anticoagulation guidelines in very sick COVID-19 patients.

Similar results were obtained about non-vascular findings. That means patients with higher CT chest score, had more often and more prominent abdominal and pelvis findings, such as cholestasis, hepatitis, acute pancreatitis, bowel ischemia, acute diverticulitis, renal infarcts etc. Therefore, another highlight of this study is the necessity for performing abdominal and pelvis CT, as a routine (5).

In conclusion, this efficient study used a relatively small sample, but it is an adequate cohort for CTA of abdomen and pelvis, proving the hypothesis of the study, that critically ill COVID-19 patients (high scores of CT chest), have significantly higher rates of vascular and non-vascular complications.

 

References:

 

  1. COVID-19- A vascular disease. Hasan K. Siddiqi et al. Trends Cardiovasc Med. 2021 Jan;31(1):1-5
  2. Vascular comorbidities worsen prognosis of patients with heart failure hospitalized with COVID-19. Jacob Mok et al. Open Heart. 2021 Jun;8(1):e001668. doi:10.1136/openhrt-2021-001668
  3. Anticoagulation, Bleeding, Mortality, and Pathology in hospitalized patients with COVID-19. Nadkarni et al. J Am Coll Cardiol. 2020;76(16):1815-26
  4. Thromboembolic risk and anticoagulant therapy in COVID-19 patients: emerging and call for action. Kollias A et al. Br J Haematol. 2020;189(5):846-7.
  5. Abdominal Imaging Findings in COVID-19: Preliminary Observations. Rajesh Bhayana et al. Radiology. 2020 Oct; Published Online https://doi.org/10.1148/radiol.2020201908

 

Paraskevi Vlachou MsC, is a young radiologist at ‘Konstantopouleion’ General Hospital of Nea Ionia-Athens, Greece. She is an active ESGAR member, attending regularly annual meetings and workshops. Her main interest is in abdominal and breast radiology. She completed a postgraduate programme at Athens University in Interventional Radiology and in 2016 she won a 3-month ESOR scholarship in Breast Imaging, at Policlinico Agostino Gemelli in Rome.

Comments may be sent to: vivi_vlachou@remove-this.hotmail.com


The split scar sign as an indicator of sustained complete response after neoadjuvant therapy in rectal cancer

Inês Santiago, Maria Barata, Nuno Figueiredo, Oriol Parés, Vanessa Henriques, António Galzerano, Carlos Carvalho, Celso Matos, Richard J. Heald.

Eur Radiology 2020 Jan;30(1):224-238.  doi: 10.1007/s00330-019-06348-9

 

Total mesorectal excision (TME) is nowadays a standard surgery for rectal cancer, that showed significant increase in 5-year survival and decrease in local recurrence.[1]
Moreover, clinical trials and guidelines support the use of neoadjuvant radiation for further oncologic improvement in high-risk patients.[2] It was shown that up to 15–27% of patients who underwent preoperative chemoradiation had no residual viable tumor cells detected in the resected specimen.[3,4]
The studies demonstrated similar outcomes in those patients who later underwent surgery and those who were managed with “watch and wait protocol”, avoiding significant morbidity and mortality risks associated with TME in a second group.[5]
Watchful waiting is now an established policy in many colorectal centers worldwide.  This strategy requires close surveillance protocols for early detection of regrowth, including both imaging studies and colonoscopy. MRI is playing a fundamental role in assessing rectal wall and mesorectum before, during and after treatment. During the last decade, MRI response assessment is mainly based on tumor regression grade, evaluating intermediate residual tumor signal and low fibrosis signal on T2 weighted imaging6, and diffusion weighted imaging, that improves accuracy, but still depends on reader’s experience and quality of the image.

Inês Santiago and co-authors reported a new radiologic pattern of sustained complete response, that they called “split scar sign” (mrSSS), evaluated on high resolution T2-weighted images, and measured its diagnostic performance. This new pattern, according to the authors, is easy to assess and has a high specificity and PPV.

This is a retrospective study that enrolls fifty-eight patients who underwent neoadjuvant therapy for rectal adenocarcinoma in their institution between 1/10/2012 and 1/3/2017.
Patients’ demographics and clinical data was collected by physician uninvolved in imaging reading. Rectal MRI images were blindly and independently analyzed by two gastrointestinal radiologists, with 12 and 10 years of experience, respectively. Observers performed initial rectal cancer staging and later analyzed post neoadjuvant pelvic MR, acquired with a mean interval of 9.1 weeks after the end of radiotherapy.

On the first round: the presence of the split scar sign (mrSSS+) -a radiologic sign observed on T2-WI and characterized by a particular morphologic pattern of the tumor scar- was considered indicative of a sustained clinical response (SCR). It is characterized by the presence of an inner, markedly T2-hypointense, regular layer of tissue at tumor location, corresponding to the fibrosed submucosa, covered by normal mucosa, or denuded when ulceration is present; and a homogeneous intermediate signal intensity layer underneath it, corresponding to a markedly thickened and partially fibrotic muscularis propria. At the periphery, a T2-hypointense layer of variable regularity and thickness is usually apparent, translating perirectal fibrosis. It may, however, be absent, particularly in early-staged tumors. In mucinous tumors or tumors which respond with mucinous degeneration, the intermediate signal intensity may be replaced with high signal intensity, corresponding to mucin pooling. Vessels may pierce the outer hypointense layer in positive cases. On the other hand, the split scar sign is considered absent (mr SSS-) when the inner or the outer hypointense layer (when present) are bulged or breached by intermediate signal intensity, either the scar is completely hypointense or heterogeneous, with a “disorganized” appearance.

On a second round the authors assessed the relative proportion of intermediate signal intensity on T2-WI (mrT2), and of high signal intensity on high b-value diffusion-weighted imaging (mrDWI), separately and without taking into consideration morphologic pattern of the scar.

Endoscopy was performed upon patient restaging and tumor p stage was retrieved from the pathology reports in operated patients.
The reference standard was SCR, defined as pathologic complete response or long-term local recurrence-free clinical follow-up (minimum follow-up period of 1 year).

Qui-square test was employed in search for associations between SCR and mrSSS, mrT2, mrDWI and endoscopy. Interobserver agreement for imaging parameters was estimated using Cohen’s kappa (k).

The obtained results were the following: mrSSS was significantly associated with SCR, with specificity= 0.97/0.97, sensitivity= 0.52/0.64, PPV= 0.93/0.94, NPV= 0.73/0.78, and AuROC= 0.78/0.83 for observers 1/2, respectively. According to their results, the authors divided all patients in two main groups: mr SSS+ patients have a 97% chance of achieving a SCR, and those with mr SSS- have a 73–78% chance of failing to do so.

Despite some limitations (e.g., retrospective nature, cases from one institution, absence of lymph-node assessment, the time interval between the end of chemoradiation and MR imaging, minimal follow-up of one year, and a type of radiotherapy applied in their institution), this study demonstrated that split scar sign, though not sensitive, is very specific morphologic pattern for the identification of sustained complete responders after neoadjuvant therapy in rectal cancer.
Observers that mrSSS has even higher specificity than combined morphologic and functional visual pattern approach, based on T2-WI and DWI: 94% vs 77% respectively [7].

This morphologic pattern is state of art in rectal cancer response, already widely accepted by GI radiologists and appearing with increasing frequency in the scientific presentations of ESGAR. I encourage GI radiologists to apply it routinely, not only for improvement in patient selection for “watch-and-wait” after neoadjuvant therapy, but also for surgery planification after radiation in low rectal cancer, for example, evaluating external sphincter possible preservation in selected patients.

 

References:

 

  1. Heald RJ, Ryall RD. Recurrence and survival after total mesorectal excision for rectal cancer. Lancet. 1986 Jun 28;1(8496):1479-82. doi: 10.1016/s0140-6736(86)91510-2. PMID: 2425199.
  2. Glimelius B, Tiret E, Cervantes A, Arnold D; ESMO Guidelines Working Group. Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment, and follow-up. Ann Oncol. 2013 Oct;24 Suppl 6:vi81-8. doi: 10.1093/annonc/mdt240. PMID: 24078665.
  3. Janjan NA, Khoo VS, Abbruzzese J, et al. Tumor downstaging and sphincter preservation with preoperative chemoradiation in locally advanced rectal cancer: the M. D. Anderson Cancer Center experience. Int J Radiat Oncol Biol Phys 1999; 44: 1027–38.
  4. Pucciarelli S, Toppan P, Friso ML, et al. Complete pathologic response following preoperative chemoradiation therapy for middle to lower rectal cancer is not a prognostic factor for a better outcome. Dis Colon Rectum 2004; 47: 1798–807.
  5. Dossa F, Chesney TR, Acuna SA, Baxter NN. A watch-and-wait approach for locally advanced rectal cancer after a clinical complete response following neoadjuvant chemoradiation: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2017 Jul;2(7):501-513. doi: 10.1016/S2468-1253(17)30074-2. Epub 2017 May 4. PMID: 28479372.
  6. Patel UB, Taylor F, Blomqvist L, George C, Evans H, Tekkis P, Quirke P, Sebag-Montefiore D, Moran B, Heald R, Guthrie A, Bees N, Swift I, Pennert K, Brown G. Magnetic resonance imaging-detected tumor response for locally advanced rectal cancer predicts survival outcomes: MERCURY experience. J Clin Oncol. 2011 Oct 1;29(28):3753-60. doi: 10.1200/JCO.2011.34.9068. Epub 2011 Aug 29. PMID: 21876084.
  7. Lambregts DMJ, Delli Pizzi A, Lahaye MJ, van Griethuysen JJM, Maas M, Beets GL, Bakers FCH, Beets-Tan RGH. A Pattern-Based Approach Combining Tumor Morphology on MRI With Distinct Signal Patterns on Diffusion-Weighted Imaging to Assess Response of Rectal Tumors After Chemoradiotherapy. Dis Colon Rectum. 2018 Mar;61(3):328-337. doi: 10.1097/DCR.0000000000000915. PMID: 29369900.

 

Polina Rudenko is a young consulting gastrointestinal radiologist from La Fe University Hospital (Valencia, Spain) mainly specializing in colorectal cancer and inflammatory bowel disease. She is an active ESGAR member since 2015.

Comments may be sent to: rudenko_pol@remove-this.gva.es


Postoperative complications of colorectal cancer

Pallan A, Dedelaite M, Mirajkar N, Newman P.A, Plowright J, Ashraf S

Clinical Radiology. July 2021. DOI: doi.org/10.1016/j.crad.2021.06.002

 

Colorectal cancer (CRC) imaging, both pre and post op, has become a more common and complex imaging finding. Sound radiological and surgical knowledge is required to promptly detect and aid manage of post-surgical complications as colorectal surgery is associated with high morbidity of 35%, and mortality of 1-16.4% [1].

This educational review article, in the first part illustrates in a detailed yet diagrammatic style, the type of colorectal surgeries. The second part of the review, focuses on the post-operative complications which are logically described with their incidence together with which imaging techniques are best suited to identify these complications.

Surgeries are described in detail and include traditional surgeries like segmental resection, Hartmann’s procedure, anterior resection, abdominoperineal resection and new minimal invasive procedure’s such as trans-anal endoscopic microsurgery (TEMS) and trans-anal minimally invasive surgery (TAMIS). The descriptions and illustrations including the anatomy are easy to understand and will help guide the radiologist; particularly of note was a systematic explanation of different type of anterior resection depending on the level tumour. Those who may not have done a surgical rotation in the past would benefit from these.

Second part of the review focuses on complications; firstly focusing on anastomosis leak (AL) as a common complication with a rate of 1-19 % [2]. Interestingly the paper divided the leaks into three clinical grades A to C as this effects clinical management [8], and the review also categorised these in terms of onset after surgery. Lower rectal anastomoses are associated with higher leak rates [ 3,4]. CT with intravenous contrast medium (CECT) and endoluminal contrast medium is the preferred imaging modality in diagnosing AL and is superior to water-soluble contrast medium enema (WSCE) [4]. Tabulation of the imaging protocol provided for use on left and right sided anastomosis was given. There was a good description of radiological findings with appropriate illustration; these were further separated by what to expect given the number of post-operative days. The pitfalls of using WSCE was described.

Multiple modalities can be used to characterise fistula along with associated findings. Although the review describes fluoroscopic fistulography as excellent in visualising the tract, it is limited in use of extra luminal findings. The review compares use of CECT with both oral and direct luminal contrast with MRI. MRI was suggested to be useful for diagnosing chronic fistulation.

Associated collections, anatomical distortion or inflammatory change are seen with both CT and MRI. It was suggested luminal distension when using MRI with water-based soluble solution can aid diagnosis. These practices however vary depending on local protocol and individuals.

Post-operative strictures are common with incidence of between 3-30% [5]. The review clearly identified risk factors that would help the radiologist plan studies; with ischemia, previous anastomotic leak and radiotherapy quoted as risk factors. Although they can be identified on either WSCE, CT colography or water enema CT examinations, the radiological features are universal as described in the review as short, smooth narrowing with normal mural thickness and no extra luminal mass. There are very useful illustration in multiple modalities in the review.

Although a rare complication (0.5-4.9%), post-operative bleeding can be serious [6,7]. The paper gives a detail illustration on use of multiphasic CECT with high flow rate to aid diagnosis of active bleeding. There is an adequate explanation on the type of vascular injury to be expected depending on the type of surgery that has been performed as well as pointers to make note previous history of radiotherapy. This provides a good illustration on where to look out for the bleed. Interestingly left sided colonic resection was noted to be associated with an iatrogenic injury of the spleen at rate of 1.1% and right hemi-colectomies associated with a 1.6% incidence of injury of the superior mesenteric vein.

Intestinal obstruction findings are reviewed in detail. Plain radiograph was quoted to identify up to 60% of obstruction cases and one could argue that this simple test could remain the initial modality of choice. Intraluminal fluid in obstruction was suggested to provide neutral luminal contrast medium. The paper later went on to state a further advantage that CECT alone without oral contrast of being 95% specific for ischemia. Interestingly the paper has stated that if there is bowel wall enhancement and no mesenteric stranding, bowel ischemia can be confidently excluded.

Brief review and illustration of adhesions, ileus and hernia as well as stoma complications were also described. Although iatrogenic genitourological injury following CRC resection is rare, there was an in-depth review with excellent illustration and description.

This review article is logically structured, provides not only excellent anatomical illustration of surgical methodology but also good illustration of potential CRC surgical complications together with discussion on how best to image these. Those radiologists who may have not had a background in surgery will benefit the most from the first half of the review. There are however no illustrations on complications specifically related to minimal invasive surgery. In addition, medium to longer term post op complication and recurrence symptoms can overlap; this paper does not help guide the reader on when these should be suspected or how to modify imaging techniques to aid diagnosis.

 

References:

 

  1. Tevis SE, Kennedy GD. Postoperative complications: looking forward to a safer future. Clin Colon Rectal Surg 2016;29(3):246e52.
  2. McDermott FD, Heeney A, Kelly ME, et al. Systematic review of preoperative, intraoperative and postoperative risk factors
  3. Hyman N, Manchester TL, Osler T, et al. Anastomotic leaks after intestinal anastomosis: it’s later than you think. Ann Surg 2007;245(2):254e8.
  4. Khan AA, Wheeler JM, Cunningham C, et al. The management and outcome of anastomotic leaks in colorectal surgery. Colorectal Dis 2008;10(6):587e92
  5. Luchtefeld MA, Milsom JW, Senagore A, et al. Colorectal anastomotic stenosis results of a survey of the ASCRS membership. Dis Colon Rectum 1989;32(9):733e6.
  6. Martinez-Serrano MA, Pares D, Pera M, et al. Management of lower gastrointestinal bleeding after colorectal resection and stapled anastomosis. Tech Coloproctol 2009;13(1):49e53.
  7. Golda T, Zerpa C, Kreisler E, et al. Incidence and management of anastomotic bleeding after ileocolic anastomosis. Colorectal Dis 2013;15(10):1301e8.
  8. Rahbari NN, Weitz J, Hohenberger W, et al. Definition and grading of anastomotic leakage following anterior resection of the rectum: a proposal by the International Study Group of Rectal Cancer. Surgery 2010;147(3):339e51.

 

Dr. Muhammad Bilal Fayyaz is working as an Associate Specialist at Chesterfield Royal NHS trust since 2020 with a sub-specialty interest in GI, Paediatrics and IR. He graduated from Khyber Medical College, Peshawar, Pakistan in 2010. Afterwards, he completed his radiology training in Shaukat Khanum Memorial Cancer Hospital, in Lahore (2013-2018). He did a fellowship in Paediatric Interventional Radiology at Alder Hey Children NHS trust, Liverpool, UK in 2019. He is currently working alongside an experienced team of GI radiologists including Dr. Rajiv Karia.

Comments may be sent to: muhammad.fayyaz@remove-this.nhs.net


Imaging of abdominal complications of COVID-19 infection

Caruso D, Zerunian M, Pucciarelli F, Lucertini E, Bracci B, Polidori T, Guido G, Polici M, Rucci C, Iannicelli E, Laghi A.

BJR Open. 2021 Jul 5;2(1):20200052. doi:10.1259/bjro.20200052

 

The severe acute respiratory syndrome Coronavirus 2 (Sars-CoV-2) is typically characterized by respiratory symptoms. However, during the pandemic, other abdominal organs seem to be involved in the disease due to systemic effects of the SARS-CoV-2.
Currently, it is world-wide accepted that in some cases COVID-19 infection can present primarily with abdominal symptoms such as abdominal pain, diarrhea.
Abdominal symptoms seem to be related to angiotensin converting enzyme 2 (ACE) expression in the gastrointestinal and biliary tract. Briefly, COVID-19 may affect various abdominal organs, and cause typical and less typical abdominal imaging findings. Caruso et al. reported in their review article the imaging of abdominal complications related to COVID-19 infection [1].

1. Small and large bowel - high expression of ACE2 receptors on enterocytes membrane. CECT (contrast-enhanced CT) is the imaging modality of choice and shows gastrointestinal complications in up to 49% of the cases [2,4]:
- typical bowel wall thickening, submucosal oedema, bowel dilatation, pericolic fluid and fat stranding; bowel ischemia due to mesenteric and portal vein thrombosis
- atypical CECT findings include pneumatosis intestinalis, appendicitis

2. Liver - direct cytopathic virus effect; up to 62% of the COVID-19 patients have elevated ALS, AST and GGT enzymes, with hepatic steatosis, but no typical imaging features have been reported [5].

3. Kidneys - expression of ACE2 receptors on podocytes and proximal convoluted tubules cells and also direct virus-induced cytopathic effect; up to 19% of COVID-19 patients develop acute renal dysfunction; no typical imaging findings were reported [6].

4. Pancreas - SARS-CoV-2 was isolated from a pancreatic pseudocyst, but the pathogenesis is not totally clear yet. Up to 16% of the patients have pancreatic involvement, with acute pancreatitis associated with COVID-19 as the main finding [7].

5. Gallbladder - expression of ACE2 receptors in the biliary system. Imaging shows typical acute cholecystitis findings: gallbladder distension, wall thickening, with mural/mucosal hyperenhancement, fluid and fat stranding [8].

6. Spleen - involvement is related to the prothrombotic effect of COVID-19. Splenic infarction with typical CECT findings was reported: peripheral, wedge-shaped hypo enhancing area [9,10].

In conclusion, abdominal involvement of COVID-19 is related in many cases to the ACE2 receptors expression, and it is not such a rare event. It is crucial that radiologists keep in mind a possible abdominal finding of COVID-19 patients. The above-mentioned paper provides an overview of all COVID-19-related abdominal complications and should be kept in mind by members-in-training as well as senior doctors.

References:

 

  1. Caruso D, Zerunian M, Pucciarelli F, Lucertini E, Bracci B, Polidori T, Guido G, Polici M, Rucci C, Iannicelli E, Laghi A. Imaging of abdominal complications of COVID-19 infection. BJR Open. 2021 Jul 5;2(1):20200052. doi: 10.1259/bjro.20200052.
  2. Carvalho A, Alqusairi R, Adams A, Paul M, Kothari N, Peters S, et al. SARSCoV-2 gastrointestinal infection causing hemorrhagic colitis: implications for detection and transmission of COVID-19 disease. Am J Gastroenterol 2020; 115: 942–6. doi: doi.org/10.14309/ajg. 0000000000000667
  3. Zhang J-J, Dong X, Cao Y-Y, Yuan Y-D, Yang Y-B, Yan Y-Q, et al. Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China. Allergy 2020; 75: 1730–41. doi: doi.org/10.1111/all.14238
  4. Pan L, Mu M, Yang P, Sun Y, Wang R, Yan J, et al. Clinical characteristics of COVID-19 patients with digestive symptoms in Hubei, China: a descriptive, cross-sectional, multicenter study. Am J Gastroenterol 2020; 115: 766–73. doi: doi.org/10.14309/ ajg.0000000000000620
  5. Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med 2020; 8: 420–2. doi: doi.org/10.1016/S2213- 2600(20)30076-X
  6. Behzad S, Aghaghazvini L, Radmard AR, Gholamrezanezhad A. Extrapulmonary manifestations of COVID-19: radiologic and clinical overview. Clin Imaging 2020; 66: 35–41. doi: doi.org/10.1016/j. clinimag.2020.05.013
  7. Mukherjee R, Smith A, Sutton R. Covid-19- related pancreatic injury. Br J Surg 2020; 107: e190. doi: doi.org/10.1002/bjs.11645
  8. Xiao F, Tang M, Zheng X, Liu Y, Li X, Shan H. Evidence for gastrointestinal infection of SARS-CoV-2. Gastroenterology 2020; 158: 1831–3. doi: doi.org/10.1053/j.gastro. 2020.02.055 11. Behzad S, Aghagh
  9. Santos Leite Pessoa M, Franco Costa Lima C, Farias Pimentel AC, Godeiro Costa JC, Bezerra Holanda JL. Multisystemic infarctions in COVID-19: focus on the spleen. Eur J Case Rep Intern Med 2020; 7: 001747. doi: doi.org/10.12890/2020_ 001747
  10. Bhayana R, Som A, Li MD, Carey DE, Anderson MA, Blake MA, et al. Abdominal imaging findings in COVID-19: preliminary observations. Radiology 2020; 297: E207–15. doi: doi.org/10.1148/radiol. 2020201908

 

Dr. Roxana Pintican is a fourth year radiology resident at the County Clinical Emergency Hospital in Cluj-Napoca, Romania and also a PhD student at the “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca. Abdominal imaging is one of many fields she is interested in. She is very engaged in research and has also spent three months at the Cambridge University Hospital. She has participated in many congresses and conferences and published several articles in international journals as author/co-author.
Besides radiology, Roxana is also passionate about travelling and sports.

Comments may be sent to roxana.pintican@remove-this.gmail.com

 


Multiparametric US for Identifying Patients with High-Risk NASH: A Derivation and Validation Study

Sugimoto K, Lee DH, Lee JY, Yu SJ, Moriyasu F, Sakamaki K, et al.

Radiology 2021; 000: 1-10. https://doi.org/10.1148/radiol.2021210046

 

Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of the metabolic syndrome and is defined as the presence of 5% or greater hepatic steatosis in the absence of competing liver disease etiologies, use of drugs causing steatosis or other chronic liver diseases (1).
It encompasses a spectrum of clinical conditions, from simple hepatic steatosis to non-alcoholic steatohepatitis (NASH). Patients with NASH have a higher risk of developing fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). NAFLD is becoming a concerning health problem worldwide and the most common cause of liver disease globally (2).

Liver biopsy is the gold standard for the diagnosis of NASH. Its histological defining features are hepatic steatosis, hepatocellular damage (ballooning degeneration), inflammation, and fibrosis (3). Two previous studies observed that NAFLD with stage 2 or higher fibrosis and liver injury have a particularly high risk to develop complications (cirrhosis and HCC). They identified these patients as having high-risk NASH and proposed them as candidates for pharmacological treatment with anti-inflammatory and anti-fibrotic agents (4,5).

In this study, the authors aimed to identify patients with high-risk NASH using noninvasive methods. This was a retrospective cross-sectional study that analyzed data collected between April 2017 and March 2019 in Japanese patients with NAFLD. Findings were validated in an independent Korean dataset. Patients with suspected NAFLD were included and were evaluated with ultrasonography (US), liver biopsy, and clinical tests. Ultrasonography was performed immediately before liver biopsy, after 6 hours of fasting. The authors chose three US markers to estimate the degree of liver steatosis, fibrosis, and inflammation: liver stiffness (LS), attenuation coefficient (AC), and dispersion slope (DS), respectively. Liver biopsy was performed in all patients to be used as a reference standard, and NASH was defined as the presence of steatosis, hepatocyte ballooning, and lobular inflammation. Each patient underwent standard clinical evaluation with biochemical testing including aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels, and AST-ALT ratio.

Three multivariate regression models for high-risk NASH were built. Model 1 comprised US-based markers (LS, AC, and DS, defined as the LAD-NASH score), Model 2 serum-based markers, and Model 3 US-based and serum-based markers. Model 1 showed the second-highest area under the receiver operating characteristics (AUC) for detection of high-risk NASH, at 0.86 in the derivation study sample and 0.88 in the validation study sample. A dual cut-off approach was used to assess the diagnostic performance of Model 1 in the detection of high-risk NASH in the training cohort. With a cut-off for sensitivity greater than 90%, positive predictive value (PPV) was 69% and negative predictive value (NPV) was 87.5%. With a cut-off for specificity greater than 90%, they were 86.5% and 71.4%, respectively.

The LAD-NASH score resulted useful in both groups to identify patients with high-risk NASH, with a positive predictive value (PPV) of 86.5% and a negative predictive value (NPV) of 87.5% for respectively ruling in and ruling out patients with high-risk NASH among the population of patients with NAFLD. Having been configured to have two thresholds, a rule-in and a rule-out cut-off, the score can be used either as a screening tool or as a diagnostic test.

Using the LAD-NASH score, 59% of patients could have been diagnosed with high-risk NASH without undergoing liver biopsy.
The greatest limitation of this study (and this score) is that 26% of patients were categorized as being in a gray zone beyond PPV and NPV requiring additional, different evaluations to receive the correct diagnosis.

NAFLD is a prominent cause of liver disease. A simple screening and diagnostic tool, that takes advantage of a single, well-diffused, low-cost, non-invasive technique to detect high-risk NASH and therefore patients requiring medical treatment, is promising for the future assessment of this disease.

 

References:

 

  1. Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global Epidemiology of Nonalcoholic Fatty Liver Disease-Meta-Analytic Assessment of Prevalence, Incidence, and Outcomes. Hepatology 2016; 64(1): 73-84.
  2. Ekstedt M, Hagström H, Nasr P, Fredrikson M, Stål P, Kechagias S, et al. Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology 2015; 61(5): 1547–54.
  3. Hashimoto E, Taniai M, Tokushige K, Etsuko Hashimoto C. Characteristics and diagnosis of NAFLD/NASH. Journal of Gastroenterology and Hepatology 2013; 28(Suppl.4): 64-70.
  4. Sugimoto K, Moriyasu F, Oshiro H, Takeuchi H, Abe M, Yoshimasu Y, et al. The Role of Multiparametric US of the Liver for the Evaluation of Nonalcoholic Steatohepatitis. Radiology 2020; 296: 532–540.
  5. Lee DH, Cho E, Bae J, Lee JY, Yu S, Kim H, et al. Accuracy of Two-Dimensional Shear Wave Elastography and Attenuation Imaging for Evaluation of Patients With Nonalcoholic Steatohepatitis. Clin Gastroenterol Hepatol 2021; 19(4): 797-805.

 

Matilde Bariani is a third-year radiology resident at Policlinico G.B.Rossi, Verona, Italy. She graduated in 2017 in Medicine and Surgery at the University of Verona. She is affiliated to the Associazione Italiana Studio Pancreas (AISP) and European Society of Radiology (ESR). Her interests include pulmonary and gastrointestinal radiology, in particular she focused on the CT assessment of postoperative complications after DCP.

Comments may be sent to matildebariani@remove-this.gmail.com

 


MRI radiomics features of mesorectal fat can predict response to neoadjuvant chemoradiation therapy and tumor recurrence in patients with locally advanced rectal cancer

Jayaprakasam VS, Paroder V, Gibbs P, Bajwa R, Gangai N, Sosa RE, Petkovska I, Golia Pernicka JS, Fuqua JL 3rd, Bates DDB, Weiser MR, Cercek A, Gollub MJ.

Eur Radiol. 2021 Jul 29. doi: 10.1007/s00330-021-08144-w. Epub ahead of print.

 

Colorectal cancer is the third most common cancer worldwide and the second cause of oncologic-related mortality. Rectal cancer accounts for ~30% of the total cases of colorectal malignancies (1). The standard-of-care treatment for patients with locally advanced rectal cancer (LARC) is neoadjuvant chemotherapy (nCRT) followed by total mesorectal excision (TME) (2). However, the individual response is very heterogeneous, ranging from a pathological complete response to no tumor regression or even disease progression (3). Recently, radiomics has gained increasing interest, more and more papers investigating the efficacy of radiomics features as biomarkers for lesion characterization and tumor prognosis, including for rectal cancer (4,5).

In this new study by Jaypar and colleagues, the focus is on the radiomics features extracted not from the rectal tumor, but from the mesorectal fat. The authors aimed to assess the potential role of radiomics analysis of mesorectal fat for the prediction of clinical outcomes of LARC.

This retrospective study included 236 patients with LARC who underwent total nCRT and TME. The following clinical outcomes were evaluated: pathologic complete response (pCR), local and distant recurrence, clinical (cT) and post-treatment (ypT) T categories, clinical (cN) and post-treatment (ypN) N categories, and clinical (cTNM) and post-treatment (ypTNM) TNM stages. Most patients had a cT category <4 (n=201), cN category>0 (n=213), post-treatment ypT category >0 (n=190), were post-treatment node-negative patients (n=176) and without local or distant recurrence (n=164, n=171 respectively). 101 radiomics features were extracted from the unfiltered, T2-weighted axial images of the baseline rectal MRI scans. Mesorectal fat segmentation was performed individually by three radiologists, excluding other structures such as tumor deposits, lymph nodes and extramural vascular invasion. Only features with a good intraclass coefficient (ICC>0.6) were included for further analysis (81 features).

Mann-Whitney test was firstly employed to select the significantly different radiomics parameters among each clinical outcome. Afterwards, using support vector machine algorithms and 5-fold cross validation, the authors developed different predictive models for each outcome. ROC curve analysis was conducted and area under the curve (AUC), sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated to evaluate the performance of each model. The best performing model was the one for distinguishing between pCR and non-responders (AUC=0.89, Se=78.0%, Sp=85.1%). Also, radiomics models significantly distinguished patients with local and distant recurrence from those with no recurrences (AUC=0.79 and 0.87, respectively). The resulting AUCs for discriminating between patients with cT4 category/those with <cT4 category and between post-treatment node-negative patients/node-positive patients were 0.80 and 0.74 respectively. The radiomics model for predicting the post-treatment ypT category achieved an AUC=0.86. However, the radiomics features did not differ significantly between cN<0 and cN>0 patients or between cTNM stage 2 and stage 3 patients, therefore no models were built for these outcomes.

The novelty of this research consists of shifting the focus of radiomics analysis from the tumour itself to the peritumoral environment in predicting cancer outcome. This issue has been investigated in several malignancies such as breast or lung cancer (6,7). However, only one recent study by Shaish et al included features obtained from the peritumoral region in the development of predictive models for assessing tumor response and prognosis of rectal cancer (8). Similar with the current study, their research has reported promising results, achieving an AUC=0.80 for predicting pCR using only features derived from mesorectal compartment.

Evaluation of the mesorectal fat may offer valuable prognostic information since the growth and dissemination of rectal cancer is closely related with the changes of the nearby adipocytes. Recent papers have showed that metabolic alterations in cancer-associated adipocytes can lead to secretion of various growth factors and remodeling factors that can interfere with cancer development and even therapeutic response (9,10). Therefore, assessment of peritumoral fatty environment may represent a new area of research, not only for rectal cancer but also for other types of abdominal/gastrointestinal tumors.

This paper has a few limitations, namely its retrospective design and the limited sample size. Due to the latter one, the data were not split into test and training sets, using a cross-validation approach instead. Still, this is the largest study which investigated the potential of mesorectal fat radiomics analysis for prediction of cancer outcome and it may represent a pathfinder for future research of peritumoral environment.

 

References:

 

  1. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. CA Cancer J Clin. 2021 Jan;71(1):7-33.
  2. Benson AB, Venook AP, Al-Hawary MM, Cederquist L., Chen YJ, Ciombor KK, Cohen S, Cooper HS, Deming D, Engstrom PF et al. Rectal Cancer, Version 2.2018, NCCN clinical practice guidelines in oncology. J. Natl. Compr. Cancer Netw. 2018, 16, 874–901
  3. Kong, JC, Guerra GR, Warrier SK, Lynch, AC, Michael, M, Ngan, SY, Phillips, W, Ramsay, G, Heriot, AG. Prognostic value of tumour regression grade in locally advanced rectal cancer: A systematic review and meta-analysis. Colorectal Dis. 2018, 20, 574–585
  4. Cui Y, Yang X, Shi Z, Yang Z, Du X, Zhao Z, Cheng, X. Radiomics Analysis of Multiparametric MRI for Prediction of Pathological Complete Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer. Eur. Radiol. 2019, 29, 1211–1220.
  5. Petresc B, Lebovici A, Caraiani C, Feier DS, Graur F, Buruian MM. Pre-Treatment T2-WI Based Radiomics Features for Prediction of Locally Advanced Rectal Cancer Non-Response to Neoadjuvant Chemoradiotherapy: A Preliminary Study. Cancers (Basel). 2020 Jul 14;12(7):1894.
  6. Braman NM, Etesami M, Prasanna P, Dubchuk C, Gilmore H, Tiwari P, Plecha D, Madabhushi A. Intratumoral and peritumoral radiomics for the pretreatment prediction of pathological complete response to neoadjuvant chemotherapy based on breast DCE-MRI. Breast Cancer Res. 2017 May 18;19(1):57.
  7. Pérez-Morales J, Tunali I, Stringfield O, Eschrich SA, Balagurunathan Y, Gillies RJ, Schabath MB. Peritumoral and intratumoral radiomic features predict survival outcomes among patients diagnosed in lung cancer screening. Sci Rep. 2020 Jun 29;10(1):10528.
  8. Shaish H, Aukerman A, Vanguri R, Spinelli A, Armenta P, Jambawalikar S, Makkar J, Bentley-Hibbert S, Del Portillo A, Kiran R, Monti L, Bonifacio C, Kirienko M, Gardner KL, Schwartz L, Keller D. Radiomics of MRI for pretreatment prediction of pathologic complete response, tumor regression grade, and neoadjuvant rectal score in patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiation: an international multicenter study. Eur Radiol. 2020 Nov;30(11):6263-6273.
  9. Duong MN, Geneste A, Fallone F, Li X, Dumontet C, Muller C. The fat and the bad: Mature adipocytes, key actors in tumor progression and resistance. Oncotarget. 2017 May 20;8(34):57622-57641.
  10. Jiramongkol Y, Lam EW. Multifaceted Oncogenic Role of Adipocytes in the Tumour Microenvironment. Adv Exp Med Biol. 2020;1219:125-142.

    Dr. Bianca Boca (Petresc) is a fifth-year radiology resident at the County Clinical Emergency Hospital in Cluj-Napoca, Romania. Her main areas of focus include abdominal and urogenital imaging, especially rectal and liver imaging. She has been developing a particular interest in using software for texture analysis and since 2019 she is a PhD student at “George Emil Palade” University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, investigating the role of radiomics in pelvic cancers. Passionate about research, Bianca has actively participated in previous ESGAR/ECR events and has published several papers as an author/co-author in international journals.

    Comments may be sent to bianca.petresc@remove-this.gmail.com

     


    CT abnormalities of the pancreas associated with the subsequent diagnosis of clinical stage I Pancreatic Ductal Adenocarcinoma more than one year later: a case-control study

    Toshima F, Watanabe R, Inoue D, Yoneda N, Yamamoto T, Sasahira N, Sasaki T, Matsuyama M, Minehiro K, Tateishi U, Gabata T.

    AJR Am J Roentgenol. 2021 Jun 23. doi: 10.2214/AJR.21.26014.

     

    Pancreatic ductal adenocarcinoma (PDAC) is an aggressive pancreatic cancer with very poor prognosis. PDAC accounts for about 90% of primary pancreatic cancers and the 5-year overall survival is reported to be lower than 5% [1]. Surgical resection with complete tumor eradication (R0 margins) is the only curative option for patients with PDAC. However, most of patients are not candidate to surgical resection as the PDAC presents with locally advanced disease and extensive vascular infiltration, or metastatic disease. Early diagnosis of PDAC can improve the prognosis but it is often challenging in clinical practice as small lesions are commonly isodense to the background nontumoral pancreatic parenchyma on contrast-enhanced Computed Tomography (CT). Early PDAC may lack of clinical symptoms and tumor markers are not routinely adopted as screening test. The only imaging manifestations of early-stage PDAC could be the presence of secondary findings such as pancreatic ductal dilatation, glandular atrophy, and abrupt main pancreatic duct cut-off [2-4].

    A recent retrospective study published by Toshima et al. [5] investigated the early findings of PDAC observed on the pre-diagnostic CT acquired at least one year before the clinical diagnosis. The authors performed a case-control study with a study group including patients with stage I PDAC who had a pre-diagnostic CT acquired at least one year before the diagnostic CT for PDAC, and a matched control group of patients without PDAC who underwent CT examination at least 10 years before the diagnostic exams [5]. Imaging analysis was performed by two radiologists who reviewed the most recent pre-diagnostic CTs in the PDAC and control groups, reporting six main focal pancreatic abnormalities: pancreatic mass, focal main pancreatic duct dilatation, focal pancreatic atrophy, focal faint parenchymal enhancement, cyst, and calcifications [5].

    A total number of 103 patients with PDAC and 103 controls were included in this study [5]. When comparing the most recent pre-diagnostic CTs, patients with PDAC showed more frequently focal pancreatic abnormalities than the control group (53% vs 23%). Particularly, patients with PDAC had more commonly focal main pancreatic duct changes (13.6%), focal pancreatic atrophy (37.6%), and focal faint enhancement (26.2%) compared to controls without PDAC. A pancreatic mass was retrospectively identified in only 5% of cases on the pre-diagnostic CT in patients who developed PDAC. Interestingly, the site of focal abnormality on the pre-diagnostic CT corresponded to the site of PDAC in the diagnostic CT in 98% of patients. After the review of all pre-diagnostic CTs, focal pancreatic abnormalities were observed with higher frequencies on pre-diagnostic studies acquired 1-2 years before the PDAC diagnosis (65%), while no abnormality was observed in studies acquired with an interval time greater than 10 years before the diagnosis. Moreover, the authors observed that patients who developed PDAC demonstrated more frequently progression of these abnormalities over time compared to controls (10% vs 0%).

    This study provides important information for the evaluation of focal pancreatic abnormalities that can predate the diagnosis of stage I PDAC [5]. The recognition of these focal findings could allow the early diagnosis of PDAC and improve the overall prognosis of those patients. It is important to note that the site of these findings corresponded to the site of PDAC diagnosis in 98% of cases. Moreover, temporal changes of focal abnormalities were exclusively observed in patients who developed PDAC. Therefore, a strict follow-up or further imaging assessment with MRI or endoscopic ultrasound should be considered in presence of these focal pancreatic abnormalities.

    The frequency of focal abnormalities reported in this study was lower compared to some prior investigations including pre-diagnostic CTs with different interval time [6, 7]. This could be explained by the inclusion on only CTs acquired with an interval time greater than one year before the PDAC diagnosis in the study by Toshima et al. [5], while a higher frequency on pancreatic abnormalities is more likely to be observed in other studies that performed imaging closer to the clinical diagnosis [6]. Moreover, histopathological samples of these focal abnormalities has not been obtained at the time of pre-diagnostic CT due to this retrospective study design [5]. The pathophysiological changes of these abnormalities remains debated as they can be related to early tumoral changes or underlying non-tumoral conditions that can predispose to PDAC development [5].

    The main limitations of this retrospective study include the lack of surgical resection in 26% patients with PDAC and the heterogeneous study protocols on pre-diagnostic CT, with lack of post-contrast imaging in 36% of patients, which limited the assessment of post-contrast focal abnormalities [5].

    In conclusion, this study [5] highlight the importance of focal pancreatic abnormalities that can predate the diagnosis of PDAC. On pre-diagnostic CT obtained at least one year before the diagnosis, focal pancreatic abnormalities were present in 54% of patients and most frequently include focal parenchymal atrophy, focal faint enhancement, and focal main pancreatic duct changes. Their recognition may be helpful in clinical practice to facilitate early diagnosis of pancreatic cancer and to improve tumor resectability and patients’ prognosis.

     

    References:

     

    1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin 2016; 66:7-30.
    2. Vernuccio F, Borhani AA, Dioguardi Burgio M, Midiri M, Furlan A, Brancatelli G. Common and uncommon pitfalls in pancreatic imaging: it is not always cancer. Abdom Radiol (NY). 2016;41:283-94.
    3. Gangi S, Fletcher JG, Nathan MA, Christensen JA, Harmsen WS, Crownhart BS, Chari ST. Time interval between abnormalities seen on CT and the clinical diagnosis of pancreatic cancer: retrospective review of CT scans obtained before diagnosis. AJR Am J Roentgenol. 2004;182:897-903.
    4. Yoon SH, Lee JM, Cho JY, Lee KB, Kim JE, Moon SK, Kim SJ, Baek JH, Kim SH, Kim SH, Lee JY, Han JK, Choi BI. Small (≤ 20 mm) pancreatic adenocarcinomas: analysis of enhancement patterns and secondary signs with multiphasic multidetector CT. Radiology. 2011;259:442-52.
    5. Toshima F, Watanabe R, Inoue D, Yoneda N, Yamamoto T, Sasahira N, Sasaki T, Matsuyama M, Minehiro K, Tateishi U, Gabata T. CT Abnormalities of the Pancreas Associated With the Subsequent Diagnosis of Clinical Stage I Pancreatic Ductal Adenocarcinoma More Than One Year Later: A Case-Control Study. AJR Am J Roentgenol. 2021. doi: 10.2214/AJR.21.26014.
    6. Singh DP, Sheedy S, Goenka AH, Wells M, Lee NJ, Barlow J, Sharma A, Kandlakunta H, Chandra S, Garg SK, Majumder S, Levy MJ, Takahashi N, Chari ST. Computerized tomography scan in pre-diagnostic pancreatic ductal adenocarcinoma: Stages of progression and potential benefits of early intervention: A retrospective study. Pancreatology. 2020;20:1495-1501.
    7. Kang JD, Clarke SE, Costa AF. Factors associated with missed and misinterpreted cases of pancreatic ductal adenocarcinoma. Eur Radiol. 2021;31:2422-2432.

      Dr. Roberto Cannella is a young radiologist, a PhD student in Molecular and Clinical Medicine at the University of Palermo (Italy), and an active ESGAR member regularly attending the annual meetings since 2016. During his radiology residency, Dr. Cannella spent 17 months as research scholar at the Abdominal Imaging Division of the University of Pittsburgh Medical Center (UPMC) in Pittsburgh (Pennsylvania, USA). His main research interests include diagnosis and management of focal liver lesions and preoperative assessment of pancreatic ductal adenocarcinoma, with multiple publications on these topics.

      Comments may be sent to rob.cannella89@remove-this.gmail.com

       


      Radiomics of hepatocellular carcinoma

      Sara Lewis, Stefanie Hectors, Bachir Taouli

      Springer Science+Business Media, LLC, part of Springer Nature 2020

       

      Radiomics is defined as the quantitative extraction, analysis and modeling of a large amount features from medical images (mostly CT and MRI images, but also US and PET), in relation to prediction targets, such as clinical end-points, and pathological and genomic features.

      Hepatocellular carcinoma (HCC), the third leading cause of cancer-related death in the US and the fourth worldwide, is a heterogeneous and therapy-resistant disease. The HCC characterization at the individual patient level is urgently needed [1, 2, 3].

      The aim of the authors is to promote the use of radiomics in clinical practice in order to obtain, using non-invasive methods, information about the tumor, reflective of HCC heterogeneity and aggressiveness, to stratify patients to a personalized therapy.

      Several studies have demonstrated the validity of radiomics in the recognition of many HCC features: from histopathological characterization to the prediction of response to therapy, from the risk of recurrence to the prediction of patient’s outcome; all this succeeding in overcoming the limits of invasiveness and of small sample size of liver biopsy.

      Among the main characteristics of HCC detected by radiomics, has been proposed the presence of microvascular invasion (MVI, defined by the invasion of tumor cells into a vascular space lined by endothelium), for which specific features have been elaborated: the “radiogenomic venous invasion” (RVI) score and the “two-trait predictor of venous invasion” (TTPVI). The role of radiomics in the detection of MVI is crucial, as the MVI has been reported as the strongest independent predictor of early tumor recurrence and poor prognosis [4, 5, 6].

      Genetic and immune phenotypes also contribute to define the prognosis of patient affected by HCC: several studies have shown the validity of radiomics in the detection of these tumor features. In particular, a study involving 39 patients has proven the possibility, starting from qualitative CT and MRI imaging data, of demonstrating a significative association of these phenotypes with gene signatures of aggressive HCC phenotype, with odds ratios (OR) ranging from 4.44 to 12.73 (p < 0.045) [7, 8, 9].

      Radiomics plays a role throughout all the diagnostic and therapeutic process of HCC, as it can be used to predict the tumor’s response to therapy. Kim et al. have demonstrated the superiority of a combined model in which are associated pre-treatment radiomics features and clinical factors of the patients (HR 19.88; p < 0.0001) in predicting patient survival, compared to either the clinical or imaging data alone [10].

      Finally, outcome has been investigated in patients after surgical and non-surgical therapies. In particular, recurrence of disease after surgery is a frequent occurrence (from 31,6 to 40% of patients), depending on whether they perform a liver transplant or a partial resection, respectively [11, 12]. In addition, a pre-operative MRI imaging study involving 100 patients has identified the radiomics feature most predictive of ER after partial resection, regardless of the HCC size: the entropy, the manifestation of tumor heterogeneity [11, 12, 13].

      Nowadays there is an increasing evidence that encourages the implementation of radiomics in all stages of the diagnostic and therapeutic process of HCC; although its use is currently limited by several factors, such as the need for dedicated softwares and trainings, which result in additional costs, and the lack of standardization in the various stages of radiomics studies.
      In conclusion, a greater diffusion of radiomics in clinical practice could translate into a concrete benefit for the patients in terms of outcome, and its use could be considered also as an instrument for early diagnosis.

      References:

       

      1. Villanueva, A., Hepatocellular Carcinoma. N Engl J Med, 2019 Apr 11;380(15):1450-1462.
      2. Kim, E., Viatour, P., Hepatocellular carcinoma: old friends and new tricks. Experimental & Molecular Medicine volume 52, pages 1898–1907 (2020).
      3. Liver. Globoscan 2020 WHO, International Agency for Research on Cancer, The Global Cancer Observatory.
      4. Roayaie, S., et al., A system of classifying microvascular invasion to predict outcome after resection in patients with hepatocellular carcinoma. Gastroenterology, 2009. 137(3): p. 850-5.
      5. Lim, K.C., et al., Microvascular invasion is a better predictor of tumor recurrence and overall survival following surgical resection for hepatocellular carcinoma compared to the Milan criteria. Ann Surg, 2011. 254(1): p. 108-13.
      6. Mazzaferro, V., et al., Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol, 2009. 10(1): p. 35-43.
      7. Segal, E., et al., Decoding global gene expression programs in liver cancer by noninvasive imaging. Nat Biotechnol, 2007. 25(6): p. 675-80.
      8. Furlan, A., et al., A radiogenomic analysis of hepatocellular carcinoma: association between fractional allelic imbalance rate index and the liver imaging reporting and data system (LIRADS) categories and features. Br J Radiol, 2018. 91(1086): p. 20170962.
      9. Taouli, B., et al., Imaging-based surrogate markers of transcriptome subclasses and signatures in hepatocellular carcinoma: preliminary results. Eur Radiol, 2017. 27(11): p. 4472-4481.
      10. Kim, J., et al., Predicting Survival Using Pretreatment CT for Patients With Hepatocellular Carcinoma Treated With Transarterial Chemoembolization: Comparison of Models Using Radiomics. AJR Am J Roentgenol, 2018. 211(5): p. 1026-1034.
      11. Shah, S.A., et al., Recurrence after liver resection for hepatocellular carcinoma: risk factors, treatment, and outcomes. Surgery, 2007. 141(3): p. 330-9.
      12. Guo, D., et al., Radiomics analysis enables recurrence prediction for hepatocellular carcinoma after liver transplantation. Eur J Radiol, 2019. 117: p. 33-40.
      13. Zhang, J., et al., Texture Analysis Based on Preoperative Magnetic Resonance Imaging (MRI) and Conventional MRI Features for Predicting the Early Recurrence of Single Hepatocellular Carcinoma after Hepatectomy. Acad Radiol, 2018.

        Dr. Caterina Di Manna is a first-year radiology resident on the “Sapienza, University of Rome” training scheme in Italy. She completed her undergraduate medical degree at “Sapienza, University of Rome” in 2019. She joined the Medical Imaging Department in 2021 where she is undertaking training in diagnostic and interventional radiology.

        Comments may be sent to caterinadimanna@remove-this.gmail.com

         


        A comparative study of the pancreas in paediatric patients with cystic fibrosis and healthy children using two‑dimensional shear wave elastography

        Ferhat Can Piskin, Sibel Yavuz, Sevgul Kose, Cagla Cagli, Dilek Dogruel, Gokhan Tumgor, Kairgeldy Aikimbaev

        J Ultrasound 2020 Dec;23(4):535-542. doi: 10.1007/s40477-020-00432-3. Epub 2020 Feb 7.

         

        Cystic fibrosis (CF) is a monogenic disease [1] with an incidence of 1/2500 live births, characterised by an autosomal recessive inheritance caused by mutations in the CFTR gene on chromosome 7. The deficiency of the cystic fibrosis transmembrane regulator (CFTR) protein leads to clinical manifestations of CF [2]. This protein is expressed on the surface of membrane of secretory and absorptive epithelial cells of several organs like pancreas, liver, intestine, airway and sweat gland [3]. In particular, pancreatic insufficiency affects about the 85% of the CF patients and results in the malabsorption of fat and protein [4]. In CF disease the progressive loss of acinar tissue caused by enzyme autodigestion of pancreas parenchyma starts in the intrauterine life and leads to inflammation and fibrosis [5, 6]. Ultrasound is a methodical frequently used in patients with CF due to absence of radiation exposure and due to large access to the methodical. Has been described in literature that CF patients frequently have ultrasonographic alteration in pancreatic parenchyma  [7]. In particular, the severely affected pancreas appears hyperechoic and small, as expression of pancreatic atrophy and replacement of the pancreatic parenchyma by fibrous tissue and fat [8]. However, the majority of studies in literature only describe qualitative ultrasounds pancreatic characteristics of CF patients.

        The aim of the authors of the present study is to compare quantitative sonographic values obtained with shear wave elastography (SWE) on paediatric patients with already diagnosed cystic fibrosis, with healthy paediatric cohort. They conducted their study on 38 CF and 38 healthy children who underwent a first evaluation through conventional B-mode and a second 2D-SWE evaluation. Some parenchymal characteristics of pancreas such as echogenicity (compared to the liver echogenicity), homogeneity, stiffness, size of the head, body and tail and capsule sharpness were evaluated during B-mode evaluation. During the 2D-SWE evaluation 2D elastography colour maps were obtained and circular ROIs of 5x5 mm were placed in, during a single breath-hold. This was repeated five time separately for the head, body and tail. Then, mean values were recorded. For the CF group, on the conventional US evaluation the mean diameters of the head, body, and tail of the pancreas were significantly higher in the health children group than in the CF group (p = 0.016, p < 0.005, and p < 0.005, respectively). The mean 2D-SWE values of the patients with CF were 1.01 ± 0.16 m/s for the head, 1.03 ± 0.05 m/s for the body, and 1.02 ± 0.05 m/s for the tail, while those of the healthy control group were 1.31 ± 0.01 m/s for the head, 1.28 ± 0.08 m/s for the body, and 1.30 ± 0.10 m/s for the tail. On 2D-SWE evaluation, pancreatic values of the CF group were significantly lower than those of the healthy control group (all p < 0.005 for the pancreatic head, body, and tail, respectively). Using ROC values the threshold value for the head, body, and tail of the pancreas were determined as 1.19, 1.13, and 1.12 m/s respectively and the sensitivity of the test was determined as 81.5%, 76.3%, and 73.3%, while the specificity was 97.3%, 100%, and 100%, respectively.

        The study carried out and the results obtained could be very relevant in the CF scenario because literature lacks quantitative information about pancreatic status in the evolution of CF in children. Engjom T. et al. assessed some qualitative pancreatic parenchymal characteristics in patient with CF > 15 years old, such as hyper-echogenicity and lipomatosis, which are related to the exocrine insufficiency. Nevertheless they only performed a qualitative evaluation, based on a visual analogue scale (VAS), with an acceptable inter-observer variability [9].

        Some limitations of the study included a significant difference found by the authors in BMI between the two groups that can affect SWE values and a minimum threshold age of 5 years old of the population included, due to patient incompatibility. Further study with wider age range would be advisable to confirm these interesting results in order to detect a pancreatic involvement in early period.

        In conclusion, the authors found a non-invasive quantitative evaluation of pancreas damage with a high sensitivity and specificity, establishing some cut-off values of SWE. This could be decisive for therapy management and follow-up of CF patients.

         

        References:

         

        1. Scotet, V., C. L'Hostis, and C. Férec, The Changing Epidemiology of Cystic Fibrosis: Incidence, Survival and Impact of the. Genes (Basel), 2020. 11(6).
        2. Castellani, C. and B.M. Assael, Cystic fibrosis: a clinical view. Cell Mol Life Sci, 2017. 74(1): p. 129-140.
        3. McCarthy, V.A. and A. Harris, The CFTR gene and regulation of its expression. Pediatr Pulmonol, 2005. 40(1): p. 1-8.
        4. Paranjape, S.M. and P.J. Mogayzel, Cystic fibrosis. Pediatr Rev, 2014. 35(5): p. 194-205.
        5. Ooi, C.Y. and P.R. Durie, Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in pancreatitis. J Cyst Fibros, 2012. 11(5): p. 355-62.
        6. Ishiguro, H., et al., Physiology and pathophysiology of bicarbonate secretion by pancreatic duct epithelium. Nagoya J Med Sci, 2012. 74(1-2): p. 1-18.
        7. Engjom, T., et al., Sonographic pancreas echogenicity in cystic fibrosis compared to exocrine pancreatic function and pancreas fat content at Dixon-MRI. PLoS One, 2018. 13(7): p. e0201019.
        8. Haber, H.P., Cystic fibrosis in children and young adults: findings on routine abdominal sonography. AJR Am J Roentgenol, 2007. 189(1): p. 89-99.
        9. Engjom, T., et al., Ultrasound echo-intensity predicts severe pancreatic affection in cystic fibrosis patients. PLoS One, 2015. 10(3): p. e0121121.

          Dr. Benedetta Bracci is a radiology resident at the University of Rome "Sapienza" - Sant'Andrea University Hospital in Rome, attending the third year of residency. Her main field of interest is paediatric radiology, with a particular attention to the Abdominal area. During the years she trained 7 months at the Paediatric Hospital “Bambino Gesù” in Rome to gain experience in this field. She has also been actively involved in clinical imaging research, and she has contributed as a co-author in some publications.

          Comments may be sent to benedetta.bracci@remove-this.uniroma1.it

           


          Portal phase alone is equivalent to multiphasic phase for CT diagnosis of acute non-traumatic pains in an emergency context

          Herpe G, Boucebci S, Cassan T, Verdier M, Simonet C, Sztark G, Tasu JP

          Emerg Radiol. 2020 Apr;27(2):151-156

           

          Acute non-traumatic abdominal emergencies (ANTAE) represent one of the most frequent causes of access in the ED (1), embracing life-threatening conditions and self-limiting ones. Due to the comparable clinical findings and lack of sensibility and specificity of laboratory tests, ANTAE is a medical challenge for emergency physicians. For this reason, imaging is often required for definitive diagnosis and treatment (2).

          Although ultrasonography is the first-choice non-invasive imaging modality, multidetector computed tomography (MDCT) has shown stronger accuracy in reaching the correct diagnosis (3). Multiphasic scanning protocol – which includes the acquisition in pre-contrast, arterial, portal venous, and delayed phases of contrast enhancement – is usually the most common approach (3), even though many recent publications (2, 4, 5) have demonstrated that in specific clinical non-traumatic abdominal settings the correct diagnosis can be reached with the same accuracy cutting off unnecessary phases and thus significantly lowering radiation exposure.

          Herpe G. and coworkers emphasize the importance of lowering radiation exposure assessing that portal-phase only (PVP) acquisition protocol is equivalent to a multiphasic one, in term of radiological diagnosis concordance of ANTAE in the ED. The authors performed a retrospective study including 250 patients admitted to the ED for suspected ANTAE, including at least a pre-contrast phase, late arterial phase (LAP) and portal phase (PVP). Cases of suspected active hemorrhage and known malignancies were secondarily excluded since the multiphasic protocol is here recommended (6). 196 CT studies were examined. The multiphasic protocol (pre-contrast phase ± LAP + PVP) and the PVP alone were reviewed independently by nine radiologists who determined the most appropriate diagnosis with five-point confidence scale. Diagnosis concordance and radiation were compared by chi-square test: PVP-alone diagnosis was concordant with the multiphasic protocol without difference in term of confidence reading (kappa coefficient between the two diagnosis 98,5% (CI 95%= 95.6–99.7, p < 0.001), with a 61% decrease of radiation dose.

          Results are consistent with other previous publications, confirming the inter-observer agreement between multiphasic and simplified acquisition protocol in abdomino-pelvic CT in the ED (2, 4, 5, 7), suggesting that in this scenario limiting radiation exposure does not have an impact on the management of patients.

          However, to the best of our knowledge, there are no guidelines on how to standardize CT protocol in ANTAE since the most appropriate protocol relies upon clinical presentation (8). For this reason, when it is not possible to exclude malignancies and/or active bleeding from the initial clinical evaluation, multiphasic protocol should remain the gold standard (6). The most clinically relevant limit of this approach remains misinterpretation of spontaneously hyper-dense structures (i.e. biliary tract stones), difficult to detect and characterized with the only PVP phase. Nevertheless, some authors have suggested that additional scan might be taken with minimal doses (9, 10) just to obtain the additional necessary information limiting radiation exposure and without compromising the diagnostic accuracy of the exam.

          In conclusion, considering the limitations of the study (e.g., retrospective design, low number of patients, lack of data about diagnostic accuracy) it is important to bear in mind the importance of using adequate protocols in the ED avoiding unnecessary ionizing radiation exposure, as many patients admitted in the ED suffer from acute self-limiting benign diseases.

          References:

          1. Pines JM. Trends in the rates of radiography use and important diagnoses in emergency department patients with abdominal pain. Med Care. 2009;47(7):782–786.
          2. Hwang SH, You JS, Song MK, Choi JY, Kim MJ, Chung YE. Comparison of diagnostic performance between single- and multiphasic contrast-enhanced abdominopelvic computed tomography in patients admitted to the emergency department with abdominal pain: potential radiation dose reduction. European radiology 2015;25(4):1048-58.
          3. Laméris W, van Randen A, van Es HW, van Heesewijk JP, van Ramshorst B, Bouma WH, ten Hove W, van Leeuwen MS, van Keulen EM, Dijkgraaf MG, Bossuyt PM, Boermeester MA, Stoker J. Imaging strategies for detection of urgent conditions in patients with acute abdominal pain: diagnostic accuracy study. BMJ (Clinical research ed.) 2009;338:b2431.
          4. Esposito AA, Zilocchi M, Fasani P, Giannitto C, Maccagnoni S, Maniglio M, Campoleoni M, Brambilla R, Casiraghi E, Biondetti PR. The value of precontrast thoraco-abdominopelvic CT in polytrauma patients. European journal of radiology 2015;84(6):1212-8.
          5. Naulet P, Wassel J, Gervaise A, Blum A. Evaluation of the value of abdominopelvic acquisition without contrast injection when performing a whole body CT scan in a patient who may have multiple trauma. Diagnostic and interventional imaging 2013;94(4):410-7.
          6. Wells ML, Hansel SL, Bruining DH, Fletcher JG, Froemming AT, Barlow JM, Fidler JL. CT for Evaluation of Acute Gastrointestinal Bleeding. Radiographics : a review publication of the Radiological Society of North America, Inc 2018;38(4):1089-107.
          7. van Randen A, Laméris W, Nio CY, Spijkerboer AM, Meier MA, Tutein Nolthenius C, Smithuis F, Bossuyt PM, Boermeester MA, Stoker J. Inter-observer agreement for abdominal CT in unselected patients with acute abdominal pain. European radiology 2009;19(6):1394-407
          8. Scheirey CD, Fowler KJ, Therrien JA, Kim DH, Al-Refaie WB, Camacho MA, Cash BD, Chang KJ, Garcia EM, Kambadakone AR, Lambert DL, Levy AD, Marin D, Moreno C, Noto RB, Peterson CM, Smith MP, Weinstein S, Carucci LR. ACR Appropriateness Criteria® Acute Nonlocalized Abdominal Pain. Journal of the American College of Radiology: JACR 2018;15(11S):S217-S231.
          9. Tack D, Sourtzis S, Delpierre I, de Maertelaer V, Gevenois PA. Low-dose unenhanced multidetector CT of patients with suspected renal colic. AJR. American journal of roentgenology 2003;180(2):305-11.
          10. Pooler BD, Lubner MG, Kim DH, Ryckman EM, Sivalingam S, Tang J, Nakada SY, Chen GH, Pickhardt PJ. Prospective trial of the detection of urolithiasis on ultralow dose (sub mSv) noncontrast computerized tomography: direct comparison against routine low dose reference standard. The Journal of urology 2014;192(5):1433-9.

            Dr. Alessandro Onori is a first-year radiology resident at Sapienza, University of Rome. He graduated at Sapienza University of Rome with a dissertation on AI applications in differential diagnosis of interstitial lung diseases. He is currently involved in both diagnostic and interventional radiology training, polarizing his interests towards emergency radiology and vascular minimally-invasive procedures.

            Comments may be sent to alexonori@remove-this.yahoo.com

             


            Quantification of liver fat content in liver and primary liver lesions using triple-echo-gradient-echo MRI

            Nougaret S, Monsonis B, Molinari N, Riviere B, Piron L, Kassam Z, Cassinotto C, Guiu B

            Eur Radiol. 2020 Sep;30(9):4752-4761. doi: 10.1007/s00330-020-06757-1. Epub 2020 Apr 22. PMID: 32318848

             

            Incidence of focal liver lesions (FLL) detection parallels growth in imaging utilization. Hemangiomas, focal nodular hyperplasias (FNH), and adenomas (HCA) are the most commonly solid benign lesions that arise in noncirrhotic liver. Metastases are the most common malignant lesions in noncirrhotic livers. Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) occur in the setting of chronic liver disease. Despite FLL usually having typical imaging characteristics, differential diagnosis by visual assessment only can be difficult sometimes or it requires contrast media administration mandatorily.
            However, quantitative MRI imaging is an emerging research field that is increasingly assuming an important role in the characterization of FLL with unenhanced MRI protocol.

            Authors, with their study, aim to quantify and compare whole liver parenchymal and intralesional fat fraction in primary liver lesions, such as HCC, HCA and FNH, using a triple-echo-gradient-echo-sequence.
            Chemical shift MRI techniques are a non-invasive method for fat quantification within a specified volume [1, 2]. Routinely dual-echo in-phase (IP)/out of phase (OP) imaging is used for subjective evaluation of intralesional fat in liver lesions. However, the dual-echo technique is hampered by T1 and T2* relaxation times which may underestimate fat fraction when T2* is short (for example in the setting of iron-containing lesions) [3]. A triple-echo technique has been developed, which consists of a breath-hold, triple-echo spoiled gradient-echo sequence with consecutive first IP, OP, and second IP echo times. This method enables the quantification of fat fraction, corrected for T2* decay and minimizing T1-related effects (by decreasing the flip angle at 20°) [4-6].

            It is a retrospective study that included 128 consecutive patients that underwent a liver MRI for lesion characterization. For each patient, a triple-echo sequence was performed before contrast medium injection on 1.5T scanner for fat evaluation. Then, the obtained images were post-processed and analyzed quantitatively and qualitatively by a radiologist. Quantitative analysis was performed by a Radiologist, with 3 years of experience in gastrointestinal imaging, by drawing regions of interest (ROIs) around the liver lesion on each slice of the fat fraction map, referring to the other sequences to delineate the whole tumor volume. Care was taken to avoid contamination of these ROIs by the normal liver parenchyma. Further, a large ROI representing the “normal” liver parenchyma was drawn for each patient. The same radiologist performed a qualitative analysis of fat quantification by visual evaluating the decrease in signal intensity on OP/IP images.

            Among the 128 included patients, there were 47 HCCs, 25 HCA, and 56 cases of FNH suspected on MRI. Forty-nine patients had histologic confirmation of the diagnosis following ultrasound-guided biopsy. Where biopsy was not performed (27 patients in the HCC group (57%), 47 patients in the FNH group (84%), and 5 in the HCA group (20%)), lesion characterization was made on MRI in conjunction with clinical history, follow-up MRI, and laboratory results.

            Results confirmed that this technique is accurate to quantify fat fraction in a tumor volume. According with pathologic findings, results demonstrated the relatively higher intralesional fat content of HCC and HCA compared to FNH. Furthermore, the previously published 5.56% threshold to assess liver steatosis might not be applicable in analysis of a solitary liver lesion when used to distinguish between fat-containing and non-fat-containing lesions because was solely used to determine liver steatosis. Authors, in their cohort, found that a lower cutoff of 2.7% was able to accurately diagnose FNH over HCA.

            This study had some limitations: due to the retrospective nature not all data (e.g. BMI) were available. Pathology correlation could not be obtained for all patients. The heterogeneity of fat distribution within the lesion was not evaluated. Inter/intraobserver reproducibility was not evaluated.

            In conclusion this study quantified for the first-time intralesional fat fraction using triple-echo chemical shift gradient-echo approach. An intralesional fat fraction of less than 2.7% may indicate high likelihood of FNH over HCA.
            This study has important implication in abdominal radiology as an aid in the study and characterization of liver lesions also because triple-echo-gradient-echo-sequence sequences have short acquisition time so could be routinely inserted and performed in clinical liver study protocols.

            .

             

            References:

            1. Reeder, S.B., et al., Quantitative Assessment of Liver Fat with Magnetic Resonance Imaging and Spectroscopy. J Magn Reson Imaging, 2011. 34(4): p. 729-749.
            2. Dixon, W.T., Simple proton spectroscopic imaging. Radiology, 1984. 153(1): p. 189-94.
            3. Westphalen, A.C., et al., Liver fat: effect of hepatic iron deposition on evaluation with opposed-phase MR imaging. Radiology, 2007. 242(2): p. 450-5.
            4. Guiu, B., et al., Multiecho MR imaging and proton MR spectroscopy for liver fat quantification. Radiology, 2008. 249(3): p. 1081.
            5. Guiu, B., et al., Mapping of liver fat with triple-echo gradient echo imaging: validation against 3.0-T proton MR spectroscopy. Eur Radiol, 2009. 19(7): p. 1786-93.
            6. Guiu, B., et al., Liver methylene fraction by dual- and triple-echo gradient-echo imaging at 3.0T: Correlation with proton MR spectroscopy and estimation of robustness after SPIO administration. J Magn Reson Imaging, 2011. 33(1): p. 119-27.

             

            Francesco Pucciarelli is a third-year radiology resident at Sant’Andrea Hospital, Sapienza University of Rome and graduated at Università Cattolica del Sacro Cuore, Policlinico Gemelli of Rome with merit in 2017. Dr. Pucciarelli is an ESGAR member and he was awarded as “ESGAR Top 20 presenter” on the occasion of the ESGAR 2020 virtual event. He has a wide range of interests in abdominal diagnostic imaging and is currently involved in scientific research centered on quantitative MRI of focal and diffuse liver diseases.

            Comments may be sent to pucciarelli.fra@remove-this.gmail.com

             


            Clinical relevance of gallbladder polyps; is cholecystectomy always necessary?

            Madelon J.H. Metman, Pim B. Olthof, Johannes B.C. van der Wal, Thomas M. van Gulik, Daphne Roos & Jan Willem T. Dekker

            International Hepato-Pancreato-Biliary Association

            DOI: https://doi.org/10.1016/j.hpb.2019.08.006

             

            Gallbladder polyps are lesions of the gallbladder wall that protrude into the gallbladder lumen. They are commonly seen at ultrasound of the abdomen with a prevalence of 0.3 to 9.5%3,5. After cholecystectomy, polyps are observed in 0.004 to 13.8% of specimens3.

            The differential diagnosis for a gallbladder polyp is wide and includes pseudotumours, in addition to benign and malignant tumours. Pseudotumours include cholesterol polyps, focal adenomyomatosis and inflammatory lesions that can be caused by infection2. Sludge is another potential mimic of a polyp. The literature estimates 30% of polyps are adenomatous polyps of the gallbladder, which have potential for malignant transformation. Patients with gallbladder carcinoma have a poor five-year survival rate of less than 5% due to a hidden and rapid progression of spread, which makes most disease unresectable at diagnosis4. Cholecystectomy is favoured for patients who are deemed to have malignant potential of a gallbladder polyp.

            Most gallbladder polyp guidelines advocate for cholecystectomy if the polyp size at ultrasound is larger than or equal to 10 mm, or if the size has increased beyond a threshold during ultrasound surveillance2.

            This study looks at the correlation between ultrasound and histopathological findings after cholecystectomy for suspected gallbladder polyps. A retrospective analysis was performed at two Dutch institutions for all cholecystectomies performed between January 2010 and August 2017, with a total of 3547 operations. Of these 110 were performed for suspected gallbladder polyps. 2 patients were excluded due to a known diagnosis of primary sclerosing cholangitis, which is known to increase malignant potential of polyps. Most patients (60%) had multiple polyps; median diameter 10 mm. 54 patients underwent ultrasound surveillance with an increase in growth of their polyps prompting cholecystectomy.

            Surprisingly, most pathological specimens (65%) did not identify any macroscopic abnormality. Polyp-like lesions were observed in 22 (20%) of the specimens. The remaining specimens showed cholesterolosis and irregular foci of the gallbladder wall. Three pyloric gland adenomas were identified. The remaining specimens showed benign entities. None of the pyrloric gland adenomas had features of dysplasia or malignant transformation.

            Out of the 108 operations, adverse events were recorded for 3 patients and classified as Dindo IIIa (complications requiring surgical, endoscopic or radiological intervention) or higher. The adverse events were sepsis secondary to bile leak, re-admission for percutaneous drainage of a biloma and surgery for an incarcerated trocar hernia.

            This study reflects similar findings observed in the literature, which is that most gallbladder specimens following surgery for suspected gallbladder polyps predominantly showed pseudopolyps with no malignant potential. Pyloric gland adenomas have an unknown risk of malignant transformation. In a separate study of 165 polyps with pyloric subtype there were 44 showing high grade dysplasia and 2 showing adenocarcinoma1. In this same study 48 had no abnormality and 51 had cholesterolosis.

            There are limitations to only using ultrasound assessment, other techniques such as contrast enhanced ultrasound, endoscopic ultrasound and MRI can have a role to help differentiate between benign from malignant polypoid gallbladder, although there is a lack of evidence for their use. Clinicians face a challenge to counsel patients about their suspected gallbladder polyps without a strong evidence base, as currently there is a poor correlation between imaging and histopathologic findings, and a high probability of no abnormality after surgery. Ongoing studies are attempting to improve our understanding, but most large studies are from Asian centres with a higher incidence of biliary malignancy compared to Western centres. The Netherlands is currently recruiting for a national prospective study (NTR7198), which will hopefully improve guidance.

            This small study of 108 patients highlights a weak correlation between ultrasound and histopathology findings for suspected gallbladder polyps based on current guidelines, which ultimately leads to a high proportion of unnecessary operations. Laparoscopic cholecystectomy is a relatively routine procedure with a small but significant potential to cause harm. The hope is to develop better guidance and use of imaging to select the correct patients for surgery.

             

            References:

            1. Albores-Saavedra, J., Chablé-Montero, F., González-Romo, M. A., Ramírez Jaramillo, M., & Henson, D. E. (2012). Adenomas of the gallbladder. Morphologic features, expression of gastric and intestinal mucins, and incidence of high-grade dysplasia/carcinoma in situ and invasive carcinoma. Human Pathology, 43(9), 1506–1513. https://doi.org/10.1016/j.humpath.2011.11.011
            2. Elmasry, M., Lindop, D., Dunne, D. F. J., Malik, H., Poston, G. J., & Fenwick, S. W. (2016). The risk of malignancy in ultrasound detected gallbladder polyps: A systematic review. International Journal of Surgery, 33, 28–35. https://doi.org/10.1016/j.ijsu.2016.07.061
            3. Kratzer, W., Haenle, M. M., Voegtle, A., Mason, R. A., Akinli, A. S., Hirschbuehl, K., Schuler, A., & Kaechele, V. (2008). Ultrasonographically detected gallbladder polyps: A reason for concern? A seven-year follow-up study. BMC Gastroenterology, 8(1). https://doi.org/10.1186/1471-230x-8-41
            4. Mellnick, V. M., Menias, C. O., Sandrasegaran, K., Hara, A. K., Kielar, A. Z., Brunt, E. M., Doyle, M. B. M., Dahiya, N., & Elsayes, K. M. (2015). Polypoid Lesions of the Gallbladder: Disease Spectrum with Pathologic Correlation. RadioGraphics, 35(2), 387–399. https://doi.org/10.1148/rg.352140095
            5. Park, J. K., Yoon, Y. B., Kim, Y.-T., Ryu, J. K., Yoon, W. J., Lee, S. H., Yu, S.-J., Kang, H. Y., Lee, J. Y., & Park, M. J. (2008). Management Strategies for Gallbladder Polyps: Is It Possible to Predict Malignant Gallbladder Polyps? Gut and Liver, 2(2), 88–94. https://doi.org/10.5009/gnl.2008.2.2.88

             

            Dr Matthew Gale is a 5th year radiology registrar at the Queens Medical Centre, Nottingham, UK. His interests include gastro-intestinal, hepato-pancreato-biliary radiology and general and non-vascular intervention.

            Comments may be sent to mdgale@remove-this.gmail.com

             


            LI-RADS v2018 major criteria: Do hepatocellular carcinomas in non-alcoholic steatohepatitis differ from those in virus-induced chronic liver disease on MRI?

            Barat M, Nguyen TTL, Hollande C, Coty JB, Hoeffel C, Terris B, Dohan A, Mallet V, Pol S, Soyer P.

            Eur J Radiol. 2021 May; 138:109651.

            DOI: 10.1016/j.ejrad.2021.109651. PMID: 33740627

             

            Currently, the diagnosis of hepatocellular carcinoma (HCC) is based on cross-sectional imaging, namely contrast-enhanced computed tomography (CECT) and magnetic resonance imaging (MRI), setting the primary endpoint in the identification of the tumor in the early stage, when patient's condition and liver function can lead to surgical treatment. The main risk factors for developing HCC are virus- and alcohol-induced cirrhosis (1). Patients with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), especially in the Western countries, also have a mild risk for developing HCC (2). Contrast-enhanced CT and MR imaging features of HCC, i.e. enhancement during the arterial phase and wash-out in the portal-venous phase, are worldwide accepted and endorsed by the LI-RADS (3). However, LI-RADS can't be applied to NASH patients, which have a twofold increased risk of HCC-related mortality (4).

            In this setting the Authors of the present paper have retrospectively validated MRI LI-RADS major features in patients affected by NASH, enrolling a total of 82 patients (41 HCC with virus-induced cirrhosis and 41 with NASH) from two centers. The final diagnosis was obtained according to the histopathological results. All patients underwent liver MRI examination on a 1.5T scanner before and after intravenous administration of a gadolinium-based extracellular contrast agent (gadoterate meglumine and gadobenate dimeglumine in 32 and 9 patients with NASH and in 33 and 8 patients with virus-induced cirrhosis, respectively). MRI examinations of the two groups were compared for imaging presentation, LI-RADS major criteria, and LI-RADS categorization (5) by two independent readers, blinded to clinical and histopathological data.

            Authors reported no statistically significant differences regarding tumor longest diameter (30.3 ± 20.9 in NASH vs 38.0 ± 26.3 mm in virus group, respectively, p=0.121), signal drop on IP/OP T1W imaging (11.8 ± 18.5 vs 6.0 ± 9.7%, p=0.464) and ADC value (975 ± 257 vs 1048 ± 253 ×10-3 mm2/s, p=0.197). Moreover, no significant differences were found regarding qualitative variables, in particular location (right liver lobe 76 vs 63%, p=0.337), arterial phase hyperenhancement (93 vs 98%, p=0.616), wash-out (63 vs 83%, p=0.502), tumor capsule (68 vs 61%, p=0.488), and portal vein invasion (12 vs 24%, p=0.253), with an overall good agreement for all features, except for tumor capsule in NASH patients (k=0.367).

            In both groups, the most represented LI-RADS category was 5 (63 vs 80%), followed by 4 (22 vs 12%) and 3 (15 vs 7%), with no significant difference between groups (p=0.303) and a good agreement between the two readers (k=0.802 for NASH patients and k=0.720 for virus-induced cirrhotic patients).

            Two important previous studies published in literature examined the importance of imaging features of HCC in NASH patients: Alsharan et al. (6) and Thompson et al. (7) reported the non-rim like hyperenhancement during the arterial phase in the majority of patients (100% and 93%, respectively).  Same results were reported by the three groups regarding tumor capsule, observed in 63% of patients enrolled by the present study, 60% by Alsharan et al., and 71% by Thompson et al. However, similar results were not reported for the wash-out appearance on the portal-venous phase, observed in 40% and 21% (lsharan et al., and Thompson et al) respectively).

            Some limitations should be reported: firstly, the small sample size and the population analyzed including patients with S4 or F4 underlying chronic liver disease. Second, a not negligible percentage of patients received an hepatocyte selective contrast agent even if the risk of bias was limited to the lack of analysis of the hepatobiliary phase. Third, the retrospective design did not allow the evaluation of LI-RADS 1, 2, and 3 because only histopathologically proven HCC were included.

            In conclusion, the Authors provided original data regarding HCC in NASH patients showing that MRI features are similar to those of HCC in virus-induced chronic liver disease and resulting in similar LI-RADS categorization. In this setting, additional studies are needed to further validate LI-RADS applicability to NASH patients.

             

            References:

            1. Ayuso C, Rimola J, Vilana R, et al (2018) Diagnosis and staging of hepatocellular carcinoma (HCC): current guidelines. European Journal of Radiology 101:72–8 doi.org/10.1016/j.ejrad.2018.01.025
            2. Anstee QM, Reeves HL, Kotsiliti E, et al (2019) From NASH to HCC: current concepts and future challenges. Nat Rev Gastroenterol Hepatol 16:411–428. doi.org/10.1038/s41575-019-0145-7
            3. Chernyak V, Fowler KJ, Kamaya A, et al (2018) Liver Imaging Reporting and Data System (LI-RADS) Version 2018: Imaging of Hepatocellular Carcinoma in At-Risk Patients. Radiology 289:816–830. doi.org/10.1148/radiol.2018181494
            4. Gupta A, Das A, Majumder K, et al (2018) Obesity is Independently Associated With Increased Risk of Hepatocellular Cancer-related Mortality: A Systematic Review and Meta-Analysis. Am J Clin Oncol 41:874–88 doi.org/10.1097/COC.0000000000000388
            5. Elsayes KM, Kielar AZ, Elmohr MM, et al (2018) White paper of the Society of Abdominal Radiology hepatocellular carcinoma diagnosis disease-focused panel on LI-RADS v2018 for CT and MRI. Abdom Radiol (NY) 43:2625–2642. doi.org/10.1007/s00261-018-1744-4
            6. Al-Sharhan F, Dohan A, Barat M, et al (2019) MRI presentation of hepatocellular carcinoma in non-alcoholic steatohepatitis (NASH). Eur J Radiol 119:108648. doi.org/10.1016/j.ejrad.2019.108648
            7. Thompson SM, Garg I, Ehman EC, et al (2018) Non-alcoholic fatty liver disease-associated hepatocellular carcinoma: effect of hepatic steatosis on major hepatocellular carcinoma features at MRI. Br J Radiol 91:20180345. doi.org/10.1259/bjr.20180345

             

            Dr. Cesare Maino is a young attending radiologist working at San Gerardo Hospital in Monza, Lombardy, Italy, graduated at the Vita-Salute San Raffaele University of Milan in July 2015 and post-graduated at the University of Milano Bicocca in November 2020. He attends ESGAR annual meetings since 2017 and is a mentee of the ESGAR mentorship program.

            Comments may be sent to mainocesare@remove-this.gmail.com


            Adrenal metastases: early biphasic contrast-enhanced CT findings with emphasis on differentiation from lipid-poor adrenal adenomas

            F. Zhu, X. Zhu, H. Shi, C. Liu, Z. Xu, M. Shao, F. Tian J. Wang

            Clinical Radiology 76 (2021) 294-301

            Dr Rajiv B. Karia (Consultant GI/HPB and Interventional Radiologist, Chesterfield Royal Hospital & Nottingham University Hospitals, UK)

             

            The adrenal gland is a site of both primary and metastatic malignant tumours as well as the most commonly identified benign tumour, adrenal adenomas. With a significant increase in use of CT for patients with previously known malignancies as well as for non-oncology patients, there has been an increase in number of incidentally identified adrenal tumours.

            Adrenal metastasis (AM) and adrenal adenomas (AA), are the most common malignant and benign tumours[1]. Although on un-enhanced CT, attenuation of less that 10HU would be highly suggestive of an AA [1], approximately 30% of AAs are lipid poor[2] having a HU above 10[3] and hence un-enhanced CT are unable to reliably differentiate the two on un-enhanced CT.

            Further imaging usually requires a chemical shift MRI or a delayed contrast-enhanced CT identifying relative washout of the lesion[4]. This retrospective study was used to identify imaging features to help differentiate AMs from AA, using un-enhanced CT and early biphasic contrast-enhanced CTs. This study identified 123 patients mostly based on histological diagnosis either at surgery or biopsy. However it also identified a few cases from follow-up imaging based on rapid increase in size (more than double within 6 months suggestive of AMs). One can be confident of the end point differential between AM and AA from this. All patients had unenhanced CTs, and biphasic arterial and portal venous CTs.

            The study reviewed multiple imaging parameters; size: longest diameter (LD), shortest diameter (SD) and its ratio (LD/SD ratio); CT attenuation: unenhanced phase (CTu), arterial phase (CTa) and venous phase (CTv); degree of enhancement: degree of enhancement in arterial phase (DEAP), portal venous phase (DEPP); peak enhancement ratio PE/U (where PE was the highest value between DEAP and DEEP and U was the CTu). Further parameters such has absolute percentage washout (APW), and relative percentage washout (RPW) were also calculated.

            This paper clearly identifies the presence of necrosis, location (unilateral/bilateral) and shape as significant differences between the two lesions. However, one can see the limitations of identifying necrosis particularly within smaller lesions, as it is at times difficult to differentiate necrosis from foci of low attenuation due to small quantities of microscopic fat component. This is not an issue with large lesions which are prone to cystic necrosis [5]. Although bilateral lesions maybe more commonly associated adrenal metastasis, we have all seen bilateral lipid poor AA, diagnosed on MRI. I think the qualitative assessment tools identified within this paper may not provide the reporter with the confidence to call AM over AA.

            This paper has gone into great depth illustrating the quantitative analysis performed at identifying statistically significant radiological characteristics. The study identified as CTu, DEAP, DEPP, DEpeak and PE/U as all parameters providing statistically significance in differentiating AM from AA. However for a reporter to benefit from this, these findings need to simple to identify, a logical part of the reporting process and intuitive to use.

            Univariate and ROC analysis showed PE/U ratio (<1.25), CTu (>32.2 HU), DEpeak (<43.15 HU), DEPP (<37.65 HU), presence of intralesional necrosis, location (bilateral adrenal), and irregular shape were independent factors for distinguishing AMs from AAs. However interestingly and more important for a reporter, when at least four of the criteria were combined, a sensitivity of 88% and specificity of 93% was achieved. I think with such high specificity using these parameters may prevent patients undergoing unnecessarily delayed ‘washout’ phase CTs or further assessment with time consuming MRIs.

            The results of this study are worth noting; although this was a retrospective study, histological evidence was present in most cases; and there has been a great in-depth analysis of the parameters captured. There will obviously be some observer variation however two abdominal radiologists reviewed all the CT findings, blinded from the pathologies.

            Often the findings of an incidental adrenal lesion, in day-to-day practice usually involve a single phase portal venous phase abdomen, and hence the data of the arterial, portal venous, and un-enhanced images are not always available. If this is the case, to further assess adrenal lesions, should one carry out an early biphasic/multiphase CT to capture the above, a delayed CT identifying lesional washout or an adrenal MRI? I suspect many places would still benefit from carrying out their usual practice and therefore I feel this will have very limited impact on the day-to-day practice.

            However the paper has prompted discussion, and if we have these un-enhanced and bi-phasic data are we, as radiologists, confident enough with the above findings based on the 3 of the criteria’s to call an AM from an AA without the need for further imaging?

             

            References:

            1. Meng X, Chen X, Shen Y, et al. Proton-density fat fraction measurement: a viable quantitative biomarker for differentiating adrenal adenomas from non-adenomas. Eur J Radiol 2017;86:112e8.
            2. Ganeshan D, Bhosale P, Kundra V. Current update on cytogenetics, taxonomy, diagnosis, and management of adrenocortical carcinoma: what radiologists should know. AJR Am J Roentgenol 2012;199(6):1283e93.
            3. Kim YK, Park BK, Kim CK, et al. Adenoma characterization: adrenal protocol with dual- energy CT. Radiology 2013;267(1):155e63.
            4. Park SW, Kim TN, Yoon JH, et al. The washout rate on the delayed CT image as a diagnostic tool for adrenal adenoma verified by pathology: a multicenter study. Int Urol Nephrol 2012;44(5):1397e402.
            5. Ctvrtlik F, Tudos Z, Szasz P, et al. Characteristic CT features of phaeo- chromocytomasdprobability model calculation tool based on a multicentric study. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2019;163(3):212e9.

              Dr Rajiv Karia is a radiologist from Chesterfield Royal Hospital (Chesterfield, UK), specialising in GI/HPB and interventional radiology. Graduated from University of Nottingham and completed radiology training in Nottingham, having previously worked in surgery. Active ESGAR member since 2012, regularly attending annual meetings and has also completed the ESGAR/ESOR Exchange Programme for Abdominal Radiology Fellowship. Rajiv has a keen interest in technology and advances in medical applications, and is an associate member of the institution of Engineering and Technology (IET).

              Comments may be sent to rajiv.karia@remove-this.doctors.org.uk

               


              Observer agreement for small bowel ultrasound in Crohn’s disease: results from the METRIC trial

              Gauraang Bhatnagar · Laura Quinn · Antony Higginson · Andrew Plumb · Steve Halligan · Damian Tolan · Roger Lapham · Susan Mallett · Stuart A. Taylor · METRIC study investigators

              Abdom Radiol (NY). 2020 Oct;45(10):3036-3045

              DOI: 10.1007/s00261-020-02405-w

               

              Crohn’s disease (CD) is a chronic inflammatory bowel disease affecting individuals of any age that can cause significant morbidity and impact in quality of life (1). Imaging is crucial for the diagnosis and plays an essential role in the management of these patients, allowing the disease activity assessment and detection of complications. In fact, all newly diagnosed CD patients should undergo small bowel assessment, either with intestinal ultrasound (IUS), MR enterography (MRE) and/or capsule endoscopy (2).

              The METRIC was a prospective multicenter cohort study comparing diagnostic accuracy, observer variability, acceptability, diagnostic impact and cost-effectiveness of MRE and IUS in newly diagnosed or relapsing CD patients (3). In the main analysis, MRE outperformed IUS in the detection, extent and activity of small bowel CD, while IUS was more sensitive in the detection of colonic disease in newly diagnosed patients (4).

              In this substudy of the METRIC trial, the authors aimed to evaluate interobserver agreement for small bowel ultrasound in newly diagnosed and relapsing CD. 38 patients (11 new diagnosis and 27 relapses) were recruited from two sites. A second ultrasound examination was performed by one of a pool of six practitioners (5 radiologists and one sonographer) with variable levels of experience – ranging from 3 to 20 years of experience in gastrointestinal imaging and from 50 to >1000 small bowel ultrasound exams performed at the beginning of the trial. The presence, activity and location of small bowel and colonic disease were recorded. Comparisons were made against the reference standard (previously defined on the METRIC trial) and between practitioners. Against the reference standard, agreement for small bowel disease presence was 82% in new diagnosis and 81% in the relapsing group. For colonic disease presence the agreement was 64% in new diagnosis and 78% in relapsing group. Agreement between practitioners was 84% for small bowel and 87% for colonic disease presence.

              The latest ECCO-ESGAR Guideline for the Diagnostic Assessment in IBD, published in 2019, emphasizes the role of MRE and IUS in the assessment of CD patients. CT enterography should largely be reserved for the emergency setting due to radiation exposure (2).

              IUS has various advantages over MRE – it does not require oral or intravenous contrast, scanning times are faster and it is widely available. Also, while both methods are well tolerated by patients, IUS is generally preferred to MRE (5). By design, IUS is operator dependent and therefore interobserver variability has always been regarded as an important limitation. These results show that IUS evaluation in CD is reproducible and performs well against the reference standard in identifying CD presence, even amongst practitioners with different levels of experience. In this way, these results help to pave the way for wider implementation of IUS in CD in clinical practice.

              On the other hand, against the reference standard, the agreement on disease activity on a per-patient basis was only fair. Although there are MRE-based disease activity scores with high accuracy, currently there are no validated scores for IUS (6,7). Further research is needed to find a reliable IUS activity index.

              Finally, I would like to suggest revisiting the ESGAR-ECCO joint session during ESGAR 2019, available on the e-education portal, which I believe further enlightens the topic.

               

              References:

              1. Torres J, Bonovas S, Doherty G, et al. ECCO guidelines on therapeutics in Crohn’s disease: Medical treatment. J Crohn’s Colitis. 2020;14(1):4-22. doi:10.1093/ecco-jcc/jjz180
              2. Maaser C, Sturm A, Vavricka SR, et al. ECCO-ESGAR Guideline for Diagnostic Assessment in IBD Part 1: Initial diagnosis, monitoring of known IBD, detection of complications. J Crohn’s Colitis. 2019;13(2):144-164. doi:10.1093/ecco-jcc/jjy113
              3. Taylor S, Mallett S, Bhatnagar G, et al. METRIC (MREnterography or ulTRasound in Crohn’s disease): A study protocol for a multicentre, non-randomised, single-arm, prospective comparison study of magnetic resonance enterography and small bowel ultrasound compared to a reference standard in those . BMC Gastroenterol. 2014;14(1):1-10. doi:10.1186/1471-230X-14-142
              4. Taylor SA, Mallett S, Bhatnagar G, et al. Magnetic resonance enterography compared with ultrasonography in newly diagnosed and relapsing crohn’s disease patients: The METRIC diagnostic accuracy study. Health Technol Assess (Rockv). 2019;23(42):vii-161. doi:10.3310/hta23420
              5. Miles A, Bhatnagar G, Halligan S, et al. Magnetic resonance enterography, small bowel ultrasound and colonoscopy to diagnose and stage Crohn’s disease: patient acceptability and perceived burden. Eur Radiol. 2019;29(3):1083-1093. doi:10.1007/s00330-018-5661-2
              6. Sturm A, Maaser C, Calabrese E, et al. Ecco-esgar guideline for diagnostic assessment in ibd part 2: Ibd scores and general principles and technical aspects. J Crohn’s Colitis. 2019;13(3):273-284E. doi:10.1093/ecco-jcc/jjy114
              7. Bots S, Nylund K, Löwenberg M, Gecse K, Gilja OH, D’Haens G. Ultrasound for assessing disease activity in IBD patients: A systematic review of activity scores. J Crohn’s Colitis. 2018;12(8):920-929. doi:10.1093/ecco-jcc/jjy048

               

              Dr. João Carvalho is a fourth-year Radiology resident at the Centro Hospitalar Universitário do Porto, in Portugal. He is an active member of ESGAR and attends regularly ESGAR workshops and annual meetings.

              Comments may be sent to joaocarvalho.radiologia@remove-this.chporto.min-saude.pt


              Radiological evaluation of pancreatic cancer: What is the significance of arterial encasement >180° after neoadjuvant treatment?

              P. Mayer, A. Giannakis, M. Klaub, M.M. Gaida, F. Bergmann, H. U. Kauczor, M. Feisst, T. Hackert, M. Loos

              European Journal of Radiology Volume 137, 109603, 2021

              https://doi.org/10.1016/j.ejrad.2021.109603

               

              Pancreatic ductal adenocarcinoma (PDAC) is a malignant neoplasm with poor prognosis and only 4% 5-years survival due to precocious disease spread beyond pancreatic borders, with encasement of near vessels (1). Currently, the only potentially curative therapy is complete surgical resection. However, less than 30% of patients with newly diagnosed PDAC are eligible for it. In the absence of distant metastases, pancreatic cancer resectability is determined by the degree of tumor vascular infiltration.

              Arterial encasement >180° of the celiac axis, the superior mesenteric or the common and proper hepatic arteries makes non-treated PDAC unresectable according to current classifications (2).

              Therapeutic planning may be troublesome in patients with PDAC after neoadjuvant therapy (NAT) due to the difficulty in differentiating real arterial infiltration by neoplastic tissue from fibro-inflammatory perivascular alterations in post-therapy CT-scans: an encasement >180° may not correlate with vascular infiltration (3,4).

              Mayer and colleagues tried to provide criteria to establish vessels infiltration on CT-scans in Patients with more than 180° arterial encasement after NAT. 70 CT scans were analyzed before and after NAT and the interpretation was then confirmed by surgical and histological examinations.
              According to the surgical findings, patient arteries were divided into two groups: 51 non–invaded arteries and 24 invaded arteries.

              The CT evaluations and the statistical analyses of the acquired data identified two parameters that held high negative predictive value (NPV) in differentiating invaded and non-invaded arteries after NAT.
              The first is an arterial encasement >270°. In this series, this was the most appropriate threshold in differentiating invaded and non-invaded blood vessels after NAT (NPV=89.3%). In fact, only 24 out of 75 analyzed arteries with post-NAT >180° encasement were actually invaded by the tumor.
              The second is a solid soft tissue contact with arteries <26 mm: in this case, the arteries are less likely to be infiltrated (NPV=87.5%).
              After NAT, non-infiltrating lesions showed a significant decrease in length of solid tissue contact with blood vessels (≥20%), a marked reduction in size (≥20%), and presented significantly lower contiguity scores than infiltrating lesions.
              Another interesting result of this study concerns the post NAT levels of Carbohydrate 19.9 antigen (CA 19-9) and of Carcinoembryonic antigen (CEA). In fact, the levels of these serum tumor markers represent another aspect to be taken into consideration in differentiating between non-invaded and invaded arteries, with optimal cut-off values of > 73 U/ml for CA 19-9 and 2,3 mcg/L for CEA.

              In conclusion, this article, given that surgical resection is the only cure of PDAC, emphasizes the importance of the defining standardized criteria for a better CT assessment of resectability of PDAC after NAT. Neoadjuvant therapy plays a fundamental role in inducing tumor regression and in converting locally advanced, non-metastatic disease into surgically resectable disease, but after this treatment it is difficult to differentiate viable tumor from fibroinflammatory tissue (5). The major strength of this study is to describe radiological parameters useful in predicting tumor invasion of arteries that present a contiguity by solid soft tissue >180° post NAT. In fact, according to the results of this study, arteries with after NAT encasement >180° and ≤ 70° and with a length of tissue contact <26 mm are unlikely to be invaded. These radiological criteria may have important implications in the treatment of patients with pancreatic cancer because they can contribute to increase chances of surgical approach. However, post NAT discrimination of invaded from non-invaded arteries is still complex and a multidisciplinary assessment is always necessary to optimize treatment planning.

              References:

              1. Audrey Vincent, Joseph Herman, Rich Schulick, Ralph H Hruban, Michael Goggins (2011) Pancreatic cancer Lancet. 13; 378(9791): 607–620
              2. Seung Baek Hong, Seung Soo Lee, Jin Hee Kim, Hyoung Jung Kim, Jae Ho Byun, Seung MoHong, Ki-ByungSong, SongCheolKim (2018) Pancreatic Cancer CT: Prediction of Resectability according to NCCN Criteria Radiology; 289:710–718
              3. Ferrone CR, Marchegiani G, Hong TS, et al. (2015) Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer. Ann Surg; 261:12–17.
              4. Wanebo HJ, Glicksman AS, Vezeridis MP, Clark J, Tibbetts L, Koness RJ, Levy A (2000) Preoperative chemotherapy, radiotherapy, and surgical resection of locally advanced pancreatic cancer. Arch Surg135:81–87
              5. Yeo-Eun Kim, Mi-Suk Park, Hye-Suk Hong, Chang Moo Kang Jin-Young Choi, Joon Seok Lim, Woo Jung Lee, Myeong-Jin Kim, Ki Whang Kim (2009) Effects of Neoadjuvant Combined Chemotherapy and Radiation Therapy on the CT Evaluation of Resectability and Staging in Patients with Pancreatic Head Cancer Radiology: Volume 250: Number 3

               

              Martina Borzi is a third-year radiology resident at the Medical Imaging Department of the University of Verona, Italy. In 2017, Dr. Borzi graduated in Medicine and Surgery at the University of Rome Tor Vergata. Her main area of focus is abdominal imaging, especially pancreas and liver imaging. She has been developing particular interest in using software for texture analysis of intrahepatic cholangiocarcinoma.

              Comments may be sent to marti.borzi@remove-this.gmail.com


              Prognostic role of spleen volume measurement using computed tomography in patients with compensated chronic liver disease from hepatitis B viral infection

              Yoo J., Kim S.W., Lee D.H., Bae J.S., Cho E.J.

              European Radiology. March 2021; 31(3):1432-42.

              DOI: 10.1007/s00330-020-07209-6  PMID: 32880698

               

              Predict the development of decompensation (considered as the presence of variceal bleeding, ascites, jaundice, or encephalopathy) in patients with compensated chronic liver disease (cCLD) is important because it is one of the main determinants of survival (1). Furthermore, the risk of hepatocellular carcinoma (HCC) (2,3) or death (4,5) is higher in the decompensated stage than in compensated one.

              The authors of this study have investigated retrospectively the prognostic role of spleen volume measurement in patients with compensated chronic liver disease (cCLD) from chronic hepatitis B (CHB), particularly regarding the occurrence of HCC, the development of decompensation, and overall survival (OS), since splenomegaly is a common finding in patients with cirrhosis and portal hypertension (6).

              A total of 584 patients underwent contrast-enhanced multiphasic liver CT scan, including quadruple-phase with pre-contrast, late arterial phase (LAP), portal venous phase (PVP), and delayed phase (DP) for surveillance of HCC were included. The inclusion criteria include patients with CLD from CHB with Child-Pugh class A liver function without ascites, previous history of HCC treatment or hepatic decompensation, and absence of concomitant serious medical illness; who pursued at least more than 5 years of follow-up after the CT examination date without HCC occurrence, the development of decompensation, or death.

              The PVP images were used to measure the spleen. Unidimensional measurement size was performed by a board-certified radiologist. The longest dimension between the poles of the spleen was manually measured and recorded. The same radiologist, performed volumetric analysis independently using a semi-automated volumetric software program that was approved for liver volumetry. In each patient, less than 1 minute was needed for spleen volume measurement.

              Spleen length and volume were successfully measured in all patients. Mean spleen length ± standard deviation (SD) was 116.1 ± 23.3 mm, and mean spleen volume ± SD was 333.0 ± 216.4 mL (range, 40.5– 2206.1 mL).

              During a median follow-up period of 92 months, HCC occurred in 114 of 584 patients (19.5%), 30 patients (5.1%) experienced hepatic decompensation, and 23 patients (3.9%) died. Multivariate analysis revealed that spleen volume was an independent prognostic factor for HCC occurrence (hazard ratio (HR) = 1.01, 95% confidence interval = 1.01–1.01, p = 0.009), was a significant predictive factor for hepatic decompensation (HR = 1.01, 95% CI = 1.01–1.01, p = 0.005) and also was an independent predictor of OS (HR = 1.01, 95% CI = 1.01–1.01, p = 0.007). The optimal cutoff spleen volume was set at 532 mL for HCC occurrence, 656.9 mL for the development of decompensation, and 741.1 mL for OS. Conversely, the results after multivariate analysis were not statistically significant for spleen length. In this study, larger spleen volume was a significant risk factor for the development of HCC, decompensation, and death in CHB patients.

              We believe that this study is relevant because although US is currently the surveillance imaging modality of choice for HCC in patients at high risk (7,8), multiphasic CT scans are frequently performed. To measure the spleen volume could be easily acquired using a semi-automated 3D volumetric software program, and would provide relevant prognostic information regarding HCC occurrence, the development of decompensation, and OS.

              The study had some limitations. Firstly, there may be a potential risk of selection bias owing to the retrospective design of this study, particularly since patients that were enrolled had cCLD from CHB, and underwent multiphasic liver CT scans for HCC surveillance. Secondly, only patients with cCLD from CHB were studied, consequently, further studies in patients with other etiologies of chronic liver disease are needed to extrapolate the results on the prognostic role of splenic volume.

              In conclusion, spleen volume obtained using CT and semi-automated 3D volumetry software can provide prognostic information easily to obtain in patients with cCLD from CHB, regarding the probability of HCC occurrence, development of decompensation, and death.

              References:

              1. Garcia-Tsao G, Abraldes JG, Berzigotti A, Bosch J (2017) Portal hypertensive bleeding in cirrhosis: risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the Study of Liver Diseases. Hepatology 65:310–335
              2. Shim J-J, Oh CH, Kim JW, Lee CK, Kim B-H (2017) Liver cirrhosis stages and the incidence of hepatocellular carcinoma in chronic hepatitis B patients receiving antiviral therapy. Scand J Gastroenterol 52:1029–1036
              3. D'Amico G, Morabito A, D'Amico M et al (2018) Clinical states of cirrhosis and competing risks. J Hepatol 68:563–576
              4. D'Amico G, Garcia-Tsao G, Pagliaro L (2006) Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies. J Hepatol 44:217–231
              5. Asrani SK, Kamath PS (2013) Natural history of cirrhosis. Curr Gastroenterol Rep 15:308
              6. Berzigotti A, Zappoli P, Magalotti D, Tiani C, Rossi V, Zoli M (2008) Spleen enlargement on follow-up evaluation: a noninvasive predictor of complications of portal hypertension in cirrhosis. Clin Gastroenterol Hepatol 6:1129–1134
              7. Marrero JA, Kulik LM, Sirlin CB et al (2018) Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American Association for the Study of Liver Diseases. Hepatology 68:723–750
              8. European Association for the Study of the Liver (2018) EASL clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 69:182–236

               

              Vicente Belloch-Ripollés is a second-year radiology resident at the Hospital Universitari i Politècnic La Fe in Valencia, Spain. Dr. Belloch-Ripollés graduated at Universitat de Valencia with merit in June 2018. He has a wide range of interests in diagnostic imaging and is considering pursuing his career in abdominal radiology, with a special focus on liver imaging.

              Comments may be sent to belloch_vicrip@remove-this.gva.es


              Interobserver Variability and Diagnostic Performance of Gadoxetic Acid–enhanced MRI for Predicting Microvascular Invasion in Hepatocellular Carcinoma

              Min J.H., Lee M.W., Park H.S., Lee D.H., Park H.J., Lim S., Choi S.-Y., Lee J., Lee J.E., Ha S.Y., Cha D.I., Carriere K.C., Ahn J.H.

              Radiology 2020; 297:573–581. https://doi.org/10.1148/radiol.2020201940

               

              Hepatocellular carcinoma (HCC) is the sixth most prevalent neoplasm and the third leading cause of cancer death [1]. The progression of HCC is rapid with high invasiveness, and among the current treatment strategies, radical surgical resection is the preferred treatment strategy in patients with localized disease and preserved hepatic function. Despite optimal surgical resection, the outcome of HCC patients remains poor, and the postoperative 5-year recurrence rate of HCC is approximately 70%, of which two-thirds of all recurrences occur within 2 years after surgery and <35% after liver transplantation [2-4]. Microvascular invasion (MVI) is a histopathologic feature of tumor aggressiveness, observed in 15-57% of HCC, and it is considered as a strong predictor that leads to a high recurrence rate and poor survival rate in HCC patients [5]. An accurate preoperative noninvasive evaluation of the MVI presence can contribute to the optimal treatment strategy and prognosis stratification in patients with HCC based on risk-benefit assessment [6]. Despite several improvements in imaging technique and radiological diagnosis, the preoperative prediction of MVI remains challenging in clinical practice and different imaging features have been proposed as predictors of MVI.

              A recent study on the diagnostic performance of gadoxetic acid-enhanced magnetic resonance imaging (MRI) for predicting MVI in patients with diagnosis of HCC has been published by Min et al [7]. In this retrospective analysis, the Authors have evaluated the interobserver agreement and diagnostic performance in the preoperative MRI assessment of the presence of MVI in patients with surgically confirmed HCCs smaller than 5 cm. In their cohort of 100 patients, the most common cause of chronic liver disease was hepatitis B virus (88%) and 51 of 100 patients (51%) had liver cirrhosis. The mean tumor size was 2.8 cm ± 0.9 (62% <3 cm and 38% >3 cm) and MVI have been diagnosed in 39 of the 100 HCCs (39%) at histopathology. Considering the size of the tumor, HCCs >3 cm had a higher frequency of MVI than HCCs measuring 3 cm or less (55% vs 29%, respectively).

              Imaging analysis was performed by eight independent fellowship-trained radiologists. Different imaging features for the prediction of MVI have been assessed, and among these nonsmooth tumor margin showed the highest sensitivity (38-90%) and peritumoral arterial phase hyperenhancement showed the highest specificity (84-98%) for all readers. The specificity (95-100%) and positive predictive value (67-100%) were higher compared with other combinations of imaging features for all reviewers (irregular rim-like enhancement in the arterial phase, peritumoral hepatobiliary phase hypointensity). The analysis revealed a fair-to-moderate overall interobserver agreement (k range: 0.24-0.41) regarding each MVI imaging feature or their combination and MVI probability between observers.

              Diagnostic performance of each reader was modest for MVI prediction (area under the receiver operating characteristic curve [AUC] range, 0.60–0.74). The sensitivity for the diagnosis of MVI ranged from 15% to 69%, and the specificity ranged from 57% to 92%. Interestingly, when considering the size subgroup, the interobserver agreement for MVI probability was poor-to-fair and there were no differences in interobserver agreement for MVI according to the readers’ experience with regard to HCCs measuring 3 cm or less, while for HCCs larger than 3 cm, five more experienced readers showed higher sensitivity for the diagnosis of MVI. In the MVI probability categorization, more experienced readers showed higher agreement than less experienced readers.

              According to recent studies, a considerable interobserver variability exists in the assessment of MVI in HCC imaged with MRI, even for more experienced radiologists. Despite evidences has reported good interobserver agreement for the preoperative prediction on MVI with MRI, in particular regarding the nonsmooth tumor margin peritumoral arterial phase hyperenhancement, peritumoral HBP hypointensity [8], and irregular rim-like enhancement in the arterial phase [9], currently the preoperative diagnostic performance of imaging features for prediction of MVI is still highly variable.

              Therefore, other quantitative imaging analysis have been explored. Recent studies have reported that use of artificial intelligence and automated computerized image analysis, including radiomics, could improve the preoperative prediction of MVI and overcome the limits of the subjective assessment of MVI, but still need to be implemented and integrated in the clinical practice [10,11].

              In conclusion, this study [7] reports a considerable interobserver variability and a limited diagnostic performance in the MRI assessment of MVI in HCC, even by experienced radiologists. More standardized imaging criteria and further researches evaluating the diagnostic performance of MVI imaging features and their combinations are warranted, in order to provide valuable information to guide a more objective clinical decision-making and appropriate therapeutic strategy for patients with HCC.

               

              References:

              1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin (2018);68:394–424.
              2. Kardashian A, Florman SS, Haydel B et al. Liver transplantation outcomes in a U.S. multicenter cohort of 789 patients with hepatocellular carcinoma presenting beyond Milan criteria. Hepatology (2020).
              3. Vogel A, Cervantes A, Chau I et al. Hepatocellular carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol (2018);29:238–255
              4. Mazzaferro V, Sposito C, Zhou J et al (2018) Metroticket 2.0 Model for analysis of competing risks of death after liver transplantation for hepatocellular carcinoma. Gastroenterology (2018);154:128–139.
              5. Chong, HH., Yang, L., Sheng, RF. et al. Multi-scale and multi-parametric radiomics of gadoxetate disodium–enhanced MRI predicts microvascular invasion and outcome in patients with solitary hepatocellular carcinoma ≤ 5 cm. Eur Radiol (2021).
              6. Huang J, Tian W, Zhang L, et al. Preoperative Prediction Power of Imaging Methods for Microvascular Invasion in Hepatocellular Carcinoma: A Systemic Review and Meta-Analysis. Front Oncol (2020);10:887.
              7. Min JH, Lee MW, Park HS, Lee DH, Park HJ, Lim S et al. Interobserver Variability and Diagnostic Performance of Gadoxetic Acid-enhanced MRI for Predicting Microvascular Invasion in Hepatocellular Carcinoma. Radiology (2020) 297:3,573-581.
              8. Lee S, Kim SH, Lee JE, Sinn DH, Park CK. Preoperative gadoxetic acid-enhanced MRI for predicting microvascular invasion in patients with single hepatocellular carcinoma. J Hepatol (2017);67(3):526–534.
              9. Rhee H, An C, Kim HY, Yoo JE, Park YN, Kim MJ. Hepatocellular Carcinoma with Irregular Rim-Like Arterial Phase Hyperenhancement: More Aggressive Pathologic Features. Liver Cancer (2019);8(1):24–40.
              10. Ma X, Wei J, Gu D, et al. Preoperative radiomics nomogram for microvascular invasion prediction in hepatocellular carcinoma using contrast-enhanced CT. Eur Radiol 2019;29(7):3595–3605.
              11. He M, Zhang P, Ma X, He B, Fang C, Jia F. Radiomic Feature-Based Predictive Model for Microvascular Invasion in Patients With Hepatocellular Carcinoma. Front Oncol. 2020 Nov 5;10:574228.

               

              Dr. Francesco Matteini is a second-year young radiology resident at the University of Palermo (Italy) and an ESGAR member. Dr. Matteini graduated at the University of Palermo in October 2018. He is actually involved in scientific researches centered on hepatobiliary topics, and specifically on CT and MR imaging of focal liver lesions.

              Comments may be sent to dott.francescomatteini@remove-this.gmail.com


              Quality of same-day CT colonography following incomplete optical colonoscopy

              O’Shea, A., Foran, A. T., Murray, T. E., Thornton, E., Dunne, R., Lee, M. J., & Morrin, M. M. (2020)

              European Radiology, 30(12), 6508-6516. https://doi.org/10.1007/s00330-020-06979-3

               

              Performing a complete colonoscopy is vital for identifying colorectal malignancy and minimising polyp miss rates in all segments of the colon1. Unfortunately the success of colonoscopy is dependent on several factors including adequate bowel preparation and patient tolerance2. Estimated rates of incomplete colonoscopy vary between 4 and 24%1. Thankfully, CT colonography (CTC) is not as significantly limited by these factors. ESGAR consensus guidelines now state that CTC is the recommended tool for imaging the colon in the setting of incomplete endoscopic colonoscopy3-5. Increasingly centres with capacity can offer patients CT colonography on the same day or next day following incomplete optical colonoscopy, but there have been some questions regarding the quality of these studies6.

              A group of radiologists at the Beaumont hospital in Dublin conducted a retrospective review of 245 patients who underwent same-day CT colonography following an incomplete optical colonoscopy, in order to study the diagnostic quality of these scans.

              Following incomplete colonoscopy, patients underwent a low dose non-contrast CT scan of the abdomen and pelvis to exclude a perforation. Once they had recovered from any sedation administered at the time of colonoscopy faecal tagging was commenced using 30mL Gastrografin in 1 pint of water, consumed over 20 minutes. CTC was scheduled for approximately 3 hours later.

              In order to evaluate the quality of the same-day CTC studies, the colon was divided into thirteen sections extending from rectum to caecum. Each section was evaluated for adequacy of luminal distension, residual fluid volume and density, residual stool, and adequacy of faecal tagging. A scoring system was devised by a consultant radiologist, then taught to and employed by a single radiology fellow who reviewed all 245 scans. Scores for each aspect of diagnostic quality were allocated to each of the thirteen sections of the colon.

              Results showed that the median residual volume of fluid in each examined segment was estimated at less than 25%, and the mean score for tagging of residual fluid was between 0 (complete) and 1 (incomplete but adequate). Minimal residual stool was noted in the large bowel and, when present, was most frequently identified in the rectum or proximal sigmoid colon. Finally, luminal distension in all segments showed median values ranging from 3 to 4 on the semi-quantitative scale, indicating either “entire segment seen” or “well distended”. Contrast reached, at least, the left hemi-colon in 84% of patients and the rectum in 57% of patients. Perhaps most importantly, 99% of studies did not require a repeat CTC or optical colonoscopy.

              Overall the results give strong evidence for the concept that same-day CT colonography is a high quality study which can provide complete colonic evaluation following an incomplete colonoscopy.

              The benefits of offering same day CTC to patients who undergo incomplete colonoscopy are clear. Patients are saved having to present for another appointment, and enduring the uncomfortable process of bowel preparation for a second time. The study recognises this method’s potential to reduce patient ‘attrition’, by which a proportion of patients may never return for a repeat study, potentially leading to a delayed or missed diagnosis.

              Whilst the results of this study are impressive, it somewhat limited by the nature of its design as a retrospective, observational study. It would be interesting to see a matched cohort study comparing same day CTC scan quality with a group of patients undergoing CTC as their first test. A clever scoring system was devised as an attempt to categorise subjective parameters such as luminal distension, however a single radiology fellow evaluated all the scans, potentially introducing a degree of observer bias. Finally, the use of a low-dose non-contrast CT scan to exclude a perforation prior to the CTC results in a higher radiation dose, perhaps unnecessarily given that no perforations were identified in any of the 245 studies.

              This paper prompted intense discussion in our department when it was presented at the journal club meeting. The potential cost-effectiveness and patient-friendly advantages achieved by same-day CTC are a fantastic opportunity, but these must be weighed against a department’s capacity. The proportion of incomplete colonoscopies occurring during each endoscopy list would need to be determined in order to plan how many CT scan slots should be made available each day.

              References:

              1. Franco DL, Leighton JA, Gurudu SR (2017) Approach to incomplete colonoscopy: new techniques and technologies. Gastroenterol Hepatol 13:476–483 

              2. Sachdeva R, Tsai S, El Zein M et al (2016) Predictors of incomplete optical colonoscopy using computed tomographic colonography. Gastroenterol Hepatol (N Y) 22:43–49. https://doi.org/10.4103/1319- 3767.173758
              3. Neri E, Halligan S, Hellström M et al (2013) The second ESGAR consensus statement on CT colonography. Eur Radiol 23:720–729. https://doi.org/10.1007/s00330-012-2632-x
              4. Lara LF, Avalos D, Huynh H et al (2015) The safety of same-day CT colonography following incomplete colonoscopy with polypectomy. United European Gastroenterol J 3:358–363. https://doi.org/10.1177/2050640615577881
              5. Yucel C, Lev-Toaff AS, Moussa N, Durrani H (2008) CT colonography for incomplete or contraindicated optical colonosco- py in older patients. AJR Am J Roentgenol 190:145–150. https:// doi.org/10.2214/AJR.07.2633
              6. Theis J, Kim DH, Lubner MG, del Rio AM, Pickhardt PJ (2016) CT colonography after incomplete optical colonoscopy: bowel 
 preparation quality at same-day vs. deferred examination. Abdom Radiol (NY) 41:10–18. https://doi.org/10.1007/s00261-015-0595-5

               

              Donal Bradley is a clinical radiology fellow in St. James’ University Hospital in Leeds, UK. He is a fellow of the Royal College of Radiologists and an ESGAR member. Having completed his training in Manchester, he is undertaking a fellowship in gastrointestinal radiology.

              Comments may be sent to Donal.bradley@remove-this.doctors.org.uk


              Two-Dimensional-Shear Wave Elastography with a Propagation Map: Prospective Evaluation of Liver Fibrosis Using Histopathology as the Reference Standard

              Dong Ho Lee, Eun Sun Lee, Jae Young Lee, Jae Seok Bae, Haeryoung Kim, Kyung Bun Lee, Su Jong Yu, Eun Ju Cho, Jeong-Hoon Lee, Young Youn Cho, Joon Koo Han, Byung Ihn Choi

              Korean J Radiol. 2020 Dec;21(12):1317-1325. https://doi.org/10.3348/kjr.2019.0978

               

              The liver responds to sustained insult by a scarring process known as fibrosis. A stiff liver can regenerate when managed appropriately in its early stages but when gone unrecognised or untreated, can progress to irreversible cirrhosis and hepatocellular carcinoma.

              Transient elastography (TE), point shear wave elastography (SWE) and two-dimensional (2D) SWE of supersonic shear imaging (SSI) are ultrasound (US) techniques that have been developed to provide a reliable non-invasive measurement of liver stiffness comparable to the reference diagnostic standard which is fibrosis stage obtained from liver biopsy specimens. Accurate values for liver stiffness are achieved by using a measurement reliability index with point SWE and propagation map in 2D SWE. SWE techniques, unlike TE, can provide B-mode and elastography exams concurrently. Other limitations of TE include small sample volume and physical impediment to push-pulse technique in patients with ascites and obesity [1].

              In this prospective review, fibrosis detection and staging by 2D SWE using a propagation map was compared to results of histopathological specimens obtained from the same patients. The final study population comprised of 114 patients from two separate hospitals with a male to female ratio of 0.5:1 who met the following inclusion criteria: a) age between 20 – 85 years, b) liver biopsy indicated to ascertain cause of diffuse liver disease, c) valid informed consent and d) no bleeding risk (platelet count > 80,000/mm3, INR <1.5).

              One of three radiologists performed US evaluation of the liver parenchyma on all patients prior to liver biopsy. Patients were fasted for at least 6 hours before their scheduled appointment and they were scanned using a curvilinear probe in the supine position with their right arm above their head. Greyscale B-mode was first used to detect any focal lesions. 2D SWE mode was then activated, a 2 x 2 cm sample box was placed 1cm below Glisson’s capsule avoiding large vessels and a shear wave propagation was emitted using an acoustic radiation force while the patient held their breath for 1 second. Smooth parallel lines within the sample box were taken to represent stable measurement conditions. Shear wave propagation and data filling of the sample box was performed three times for each patient with one of the propagation maps having three further measurements taken from smaller 1cm-sized circular ROIs; this amounted to nine values of liver stiffness per patient. An elasticity map was then used to measure degree of liver stiffness in kilopascal (kPa).

              Out of the 9 values per patient, median measurements were selected for further analysis. Values >30% of the interquartile range (IQR) were considered unreliable. The rate of unreliable measurements in this study was estimated at 7.3%, similar to another study using 2D-SWE with a propagation map which had a rate of 5.2% [2] and less than another study using 2D-SWE with SSI which had a rate of 23% [3].

              The same radiologist performing the 2D SWE proceeded to perform a liver biopsy from segment V/VIII using an 18-gauge biopsy gun. Two 2.2cm long cores were obtained for each patient; these were fixed in formalin, embedded in paraffin and stained using haematoxylin and eosin as well as Masson’s trichrome stain. Two histopathologists reviewed all biopsy specimens assigning a stage of fibrosis (F0 – F4) and grade of necroinflammatory activity (A0 – A4).

              According to a multivariate linear regression analysis, stage of fibrosis was the only significant factor (p <0.001) determining liver stiffness value obtained by 2D-SWE with a propagation map. The latter provided good diagnostic performance in terms of grading each stage of liver fibrosis having a sensitivity of 91.7% and specificity of 87.8% for detecting F ≥ 3 stage and sensitivity of 90.9% and specificity of 88.4% for detecting cirrhosis.

              The authors highlight a number of limitations of this study namely, the heterogeneous nature of the study population with various aetiologies of chronic liver disease, uneven distribution of liver fibrosis stages, each patient was scanned by only one radiologist hence there was no assessment of interobserver agreement on liver stiffness values for individual patients and lack of head-to-head comparison with prospective studies using other elastography techniques.

              This study confirms that 2D-SWE with a propagation map is a reliable and accurate non-invasive technique to evaluate liver fibrosis.

               

              References:

              1. Jeong WK, Lim HK, Lee HK, Jo JM, Kim Y. Principles and clinical application of ultrasound elastography for diffuse liver disease. Ultrasonography 2014;33:149–160.
              2. Lee ES, Lee JB, Park HR, Yoo J, Choi JI, Lee HW, et al. Shear wave liver elastography with a propagation map: diagnostic performance and inter-observer correlation for hepatic fibrosis in chronic hepatitis. Ultrasound Med Biol 2017;43:1355–1363.
              3. Yoon JH, Lee JM, Joo I, Lee ES, Sohn JY, Jang SK, et al. Hepatic fibrosis: prospective comparison of MR elastography and US shear-wave elastography for evaluation. Radiology 2014;273:772–782.

               

              Dr. Daniel Borg is a third-year radiology resident at Mater Dei Hospital, Malta. He completed his undergraduate medical degree at the University of Malta in 2016 and joined the Medical Imaging Department in 2018 where he is undertaking training in diagnostic and interventional radiology.

              Comments may be sent to dannyborg22@remove-this.gmail.com


              Submucosal Enhancing Stripe as a Contrast Material–enhanced MRI-based Imaging Feature or the Differentiation of Stage T0–T1 from Early T2 Rectal Cancers

              Li-Juan Wan, MM* • Yuan Liu, MM* • Wen-Jing Peng, MM • Shuang-Mei Zou, MD • Feng Ye, MD •Han Ouyang, MD • Xin-Ming Zhao, MD • Chun-Wu Zhou, MD • Hong-Mei Zhang, MD

              Radiology 2020; 00:1–9

               

              Screening programmes have led to increased detection of early rectal cancers. Patients with early-stage rectal cancers can now be treated with chemo-radiotherapy or transanal endoscopic mucosal surgery (TEMS) rather than a total mesorectal excision which can carry significant morbidity. The treatment decision is often guided by local staging using MRI. Currently T0-T1 and T2 tumours are differentiated by assessing the status of the muscularis propria (SMP) on high resolution T2 weighted imaging.

              This paper introduces a novel and interesting radiological sign to differentiate T0-T1 from T2 rectal tumours - the submucosal enhancing stripe (SES). The submucosa of the rectum contains an abundance of vessels, which enhances on administering intravenous contrast, forming a continuous enhancing stripe. This stripe is lost or interrupted by a rectal tumour which crosses through the submucosa into the muscularis propria (i.e a T2 tumour). The main aim of the study was to assess how good the SES is at differentiating T0-T1 from T2 tumours and to compare which is better at differentiating T0-T1 and T2 rectal tumours; the conventional method of assessing the SMP or the novel SES.

              The authors performed a retrospective study of rectal MRI scans performed at their institute from 2012 to 2019. Only T0-T1 and T2 tumours with no prior chemo-radiotherapy which then underwent surgical resection within 3 weeks of the MRI were included. To further increase the validity of the findings only early T2 tumours were included, as the authors felt larger T2 tumours that infiltrated into the outer layer of muscularis propria could be easily distinguished from T1 tumours.

              The authors provide a thorough description of the inclusion and exclusion criteria, their MRI imaging protocol and the methodology of how the scans were reviewed. 431 patients met the inclusion criteria and their scans were reviewed independently by two GI radiologists with 38 years of rectal MRI experience between them. The imaging features which were assessed included tumour location, length, circumference, shape, distance from the anal verge, if the SES was present or absent and if the SMP was regular or irregular.

              249 patients had T0, Tis, T1 tumours and 182 T2 rectal tumours. In the T0-T1 group 84% had an intact SES whereas in the T2 group 92% had a disrupted SES.

              The diagnostic accuracy, sensitivity and specificity for the SES was 87% (95% CI: 84, 90), 84% (95% CI: 79, 88) and 92% (95% CI: 87, 95) respectively. For the SMP the diagnostic accuracy, sensitivity and specificity was 67% (95% CI: 63, 72), 63% (95% CI: 57, 69) and 73% (95% CI: 66, 79) respectively. Cohens Kappa Coefficient was used to calculate inter observer agreement. There was excellent inter observer agreement with the SES (indicating that it is a reproducible sign) whilst with SMP it was only moderate.

              Multivariate analysis performed on different imaging features showed that the SES, SMP and tumour shape are independent factors which allows the differentiation of T0–T1 from T2 tumours. Lesions with a SES, a regular SMP and carpetlike shape or a combination of the three features has a greater likelihood of being T0–T1 tumour. These key features from the multivariable model yielded an area under the receiver operating characteristic curve of 0.92 (95% CI: 0.90, 0.95).

              This paper introduces a promising fresh new sign to aid local staging of rectal cancer, backed by an extensive retrospective review of a large volume of rectal MRIs. The SES is a reproducible sign with a high diagnostic accuracy. The paper clearly describes the underlying principles of this novel sign with good, clear accompanying images and histological correlation.

              The study did have some limitations as it was performed at a single centre and it was retrospective so did not influence treatment decisions and no data were provided on outcomes. Gadolinium enhanced MRI is not routinely recommended in the most recent ESGAR Rectal Cancer guidelines from 2016 and the investigators used rectal gel to distend the lumen which is also not used routinely.2 Nevertheless this paper describes and investigates a new and interesting sign in rectal MRI staging which may have a role in the future.

               

              References:

              1. Wan LJ, Liu Y, Peng WJ, et al. Submucosal Enhancing Stripe as a Contrast enhanced MRI-based Imaging Feature for the Differentiation of Stage T0-1 from Early T2 Rectal Cancers. Radiology 2020. https://doi.org/10.1148/ radiol.2020201416. Published online November 10, 2020.
              2. Beets-Tan, R.G.H., Lambregts, D.M.J., Maas, M. et al. Magnetic resonance imaging for clinical management of rectal cancer: Updated recommendations from the 2016 European Society of Gastrointestinal and Abdominal Radiology (ESGAR) consensus meeting. Eur Radiol 28, 1465–1475 (2018). doi.org/10.1007/s00330-017-5026-2

               

              Dr Varun Chillal is currently completing a fellowship in Gastrointestinal Imaging at St James Hospital, Leeds, UK. He studied Medicine at the University of Leicester and undertook an intercalated BSc in Medical Management at Imperial Business School. As part of his foundation training, he worked as clinical demonstrator at the University of Leicester. He completed his specialist radiology training in West Midlands Deanery within the Birmingham rotations. He intends to take up a Consultant Gastrointestinal Radiologist post in the NHS next year.

              Comments may be sent to varun.chillal1@remove-this.nhs.net

               

               


              Adhesive Small Bowel Obstruction: Predictive Radiology to Improve Patient Management

              Marc Zins, Ingrid Millet, Patrice Taourel

              Radiology 2020; 00:1-13. https://doi.org/10.1148/radiol.2020192234

              Dr. Bruno Giesteira, 2nd year Radiologist Resident, Department of Radiology, Oporto Hospital and University Center, Oporto (Portugal).
              Prof. Dr. Manuela França, Hospitalar Assistant and Head of Radiology Department, Oporto Hospital and University Center, Oporto (Portugal).

               

              Small bowel obstruction (SBO) is a main reason of emergency room admissions, with adhesions being its most common cause. The management of SBO has been changing in recent years, with increasing non-surgical attitude instead of performing immediate surgery. Clinical and laboratory signs lack sensibility in predicting the need of surgery and, conversely, imaging studies have been playing a major role for treatment guidance. Imaging is performed to confirm the diagnosis of SBO, to locate the site of obstruction, to identify its cause and to evaluate for potential complications. In this paper, Zins et al. review the ability of imaging to personalize management decisions, namely, highlighting predictors of ischemia, bowel infarction and need for bowel resection, differentiators of open-loop from closed-loop adhesive SBO and, moreover, how to distinguish single band from matted adhesions.

              In spite of being widely used for evaluating small bowel loop dilation or air-fluid levels, abdominal radiographs lack sensibility and specificity compared to CT scans and are unable to identify the cause of SBO and its main complications. Nowadays, abdominal radiographs are not recommended as part of the work-up of suspected SBO by the American College of Radiology (ACR) appropriateness criteria (1) and Bologna guidelines (2). Ultrasound examination also fails in the identification of the transient point and the cause of obstruction. Therefore, it is not used as a first-line imaging technique, except in pregnancy and pediatrics patients.

              CT is the modality of choice for patients with a suspected SBO, being strongly recommended in both ACR appropriateness criteria (1) and Bologna guidelines (2). The authors suggest a multidetector CT protocol, with unenhanced acquisition plus intravenous contrast-enhanced acquisition on a portal venous phase, with multiplanar reconstruction. Oral contrast administration is not advised. Although not recommended by the ACR guidelines, the acquisition of unenhanced images may increase the detection of decreased bowel wall enhancement (3). Furthermore, they allow detecting increased bowel wall attenuation related to ischemia and transmural necrosis (4).

              Although MRI is nearly as accurate as CT imaging, it is limited by low availability and the need of patient cooperation.

              Strangulation with ischemia is the main source of morbi-mortality in patients with SBO and it requires emergent surgery. Determining signs of ischemia is the most important task for the radiologist. A recent meta-analysis concluded that decreased bowel wall enhancement had the highest specificity for strangulation and the absence of mesenteric fluid was reliable to exclude the diagnosis (5). Three major signs were associated with ischemia: decreased bowel wall enhancement, mesenteric haziness and closed-loop obstruction (6). The presence of at least two of these signs had a high positive likehood ratio and suggest a need for surgical intervention, whereas their total absence had a high negative predictive value suggesting non-surgical management.

              CT findings potentially associated with bowel resection include parietal pneumatosis, lack of bowel wall enhancement in portal venous phase, and increased bowel wall attenuation at unenhanced CT. The later has high specificity for necrosis but low sensitivity and, when present, it indicates irreversible ischemia and requires emergent bowel resection (4,7).

              The differentiation of the mechanism of adhesive SBO, as open-loop or closed-loop variants, is important because closed-loop adhesive is associated with a higher risk of bowel ischemia and failure of non-surgical treatment. The diagnosis of closed-loop SBO on CT is challenging. Characteristically, fusiform tapering of the loops is seen at the two adjacent transition zones as well as indirect signs, such as a C-/U-shaped bowel loop and radial distribution of the loops pointing to the transition zone. It is not straightforward that identifying a closed-loop SBO requires surgical intervention. In fact, a distance greater or equal to 8 mm between the two transition zones was predictive of a successful nonoperative treatment (8), still additional studies are needed.

              Usually, single band adhesion is more common in the absence of previous abdominal surgery and is more likely to cause strangulation. Extraluminal bowel compression by the band may be seen at the transition zone (fat notch sign) (9). In turn, matted adhesions cause obstruction by angulation, kinking and twisting the bowel (10).

              In conclusion, the authors review the major role of imaging in the management of adhesive SBO. They highlight the CT findings that indicate the mechanism of obstruction (open-loop vs closed-loop as well as single band vs matted adhesions), and those which predict ischemia or the need for bowel resection.
               

              References

              1. American College of Radiology. ACR Appropriateness Criteria Suspected Small Bowel Obstruction. acsearch.acr.org/docs/69476/Narrative/. pdf. Accessed January 2, 2020.
              2. Ten Broek RPG, Krielen P, Di Saverio S, et al. Bologna guidelines for diagnosis and management of adhesive small bowel obstruction (ASBO): 2017 update of the evidence-based guidelines from the world society of emergency surgery ASBO working group. World J Emerg Surg 2018;13(1):24.
              3. Chuong AM, Corno L, Beaussier H, et al. Assessment of Bowel Wall Enhancement for the Diagnosis of Intestinal Ischemia in Patients with Small Bowel Obstruction: Value of Adding Unenhanced CT to Contrast-enhanced CT. Radiology 2016;280(1):98–107.
              4. Rondenet C, Millet I, Corno L, Boulay-Coletta I, Taourel P, Zins M. Increased unenhanced bowel-wall attenuation: a specific sign of bowel necrosis in closed-loop small-bowel obstruction. Eur Radiol 2018;28(10):4225–4233
              5. Millet I, Taourel P, Ruyer A, Molinari N. Value of CT findings to predict surgical ischemia in small bowel obstruction: A systematic review and metaanalysis. Eur Radiol 2015;25(6):1823–1835.
              6. Millet I, Boutot D, Faget C, et al. Assessment of Strangulation in Adhesive Small Bowel Obstruction on the Basis of Combined CT Findings: Implications for Clinical Care. Radiology 2017;285(3):798–808.
              7. Nakashima K, Ishimaru H, Fujimoto T, et al. Diagnostic performance of CT findings for bowel ischemia and necrosis in closed-loop small-bowel obstruction. Abdom Imaging 2015;40(5):1097–1103.
              8. Rondenet C, Millet I, Corno L, et al. CT diagnosis of closed loop bowel obstruction mechanism is not sufficient to indicate emergent surgery. Eur Radiol 2020;30(2):1105–1112.
              9. Petrovic B, Nikolaidis P, Hammond NA, Grant TH, Miller FH. Identification of adhesions on CT in small-bowel obstruction. Emerg Radiol 2006;12(3):88–93; discussion 94–95.
              10. Osada H, Watanabe W, Ohno H, et al. Multidetector CT appearance of adhesion-induced small bowel obstructions: matted adhesions versus single adhesive bands. Jpn J Radiol 2012;30(9):706–712.

               

              Dr. Bruno Giesteira is a 2nd year radiology resident at the Centro Hospitalar Universitário do Porto, in Portugal. He completed his undergraduate medical degree at Escola de Ciências da Saúde, Universidade do Minho, Braga, in 2017. He is an active member of the ESGAR and has been developing a particular interest in diagnostic genitourinary and abdominal radiology, especially in gastrointestinal imaging.

              Comments may be sent to brunogiesteira6@remove-this.gmail.com

               


              MRI Findings of Liver Parenchyma Peripheral to Colorectal Liver Metastasis: A Potential Predictor of Long-term Prognosis

              Authors: Nakai Y, Gonoi W, Kurokawa R, Nishioka Y, Abe H, Arita J, Ushiku T, Hasegawa K, Abe O.

              Journal: Radiology. 2020 Dec;297(3):584-594.
              doi: 10.1148/radiol.2020202367.
              Epub 2020 Oct 6. PMID: 33021892.

               

              Curative liver resection is recommended as the most effective therapy for colorectal liver metastasis (CRLM). Histopathological analysis of resected CRLM usually aims to confirm malignancy or evaluate surgical margins, but other aspects such as vascular or bile duct invasion have been proposed as poor prognostic factors after resection of CRLM (1,2).

              For an accurate surgical planning, gadoxetic acid (Gd-EOB-DTPA)-enhanced MRI is usually performed. Some authors have tried to predict long-term prognosis after hepatectomy based on some MRI findings, such as delayed tumor enhancement (3), but there have been no reports of prediction of microscopic vascular invasion of CRLM based on Gd-EOB-DTPA–enhanced MRI.

              The authors aim to investigate whether EOB-DTPA–enhanced MRI findings peripheral to the CRLM could be used to predict pathologic vessel invasion, overall survival (OS) and recurrence-free survival (RFS) after curative surgery in patients without neoadjuvant chemotherapy. Their retrospective study included 148 metastases in 106 patients, excluding patients with five or more metastases, CRLM of <10 mm and portal vein embolization before surgery. Some clinical and analytical variables were recorded, such as the primary site of the tumor, primary tumor nodal status, history of extrahepatic disease, history of synchronous liver metastasis, number of hepatectomies, history of adjuvant chemotherapy, and preoperative serum carcinoembryonic antigen (CEA) level.

              Imaging follow-up was performed every three months for the first two years, and then every six months. The MRI dynamic study involving liver acquisition included double arterial and portal venous phase or arterial, portal venous, and delayed phase images. Hepatobiliary phase images were obtained.

              The MRI images were examined by three independent abdominal radiologists who were blinded to the clinical and pathologic findings, and they evaluated for number and diameter of CRLMs, presence or absence of early enhancement of liver parenchyma, reduced Gd-EOB-DTPA uptake area and bile duct dilatation peripheral to the tumor.

              Histologic specimens were reevaluated and analyzed by a board-certified pathologist also blinded to the clinical and imaging findings, to assess surgical margin status and the presence or absence of portal vein, hepatic vein and bile duct invasion.

              Authors developed two multivariable analysis model. In the first, they analyzed separately three findings: the presence or absence of early enhancement, reduced Gd-EOB-DTPA uptake and bile duct dilatation. In the second model, they included the integrated MRI finding of CRLM positive for one or more of the three findings.

              Bile duct dilatation peripheral to the tumor was associated with pathologic portal vein invasion (sensitivity, 12 of 50 [24%]; specificity, 89 of 98 [91%]; P = .02), bile duct invasion (sensitivity, 8 of 19 [42%]; specificity, 116 of 129 [90%]; P = .001), poor RFS (P = .03; hazard ratio [HR] = 2.4 [95% confidence interval {CI}: 1.3, 4.2]), and poor OS (P = .01; HR = 2.4 [95% CI: 1.2, 4.9]).

              Early enhancement and reduced Gd-EOB-DTPA uptake peripheral to the CRLM were not associated with pathologic vessel invasion or RFS and were associated with OS only in univariable analysis. However, a combination of early enhancement and reduced Gd-EOB-DTPA uptake peripheral to the CRLM with bile duct dilatation at MRI was predictive of poor OS (P = .001, HR = 3.3).

              The main weakness of this study is its retrospective design, and some limitations in the patient’s selection and evaluation. In patients who had undergone multiple hepatectomies, imaging findings at the time of the other hepatectomies were not reviewed. Besides, they did not evaluate tumors smaller than 10 mm and patients with neoadjuvant chemotherapy were not included. Furthermore, different patterns of recurrence were not evaluated. Future studies should investigate the tumor recurrence pattern and whether neoadjuvant chemotherapy improves prognosis in patients with tumors showing abnormal peritumoral imaging findings.

              Previously other authors studied peritumoral MRI changes to evaluate microvascular invasion in hepatocellular carcinoma (4) and reported a clinical-pathological-radiomic model to predict early recurrence of hepatocellular carcinoma (5). Thus, this study could provide a background for elaborating a radiomic model of CRLM.

              In conclusion, it is important for radiologists to bear in mind the importance the assessment of peritumoral imaging findings, as it adds clinical value to preoperative routine MRI and may help planning a wide surgical margin, facilitating the treatment of patients with a high preoperative probability of recurrence or poor estimates of overall survival.

               

              References:

              1. Knijn N, de Ridder JA, Punt CJ, de Wilt JH, Nagtegaal ID. Histopathological evaluation of resected colorectal cancer liver metastases: what should be done? Histopathology 2013;63(2):149–156.
              2. Reijonen P, Österlund P, Isoniemi H, Arola J, Nordin A. Histologically Verified Biliary Invasion was Associated with Impaired Liver Recurrence-Free Survival in Resected Colorectal Cancer Liver Metastases. Scand J Surg 2019;108(3):201–209.
              3. Cheung HMC, Karanicolas PJ, Coburn N, Seth V, Law C, Milot L. Delayed tumour enhancement on gadoxetate-enhanced MRI is associated with overall survival in patients with colorectal liver metastases. Eur Radiol 2019;29(2):1032–1038.
              4. Kim H, Park MS, Choi JY, et al. Can microvessel invasion of hepatocellular carcinoma be predicted by pre-operative MRI? Eur Radiol 2009;19(7):1744–1751.
              5. Kim S, Shin J, Kim DY, Choi GH, Kim MJ, Choi JY. Radiomics on Gadoxetic Acid-Enhanced Magnetic Resonance Imaging for Prediction of Postoperative Early and Late Recurrence of Single Hepatocellular Carcinoma. Clin Cancer Res 2019;25(13):3847–385

               

              Diana Veiga-Canuto is a fourth-year radiology resident at Hospital Universitari i Politècnic La Fe (València, Spain). She started her residency after completing her medical studies in Universitat de València, where she is currently a PhD student in Medicine. Diana has a broad range of interests in diagnostic imaging, especially abdominal adult and pediatric imaging. She is an ESGAR member and has attended some ESGAR/ESOR biomarkers workshops and courses. She has been actively involved in clinical imaging research and has participated as an author or co-author in different national and international publications.

              Comments may be sent to veiga_dia@remove-this.gva.es


              Comparison of a coaxial versus non-coaxial liver biopsy technique in an oncological setting: diagnostic yield, complications and seeding risk. 

              Nicos Fotiadis, Katja N. De Paepe, Lawrence Bonne,Nasir Khan, Angela Riddell, Nicholas Turner, Naureen Starling, Marco Gerlinger , Sheela Rao, Ian Chau, David Cunningham & Dow-Mu Koh

              Eur Radiol 30, 6702–6708 (2020).
              https://doi.org/10.1007/s00330-020-07038-7


              Interventional radiology skills form workload for many gastrointestinal radiologists.  The complexity of oncological therapies continues to increase, requiring routine sophisticated tumour analysis for molecular and genomic analysis, such as for deficient mis match repair in colorectal carcinoma, which indicates chemotherapy resistance of tumours to 5-FU based chemotherapy.1 Since the liver is a common site for metastasis the optimal method for tissue sampling must be considered.  While CIRSE has issued guidance on percutaneous needle biopsy in 2017, no specific guidance was issued regarding the optimal needle combination (Coaxial vs Non-coaxial).2 However they noted that coaxial systems have no increase in complications and may reduce procedure time compared with non-coaxial techniques.

              The Royal Marsden research group (London, UK) performed this important comparative study to assess the optimal technique for coaxial needle biopsy of the liver, comparing diagnostic yield, safety and seeding risk with a coaxial percutaneous liver biopsy (C-PLB) and a non-coaxial (NC-PLB) liver biopsy technique in a cancer patient cohort.   

              The group evaluated the outcomes in 741 patients undergoing 932 liver biopsies with 9.1% under CT guidance with the remaining 90.9% using ultrasound with patients given fentanyl and optional midazolam for comfort.  Patients had a full range of malignancies, with the commonest being Colorectal (20.4%), Breast (15.5%) and Lung (9%). The operator was able to choose the type of needle and the diameter (C-PLB 15G or 17G vs NC-PLB 16G or 18G) depending on preference and clinical situation. In the group undergoing C-PLB all patients had gelatin pledgets inserted along the needle track for haemostasis at the end of the procedure. All patients without complications were observed for 4 hours prior to discharge. Outcomes and complications were assessed by follow up of patient records and imaging studies.

              C-PLB was most commonly performed (72.9% vs 27.1% for NC-PLB) with 18G biopsy diameter selected in 69.1% and 85% respectively.  Diagnostic yield was high (92.6%) with no significant difference in diagnostic yield between C-PLB and NC-PLB or differences in needle diameter. However more cores were obtained in the C-PLB group (median 4 vs 2 in NC-PLB, p<0.001).  

              While the overall complication rate was 9.3%, complications were lower with C-PLB (8.2% vs 12.3% in NC-PLB; p = 0.024), with pain and sepsis/fever featuring more commonly in the NC-PLB group. While the 1.8% tumour seeding rate was low, this was significantly higher in the NC-PLB group (3% compared with 1.3% in C-PLB,P=0.021). Seeding rate was noted to be higher in melanoma, GIST and cholangiocarcinoma tumour subtypes and were only detected as small lesions on retrospective review of the imaging in all 13 cases. However, the overall tumour seeding rate was lower than expected in colorectal cancer where rates of up to 16% have been published, compared to 2% in this group.  The team hypothesise that this is related to single puncture of the liver capsule and that the outer coaxial needle does not contact the tumour metastasis.

              While the group recognises drawbacks in the study design including selection bias and retrospective design, overall some important messages come from this large study. This reflects a ‘routine’ oncology workload and shows that C-PLB with track plugging is a safe technique with a lower complication rate and lower risk of tumour seeding then NC-PLB. Perhaps it is time to consider this as the optimal method for tumour sampling in the liver?

               

              References:

              1.Kawakami H, Zaanan A, Sinicrope FA. Implications of mismatch repair-deficient status on management of early stage colorectal cancer. J Gastrointest Oncol. 2015;6(6):676-684. doi:10.3978/j.issn.2078-6891.2015.065

              2. Veltri A, Bargellini I, Giorgi L, Almeida PAMS, Akhan O. CIRSE Guidelines on Percutaneous Needle Biopsy (PNB). Cardiovasc Intervent Radiol. 2017 Oct;40(10):1501-1513. doi: 10.1007/s00270-017-1658-5.

               

              Dr. Damian Tolan is a gastrointestinal radiologist from St James’s University Hospital (Leeds, UK) specialising in luminal gastrointestinal imaging with a particular clinical and research interest in colorectal cancer, inflammatory bowel disease and perianal disease. He is a regular faculty member at ESGAR conferences and a member of guideline groups and the Education committee of ESGAR.

              Comments may be sent to: damian.tolan@remove-this.nhs.net


              Ileocolic vascular curvature: a new CT finding of cecal volvulus

              Authors
              : Margaret Wong, R. Brooke Jeffrey, Adam N. Rucker, Eric W. Olcott

              Journal Abdominal Radiology 2020 Oct; 45(10):3057-3064.

              doi: https://doi.org/10.1007/s00261-020-02491-w


              Dr. Smarda Magdalini, Radiology Consultant at Computed Tomography Department of Konstantopouleio General Hospital of Athens, Greece

              Cecal volvulus constitutes a relatively rare and potentially fatal emergency condition, in need for immediate open surgery. Less invasive methods of treatment (for example operative detorsion, cecopexy and cecostomy) have been proven to be associated with more complications and higher rates of mortality, so they are not usually preferred [1, 2].

              The symptoms of cecal volvulus are not specific and therefore, the clinical image can be misleading. Patients often present to the hospital with acute abdominal pain, abdominal distention, nausea, vomiting and reduction – inhibition of stool output, that is, with symptoms of bowel dilatation of any reason [3].

              Apart from the aforementioned nonspecific clinical findings, laboratory findings are also not typical for the disease. So, abdominal imaging and specifically imaging evaluation with computed tomography (CT), plays an important role in the early diagnosis of this potentially fatal nosological entity. Several imaging CT features have been proposed so far as indicative of this condition, including the ‘whirl’ sign, the ‘coffee bean’ sign, decompression of the colon distally to the cecum, small bowel dilation, transition point existence, abnormal appendix position (near the midline, with small bowel being lateral to the cecum) and finally, the ectopic position of cecum [4 – 7].

              This article focuses on a new CT observation concerning a mesenteric vasculature differentiation in patients with cecal volvulus that has not been described so far in the literature. More specifically, the authors of this article reported a hook-like curvature of distal ileocolic vessels (‘ileocolic vascular curvature’) in the vast majority of patients who had undergone an urgent abdominal CT examination at their Department because of having the aforementioned symptoms, and afterwards, they proved to suffer from this emergency condition. This finding contradicts the normal linear course of ileocolic vasculature encountered in patients without proven cecal volvulus. A patient search was conducted using the Department’s Picture Archiving and Communication System (PACS) throughout 12.5 years and with the selection of keywords relative to the disease in the Department’s existing CT reports, using the institution’s search engine.

              A total number of 14 patients with cecal volvulus from the original CT reports were compared with 40 control patients with cecum dilation without volvulus on original CT reports concerning the existence of the above-mentioned CT features, including ileocolic vascular curvature. Among all 8 CT features examined in this quantitative study, only ileocolic vascular curvature and ectopic cecum were independently and significantly associated with cecal volvulus in multivariable regression (odds ratio 178, p = 0.014, and 63, p = 0.013, respectively). In addition, their sensitivity (12/14 [85.7%, 95% CI 57.2–98.2%] and 13/14 [92.9%, 95% CI 66.1–99.8%], respectively) and specificity (40/40 [100.0%, 95% CI 91.2–100.0%] and 38/40 [95.0%, 95% CI 83.1–99.4%], respectively) were high, differing remarkably from the respective percentages of the rest CT features, which approximated 50%.

              The most important limitation of this study is the small sample size, also encountered in previously published studies of the same topic, having to do with the infrequent occurrence of this emergency condition. The small number of patients is considered to be the reason for the deviations of findings between this study and the few previously published quantitative studies concerning the same pathology [8, 9]. It should be pointed out as well, that differences in the results among relevant studies may reflect differences in study design (for example, different criteria for the selection of patients taking part in the study). In addition, this study’s low sensitivity and/or specificity of most CT features apart from ileocolic vascular curvature and ectopic cecum may not correspond to reality, since these values could change dramatically with substantially larger sample size.

              To conclude, the new CT observation of ileocolic vascular curvature in patients with cecal volvulus may prove to be a valuable tool for the diagnosis of this relatively rare but of high mortality condition if diagnostically missed. Further studies with larger sample sizes could provide more safe results concerning the contribution of this new CT finding in the diagnosis and treatment of cecal volvulus.

               

              References:

              [1] Halabi WJ, Jafari MD, Kang CY, Nguyen VQ, Carmichael JC, Mills S,  igazzi A, Stamos MJ (2014) Colonic volvulus in the United States: trends, outcomes, and predictors of mortality. Ann Surg 259 (2): 293–301

              [2] Madiba TE, Thomson SR (2002) The management of cecal volvulus. Dis Colon Rectum 45 (2): 264–267

              [3] Gingold D, Murrell Z (2012) Management of colonic volvulus. Clin Colon Rectal Surg 25 (4): 236–244

              [4] Fisher JK (1981) Computed tomographic diagnosis of volvulus in intestinal malrotation. Radiology 140 (1): 145–146.

              [5] Frank AJ, Goffner LB, Fruauff AA, Losada RA (1993) Cecal volvulus: the CT whirl sign. Abdom Imaging 18 (3): 288–289

              [6] Moore CJ, Corl FM, Fishman EK (2001) CT of cecal volvulus: unraveling the image. AJR Am J Roentgenol 177 (1): 95–98

              [7] Figiel LS, Figiel SJ (1953) Volvulus of the cecum and ascending colon.  Radiology 61 (4): 496–515

              [8] Dane B, Hindman N, Johnson E, Rosenkrantz AB (2017) Utility of CT Findings in the Diagnosis of Cecal Volvulus. AJR Am J Roentgenol 209 (4): 762–766

              [9] Rosenblat JM, Rozenblit AM, Wolf EL, DuBrow RA, Den EI, Levsky JM (2010) Findings of cecal volvulus at CT. Radiology 256 (1): 169–175

               

              Dr. and PhD. Smarda Magdalini is a Radiology Consultant at Computed Tomography Department of Konstantopouleio General Hospital of Athens, Greece. She has completed postgraduate studies in Interventional Radiology and Vascular Imaging as well. Her main interests in Diagnostic Radiology are Abdominal and Vascular Imaging and recently, Neuroimaging.

              Comments may be sent to magda.3110@remove-this.hotmail.com


              Contrast-enhanced US with Sulfur Hexafluoride and Perfluorobutane for the Diagnosis of Hepatocellular Carcinoma in Individuals with High Risk
              Authors:
              Hyo-Jin Kang,  Jeong Min Lee , Jeong Hee Yoon, Kyoungbun Lee, Haeryoung Kim, Joon Koo Han
              Journal: . Radiology. 2020 Aug 4
              DOI: doi.org/10.1148/radiol.2020200115

              Dr. Ivo Sá Marques, Resident, Department of Medical Imaging, Coimbra Hospital and University Centre, Coimbra (Portugal).
              Dr. Daniel Ramos Andrade, Radiology Consultant, Coimbra Hospital and University Centre, Coimbra (Portugal).
              Prof. Dr. Luís Curvo Semedo, Radiology Consultant, Coimbra Hospital and University Centre; Assistant Professor, Faculty of Medicine - University of Coimbra (Portugal).

              Contrast ultrasound (CEUS) is increasingly used in the liver given its high accuracy in the differential diagnosis of focal liver lesions. This technique is readily available, cost-effective and has almost no contraindications and adverse events. Its disadvantages are closely related to the ultrasound technique itself. The ultrasound contrast agent available in Europe -  sulphur hexafluoride (SHF) consists of sulphur hexafluoride microbubbles coated with phospholipids, with a diameter of <10 μm that remain strictly intravascular, with no diffusion into the interstice. [2]

              Perfluorobutane (PFB) is a contrast agent that contains perfluorobutane microbubbles inside a phosphatidylserine shell (diameter 2–3 μm). They reach the liver in about 15 s, allowing imaging of the hepatic arterial vascularization and are also captured by Kupffer cells in the reticuloendothelial system of the liver, which enables parenchyma-specific liver imaging. This Kupffer phase imaging is generally performed 10 minutes after intravenous contrast media administration, at which time the normal hepatic parenchyma is enhanced. Therefore, malignant lesions containing few or no Kupffer cells are clearly shown as contrast defects in this phase. An advantage of PFB microbubbles over SHF is their ability to resonate with moderate ultrasound pressure without collapsing, which facilitates the scanning of the entire liver in a Kupffer phase for several hours. [3,4]

              In this article, Kang et al. compared the enhancement patterns and diagnostic performance of CEUS with PFB and SHF, in the characterization of liver nodules in patients with a high probability of HCC, based on the CEUS Liver Image Reporting and Data System (LI-RADS®) of the American College of Radiology (ACR). CEUS LI-RADS® standardizes the CEUS technique, interpretation, reporting and data collection for patients at risk of developing hepatocellular carcinoma (HCC). [5]

              The study included, from February to August 2019, patients older than 18 years old, at risk of HCC, with one or more treatment-naive hepatic observations (>1 cm) of LR -3, LR-4, LR-5 or LR-M according to CT / MRI LI-RADS version 2018 in acceptable diagnostic images obtained 6 weeks before enrolment. Patients with congestive liver disease, an obvious tumour in a vein and severe cardiovascular dysfunction were excluded. First, an operator radiologist studied the observations with the US-SHF and, soon after the degradation of the microbubbles with high mechanical index pulses in B-mode, the study with PFB proceeded with an interval of at least 30 minutes. The dynamic imaging characteristics (arterial phase hyperenhancement, washout time and degree, and echogenicity in the Kupffer phase) were recorded and then later observed by a reviewer. Only LR-5 observations were assumed to be diagnostic of HCC.

              43 of the 59 included observations were confirmed as HCCs. Specificity was 100% for both types of contrast-enhanced US exams. PFB-enhanced US provided higher sensitivity (79% and 74%) and accuracy 0.90 and 0.87 for HCC diagnosis compared with SHF-enhanced US (sensitivity, 54% and 58%; p = .01 and p = .048; accuracy, 0.77 and 0.79, p = .01 and p = .04, for the operator and reviewer, respectively) with implementation of diagnostic criteria for CEUS LI-RADS.

              Despite most of the malignancies manifesting clear hypoenhancement in the Kupffer phase with PFB, the degree and prevalence of hypoenhancement did not differ between HCCs and non-HCC malignancies, so the Kupffer phase, in isolation, has no increased specificity. However, reassuringly, none of the benign lesions had hypoenhancement in this phase. These findings suggest we can get a more confident diagnosis of malignancy with the Kupffer phase of PFB.

              A possible explanation by the authors for the marginally better results of PFB is that high acoustic pressure, which offers higher spatial resolution, may contribute to improved lesion-to-parenchymal echogenicity differences during the late phase, and thus increase the sensitivity.

              As stated by their authors, this study has some limitations. In addition to having a small population of a single centre, the biggest constraint could be the fact that both CEUS examinations were performed by one operator per participant with short intervals between them and after CT / MR pre-selection observations, which could produce a selection bias and affect the diagnostic performance of the CEUS.

              In conclusion, even for the most critical, CEUS is a technique that might be useful in the future. For the follow-up of suspicious HCC nodules, it has economic and security advantages. It’s doubtful if PFB will be able to replace SHF in the characterization of suspicious HCC nodules. In theory, PFB has advantages over SHF in lesion-to-parenchymal contrast, however, the importance of the Kupffer phase in isolation remains to be seen.

               

              References

              1. Kang HJ, Lee JM, Yoon JH, Lee K, Kim H, Han JK. Contrast-enhanced US with Sulfur Hexafluoride and Perfluorobutane for the Diagnosis of Hepatocellular Carcinoma in Individuals with High Risk. Radiology. 2020 Oct; 297(1):E24 doi: 10.1148/radiol.2020209017.
              2. Schellhaas B, Strobel D. Tips and Tricks in Contrast-Enhanced Ultrasound (CEUS) for the Characterization and Detection of Liver Malignancies. Ultraschall Med. 2019 Aug;40(4):404-424. English. doi: 10.1055/a-0900-396
              3. Park HS, Kim YJ, Yu MH, Jung SI, Jeon HJ. Real-time contrast-enhanced sonographically guided biopsy or radiofrequency ablation of focal liver lesions using perflurobutane microbubbles (sonazoid): value of Kupffer-phase imaging. J Ultrasound Med. 2015 Mar;34(3):411-21. doi: 10.7863/ultra.34.411
              4. Goto E, Masuzaki R, Tateishi R, Kondo Y, Imamura J, Goto T, Ikeda H, Akahane M, Shiina S, Omata M, Yoshida H, Koike K. Value of post-vascular phase (Kupffer imaging) by contrast-enhanced ultrasonography using Sonazoid in the detection of hepatocellular carcinoma. J Gastroenterol. 2012 Apr;47(4):477-85. doi: 10.1007/s00535-011-0512-9
              5. Kono Y, Lyshchik A, Cosgrove D, Dietrich CF, Jang HJ, Kim TK, Piscaglia F, Willmann JK, Wilson SR, Santillan C, Kambadakone A, Mitchell D, Vezeridis A, Sirlin CB. Contrast Enhanced Ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS®): the official version by the American College of Radiology (ACR). Ultraschall Med. 2017 Jan;38(1):85-86. doi: 10.1055/s-0042-124369.

               

              Dr. Ivo Sá Marques is a second-year resident of Radiology at the Centro Hospitalar e Universitário de Coimbra, Portugal. He started his medical course at Nova Medical School in Lisbon and completed it at the Faculdade de Medicina da Universidade do Porto. He is author of several national papers and was a speaker at the 2019 Portuguese Radiology Society Conference. His main interests in diagnostic radiology are abdomen and trauma.

              Comments may be sent to sa.marques.ivo@remove-this.gmail.com


              Observer agreement for small bowel ultrasound in Crohn’s disease: results from the METRIC trial1
              Authors
              : Gauraang Bhatnagar, Laura Quinn, Antony Higginson, Andrew Plumb, Steve Halligan, Damian Tolan, Roger Lapham, Susan Mallett, Stuart A. Taylor & METRIC study investigators
              Journal Abdominal Radiology 45:3036-3045. 2020 Feb 10. DOI: https://doi.org/10.1007/s00261-020-02405-w

              The METRIC trial2 was a prospective multicentre trial which recently demonstrated the high sensitivity of small bowel ultrasound (SBUS) for both the presence and extent of small bowel Crohn’s disease. Small bowel ultrasound has advantages over magnetic resonance enterography (MRE); it is widely available, cheaper, does not require IV contrast and is generally preferred by patients3. The perceived drawback of SBUS is the high operator dependence to both identify subtle disease but also to localise disease. Whilst Parente et al.4 found excellent inter-observer agreement when localising affected segments of bowel in Crohn’s disease, there is a paucity of research assessing inter-observer variability of active disease on SBUS which is particularly important to guide management.

              This study by Taylor et al. set out to assess inter-observer variability for the presence, extent and descriptive features of small bowel and colonic Crohn’s disease.

              A proportion of patients previously recruited in the METRIC trial underwent a repeat ultrasound by a different practitioner who was blinded to the findings from the previous SBUS as well as other imaging, and all endoscopic and clinical data other than under which cohort the patient was recruited. There were two cohorts, patients with a new diagnosis of Crohn’s disease and patients with established disease and clinically suspected of luminal relapse. The second SBUS was performed on the same day as the first SBUS by one of 6 practitioners (5 radiologists and 1 sonographer trained in SBUS) and assessed disease presence, activity and location with more detailed mural and extra-mural observations for each segment based on a case report form which included the practitioner’s confidence of these findings. Findings in the main METRIC trial protocol such as wall thickening, focal hyperechoic mesentery (with or without fat wrap), isolated thickened submucosa, increased doppler vascular pattern, ulceration or abscess were assessed. Statistical analysis identified the percentage agreement between practitioners as well as prevalence adjusted bias adjusted kappa (PABAK) to assess inter-observer variability.

              There was excellent sonographic agreement for small bowel disease presence in both cohorts with an 82% agreement in patients within the new diagnosis cohort and 81% agreement in the relapsed disease cohort, both with substantial agreement upon assessment of kappa coefficient. There was a lower percentage agreement for colonic disease presence in new diagnosis (64%) with fair agreement (κ = 0.27) although there was 78% agreement in the relapsing cohort with moderate agreement (κ = 0.56).  The study also replicated the high levels of sensitivity of SBUS for small bowel disease presence as in the METRIC trial2.

              There were cases where practitioners agreed with one another, but they were both incorrect when compared to MRE which was likely due to the limitations of SBUS. These include difficulty identifying disease due to patient factors, subtle findings or abnormal disease site. SBUS had limitations when assessing small bowel disease extent in both cohorts (64% agreement in new diagnosed patients and 56% in suspected relapse patients).  There were also much lower kappa values suggestive of slight (relapse cohort) and fair (new diagnosis cohort) agreement in segmental localisation which differs to the aforementioned findings by Parente et al.4

              The radiologists participating in this study all had a declared subspecialty interest in gastrointestinal radiology, and the sonographer had undergone formal training and performed SBUS routinely, so these results may not be applicable to general radiologists in a non-specialist setting.

              The study demonstrates that there is substantial agreement between practitioners using SBUS when assessing for the presence of small bowel Crohn’s disease, although assessing the extent of disease had lower inter-observer agreement in keeping with the known difficulties of assessing small bowel with ultrasound. In clinical practice this study supports the use of using a combination of MRE for disease identification and SBUS to assess for ongoing disease presence.

               

              References

              1. Bhatnagar G, Quinn L, Higginson A, Plumb A, Halligan S, Tolan D, et al. Observer agreement for small bowel ultrasound in Crohn’s disease: results from the METRIC trial. Abdom Radiol. 2020
              2. Taylor SA, Mallett S, Bhatnagar G, Baldwin-Cleland R, Bloom S, Gupta A, et al. Diagnostic accuracy of magnetic resonance enterography and small bowel ultrasound for the extent and activity of newly diagnosed and relapsed Crohn’s disease (METRIC): a multicentre trial. Lancet Gastroenterol Hepatol. 2018
              3. Miles A, Bhatnagar G, Halligan S, et al. Magnetic resonance enterography, small bowel ultrasound and colonoscopy to diagnose and stage Crohn’s disease: patient acceptability and perceived burden. Eur Radiol 2019;29:1083-1093
              4. Parente F, Greco S, Molteni M, Anderloni A, Sampietro GM, Danelli PG, et al. Oral contrast enhanced bowel ultrasonography in the assessment of small intestine Crohn’s disease. A prospective comparison with conventional ultrasound, x ray studies, and ileocolonoscopy. Gut. 2004

               

              Rahul Munyal (Radiology ST5 Registrar, Queen’s Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham, England)
              Dr. Rahul Munyal is a fifth and final year radiology resident at Nottingham University Hospitals NHS Trust (UK) and an ESGAR member.  He is a fellow of the RCR (Royal College of Radiologists) and is undertaking subspecialty training in Gastrointestinal and Hepatobiliary imaging with an interest in non-vascular intervention.

              Comments may be sent to Rahul.munyal@remove-this.nhs.net


              Intrahepatic cholangiocarcinoma: pathogenesis, current staging, and radiological findings
              Authors:
              Mohammed Saleh, Mayur Virarkar, Vlad Bura, Raul Valenzuela, Sanaz Javadi, Janio Szklaruk & Priya Bhosale
              Journal: Abdominal Radiology, 2020 May 16
              DOI: 10.1007/s00261-020-02559-7

              Dr. Adriana Mirela Călin-Vainak, ESGAR Social Media Advocate and member of the Education Committee, Affidea Cluj-Napoca/RO
              Dr. Vlad Bura, 4th year radiology resident, University Hospital, Cluj-Napoca/RO

              Cholangiocarcinoma, the second most common primary liver malignancy following hepatocellular carcinoma (HCC), represents approximately 3% of gastrointestinal tumors. It comprises a heterogeneous group of malignancies emerging anywhere between the canals of Hering to the main bile duct: intrahepatic-cholangiocarcinoma (ICC) – from proximal bile ducts to the hepatic duct bifurcation, and extrahepatic-cholangiocarcinoma (ECC) – from the bifurcation to the main bile duct. Although ICC’s comprise only 10-20% of cholangiocarcinomas, its incidence is rising as compared to ECCs, according to World Health Organization databases and other national registries.

              Imaging plays an important role not only for diagnosis and staging of ICC, but also for management and treatment guidance. In this comprehensive article, the authors discuss epidemiology, genetics, pathogenesis, clinical presentation, multimodal imaging features, staging, treatment options and management of ICC.

              The risk factors for ICC are not so well defined as for HCC. However, factors that promote malignant transformation of premalignant conditions (e.g. biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct) have been linked to ICC development: liver flukes, chronic biliary and liver diseases, and lifestyle-related aspects causing chronic inflammation and cholestasis.

              The clinical picture is nonspecific – abdominal pain – leading to its late diagnosis and fatal outcome (5y-survival as low as 10%). Unlike ECC, ICC rarely causes jaundice and is often asymptomatic. More than 50% of ICCs are unresectable by the time of diagnosis. A fortunate situation is that of cirrhotic patients undergoing HCC-screening, when ICCs can be incidentally depicted.

              ICC rarely causes alteration of liver function tests; thus, initial evaluation mostly relies on imaging alone. The use of CA 19-9 tumor marker (>100U/ml) may be a useful addition for the differential diagnosis of ICC, although its sensitivity and specificity vary among the available literature. It is more useful for radical resection assessment and treatment monitoring.

              The role of different imaging modalities in diagnosis, staging and post-treatment follow-up of ICC is largely discussed within the review. As ICC causes nonspecific abdominal symptoms, it may be firstly evaluated by US, but US-features are non-specific. Except for small tumors, CEUS may help differentiate ICC from HCC, mostly based on arterial-phase hyperenhancement pattern (homogeneous for HCC, heterogeneous or peripheral rim for ICC). The most common imaging modality for detection, diagnosis and staging of ICC is CT. Typical behavior of ICC on CT includes: irregular margins, capsular retraction, early rim hyperenhancement (arterial phase) and delayed central enhancement (portal and delayed phases).

              At MRI, the enhancement pattern of ICC most commonly resembles the one seen at CT. However, different enhancement patterns exist, carry different prognoses and are better depicted at MRI. Additionally, DWI target appearance of the tumor has a diagnostic sensitivity and specificity as high as 80% and 99%, respectively. MRI is also very helpful to determine treatment response in unresectable cases (post-radiotherapy/TACE): treatment-responsive tumors have not been showing significant size decrease, but rather continuous ADC increase on serial MRI. Due to higher spatial resolution, CT is the modality used for surgical planning –  resectability is assessed with greater accuracy than at MRI. CT is also preferred for assessing distant metastasis – most commonly peritoneal, pulmonary and osseous. With the advantage of assessing tumors’ metabolic activity, PET-CT can be more accurate than CT for distant metastasis detection (including lymph node metastasis), possibly altering management for up to 25% of ICC patients.

              A separate staging system for ICC was only introduced in 2010 within the 7th edition of the AJCC cancer staging manual, proving to be more prognosis-predictive than the previously used model, extrapolated from HCC patients’ analysis. The 8th edition of AJCC’s manual (2017), also has some additions reflecting prognostic value, briefly and clearly discussed.

              Treatment options closely depend on imaging staging and are briefly reviewed. Post-treatment recurrence, a frequent complication of ICC, is usually evaluated using CT. Recurrent lesions often have the same imaging features as the pre-treatment tumor. When recurrent disease is difficult to discern from post-operative changes on CT, DWI-MRI can help. Post-operative changes exhibit higher ADC values, while low ADC indicates recurrence.

              Diagnosis and management of patients with ICC represent a major challenge in oncology. This review is of valuable importance for abdominal radiologists and trainees, as appropriate imaging diagnosis and staging are crucial for treatment planning and management of ICC patients.

               

              References

              1. Kirstein MM, Vogel A. Epidemiology and Risk Factors of Cholangiocarcinoma [published correction appears in Visc Med. 2017 Jun;33(3):226]. Visc Med. 2016;32(6):395-400. doi:10.1159/000453013
              2. Endo I, Gonen M, Yopp AC, Dalal KM, Zhou Q, Klimstra D, et al. Intrahepatic cholangiocarcinoma: rising frequency, improved survival, and determinants of outcome after resection. Annals of surgery. 2008;248(1):84‐96.
              3. Cravo M. Is CA 19-9 of Any Help in the Management of Cholangiocarcinoma? GE Port J Gastroenterol. 2017;24(3):108-109. doi:10.1159/000457910
              4. Slattery JM, Sahani DV. What is the current state‐of‐the‐art imaging for detection and staging of cholangiocarcinoma? The oncologist. 2006;11(8):913‐22.
              5. Vilgrain V. Staging cholangiocarcinoma by imaging studies. HPB. 2008;10(2):106‐9.
              6. You M‐W, Yun S. Differentiating between hepatocellular carcinoma and intrahepatic cholangiocarcinoma using contrast‐ enhanced MRI features: a systematic review and meta‐analysis. Clinical radiology. 2019;74(5):406. e9‐. e18.
              7. Corvera CU, Blumgart LH, Akhurst T, DeMatteo RP, D’Angelica M, Fong Y, et al. 18F‐fluorodeoxyglucose positron emission tomography influences management decisions in patients with biliary cancer. Journal of the American College of Surgeons. 2008;206(1):57‐65.
              8. Mar WA, Shon AM, Lu Y, Jonathan HY, Berggruen SM, Guzman G, et al. Imaging spectrum of cholangiocarcinoma: role in diagnosis, staging, and posttreatment evaluation. Abdominal Radiology. 2016;41(3):553‐67.

              Dr Vlad Bura is a 4th-year radiology resident at the County Clinical Emergency Hospital in Cluj-Napoca, Romania. His main fields of interest are abdominal and urogenital radiology, and more recently, pediatric radiology. He is an active ESGAR member and has attended Junior ESGAR Summer School in Portugal in 2018. Dr Bura has also been actively involved in clinical imaging research, and he has contributed as a co-author in projects leading to conference presentations, awards and publications. In 2019, he applied and participated in ESOR Visiting Scholarship Programme in Oncologic Imaging; he closely worked with doctors Evis Sala and Tristan Barrett from Addenbrooke's Hospital at Cambridge University, UK, where he recently got a position as a Clinical Research Fellow.

              Comments may be sent to vlad.t.bura@remove-this.gmail.com

               


              Comparison of guidelines for diagnosis of hepatocellular carcinoma using gadoxetic acid–enhanced MRI in transplantation candidates

              Authors: Sun Kyung Jeon, Jeong Min Lee, Ijin Joo, Jeongin Yoo & Jin-young Park.

              Journal: European Radiology. 2020 Apr 25. doi:

              https://doi.org/10.1007/s00330-020-06881-y.

              Domenico Salvatore Gagliano (radiology resident, University of Palermo, Palermo/IT) and Roberto Cannella (radiologist and PhD student, University of Palermo, Palermo/IT).

              Liver cancers occupy the fourth place in the world as cancer-related mortality and the seventh place in terms of incidence according to WHO data [1]. Hepatocellular carcinoma (HCC) represents one of the few cancers that can be diagnosed by imaging without histopathological examination. Currently, four different guidelines – American Association for the Study of Liver Disease (AASLD), which integrated the Liver Imaging Reporting and Data System (LI-RADS) [2]; European Association for the Study of the Liver (EASL) [3]; Asian Pacific Association for the Study of the Liver (APASL) [4]; and Korean Liver Cancer Association-National Cancer Center (KLCA-NCC) [5] – are used worldwide for the diagnosis of HCC. These guidelines have been updated between the years 2017 and 2018. Furthermore, through the Milan criteria, imaging is fundamental in the assessment of patients who can take advantage of the liver transplant, which in practice represents the only definitive therapy (removes HCC and liver disease).

              Recently, Jeon et al. [6] retrospectively compared the diagnostic performances of these four guidelines in patients undergoing gadoxetic acid-enhanced MR imaging within three months of liver transplantation, in the absence of previous treatments for HCC. The reference standard was based on histopathological examination of explanted livers. The pre-transplant MR images of 81 patients were independently examined by three board-certified abdominal radiologists. A total of 154 nodules were assesses, including 116 HCCs, 24 dysplastic nodules, 6 FNH-like nodules, 5 combined hepatocellular-cholangiocarcinomas, and 3 hemangiomas.

              The study results revealed that the per-lesion specificity for the diagnosis of HCC of AASLD/LI-RADS (97.4%) was the highest compared to EASL (92.1%), KLCA-NCC (92.1%) and APASL (78.9%). Particularly, APASL demonstrated significantly lower specificity compared to AASLD/LI-RADS. However, the sensitivity of APASL (75.9%) and KLCA-NCC (65.6%) was significantly higher than EASL (38.8%) and AASLD/LI-RADS (34.5%). KLCA-NCC resulted in significantly greater accuracy than EASL in classifying patients unsuitable for transplantation (68.4% vs. 31.8% respectively). Based on the Milan criteria for patients’ allocation, APASL (80.2%) and KLCA-NCC (75.3%) provided better accuracy than AASLD/LI-RADS (64.2%) and EASL (64.2%);

              These data suggest that KLCA-NCC an APASL guidelines focus more on sensitivity and therefore on early diagnosis of HCC since the most common approach is to treat the tumor with locoregional therapies, while the AASLD/LI-RADS and EASL guidelines prioritize high specificity in order to reduce false positives as much as possible. The difference between these two different approaches is mainly reflected in the washout appearance definition, which in the AASLD/LI-RADS is limited to portal venous phase only when using gadoxetic acid, while KLCA-NCC guidelines also includes the transitional and hepatobiliary phases, thus achieving greater sensitivity. However, the diagnosis of HCC is excluded if there is hyperintensity on T2-weighted imaging, which may suggest cavernous hemangioma.

              The difference in terms of specificity between APASL and KLCA-NCC, on the other hand, is likely due to excluded diagnosis of HCC not only after exclusion of hemangioma, but also in presence of targetoid appearance on diffusion-weighted images or contrast-enhanced sequences, which is an imaging feature of intrahepatic cholangiocarcinoma and other non-HCC hepatic malignancies [5]. The definition of targetoid appearance in KLCA-NCC, shared with the AASLD/LI-RADS, allows to increase the accuracy in the diagnosis of non-HCC malignancies.

              Moreover, it is important to note that APASL is the only guideline that allows the definitive diagnosis of HCC, regardless for nodule size, while other guidelines can diagnose HCC only for nodules greater than 10 mm in diameter [7].

              The combination of high sensitivity and specificity of the KLCA-NCC guideline allows better accuracy in patient allocation for liver transplant and in particular in classifying unsuitable for transplantation (with non-HCC malignancies or HCCs beyond the Milan criteria) compared to European guidelines.

              In conclusion, when using gadoxetic acid-enhanced MR imaging in transplant candidates, the specificity of the AASLD/LI-RADS (97.4%), EASL (92.1%), and KLCA-NCC (92.1%) guidelines was higher than that of APASL (78.9%) and the KLCA-NCC guideline is more accurate in the selection of unsuitable liver transplant candidates.
               

              REFERENCES

              1. International Agency for Research on Cancer, World Health Organization. Cancer today (https://gco.iarc.fr/today/home).
              2. Marrero JA, Kulik LM, Sirlin CB, et al. Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology. 2018;68:723-750. doi:10.1002/hep.29913.
              3. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol. 2018;69:182-236. doi:10.1016/j.jhep.2018.03.019.
              4. Omata M, Cheng AL, Kokudo N, et al. Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update. Hepatol Int. 2017;11:317-370. doi:10.1007/s12072-017-9799-9.
              5. Korean Liver Cancer Association (KLCA), National Cancer Center (NCC), Goyang, Korea. 2018 Korean Liver Cancer Association–National Cancer Center Korea Practice Guidelines for the Management of Hepatocellular Carcinoma. Korean J Radiol. 2019;20:1042-1113. doi.org/10.3348/kjr.2019.0140.
              6. Jeon, S.K., Lee, J.M., Joo, I. et al. Comparison of guidelines for diagnosis of hepatocellular carcinoma using gadoxetic acid–enhanced MRI in transplantation candidates. Eur Radiol. 2020. doi.org/10.1007/s00330-020-06881-y.
              7. Kim TH, Kim SY, Tang A, Lee JM. Comparison of international guidelines for noninvasive diagnosis of hepatocellular carcinoma: 2018 update. Clin Mol Hepatol. 2019;25:245-263. doi:10.3350/cmh.2018.0090.

               

              Dr. Domenico Salvatore Gagliano is a second-year young radiology resident at the University of Palermo (Italy) and an ESGAR member. Dr. Gagliano graduated at the University of Palermo in July 2017 with a thesis on MR imaging with gadoxetic acid. He recently won the Invest in the Youth application with the EPOS titled “Hyperintense liver lesions on hepatobiliary phase MR imaging in different clinical settings” presented during the 2020 European Congress of Radiology online. He is also involved in scientific researches regarding MR imaging of focal liver lesions.

              Comments may be sent to domenicosalvatore.gagliano@remove-this.gmail.com


              Abdominal CT manifestations of adverse events to immunotherapy: a primer for radiologists

              Authors: Ali Pourvaziri1 · Anushri Parakh1 · Pierpaolo Biondetti1 · Dushyant Sahani2 · Avinash Kambadakone1

              Journal: Abdominal Radiology (2020) 45:2624–2636


              Dr Rajiv B. Karia (Consultant GI/HPB and Interventional Radiologist. Chesterfield Royal Hospital & Nottingham University Hospitals, UK)


              Cancer treatment with chemotherapy has been expanded from conventional chemotherapy agents which cause death of rapidly dividing cells to also involve new therapies which target specific molecules or pathways and also more recently immunotherapeutic  agents which rely on the patient’s immune system to act on the neoplastic cells.  As more and more immunotherapies have become approved over last few years these are becoming a mainstream option for variety of advanced malignancies [1]. The adverse effects of these therapies are unique and diverse.  This paper reviewed the radiological findings of the adverse effects and concentrated on the gastrointestinal tract.

              Immunotherapeutic agents are either passive or active.  Passive immunotherapy target cancer cells with specific antibodies (prepared outside the body), and do not stimulate the immune system, but cause destruction of the cells by complement mediated response or elicit antibody dependent cellular cytotoxicity (ADCC). Active immunotherapy however, utilises the immune system (humoral and cellular immunity) to fight the tumour.  Recombined interleukins (IL), cytokines, vaccines (e.g. for prostate cancer), and check point inhibitors (CPI) are all examples of these agents. In addition autologous T-cells can be genetically modified to express T-cell receptors (TCR) that recognise tumour antigen or chimeric antigen receptors (CARs).

              Immune related adverse events (irAE) are wide spectrum of side effects that arise from immunotherapeutic agents. Check point inhibitors prevent immune system inhibition mechanisms, and hence favour development of autoimmune manifestations. Side effects of conventional cytotoxic agents are generally more predictable, and usually directed to specific organs. Adverse effects discussed in this paper were outlined generally and specific to type of agents used.  It is suggested that irAE appear to be dose dependent with anti-CTLA-4 inhibitors but not with anti-PD/PD-1 inhibitors [2, 3].

              The paper illustrates the various presentations of colitis with the use of immunotherapy. Colitis is the most common irAE that often necessitates discontinuation of therapy [4]. There is a mortality rate of approximately 1% and generally occurs 5 to 10 weeks after initiation therapy. Knowing this helps focuses reporting radiologist’s interpretation and direct the report to the most likely aetiology. The paper described the different types and distribution of colitis with good examples together with pointers on how to differentiate with other causes. Interestingly it was described by the authors that CAR T-cell therapy has been implicated in colonic perforations.

              Within the hepatobiliary system, two general patterns have been described; hepatocellular and cholestatic [5, 6]. Immune related hepatitis occur between 6 and 14 weeks after initiation of therapy. Ultrasound demonstrates periportal oedema and gall bladder wall oedema. CT demonstrates hepatomegaly, diffuse parenchymal hypo-attenuation and patchy enhancement together with periportal lymphadenopathy. It was suggested by the authors that MRI maybe needed to differentiate parenchymal changes from metastatic disease.  Following discontinuation of therapy and administration of steroids there is regression of the imaging findings [7-9]. The paper also illustrated these findings using dual energy CT.

              Pancreatitis related to the immunotherapy can manifest similar to “classic” autoimmune pancreatitis with diffuse enlargement of the gland, stranding in the peripancreatic fat and heterogeneous enhancement pattern. Authors gave pointers to help differentiate this from autoimmune pancreatitis. Imaging illustrations in the paper demonstrate patients on nivolumab and ipilimumab, showing diffuse enlargement with loss of pancreatic lobulations, but with later images following treatment with steroids showing an atrophic pancreas.

              The paper also illustrated renal injuries secondary to different immunotherapy together with illustrations of rheumatological and musculoskeletal adverse effects.  Interestingly manifestation of sarcoid like reaction was described in great detail and there was focus on illustrations of how to help differentiate this from progressive disease. These changes have been reported with the use of CPI’s, and involve the abdomen, lungs, skin and lymph nodes. Biopsy may demonstrate non-caseating granulomas [10]. With these changes care must be taken not to over diagnose this benign finding as progressive disease.

              This review paper has clearly outlined the mechanisms of action of these new agents in a systematic and illustrative format, helping the reader to understand the irAR and their radiological findings. The paper points out that the abdomen is a common site for both disease recurrence and manifestation of irAR.Imagining findings can only be interpreted based on appropriate clinical history and within a clinical context; this paper has shown the importance of this in the context of cancer therapies.   It is hence imperative that clinicians who request imaging, communicate accurately which agents the patient is on.

              Abdominal imaging review papers focusing on oncological methodologies, their actions, together with their imaging findings are not very common and hence this is a refresher for all GI radiologist; a worthy read.

               

              References

              1. Wolchok J (2012) How recent advances in immunotherapy are changing the standard of care for patients with metastatic melanoma. Ann Oncol 23:viii15–viii21. https ://doi.org/10.1093/annon c/mds25 8
              2. Ipilimumab: Developmental History, Clinical Considerations, and Future Perspectives - SkinCancer.org. https ://www.skincancer.org/publi catio ns/the-melan oma-lette r/sprin g-2012-vol-30-no-1/ipilm umab. Accessed 26 Apr 2019
              3. Tang YZ, Szabados B, Leung C, Sahdev A (2018) Adverse effects and radiological manifestations of new immunotherapy agents. Br J Radiol 20180164. https ://doi.org/10.1259/bjr.20180164
              4. Horvat TZ, Adel NG, Dang T-O, et al (2015) Immune-Related Adverse Events, Need for Systemic Immunosuppression, and Effects on Survival and Time to Treatment Failure in Patients With Melanoma Treated With Ipilimumab at Memorial Sloan Kettering Cancer Center. J Clin Oncol 33:3193–3198. https ://doi.org/10.1200/JCO.2015.60.8448
              5. Nishino M, Hatabu H, Hodi FS (2018) Imaging of Cancer Immunotherapy: Current Approaches and Future Directions. Radiology 290:9–22. https ://doi.org/10.1148/radio l.20181 81349
              6. Alessandrino F, Tirumani SH, Krajewski KM, et al (2017) Imaging of hepatic toxicity of systemic therapy in a tertiary cancer centre: chemotherapy, haematopoietic stem cell transplantation, molecular targeted therapies, and immune checkpoint inhibitors. Clinical Radiology 72:521–533. https ://doi.org/10.1016/j.crad.2017.04.003
              7.  Min JH, Lee HY, Lim H, et al (2011) Drug-induced interstitial lung disease in tyrosine kinase inhibitor therapy for non-small cell lung cancer: a review on current insight. Cancer Chemother Pharmacol 68:1099–1109. https ://doi.org/10.1007/s00280-011-1737-2
              8. Kim KW, Ramaiya NH, Krajewski KM, et al (2013) Ipilimumab associated hepatitis: imaging and clinicopathologic findings. Invest New Drugs 31:1071–1077. https ://doi.org/10.1007/s10637-013-9939-6
              9. Kwak JJ, Tirumani SH, Van den Abbeele AD, et al (2015) Cancer Immunotherapy: Imaging Assessment of Novel Treatment Response Patterns and Immune-related Adverse Events. RadioGraphics 35:424–437. https ://doi.org/10.1148/rg.35214 0121
              10. Firwana B, Ravilla R, Raval M, et al (2017) Sarcoidosis-like syndrome and lymphadenopathy due to checkpoint inhibitors. J Oncol Pharm Pract 23:620–624. https ://doi.org/10.1177/1078155216 667635

               

              Dr Rajiv Karia is a radiologist from Chesterfield Royal Hospital (Chesterfield, UK), specialising in GI/HPB and interventional radiology. Graduated from University of Nottingham and completed radiology training in Nottingham, having previously worked in surgery. Active ESGAR member since 2012, regularly attending annual meetings and has also completed the ESGAR/ESOR Exchange Programme for Abdominal Radiology Fellowship. Rajiv has a keen interest in technology and advances in medical applications, and is an associate member of the institution of Engineering and Technology (IET).

              Comments may be sent to rajiv.karia@remove-this.doctors.org.uk

               


              Contrast-enhanced ultrasound for the characterization of portal vein thrombosis vs tumor-in-vein in HCC patients: a systematic review and meta-analysis.

              Chen J, Zhu J, Zhang C, Song Y,  Huang P. European Radiology. 2020

              Portal vein thrombosis (PVT) and tumor invasion of portal vein (TIV) are both possible complications of Hepatocellular carcinoma (HCC). The importance of differential diagnosis consists in different therapies that should be made. In fact, HCC patients with TIV are not eligible for resection or liver transplantation, but only for Sorafenib. The second approach negatively affects the median survival rate, that decreases from more than 60 months to less than 11 months in patients with TIV.

              There are many evidences in literature that B-mode and Color Doppler ultrasound are functional for detecting HCC, as well as PVT. According to AASLD 2018 Practice Guideline these procedures are recommended biannually in cirrhosis patients as a screening for HCC. However, the accuracy of US for detecting TIV is not optimal [2-3].

              This paper, published in European Radiology by Chen and coworkers in February 2020, aims to provide based evidence advice about the diagnostic value of Contrast-enhanced ultrasound (CEUS) in differentiating TIV from PVT in HCC patients.

              Authors performed a systematic review and meta- analysis of seven studies (including 425 patients) selected from PubMed, Embase, Cochrane Library, and Web of Science, published up to the 5th of May 2019. The risk of biases within the studies included were evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADS 2) tool. The included studies showed a low risk of bias in patient selection and index test categories but might be at risk in the categories of reference standard and flow and timing.Heterogeneity was calculated by I2 index; publication bias was evaluated by Deek's funnel plot demonstrating a low risk of bias among studies, p=0.54 Diagnostic value of CEUS in differential diagnosis between TIV and PVT was evaluated by the receiver-operating characteristic (ROC) curve analysis and the computed cumulative value of area under the curve (AUC) was 0.97 (95% CI, 0.95-0.98). The pooled sensitivity and specificity of CEUS in diagnosing TIV were 0.94 (95% CI, 0.89-0.97) and 0.99 (95% CI, 0.80-1.0) respectively Combining the results of I2 and sensitivity analysis, the overall heterogeneity was acceptable.
              The Fagan plot demonstrated that CEUS increases the probability of diagnosing TIV from 50 to 99% when positive and lowers the probability of malignancy to as low as 5% when negative.

              This is the first meta-analysis that summarizes CEUS studies for the diagnosis of TIV and PVT in HCC patients, providing the best level of evidence actually available on this topic. 

              According with this paper CEUS demonstrated an excellent diagnostic accuracy. It showed a superior sensitivity and specificity than B mode and Color Doppler ultrasound.

              Moreover, for its excellent safety profile and diagnostic accuracy in distinguishing between TIV and PVT, authors also suggested CEUS as alternative or substitute for CT and/or MRI. However, we believe that in this specific clinical scenario, more studies are still necessary before suggesting CEUS as alternative to CT or MRI, considering that a direct comparison between CEUS and TC or RM in the same patients’ population remains unsettled.

              We should also consider the diagnostic accuracy of CEUS could vary depending on user’s proficiency and experience, and according to the presence of abdominal gas or patients’ body habitus.

              Two limitations of the study should be mentioned: this meta-analysis included a limited number of studies; moreover, the reference standard was not consistent among studies and the time interval between CEUS and the standard reference was unclear.

               

              REFERENCES

              1. Contrast-enhanced ultrasound for the characterization of portal vein thrombosis vs tumor-in-vein in HCC patients: a systematic review and meta-analysis.Chen J, Zhu J, Zhang C, Song Y, Huang P.  European Radiology. 2020
              2. Tarantino L, Francica G, Sordelli I et al (2006) Diagnosis of benign and malignant portal vein thrombosis in cirrhotic patients with hepatocellular carcinoma: color Doppler US, contrast-enhanced US, and fine-needle biopsy. Abdom Imaging 31:537–544
              3. Dodd GD 3rd, Memel DS, Baron RL, Eichner L, Santiguida LA (1995) Portal vein thrombosis in patients with cirrhosis: does sonographic detection of intrathrombus flow allow differentiation of benign and malignant thrombus? AJR Am J Roentgenol 165:573–577

               

              Dr. Elena Orlando is a first-year radiology resident on the “Sapienza, University of Rome” training scheme in Italy. She completed her undergraduate medical degree at “Sapienza, University of Rome” in 2018. She joined the Medical Imaging Department in 2019 where she in undertaking training in diagnostic and interventional radiology. Her main interests are abdominal and vascular diagnostic radiology.

              Comments may be sent to dr.elenaorlando@remove-this.gmail.com


              Clinical features and MRI progression of small duct primary sclerosis cholangitis (PSC)

              Kristina I. Ringe, Annika Bergquist, Henrike Lenzen, Nikolaos Kartalis, Michael P. Manns, Frank Wacker, Arsteidis Grigoriadis.
              European Radiology – May 2020

               

              Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disorder with fibrosis of the intrahepatic and/or extrahepatic bile ducts. Histologically periductal fibro-obliterative “onion skin” concentric fibrosis and bile duct strictures are characteristic of the disease, with cholangiographically identifiable duct changes being the hallmark of PSC. Its course is very variable and in a minority of cases can be benign, however in the majority of cases, PSC is a progressive disease, eventually leading to cirrhosis and potential development of cholangiocarcinoma.

              To this day it is uncertain whether small duct PSC (sdPSC) represents an early stage of large duct PSC, a mild variant of it or a separate disease condition altogether.

              SdPSC is characterized by clinical and histological features of large duct PSC, but with a normal cholangiogram on endoscopic retrograde cholangiopancreatography (ERCP) or magnetic resonance cholangiopancreatography (MRCP). Currently there is no specific disease marker for sdPSC, and histology remains the cornerstone of diagnosis. Histologic features of sdPSC are the same as those of PSC, surrounding the small interlobular and medium-sized bile ducts, along with a reduced number of interlobular bile ducts.

              SdPSC is much less common than large duct PSC and has a favorable disease course, with a lower risk of hepatobiliary malignancy, liver transplantation or death.

              The aim of this study was two-fold, first to evaluate and describe the clinical and MRI progression of patients with sdPSC, and second to evaluate MRI features associated with disease progression to large duct PSC.

              A retrospective dual-center study was carried out from records of 16 patients with a known diagnosis of sdPSC and available MR imaging. Imaging and liver function tests were reviewed in consensus by two radiologists at baseline and follow-up. Due to the retrospective design, the MR protocol was not standardized. In all patients 3D MRCP, 2D MRCP or single shot MRCP sequences were available for dedicated bile duct evaluation. Some patients also had additional imaging in the form of diffusion-weighted sequences (DWI), T2w and T1w pre and post-contrast imaging (liver specific or extracellular). Images were evaluated for bile duct changes, gallbladder findings, parenchymal changes and associated findings such as hilar lymphadenopathy, ascites, varices, portal vein thrombosis and spleen volume.

              Baseline MRI showed the commonest findings, with regards to sdPSC, to be inhomogeneous diffusion-weighted signal and enhancement, altered liver morphology and periportal lymphadenopathy. These changes showed pronounced manifestation at follow-up imaging. Unfortunately, no prognostic MRI marker for prediction of large duct PSC development could be determined at baseline imaging.

              The progression rate in this study was high in comparison to previously published data, with 55.5% of sdPSC patients with available follow up imaging, progressing to large duct PSC, supporting the theory that sdPSC may be an early stage of large duct PSC, not a seperate entity. The largest study to date, which included 83 patients with sdPSC, showed a progression rate to large duct PSC of 22.9% in a median of 7.4 years. Ringe et al. (2020) propose the longer follow up period (median 10.6 years) and the fact that all available MRCPs were reviewed (not just those of symptomatic patients), as a possible reason for this discrepancy.

              The authors highlight a number of limitations within the study, such as the study population being relatively small, the fact that follow-up imaging for sdPSC is not yet standardized and that due to the retrospective aspect of the study, the MRI protocol was very heterogenous.

              The major strength of this study is that it is the first to describe MRI findings beyond cholangiographic changes in patients with sdPSC. The authors strongly suggest that assessment should not only be focused on MRCP images and cholangiographic images, but also on evaluation of parenchymal changes, inhomogeneous enhancement and associated findings (eg: hilar lymphadenopathy).

               

              REFERENCES

              1. J. Ludwig, (1991) Small-duct Primary Sclerosing Cholangitis, Semin. Liver Dis. 11(1):11-7. doi: 10.1055/s-2008-1040417
              2. Small duct primary sclerosis cholangitis without inflammatory bowel disease is genetically different from large duct disease.
              3. E. Bjornsson, r. Olsson, A. Berquist et al (2008) The natural history of small-duct primary sclerosing cholangitis, gastroenterology 134: 975-980
              4. E. Bjornsson, K.M. Boberg, S. Cullen, K. Fleming, O.P. Clusen, O. Fausa, E. Schrumpf, R.W. Chapman (2002) Patients with small duct primary sclerosis cholangitis have a favourable long term prognosis, Gut 51 (5): 731-735. doi: 10.1136/gut.51.5.731

               

               

              Dr. Ruth Gatt is a second-year radiology resident at Mater Dei Hospital, Malta. She completed her undergraduate medical degree at the University of Malta in 2016 and joined the Medical Imaging Department in 2018 where she is undertaking training in diagnostic and interventional radiology.

              Comments may be sent to ruth.d.gatt@remove-this.gov.mt


              Abdominal Imaging Findings in COVID-19: Preliminary Observations

              Authors: Rajesh Bhayana , Avik Som, Matthew D Li, Denston E Carey, Mark A Anderson, Michael A Blake, Onofrio Catalano, Michael S Gee, Peter F Hahn, Mukesh Harisinghani, Aoife Kilcoyne, Susanna I Lee, Amirkasra Mojtahed, Pari V Pandharipande, Theodore T Pierce, David A Rosman, Sanjay Saini, Anthony E Samir, Joseph F Simeone, Debra A Gervais, George Velmahos, Joseph Misdraji, Avinash Kambadakone

              Journal: Radiology, 201908. 11 May. 2020, doi:10.1148/radiol.2020201908
               

              Dr. Damiano Caruso, Young ESGAR, ESGAR Educational Committee, Radiology Department, Sant’Andrea Academic Hospital, Sapienza University of Rome, Rome, Italy.

              Dr. Elena Lucertini, ESGAR Member and radiology resident, Radiology Department, Sant’Andrea Academic Hospital, Sapienza University of Rome, Rome, Italy.

              Prof. Andrea Laghi, ESGAR Vice President and Director of the Radiology Department, Sant’Andrea Academic Hospital, Sapienza University of Rome, Rome, Italy.


              The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rapidly spread all over the world and it was declared pandemic on March 2020 [1, 2].

              Despite most common clinical symptoms are fever, cough, and dyspnea, several cases of COVID-19 patients with gastrointestinal (GI) symptoms such as diarrhea, nausea/vomiting, abdominal pain have been observed [3].

              Angiotensin-converting enzyme 2 (ACE2) receptors, considered the main virus cellular carriers, are highly surface expressed on enterocytes of the small intestine and biliary epithelium, offering a possible explanation of GI manifestations in COVID-19 patients [4, 5].

              A recent retrospective cross-sectional study on the GI manifestations of COVID-19 has been published by Bhayana et al. The Authors have enrolled a total of 412 adult patients consecutively admitted at their institution, from March 27 to April 10, who tested positive for SARS-CoV-2.

              Abdominal symptoms were reported in 34% of these patients (142/412) and imaging findings of 134 patients (33%) were analyzed by a team of expert abdominal radiologists: radiography, US, CT of the abdomen and pelvis and MRI images were included in data collection.

              CT imaging findings includes abnormalities of bowel wall (such as colonic or small bowel thickening, pneumatosis or portal venous gas and perforation), fluid-filled colon, solid organ infarct, pancreatitis and other findings suggestive of hepatitis.

              Otherwise, US imaging findings includes presence of biliary sludge in gallbladder lumen, with or without distension, gallbladder wall thickening, pericholecystic fluid, fatty liver, portal venous gas and portal vein thrombosis.

              Finally, the Authors compared demographic, clinical, and imaging data between intensive care unit (ICU) patients and other inpatients. The aim of this retrospective study is to investigate abdominal imaging findings in COVID-19 patients.

              Statistical analysis revealed on CT scans presence of bowel abnormalities in 31% of patients, including pneumatosis/thickening of bowel wall and portal venous gas; these findings resulted significantly associated with ICU admission (OR 15.5, p=0.01).

               

              Dr. Gisella Guido is a radiology resident at the University of Rome "Sapienza" - Sant'Andrea University Hospital in Rome, attending the second year of residency. Her main field of interest is abdominal and oncologic radiology. She already worked in this area during the residency and considering pursuing her career in oncological radiology.

              Comments may be sent to gisella.guido@remove-this.uniroma1.it

              Direct viral infection sustained by ACE2 surface expression in enterocytes of small intestine and vascular endothelium [5, 6], and small vessel thrombosis or nonocclusive mesenteric ischemia, both probably caused by systemic coagulopathy [7], could explain the spectrum of bowel disease in COVID-19 patients.

              US imaging showed detection of cholestasis in 54% of patients, mainly in critically ill ones.

              Nevertheless, ICU patients with COVID-19 are often hypercoagulable [8], the authors did not identify portal vein thrombosis with US, as reported in other studies [9].

              The retrospective single center nature of the study represents the major limitation because of the introduction of selection bias. Furthermore, the lack of pathologic correlation and clinical follow-up for many patients with imaging abnormalities is another weak point of the study.

              In conclusion, this study, despite the limits demonstrated, showed that abdominal symptoms should not be underestimate and radiologist should be aware of abdominal imaging findings, such as bowel abnormalities and cholestasis, in patients with COVID-19.

               

              REFERENCES

              [1] Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395(10223):497-506. doi: 10.1016/s0140-6736(20)30183-5

              [2] Cholankeril G, Podboy A, Aivaliotis VI, et al. High Prevalence of Concurrent Gastrointestinal Manifestations in Patients with SARS-CoV-2: Early Experience from California. Gastroenterology.2020;http://dx.doi.org/10.1053/j.gastro.2020.04.008.

              [3] Cheung KS, Hung IF, Chan PP, et al. Gastrointestinal Manifestations of SARS-CoV-2 Infection and Virus Load in Fecal Samples from the Hong Kong Cohort and Systematic Review and Meta-analysis. Gastroenterology. 2020;http://dx.doi.org/10.1053/j.gastro.2020.03.065

              [4] Zou X, Chen K, Zou J, Han P, Hao J, Han Z. Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front Med. 2020;http://dx.doi.org/10.1007/s11684-020-0754-0.

              [5] Xiao F, Tang M, Zheng X, Liu Y, Li X, Shan H. Evidence for Gastrointestinal Infection of SARS-CoV2. Gastroenterology. 2020;http://dx.doi.org/10.1053/j.gastro.2020.02.055.

              [6] Hamming I, Timens W, Bulthuis MLC, Lely AT, Navis GJ, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004;203(2):631–637.

              [7] Varga Z, Flammer AJ, Steiger P, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020;https://linkinghub.elsevier.com/retrieve/pii/S0140673620309375.

              [8] Spiezia L, Boscolo A, Poletto F, et al. COVID-19-Related Severe Hypercoagulability in Patients Admitted to Intensive Care Unit for Acute Respiratory Failure. Thromb Haemost. 2020;http://dx.doi.org/10.1055/s-0040-1710018

              [9] Franco-Moreno A, Piniella-Ruiz E, Montoya-Adarraga J, et al. Portal vein thrombosis in a patient with COVID-19 [published online ahead of print, 2020 Jun 13]. Thromb Res. 2020;doi:10.1016/j.thromres.2020.06.019

               

              Dr. Tiziano Polidori is a radiology resident at the University of Rome "Sapienza" - Sant'Andrea University Hospital in Rome, attending the second year of residency. His main fields of interest are clinical radiology and research. He has numerous ongoing projects and aspires to take part in further research studies in the near future.

              Comments may be sent to tiziano.polidori@remove-this.uniroma1.it


              MRI of the liver: choosing the right contrast agent

              Authors:  Welle C.L., Guglielmo F.F., Venkatesh S.K.

              Journal:   Abdom Radiol (NY), 2020 February, 45:384–392
              doi 10.1007/s00261-019-02162-5

              Liver MRI is the modality of choice due to its excellent contrast resolution. Correct imaging protocol is crucial for obtaining a correct final diagnosis. Radiologist performing liver MRI should be familiar with types of contrast agents available, diagnostic data they provide as well as their contraindications. Failing to do so can cause diagnosis delay, unnecessary additional imaging and interventional procedures increasing healthcare costs and patient’s morbidity.

              In this review article, the authors present contrast agents currently available for liver imaging in United States. They discuss advantages and disadvantages and speculate about product choice in controversial clinical scenarios.

              Majority contrast agents used in liver MRI are gadolinium-containing agents. They differ in terms of relaxativity characteristics, protein binding and biodistribution.    There are extracellular contrast agents (ECA) and hepatobiliary agents (HBA). Intravascular agents are not considered in this review (1).

              ECAs are extracellular compounds which circulate in blood flow and accumulate in areas with increased extracellular space. Based on their molecular composition, ECAs can be either macrocyclic or linear.

              HBA agents are actively taken by hepatocytes. They get excreted into the bile, allowing for additional evaluation of hepatic parenchyma and biliary system. Gd-EOB-DTPA (Eovist/Primovist®) is primary HBA compound used for hepatobiliary applications. Gd-BOPTA (MultiHance®) is another product which can also be applied as ECA due to its strong relaxativity. Its HBA properties are inferior to Gd-EOB-DTPA because it has 5% of biliary excretion versus 50% for Gd-EOB-DTPA what accounts for a prolonged hepatobiliary phase which occurs around 1-3 hours after injection (2).

              When comparing different types of agents, ECAs offer better evaluation during the arterial phase than HBAs. This is due to less frequent respiratory motion artefacts and higher Gd concentration. ECAs are also excellent for lesion wash-out. Gd-EOB-DTPA uptake by hepatocytes lowers its concentration in extracellular space. Gd-BOPTA, however, has later cellular uptake compared to Gd-EOB-DTPA and can compete with ECA agents in wash-out properties. Biological and relaxativity characteristics of ECAs provide better evaluation of extrahepatic organs and shorten examination time (3).

              HBA advantages are their liver-specific biology and subsequent biliary excretion. It is especially useful for liver lesions differentiation as well as for evaluation of biliary ducts diseases.

              What contrast agent is right for liver MRI? Different factors will contribute to this decision. If the purpose of examination is to evaluate a lesion detected by another modality, ECA agents are commonly recommended. Optimal arterial, portal venous, and equilibrium phases help in characterization of common lesions like hemangiomas. ECAs are also superior for evaluation and follow-up malignances in extrahepatic organs

              Patients with severe hepatic iron deposition/steatosis, poor hepatic function or elevated blood bilirubin level are often suboptimally evaluated with HBAs due to decreased enhancement of liver parenchyma. In such cases, ECAs are also preferred (4).

              HBAs are agents of choice for differentiating lesions originating from hepatocytes: FNH vs hepatic adenoma. Other indications for HBAs include detection of liver metastasis in surgical candidates; evaluation of bile ducts abnormalities; anatomical biliary mapping and evaluation of hepatic function (5).

              Authors emphasize awareness about genetic variations in Gd-EOB-DTPA uptake. Polymorphisms of liver human anion transporting polypeptide (OATP) 1B1 and OATP1B3 are signal confounders in Gd-EOB-DTPA enhanced liver imaging responsible up to 40% of signal reduction. Several drugs can also compete with Gd-EOB-DTPA uptake.

              Sometimes, it is difficult to decide between ECA and HBA. HCC is one of such examples. While ECAs offer better arterial phase, enhancement and wash-out characteristics; HBAs help in detection of small lesions and differentiation between perfusion abnormalities and true lesions. Similarly, small recurrences at the periphery of a treated lesion with ablation are easy to detect with ECA. However, due to unspecific hyperenhancement it the same area, HBA can be more useful sometimes.

              Last, it is important to bear in mind differences in international regulations concerning use of contrast agents for MRI. Thus, in Europe restrictions regarding linear agents apply (6). Primovist® and Multihance® are allowed for liver MRI while others like Omiscan®, Magnevist® and OptiMARK® are suspended by European Medicines Agency.

              Finally, authors conclude that both ECAs and HBAs offer unique advantages for liver evaluation. Information about examination’s purpose, patient’s history and knowledge about agent’s benefits and drawbacks and local regulations will define the choice of contrast media for specific clinical situation.

               

              REFERENCES

              1. Hadizadeh DR, Gieseke J, Lohmaier SH, Wilhelm K, Boschewitz J, Verrel F, Schild HH, Willinek WA (2008) Peripheral MR angiography with blood pool contrast agent: prospective intraindividual comparative study of high-spatial-resolution steady-state MR angiography versus standard-resolution first-pass MR angiography and DSA. Radiology 249 (2):701-711.
              2. Hope TA, Fowler KJ, Sirlin CB, Costa EA, Yee J, Yeh BM,  Heiken JP (2015) Hepatobiliary agents and their role in LI-RADS. Abdom Imaging 40 (3):613-625.
              3. Van Beers BE, Pastor CM, Hussain HK (2012) Primovist, Eovist: what to expect?  J Hepatol 57 (2):421-429.
              4. Ding Y, Rao SX, Zhu T, Chen CZ, Li RC, Zeng MS (2015) Liver fibrosis staging using T1 mapping on gadoxetic acid-enhanced MRI compared with DW imaging. Clin Radiol 70 (10):1096-1103.
              5. Ding Y, Rao SX, Zhu T, Chen CZ, Li RC, Zeng MS (2015) Liver fibrosis staging using T1 mapping on gadoxetic acid-enhanced MRI compared with DW imaging. Clin Radiol 70 (10):1096-1103.
              6. https://www.ema.europa.eu/en/medicines/human/referrals/gadolinium-containing-contrast-agents.



              Viktoria Pozdniakova is a fourth-year radiology resident at Diakonhjemmet Hospital in Oslo. She started her residency in Norway after completing undergraduate medical studies in Saint-Petersburg Medical University in Russia in 2009. Viktoria has a broad range of interests in diagnostic imaging and several visiting internships from the Medical University of Graz and Vienna, the Technical University of Zürich, and the harite Klinikk in Berlin. She also did an ESOR visiting scholarship at La Fe University Hospital in Valencia. Viktoria is passionate about liver imaging and considering pursuing her career in abdominal radiology.

              Comments may be sent to: v.a.pozdnyakova@remove-this.gmail.com


              Gastrointestinal Manifestations of SARS-CoV-2 Infection and Virus Load in Fecal Samples from the Hong Kong Cohort and Systematic Review and Meta-analysis.

              Authors: Cheung KS, Hung IF, Chan PP, Lung KC, Tso E, Liu R, Ng YY, Chu MY, Chung TW, Tam AR, Yip CC, Leung KH, Yim-Fong Fung A, Zhang RR, Lin Y, Cheng HM, Zhang AJ, To KK, Chan KH, Yuen KY, Leung WK.

              Journal: Gastroenterology. 2020 Apr 3. doi: 10.1053/j.gastro.2020.03.065.

              Roberto Cannella (radiologist and PhD student, University of Palermo, Palermo/IT) and Federica Vernuccio (radiologist and PhD student, University of Palermo, Palermo/IT)

              The current pandemic of SARS-CoV-2 (also known as COVID-19) is having a tremendous impact on global human health. The high viral infectivity and the lack of prior immunization results in more than 1770000 confirmed cases and 110000 deaths reported by the World Health Organization up to April 13th 2020 [1]. The most common presentation of COVID-19 includes fever and respiratory symptoms (i.e. cough, shortness of breath and dyspnea), but it may also cause a life-threatening acute respiratory syndrome in most severe cases. Extra-pulmonary symptoms may also be present during the infection. Particularly, gastrointestinal symptoms have been commonly described in COVID-19 patients. Gastrointestinal manifestations have been reported with different frequencies and may include diarrhea, nausea and vomiting, elevated liver function tests, abdominal pain and discomfort [2].

              A recent systematic review and meta-analysis on the gastrointestinal manifestations of COVID-19 has been published by Cheung et al. [3]. The Authors have analyzed the prevalence of gastrointestinal symptoms and detection of virus in stool in a local cohort of 59 confirmed COVID-19 patients in Hong Kong and reviewed the data from 60 published studies including 4243 patients.

              In their local COVID-19 cohort gastrointestinal symptoms have been recorded in 25% of patients, most commonly including diarrhea (22.0%), abdominal pain/discomfort (11.9%), and vomiting (1.7%). Interestingly, 53% of COVID-19 patients with gastrointestinal manifestation did not have cough or dyspnea, while fever was constantly present. Presence of virus RNA in stool was reported in 15% of patients on the day of hospitalization with a significantly higher frequency in patient with diarrhea. However, 9.1% of patients had positive stool RNA even without gastrointestinal symptoms. 

              Their meta-analysis of 4243 COVID-19 patients revealed a pooled prevalence of gastrointestinal symptoms of 17.6%, with a significant heterogeneity among the included studies. Most common manifestations included anorexia (26.8%), diarrhea (12.5%), nausea and vomiting (10.2%), and abdominal pain or discomfort (9.2%). Heterogeneity of the reported symptoms was more prominent in studies originating from China than other countries. The Authors detailed that 11 studies compared the prevalence of gastrointestinal symptoms with the severity of COVID-19, with a resulted pooled prevalence of 17.1% and 11.1% in patients with severe and mild COVID-19 disease, respectively. Furthermore, the pooled prevalence of gastrointestinal symptoms was evaluated in adults, pediatrics and pregnant women and was reported to be 16.7%, 24.8%, and 20.0%, respectively. Detection of viral RNA in stool was reported in 12 studies, with a pooled prevalence of stool positive samples of 48.1%. Interestingly, the Authors also describes that in 9 studies with serial RNA tests, 70.3% patients had had persistent positive stool viral RNA despite negative respiratory samples. Therefore, persistence viral RNA in stool was longer than respiratory specimens.

              This meta-analysis provides important information regarding the prevalence of gastrointestinal manifestations in COVID-19 patients. Even if gastrointestinal symptoms are not the major cause of morbidity and mortality during COVID-19 infection, they should be promptly recognized also by abdominal radiologists as patients may be referred to imaging evaluation for abdominal symptoms. Importantly, gastrointestinal manifestations may be the only initial symptoms in some COVID-19 patients, presenting even without respiratory symptoms or fever in a minority of patients. Moreover, gastrointestinal symptoms are associated with more severe COVID-19 disease.

              Regarding other possible abdominal manifestations of COVID-19, some studies have also reported that COVID-19 may be associated with elevated liver enzymes [4]. Particularly, patients with more severe COVID-19 disease seem to have higher frequency of liver injury [5]. This may manifest with abnormal ALT/AST levels accompanied by slightly elevated bilirubin levels [6].

              Notably, despite evidences are accumulating on the gastrointestinal and liver clinical manifestations of COVID-19, there is still a lack in knowledge regarding the possible abdominal imaging findings in COVID-19 patients. Further studies are needed to evaluate the possible presence of radiological abdominal manifestations of COIVD-19 infection.

              In conclusion, this meta-analysis [3] reports that gastrointestinal symptoms were present in 17.6% of patients diagnosed with COVID-19, and may be the only initial manifestations of the infection in some cases. Their knowledge may be helpful in radiologists clinical practice to suggest the correct diagnosis.

               

              REFERENCES

              1. World Health Organization. Coronavirus disease (COVID-2019) situation reports. Available at www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports/.
              2. Li LY, Wu W, Chen S, Gu JW, Li XL, Song HJ, Du F, Wang G, Zhong CQ, Wang XY, Chen Y, Shah R, Yang HM, Cai Q. Digestive system involvement of novel coronavirus infection: prevention and control infection from a gastroenterology perspective. J Dig Dis. 2020 Apr 8. doi: 10.1111/1751-2980.12862.
              3. Cheung KS, Hung IF, Chan PP, Lung KC, Tso E, Liu R, Ng YY, Chu MY, Chung TW, Tam AR, Yip CC, Leung KH, Yim-Fong Fung A, Zhang RR, Lin Y, Cheng HM, Zhang AJ, To KK, Chan KH, Yuen KY, Leung WK. Gastrointestinal Manifestations of SARS-CoV-2 Infection and Virus Load in Fecal Samples from the Hong Kong Cohort and Systematic Review and Meta-analysis. Gastroenterology. 2020 Apr 3. pii: S0016-5085(20)30448-0. doi: 10.1053/j.gastro.2020.03.065.
              4. Zhang Y, Zheng L, Liu L, Zhao M, Xiao J, Zhao Q. Liver impairment in COVID-19 patients: a retrospective analysis of 115 cases from a single center in Wuhan city, China. Liver Int. 2020 Apr 2. doi: 10.1111/liv.14455.
              5. Zhang C, Shi L, Wang FS. Liver injury in COVID-19: management and challenges. Lancet Gastroenterol Hepatol. 2020 Mar 4. pii: S2468-1253(20)30057-1. doi: 10.1016/S2468-1253(20)30057-1.
              6. Xu L, Liu J, Lu M, Yang D, Zheng X. Liver injury during highly pathogenic human coronavirus infections. Liver Int. 2020 Mar 14. doi: 10.1111/liv.14435.

               

              Dr. Roberto Cannella is a young radiologist, a PhD student in Molecular and Clinical Medicine at the University of Palermo (Italy) and an active ESGAR member regularly attending the annual meetings. During his radiology residency, Dr. Cannella spent 17 months as research scholar at the Abdominal Imaging Division of the University of Pittsburgh Medical Center (UPMC) in Pittsburgh (Pennsylvania, USA). He has been involved in several research studies centered on hepatobiliary topics, and specifically on CT and MR imaging of focal liver lesions.

              Comments may be sent to: rob.cannella89@remove-this.gmail.com


              Complementary role of computed tomography texture analysis for differentiation of pancreatic ductal adenocarcinoma from pancreatic neuroendocrine tumors in the portal‐venous enhancement phase 

              Christian Philipp Reinert, Karolin Baumgartner, Tobias Hepp, Michael Bitzer, Marius Horger 

              Abdominal Radiology (2020) 45:750–758 doi.org/10.1007/s00261-020-02406-9&nbsp;

              Pancreatic ductal adenocarcinoma (PDAC) and pancreatic neuroendocrine tumors (PNEN) are the two most frequently encountered pancreatic solid lesions. Approximately 60–70% of PNEN typically appear as well-defined hypervascular solid lesions in the arterial phase, which can be easily differentiated from PDAC when performing multiphasic imaging. However, PNEN can show various atypical features, including hypovascular enhancement, ill-defined margins, dilatation of pancreatic and/or biliary duct, and encasement of peripheral vessels: in this cases, the differential diagnosis with PDAC can be difficult (1). 

              Many patients with pancreatic lesions, however, undergo first portal-venous CT for the elucidation of the cause of cholestasis (e.g., in case of a pancreatic head mass) and of other non-specific symptoms, or the tumors are detected incidentally. Furthermore, as a progression towards malignancy is associated with derangement in vessel architecture and function, larger PNEN have a less homogenous hypervascular pattern and may show delayed contrast enhancement. Hence, pancreatic neuroendocrine tumors can be misdiagnosed as pancreatic ductal adenocarcinoma (PDAC)(2).

              Therefore the aim of this study was to explore the application value of computed tomography (CT) texture analysis in differentiating pancreatic neuroendocrine tumors (PNEN) from pancreatic ductal adenocarcinomas (PDAC) in the portal-venous phase. 

              Texture analysis is an emerging and noninvasive method of assessing organizational characteristics, which can provide objectively quantified parameters for differential diagnosis independent of subjective analysis (3). Texture analysis can extract much more data from medical images than the naked eye by means of quantitatively analyzing greyscale distribution features, inter-pixel relations, and spatial features of images. Texture features might detect distinct quantifiable phenotypic differences of tissues which cannot be assessed through a qualitative, visual evaluation of radiological images alone. Based on these texture features, it is possible to differentiate between different tissues (4). 

              The study retrospectively analyzed the CT scans in the portal-venous phase (60–70 s delay) of 95 patients, 53 affected by PDAC and 42 by PNEN. Volumes of interests (VOIs) were drawn freehand by a senior radiologist with 25 years of experience in abdominal and oncologic imaging, including only the tumor tissue excluding adjacent structures. Using a commercially available software, 92 textural features were extracted including 1st, 2nd, and higher-order features, and then compared between PNEN and PDAC. Finally, radiomics analysis was used to differentiate between grades for PNEN (G2 + G3 vs G1) and PDAC (G1 vs G2 vs G3).

              Compared with PNEN, PDAC had statistically lower “median”, “maximum”, “90th percentile” and “10th percentile” (p=0.0003, p=0.04, p=0.001, p=0.001, respectively). The other first-order features “energy”, “total energy” and “minimum” (p=0.00002) were significantly higher in PNEN compared to PDAC (p=0.02, p=0.0001, p=0.00002, respectively). There was no statistical significance (p >.05) for entropy between these two tumors. The 2nd order feature GLCM Imc2 was significantly higher in PDAC than in PNEN (p=0.0002). In PNEN, the higher-order feature GLSZM Small Area High Gray-Level Emphasis proved significantly higher in patients with G1 compared to patients with G2/G3 tumors (p < 05). No significant differences were found in radiomics features between different gradings of PDAC. In PNEN, the higher-order feature GLSZM Small Area High Gray-Level Emphasis was significantly higher in patients with G1 tumors compared to patients with G2/G3 tumors (p< 05). In PDAC, no significant differences were observed in textural features between patients with G1 and G2/G3 tumors. The tumor/parenchyma ratios, as well as the visual assessment into hypo-/iso-/yperdense or homogeneous/heterogeneous, did not significantly differ between PDAC and PNEN.

              In conclusion, this study shows that CT-textural features quantified on portal-venous CT-image data are capable of differentiating between PDAC and PNEN, and also between G1 and G2/3 PNEN. These results may have important clinical implications as they may lead to a more individualized approach and affect clinical or surgical decisions.


              REFERENCES:

              [1] He M, Liu Z, Lin Y, Wan J, Li J, Xu K, et al. Differentiation of atypical non-functional pancreatic neuroendocrine tumor and pancreatic ductal adenocarcinoma using CT based radiomics. Eur J Radiol. 2019;117:102-11.

              [2] Saif MW. Pancreatic neoplasm in 2011: an update. JOP. 2011;12:316-21.

              [3] Incoronato M, Aiello M, Infante T, Cavaliere C, Grimaldi AM, Mirabelli P, et al. Radiogenomic Analysis of Oncological Data: A Technical Survey. Int J Mol Sci. 2017;18.

              [4] Ganeshan B, Miles KA. Quantifying tumour heterogeneity with CT. Cancer Imaging. 2013;13:140-9.

               

              Dr. Lorenzo Costa is a third-year radiology resident at University Hospital of Verona. He completed his undergraduate medical degree at the University of Bologna in 2015. He joined the Medical Imaging Department of Verona in 2017 where he is undertaking training in diagnostic and interventional radiology.
              Comments may be sent to lorenzo.costa5@remove-this.icloud.com


              Hepatic hemangioendothelioma: CT, MR, and FDG-PET-CT in 67 patients—a bi-institutional comprehensive cancer center review

              Dhakshinamoorthy Ganeshan, Perry J. Pickhardt, Ajaykumar C. Morani, Sanaz Javadi, Meghan G. Lubner, Mohab M. Elmohr, Cihan Duran & Khaled M. Elsayes
              European Radiology – January 2020   doi.org/10.1007/s00330-019-06637-3


              Hepatic epithelioid haemangioendothelioma (HEH) is a rare malignant mesenchymal tumour of the liver. Its aetiology is unclear, however a number of risk factors have been implicated including liver trauma, hepatitis, asbestos and vinyl chloride exposure, OCP use and alcohol. It usually arises in the 3rd to 4th decade of life, with a reported female predilection. Diagnosis of these tumours is challenging in view of the non-specific nature of their presentation and the absence of significant serological abnormalities. They are in fact often misdiagnosed. Prior to this study, there were only a few small case series describing the cross-sectional imaging features of HEH.

              One of the described imaging features of HEH is the target appearance, which reflects the histology of the lesion composed of a central core of dense fibrosis surrounded by a concentric layer of proliferating tumour cells, which is in turn often enclosed by a peripheral avascular rim. On T2 weighted MRI, HEH demonstrates a central area of high-signal intensity surrounded by a layer of low signal intensity and a mildly hyperintense outer layer. A similar target appearance is seen on DWI. On hepatobiliary-phase imaging, a central core is non-enhancing and surrounded by a layer of relatively higher signal intensity due to entrapment of contrast within fibrous stroma with a peripheral hypointense halo corresponding to the presence of tumour cells. The lollipop sign has also been described, and refers to the appearance of hepatic and portal veins tapering towards and terminating at or just within the edge of these lesions. Capsular retraction is another associated feature of HEH.

              The aim of this study was to evaluate a larger cohort of patients in order to create a more validated description of the potentially specific imaging features for this tumour.

              A retrospective review was carried out from records of patients with pathologically proven HHE in two major cancer institutions in the United States from 2008 to 2016. A cohort of 67 patients with a mean age of 47 years and F:M ratio of 2:1 was studied. Contrast enhanced CT examinations were available in 67 cases. Dynamic contrast-enhanced MRI was available in 30 patients, of whom hepatobiliary contrast was used in 8 patients. Diffusion-weighted MRI was available in 18 cases and FDG PET-CT in 13 patients. Imaging was retrospectively reviewed by 3 abdominal radiologists. Note was made of the number, size and location off tumours and the presence of previously reported imaging features described above.

              Multifocal HHE was seen in 88% of patients and 96% demonstrated a peripheral subcapsular location. Capsular retraction was noted in 81%. These findings were similar to other studies. Tumour coalescence was seen in 61% of cases, a higher incidence when compared to other studies, possibly due to the fact that there was a higher incidence of multifocal tumours in this cohort. Peripheral ring arterial phase enhancement was present in 33% of CT cases and the targetoid appearance on portovenous phase imaging was seen in 69% of patients. MRI demonstrated heterogenous high T2 signal intensity in 97% of the cases, with the target sign being present in 67% - a higher incidence than in another study; however the latter considered only 10 patients. Diffusion restriction was seen in 61% of the patients who had DWI included which tallies with other studies. Of the 7 patients who had hepatobiliary phase MR imaging performed, the targetoid appearance was seen in 57% of cases. The lollipop sign was demonstrated in 30% of patients (other studies reported this finding in 4 - 54% of cases) and increased FDG uptake in 62% (reported as 67% in a smaller cohort study).

              The authors highlight a number of limitations of this study, including this being a retrospective review associated with selection bias, as well as variation in imaging protocols used during the years of the study.

              Whilst the above mentioned imaging features are not pathognomonic for HEH, as metastases and cholangiocarcinoma may also demonstrate similar findings, this study serves to validate how the described imaging features should raise the possibility of HEH, aiding in more accurate radiological diagnosis.

               

              REFERENCES:

              1. Kehagias DT, Moulopoulos LA, Antoniou A, Psychogios V, Vourtsi A, Vlahos LJ. Hepatic epithelioid hemangioendothelioma: MR imaging findings. Hepatogastroenterology 2000; 47:1711 –1713
              2. Lyburn ID, Torreggiani WC, Harris AC, et al. Hepatic epithelioid hemangioendothelioma: sonography, CT and MR imaging appearances. Am J Roentgenol 2003;180:1359–1364.
              3. Bartolozzi C, Cioni D, Donati F, et al. Focal liver lesions: MR imaging pathologic correlation. Eur Radiol 2001;11:1374–1388.

               

              Dr. Stephanie Vella is a second-year radiology resident at Mater Dei Hospital, Malta. She completed her undergraduate medical degree at the University of Malta in 2015 and joined the Medical Imaging Department in 2018 where she is undertaking training in diagnostic and interventional radiology.
              Comments may be sent to svel0053@remove-this.gmail.com

               


              CT and MR perfusion techniques to assess diffuse liver disease

              Authors: Ronot M, Leporq B, Van Beers BE, Vilgrain V.
              Journal: Abdom Radiol (NY). Published online 25 Nov 2019. https://doi.org/10.1007/s00261-019-02338-z

              Perfusion imaging provides quantitative information about tissue microcirculation and relies on monitoring the variation of the injected contrast medium over time with the acquisition of signal intensity/time curves. Perfusion imaging in the liver permits the quantitative extraction of physiological perfusion parameters of liver microcirculation at levels far below the spatial resolution of conventional CT and MR imaging. It enables not only malignant liver tumours assessment but also the evaluation of chronic liver diseases. Liver perfusion imaging is challenging and demanding due to the dual blood supply of the liver, the fenestration of its sinusoidal capillaries and its movement during respiration.

              In this comprehensive review article, the authors describe the pathophysiology of hepatic architecture and function changes in chronic liver diseases and the characteristics of liver CT and MR perfusion imaging for chronic liver disease assessment. In addition, they analyze difficulties of liver perfusion imaging and provide useful suggestions for reliable perfusion imaging analysis.  

              In a normal liver, portal perfusion varies over time depending on the splanchnic venous flow and respiratory movements. When portal perfusion decreases, arterial blood supply increases (1). In patients with chronic liver disease, chronic liver injuries lead to progressive deposition of extravascular fibrous tissue that causes capillarization of the sinusoids, intrahepatic vascular resistance increase and eventually portal venous perfusion decrease (2). This decrease is only partially compensated by an increase in arterial blood supply resulting in global liver perfusion decrease.

              High spatial and temporal resolution and whole liver imaging are the most important requirements that should be fulfilled in order to perform reliable liver perfusion analysis with CT and MR (3).

              The main advantages of CT perfusion imaging are low cost, high spatial and temporal resolution and accurate measurement of tracer concentrations. To obtain reliable CT perfusion imaging analysis, the quality of injection and the reduction of respiratory artefacts are of utmost importance. The authors suggest contrast agent injection (350mg of iodine/mL) at a rate of 4 mL/s and slow and superficial breathing.

              The most common technique used for MR perfusion imaging is dynamic contrast-enhanced imaging (DCE imaging). In order to achieve high temporal resolution and to reduce motion sensitivity, partial k-space updating methods are used combined with partial Fourier and parallel imaging. To avoid signal enhancement saturation at high concentrations, low contrast agent concentrations (0.025 mmol/kg) and/or lower injection rates are recommended. The intravoxel incoherent motion (IVIM) model of diffusion-weighted MR imaging can also be used to calculate microperfusion without contrast injection.

              Analysis of hepatic perfusion is performed with a semi-quantitative and a quantitative mathematical approach. The first is based on the analysis of the shape of the signal intensity/time curves and the latter on various pharmacokinetic models, that allow calculation of various parameters such as perfusion and extraction fraction.

              Temporal noise caused by respiratory motion is the main difficulty of liver perfusion imaging. The use of coronal views, registration-based motion correction methods and motion insensitive pulse sequences such as golden-angle radial sparse parallel (GRASP) can help overcome this problem (4).

              Perfusion imaging in the liver is usually performed with extracellular contrast agents, which enable discrimination of patients with various stages of liver fibrosis (5) since perfusion alteration is correlated with the severity of portal hypertension and the degree of liver dysfunction (6). Recently, hepatobiliary contrast agents have been introduced, allowing quantification of both liver perfusion and hepatocyte transport function (7). In chronic liver disease, liver signal intensity decrease is observed during the hepatobiliary phase, and pharmacokinetic rate constants decrease during dynamic MR (8). It has been shown that changes in the hepatocyte transfer rates are earlier markers of liver fibrosis than perfusion parameters (9). Finally, the IVIM model of diffusion MR is another technique that enables liver perfusion evaluation. In patients with liver cirrhosis, an ADC decrease is observed compared with controls due to changes in microperfusion (10).

              Overall, the authors provide an important review and enhance the latest knowledge on perfusion imaging of the liver, highlighting its complementary role in assessing the severity of cirrhosis and portal hypertension. The authors also suggest that MR perfusion with the use of hepatobiliary contrast agents is very promising since it can help in recognition of earlier stages of chronic liver disease.

              References

              1. Itai Y, Matsui O (1997) Blood flow and liver imaging. Radiology 202 (2):306-314. https ://doi.org/10.1148/radio logy.202.2.9015047

              2. Friedman SL (2003) Liver fibrosis – from bench to bedside. J Hepatol 38 Suppl 1:S38-53

              3. Pandharipande PV, Krinsky GA, Rusinek H, Lee VS (2005) Perfusion imaging of the liver: current challenges and future goals. Radiology 234 (3):661-673. doi.org/10.1148/radio l.2343031362

              4. Weiss J, Ruff C, Grosse U, Grozinger G, Horger M, Nikolaou K, Gatidis S (2019) Assessment of Hepatic Perfusion Using GRASP MRI: Bringing Liver MRI on a New Level. Invest Radiol. https ://doi.org/10.1097/rli.00000 00000 00058 6

              5. Ronot M, Asselah T, Paradis V,Michoux N, Dorvillius M, Baron G, Marcellin P, Van Beers BE, Vilgrain V (2010) Liver fibrosis inchronic hepatitis C virus infection: differentiating minimal from intermediate fibrosis with perfusion CT. Radiology 256 (1):135- 142. https ://doi.org/10.1148/radio l.10091 295

              6. Annet L, Materne R, Danse E, Jamart J, Horsmans Y, Van Beers BE (2003) Hepatic flow parameters measured with MR imagingand Doppler US: correlations with degree of cirrhosis and portal hypertension. Radiology 229 (2):409-414. https ://doi.org/10.1148/radio l.22920 21128

              7. Van Beers BE, Garteiser P, Leporq B, Rautou PE, Valla D (2017) Quantitative Imaging in Diffuse Liver Diseases. Semin Liver Dis 37 (3):243-258. doi.org/10.1055/s-0037-16036 51

              8. Lagadec M, Doblas S, Giraudeau C, Ronot M, Lambert SA, FasseuM, Paradis V, Moreau R, Pastor CM, Vilgrain V, Daire JL, Van Beers BE (2015) Advanced fibrosis: Correlation betweenpharmacokinetic parameters at dynamic gadoxetate-enhanced MR imaging and hepatocyte organic anion transporter expression in rat liver. Radiology 274 (2):379-386.https ://doi.org/10.1148/radio l.14140 313

              9. Leporq B, Daire JL, Pastor CM, Deltenre P, Sempoux C, Schmidt S, Van Beers BE (2018) Quantification of hepatic perfusion and hepatocyte function with dynamic gadoxetic acid enhanced MRI in patients with chronic liver disease. ClinSci (Lond) 132 (7):813-824. https ://doi.org/10.1042/cs201 71131

              10. Yoon JH, Lee JM, Baek JH, Shin CI, Kiefer B, Han JK, Choi BI (2014) Evaluation of hepatic fibrosis using intravoxel incoherent motion in diffusion-weighted liver MRI. J Comput Assist Tomogr38 (1):110-116. https ://doi.org/10.1097/rct.0b013e3182a589be

               

              Dr. Ekaterini Xinou, PhD, is a consultant radiologist at the Computed Tomography Department of ‘Theagenion’ Cancer Hospital in Thessaloniki, Greece. She is an active ESGAR member since 2005, attending regularly annual meetings and workshops. Her main interest is in abdominal and oncologic radiology, and also in swallowing disorders. She completed her thesis at the Aristotle University of Thessaloniki regarding swallowing disorders encountered during videofluoroscopy in head and neck cancer patients after chemoradiotherapy.

              Comments may be sent to katxinou@remove-this.otenet.gr


              Focal Liver Lesions: Computer-aided Diagnosis by Using Contrast-enhanced US Cine Recordings

              Ta CN, Kono Y, Eghtedari M, Oh YT, Robbin ML, Barr RG, Kummel AC, Mattrey RF.
              Radiology. 2018 Mar;286(3):1062-1071. doi: 10.1148/radiol.2017170365. Epub 2017 Oct 25.
              PMID: 29072980

              Dr. Nuno Campos, Resident, Department of Medical Imaging, Coimbra Hospital and University Centre, Coimbra (Portugal).
              Prof. Dr. Luís Curvo Semedo, Radiology Consultant, Coimbra Hospital and University Centre; Assistant Professor, Faculty of Medicine - University of Coimbra (Portugal).

              At autopsy, as many as 52% of noncancer patients have benign hepatic lesions, and liver metastases are found in as many as 36% of patients dying with cancer (1). Contrast enhanced ultrasound (CEUS) has improved the characterization of focal liver lesions (FLL), offering comparable results to those of computed tomography (CT) and magnetic resonance imaging (MRI) when the ultrasound exploration is technically satisfactory (2-5). Despite their known advantages and potential, CEUS is not included as an indicated imaging modality for the diagnosis of hepatocellular carcinoma (HCC) in recent guidelines, based on a study reporting similar contrast-enhancement patterns between HCC and intrahepatic cholangiocarcinoma (6-8). The concept of computer-aided diagnosis (CAD), developed in order to assist radiologists in detecting abnormal lesions and improving the accuracy of their characterization, has been studied and applied on several imaging modalities, with promising results (9-11).

              In this multicenter trial, the authors aimed to assess the ability of CAD systems to distinguish benign from malignant FLL compared to the gold-standard (histologic examination), or, when that was not possible, well-accepted criteria at contrast-enhanced CT and/or MRI. Secondary aims of the study were to determine which features had the greatest impact on the CAD classification of FLLs and to compare its performance to that of two observers, one experienced and one inexperienced.

              Two CAD systems were developed by the authors, applying artificial neural networks and support vector machine technology, which were then used to classify benign or malignant lesions given 92 independent features (6 in B-mode, 20 enhancement features, and 66 time-intensity curve features).

              The results of the study showed that CAD systems can classify benign and malignant FLL in contrast-enhanced US cine recordings with an accuracy comparable to that of an experienced blinded observer (81.1% vs 81.4%) and had better discrimination than the inexperienced reader (81.1% vs 72.0%). Of all the features analyzed by the CAD system, FLL B-mode homogeneity pre-contrast and time-dependent post-contrast enhancement features (most notably the washout features) were the most discriminating.

              Also importantly, when CAD classification was in agreement with that of an experienced or inexperienced reader, it increased their global accuracy to nearly 90%, indicating these systems could provide a second opinion to improve the diagnostic confidence and accuracy when classifications agree or to flag ambiguous lesions for additional review and characterization when they disagree.

              As stated by their authors, this study as some limitations, one being the relatively small sample size (105 lesions), with a limited number of lesions smaller than 2 cm (20 lesions). One positive feature of this work is that it included a broad number of FLLs (11 types) attempting to classify them as either benign or malignant, while other published reports are usually limited to three to five lesion types (2,3).

              In conclusion, this is an easily readable article, not describing computational analysis exhaustively, but rather focusing on the clinical applicability of this emerging technology. Nevertheless, the study was limited by its relatively small sample size, lacking a representative number of the variety of all FLL types, thus potentially hampering the development of better algorithms to differentiate not only benign from malignant lesions, but also to accurately classify and discriminate different malignant lesions. This may be a leading point for future similar studies that will deal with this same challenge.

              References:

              1.    Berland, Lincoln L., et al. “Managing Incidental Findings on Abdominal CT: White Paper of the ACR Incidental Findings Committee.” Journal of the American College of Radiology, vol. 7, no. 10, 2010, pp. 754–773., doi:10.1016/j.jacr.2010.06.013.

              2.    Bertolotto, M., et al. “Characterization of Unifocal Liver Lesions with Pulse Inversion Harmonic Imaging after Levovist Injection: Preliminary Results.” European Radiology, vol. 10, no. 9, 2000, pp. 1369–1376., doi:10.1007/s003300000497.

              3.    Brannigan, Margot, et al. “Blood Flow Patterns in Focal Liver Lesions at Microbubble-Enhanced US.” RadioGraphics, vol. 24, no. 4, 2004, pp. 921–935., doi:10.1148/rg.244035158.

              4.    Strobel, D, et al. “Contrast-Enhanced Ultrasound for the Characterization of Focal Liver Lesions – Diagnostic Accuracy in Clinical Practice (DEGUM Multicenter Trial).” Ultraschall in Der Medizin - European Journal of Ultrasound, vol. 29, no. 05, Jan. 2008, pp. 499–505., doi:10.1055/s-2008-1027806.

              5.    Tranquart, F., et al. “Role of Contrast-Enhanced Ultrasound in the Blinded Assessment of Focal Liver Lesions in Comparison with MDCT and CEMRI: Results from a Multicentre Clinical Trial.” European Journal of Cancer Supplements, vol. 6, no. 11, 2008, pp. 9–15., doi:10.1016/j.ejcsup.2008.06.003.

              6.    Vilana, Ramón, et al. “Intrahepatic Peripheral Cholangiocarcinoma in Cirrhosis Patients May Display a Vascular Pattern Similar to Hepatocellular Carcinoma on Contrast-Enhanced Ultrasound.” Hepatology, vol. 51, no. 6, 2010, pp. 2020–2029., doi:10.1002/hep.23600.

              7.    Claudon, M., et al. “Guidelines and Good Clinical Practice Recommendations for Contrast Enhanced Ultrasound (CEUS) in the Liver – Update 2012.” Ultraschall in Der Medizin - European Journal of Ultrasound, vol. 34, no. 01, May 2012, pp. 11–29., doi:10.1055/s-0032-1325499.

              8.    “EASL–EORTC Clinical Practice Guidelines: Management of Hepatocellular Carcinoma.” Journal of Hepatology, vol. 56, no. 4, 2012, pp. 908–943., doi:10.1016/j.jhep.2011.12.001.

              9.    Doi, Kunio. “Computer-Aided Diagnosis in Medical Imaging: Historical Review, Current Status and Future Potential.” Computerized Medical Imaging and Graphics, vol. 31, no. 4-5, 2007, pp. 198–211., doi:10.1016/j.compmedimag.2007.02.002.

              10.    Gatos, Ilias, et al. “A New Automated Quantification Algorithm for the Detection and Evaluation of Focal Liver Lesions with Contrast-Enhanced Ultrasound.” Medical Physics, vol. 42, no. 7, Oct. 2015, pp. 3948–3959., doi:10.1118/1.4921753.

              11.    Shiraishi, Junji, et al. “Computer-Aided Diagnosis for the Classification of Focal Liver Lesions by Use of Contrast-Enhanced Ultrasonography.” Medical Physics, vol. 35, no. 5, Oct. 2008, pp. 1734–1746., doi:10.1118/1.2900109.


              Dr. Nuno Campos is a second-year resident at Coimbra Hospital and University Centre in Portugal. He completed his undergraduate medical degree at University of Minho in 2016. His main interests are abdominal and musculoskeletal diagnostic radiology.

              Comments may be sent to: nunocampos.bf@remove-this.gmail.com


              Molecular Classification of Hepatocellular Adenoma Associates With Risk Factors, Bleeding, and Malignant Transformation.

              Nault JC, Couchy G, Balabaud C, Morcrette G, Caruso S, Blanc JF, Bacq Y, Calderaro J, Paradis V, Ramos J, Scoazec JY, Gnemmi V, Sturm N, Guettier C, Fabre M, Savier E, Chiche L, Labrune P, Selves J, Wendum D, Pilati C, Laurent A, De Muret A, Le Bail B, Rebouissou S, Imbeaud S; GENTHEP Investigators, Bioulac-Sage P, Letouzé E, Zucman-Rossi J.

              Journal: Gastroenterology. 2017;152:880-894.e6.

              Dr. Roberto Cannella, radiology resident, University of Palermo (Palermo/IT)

              Hepatocellular adenomas (HCAs) are uncommon benign liver lesions, most frequently occurring in young women. HCA is not a single and uniform entity, but it may be classified in different subtypes according to a immunohistochemical and molecular classification. In 2006, HCAs have been initially divided in 4 different subtypes, including: 1) HNF1α-mutated (35-40% of all lesions); 2) Inflammatory (40-50%); 3) β-catenin mutated (10%); 4) Unclassified (10%) HCAs [1, 2]. The sub-classification of HCAs has significant clinical implications. Each subtype carries a different risk of complications, with hemorrhage and malignant transformation mostly commonly occurring in patients with inflammatory and β-catenin mutated subtypes, respectively. Surgical resection has been recommended in lesion larger than 5 cm, HCAs arising in males, or presence of β-catenin mutation.

              Magnetic resonance imaging (MRI) has demonstrated a high accuracy for the differential diagnosis of HCAs from other indolent hepatic lesions, such as focal nodular hyperplasia (FNH) [3] and for the noninvasive sub-classification of those four histopathological subtypes [4]. The presence of lesion hypointensity on images obtained during the hepatobiliary phase acquired after the administration of hepatobiliary contrast agent (Gadoxetic acid, Gd-EOB-DTPA) has a pooled sensitivity and specificity of 95% and 92%, respectively, for differentiation of HCA from FNH [5]. Presence of intra-lesional fat, appearing as marked signal drop on out-of-phase images, is associated with the HNF1α-mutated HCAs, while inflammatory HCAs are described as lesions with intense arterial phase hyperenhancement, hyperintensity on T2-weighted images and with possible presence of a characteristic “atoll” sign [4].

              Recently, a new milestone has been reached for the sub-classification of HCA. The study published by Nault et al. aimed to update the molecular classification of HCA [6]. In their study 533 HCAs from 411 patients, collected among 28 centers, were pathologically analyzed. HCAs were largely present in women (85%) with a median age median age of 38 years (range 7-82 years). HCAs were multiple in 45% of the cases and in 12% a liver adenomatosis (i.e. >10 HCAs) was noted. Hepatic steatosis was present in 12% of cases in the non-tumoral liver parenchyma.

              Based on molecular analysis, HCAs were classified in 8 different molecular subgroups. Four new subtypes were described, including the Sonic Hedgehog HCA (4% of all HCAs) which were previously considered as unclassified HCAs, two subtypes with different sites of mutation in β-catenin (CTNNB1) located in exon 7/8 (3%) and exon 3 (7%), respectively, and two mixed inflammatory and β-catenin subtypes (figure below, from the article [6]).

              The novel molecular classification and new subtypes were associated with risk factors and complications, including the risk of intralesional hemorrhage and malignant transformation. History of oral contraceptive use was present in 87% of female patients. The cumulative intake of oral contraceptive, estrogens or androgens, as well as obesity, hepatic steatosis, glycogenosis or liver vascular disease were described as risks factors associated with different molecular subtypes.
              Intralesional hemorrhage was histologically observed in about half of the tumors (52%). However, symptomatic bleeding was present only in 14% of the lesions and it was significantly associated with the new subtype of Sonic Hedgehog HCA. The new classification aimed also to stratify patients according to the risk of malignant transformation. Particularly, malignant transformation into hepatocellular carcinoma was associated with male gender and presence of CTNNB1 mutation in exon 3.

              Despite the recent advances on molecular classification of HCAs, there are still many gaps in knowledge regarding their imaging characteristics that need to be further studied. The imaging appearance of the new Sonic hedgehog subtype has not been described yet. Although rare, this subtype has the highest risk of macroscopic symptomatic bleeding, so its diagnosis and description of imaging characteristics will have significant clinical implications. Moreover, no studies have explored the value MRI features of HCAs according to the new molecular classification. Analysis of such rare tumors will require multicentric studies including large number of lesions to determine the role of MRI for the non-invasive differentiation of HCAs subtypes according to the new molecular classification. Knowledge of the imaging appearance of HCAs needs to be redefined taking into account the new molecular description of HCA.


              References

              1.    Zucman-Rossi J, Jeannot E, Nhieu JT, Scoazec JY, Guettier C, Rebouissou S, Bacq Y, Leteurtre E, Paradis V, Michalak S, Wendum D, Chiche L, Fabre M, Mellottee L, Laurent C, Partensky C, Castaing D, Zafrani ES, Laurent-Puig P, Balabaud C, Bioulac-Sage P. Genotype-phenotype correlation in hepatocellular adenoma: new classification and relationship with HCC. Hepatology. 2006;43:515-524.

              2.    Bioulac-Sage P, Rebouissou S, Thomas C, Blanc JF, Saric J, Sa Cunha A, Rullier A, Cubel G, Couchy G, Imbeaud S, Balabaud C, Zucman-Rossi J. Hepatocellular adenoma subtype classification using molecular markers and immunohistochemistry. Hepatology. 2007;46:740-748.

              3.    Grazioli L, Bondioni MP, Haradome H, Motosugi U, Tinti R, Frittoli B, Gambarini S, Donato F, Colagrande S. Hepatocellular adenoma and focal nodular hyperplasia: value of gadoxetic acid-enhanced MR imaging in differential diagnosis. Radiology. 2012;262:520-529.

              4.    Ba-Ssalamah A, Antunes C, Feier D, Bastati N, Hodge JC, Stift J, Cipriano MA, Wrba F, Trauner M, Herold CJ, Caseiro-Alves F. Morphologic and Molecular Features of Hepatocellular Adenoma with Gadoxetic Acid-enhanced MR Imaging. Radiology. 2015;277:104-113.

              5.    Guo Y, Li W, Cai W, Zhang Y, Fang Y, Hong G. Diagnostic Value of Gadoxetic Acid-Enhanced MR Imaging to Distinguish HCA and Its Subtype from FNH: A Systematic Review. Int J Med Sci. 2017;14:668-674.

              6.    Nault JC, Couchy G, Balabaud C, Morcrette G, Caruso S, Blanc JF, Bacq Y, Calderaro J, Paradis V, Ramos J, Scoazec JY, Gnemmi V, Sturm N, Guettier C, Fabre M, Savier E, Chiche L, Labrune P, Selves J, Wendum D, Pilati C, Laurent A, De Muret A, Le Bail B, Rebouissou S, Imbeaud S; GENTHEP Investigators, Bioulac-Sage P, Letouzé E, Zucman-Rossi J. Molecular Classification of Hepatocellular Adenoma Associates With Risk Factors, Bleeding, and Malignant Transformation. Gastroenterology. 2017;152:880-894.e6.


              Dr. Roberto Cannella is a fifth-year resident at the Radiology Department at the University of Palermo (Palermo, Italy) and an active ESGAR member who is regularly attending the annual meetings. Dr. Cannella spent 17 months as a research scholar at the Abdominal Imaging Division of the University of Pittsburgh Medical Center (UPMC) in Pittsburgh (Pennsylvania, USA). He has been involved in several research studies centered on hepatobiliary topics, and specifically on CT and MR imaging of hepatocellular adenoma.

              Comments may be sent to: rob.cannella89@remove-this.gmail.com



              Prospective Intraindividual Comparison of Magnetic Resonance Imaging With Gadoxetic Acid and Extracellular Contrast for Diagnosis of Hepatocellular Carcinomas Using the Liver Imaging Reporting and Data System.

              Min JH, Kim JM, Kim YK, Kang TW, Lee SJ, Choi GS, Choi SY, Ahn S.

              Journal: Hepatology. 2018; 68(6):2254-2266.

              Mariangela Dimarco (radiology resident, University of Palermo, Palermo/IT)
              Federica Vernuccio (radiologist and PhD student, University of Palermo, Palermo/IT)

              Hepatocellular carcinoma (HCC) is the most common primary hepatic malignant tumor worldwide. The diagnosis of HCC is oftentimes made non invasively on CT or MR imaging, thus reducing the need for biopsy. In their study, Min et al performed an intraindividual prospective comparison of the diagnostic accuracy of extracellular contrast enhanced MRI and hepatobiliary contrast enhanced MRI for the diagnosis of HCC. The study population included 91 patients at risk for HCC with a suspicious focal liver lesion detected on US and indicated for surgery between November 2016 and November 2017. Prior to surgery, each patient performed an extracellular contrast enhanced MRI and a hepatobiliary contrast enhanced MRI. MRI images were reviewed by two expert radiologists and lesions were categorized according to LI-RADS. The comparison of sensitivity, specificity and diagnostic accuracy of the two contrast agents resulted in a significantly higher sensitivity and diagnostic accuracy for the diagnosis of HCC with the extracellular contrast agent (77.9% and 82.1%, respectively) compared to the hepatobiliary one (66.3% and 72.6%, respectively), while specificity was 100% for both contrast agents. The values of sensitivity in this prospective study are equal or slightly lower than those reported by Roberts et al in a recent metanalysis (i.e. 75% and 87% for extracellular contrast enhanced MRI and hepatobiliary contrast enhanced MRI, respectively). However, this slight reduction in sensitivity in the study by Min et al is associated with a specificity of 100% with both contrast agents, which is higher compared to the results of the metanalysis (86% and 94% for extracellular contrast enhanced MRI and hepatobiliary contrast enhanced MRI, respectively).

              Min et al evaluated also the diagnostic role of a "modified" washout – i.e. relative hypointensity in portal venous or transitional phases using hepatobiliary agent or isointensity with capsule on the portal venous or delayed phases using extracellular contrast agent (i.e., illusional washout) – for the diagnosis of HCC. According to the results, the "modified" washout was associated with greater diagnostic performance compared to conventional washout (as defined by LI-RADS). Of 95 HCC confirmed at pathology, 87 (91.6%) showed a “modified” washout while only 76 (80%) and 74 (78%) lesions showed a conventional washout using an extracellular or a hepatobiliary agent, respectively. The analysis of the diagnostic performance of a "modified" version of LI-RADS with the adoption of the "modified" washout as a major criterion for the diagnosis of HCC resulted in a greater sensitivity and accuracy using the extracellular contrast agent (89.5% and 91.5%, respectively) compared to the hepatobiliary one (80% and 83.8%, respectively), with 100% specificity in both cases.

              LI-RADS categorization categorized primary and secondary liver malignancies lacking the imaging findings typical for HCC as LR-M. In the study of Min et al, of the 2 intrahepatic cholangiocarcinomas, one was correctly categorized as LR-M with both agents, while one was categorized as LR-M using the hepatobiliary agent because of a target appearance (i.e. central enhancing area with a peripheral hypointense rim) in the transitional phase, but it was categorized as LR-4 using the extracellular contrast agent because it was purely hypointense on the portal venous and delayed phases. In addition, the results of the study by Min et al highlighted the importance of the capsule for the differential diagnosis between HCC and other hepatic tumors. The “enhancing” capsule is considered a major criterion by LI-RADS and AASLD for the diagnosis of HCC while other classification systems (i.e. EASL, APASL) underestimate its importance and do not include this important feature for the diagnosis of HCC. However, while an enhancing capsule was observed in 87% HCCs on extracellular contrast based MRI, only 47% HCCs showed this important feature on hepatobiliary contrast based-MRI.

               

               

              In conclusion, the prospective study by Min et al emphasizes the increased sensitivity and diagnostic accuracy of the extracellular contrast agent compared to the hepatobiliary one in the final diagnosis of HCC, along with an equal strikingly high specificity (100%). Min et al suggest a modified version of LI-RADS, which includes a “modified” washout as a major imaging features for the diagnosis of HCC due to its high diagnostic performance. In addition to the analysis of the typical vascular behavior of HCC for the diagnosis, the enhancing capsule is of utmost importance for the diagnosis of HCC, since this imaging feature is usually not detected in other hepatic lesions (i.e. dysplastic nodule, cholangiocarcinoma or hemangioma).

               

              References

              1.    McGlynn KA, Petrick JL, London WT. Global epidemiology of hepatocellular carcinoma: an emphasis on demographic and regional variability. Clin Liver Dis. 2015;19(2):223-38.

              2.    https://www.acr.org/-/media/ACR/Files/RADS/LI-RADS/LI-RADS-2018-Core.pdf?la=en Accessed on Jan 17, 2019

              3.    Min JH, Kim JM, Kim YK, Kang TW, Lee SJ, Choi GS, Choi SY, Ahn S. “Prospective Intraindividual Comparison of Magnetic Resonance Imaging With Gadoxetic Acid and Extracellular Contrast for Diagnosis of Hepatocellular Carcinomas Using the Liver Imaging Reporting and Data System” (2018) Hepatology. 68(6):2254-2266.

              4.    Marrero JA, Kulik LM, Sirlin CB, et al.  Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology. 2018;68(2):723-750.

              5.    Roberts LR, Sirlin CB, Zaiem F, et al. Imaging for the Diagnosis of Hepatocellular Carcinoma: A Systematic Review and Meta-analysis. Hepatology 2018; 67(1):401-421

              6.    EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu; European Association for the Study of the Liver. J Hepatol. 2018;69(1):182-236.

              7.    Omata M, Cheng AL3, Kokudo N, et al Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update. Hepatol Int. 2017; 11(4):317-370.

              _________________________________________________________________________________________________________________________________________________________________________________

              Dr. Mariangela Dimarco is a third-year Radiology resident working in the Radiology Department at the University of Palermo (Palermo, Italy), where she graduated as a medical doctor in March 2015. She is a junior ESGAR member and her main interests are clinical radiology and research, especially emergency and abdominal imaging.

              Comments may be send to: maridimarco33@remove-this.gmail.com

               



              Pretreatment prediction of immunoscore in hepatocellular cancer: a radiomics-based clinical model based on Gd-EOB-DTPA-enhanced MRI imaging
              Shuling Chen, Shiting Feng, Jingwei Wie, Fei Liu, Bin Li, Xin Li, Yang Hou, Dongsheng Gu, Mimi Tang, Han Xiao, Yingmei Jia, Sui Peng, Jie Tian, Ming Kuang. European Radiology, 2019

              Reviewed By Naik Vetti Violi CHUV University hospital Lausanne Switzerland

              Systemic immunotherapy is a recent treatment alternative for non-resectable hepatocellular carcinoma (HCC). However, the expected response rate is low, around 20% (1). Patient selection tool is indeed needed to avoid unnecessary costs and side effects. Density of tumor infiltration lymphocytes (TILs) has shown to be associated to immunotherapy response and survival. Immunoscore based on the characteristics of TILs has been described for different cancers including HCC (2, 3). In HCC, high immunoscore has shown to be associated with low recurrence rate and longer progression-free survival (4, 5). However, such a score is based on histologic examination and requires invasive tissue sampling. New imaging tools as radiomics have been proposed as surrogate for histologic examination, avoiding tissue sampling risks and allowing repetitive measurements of the entire tumor volume (6).

              Radiomics is based on the concept that images contain information about pathophysiology that can be expressed by the extraction of a large number of quantitative features. Radiomics analysis provides a large amount of data that are not limited to the visual evaluation and can be extracted from the entire tumor volume and at each imaging follow-up in the course of the cancer. Qualitative and quantitative features based on intensity, shape, size, volume or texture can provide information about tumor phenotype and microenvironment that can be correlated to clinical outcomes.

              Correlation between immunoscore and radiomics feature has already been shown in lung cancer but not in HCC (7).

              In this retrospective single center study performed in China, Dr Chen and colleagues developed a radiomics model for the prediction of immunoscore in HCC. They include patients with histologically proven HCC who underwent hepatectomy between 2011 and 2017 for a single lesion or multiple lesions within the same liver lobe and who underwent MRI using gadoxetic acid within one month before surgery. All the MRIs were performed using the same machine (Siemens Sector 3.0-T) and protocol. Exclusion criteria were any anti-tumor therapies, any concomitant malignancies or incomplete data. The study population consisted of 207 patients.

              The immunoscore was already validated and was based on the degree of CD3 and CD8 infiltration in the tumor center and margin (3).

              Each lesion was manually delineated on hepatobiliary phase (HBP) in 3D in order to get a volume of interest (VOIs) by three independent experienced radiologists, with good correlation scores. An algorithm that dilated the tumoral region of 1 cm determined the peritumoral region. MR features were extracted and analyzed using a house-made software. A large number of first and second order radiomics features were included in the analysis (1044 imaging features) including histogram features, texture, form factor and grey level parameters. An extremely randomized tree method was used to select the most relevant features. A training set (n=150 patients) was used to build the radiomics model and validation set (n=57 patients) to test it. Different models were tested using either intratumoral region or combined intratumoral with peritumoral regions features. Additionally, the model was tested by combining clinical data to the radiomics features. Included clinical data were AFP, GGT, AST.

              The final models consisted of 70 radiomics features. Results showed that the model integrating intra and peritumoral radiomics features with combination of clinical data showed the best prediction performance for immunoscore (validation set: AUC: 93.4%. sensitivity: 84.6%, specificity: 84.1%), despite no statistical difference with the combined intra and peritumoral radiomics model.

              This study presents several points of methodology that have to be highlighted. (1) The integration of the peritumoral region is meaningful when considering TILs. Rate of peritumoral lymphocytes infiltration has shown to be associated in HCC recurrence (8). Furthermore, radiomics model integrating peritumoral region has been successfully achieved in breast cancer already (9). Consequently, there is an interest of considering not only the tumor itself but also the liver surrounding the tumor. (2) Integration of clinical data – that improved the model performance - evidenced the complementarity of information and the potential interest of combining radiologic and clinical data in the model. (3) 3D lesion evaluation is interesting as it reflects the entire tumor architecture and heterogeneity. It is one of the main advantages of radiomics analysis compared to biopsy, which only represents a sample with a potential risk of sampling error and inter-observer variations (10, 11). (4) The use of HBP for radiomics extraction is valuable as it has shown to allow higher lesion conspicuity comparing to dynamic phases (12). HBP could be useful to develop software for automatic lesion boundaries drawing in order to avoid manual lesion delineation.

              Authors acknowledge some study limitations that are classical limitations inherent to radiomics analysis: the limited population size compared to the large number of integrated features, the absence of external validation set and the correlation only with TILs, not integrating other predictor of immunotherapy response. Additional limitations have to be highlighted: the manual segmentation and the use of house-made radiomics software can be cited as limitations for generalization. When looking at the study population, most of the patients presented limited liver disease extension (BCLC A in 52.2%) and small tumor size (<5cm in 59.4%) which typically not represent the target population for immunotherapy. A validation with more advanced HCC is indeed needed.

              Systemic immunotherapy seems to be a promising future direction for HCC treatment, in particular when considering advanced stages. Due to its high cost and low rate of tumor response, an accurate patient selection tool is needed. This study showed the feasibility of developing a radiomics-based model as a surrogate to immunoscore that could be used for patient selection based on imaging avoiding the need for tissue sample. However, this study also showed the missing steps that have to be overpassed in order to be a clinical practice tool: the need for software harmonization, external validation and accurate automated software for lesion delineation. Further investigations in order to transfer these promising results to clinical practice are needed, particularly by correlating the present results with patient outcomes (rate of tumor response, progression free survival, overall survival for instance) in order to validate them.

               

              References

              1.    El-Khoueiry AB, Sangro B, Yau T, Crocenzi TS, Kudo M, Hsu C, Kim TY, et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet 2017;389:2492-2502.
              2.    Brunner SM, Rubner C, Kesselring R, Martin M, Griesshammer E, Ruemmele P, Stempfl T, et al. Tumor-infiltrating, interleukin-33-producing effector-memory CD8(+) T cells in resected hepatocellular carcinoma prolong patient survival. Hepatology 2015;61:1957-1967.
              3.    Galon J, Mlecnik B, Bindea G, Angell HK, Berger A, Lagorce C, Lugli A, et al. Towards the introduction of the 'Immunoscore' in the classification of malignant tumours. J Pathol 2014;232:199-209.
              4.    Garnelo M, Tan A, Her Z, Yeong J, Lim CJ, Chen J, Lim KH, et al. Interaction between tumour-infiltrating B cells and T cells controls the progression of hepatocellular carcinoma. Gut 2017;66:342-351.
              5.    Yao Q, Bao X, Xue R, Liu H, Liu H, Li J, Dong J, et al. Prognostic value of immunoscore to identify mortality outcomes in adults with HBV-related primary hepatocellular carcinoma. Medicine (Baltimore) 2017;96:e6735.
              6.    Jeong WK, Jamshidi N, Felker ER, Raman SS, Lu DS. Radiomics and radiogenomics of primary liver cancers. Clin Mol Hepatol 2018.
              7.    Tang C, Hobbs B, Amer A, Li X, Behrens C, Canales JR, Cuentas EP, et al. Development of an Immune-Pathology Informed Radiomics Model for Non-Small Cell Lung Cancer. Sci Rep 2018;8:1922.
              8.    Cai XY, Wang JX, Yi Y, He HW, Ni XC, Zhou J, Cheng YF, et al. Low counts of gammadelta T cells in peritumoral liver tissue are related to more frequent recurrence in patients with hepatocellular carcinoma after curative resection. Asian Pac J Cancer Prev 2014;15:775-780.
              9.    Braman NM, Etesami M, Prasanna P, Dubchuk C, Gilmore H, Tiwari P, Plecha D, et al. Intratumoral and peritumoral radiomics for the pretreatment prediction of pathological complete response to neoadjuvant chemotherapy based on breast DCE-MRI. Breast Cancer Res 2017;19:57.
              10.    Clauson J, Hsieh YC, Acharya S, Rademaker AW, Morrow M. Results of the Lynn Sage Second-Opinion Program for local therapy in patients with breast carcinoma. Changes in management and determinants of where care is delivered. Cancer 2002;94:889-894.
              11.    Robert M, Sofair AN, Thomas A, Bell B, Bialek S, Corless C, Van Ness G, et al. A comparison of hepatopathologists' and community pathologists' review of liver biopsy specimens from patients with hepatitis C. Clin Gastroenterol Hepatol 2009;7:335-338.
              12.    Besa C, Kakite S, Cooper N, Facciuto M, Taouli B. Comparison of gadoxetic acid and gadopentetate dimeglumine-enhanced MRI for HCC detection: prospective crossover study at 3 T. Acta Radiol Open 2015;4:2047981614561285.

              _________________________________________________________________________________________________________________________________________________________________________________

              Dr. Naik Vietti Violi is a radiologist at Mount Sinai Hospital (New York, USA) where she is working as a research fellow. She completed her residency at Lausanne University Hospital (CHUV, Lausanne, Switzerland) where she will come back after her fellowship. She specialized in oncology and abdominal imaging. Her main research projects include inflammatory bowel diseases, tumor response after loco-regional therapy in liver and more recently abbreviated MRI for hepatocellular cancer detection.

              Comments may be sent to: nviettivioli@remove-this.gmail.com

               



              Radiomic Analysis of Contrast-Enhanced CT Predicts Microvascular Invasion and Outcome in Hepatocellular Carcinoma

              Xun Xu, Hai-Long Zhang, Qiu-Ping Liu, Shu-Wen Sun, Jing Zhang, Fei-Peng Zhu, Guang Yang, Xu Yan, Yu-Dong Zhang, Xi-Sheng Liu
              PII: S0168-8278(19)30145-X
              DOI: doi.org/10.1016/j.jhep.2019.02.023
              Reference: JHEPAT 7291
              To appear in: Journal of Hepatology

              Recurrence  after curative treatment for hepatocellular carcinoma (HCC) (surgery, percutaneous thermal ablation or liver transplantation) is up to 70% within 5 years after surgical resection or thermal ablation, and 35% after liver transplantation 1–3. Macro and micro-vascular invasion are both prognosis factor of recurrence 4–6, but at odd to macrovascular invasion that can be detected by cross-sectional imaging, micro-vascular invasion (MVI) is a histological finding that can only be post operatively diagnosed with surgical specimen 7. Several biological, genetic and imaging factors have showed association with MVI. More recently radiomics showed promising results 3,8,9. Radiomics is a newly emerging form of imaging analysis using a series of datamining algorithms or statistical analysis tools on high-throughput imaging features to obtain predictive or prognostic information. However these parameters are not widely used in practice. Therefore the aim of this study was to to investigate whether a computational approach integrating large-scale clinical and imaging modalities, especially radiomic features extracted from contrast-enhanced CT (CECT), could be useful to predict MVI and the long-term clinical outcomes of HCC patients.

              In their retrospective study, Xun Xu et al included  495 cases from liver specimen (after surgery or liver transplantation). Routine preoperative laboratory examinations before liver surgery were performed and CECT according to AASLD guidelines was used to radiomics analysis. Radiomics was performed on the entire tumor volume and in a region at a 5mm distance from tumor surface(because MVI is around the tumor).  A model was computed on a training group (n=300), and then validated on a validation group (n=50) and a testing group (n=145).

              In the multivariate regression model, 8 predictors were independent prognostic factors of histologic MVI: higher AST (> 40 U/L), higher AFP (> 400ng/mL), non-smooth tumor margin, extrahepatic growth pattern, ill-defined pseudocapsule, peritumoral arterial enhancement, positive of radio-genomic venous invasion score-8-, and higher Radiomics-score. A risk model integrating clinicoradiologic factors and Rariomics-scores can identify more than 88% of the MVI-positive cases with a specificity of 76.8%-79.2%. The median PFS was 12.9 (7.1-25.5) months for patients with Model-predicted MVI presence and 49.5 (42.3-93.7) months for those with Model-predicted MVI absence (log-rank test, p < 0.001). The median OS was 47.3 (40.6–54.1) months for those with Model-predicted MVI presence and 76.3 (71.6–80.8) months for those with Model -predicted MVI absence (log-rank test, p < 0.001).

              So Xun Xu et al found that combining biological, genomic, imaging features and radiomics analysis offered a viable solution to predict MVI for HCC. However these results need to be confirmed in a different population. Indeed this study was performed in china where the main cause of HCC is hepatitis B without cirrhosis. In Europe HCC occurred mainly on non-viral cirrhosis, therefore we can assume this could lead to different results due to the heterogeneity of a liver  parenchyma in case of cirrhosis and to the different oncologic pathway between HCC occurring on hepatitis B compared to non-viral cirrhosis. Nevertheless radiomics is a promising and emerging tool in the radiological and oncological field.

              Bibliography

              1. Hepatocellular carcinoma recurrence and death following living and deceased donor liver transplantation. - PubMed - NCBI. Available at: www.ncbi.nlm.nih.gov/pubmed/17511683. (Accessed: 26th March 2019)

              2. Marshall, A. E. et al. Tumor recurrence following liver transplantation for hepatocellular carcinoma: role of tumor proliferation status. Liver Transplant. Off. Publ. Am. Assoc. Study Liver Dis. Int. Liver Transplant. Soc.16, 279–288 (2010).

              3. Banerjee, S. et al. A computed tomography radiogenomic biomarker predicts microvascular invasion and clinical outcomes in hepatocellular carcinoma. Hepatol. Baltim. Md62, 792–800 (2015).

              4. Shah, S. A. et al. Recurrence after liver resection for hepatocellular carcinoma: risk factors, treatment, and outcomes. Surgery141, 330–339 (2007).

              5. Nakashima, Y. et al. Portal vein invasion and intrahepatic micrometastasis in small hepatocellular carcinoma by gross type. Hepatol. Res. Off. J. Jpn. Soc. Hepatol.26, 142–147 (2003).

              6. D’Amico, F. et al. Predicting recurrence after liver transplantation in patients with hepatocellular carcinoma exceeding the up-to-seven criteria. Liver Transplant. Off. Publ. Am. Assoc. Study Liver Dis. Int. Liver Transplant. Soc.15, 1278–1287 (2009).

              7. Rodríguez-Perálvarez, M. et al. A systematic review of microvascular invasion in hepatocellular carcinoma: diagnostic and prognostic variability. Ann. Surg. Oncol.20, 325–339 (2013).

              8. Renzulli, M. et al. Can Current Preoperative Imaging Be Used to Detect Microvascular Invasion of Hepatocellular Carcinoma? Radiology279, 432–442 (2016).

              9. Lei, Z. et al. Nomogram for Preoperative Estimation of Microvascular Invasion Risk in Hepatitis B Virus-Related Hepatocellular Carcinoma Within the Milan Criteria. JAMA Surg.151, 356–363 (2016).

               

              Dr. Arnaud Hocquelet is a radiologist working in the interventional radiology unit at Vaud University Hospital (Lausanne,Switzerland). Dr Hocquelet's main interest is oncological  interventional radiology and he already published several articles about thermal ablation and abdominal imaging.

              Comments may be sent to: Arnaud.Hocquelet@remove-this.chuv.ch



              MRI assessment of hepatocellular carcinoma after locoregional therapy

              Rasha S. Hussein, Wahid Tantawy and Yasser A. Abbas
              Journal: Insights into Imaging  2019 Jan 29;10(1):8. doi: 10.1186/s13244-019-0690-1

              Dra. Asunción Torregrosa Andrés, ESGAR fellow and Head of the Abdominal Radiology Section and Dr. Alberto Alegre-Delgado, ESGAR Member and Radiology Resident in his fourth and last year of training, both working in Hospital La Fe, Valencia (Spain).

              Hepatocellular carcinoma is well-known to be the most frequent primary malignant tumor of the liver, usually in the setting of liver cirrhosis, and an important cause of morbidity and mortality worldwide (1,2). There has been in the last decades an important development of locoregional therapies for the HCC with curative, downstaging or palliative aim. In this article, the Egyptian team of Hussein et al made a bibliographic review to illustrate the current state-of-the-art MRI techniques and imaging appearances in the evaluation of tumor response based on LI-RADS v2018 and mRECIST criteria.

              There are several therapeutic options depending on size, location of the tumor, and clinical state of the patient (3). Locoregional therapies include 1) thermal ablation (either radiofrequency or microwave ablation) with curative intention, usually prefered in early-HCC stages with high response rates; 2) transarterial chemoembolization (TACE) with PVA spheres loaded with doxorubicin (QT) in combination with lipiodol, which may be applied in order to understage the tumor and making it a candidate for a curative technique, so this technique is preferred in intermediate stages; and, finally, 3) transarterial radioembolization (TARE) by means of ytrium-loaded microspheres (Y90) that exert local effect.

              In response evaluation criteria, it is important to take into account vascularization and tumor necrosis apart from the size of the lesion itself, which may not vary or even increase, as several articles in the literature corroborate Kielar et al (3). Based on the limitation of the one-dimensional measurement required by the RECIST, the EASL-mRECIST system uses the largest diameter of the hyperenhanced portion of the lesion as a residual viable tumor emerged. In addition, the LI-RADS algorithm for treated lesions (LR-TR) includes the variability of the image before applying the mRECIST, so the response to treatment may be 1) non-evaluable, if the image quality is suboptimal; 2) non-viable, if there is no suggestive enhancement of residual viable tumor; 3) viable, if nodular enhancement persists and 4) equivocal, if doubts are present.

              Locorregional treatments lead to inflammatory changes in the surrounding parenchyma (hyperemia and edema) that may represent a challenge for the radiologist in differentiating normal post-treatment changes and residual viable tumor. Multiparametric MRI imaging including diffusion- and perfusion-weighted imagens may help to discriminate between both conditions (4).

              In dinamic contrast-enhanced MRI, linear and transitory surrounding enhancement is usually seen in post-treatment inflammatory changes, while a gross, heterogeneous and nodular enhancement indicates residual tumor. Subtraction sequences may help differentiate real hyperenhancement from T1 bright components like post-treatment hemorrhagic debris. Analysis of contrast kinetics may also be helpful to depict residual tumor as some articles have showed HCC tissue to lower mean transit time and a higher volume of distribution (4).

              Restriction in DWI with high b-values (800-1000) is a reliable indicator of cellularity and the ADC value can be used as an image biomarker of tumor response. Several studies have correlated higher ADC values with good tumor response in 6 months after treatment applying mRECIST criteria and also with a longer disease-free survival. The value of ADC is currently being investigated as an imaging biomarker in order to predict tumor response before the HCC is even treated, so that lesions with low pretreatment ADC values may respond better due to its high rate of cellularity and vascularization (5).

              The intravoxel incoherent motion (IVIM) MR technique is highlighted in this article review. This technique is able to study diffusion and perfusion without the need to introduce contrast (6). It distinguishes the pure diffusion attributable to cellularity, and pseudodiffusion attributable to microvascularization, so IVIM can substract the value of vascularization (D*) and provide a more reliable diffusion coefficient (D), which reflects directly the cellularity of the lesion. IVIM is a promising imaging biomarker to early detect local recurrence or viable residual tumor.

              This article is of great interest for every abdominal radiologist who has to assess HCC tumor response on MRI, since it provides the basis for a common reporting language (LI-RADS and EASL-mRECIST criteria), usual imaging appearances, as well as a global view of established MRI techniques and promising biomarkers for the evaluation of HCC response to locoregional therapies.


              References
              1.     McEvoy SH, McCarthy CJ, Lavelle LP, Moran DE, Cantwell CP, Skehan SJ, et al. Hepatocellular Carcinoma: Illustrated Guide to Systematic Radiologic Diagnosis and Staging According to Guidelines of the American Association for the Study of Liver Diseases. RadioGraphics. October 2013;33(6):1653-68.
              2.     Yaghmai V, Besa C, Kim E, Gatlin JL, Siddiqui NA, Taouli B. Imaging Assessment of Hepatocellular Carcinoma Response to Locoregional and Systemic Therapy. Am J Roentgenol. July 2013;201(1):80-96.
              3.     Kielar A, Fowler KJ, Lewis S, Yaghmai V, Miller FH, Yarmohammadi H, et al. Locoregional therapies for hepatocellular carcinoma and the new LI-RADS treatment response algorithm. Abdom Radiol. January 2018;43(1):218-30.
              4.     Taouli B, Johnson RS, Hajdu CH, Oei MTH, Merad M, Yee H, et al. Hepatocellular Carcinoma: Perfusion Quantification With Dynamic Contrast-Enhanced MRI. Am J Roentgenol. October 2013;201(4):795-800.
              5.     Mannelli L, Kim S, Hajdu CH, Babb JS, Clark TWI, Taouli B. Assessment of Tumor Necrosis of Hepatocellular Carcinoma After Chemoembolization: Diffusion-Weighted and Contrast-Enhanced MRI With Histopathologic Correlation of the Explanted Liver. Am J Roentgenol. October 2009;193(4):1044-52.
              6.     Kakite S, Dyvorne HA, Lee KM, Jajamovich GH, Knight-Greenfield A, Taouli B. Hepatocellular carcinoma: IVIM diffusion quantification for prediction of tumor necrosis compared to enhancement ratios. Eur J Radiol Open. 2016;3:1-7.

               

              Dr. Alberto Alegre Delgado is a radiologist in his fourth and last year of training and is currently working at University and Polytechnic La Fe Hospital in Valencia (Spain). Since the beginning of his training, he has been interested in abdominal radiology and worked extensively in this area. He is an active ESGAR member and attended various ESGAR biomarkers workshops and events such as the Junior ESGAR Summer School in Portugal in 2018. During his residency,  he also specifically collaborated in multidisciplinary investigation projects with hepatic surgeons including pre- and postoperative liver volumetry in patients with liver metastases, and in other hepatic segmentation projects with QuiBimÓ biomarkers group.

              Comments shall be sent to: alberto.alegre@remove-this.hotmail.com



              Error and discrepancy in radiology: inevitable or avoidable?

              Brady AP. Insights Imaging. 2017 Feb;8(1):171-182. doi: 10.1007/s13244-016-0534-1. Epub 2016 Dec 7. Review. PubMed PMID: 27928712; PubMed Central PMCID: PMC5265198.

              Dr. Damian Tolan
              ESGAR Fellow and Clinical Lead for CT and GI/HPB imaging, St James’s University Hospital, Leeds Teaching Hospitals, Leeds, UK.

              Over the last few years the ESGAR Journal watch articles have highlighted scientific observations related to organ specific assessment with CT, MRI and ultrasound in liver, pancreatic and gastrointestinal diseases.  Perhaps we have neglected the most important organ of all, and the one that we rely upon the most: the radiologist’s brain! How do we interact with patient imaging? How does variance occur in interpretation and how does underperformance arise? How do we cope with error and discrepancy when assessing scans?

              In an era when psychology and performance analysis is increasingly recognised as critical in high level sport and aviation, this paper successfully leads us through the subject with a radiology focus. Irish Radiologist Dr. Adrian Brady provides a superb structured appraisal of a complex area, and one that many radiologists have not been taught during training.  It is more important than ever that we have a thorough personal understanding of the human factors that influence us when we face an ever-increasing reporting workload. This is essential when we personally reflect on cases that have not achieved the desired outcome for our patients, so that we a can effectively learn lessons to openly share with our colleagues.

              After defining what error, discrepancy, negligence and hindsight bias mean, the ‘distribution’ of radiologist performance is discussed and how prevalent error is, not only in radiology practice but in other medical specialities.

              While we all recognise that errors can occur as a consequence of poor communication in our reporting, compounded by transcription errors in voice recognition, visual fatigue, decision fatigue and inattentional blindness while viewing images all contribute to suboptimal performance.  This is further compounded by a series of cognitive biases that lead us to make the wrong conclusion when the available information is presented to us that might allow us to make the right diagnosis.

              A series of strategies are provided that may be considered to minimize error, including departmental Quality Improvement programmes to share learning from cases, performing root cause analysis to assess the cause for discrepancies and to encourage openness and shared learning by educating both senior radiologists and trainees by avoiding a blame culture. 

              If you only read one full journal article this year then read this one – it is open access so there is no reason not to!  Take time to reflect on it and to really understand how we each fail from time to time (and every one of us does, without exception).  We all need a thorough education in these human factors in advance of Artificial (or Augmented) Intelligence being introduced to our personal practice if we are going to translate the potential benefits of this technology  into improved diagnostic performance for our patients.

               

              Dr. Damian Tolan is a gastrointestinal radiologist from St James’s University Hospital (Leeds, UK) specialising in luminal gastrointestinal imaging with a particular clinical and research interest in colorectal cancer, inflammatory bowel disease and perianal disease. He co-chaired the ‘One case - three lessons’ session at the ESGAR Annual Meetings in 2018 and 2019.

              Comments may be sent to: damian.tolan@remove-this.nhs.net



              Straight-to-test faecal tagging CT colonography for exclusion of colon cancer in symptomatic patients under the English 2-week-wait cancer investigation pathway: a service review.
              J.A. Stephenson, J. Pancholi, C.V. Ivan, J.H. Mullineux, H. Patel, R. Verma, M. Elabassy.
              Clinical Radiology, Volume 73, Issue 9, 2018.

              Dr. Adam Laverty
              Radiology ST4, St James’s University Hospital, Leeds Teaching Hospitals, Leeds, UK.

              Dr. Damian Tolan
              ESGAR Fellow and Clinical Lead for CT and GI/HPB imaging, St James’s University Hospital, Leeds Teaching Hospitals, Leeds, UK.

              The stage of colorectal cancer (CRC) at the time of diagnosis has a major impact on survival. UK NICE guidelines and the English NHS 2 week wait (2WW) pathway aim to improve the prognosis and survival through early diagnosis of CRC. Symptomatic patients in primary care are referred directly for assessment in secondary care or straight to test (STT) colonoscopy via the 2WW pathway. However, this has placed substantial demands upon endoscopy services.

              The University Hospitals of Leicester developed a CT colonography (CTC) radiology based investigation pathway for the detection of CRC in symptomatic patients with those meeting the following criteria being referred for STT:

              • >60 years old

              • Change in bowel habit and/or iron deficient anaemia 

              • World Health Organisation Performance status of 2 or better

              To the publishing authors’ knowledge, this was the first pathway where STT CTC had replaced colonoscopy in such a population. The authors of the article present their experience and prospectively collected data in the first 12 months of using this pathway.

              In total there were 2,072 requests for a 2WW STT CTC from primary care of which 1792 were performed. Only one complication was attributed to CTC related to a single case of perforation secondary to insufflation and only 1.6% of the studies were non-diagnostic.

              In terms of the colonic findings, performance data is comparable to the SIGGAR multicentre randomised controlled trial1 with a CRC detection rate of 4.9% (versus 5.6%) and large polyp (≥10mm) detection rate of 8.3% (versus 5.1%). Suspicious colonic findings including indeterminate thickening and active colitis were seen in 3.9%. All of these patients were referred for subsequent endoscopic evaluation.  A further 29 patients required another colonic test (CTC or colonoscopy) due to a non-diagnostic CTC examination. In total, the rate of additional colonic investigation was 20% (compared to 30% in the SIGGAR trial). In subsequent correspondence to Clinical Radiology the authors have stated that that they now have 24-36 months of follow-up data with no recorded interval (missed) colonic cancers2.

              The additional benefit of CTC compared to colonoscopy is the ability for extra-colonic assessment. Incidental extra-colonic findings were found in 484 (27%) patients; 122 were defined as being incompletely characterised and needing further radiological investigation and 214 defined as a significant or potentially significant incidental findings. Extra-colonic cancer was identified in 4.3% of patients in 20 different locations with renal and gastric carcinoma being most common.

              The article also addresses a number of the perceived issues surrounding the use of CTC. This includes the potential harm associated with ionising radiation and additional costs of further investigation following CTC. However, in this study the calculated harm from radiation doses have been shown to be at levels considered ‘too small to be observed or inexistent” by the Health Physics Society in this group of patients. They have also estimated that the introduction of a CTC led pathway has resulted in local cost-savings of at least £500,000 annually, even when subsequent endoscopic assessment and the further investigation of incidental findings are factored in. In addition, national targets (for referral to test within 14 days) were achieved in 95%, which the authors describe as a significant improvement on the prior colonoscopy led service.  

               

              The main limitation of the study was the relatively short follow-up period, but the subsequent correspondence from the authors showed no interval (missed) cancers between 24-36 months. However, it is reasonable to assume that in a symptomatic population, any missed symptomatic CRC’s would be identified within 2 years from initial presentation.

              The authors should be commended for their work in developing such a substantial service. This study highlights that a CTC led symptomatic service in a single centre can achieve comparable performance data to that of a large multicentre trial like SIGGAR​, while also balancing common arguments against CTC including the perceived radiation risk and additional costs, with the benefit of assessing for extra-colonic pathology. CTC is a viable, cost saving and pragmatic alternative to colonoscopy in this cohort of symptomatic patients at a time when endoscopy services are overwhelmed and cancer related targets are becoming increasingly difficult to achieve.

               

              References:
              1. Atkin, W., Dadswell, E., Wooldrage, K. et al. Computed tomographic colonography versus colonoscopy for investigation of patients with symptoms suggestive of colorectal cancer (SIGGAR): a multicentre randomized trial. Lancet. 2013; 381: 1194–1202

              2. RE: Straight-to-test faecal tagging CT colonography for exclusion of colon cancer in symptomatic patients under the English 2-week-wait cancer investigation pathway: a service review. A reply. Stephenson, J.A. et al. Clinical Radiology, Volume 74, Issue 8, 644

               

              Dr. Adam Laverty is a radiology trainee heading into his fifth and final year on the West Yorkshire radiology training scheme. He is currently based at St. James University Hospital (Leeds/UK) where he is undertaking speciality training in GI/HPB imaging and non-vascular intervention.

              Coments may be sent to: lavertya@remove-this.doctors.org.uk

               



              Diagnostic Accuracy of Whole-Body MRI Versus Standard Imaging Pathways for Metastatic Disease in Newly Diagnosed Colorectal Cancer: the Prospective Streamline C Trial

              Stuart A Taylor, Sue Mallett, Sandy Beare, Gauraang Bhatnagar, Dominic Blunt, Peter Boavida, John Bridgewater, Caroline S Clarke, Marian Duggan, Steve Ellis, Robert Glynne-Jones, Vicky Goh, Ashley M Groves, Ayshea Hameeduddin, Sam M Janes, Edward W Johnston, Dow-Mu Koh, Anne Miles, Stephen Morris, Alison Morton, Neal Navani, John O’Donohue, Alfred Oliver, Anwar R Padhani, Helen Pardoe, Uday Patel, Shonit Punwani, Laura Quinn, Hameed Rafiee, Krystyna Reczko, Andrea G Rockall, Khawaja Shahabuddin, Harbir S Sidhu, Jonathan Teague, Mohamed A Thaha, Matthew Train, Katherine van Ree, Sanjaya Wijeyekoon, Steve Halligan.

              Lancet Gastroenterol Hepatol  2019; 4: 529–37

              Prof. Søren Rafaelsen and Dr. Leo Nygaard – Department of Radiology, Vejle University Hospital, Clinical Cancer Centre,  Institute of Regional Health Research, University of Southern Denmark, Denmark

              This study is an impressive prospective multicentre trial with the aim to clarify and directly compare the diagnostic accuracy and efficiency of WB-MRI-based staging pathways with standard pathways in colorectal cancer. The study patients had both WB-MRI plus all standard staging investigations performed in the period from 2013 to 2016.  WB-MRI included diffusion, T2-weighted, and T1-weighted pre-intravenous and post-intravenous gadolinium contrast imaging with an examination time less than one hour. The radiologists interpreting the standard staging investigations were blinded to the WB-MRI and vice versa for the MRI radiologist. A total of 299 patients had all examinations performed, 23 % of these had synchronous metastases. The sensitivity was 63% for the standard pathway and 67% for WB-MRI. Both methods had high specificity for metastatic disease. The WB-MRI pathway had a similar agreement for T stage compared with the standard pathway. The overall time to complete staging was shorter for WB-MRI and required fewer additional tests. The staging costs were lower for WB-MRI than for standard pathways. The authors also suggest research WB-MRI in the assessment of treatment response and follow-up.

              According to this study WB-MRI seems to be an efficient and safer alternative to multimodality staging pathways that does not compromise the accuracy of the existing method. Other studies with a limited number of patients have previously focused on MRI accuracy of local staging and found a high accuracy using MRI.  Further studies on the accuracy of WB-MRI with focus on both local staging and distant metastases are however needed and development of an optimal protocol for both staging local and distant disease with a reasonable examination time. WB-MRI is already recommended by the International Myeloma Working Group for patients with multiple myeloma and solitary plasmacytoma. The present pioneering multicenter WB-MRI study by Taylor et al. also provides hope for better and faster staging of colon cancer at a time when survival for rectum cancer has surpassed that of colon cancer patients.The main limitation of the study was the relatively short follow-up period, but the subsequent correspondence from the authors showed no interval (missed) cancers between 24-36 months. However, it is reasonable to assume that in a symptomatic population, any missed symptomatic CRC’s would be identified within 2 years from initial presentation.

              The authors should be commended for their work in developing such a substantial service. This study highlights that a CTC led symptomatic service in a single centre can achieve comparable performance data to that of a large multicentre trial like SIGGAR​, while also balancing common arguments against CTC including the perceived radiation risk and additional costs, with the benefit of assessing for extra-colonic pathology. CTC is a viable, cost saving and pragmatic alternative to colonoscopy in this cohort of symptomatic patients at a time when endoscopy services are overwhelmed and cancer related targets are becoming increasingly difficult to achieve.

              References

              1. Taylor SA, Mallett S, Beare S et al.  Diagnostic Accuracy of Whole-Body MRI Versus Standard Imaging Pathways for Metastatic Disease in Newly Diagnosed Colorectal Cancer: the Prospective Streamline C Trial. Lancet Gastroenterol Hepatol  2019; 4: 529–37
              2. Nerad E, Lambregts DM, Kersten EL et al. MRI for Local Staging of Colon Cancer: Can MRI Become the Optimal Staging Modality for Patients With Colon Cancer? Dis Colon Rectum. 2017;60:385-392
              3. Dam C, Lindebjerg J, Jakobsen A et al. Local staging of sigmoid colon cancer using MRI. Acta Radiol Open. 2017;6:2058460117720957
              4. Lai AYT, Riddell A, Barwick T et al. Interobserver agreement of whole-body magnetic resonance imaging is superior to whole-body computed tomography for assessing disease burden in patients with multiple myeloma. Eur Radiol. 2019 Jul 2. doi: 10.1007/s00330-019-06281-x. [Epub ahead of print]

              Dr. Leo Nygaard graduated as a medical doctor from the University of Southern Denmark in January 2016. During his medical studies he authored a paper on biological treatment with Omalizumab for severe allergic asthma and he presented his scientific studies at the Danish Society of Respiratory Medicine’s annual meeting. Leo has previously worked at the Department of Infectious and Respiratory Medicine as well as the Department of Surgery in the region of Southern Denmark. He is particularly interested in abdominal and interventional radiology and is currently working as a second-year radiology resident at the Department of Radiology, Vejle University Hospital, Clinical Cancer Centre, Denmark.

              Comments may be sent to: Leo.Nygaard4@remove-this.rsyd.dk



              Comparison between M-score and LR-M in the reporting system of contrast-enhanced ultrasound LI-RADS

              Li-Da Chen, Si-Min Ruan, Yuan Lin, Jin-Yu Liang, Shun-Li Shen, Hang-Tong Hu, Yang Huang, Wei Li, Zhu Wang, Xiao-Yan Xie, Ming-De Lu, Ming Kuang, Wei Wang

              Eur Radiol (2019) 29: 4249. https://doi.org/10.1007/s00330-018-5927-8

              Dr. Joana Ferreira Pinto, 3rd year Radiologist Resident, Department of Radiology, Oporto Hospital and University Centre, Oporto (Portugal). 
              Prof. Dr. Manuela França, Hospitalar Assistant and Head of Radiology Department, Oporto Hospital and University Centre, Oporto (Portugal).

              The distinction between intra-hepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) in high-risk patient has been a challenge all over the time for identifying HCC in focal liver lesions. Although contrast-enhanced ultrasound (CEUS) showed initial problems for this purpose, it has recently emerged as a promising technique. In 2016, an initial version of CEUS Liver Imaging Reporting and Data System (LI-RADS) was announced by The American College of Radiology (ACR) with the main goal of achieving high specificity for HCC diagnosis in LR-5 lesions, without the need of biopsy. A category of LR-M was also introduced for the inclusion of a group of lesions which were either definitely or probably malignant. Although this categorization has shown a high positive predictive value (PPV) of 98.5% for the detection of HCC [1], some concerns remain about the accuracy in ICC detection.

              Chen LD et al aimed to develop a CEUS M-score that could be used to accurately predict the risk of ICC in high-risk patients and compared it with LR-M in CEUS LI-RADS. Also, they assessed the diagnostic performance of HCC and ICC with the modified CEUS LI-RADS.

              Their retrospective study included 105 high-risk patients with HCC and 105 with ICC selected by propensity score matching between November 2003 and December 2017. The CEUS features evaluated in all patients were the following: the number of the lesions; maximum diameter of the target nodule; shape of the nodule; boundary of the lesion; enhancement level in the arterial/portal/late phase; enhancement patterns of the lesion in the arterial phase; time of enhance onset; washout time; duration of enhancement; tumour supply artery; peripheral circular artery; intratumoural vein; boundary of the intratumoural non-enhanced area; and marked washout.

              Among these, the most useful CEUS independent variables for predicting ICC were poorly circumscribed (69.52%), rim enhancement (63.81%), early washout (92.38%), intratumoural vein (56.19%), obscure boundary of intratumoural non-enhanced area (57.14%) and marked washout (59.05%, all p<0,001). A M-score was developed and supported by the previous listed independent variables, using a method of least absolute shrinkage and selection operator (LASSO) regularized regression for predicting ICC. The M-score was validated and used to develop a modified CEUS LI-RADS in which the typical LR-M category was replaced by the new M-score. This modified CEUS LI-RADS was used for diagnosing lesions as HCC and ICC in comparison to the ACR CEUS LI-RADS using LR-M.

              The M-score had a higher specificity (88.57% vs. 63.81%) with lower sensitivity (89.52% vs. 95.24%) compared with LR-M for detecting ICC. According to Wilson SR et al [2], the majority of LR-M nodules refer to ICC, and in this study the use of M-Score greatly improved specificity in the diagnosis of ICC.

              Another important result in this study was the differentiation in the vascular architecture of both tumours. The HCC showed a singular vascular feature of a peripheral circular artery around the tumour [3], which had a high specificity (97.1%) and could be an additional ancillary feature in CEUS LI-RADS.

              The authors recognized some limitations, such as not including benign lesions or other rare liver cancers for validating the diagnostic accuracy of the CEUS LI-RADS. In particular, the inclusion of combined HCC-ICC should be done in future studies. Moreover, it was a single center study and they did not compare the diagnostic performance of CEUS with other modalities as MRI/CT.

              In conclusion, the authors proposed a CEUS M-score for predicting ICC in high-risk patients, with higher specificity than ACR LI-RADS. Nevertheless, the original intent of the CEUS LI-RADS classification was to achieve high specificity to HCC diagnosis, close to 100%. When using the modified CEUS LI-RADS, the sensitivity for diagnosing HCC is improved, but consequently the specificity is reduced. Therefore, it is important to understand that it should be still regarded as a complementary tool to ACR LI-RADS, which remains the most effective tool for the detection of HCC with high specificity, obviating the need for biopsy. Multicenter and prospective research will be necessary to validate the applicability of the proposed CEUS M-score.

              References

              [1]      E. Terzi et al., “Contrast ultrasound LI-RADS LR-5 identifies hepatocellular carcinoma in cirrhosis in a multicenter restropective study of 1,006 nodules,” J. Hepatol., 2018.

              [2]      S. Wilson, A. Lyshchik, and F. Piscaglia, “CEUS LI-RADS: algorithm, implementation, and key differences from CT/MRI,” Abdom Radiol, vol. 43, pp. 127–142, 2018.

              [3]      C. Dietrich, X. Cui, B. Boozari, M. Hocke, and A. Ignee, “Contrast-Enhanced Ultrasound (CEUS) in the Diagnostic Algorithm of Hepatocellular and Cholangiocellular Carcinoma, Comments on the AASLD Guidelines,” Ultraschall der Medizin - Eur. J. Ultrasound, 2013.

              Dr. Joana Ferreira Pinto is a 3rd year radiology resident at the Centro Hospitalar Universitário do Porto, in Portugal. She completed her undergraduate medical degree at the Instituto de Ciências Biomédicas Abel Salazar in 2015. She is an active member of the ESGAR and regularly attends ESGAR workshops and annual meetings. She also participated in the last Junior ESGAR Summer School in Malta. She has been developing particular interest in diagnostic abdominal radiology, especially in liver imaging.

              Comments may be sent to: joanapintodx@remove-this.gmail.com



              CT radiomics associations with genotype and stromal content in pancreatic ductal adenocarcinoma 

              Authors: Attiyeh MA, Chakraborty J, McIntyre CA, Kappagantula R, Chou Y, Askan G, Seier K, Gonen M, Basturk O, Balachandran VP, Kingham TP, D'Angelica MI, Drebin JA, Jarnagin WR, Allen PJ, Iacobuzio‐Donahue CA, Simpson AL, Do RK.

              Journal: AbdomRadiol (NY). 2019 Jun 26. doi: 10.1007/s00261-019-02112-1. PubMed PMID: 31243486.

              Prof. Andrea Laghi, ESGAR Vice President and Head of the Abdominal Radiology Department, and Dr. Elena Lucertini, ESGAR Member and radiology resident, Department of Radiological, Oncological and Pathological Sciences University of Rome "Sapienza" Radiology Unit - Sant'Andrea University Hospital, (Rome, Italy).
              Dr. Riccardo Ferrari, ESGAR Education Committee Member, working in the Department of Emergency Radiology at San Camillo–Forlanini Hospital (Rome, Italy).

              The paper correlates texture analysis of CT exams of the pancreas with the genomic and histological type of pancreatic cancers with promising results in differentiating histological type and stromal content; that information affects the patients' prognosis and treatment.

              Pancreatic cancer is the 11th most common cancer in the world, and it is one of the most common causes of cancer-related death [1]. In particular, pancreatic ductal adenocarcinoma (PDAC) is the most common primary pancreatic malignancy [2]. At the time of the diagnosis, less than 20% of patients affected by PDAC are surgical candidates and many of the patients who undergo surgery, develop local recurrence [3]. Some studies have demonstrated a relationship between gene mutations in PDAC (the most common of which are in KRAS, TP53, CDKN2A and SMAD4) and the prognosis after treatment [4, 5]. Early and non-invasively gene mutations identification in PDAC could be useful as a predicting factor of response to therapy and, furthermore, to eventually develop targeted immunotherapies [6].

              Radiomic tools applied to pancreatic adenocarcinoma have been already evaluated in the literature to predict survival rate [7, 8]; furthermore, radiogenomics has been applied to evaluate the alternative lengthening of telomeres phenotype in pancreatic neuroendocrine tumours [9]. Attiyeh and colleagues' study exposed in this paper the use of radiomic to identify gene mutations in PDAC. Moreover, they used radiomic features also to predict the quantity of stromal component of the tumour, having a potential role in adapting treatment modalities to the amount of stromal component [10].

              The study retrospectively analysed preoperative CT scans of 35 patients affected by PDAC who underwent surgical tumour resection. Immunohistochemistry staining for TP53, CDK2NA and SMAD4 and a targeted sequencing of DNA were performed on resected tumour specimens, percentages of the stromal component were evaluated in a semiquantitative manner. KRAS and CDK2NA alterations were not included in the analysis because of their high frequency (approximately 90%). An alteration in SMAD4 was observed in 16/35 patients (46%), and altered expression of TP53 was found in 29/35 patients (83%).

              A contrast-enhanced CT examination of the pancreatic tumour was obtained, and the tumour images were manually segmented in the portal venous phase. 255 radiomic features were extracted from the segmented volume, averaging features extracted from each axial slice, using gray-level co-occurrence matrices (GLCM), run-length matrices (RLM), local binary patterns (LBP), fractal dimension (FD), intensity histogram (IH) and angle co-occurrence matrices (ACM).

              Discriminatory features were investigated for four variables: SMAD4 status (normal vs abnormal), TP53 status [wildtype (WT) vs gain of function (GOF) vs loss of function (LOF)], number of genes altered (less than or equal to and greater than 4, which resulted to be the median number of mutations in analysed patients) and quantity of stromal content.

              For SMAD4 and TP53 alterations, discriminatory radiomic features were selected by using fuzzy minimum-redundancy-maximum-relevance (fMRMR) and Kruskal-Wallis test respectively and in both case a multidimensional scaling (MDS) plot with the selected features (a total of 28 for SMAD4 and 32 for TP53) was created, demonstrating a good capacity in discriminating normal SMAD4 vs abnormal SMAD4 and GOF and LOF of TP53, while a not clear power was observed in distinguishing WT from abnormal TP53 status.

              fMRMR was used to identify 14 significant radiomic features able to differentiate tumours with ≤ 4 from> 4 altered genes, and MDS plot showed a good discriminating power of selected features in this case too.

              Lastly, radiomic features are capable of assessing stromal content of PDAC by mean of univariate analysis, obtaining a total of 14 features; that features underwent further multivariate analysis obtaining a continuous prediction model with an R2value of 0.731, demonstrating a solid correlation between selected radiomic features and the quantity of stromal component of PDAC.

              The weak point of the study is the small sample size and the possible technical variance due to the different CT protocols; that limits are common to all literature about radiomic.

              In conclusion, this study, despite the limits demonstrates that radiomic features can predict SMAD4 and TP53 alterations in PDAC and the tumour stromal content; these results allow not only to predict response to therapy and survival but also to develop specific targeted therapy.


              REFERENCES

              1. Ilic, M. and I. Ilic, Epidemiology of pancreatic cancer. World J Gastroenterol, 2016. 22(44): p. 9694-9705.

              2. Becker, A.E., et al., Pancreatic ductal adenocarcinoma: risk factors, screening, and early detection. World J Gastroenterol, 2014. 20(32): p. 11182-98.

              3. Bilimoria, K.Y., et al., Validation of the 6th edition AJCC Pancreatic Cancer Staging System: report from the National Cancer Database. Cancer, 2007. 110(4): p. 738-44.

              4. Singh, P., R. Srinivasan, and J.D. Wig, SMAD4 genetic alterations predict a worse prognosis in patients with pancreatic ductal adenocarcinoma. Pancreas, 2012. 41(4): p. 541-6.

              5. Xu, J.Z., et al., The Loss of SMAD4/DPC4 Expression Associated with a Strongly Activated Hedgehog Signaling Pathway Predicts Poor Prognosis in Resected Pancreatic Cancer. J Cancer, 2019. 10(17): p. 4123-4131.

              6. Knudsen, E.S., et al., Stratification of Pancreatic Ductal Adenocarcinoma: Combinatorial Genetic, Stromal, and Immunologic Markers. Clin Cancer Res, 2017. 23(15): p. 4429-4440.

              7. Eilaghi, A., et al., CT texture features are associated with overall survival in pancreatic ductal adenocarcinoma - a quantitative analysis. BMC Med Imaging, 2017. 17(1): p. 38.

              8. Sandrasegaran, K., et al., CT texture analysis of pancreatic cancer. Eur Radiol, 2019. 29(3): p. 1067-1073.

              9. McGovern, J.M., et al., CT Radiogenomic Characterization of the Alternative Lengthening of Telomeres Phenotype in Pancreatic Neuroendocrine Tumors. AJR Am J Roentgenol, 2018. 211(5): p. 1020-1025.

              10. Neesse, A., et al., Stromal biology and therapy in pancreatic cancer: a changing paradigm. Gut, 2015. 64(9): p. 1476-84.

               

              Dr. Elena Lucertini is a radiology resident at the University of Rome "Sapienza" - Sant'Andrea University Hospital in Rome, attending the second year of residency. Her main field of interest is abdominal radiology, in particular pancreas. She already worked in this area during the residency, and in the coming year, she will attend a fellowship at the Karolinska Institutet in Stockholm to more improve her skills in pancreatic radiology.

              Comments may be sent to elena.lucertini@remove-this.gmail.com



              Pancreaticobiliary involvement in treated type 1 autoimmune pancreatitis: Imaging pattern and risk factors for disease relapse.

              Liang Zhua, Hua-dan Xuea, Wen Zhangb, Qiang Wangc, Bei Tanc, Ya-min Laic, Wei-yang Zhengc, Patrick Asbachd, Bernd Hammd, Timm Deneckee, Zheng-yu Jina.
              Eur Radiol. 2019 Nov. doi: 10.1016/j.ejrad.2019.108673

              Dr. Veronica Aquilina, Higher Specialist Trainee, Mater Dei Hospital, Msida/MT
              Dr. Kelvin Cortis, Consultant Radiologist, Mater Dei Hospital, Msida/MT

              Automimmune pancreatitis (AIP), a distinct form of chronic pancreatitis first described in 1995 by Yoshika et al., comprises two clinical entities which differ both clinically and histologically. Type 1 AIP is the pancreatic manifestation of IgG4-related systemic disease which responds favorably to corticosteroid therapy [1,2]. On the other hand, the high relapse rates with which it is associated may pose a diagnostic challenge not only because of different imaging characteristics to the original lesions but also because recurrence may mimic other pathologies such as pancreatic cancer and cholangiocarcinoma.

              The aim of the study carried out by Zhua et al. was to investigate the imaging characteristics, incidence and etiology of pancreaticobiliary lesions identified on follow-up imaging in patients who had previously received steroid therapy for type 1 AIP. A total of 103 patients diagnosed with type 1 AIP, treated with steroids and who underwent regular clinical and radiological follow-ups, were included prospectively in the study.

              The key results showed a high relapse rate of 42.7% with a median time interval of 17 months from the initial diagnosis. Median follow-up time was of 38 months. The majority developed on discontinuation of steroids (63.6%) whilst the rest developed on either maintenance therapy or during weaning. All lesions responded partially or completely to corticosteroid therapy and none of these were proven to be a pancreatic tumor or cholangiocarcinoma.

              Whilst 34.1% were asymptomatic, the majority of patients presented with symptoms including painless jaundice, abdominal pain and weight loss.  In terms of imaging patterns, pancreatic involvement was noted to be less frequent at relapse (81% as opposed to all patients at initial diagnosis) whilst bile duct involvement was common both at initial diagnosis and recurrence (81.8% vs 72.7%). 11.4% developed lesions in new organs whilst 88.6% developed in the same organ as on initial presentation.

              Most patients (34.1%) relapsed in pancreaticobiliary segments previously involved whilst the remaining developed in new segments. Whilst diffuse pancreatic swelling was more common on initial presentation, the majority of recurrences (66.7%) presented as focal lesions on a background of pancreatic atrophy. Multifocal strictures involving both the distal and proximal bile ducts was the commonest manifestation of disease both at initial presentation and at relapse. Solitary bile duct strictures on the other hand were commoner amongst the relapsed cohort. The severity of bile duct thickening was also worse at relapse.  

              Risk factors that could predict recurrence included male sex, higher serum IgG4 level and extrapancreatic bile duct involvement on initial presentation, and a lower response ratio of serum IgG4 at the induction phase were commoner in the relapsed group. 

              The authors highlighted a number of limitations of the study including that this was a single center study, that the length of follow up and the cohort size were insufficient to assess the risk factors and imaging characteristics of pancreaticobiliary malignancy in AIP patients, that it did not address the risk of relapse of different therapy options and that comparative measurements of bile duct thickness at initial presentation and relapse may not be accurate as these may involve different locations.

              In conclusion, pancreaticobiliary lesions in patients with previously treated type 1 AIP are common. Although the imaging characteristics may differ from the original lesions these usually represent disease recurrence rather than malignancy. Factors which confer a higher risk of relapse are namely extra-pancreatic bile duct involvement and poorer lower response ratio of serum IgG4 serum response at the induction phase.

              REFERENCES

              1. Xiang, P., Zhang, X., Wang, C. et al. Pancreatic tumor in type 1 autoimmune pancreatitis: a diagnostic challenge. BMC Cancer 19, 814 (2019) doi:10.1186/s12885-019-6027-0.
                 
              2. Vlachou, P., Khalili, K., Jang, H., Fischer, S., Hirschfield, G., Kim, T. IgG4-related Sclerosing Disease: Autoimmune Pancreatitis and Extrapancreatic Manifestations. RadioGraphics 31:1379–1402 (2011) doi:10.1148/rg.315105735.

               

              Dr. Veronica Aquilina is a fourth-year radiology resident at Mater Dei Hospital, Malta. She completed her undergraduate medical degree at the University of Malta in 2010 and has just been admitted as a fellow of the Royal College of Radiologists (RCR), UK. Veronica has a broad range of interests in diagnostic imaging and plans to subspecialized in cardiothoracic imaging.

              Comments are to be sent directly to Dr. Cortis or Dr. Aquilina.

               



              CT and MR imaging of chemotherapy-induced hepatopathy.

              Authors: Vernuccio F, Dioguardi Burgio M, Barbiera F, Cusmà S, Badalamenti G, Midiri M, Vilgrain V, Brancatelli G.
              Journal: Abdom Radiology (NY) 2019 Oct;44(10):3312-3324
              doi: 10. 1007/s00261-019-02193-y.

              Chemotherapy-induced hepatopathy results in a wide spectrum of parenchymal and vascular hepatic changes, which subsequently may either hide or mimic liver metastases on imaging. Both situations of false negative and false positive imaging diagnosis of liver metastases in oncologic patients have great clinical implications resulting in correct management strategies. Knowledge of the imaging patterns of chemotherapy induced hepatopathies is crucial in order to avoid diagnostic errors and overcome diagnostic challenges that Radiologists may face.

              In this comprehensive review article, the authors explore the broad spectrum of chemotherapy-induced liver hepatopathy on CT and MR imaging. In addition, they emphasize the role of imaging in early recognition of certain chemotherapy- induced hepatopathies that are related to poor patient outcome and increased post-operative risk.

              Chemotherapy-induced hepatopathies, are categorized as diffuse, mainly including liver steatosis, steatohepatitis, pseudocirrhosis and sinusoidal obstruction and focal hepatopathies. The mechanism of hepatic changes induced by chemotherapy is very well explained and imaging patterns on CT and MRI are reviewed with specific or less specific-indirect findings. Strengths and weaknesses of imaging on each modality are discussed and the beneficial role of MRI with the use of hepatobiliary agents is highlighted throughout the article in both diffuse and focal hepatopathies induced by chemotherapy.

              In terms of chemotherapy-induced diffuse hepatopathy, chronic hepatocellular injury results in pseudocirrhosis, exhibiting CT and MR features similar to those of cirrhosis. Early recognition of pseudocirrhosis and portal hypertension on imaging is important, as they are related to poor patient outcome and so chemotherapy may be either discontinued or altered (1).

              In chemotherapy induced liver steatosis, mainly due to irrinotecan, a main consideration is depiction of liver metastases in background fatty changes. This may be problematic on CT, however MRI, especially with the use of hepatobiliary agents, appears to be a problem-solving tool (2).

              Pre-operative chemotherapy-induced steatohepatitis is a serious complication that should be specifically addressed and identified on imaging, as it clearly relates to increased post-operative morbidity and mortality (3). While quantification of fatty infiltration may be accurately provided on MR by calculating proton density fat fraction (PDFF), quantifying hepatic inflammation at present, is a weak point of imaging. Promising MRI advances however are discussed, though validation is still missing.

              In chemotherapy-induced sinusoidal changes, sinusoidal obstruction syndrome-SOS being the most common, the authors emphasize the role of imaging in early detection, especially in colon cancer patients receiving pre-operative oxaliplatin-based chemotherapy. Clinical importance of identifying hepatic SOS on imaging is huge, considering that this potentially life-threatening syndrome is associated with major postoperative morbidity, reduced functional liver remnant and increased complication rate after major hepatectomy (4).

              Imaging patterns of SOS are reviewed, including indirect signs due to reduced liver outflow and portal hypertension, enhancement abnormalities on contrast enhanced imaging and specific findings on Gadoxetic acid MRI, which is a sensitive and highly specific tool for diagnosing this life-threatening condition (5,6).

              Chemotherapy-induced focal hepatopathies, is a relatively new challenge for Radiologists, that may result in false positive findings of liver metastases and subsequent unnecessary biopsies.

              Post chemotherapy nodular hyperplasia, multiacinar regenerative nodules-FNH-like lesions in specific, hepatic peliosis and less frequently SOS presenting as focal hepatopathy, may be misdiagnosed as liver metastases. MR imaging with the use of hepatobiliary agents and diffusion-weighted imaging is very helpful in correct lesion characterization, thus preventing misdiagnosis (7,8). Liver biopsy, as suggested by the authors, is indicated for the characterization of atypical focal lesions only, such as atypical FNH-like lesions and peliosis as well as for grading suspected SOS when major hepatectomy is planned.

              Weaknesses of imaging in chemotherapy-induced hepatopathy mainly include acute hepatocellular injury, due to non-specific imaging findings, post-chemotherapy monoacinar regenerative nodules, which are too small to characterize on imaging and precise quantification of steatohepatitis.

              Overall, this review article in a very educational and comprehensive manner focuses on diagnostic challenges that arise in oncologic patients due to chemotherapy-induced hepatopathies. These challenges have important clinical implications as they may lead to incorrect management strategies and affect clinical or surgical decisions. Thorough knowledge of imaging patterns of chemotherapy-induced hepatopathy is crucial in order to avoid diagnostic errors and to obtain a clear clinical picture.

               

              References:

              1. Adike A, Karlin N, Menias C, Carey EJ (2016) Pseudocirrhosis: A Case Series and Literature Review. Case Rep Gastroenterol 10:381-39
              2. Berger-Kulemann V, Schima W, Baroud S, et al (2012) Gadoxetic acid-enhanced 3.0 T MT imaging versus multidetector-row CT in the detection of colorectal metastases in fatty liver using intraoperative ultrasound and histopathology as a standard of reference. Eur J Surg Oncol 38:670-676.
              3. Zhao J, van Mierlo KMC, Gómez-Ramírez J, et al (2017) Systematic review of the influence of chemotherapy-associated liver injury on outcome after partial hepatectomy for colorectal liver metastases. Br J Surg 104:990-1002.
              4. Nakano H, Oussoultzoglou E, Rosso E, et al (2008) Sinusoidal injury increases morbidity after major hepatectomy in patients with colorectal liver metastases receiving preoperative chemotherapy. Ann Sur 247:118-12
              5. Brancatelli G, Furlan A, Calandra A, Dioguardi Burgio M (2018) Hepatic sinusoidal dilatation. Abdom Radiol (NY) 43:2011-2022.
              6. Shin NY, Kim MJ, Lim JS, et al (2012) Accuracy of gadoxetic acid-enhanced magnetic resonance imaging for the diagnosis of sinusoidal obstruction syndrome in patients with chemotherapy-treated colorectal liver metastases. Eur Radiol 22:864-871.
              7. Han NY, Perk BJ, Sung DJ, et al (2014) Chemotherapy-induced focal hepatopathy in patients with gastrointestinal malignancy: gadoxetic acid-enhanced and diffusion-weighted MR imaging with clinical-pathologic correlation. Radiology 271:416-425.
              8. Yoneda N, Matsui O, Kitao A, et al (2016) Benign Hepatocellular Nodules: Hepatobiliary Phase of Gadoxetic Acid-enhanced MR Imaging Based on Molecular Background. Radiographics 36:2010-2027.

               

              Dr Kyriaki Tavernaraki is a Consultant Radiologist in Imaging and Interventional Radiology Department, “Sotiria” Hospital, Athens, Greece. She completed her subspecialty training in Upper GI and Hepatobiliary and Pancreas Imaging at the Royal Free Hospital and University College London Hospital (UCLH), NHS, London, UK. She is a PhD and MSc degree holder. She is also an ESGAR member since 2015.

              Comments may be sent to sandytavernaraki@remove-this.hotmail.com




              Non-invasive measurement of liver iron concentration using 3-Tesla magnetic resonance imaging: validation against biopsy
              Gaspard d’Assignies, Anita Paisant, Edouard Bardou-Jacquet, Anne Boulic, Elise Bannier, Fabrice Lainé, Martine Ropert, Jeff Morcet, Hervé Saint-Jalmes, Yves Gandon.
              Eur Radiol. 2017 Nov 24. doi: 10.1007/s00330-017-5106-3.

              Dr. Lara Sammut, Higher Specialist Trainee, Mater Dei Hospital, Msida/MT
              Dr. Kelvin Cortis, Consultant Radiologist, Mater Dei Hospital, Msida/MT

              Liver iron overload is the histological hallmark of hereditary hemochromatosis, transfusional hemosiderosis, as well as certain acquired liver diseases such as non-alcoholic steatohepatitis (NASH) and dysmetabolic iron overload syndrome (DIOS).  Excess accumulation of iron in the liver is toxic, and can lead to complications such as cirrhosis and hepatocellular carcinoma. The liver iron content (LIC) (mg Fe/g dry tissue) correlates strongly with total body iron, thus LIC can be used as a surrogate biomarker of body iron stores [1,2].
              MRI and genetic testing has drastically reduced the need for iron quantification through liver biopsy [3], which is both invasive and prone to sampling bias.  The two main LIC MRI quantification methods are the signal- intensity- ratio (SIR) and the relaxometry (R2*) method.  The SIR method has certain drawbacks, including failure to account for fat effects and tendency to overestimate LIC.  This is not the case for the R2* method, which is based on the calculation of T2/R2 or T2*/R2* from signal decay at various echo times.
              The aim of the study carried out by d’Assignies et al. was to evaluate the ability of the R2* method at 3T field strength to detect and quantify liver iron, using liver biopsy with biochemical LIC results as a reference method. The authors also compared both SIR and R2* methods at the 3T field strength.
              A total of 105 patients who underwent a liver biopsy with estimation of biochemical LIC (LICb) were included prospectively in this study. The LICb concentration ranged from 0 to 630 μmol/g, and 49 patients (47%) had normal LICb values (less than 36 μmol/g). 56 patients had liver iron overload, this was due to genetic haemochromatosis in 31 patients, dysmetabolic syndrome in 22 patients and to other causes (alcoholic or viral hepatitis) in 3 patients.
              All of the patients underwent a breath-hold 3T multiple-echo gradient-echo sequence (mGRE) using a body coil and the LIC was calculated using both the SIR (LICSIR) and the R2* (LICR2*) algorithm respectively. Results were correlated with LICb from liver biopsies.
              Results showed a strong positive correlation between LICb with both LICR2* (r = 0.95, p < 0.001) and LICSIR (r = 0.92, p < 0.001) methods.
              In comparison to LICb, LICR2* and LICSIR were found to detect liver iron overload with a sensitivity/specificity of 96%/93% and 92%/95% respectively.  LICR2* presented the lowest differences for patients with LICb values under 130 μmol/g. Above this value, LICSIR was found to have the lowest differences. The authors thus suggest using relaxometry for iron overload below 130 μmol/g and SIR for values above 130 μmol/g because of its better correlation with LIC.

              The authors state that the R2* calculation is well-established at 1.5T, however no such validation with biopsies has been done before with at 3T, making the study highly practical since a significant proportion of new MRI scanners use a 3T field strength.
              Dedicated DICOM freeware and detailed sequence parameters for scanners from different manufacturers are available on their website www.mrquantif.org.  This software uses both methods jointly and selects the best one, and outputs reports and curves that can be imported in the hospital PACS system.


              References
              1. Hernando D, Levin YS, Sirlin CB, Reeder SB. Quantification of Liver Iron with MRI: State of the Art and Remaining Challenges. J Magn Reson Imaging 2014; 40(5): 1003–1021.
              2. Blachier M, Leleu H, Peck-Radosavljevic M et al. The burden of liver disease in Europe: a review of available epidemiological data. J Hepatol 2013; 58:593–608
              3. Brissot PTroadec MBBardou-Jacquet E et al. Current approach to hemochromatosis. Blood Rev. 2008;22(4):195-210.


              Dr. Lara Sammut is a fourth-year radiology resident at Mater Dei Hospital, Malta. An active member of ESGAR, she regularly attends workshops organized by the society as well as had the opportunity to present scientific studies at the society’s annual meetings, amongst others. She completed her undergraduate medical degree at the University of Malta in 2011. Her main interests are breast and diagnostic abdominal radiology. She aspires to take part in research studies abroad in the near future.
              Comments are to be sent directly to Dr. Cortis or Dr. Sammut


              Long-term Risk of Pancreatic Malignancy in Patients With Branch Duct Intraductal Papillary Mucinous Neoplasm in a Referral Center
              Ilaria Pergolini, Klaus Sahora, Cristina R. Ferrone, Vicente Morales-Oyarvide, Brian M. Wolpin, Lorelei A. Mucci, William R. Brugge, Mari Mino-Kenudson, Manuel Patino, Dushyant V. Sahani, Andrew L. Warshaw, Keith D. Lillemoe, and Carlos Fernández-del Castillo.
              Gastroenterology 2017;153:1284-1294.

              Dr. Clarisse Dromain and Dr. Rafael Duran – Centre Hospitalier Universitaire Vaudois (CHUV), Department of Radiodiagnostic and Interventional Radiology, Lausanne, Switzerland.


              Intraductal papillary mucinous neoplasm (IPMN) can be classified into three types: branch duct IPMN (BD-IPMN), main duct IPMN and mixed type. Because of their increased likelihood to develop malignancy and/or symptoms, main duct and mixed-type IPMNs more often undergo surgical therapy (1). The management of BD-IPMN is more challenging and long-term outcomes are uncertain with limited knowledge of the natural evolution and malignancy potential of pancreatic cysts beyond 5 years (2).

              In the study by Pergolini et al, long-term outcomes of a large cohort of patients undergoing primary surveillance for BD-IPMN were evaluated to determine the risk of pancreatic cancer development after 5 years of follow-up (2). In addition, the authors sought to identify whether any subset of low-risk BD-IPMNs can safely forego surveillance after 5 years of follow-up.

              This is a retrospective study in which consecutive patients with a clinical diagnosis of BD-IPMN followed and treated at the Massachusetts General Hospital with a minimum of 6 months of follow-up were included. Patients had at least one cross-sectional imaging (CT, MRI and/or endoscopic ultrasound) done 3 months or longer after the initial diagnosis. Diagnosis of BD-IPMN was based on the presence of unilocular or multilocular cysts of the pancreas and a non-dilated main pancreatic duct (MPD) (<5 mm). All patients with a dilation of the MPD > 5 mm or with cysts suspicious for another diagnosis rather than BD-IPMN (e.g., serous cystadenoma, mucinous cystic neoplasm, pseudocyst) or prior diagnosis of pancreatic cancer were excluded. Imaging and medical charts were reviewed. Patients were classified at the initial diagnosis as having “suspected BD-IPMN” when communication between the cyst and the MPD was documented or when cysts were multifocal or had a cyst fluid carcinoembryonic antigen >192 ng/mL. All remaining cysts were classified as “presumed BD-IPMN” (3). Charts of patients were reviewed for high-risk stigmata (HRS) and worrisome features (WFs). HRS were defined by the presence of obstructive jaundice in a patient with cystic lesion of the head of the pancreas, MPD 10 mm, enhancing solid component within the cyst, or cytology positive for high-grade dysplasia or adenocarcinoma. WFs were acute pancreatitis, cyst size 3 cm, thickened/enhancing cyst walls, non-enhancing mural nodules, MPD size of 5-9 mm, abrupt change in caliber of the MPD and lymphadenopathy (1).

              577 patients with suspected or presumed BD-IPMN were included. Median follow-up for the entire cohort was 82 months (range, 6-329 months). 363 patients (63%) underwent surveillance for > 5 years, and 121 (21%) were followed for > 10 years. At diagnosis, a majority of the patients were asymptomatic (n=479, 83%) and of these, 48 (10%) developed symptoms during follow-up. Median cyst size at diagnosis was 14 mm (range 2-54 mm) and 53 patients (9%) had a cyst 3 cm. During follow-up, an additional 76 patients developed a lesion >3cm and the median cyst diameter had increased to 20 mm (range, 3-90 mm). At the end of the observational period, 319 patients (55%) had increased cyst size; median increase was 0.9 mm per year of follow-up. Patients who developed malignancy had a significantly larger cyst size at diagnosis compared with those without malignant transformation (19 vs. 14 mm; P =.047), as well as a greater maximum diameter during follow-up (32 vs. 19 mm; P < .001).

              Overall, 7.8% of the entire patient population (45/577) developed pancreatic malignancy during the study period; in 36 patients malignancy arose within the pancreatic cyst and 9 patients malignancy arose away from the cyst (distinct or concomitant pancreatic cancer). When looking at the risk of malignancy within 5 years of follow-up, 4.3% (25/577) of the patients developed pancreatic malignancy.

              Of the 363 patients followed for > 5 years, malignancy occurred in 5.5% (20/363) and was still present (4.1%) after 10 year follow-up. 22% of patients who were followed for > 5 years had either WFs or HRS by the 5-year time point, and 10% of them developed pancreatic malignancy subsequently. Importantly, the absence of WFs or HRS at a 5-year time point did not exclude the development of malignancy and these patients (n=282) had an 18.8 times higher age-standardized incidence rate of pancreatic malignancy than expected in the general population.

              In the analysis, a subgroup of cysts appeared to have a significantly lower risk of development of malignancy. Among the 363 patients followed for > 5 years, 108 (30%) had a cyst that was 1.5 cm in size, and only 1 patient in this group (0.9%) developed malignancy. In contrast, 19 patients (7.5%) with cysts >1.5 cm developed malignancy (P=.01). The 1.5-cm cutoff showed a negative predictive value for malignancy of 99% and a sensitivity of 95%.

              BD-IPMN is increasingly diagnosed on imaging. The main challenge is to identify which of these BD-IPMNs are susceptible to malignant transformation to define adequate surveillance programs. The overall risk of malignancy in the present study, almost 8%, lasted for 10 years or more for patients with BD-IPMNs. Although it is important to stress that this study cohort, composed of selected patients referred to surgeons and gastroenterologists, may not be representative of the population of incidentally discovered cysts, presented results support continued surveillance after 5 years from the initial diagnosis. This information is relevant because recently published American Gastroenterological Association guidelines recommend stopping surveillance after 5 years (4) while the International Consensus Guidelines 2012 provides recommendations regarding indications for surgical resection and frequency of follow-up on patients managed non-operatively, but does not give an end point to surveillance (1). Pancreatic cysts that remain 1.5 cm for more than 5 years might be considered low-risk for progression to malignancy.


              References

              1. Tanaka M, Fernandez-del Castillo C, Adsay V, Chari S, Falconi M, Jang JY, et al. International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas. Pancreatology : official journal of the International Association of Pancreatology. 2012;12(3):183-97.

              2. Pergolini I, Sahora K, Ferrone CR, Morales-Oyarvide V, Wolpin BM, Mucci LA, et al. Long-term Risk of Pancreatic Malignancy in Patients With Branch Duct Intraductal Papillary Mucinous Neoplasm in a Referral Center. Gastroenterology. 2017;153(5):1284-94 e1.

              3. Mukewar S, de Pretis N, Aryal-Khanal A, Ahmed N, Sah R, Enders F, et al. Fukuoka criteria accurately predict risk for adverse outcomes during follow-up of pancreatic cysts presumed to be intraductal papillary mucinous neoplasms. Gut. 2017;66(10):1811-7.

              4. Vege SS, Ziring B, Jain R, Moayyedi P, Clinical Guidelines C, American Gastroenterology A. American gastroenterological association institute guideline on the diagnosis and management of asymptomatic neoplastic pancreatic cysts. Gastroenterology. 2015;148(4):819-22; quize12-3.


              Rafael Duran is a junior attending in Radiology specialized in Interventional Radiology, more specifically Interventional Oncology. Dr. Duran works on the development of novel tumor response criteria and imaging biomarkers following locoregional therapies and novel drugs such as agents targeting tumor metabolism or hypoxia. His current main research focuses on liver cancer molecular biology and immnuo-oncology in the setting of image-guided locoregional therapies.

              Comments may be sent to Dr. Rafael Duran.


              MR imaging of rectal cancer: Radiomics Analysis to Assess Treatment Response after Neoadjuvant Therapy.
              Natally Horvat, Harini Veeraraghavan, Monika Khan, Ivana Blazic, Junting Zheng,Marinela Capanu, Evis Sala, Julio Garcia-Aguilar, Marc J. Gollub, Iva Petkovska. Radiology 2018: https://doi.org/10.1148/radiol.2018172300

              Dr. Carole Allimant – Centre Hospitalier Universitaire de Montpellier, Department of Radiodiagnostic and Interventional Radiology, Montpellier, France
              Dr. Clarisse Dromain – Centre Hospitalier Universitaire Vaudois (CHUV), Department of Radiodiagnostic and Interventional Radiology, Lausanne, Switzerland.

              The standard treatment for patients with MR imaging–staged locally advanced rectal cancer (LARC) is neoadjuvant chemotherapy–radiation therapy (CRT) followed by total mesorectal excision. After neoadjuvant CRT, approximately 50% to 60% of patients are downstaged and 15% to 27% show pathologic complete response (pCR)(1).

              Selected patients with cCR can be safely treated with CRT (2). However a nonsurgical “watch-and-wait” strategy is not currently supported by the National Comprehensive Cancer Network guidelines (3) and there is an increasing need for evaluation of tumor response.

              Radiomics analysis involves computer-based extraction of a large number of quantitative features representing voxel heterogeneity(5) that appears to be an interesting emergent tool for predicting response after CRT (6–8).

              This is a retrospective study of patients with LARC who underwent neoadjuvant-CRT followed by surgery at Memorial Sloan Kettering Cancer Center from March 2012 to February 2016. Rectal MR imaging was performed less than 3 months before surgery. Among others, mucinous tumor, recurrent rectal cancer and poor image quality MRI were excluded.

              Their final study population consisted of 114 patients. The minimum sequence required was high-spatial-resolution axial oblique T2WI perpendicular to the long axis of the tumor and/or area after treatment, with section thickness of 3 mm. DWI (section thickness of 5mm, 0/800 b-values) was available in only 106 patients.

              Two radiologists (5 years and 9 years of experience) reviewed T2WI and DWI, blinded to endoscopic and histopathologic results, to classify the area after treatment as either cCR or cPR in consensus. They had the primary staging MR images at their disposal to guide the delimitation of the tumor bed. For combined assessment, the patient was classified as cCR when cCR was obtained on both T2 or DW images. When combined imaging features at T2WI and DWI were used to diagnose cCR, high sensitivity (84%) and NPV (94%) were achieved; however, it resulted in low specificity (56%) and PPV (30%).

              One of the radiologists manually segmented the entire area after treatment, excluding equivocal normal rectal wall and mucosal edema on the T2WI image to provide the volume of interest for texture analysis. Thirty-four texture features consisting of first order (mean, standard deviation, kurtosis, and skewness), second-order Haralick (9) (energy, entropy, correlation, contrast, and homogeneity), Gabor edges at four different orientations and bandwidth (g = 1.4), and second-order texture measures on the Gabor edges were computed.

              They used Random Forests (RF) classifier(10) which is a complex model of multiple decision tree–based classifiers of those features. At the end they computed the relative importance of each feature by using the Gini index (10). Second-order texture measures of energy, homogeneity, and contrast were among features that resulted in the largest decrease in the Gini index ie that resulted in the least misclassification (cCR vs pCR). Patients with pCR had significantly higher energy, higher homogeneity, and lower contrast compared with patients with pPR. This indicates that tumors with a homogenous appearance were associated with pCR.

              Fourteen of the 34 features were significantly different between pCR and pPR.  Their best RF classifier produced high diagnostic performance with an area under the curve of 93% (95%CI: 0.87-0.97) for differentiating pCR from pPR, with a sensitivity of 100% (95% CI: 0.84, 1), specificity of 91% (95%CI: 0.84-0.96), PPV of 72% (95%CI:0.53-0.87),and NPV of 100% (95%CI: 0.96-1).

              When compared with the assessment of both T2WI and DWI, radiomics had significantly higher specificity and PPV; however, sensitivity and NPV were not statistically different.

              This is an interesting preliminary study showing that radiomic measures can offer better classification performance compared with the qualitative assessment for diagnosing pCR.

              They postulate that small clusters of residual tumor cells within the residual area after treatment in pPR may explain the difference in texture in pCR and pPR; however, additional studies with direct correlation to whole-specimen histopathologic analysis are necessary to investigate this further.

              Sixty-two (55%) patients were imaged with 1.5-T units, whereas the remaining 52 (45%) were imaged with 3.0-T units. Most computed texture measures showed no significant difference by magnet strength. This was an important finding given the large number of MR imagers available in the market to allow the widespread use of these new imaging techniques.

              Although promising and because radiomics classification follows data augmentation it could potentially lead to overoptimistic results, these results require validation on a larger and independent data set to assess the potential for clinical translation.

              Moreover, manual segmentation of volume of interest is a time-consuming process; therefore, it is important to develop a user-friendly tool to encourage the use of radiomic measures in daily clinical practice.


              References

              1. van de Velde CJH, Boelens PG, Borras JM, Coebergh J-W, Cervantes A, Blomqvist L, et al. EURECCA colorectal: multidisciplinary management: European consensus conference colon & rectum. Eur J Cancer Oxf Engl 1990. 2014 Jan;50(1):1.e1-1.e34.

              2. Renehan AG, Malcomson L, Emsley R, Gollins S, Maw A, Myint AS, et al. Watch-and-wait approach versus surgical resection after chemoradiotherapy for patients with rectal cancer (the OnCoRe project): a propensity-score matched cohort analysis. Lancet Oncol. 2016 Feb;17(2):174–83.

              3. NCCN Guidelines. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Rectal Cancer version [Internet]. 2017 [cited 2018 Mar 18]. Available from: www.nccn.org/pro- fessionals/physician_gls/pdf/rectal.pdf

              4. Patel UB, Brown G, Rutten H, West N, Sebag-Montefiore D, Glynne-Jones R, et al. Comparison of magnetic resonance imaging and histopathological response to chemoradiotherapy in locally advanced rectal cancer. Ann Surg Oncol. 2012 Sep;19(9):2842–52.

              5. Nie K, Shi L, Chen Q, Hu X, Jabbour SK, Yue N, et al. Rectal Cancer: Assessment of Neoadjuvant Chemoradiation Outcome based on Radiomics of Multiparametric MRI. Clin Cancer Res Off J Am Assoc Cancer Res. 2016 Nov 1;22(21):5256–64.

              6. De Cecco CN, Ciolina M, Caruso D, Rengo M, Ganeshan B, Meinel FG, et al. Performance of diffusion-weighted imaging, perfusion imaging, and texture analysis in predicting tumoral response to neoadjuvant chemoradiotherapy in rectal cancer patients studied with 3T MR: initial experience. Abdom Radiol N Y. 2016 Sep;41(9):1728–35.

              7. Cusumano D, Dinapoli N, Boldrini L, Chiloiro G, Gatta R, Masciocchi C, et al. Fractal-based radiomic approach to predict complete pathological response after chemo-radiotherapy in rectal cancer. Radiol Med (Torino). 2018 Apr;123(4):286–95.

              8. Liu Z, Zhang X-Y, Shi Y-J, Wang L, Zhu H-T, Tang Z, et al. Radiomics Analysis for Evaluation of Pathological Complete Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer. Clin Cancer Res Off J Am Assoc Cancer Res. 2017 Dec 1;23(23):7253–62.

              9. Haralick RM, Shanmugam K, Dinstein IH. Textural features for image classi cation. Trans Syst Man Cybern 1973;SMC- 3(6):610–621. 1973;

              10. Breiman L. Random Forests. Mach Learn. 2001 Oct 1;45(1):5–32.


              Dr. Carole Allimant works at the Centre Hospitalier Universitaire de Montpellier, more specifcially at the Department of Radiodiagnostic and Interventional Radiology. In 2017, Dr. Allimant finished her residency of which she spent an inter-university exchange of 7 months at the CHUV, Pr Denis, in Lausanne/CH. At this year's ECR, she held an oral presentation on «Tumor targeting and 3D voxel-based dosimetry to predict tumor response, toxicity and survival after Y-90 resin microsphere radioembolization in HCC»

              Comments may be sent to  Dr. Carole Allimant.


              Diagnostic Performance of Magnetic Resonance Imaging and 3D Endoanal Ultrasound in Detection, Staging and Assessment Posttreatment in Anal Cancer
              Alfonso Reginelli, Vincenza Granata, Roberta Fusco, Francesco Granata, Daniela Rega, Luca Roberto, Gianluca Pellino, Antonio Rotondo, Francesco Selvaggi, Francesco Izzo, Antonella Petrillo, Roberto Grassi.

              Oncotarget. 2017 Apr 4;8(14):22980-22990


              Prof. Søren Rafaelsen and Dr. Martina Kastrup Loft – Clinical Cancer Centre, University of Southern Denmark, Department of Radiology, Vejle Hospital, Denmark.

              Anal carcinoma is a rare malignancy with an increasing incidence rate in most European countries. Anal cancer includes 2.5% of all gastrointestinal malignancies.

              Tumour size in anal cancer is an important measurement in determining the T stage according to the TNM system. With the recent improvements of radiotherapy and chemotherapy as neoadjuvant therapies, however, it is possible to downstage the lesion, this allow for a more conservative treatment.

              Diffusion weighted MRI (dw-MRI) quantifies diffusion of water occurring naturally at a cellular level (Brownian movement) which is restricted in multiple neoplasms because of high cellularity. Disruption of cellular integrity secondary to therapy results in increased water diffusion across the injured membranes.  Dw-MRI has shown potential to improve the accuracy of therapeutic response prediction in rectal cancer and perhaps in anal cancer.

              The objectives of Reginelli´s study were to compare the diagnostic performance of Endoanal Ultrasound (EUS) and dw-MRI including contrast in the detection, staging and assessment of anal cancer patients after therapy (1). The study included 58 patients with biopsy proven anal cancer. A 360° multi-frequency transducer was used in the EUS examination. The MRI scan was performed using a 1.5 Tesla unit and included dw and iv contrast.  The EUS and MRI image analysis were performed blindly by experienced observers. All patients had dw-MRI, using MRI 54 of the 58 cancers were detected. The four missed were all T1 tumors. EUS detected all 58 tumors. The patients underwent neoadjuvant treatment. The authors used an ADC (apparent diffusion coefficient) increase of 30% as a definition of response. The tumour ADC increased for responders from 0.830 x 10-6 mm2/s to 1.220x10-6 mm2/s, while non-responders showed no significant difference in ADC value between pre- and posttreatment. The same was true for the lymph nodes. The dynamic MRI contrast enhancement also found a difference between responders and non-responders. The method section is in the final part of the paper.

              We performed a systematic literature review of dw-MRI in anal cancer in order to identify more literature on the subject. Embase, and PubMed were searched for full-text articles reporting results from studies of dw-MRI in anal cancer. Articles published before the year 2000, articles written in a language other than English were excluded. The search resulted in the identification of six unique publications. Of these, five were excluded following title and abstract screening. Two studies did not include anal cancer but adenocarcinomas, one paper was a review and one was a case study. Leaving only the study of Reginelli reporting combined MRI and dwi in the staging of anal cancer. However; another very recent an interesting study by Prezzi et al. published in the April issue of European Radiology showed that the maximum tumour diameter and gross tumour volume were significantly lower on dw-MRI than on the T2 w images and dwi yields higher inter-observer agreement (2).

              The study of Reginelli, although blinded, has some shortages as the authors did not use disease free survival as an end-point. Further studies are needed to compare the results of the diffusion restriction measurements in anal cancer to the clinical outcome for the patients.


              References

              1. Reginelli A, Granata V, Fusco R, Granata F, Rega D, Roberto L, Pellino G, Rotondo A, Selvaggi F, Izzo F, Petrillo A, Grassi R. Diagnostic Performance of Magnetic Resonance Imaging and 3D Endoanal Ultrasound in Detection, staging and Assessment Posttreatment in Anal Cancer. Oncotarget. 2017 Apr 4;8(14):22980-22990

              2. Prezzi D, Mandegaran R, Gourtsoyianni S, Owczarczyk K, Gaya A, Glynne-Jones R, Goh V. The impact of MRI Sequence on Tumour Staging and Gross Tumour Volume Delineation in Squamous Cell Carcinoma of the Anal Canal. Eur Radiol. 2018 Apr;28(4):1512-1519


              Dr. Martina Loft graduated as a medical doctor from the University of Aarhus in January 2016. During her medical studies she coauthored a paper on percutaneous ultrasound kidney biopsies. She had the opportunity to present her scientific studies at the national society’s annual meeting, amongst others.  Martina has a broad range of interests within diagnostic radiology and is working as a first year radiology resident at Vejle Hospital, Clinical Cancer Centre, Denmark.
              She aspires to take part in research studies in the near future.

              Comments may be sent to Dr. Martina Kastrup Loft.


              MRI for Local Staging of Colon Cancer: Can MRI Become the Optimal Staging Modality for Patients With Colon Cancer?
              Elias Nerad, Doenja M. J. Lambregts, Erik L. J. Kersten, Monique Maas, Frans C. H. Bakers, Harrie C. M. van den Bosch, Heike I. Grabsch, Regina G. H. Beets-Tan, Max J. Lahaye.
              Dis Colon Rectum 2017; 60: 385–392

              Prof. Søren Rafaelsen and Dr. Malene Roland Vils Pedersen – Clinical Cancer Centre, University of Southern Denmark, Department of Radiology, Vejle Hospital, Denmark.

              Colorectal cancer is the second most common of cancer in developed countries, and is associated with significant morbidity and mortality. Previously the treatment was surgery alone but about half of the resected patients developed incurable recurrent disease. Postoperative chemotherapy can produce a moderate improvement in survival for some patients with stage II and III colorectal cancer, whereas neoadjuvant chemotherapy (NEC) has shown to be effective in rectal cancer and is presumed to have a potential to improve outcome in colon cancer. Multi-detector computed tomography (MDCT) is currently the standard modality for preoperative local staging of colon cancer. MDCT has shown in some studies shown a reasonable accuracy in discriminating between locally and non-locally advanced colon cancer. In rectal cancer, magnetic resonance imaging (MRI) is well established for preoperative local staging and recent studies suggested that MRI may also have an advantage over CT in precise local staging of colon cancer.
              In Nerad et al. ´s study the aim was to evaluate the diagnostic performance of MRI for local staging of colon cancer. A total of 55 consecutive patients were diagnosed with colon cancer were included in the study. All patients underwent surgery and histopathological examination. Imaging was performed with a 1.5-tesla MRI unit. The scan protocol consisted of a MR liver protocol combined with an additional MR colon protocol covering the whole abdomen. Two experienced radiologist readers blindly assessed the MR colon images to evaluate the local tumor stage (T1–2 vs T3–4). In case of a T3 or T4 tumor, the depth of extramural invasion (EMD) of ≤5 mm classified as a T3ab tumor and an EMD of >5 mm classified as a T3cd tumor. Adjacent organ invasion was noted as T4. Extramural venous invasion (EMVI); and lymph nodesstatus (N0/N+) were also reported.
              The authors found a sensitivity and specificity for detecting T3cd/T4 tumors in patients with a T3 tumor of 40% and 88% for reader 1 and 60% and 75% for reader 2. The sensitivity and specificity for detecting serosal involvement were 88%/74% for reader 1 and 68%/64% for reader 2. Both readers had a high sensitivity of 100% and 88% and a moderate specificity of 62% and 70% in detecting EMVI. The sensitivity and specificity for detecting nodal involvement (N0 vs N+) were 47%/86% for reader 1 and 68%/64% for reader 2.

              The detection of T3cd/T4 tumors remained a problem with MRI, and the present study revealed a low sensitivity (40%–60%) indicates that the depth of extramural invasion is largely underestimated.  Low specificity estimates might be caused by desmoplastic reaction being interpreted as tumor expansion, resulting in overstaging.

              Another recent study, Dam et al, found a higher sensitivity and specificity for detecting T3cd/T4. However; the MRI study of Dam et al only focused on sigmoid cancers, which could explain the higher accuracy.

              The specificity of EMVI was not high, which the authors explained by possible traction on the vessels and/or thrombus formation because of altered hemodynamics caused by local inflammation.

              As stated by Nerad et al, the lymph nodes are clearly visible in diffusion weighted images. This does not necessarily represent metastatic involvement, since the high cellularity in lymph nodes causes a high DWI signal in benign lymph nodes as well. False negative results are caused by microscopic metastasis in lymph nodes with a normal diameter, and false-positive results are caused by benign lymph nodes that are enlarged because of inflammation.

              The study of Nerad et al used state of the art equipment and had a consecutive well-defined study population with clear endpoints, the study remained retrospective and the results had wide 95% CI´s.

              More prospective research is needed to define the role of MRI in colon cancer staging, and to decide whether it become the optimal staging modality for patients with colon cancer. Although it was not the focus of the study, DWI has shown to be especially useful for locating the colon tumor. The high signal on DWI makes it easier to detect small colon tumors with MRI. The role of MRI in assessing local tumor response to neoadjuvant chemotherapy and re-staging of colonic cancer has however not been explored widely.


              References

              1.    Jakobsen A, Andersen F, Fischer A, Jensen LH, Jørgensen JC, Larsen O, Lindebjerg J, Pløen J, Rafaelsen SR, Vilandt J. Neoadjuvant chemotherapy in locally advanced colon cancer. A phase II trial. Acta Oncol. 2015;54(10):1747-531.

              2.    Chang H, Yu X, Xiao WW, Wang QX, Zhou WH, Zeng ZF, Ding PR, Li LR, Gao YH. Neoadjuvant chemoradiotherapy followed by surgery in patients with unresectable locally advanced colon cancer: a prospective observational study. Onco Targets Ther. 2018;11:409-418.

              3.    Nørgaard A, Dam C, Jakobsen A, Pløen J, Lindebjerg J, Rafaelsen SR. Selection of colon cancer patients for neoadjuvant chemotherapy by preoperative CT scan. Scand J Gastroenterol. 2014;49(2):202-8

              4.    Rollvén E, Holm T, Glimelius B et al. Potentials of high resolution magnetic resonance imaging versus computed tomography for preoperative local staging of colon cancer. Acta Radiol. 2013;54:722-30

              5.    Hunter C, Blake H, Jeyadevan N et al. Local staging and assessment of colon cancer with 1.5-T magnetic resonance imaging. Br J Radiol. 2016;27:20160257

              6.    Hunter C, Siddiqui M, Georgiou Delisle T, Blake H, Jeyadevan N, Abulafi M, Swift I, Toomey P, Brown G.  CT and 3-T MRI accurately identify T3c disease in colon cancer, which strongly predicts disease-free survival. Clin Radiol. 2017;72(4):307-315.

              7.    Dam C, Lindebjerg J, Jakobsen A, Jensen LH, Rahr H, Rafaelsen SR. Local staging of sigmoid colon cancer using MRI. Acta Radiol Open. 2017;6(7):205846011772095

              8.    Dam C, Lund-Rasmussen V, Pløen J, Jakobsen A, Rafaelsen SR. Computed tomography assessment of early response to neoadjuvant therapy in colon cancer. Dan Med J. 2015 Jul;62(7). pii: A5103

              9.    Choi J, Oh SN, Yeo DM, Kang WK, Jung CK, Kim SW, Park MY.  Computed tomography and magnetic resonance imaging evaluation of lymph node metastasis in early colorectal cancer. World J Gastroenterol. 2015;21(2):556-62.

              10.    Koh FHX, Tan KK, Teo LLS, Ang BWL, Thian YL. Prospective comparison between magnetic resonance imaging and computed tomography in colorectal cancer staging. ANZ J Surg. 2017 Aug 13. doi: 10.1111/ans.14138. [Epub ahead of print]


              Dr. Malene Roland V Pedersen has a Bachelor in Radiography, University College Lillebaelt, Odense 2005 and graduated with a Master of Science in Public Health from the University of Southern Denmark in 2009. She will finish her PhD study on “Imaging aspects of testicular microlithiasis” this year. She has authored and coauthored 25 peer reviewed papers. She have had the opportunity to present her scientific studies at national and international radiological meetings.  Malene has a broad range of interests within research of diagnostic radiology and is working at the Department of Radiology at Vejle Hospital, Clinical Cancer Centre, Denmark. She has numerous ongoing projects and aspires to take part in further research studies in the near future.

              Comments may be sent to Dr. Malene Roland V Pedersen.


              Major pancreatic resections: normal postoperative findings and complications.
              Marco Chincarini - Giulia A. Zamboni - Roberto Pozzi Mucelli
              Insights into Imaging (2018) 9:173-187
              doi.org/10.1007/s13244-018-0595-4

              Dr. Charikleia Triantopoulou, Head of the Radiology Department, and Dr. Paraskevi Vlachou, Consultant Radiologist, “Konstantopouleion” General Hospital of Nea Ionia, Athens-Greece.

              Pancreatic adenocarcinoma is a lethal neoplasm and remains the forth cause of death in developed countries. (1)  The survival rates still remain extremely low (5year-old survival less than 6%), and most of people die within 6 months after diagnosis.(2). The reason for this ‘one-way’ situation, is that pancreatic cancer is characterized by early infiltration of surrounding tissues and the early formation of distant metastases, usually synchronous with diagnosis time.  The only possible curative method is tumor resection (R0) (3). Additionally, there are several other pancreatic lesions malignant, benign or intermediate that should be resected, such as mucinous cystic neoplasms, neuroendocrine tumors or chronic inflammatory lesions.

              Therefore, pancreatectomy has become an important surgery, demanding highly qualified surgeons and healthcare groups to take care of the patients in dedicated centers. Pancreatoduodenectomy was first pioneered by Whipple in 1910s (3). Since then, the method has evolved throughout decades, but still remains a technically difficult procedure, carrying the risk of possible complications.

              In this review article Chincarini et al., describes the most common methods of pancreatectomy, the postoperative anatomy and finally the possible complications after surgery. They use as the imaging method of choice CT, since it appears to offer many advantages, as best spatial solution, while it is a quick and cost effective method, compared to other imaging tools i.e. MRI.

              Since the majority of pancreatic carcinomas are located in pancreatic head, pancreatoduodenectomy preserving pylorous or not, is the most famous operation. Both include resection of pancreatic head, duodenum, gall bladder, distal bile duct, proximal jejunum and regional lymph nodes. Furthermore other techniques are mentioned, like distal pancreatectomy with splenectomy, for lesions located at pancreatic tail and the rare central pancreatectomy. The authors underline how important is to recognize the regional anatomical changes, after the necessary anastomoses and how vital is for the radiologist to be able to point them out. CT remains the method of choice, being able to show precisely the anastomotic areas and their pathologic features, if they exist, in the majority of cases.

              According to the authors, another crucial point in postoperative follow-up, is the early and direct assessment of the normal postoperative findings and the importance of not confusing them with complications or tumor recurrence. Accurate interpretation requires, understanding of which part of organ has been removed and how the remaining parts are reconstructed. (4)

              The complications after pancreatoduodenectomy are many, significant and sometimes life-threatening, so, as the authors highlight, they must be recognized as soon as possible. The most common is fistula formation (11.4-64.3%) a complication associated with delayed gastric emptying, abscess formation and sepsis (5). As Bing-Yang Hu et al. refers a lot of factors are related to the formation of pancreatic fistula: gender (male>female), age, BMI>25, pancreatic duct diameter < 3mm. and soft pancreas (5-6). Other more uncommon complications are portal and SMV thrombosis, hepatic infarction, anastomotic bile leakage or stricture.

              The aim of Chincarini’s article was to summarize in a brief but really helpful way the basic knowledge about various types of pancreatectomies, to refer to the anatomy and postsurgical alterations and to focus on complications that may happen. This article is a useful key, for every radiologist and enables him to be aware of fundamental findings that accompany pancreatectomies, so as to recognize them in a premature state. That demands adequate knowledge of physiologic anatomy, surgery techniques, postoperative changes and potential complications. The spherical view and deep knowledge of “pancreatectomies” and related imaging findings, make the radiologist a valuable cooperator, who can help and guide the surgeon providing him with significant details that are vital for patient’s better recovery and successful treatment.


              REFERENCES

              1.    Diagnosis and management of pancreatic cancer. De La Cruz MS, Young AP, Ruffin MT. Am Fam Physician. 2014 Apr 15;89(8):626-32

              2.    Pancreatic Cancer: why is it so hard to treat?  Paul E. Oberstein, Kenneth P. Olive. Therap Adv Gastroenterol. 2013 Jul; 6(4):321-337.

              3.    Pancreatic Resection for pancreatic cancer. J. Bachmann, C. Michalski, M. Martignoni, M. Buchler, H. Friess. HPB (Oxford) 2006;8(5): 346-351.

              4.    Normal Postoperative Computed Tomography Findings after a variety of Pancreatic Surgeries. Ji Won Seo, Ho Kyoung Hwang, Ki Whang Kim, Chang Moo Kang, Myeong-Jin Kim, Yong Eun Chung. Korean J Radiol. 2017 Mar-Apr; 18(2): 299-308.

              5.    Risk factors for postoperative pancreatic fistula: Analysis of 539 successive cases of pancreaticoduodenectomy. Bing-Yang Hu, Tao Wan, Wen-Zhi Zhag, Jia-Hong Dong. World J. Gastroenterol. 2016 Sep 14;22(34): 7797-7805.

              6.    Pancreatic anastomotic leakage after pancreaticoduodenectomy. Risk factors, clinical predictors, and management (single center experience .) El Nakeeb A, Salah T, Sultan A, El Hemaly M, Askr W, Ezzat H, Hamdy E, Atef E, El Hanafy E, El-Geidie A, et al. World J Surg. 2013;37:1405–1418.


              Paraskevi Vlachou, MsC, is a young radiologist in “Konstantopouleion” General Hospital of Nea Ionia-Athens. She is an active ESGAR member, attending regularly annual meetings and workshops. Her main interest is in breast and abdominal radiology. She completed a postgraduate programme at Athens University, in “Interventional Radiology” and in 2016 she won a 3 month ESOR scholarship, in Breast Imaging, at Agostino Gemelli Polyclinico in Rome.

              Comments may be sent to Dr. Paraskevi Vlachou.


              Revisions of international consensus Fukuoka guidelines for the management of IPMN of the pancreas
              Masao Tanaka, Carlos Fernandez-del Castillo, Terumi Kamisawa, Jin Young Jang, Philippe Levy, Takao Ohtsuka, Roberto Salvia, Yasuhiro Shimizu, Minoru Tada, Christopher L. Wolfgang
              Pancreatology 17 (2017) 738-753
              DOI: 10.1016/j.pan.2017.07.007

              Dr. Charikleia Triantopoulou, Head of the Radiology Department, and Dr. Fagkrezos Dimitris, Consultant Radiologist, “Konstantopouleion” General Hospital of Nea Ionia, Athens-Greece.

              Cystic pancreatic tumors and tumorlike lesions represent a wide spectrum of histopathology from purely benign to overly malignant.
              The intraductal papillary mucinous neoplasm (IPMN) was first described at ERCP by Ohhashi in 1982 [1] and the first report in the imaging literature was by Itai et al. in 1986 [2]. The lesion occurs with a slightly increased frequency in male patients compared with other pancreatic cysts. IPMN is pathologically characterized by papillary proliferation of ductal epithelium in the main or branch duct, association with ductal dilatation, and various mucin productions [3]. IPMNs are subcategorized clinically into main duct type, branch duct type and combined type. There are five histologic types: Gastric, intestinal, pancreatobilliary, intraductal, tuburopapillary and intraductal oncocytic. The different histologic types cannot be differentiated on imaging; however, the risk of malignancy varies significantly between them. Factors correlating with malignancy include advanced age, main duct involvement, concurrent diabetes or other pancreas related abdominal symptoms, lesion size (>3cm), multiplicity and presence of visible mural nodules.

              In this article Masao Tanaka and the rest of the working group, based on a consensus symposium that took place in Sendai of Japan in 2016, did not recognize the need for major revisions of the previous guidelines of 2012 in Fukuoka, making only minor revisions and added most recent articles where appropriate. The working group has revised the guidelines regarding prediction of invasive carcinoma and high grade dysplasia, surveillance, and postoperative follow up of IPMN.

              As a consequence, the majority of newly-diagnosed BD-IPMNs do not undergo surgery. However, it is also recognized that a proportion of these evolve over time and can become malignant, and also, that patients with IPMN are at increased risk of developing conventional pancreatic ductal adenocarcinoma elsewhere in the gland. Because of this, surveillance is carried out on most of these patients.

              The authors make an important reference to the role of imaging in classification of lesions. They mention that it is very important for clinicians to plan the management of IPMN, which should be based on the preoperative radiologic images, and the pathological classification can be specified a posteriori.
              Symptomatic cysts overall have a higher risk of invasive carcinoma and HGD, and, depending on the clinical circumstances, either resection or further evaluation needs to be carried out.

              “Worrisome features” on imaging include cyst of ≥3 cm, enhancing mural nodule <5 mm, thickened enhanced cyst walls, MPD size of 5-9 mm, abrupt change in the MPD caliber with distal pancreatic atrophy, lymphadenopathy, an elevated serum level of carbohydrate antigen (CA)19-9 and a rapid rate of cyst growth > 5 mm/2 years [4-5]. '

              These patients should be evaluated by endoscopic ultrasonography (EUS) to further stratify the lesion. Doppler EUS or contrast-enhanced harmonic EUS can demonstrate the presence of blood supply in mural nodule [6,7,8]. Cysts with obvious “high-risk stigmata” on CT, MRI, or EUS (i.e. obstructive jaundice in a patient with a cystic lesion of the pancreatic head, enhanced mural nodule ≥5 mm, MPD size of ≥10 mm) should undergo resection in surgically fit patients without further testing [9]. All patients with cysts of ≤3 cm in size without “worrisome features” should undergo surveillance according to size stratification.

              Although preoperative and intraoperative assessment of the grades of dysplasia of IPMNs can be difficult, ultrasonography, CT, MRI, and EUS will identify most tumors with a significant invasive component. In such patients, pancreatoduodenectomy, left pancreatectomy, or total pancreatectomy according to the site and extent of the disease with lymph node dissection remains the standard treatment.

              The purpose of this article is to enhance the latest knowledge in the management of patients with known pancreatic cystic neoplasms of IPMN type.

              This article is a useful tool for every radiologist, especially those participating in oncologic multidisciplinary meetings, and enables them to be aware of the most recent and up-to-date information and recommendations for the proper management of IPMN.


              REFERENCES

              1.    Ohhashi K, Murakami Y, Maruyama M, et al.: Four cases of mucus secreting pancreatic cancer. Prog Dig Endosc. 1982; 20:348-351

              2.    Itai Y, Ohhashi K, Nagai H, et al.: “Ductectatic” mucinous cystadenoma and cystadenocarcinoma of the pancreas. Radiology 1986;  161:697-700

              3.    Tierney WM, Francis IR, Eckhauser F, et al.: The accuracy of EUS and helical CT in the assessment of vascular invasion by peripapillary malignancy. Gastrointest Endosc 2001; 53:182-188
              4.    Kang MJ, Jang JY, Kim SJ, Lee KB, Ryu JK, Kim YT, et al. Cyst growth rate predicts malignancy in patients with branch duct intraductal papillary mucinous neoplasms. Clin Gastroenterol Hepatol 2011; 9:87-93.

              5.    Kwong WT, Lawson RD, Hunt G, Fehmi SM, Proudfoot JA, Xu R, et al. Rapid growth rates of suspected pancreatic cyst branch duct intraductal papillary mucinous neoplasms predict malignancy. Dig Dis Sci 2015; 60:2800-6.

              6.    Ohno E, Hirooka Y, Itoh A, Ishigami M, Katano Y, Ohmiya N, et al. Intraductal papillary mucinous neoplasms of the pancreas: differentiation of malignant and benign tumors by endoscopic ultrasonography findings of mural nodules. Ann Surg 2009; 249:628-34.

              7.    Kitano M, Sakamoto H, Komaki T, Kudo M. New techniques and future perspective of EUS for the differential diagnosis of pancreatic malignancies: contrast harmonic imaging. Dig Endosc 2011; 23(Suppl 1):46-50.

              8.    Ohno E, Itoh A, Kawashima H, Ishikawa T, Matsubara H, Itoh Y, et al. Malignant transformation of branch duct-type intraductal papillary mucinous neoplasms of the pancreas based on contrast-enhanced endoscopic ultrasonography morphological changes: focus on malignant transformation of
intraductal papillary mucinous neoplasm itself. Pancreas 2012; 41:855-62. 


              9.    Kim TH, Song TJ, Hwang JH, Yoo KS, Lee WJ, Lee KH, et al. Predictors of malignancy in pure branch duct type intraductal papillary mucinous neoplasm of the pancreas: a nationwide multicenter study. Pancreatology
2015; 15:405-10. 



              Dr. Fagkrezos Dimitris graduated from medical school of Patras University and completed a Master of Science programme in “Interventional Radiology” at Athens University. He is a consultant radiologist at the Computed Tomography Department in “Konstantopouleion” General Hospital of Nea Ionia-Athens. He is an active ESGAR member, attending regularly annual meetings and workshops. His main interest is in abdominal, oncologic and cardiovascular radiology. Dr Fagkrezos has a broad range of interests within research of diagnostic radiology.


              Comments may be sent to: dfagrezos@remove-this.gmail.com


              Diagnostic prediction of complicated appendicitis by combined clinical and radiological appendicitis severity index (APSI)
              Authors: Avanesov M, Wiese NJ, Karul M, Guerreiro H, Keller S, Busch P, Jacobsen F, Adam G,
              Yamamura J.
              Journal: Eur Radiol. 2018 Sep;28(9):3601-3610. doi: 10.1007/s00330-018-5339-9.

              Dr. Asuncion Torregrosa, ESGAR Fellow and Head of the Abdominal Radiology Section and Dr. Alexandre Perez Girbes, ESGAR Member and abdominal radiologist, both in University and Polytechnic La Fe Hospital, Valencia (Spain)

              Acute appendicitis (AA) is one of the most common abdominal emergencies, with life time prevalence of about 7-8% (1). Since 19th century, urgent surgery has been the standard treatment for acute appendicitis (2). However, in last decades several clinical trials have compared surgery against conservative treatment with antibiotics concluding that this is as safe and effective as appendectomy.

              The objective of Avanesov et al. is to propose a severity index based in clinical and radiological features to predict complicated AA.

              Their retrospective study included 200 adult patients with histologically proven acute appendicitis who had a presurgical contrast-enhanced CT with evidence of AA and availability of selected clinical and biological parameters on admission (body temperature, duration of symptoms before admission, C reactive protein and WBC count).

              All CT studies were visually evaluated for appendix diameter, wall thickness and the presence of periappendiceal fat stranding and fluid, intraluminal air in appendix, thinning of appendiceal wall, extraluminal air, caecal wall thickening, appendicolith and perityphlitic abscess.

              Surgical and histopathological evaluation grouped AA as uncomplicated (mucosal and suppurative AA) or complicated (gangrenous and perforated AA) according to changes and density of neutrophil infiltration in the wall. Perforation was assessed intraoperatively.

              Among the patients included, half of the patients (51%, n=103) had complicated AA, while 49% had uncomplicated AA.

              Authors developed a multivariate logistic regression model, appendicitis severity index (APSI), with 7 selected parameters (3 clinical and 4 radiological). They defined points for APSI calculation based on the corresponding β regression coefficient of each parameter. Clinical parameters were: age ≥52 years (1 point), body temperature ≥37.5 °C, (1 point), duration of symptoms ≥48 h (1 point) and the radiological ones:  appendix diameter ≥14 mm (1 point), presence of periappendiceal fluid (2 points), extraluminal air (1 point), and abscess present (3 points).

              Their results showed that the best discriminative capacity of APSI was observed for ≥ 4 points with an AUC of 0.92, a sensitivity of 82%, specificity of 93%, accuracy of 87%, PPV of 92% and NPV of 83%. The median APSI was significantly lower in patients with uncomplicated AA compared to those with complicated AA [1 (IQR, 1-2) vs 5 (IQR, 4-6), p < 0.001)].

              Previously, other authors studied imaging features to differentiate uncomplicated AA from complicated AA. A recently published systematic review by Kim HY et al. (3) identified 10 CT features informative for complicated AA. Almost all of them showed high specificity but low sensitivity.  Other papers examined the same comparison by US findings. A paper by Xu et al. (4) which compared US findings between complicated and uncomplicated AA showed that only loss of the normally echogenic submucosal layer had an independent association to complicated appendicitis in multivariate regression. Atema and colleagues (5) were the first to propose a clinical-radiological score to differentiate uncomplicated AA from complicated AA. They proposed a more detailed score with maximum 22 points for CT and 19 for US, with AUC of 0.90 and 0.85, respectively.

              According with the authors, we find very interesting to differentiate with image techniques between uncomplicated AA from complicated AA due to the new trends in the treatment. Published data suggests that will be feasible avoid surgery and its inherent risks in case of mild or very early AA.

              Nevertheless, we encourage the US role in the management of patients with right lower quadrant pain with suspected AA in emergency department. AA is more common in young adults and children, who are more sensitive to ionizing radiation exposure than adults, being US the first choice technique to evaluate this clinical scenario. So, in our opinion severity index based on clinical and US criteria, as above mentioned, would be more applicable in that population. The same occurs in patients no candidates to intravenous contrast administration.

              This paper is interesting for radiologists working in the emergency department or that are on duty, whose authors propose a reasonably easy appendicitis severity score (APSI) with high PPV and NPV for predicting complicated AA. Furthermore, the important role of the radiologists in diagnostic process of AA is very well shown helping the surgeon to make a decision between surgical and non-surgical treatment.

              The main weakness of this study is its single-center retrospective design. External validation with larger cohorts is needed to use confidently APSI in clinical practice.


              REFERENCES

              1. Addiss DG, Shaffer N, Fowler BS et al. The epidemiology of appendicitis and appendectomy in the United States. Am J Epidemiol. 1990 Nov;132(5):910-25

              2. Richardson WS. The evolution of early appendectomy as standard treatment from appendicitis: what we can learn from the past in adopting new medical therapies. Am Surg. 2015 Feb;81(2):161-5

              3. Kim HY, Park JH, Lee YJ et al. Systematic Review and Meta-Analysis of CT Features for Differentiating Complicated and Uncomplicated Appendicitis. Radiology. 2018 Apr;287(1):104-115

              4. Xu Y, Jeffrey RB, Chang ST et al. Sonographic Differentiation of Complicated From Uncomplicated Appendicitis: Implications for Antibiotics‐First Therapy. J Ultrasound Med. 2017 Feb;36(2):269-277.

              5. Atema JJ, van Rossem CC, Leeuwenburgh MM, Stoker J, Boermeester MA. Scoring system to distinguish uncomplicated from complicated acute appendicitis. Br J Surg. 2015 Jul;102(8):979-9


              Dr. Alexandre Perez-Girbes is a young radiologist at University and Polytechnic La Fe Hospital, Valencia (Spain). He completed his radiology residency last year. During his training, Alexandre actively assisted in ESGAR workshops and participated in the local organising team of Junior ESGAR Summer School held in Valencia in 2016. He is also member of the ESGAR Research Committee. His main interest is clinical radiology and research, especially abdominal imaging. He also co-authored peer reviewed neuroradiology papers.


              Comments may be sent to: perez_alegir@remove-this.gva.es


              Abdominal imaging findings in adult patients with Fontan circulation.
              Authors: Tae-Hyung ,Kim, Hyun Kyung, Yang.  Hyun-Jung, Jang.  Shi-Joon, Yoo.  Korosh, Khalili. Tae Kyoung, Kim.
              Journal: Insights into Imaging. 2018; 9: 357–67. doi.org/10.1007/s13244-018-0609-2.

              Dr. Asuncion Torregrosa, ESGAR Fellow and Head of the Abdominal Radiology Section and Dr. Helena Martinez-Maicas radiologist resident of last year, both working on University and Polytechnic La Fe Hospital, Valencia (Spain).

              The Fontan procedure [1] was designed to treat patients with single functional ventricle, by-passing right ventricle, what implies the transmission of pulmonary vascular resistance to systemic venous circulation. This inevitably provokes elevation of systemic venous pressure. Improving of surgical technique and postoperative management markedly prolongs patient survival, frequently until adulthood. Radiologists must be aware of this technique and the possible complications in order to summit a correct and early diagnosis.

              This article is a descriptive review of post-Fontan abdominal findings in adults patients, focused on hepatic changes.

              Fontan associated liver disease (FALD) is originated by chronic hepatic congestion similar to right heart failure and can lead to liver cirrhosis, portal hypertension, focal nodular hyperplasia (FNH)-like and even hepatocellular carcinoma.

              The liver is often enlarged with caudate lobe hypertrophy and irregular parenchymal fatty infiltration with perivascular distribution. The most common imaging feature in FALD is heterogeneous hepatic enhancement with mosaic or reticular pattern, resulting from slow and poor enhancement near the congested hepatics veins [2]. This abnormal enhancement is more evident in the periphery of the liver parenchyma and in the portal venous phase.
              Regenerative hepatic nodules are commonly seen in adult patients with FALD whose prevalence ranges from 20 to 30% [3]. FNH-like nodules in FALD are often small and multiple and show a predilection for the periphery of the right lobe [4]. It is important to note that benign and arterially enhancing nodules may show portal venous or delayed phase washout, mimicking hepatic carcinoma (HCC) and becoming a challenge for radiologists. Wells et al. speculated that the washout may be related to the background parenchymal contrast retention due to congestion and fibrosis or from a predominant hepatic arterial supply [5]. MRI using liver-specific contrast agent and DWI may be useful for the differentiation between FNH-like nodules and HCC, as HCC mostly show hypointensity in the hepatobiliary phase and restricted diffusion [5].  These authors suggested other ancillary findings favoring benign FNH-like nodules, including hypointensity on T2-weighted images and stability over time (>24months) [5].

              Vascular abnormalities in post-Fontan patients are similar to congestive heart failure with earlier development. Inferior cava vein and hepatic veins are dilated with increased pulsatility, regardless of the surgical technique. In contrast, the diameter of main portal vein and intrahepatic portal veins is usually small, possibly due to reduction of portal perfusion secondary to increase in sinusoidal pressure with venous stasis [6].

              Splenomegaly and ascites are commonly seen in adult Fontan patients. Thus, extrahepatic portosystemic shunts are uncommon or small in size, what is likely due to the high systemic venous pressure and relatively low pressure gradient between the portal and systemic veins [7].

              Protein losing enteropathy is a severe condition with usually delayed diagnosis. Suggestive imaging findings including ascites, diffuse bowel wall thickening, and mesenteric edema on CT or MRI should prompt a clinical evaluation to rule it out.

              The improvement in post-Fontan patient surveillance makes necessary a comprehensive approach by the radiologist. Given the clinical importance of FALD, liver biopsy has been the “gold standard” for diagnosis. Nevertheless, FALD can be not uniformly distributed [8] and complications related to biopsy are higher in this group of patients, with frequent use of warfarin and elevated systemic venous pressure. Non-invasive imaging surveillance may be essential in guiding patient management and discard potential severe complications.


              REFERENCES

              1. Fontan F, Mounicot FB, Baudet E, Simonneau J, Gordo J, Gouffrant JM. “Correction” of tricuspid atresia. 2 cases “corrected” using a new surgical technic. Ann Chir Thorac Cardiovasc. 1971; 10:39–47.

              2. Bulut OP, Romero R, Mahle WT, McConnell M, Braithwaite K, Shehata BM et al. Magnetic resonance imaging identifies unsuspected liver abnormalities in patients after the Fontan procedure. J Pediatr. 2013; 163:201-6.

              3. Bryant T, Ahmad Z, Millward-Sadler H et al. Arterialized hepatic nodules in the Fontan circulation: hepatic-cardiac interactions. Int J Cardiol. 2011;  151:268–72.

              4. Bae JM, Jeon TY, Kim JS et al. Fontan-associated liver disease: spectrum of US findings. Eur J Radiol. 2016; 85:850–56.

              5. Wells ML, Hough DM, Fidler JL, Kamath PS, Poterucha JT, Venkatesh SK. Benign nodules in post-Fontan livers can show imaging features considered diagnostic for hepatocellular carcinoma. Abdom Radiol. 2017; 42: 2623-31.

              6. Cura M, Haskal Z, Lopera J. Diagnostic and interventional radiology for Budd-Chiari syndrome. RadioGraphics. 2009; 29:669–81.

              7. Wells ML, Fenstad ER, Poterucha JT, Hough DM, Young PM, Araoz PA et al. Imaging findings of congestive hepatopathy. RadioGraphics. 2016; 36:1024–37.

              8. Poterucha JT, Johnson JN, Qureshi MY, O´Leary PW, Kamath PS, Lennon RJ et al. Magnetic Resonance Elastography: a novel technique for the detection of hepatic fibrosis and hepatocellular carcinoma after the Fontan operation. Mayo Clin Proc. 2015; 90:882–94.


              Helena Martinez-Maicas is a radiologist in her last days of Radiology residency at the University and Polytechnic La Fe Hospital. Previously, she focused on Intensive Care Medicine but redirected her professional career to Radiology. She has been particularly interested in abdominal radiology and was able to work extensively in this area during her residency.

              Comments may be sent to: hmartinezmaicas@remove-this.gmail.com


              Pancreatic Adenocarcinoma Staging in the Era of Preoperative Chemotherapy and Radiation Therapy
              Authors: Marc Zins, Celso Matos, Christophe Cassinotto
              Journal: Radiology Vol 287, No.2 (2018). https://pubs.rsna.org/doi/full/10.1148/radiol.2018171670

              Dr. João Pinheiro Amorim, radiologist resident of 4th year, and Prof. Manuela França, ESGAR Fellow and Head of Radiology Department, both working at the University Oporto Hospital Centre, Oporto (Portugal).

              Pancreatic ductal adenocarcinoma (PDA) is an aggressive malignancy, usually locally advanced or metastatic at diagnosis, with high mortality rate and challenging treatment. Accurate determination of the extent of disease during initial PDA staging is extremely important for determining patient management during multidisciplinary team discussion (1). As surgical resection of non-metastatic disease is considered the only potentially curative treatment, many strategies are being developed to increase the number of surgical candidates, which was traditionally low.

              The standard of care for PDA considered resectable at diagnosis is surgery followed by adjuvant chemotherapy. Nevertheless, neoadjuvant therapy followed by surgery is increasingly being considered for selected patients at high risk for resection margin involvement, aiming to increase the likelihood of negative resection margins and curative surgery, as well for downstaging tumors that were locally advanced at initial PDA staging (2). These changes in the patient management lead to new diagnostic imaging challenges, not only for the initial stating as also for the assessment of neoadjuvant treatment response.

              In the setting of important changes in current PDA management, the authors provide an important review and commentaries on PDA staging, highlighting the rationale for the increasing use of neoadjuvant therapy, which will have important implications on pre-operative imaging assessment.

              The authors discuss what should be the radiologist’s strategy for PDA staging, which is mostly focused on arterial and venous involvement to assess unresectability criteria related to vascular spread, classifying tumors in resectable, borderline resectable or unresectable/locally advanced (2, 3). Nevertheless, this three-stage classification system that is the based on the current National Comprehensive Cancer Network (NCCN) classification has important limitations, and the definition of borderline resectable tumors has been a cause of intense debate in the last years. Therefore, the authors encourage a more detailed staging in order to estimate the likelihood of achieving R0 margins and to guide treatment planning, allowing for neoadjuvant therapy consideration when the risk of incomplete resection is high.

              The limitations of current staging techniques are also considered in this paper, and some improvements are suggested. Multiphasic computed tomography (CT) is currently the method of choice for initial PDA staging, particularly due to its superb spatial resolution. Nevertheless, its diagnostic capability is limited for detecting isoattenuating tumors (4) and, moreover, for the assessment of important prognostic factors affecting tumor staging, including perineural invasion, lymph node involvement and liver metastasis detection.

              Magnetic Resonance (MR) imaging has high sensitivity for staging isoattenuating tumors with little or no visibility on initial multidetector CT. Furthermore, MR imaging of the liver has higher sensitivity than multidetector CT for detecting small liver metastasis, changing treatment management in up to 10% of patients after liver metastasis detection (5,6). Therefore, the authors feel that recent evidence supports hepatic MR imaging as a mandatory examination in patients with PDA considered resectable on multidetector CT. MR imaging should also be performed before and after neoadjuvant treatment for borderline resectable or locally advanced PDA.

              Dual-energy (spectral) CT may improve tumor detection and staging but more studies are needed to determine if it significantly improves the prediction of negative margin resection in everyday clinical practice.

              On the other hand, hybrid imaging still does not have a definite role in PDA staging.

              Regarding the raising importance of neoadjuvant therapy, particularly in borderline resectable or locally advanced tumors, the authors highlight that current structural imaging techniques and criteria are clearly insufficient and warrant great caution for radiologists (7). In fact, the performance of multidetector CT in predicting resectability decreases after neoadjuvant therapy and the criteria of radiological response frequently underestimate the histologic treatment response (8). For the time being, patients with evidence of any degree of radiological improvement in tumor size and/or tumor-vessel contact, even if small, should be considered good candidates for surgery, since there might be a good histological response. For the future, the use of functional imaging methods is pointed as a particularly interesting and promising research field (9).


              REFERENCES

              (1)    Fogel EL, Fogel EL, Shahda S, Sandrasegaran K, et al. A multidisciplinary approach to pancreas cancer in 2016: a review. Am J Gastroenterol 2017;112(4):537–554.

              (2)    National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology. Pancreatic adenocarcinoma. Version 2.2016. Fort Washington, Pa: National Comprehensive Cancer Network 2017.

              (3)    Varadhachary GR, Tamm EP, Abbruzzese JL, et al. Borderline resectable pancreatic cancer: definitions, management, and role of preoperative therapy. Ann Surg Oncol 2006;13(8):1035–1046.

              (4)    Kim JH, Park SH, Yu ES, et al. Visually isoattenuating pancreatic adenocarcinoma at dynamic-enhanced CT: frequency, clinical and pathologic characteristics, and diagnosis at imaging examinations. Radiology 2010;257(1):87–96.

              (5)    Kim HW, Lee JC, Paik KH, et al. Adjunctive role of preoperative liver magnetic resonance imaging for potentially resectable pancreatic cancer. Surgery 2017;161(6):1579–1587.

              (6)    Marion-Audibert AM, Vullierme MP, Ronot M et al. Value of routine MRI with diffusion weighted- sequences for the detection of liver metastases in patients with potentially resectable pancreatic ductal carcinoma and normal liver CT: a prospective multicentre study. AJR Am J Roentgenol: W1-W9. 10.2214/AJR.18.19640.

              (7)    Katz MH, Fleming JB, Bhosale P, et al. Response of borderline resectable pancreatic cancer to neoadjuvant therapy is not reflected by radiographic indicators. Cancer 2012;118(23):5749–5756.

              (8)    Cassinotto C, Cortade J, Belleannée G, et al. An evaluation of the accuracy of CT when determining resectability of pancreatic head adenocarcinoma after neoadjuvant treatment. Eur J Radiol 2013;82(4): 589–593.

              (9)    Cassinotto C, Chong J, Zogopoulos G, et al. Resectable pancreatic adenocarcinoma: Role of CT quantitative imaging biomarkers for predicting pathology and patient outcomes. Eur J Radiol 2017;90:152–158.


              Dr. João Amorim is a young radiology resident in the last years of training at the University Hospital of Centro Hospitalar do Porto, Portugal. He completed his undergraduate medical degree at the University of Minho in 2013. He is an active member of ESGAR and is regularly attending workshops organised by the society. His main interest is in abdominal and oncologic radiology and currently, he is taking part in research studies at his institution, particularly focused on imaging biomarkers and quantitative research and its translation to clinical practice.

              Comments may be sent to: joaopinheiroamorim@remove-this.gmail.com


              Reference range of liver corrected T1 values in a population at low risk for fatty liver disease—a UK Biobank sub-study, with an appendix of interesting cases

              Authors
              : Mojtahed A, Kelly CJ, Herlihy AH, Kin S, Wilman HR, McKay A, Kelly M, Milanesi M, Neubauer S, Thomas EL, Bell JD, Banerjee R, Harisinghani M.

              Journal
              : Abdom Radiol (NY). 2018 Jul 21. doi: 10.1007/s00261-018-1701-2. [Epub ahead of print] PubMed PMID: 30032383.

              Prof. Andrea Laghi, ESGAR Vice President and Head of the Abdominal Radiology Department and Dr. Marta Zerunian, ESGAR Member and radiologist resident attending the third year, both working in the Department of Radiological Sciences, Oncological and Pathological Sciences University of Rome "Sapienza" Radiology Unit - Sant'Andrea University Hospital, Rome (Italy).

              Nowadays liver disease is increasingly taking the lead among the causes of death in Western countries, in relation to the increase in obesity in the population(1). Even if steatosis (non-alcoholic fatty liver-NAFL) is not considerable as a manifest liver disease, it represents a precursor of liver inflammation (non-alcoholic steatohepatitis-NASH), fibrosis and cirrhosis, all conditions that lead to higher risk of morbidity and mortality(2). Until clinical symptoms are present the diagnosis of liver disease is difficult and that limits drastically the treatment options to keep under control the progression of the disease(3). Studies about hepatic multiparametric magnetic resonance imaging (MRI) demonstrated the prognostic role of the technique in the diagnosis of chronic liver disease and in the identification, through quantitative approach, of early stage of liver fibrosis in comparison with biopsy(4). Liver composition is objectively quantifiable with proton density fat fraction (PDFF) or T1 relaxation times, allowing furthermore a comparison of values across populations. Another powerful instrument of this new MRI tool is the Liver Inflammation and Fibrosis score, which is based on iron corrected T1 (cT1). cT1 is a novel imaging biomarker based on T1 mapping technology, which takes advantage of the increases in extracellular tissue fluid that occur in response to inflammation and fibrosis, with the possibility to correct values for elevated iron content. Preliminary studies demonstrated how cT1 can predict some liver-related clinical outcomes but the technique and the range of normality need some standardization in order to differentiate normality and different stage of abnormality (NAFL or NASH)(5).  

              Mojtahed and colleagues aimed to  provide a set of reference values for cT1 within a low-risk for fatty liver disease population. Reference population at low risk for NASH and NAFL (PDFF<5% and BMI< 25 kg/m2) counting 1037 subjects, was selected from the largest prospective population study in history, UK Biobank(6); comparison cohorts with PDFF >5% and/or BMI> 25 included 1779 individuals. MR protocol was acquired at 1.5 T, in a transverse slice located at the porta hepatis; two rapid sequences were used: a Shortened Modified Look Locker Inversion (ShMOLLI)(7) and a multiecho spoiled-gradient-echo. The T1 relaxation map acquired using the ShMOLLI sequence resulted with a decrease T1 due to the excess of iron, bias removed by an algorithm, which can be calculated from the T2* maps(8), from the T1 measurements, providing the cT1(9). Images were analyzed with a dedicated software and for each T2*, cT1 and PDFF image were drawn three circular region of interest (ROI).

              Results showed a cT1 median value of 666.0 ms for the reference group (both non-overweight and non-steatotic). Results were also compared with high risk subcohorts of non-overweight but steatotic patients (median cT1 of 712.5 ms), overweight but non-steatotic (median cT1 of 681.7 ms), and overweight and steatotic (median cT1 of 744.7). The comparison showed a cT1 values significantly higher in the higher-risk cohorts that the reference cohort.

              There were not significant differences of the cT1 values between woman and men and among age groups in men while significant decrease of cT1 values were observed in women between ages of 40-49 and 60-69 years.


              As previously reported by Scaglione et al.(3) there is a wide percentage of people affected by cirrhosis in US and identifying those individuals at risk of cirrhosis before it develops would be of enormous utility. To establish quantitative imaging biomarkers and to define normal range of them is essential in order to assess the presence, absence, or change of disease over time. In this contest the Authors hypothesize that participants with high cT1 values are more likely to suffer clinical outcomes. In addition, they underline that age and gender have a negligible influence on cT1, without needs of cT1 correction. The small, but statistically significant, increase in cT1 in the youngest female group, can be assumed to be pre-menopausal and estrogen levels related. Despite some limitation due to restricted age range (40-79 years) and definition of low-risk population just only with BMI and PDFF values, this article assesses, for the first time, the MRI reference range of cT1 values in a large population at low risk for NAFL, representing a benchmark for future studies regarding MR imaging biomarker for the quantitative assessment of fatty liver disease.


              REFERENCES

              1.    Hu K-C, Wang H-Y, Liu S-C, et al. (2014) Nonalcoholic fatty liver disease: updates in noninvasive diagnosis and correlation with cardiovascular disease. World J Gastroenterol 20:7718– 7729

              2.    Lade A, Noon LA, Friedman SL (2014) Contributions of metabolic dysregulation and inflammation to nonalcoholic steatohepatitis, hepatic fibrosis, and cancer. Curr Opin Oncol 26:100– 107

              3.    Scaglione S, Kliethermes S, Cao G, et al. (2015) The epidemiology of cirrhosis in the United States: a population-based study. J Clin Gastroenterol 49:690– 696

              4.    Banerjee R, Pavlides M, Tunnicliffe EM, et al. (2014) Multipara- metric magnetic resonance for the non-invasive diagnosis of liver disease. J Hepatol 60:69– 77

              5.    Pavlides M, Banerjee R, Sellwood J, et al. (2016) Multiparametric magnetic resonance imaging predicts clinical outcomes in patients with chronic liver disease. J Hepatol 64:308– 315

              6.    UK Biobank. (n.d.). http://www.ukbiobank.ac.uk

              7.    Piechnik SK, Ferreira VM, Dall’Armellina E, et al. (2010) Short- ened Modified Look-Locker Inversion recovery (ShMOLLI) for clinical myocardial T1-mapping at 1.5 and 3 T within a 9 heartbeat breathhold. J Cardiovasc Magn Reson 12:69

              8.    Wood JC, Enriquez C, Ghugre N, et al. (2005) MRI R2 and R2* mapping accurately estimates hepatic iron concentration in transfusion-dependent thalassemia and sickle cell disease pa- tients. Blood 106:1460– 1465. doi.org/10.1182/blood-2004- 10-3982

              9.    Tunnicliffe EM, Banerjee R, Pavlides M, Neubauer S, Robson MD (2017) A model for hepatic fibrosis: the competing effects of cell loss and iron on shortened modified Look-Locker inversion recovery T1(shMOLLI-T1) in the liver. J Magn Reson Imaging 45:450– 462. doi.org/10.1002/jmri.25392 '


              Dr. Marta Zerunian is a young radiology resident attending the third year of residency at the University of Rome "Sapienza" - Sant'Andrea University Hospital in Rome. She has been particularly interested in abdominal and oncologic radiology and was able to work extensively in this area during her residency focusing in particular on imaging quantitative biomarkers.

              Comments may be sent to: marta.zerunian@remove-this.gmail.com


              Hepatobiliary MRI as novel selection criteria in liver transplantation for hepatocellular carcinoma
              Ah Yeong Kim, Dong Hyun Sinn, Woo Kyoung Jeong, Young Kon Kim, Tae Wook Kang, Sang Yun Ha, Chul Keun Park, Gyu Seong Choi, Jong Man Kim, Choon Hyuck David Kwon, Jae-Won Joh, Min-Ji Kim, Insuk Sohn, Sin-Ho Jung, Seung Woon Paik, Won Jae Lee
              J Hepatol 2018; 68:1144-1152. doi.org/10.1016/j.jhep.2018.01.024

              Dr. Ana Margarida Alves, Resident, Department of Radiology, Oporto Hospital and University Centre, Oporto (Portugal).
              Prof. Dr. Manuela França, Hospitalar Assistant and Head of Radiology Department, Oporto Hospital and University Centre, Oporto (Portugal).

              Liver transplantation is a well-established indication for patients with early-stage hepatocellular carcinoma (HCC) and is available in most developed countries. Milan criteria are considered the gold standard for selecting these patients for liver transplantation and include: single nodule up to 5 cm; up to three nodules, none larger than 3 cm and no evidence of extrahepatic spread or macrovascular invasion [1]. In recent years, these morphological criteria have been subject of controversy because they might be too restrictive, rejecting patients with HCC whose liver transplantation would be potentially curative [2].

              Several studies have shown that HCC biology, such as microvascular invasion and tumor grade, is an important predictor of tumor recurrence after liver transplantation, but these features can only be evaluated from the explanted liver [3]. Consequently, many recent investigations aimed to establish clinical, analytical or imaging predictors of these histopathological tumor features [4].

              The objective of Kim AY et al. was to assess the risk of tumor recurrence after liver transplantation for HCC, based on pre-transplant gadoxetic acid-enhanced MRI features.

              Their retrospective study included 100 patients who received a liver transplant and had undergone pre-operative gadoxetic acid-enhanced MRI with hepatobiliary phase (HBP) from January 2009 to December 2013. All patients were evaluated for Milan criteria, tumor size, number and morphological type, tumor margins, satellite nodules, peritumoral enhancement in arterial phase, capsule or pseudocapsule in portal venous phase, peritumoral hypointensity on the HBP and apparent diffusion coefficients (ADC). The authors also evaluated the histopathological features of HCC in the explanted livers, including microvascular invasion and intrahepatic metastasis. The primary endpoint was time to recurrence.

              During the follow-up period, HCC recurrence was detected in 33 of 100 patients. In the univariate analyses, tumors with perinodular extension or a confluent multinodular type, a satellite nodule, peritumoral enhancement in the arterial phase, peritumoral hypointensity on the HBP and a lower ADC value were significantly associated with recurrence after liver transplantation in the overall group. In the multivariable-adjusted model including these factors, the presence of a satellite nodule (HR 3.07; 95% CI, 1.14–8.25) and peritumoral hypointensity on the HBP (HR 4.53; 95% CI, 1.53–13.44) were independent factors associated with recurrence. When patients were stratified according to the Milan criteria, recurrence-free survival was significantly better for those without high-risk radiological findings and who were transplanted either within the Milan criteria (88.4% vs. 33.3% at three years, p <0.001) or outside the Milan criteria (71.4% vs. 24.5% at three years, p <0.001). Most of the patients with high-risk radiological findings had microvascular invasion on histology (95%) and most of the patients without microvascular invasion on histology showed negative high-risk radiological findings (98%).

              According to the authors, the presence of satellite nodule and peritumoral hypointensity on HBP can independently predict tumor recurrence, either in patients transplanted within or outside the Milan criteria. They also suggest that the positive predictive value and specificity of these two high-risk radiological findings are adequately high for the prediction of histological microvascular invasion.

              These results are consistent with previous studies. Plessier et al. suggested that satellite lesions have a strong correlation with microvascular invasion and are an important cause of HCC recurrence [5]. Kim et al. described that peritumoral hypointensity on HBP images is a strong predictor of microvascular invasion and the decreased uptake of gadoxetic acid by hepatocytes around the tumor probably reflects the hemodynamic changes caused by minute portal venous invasion [6].

              This study has some limitations, such as its retrospective nature with potential selection bias. The study population was constituted mainly by patients with hepatitis B virus infection and, moreover, some of the patients had undergone prior treatments, such as transarterial chemoembolization, that could modify the MRI findings. However, the high-risk radiological findings were associated with recurrence-free survival either in treatment-naïve or treated patients.

              In conclusion, hepatobiliary MRI might be a valuable tool for optimizing the selection criteria for liver transplantation in HCC patients, but additional multicentric studies are needed for definitive validation.


              REFERENCES:

              1.    European Association For The Study Of The Liver & European Organization For Research And Treatment Of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J. Hepatol 2012; 56:908–943.

              2.    Yao FY, Roberts JP. Applying expanded criteria to liver transplantation for hepatocellular carcinoma: Too much too soon, or is now the time? Liver Transpl 2004; 10:919–921.

              3.    Mazzaferro V, Llovet JM, Miceli R, Bhoori S, Schiavo M, Mariani L, et al. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol 2009; 10:35–43.

              4.    Silva, M. F. & Sherman, M. Criteria for liver transplantation for HCC: what should the limits be? J. Hepatol 2011; 55:1137–1147.

              5.    Plessier A, Codes L, Consigny Y, Sommacale D, Dondero F, Cortes A, et al. Underestimation of the influence of satellite nodules as a risk factor for post-transplantation recurrence in patients with small hepatocellular carcinoma. Liver Transpl 2004; 10:S86–S90.

              6.    Kim KA, Kim MJ, Jeon HM, Kim KS, Choi JS, Ahn SH, et al. Prediction of microvascular invasion of hepatocellular carcinoma: usefulness of peritumoural hypointensity seen on gadoxetate disodium-enhanced hepatobiliary phase images. J Magn Reson Imaging 2012; 35:629–634.


              Dr. Ana Margarida Alves is a third-year radiology resident at Oporto Hospital and University Centre in Portugal. She graduated as a medical doctor at the Faculty of Medicine of Oporto University in July 2014. She is an active ESGAR member and regularly attends ESGAR annual meetings and workshops. Currently, she has a broad range of interests in diagnostic abdominal radiology, particularly liver and bowel imaging.


              Comments may be sent to: anamargarida.ca@remove-this.gmail.com



              Andrew D. Smith, Cody R. Branch, Kevin Zand, Charu Subramony, Haowei Zhang, Katherine Thaggard, Richard Hosch, Jason Bryan, Amit Vasanji, Michael Griswold, Xu Zhang.
              Liver Surface Nodularity Quantification from Routine CT Images as a Biomarker for
              Detection and Evaluation of Cirrhosis. Radiology. 2016 Sep; 280(3):771-81

              Cedric Bohyn – Resident, Department of Radiology, AZ Delta Hospital Roeselare & University Hospitals Leuven, Belgium
              Philippe Lefere – Department of Radiology, AZ Delta Hospital Roeselare, Belgium

              The goal of this retrospective study was to assess the feasibility of distinguishing a cirrhotic from a non-cirrhotic liver on routine CT-images by the use of a semi-automated scoring system that quantifies the liver surface nodularity (LSN).
              Performing a liver biopsy remains the gold standard in determining the cirrhotic stage of a liver. The sensitivity and specificity for accurate diagnosis of cirrhosis and its etiology ranges from 80 to 100 percent (1). However, biopsy should only be considered after non-invasive serologic and radiologic evaluation failed to confirm a diagnosis. The reason is that biopsy has many inherent risks like its invasive nature, sampling error, bleeding, infection and possible (but rare) even death. Because of this, non-invasive methods are necessary and they are to be examined whether they can be used for routine assessment of liver cirrhosis.
              The most frequently used non-invasive methods to diagnose compensated cirrhosis are serum laboratory tests and ultrasound (US) or MRI-guided elastography, but they have their drawbacks. Therefore, morphometric analyses are also evaluated such as liver volume ratios, splenic volume, or subjective assessment of LSN on US, CT, and MRI. None of these mentioned are proven to be adequate enough to replace the gold standard. Only severe surface nodularity in the setting of chronic liver disease strongly suggests cirrhosis and can warrant a biopsy.
              The author (A.D.S.) developed a semi-automated post-processing software able to quantify LSN on CT or MRI-images (Fig. 1). The hypothesis was that with this software LSN could reproducibly be quantified on routine CT-images, allowing accurate diagnosis and staging of the severity of HCV-induced cirrhosis. At the moment of the study, there were no known objective quantitative methods to determine LSN on routine CT imaging.
              The study group consisted of 94 patients of which 24 patients with a healthy liver and 70 with a spectrum of hepatitis C chronic liver disease (HCV CLD). HCV is the leading cause of cirrhosis and hepatocellular carcinoma in the US and it affects 200 million people worldwide. Its estimated that 10 – 20% of patients with HCV will develop liver cirrhosis and 1 - 5% will develop HCC within 20-30 years (2).
              The authors evaluated the accuracy, reproducibility, and intra- and interobserver variance of this semi-automated LSN-measurement for non-enhanced and enhanced (portal venous phase), and thin and thick-section CT-images for both acquisitions. The comparison was made with splenic volumes, LLS-to-TLV ratios (*), and total liver volume (TLV) for the different stages of CLD. (*) ratio of left lateral segment (LLS) to total liver volume (TLV).
              The accuracy of the LSN score for differentiating cirrhotic from non-cirrhotic livers was high and consistently higher compared to splenic volume and LLS/TLV (Fig 2). The sensitivity of LSN was higher than splenic volume and LLS-to-TLV ratios and had an equal specificity compared to LLS-to-TLV ratios.

              Furthermore, only LSN scores were higher for F4 decompensated versus compensated cirrhosis, suggesting an increase of LSN in size and heterogeneity with increasing severity of HCV cirrhosis.
              This accuracy is comparable to the accuracy of liver stiffness measurements by US or MR elastography. Using the dedicated software, LSN scoring obtained a high reproducibility across different section thicknesses, with or without IV contrast. This may serve as proof that it can be reliably used on different types of CT acquisitions.
              Intra- and interobserver agreement was very good with an intraclass correlation coefficient of 0.963 and 0.899, respectively.
              LSN quantification was also less time consuming (median total time 1.9 min) than measuring splenic and liver volumes or calculating the LLS-to-TLV ratios (10 – 25 min).
              Precirrhotic fibrosis was not investigated in this study. Pickhardt et al. investigated if this LSN scoring tool allows an accurate staging of hepatic fibrosis. They found accurate staging is possible of both significant (≥ F2) and advanced (≥ F3) levels of hepatic fibrosis. These stages are emerging as important clinical indicators that may influence management decisions. In addition, the diagnostic performance shows to be favourable in comparison to US and MRI elastography (3).
              A. D. Smith et al. did show in another study of patients with cirrhosis from a variety of causes, that there is a direct linear correlation between the LSN score and the clinical stage of cirrhosis. Moreover, the LSN score proved to be an independent predictor of cirrhosis decompensation and death (4). They suggest LSN could be a complementary tool in combination with the well-known MELD-score (Model End-stage Liver Disease) in evaluating cirrhosis from different causes.
              We can conclude that LSN quantifying is a promising tool to evaluate different stages of liver cirrhosis and even precirrhotic fibrosis. The main advantages are its reproducibility, time efficiency and ability to be retrospectively applied on routine CT-images.


              References

              1. Heidelbaugh, Joel J., and Michael Bruderly. "Cirrhosis and chronic liver failure: part I. Diagnosis and evaluation." Am Fam Physician 74.5 (2006): 756-62.
              2. Sebastiani, Giada, Konstantinos Gkouvatsos, and Kostas Pantopoulos. "Chronic hepatitis C and liver fibrosis." World journal of gastroenterology: WJG 20.32 (2014): 11033.
              3. Pickhardt, Perry J., et al. "Accuracy of Liver Surface Nodularity Quantification on MDCT as a Non-invasive Biomarker for Staging Hepatic Fibrosis." American Journal of Roentgenology 207.6 (2016): 1194-1199.
              4. Smith, Andrew D., et al. "Liver Surface Nodularity Score Allows Prediction of Cirrhosis Decompensation and Death." Radiology (2016): 160799.

               

               


              Dr. Cedric Bohyn is a second year resident under the University of Leuven training scheme, currently working at the AZ Delta Hospital in Roeselare (Belgium). He has interest in a wide variety of radiologic topics, yet with some predilection for abdominal radiology. He completed his undergraduate medical degree at the University of Leuven in 2015. Appointed secretary of the Young Radiologist Section (YRS – Belgian resident association as part of the Belgian Society of Radiology), he fully supports and promotes the training of residents. Moreover, he actively participated in organizing the BSR's annual conference of 2016 where he also presented various topics as he did at JFR 2016. As a junior resident, he aspires to continuously learn and strengthen his knowledge on the challenging radiological matter.
              Comments may be sent directly to Dr. Cedric Bohyn.


              Reducing Artifacts during Arterial Phase of Gadoxetate Disodium-enhanced MR Imaging: Dilution Method versus Reduced Injection Rate
              Kim YK, Lin WC, Sung K, Raman SS, Margolis D, Lim Y, Gu S, Lu D. Radiology, 2016, Ahead of Print, 10.1148/radiol.2016160241

              Dr. Domenico De Santis, "Sapienza" - University of Rome, Department of Radiological Sciences, Oncology and Pathology, Italy

              Gadolinium ethoxybenzyl dimeglumine (Gd-EOB-DTPA), labeled as Primovist in Europe and Japan and Eovist in the United States, is a liver-specific magnetic resonance (MR) contrast media characterized by a biliary excretion up to 50% in the normal liver. After it is injected intravenously, Gd-EOB-DTPA distributes throughout the vascular and extravascular spaces during the arterial, portal-venous and delayed phases. The key feature of this contrast media is its ability to be progressively taken up by the hepatocytes via the OATP1B1 and OATP1B3 transporters and excreted into the biliary duct via the MRP2 transporter during the hepatobiliary phase. This phase is typically acquired 20 minutes after the intravenous injection [1].
              These aforementioned features allow Gd-EOB-DTPA to have characteristics of a traditional gadolinium chelate contrast agent during the dynamic phases and to provide specific functional liver information, improving the detection of liver lesions and diffuse liver diseases, specifically liver metastases, hepatocellular carcinomas and liver cirrhosis [2, 3].
              An increasing number of institutions are adopting Gd-EOB-DTPA in clinical practice to evaluate patients with known or suspected focal liver disease. However, every radiologist who has performed MR examinations with Gd-EOB-DTPA has experienced the presence of ghosting artifacts during the arterial phase (AP), resulting in suboptimal or non-diagnostic AP. This issue, also documented in a number of publications [4, 5], should not be underestimated since the AP is of paramount importance in the characterization of liver lesions [6, 7].
              Different strategies have been adopted to reduce ghosting artifacts, such as diluting the contrast media or performing a slow-rate injection. However, no unanimous consent regarding the optimal injection strategy has been obtained thus far.
              The authors of this manuscript performed a retrospective study including 318 consecutive patients (mean age 62.7 years, 205 men) who underwent clinically indicated Gd-EOB-DTPA MRI examination. These patients were placed into two comparable cohorts:
              - Dilution cohort ([Gd-EOB-DTPA was diluted 1:1 with saline and injected at a rate of 2.0 mL/sec] n= 159);
              - Slow injection cohort ([Gd-EOB-DTPA was not diluted and was injected at a rate of 1.0 mL/sec] n= 159).
              The volume of Gd-EOB-DTPA injected was either 10 mL and 20 mL, the latter dose was used in patients who weighed more than 90.7 kg (200 lbs). In order to control potential bias and to assess intra-individual analysis, a sub-cohort of patients requiring imaging follow-up underwent MR examination with both methods. MR images were acquired with either 1.5 or 3 Tesla scanners. A fat-suppressed T1-weighted three-dimensional spoiled gradient echo sequence was performed in breath holding during the AP and the image analysis was subjectively performed by means of a 5-point scale by two independent readers blinded to the injection protocol (Table 1).
              In the patient-based analysis, the dilution cohort had a significantly lower mean artifact score compared to the slow injection cohort (1.46 VS 1.95; P <0.001) and was characterized by less frequent severe ghosting artifacts (3.8% VS 15.1%, P <0.001) (Fig 1).
              In the image-based analysis, the estimated log odds of mean and severe artifact score would decrease by 0.605 and 1.780, respectively, with the dilution method when compared with that attained with the slow injection method (all P <0.001).

              In the sub-cohort of patients who underwent both injection protocols there were significant differences in the mean artifact score changes and frequency of severe artifact according to the order of the two injection methods within each patient (Fig 2).Concerning the relationship of artifacts with contrast media dose, a higher incidence of severe motion artifact was reported when using 20mL of Gd-EOB-DTPA as opposed to 10mL (both injected at a rate of 2 mL/sec). However, in a subsequent analysis of dilution versus slow injection methods for the frequency of severe artifact, the effect of contrast media volume was significant only in the slow injection group, where the severe artifacts were reported in 16.8% of cases with 10mL of Gd-EOB-DTPA and 36% of cases with 20mL of Gd-EOB-DTPA (P =0.030).With this study the authors demonstrated that a 50% contrast agent dilution method outperforms a 50% injection rate reduction in minimizing ghosting artifact on AP images associated with administration of Gd-EOB-DTPA. Therefore, the dilution of Gd-EOB-DTPA with saline represents the best method to reduce the ghost artifact in AP and achieve a diagnostic MR examination. Thus, to the best of our knowedge, this approach is highly advisable in every institution dealing with advanced liver imaging.


              References
              1. Leonhardt M, Keiser M, Oswald S, Kuhn J, Jia J, Grube M, et al. Hepatic uptake of the magnetic resonance imaging contrast agent Gd-EOB-DTPA: role of human organic anion transporters. Drug Metab Dispos. 2010;38:1024-8.
              2. Reimer P, Schneider G, Schima W. Hepatobiliary contrast agents for contrast-enhanced MRI of the liver: properties, clinical development and applications. Eur Radiol. 2004;14:559-78.
              3. Kanki A, Tamada T, Higaki A, Noda Y, Tanimoto D, Sato T, et al. Hepatic parenchymal enhancement at Gd-EOB-DTPA-enhanced MR imaging: correlation with morphological grading of severity in cirrhosis and chronic hepatitis. Magn Reson Imaging. 2012;30:356-60.
              4. Davenport MS, Viglianti BL, Al-Hawary MM, Caoili EM, Kaza RK, Liu PS, et al. Comparison of acute transient dyspnea after intravenous administration of gadoxetate disodium and gadobenate dimeglumine: effect on arterial phase image quality. Radiology. 2013;266:452-61.
              5. Pietryga JA, Burke LM, Marin D, Jaffe TA, Bashir MR. Respiratory motion artifact affecting hepatic arterial phase imaging with gadoxetate disodium: examination recovery with a multiple arterial phase acquisition. Radiology. 2014;271:426-34.
              6. Cruite I, Tang A, Sirlin CB. Imaging-based diagnostic systems for hepatocellular carcinoma. AJR Am J Roentgenol. 2013;201:41-55.
              7. Wald C, Russo MW, Heimbach JK, Hussain HK, Pomfret EA, Bruix J. New OPTN/UNOS policy for liver transplant allocation: standardization of liver imaging, diagnosis, classification, and reporting of hepatocellular carcinoma. Radiology. 2013;266:376-82.


              Dr. Domenico De Santis is a fourth year Radiology Resident at "Sapienza" University of Rome, Italy. He is currently working as a research fellow at the Department of Radiology, Division of Cardiovascular Imaging at the Medical University of South Carolina, Charleston, USA. His clinical practice in Italy is primarily focused on oncological imaging with special interest in abdominal radiology-specifically liver imaging and virtual colonography-under the mentorship of Prof. Andrea Laghi. He has given scientific presentations at many international radiology meetings and he has his work has been publishing in several radiological journals.
              Comments may be sent directly to Dr. De Santis.


              Ureteral stones: Implementation
 of a Reduced-Dose CT Protocol in Patients in the Emergency Department with Moderate to High Likelihood of Calculi on the Basis of STONE Score
              Christopher L. Moore, MD; Brock Daniels, MD; Dinesh Singh, MD;
Seth Luty, MS;
Gowthaman Gunabushanam, MD; Monica Ghita, PhD; Annette Molinaro, PhD; Cary P. Gross, MD. Radiology. 2016 Sep; 280(3)

              Dr. Raquel Madaleno, Resident, Medical Imaging Department, University Hospital of Coimbra, Portugal
              Prof. Dr. Luís Curvo Semedo, Assistant Professor of Radiology, Faculty of Medicine and Medical Imaging Department, University Hospital of Coimbra, Portugal

              The main goal of this prospective study by Moore, C. et al (published in last September issue of Radiology) was to determine the sensitivity of reduced-dose CT in the diagnosis of ureteral stones in moderate to high risk patients presenting to the emergency department, requiring urologic intervention.
              Renal stones have an incidence of about 0,1-0,4% per year in the United States and in Europe. They usually reoccur, nearly in 75% of the cases during the following 20 years (1).
              CT is a method with high diagnostic accuracy in the detection of ureteral stones. The American College of Radiology Appropriateness Criteria emphasizes that, when CT is performed for stone disease, the reduced-dose CT protocols should be preferred, usually yielding an effective dose of about 3mSv. This is of special interest since, frequently, many imaging revaluations are needed (2). However, low-dose protocols are poorly implemented due to the concern of reducing the accuracy in detecting both ureteral stones and alternative diagnoses, which is one of the advantages of CT compared with other imaging techniques (1). In this study the authors used a reduced-dose CT protocol which was the subject of a previous publication, reaching an average radiation dose reduction of 88%.
              The patients were stratified based on STONE score in high (90% likelihood of ureteral stone), moderate (50% likelihood of ureteral stone) and low (<10% likelihood of ureteral stone) risk groups. The STONE score uses five criteria (sex, timing, origin, nausea and erythrocytes) that showed to consistently predict the likelihood of ureteral stones in previous studies. Reduced-dose CT was initially performed in 165 patients, including all high risk patients and 73% of patients with moderate risk. After that acquisition, a standard-dose CT was performed in 32% of the patients, when the radiologist determined that image quality was limiting the diagnostic accuracy. This value was slightly higher than expected by the authors, probably due to the radiologist discomfort with low-dose images and the decrease in diagnostic confidence. The reduced-dose CT images from patients who were rescanned with standard-dose CT were blindly reread, resulting in 30 true-positive and 18 true-negative findings for ureteral stone, and five false-negative findings for ureteral stone, without any false-positive findings, resulting in a sensitivity of 86% and a specificity of 100%. The false-negative cases represented five small stones that were expelled without need of intervention. Previous studies have shown that the reduced-dose CT is sensitive enough to detect large stones (> 5 mm) that may require urologic intervention, while it possesses a lower sensitivity in detecting small stones that usually do not require interventional procedures (2).
              Of all patients that were studied with reduced-dose CT alone, 25 procedures were necessary, namely 24 urologic procedures (lithotripsy, stent, surgical stone extraction or nephrostomy), and one non-urologic surgery for acute appendicitis.The clinical conditions that required these procedures were all correctly identified with reduced-dose CT, and therefore the study reached a sensitivity of 100% to detect abnormalities that required intervention. However, there was one case of mild diverticulitis identified on rescan with standard-dose CT only, that did not require surgical intervention.

              The results of this paper are similar to previous studies that achieved high sensitivity and specificity for diagnosing urolithiasis (3,4).The reduced-dose CT protocols were also evaluated in the management of acute appendicitis, with similar results comparably to standard-dose CT with regard to negative appendectomy rates (5). It would be interesting to see more studies about low-dose CT in the evaluation of the most relevant differential diagnoses for acute flank pain, namely cholecystolithiasis, diverticulitis, pelvic tumours and aortic aneurysms.
              In conclusion, this paper shows that reduced-dose CT protocols has a high diagnostic accuracy in the detection of ureteral stones. However, definition of an adequate level of noise that allows both the detection of urolithiasis and alternative diagnoses should be defined in order to allow a widespread implementation, specially in the emergency department.


              References
              1. Niemann, T., Kollmann, T., Bongartz, G. Diagnostic Performance of Low-Dose CT for the Detection of Urolithiasis: A Meta-Analysis. American Journal of Roentgenology 2008 191:2, 396-401
              2. Drake, T., Jain, N., Bryant, T., Wilson, I., Somani, B. Should low-dose computed tomography kidneys, ureter and bladder be the new investigation of choice in suspected renal colic?: A systematic review. Indian Journal of Urology 2014 Apr-Jun; 30(2): 137–143.
              3. Tack, D., Sourtzis, S., Delpierre, I., Maertelaer, V., Gevenois, P. Low-Dose Unenhanced Multidetector CT of Patients with Suspected Renal Colic. American Journal of Roentgenology 2003 180:2, 305-311.
              4. Poletti, P., Platon, A., Rutschmann, O., Schmidlin, F., Iselin, C., Becker, C. Low-Dose Versus Standard-Dose CT Protocol in Patients with Clinically Suspected Renal Colic. American Journal of Roentgenology 2007 188:4, 927-933.
              5. Kim, K., Kim, Y., Kim, S., Kim, S., Lee, Y., Kim, K., et al. Low-Dose Abdominal CT for Evaluating Suspected Appendicitis. The New England Journal of Medicine 2012; 366:1596-160.


              Dr. Raquel Madaleno is a third year resident working at the Medical Imaging Department, University Hospital of Coimbra, Portugal. She completed her undergraduate medical degree at the NOVA Medical School of the New University of Lisbon in 2013. She has her main interest in abdominal radiology, with particular regard to liver and bowel imaging.
              Comments may be sent to Central ESGAR Office at office@esgar.org


              Early peribilary hyperenhancement on MRI in patients with Primary Sclerosing Cholangitis: significance and association with the Mayo Risk Score.
              Ni Mhuircheartaigh JM, Lee KS, Curry MP, Pedrosa I, Mortele KJ. Abdom Radiol (NY). 2017 Jan;42(1):152-158.

              Dr. Christopher Tang, Radiology Registrar, Guy’s and St Thomas’ NHS FT, London/GB
              Dr. Sofia Gourtsoyianni, Consultant Radiologist, Guy’s and St Thomas’ NHS FT, London/GB

              This paper published by Mhuircheartaigh et al in Abdominal Radiology focused on the use of contrast enhanced MRI in patients with Primary Sclerosing Cholangitis (PSC). Two main aims were evaluated: (1) Whether there is any relationship between peribiliary hyperenhancement on MRI and the Mayo risk score, and (2) Whether peribiliary hyperenhancement on MRI correlates with overall clinical outcome.
              MRI is well established in the diagnosis of PSC, however there has been limited evidence characterising its role in terms of predicting disease severity and outcome. The Mayo risk score is a validated clinical model calculating estimated survival points for PSC patients, based on patient age, history of variceal bleeding, and blood markers including bilirubin, albumin and aspartate aminotransferase (AST).
              This study was performed retrospectively, including all patients with known or suspected PSC who underwent contrast-enhanced MRI of their liver over a 4 year period. As part of the MRI protocol, a gadolinium based contrast was used, with post-contrast images obtained during the arterial, portal venous (45s after the arterial phase), and delayed venous phase (90s after the arterial phase). Two abdominal imaging radiologists independently reviewed the MRI studies, evaluating for the absence or presence of peribiliary hyperenhancement on each phase of imaging. If hyperenhancement was present, then it was classified as localised, segmental or diffuse.
              A total of 62 patients were identified, who had their diagnosis of PSC confirmed by a combination of clinical assessment, ERCP and MRCP findings and liver biopsy (in a minority). These patients were initially stratified into low (n=41), medium (n=14) and high (n=7) risk groups based on their Mayo risk score.
              The interobserver agreement for peribiliary hyperenhancement was good (k=0.919), with a consensus reached for those cases where there was initial disagreement. Accounting for this, the authors demonstrated a significant difference in the prevalence of arterial peribiliary hyperenhancement between the intermediate and low risk groups (p<0.05), with a difference in prevalence of arterial peribiliary hyperenhancement approaching significance between the high and low risk groups (p=0.059). No significant association was noted with later phase enhancement. Furthermore, there was a significant association between the extent of peribiliary hyperenhancement with the Mayo risk group (p<0.01), with more diffuse enhancement associated with a high Mayo risk.
              A time to event analysis was also performed based on the presence of arterial peribiliary hyperenhancement, using a combined end point of death or liver transplantation. This demonstrated a statistically significant difference in survival times between patients who exhibited arterial peribiliary hyperenhancement and those who did not.
              The study finding of a statistically significant association between arterial peribiliary hyperenhancement and higher Mayo risk scores and thus poorer prognosis is interesting, since the role of MRI in monitoring PSC is currently unclear. Although no causality was demonstrated, the authors postulate that arterial peribiliary hyperenhancement is a reflection of ongoing acute inflammation and cholangitis, which would intuitively suggest a worse prognosis. PSC is a slowly progressive disease, and current management relies on continual monitoring of disease progression. Although the Mayo risk score already provides a way to prognosticate PSC patients, one potential advantage of using MRI to assess for arterial peribiliary hyperenhancement is the ability to assess for disease heterogeneity within an individual and potentially monitor treatment response.

              The authors note some study limitations. Firstly the study only demonstrated an association of arterial peribiliary hyperenhancement with the Mayo score, which is a surrogate marker of progression, rather than a true assessment of outcome. Secondly, the study cohort only included a relatively small number of patients who had high Mayo risk scores. Finally, the study only evaluated for peribiliary hyperenhancement, and other clinical features of PSC such as biliary strictures and cirrhosis were not assessed. The role of these other factors could also be evaluated in future research. Correlation with T2 weighted signal intensity and/or DWI characteristics of peribiliary hyperenhancement areas might also be worth investigating in the future.
              This is certainly an interesting study that highlights that arterial phase is of clinical value when assessing PSC patients with contrast enhanced liver MRI, and it is something that should be commented on.


              References
              1. Kim WR, Therneau TM, Wiesner RH, et al. (2000) A revised natural history model for primary sclerosing cholangitis. Mayo Clin Proc 75(7):688–694
              2. Petrovic BD, Nikolaidis P, Hammond NA, et al. (2007) Correlation between findings on MRCP and gadolinium-enhanced MR of the liver and a survival model for primary sclerosing cholangitis. Dig Dis Sci 52(12):3499–3506
              3. Ruiz A, Lemoinne S, Carrat F, et al. (2014) Radiologic course of primary sclerosing cholangitis: assessment by three-dimensional magnetic resonance cholangiography and predictive features of progression. Hepatology 59(1):242–250


              Dr. Christopher Tang is a second year radiology registrar at Guy’s and St Thomas’ Hospital, London. He graduated from the University of Oxford before completing his undergraduate medical training with distinction at King’s College London. He currently has a broad range of interests within diagnostic radiology and has presented at international radiology and nuclear medicine conferences. Comments may be sent to Central ESGAR Office at office@remove-this.esgar.org


              Magnetic Resonance Elastography is as Accurate as Liver Biopsy for Liver Fibrosis Staging
              Hiroyuki Morisaka, Utaroh Motosugi, Shintaro Ichikawa, Tadao Nakazawa, Tetsuo Kondo, Satoshi Funayama, Masanori Matsuda, Tomoaki Ichikawa, Hiroshi Onishi.
              J Magn Reson Imaging 2017 Oct 14. doi: 10.1002/jmri.25868

              Dr Nathania Bonanno, Higher Specialist Trainee, Mater Dei Hospital, Msida/MT
              Dr Kelvin Cortis, Consultant Radiologist, Mater Dei Hospital, Msida/MT

              The importance of diagnosing hepatic fibrosis at an early, potentially reversible, stage is that of preventing complications arising from progression to cirrhosis (including aggravated risk of having hepatocellular carcinoma and deranged liver function that may lead to liver failure), and also preventing the complications of portal hypertension (including ascites and variceal bleeding).  This introductory concept set the tone for the study carried out by Morisaka et al., which has just been published in the September issue of the Journal of Magnetic Resonance Imaging (impact factor 3.083).  

              Percutaneous image-guided liver biopsy is an imperfect gold standard, with limitations that include sampling errors and intra/inter-observer variability.  Various image-based methods have been employed for the non-invasive estimation of liver fibrosis, including T1 and T2 measurements, morphological assessment of hepatic architecture, contrast-enhancement, and elastography. Ultrasonography (US)-based elastography1 and magnetic resonance elastography (MRE)2 have already been well-validated for evaluating liver fibrosis. In fact, prior studies have shown that liver MRE has a high repeatability3-5 and has been cross-validated with biopsy and US-based elastography6,7.

              The study conducted by Morisaka et al. is novel, in that the authors ventured beyond the boundaries of former studies and used resected liver specimens as reference standards for liver fibrosis. The authors did so with the aim of comparing the diagnostic accuracy of fibrosis staging by MRE and liver biopsy.  This is in contrast to earlier studies wherein MRE could not be directly compared to liver biopsy because biopsy was used as a reference standard8-10.  

              The study population was retrospectively identified. In all, 200 patients who underwent preoperative MRE (using 2D liver MRE with gradient-echo sequence on a 1.5 or 3T scanner) and subsequent surgical liver resection were included in this study. Next, the patient cohort was distributed to two datasets, the preliminary set (n=80) and the validation set (n=120). Data from the former were used to estimate cut-off and distributions of liver stiffness values measured by MRE for each of the five liver fibrosis stages as determined by the METAVIR scoring system (F0-F4). In the remaining 120 patients – the study group – liver biopsy specimens were obtained from the resected liver tissues using a standard biopsy needle and then examined to compare the diagnostic accuracies of MRE- and liver biopsy-based fibrosis staging methods.

              Two experienced abdominal radiologists, blinded to the histological results, independently measured the liver stiffness value on MRE. Two types of MRE-based liver fibrosis staging methods (threshold and Bayesian prediction method) were applied to the assembled data.  Two pathologists, also blinded, evaluated all biopsy samples independently to stage liver fibrosis using surgically resected whole tissue specimens as the reference standard. 

              The results from the first radiologist and pathologist were used for the main analyses and that from the second observer was used for the assessment of inter-observer agreement.
              For the analytic part of the study, the authors compared statistical accuracy for liver fibrosis staging (graded as significant fibrosis ≥F2, severe fibrosis ≥F3, and cirrhosis F4) between liver biopsy and the two MRE-based methods using a modified McNemar’s test (which is, simply put, a test to determine whether there is statistical difference between two paired populations from which the samples are drawn).

              The overall diagnostic accuracy of MRE marginally surpassed that of liver biopsy – 59.1% (71/120) and 51.6% (62/120), respectively. Diagnostic accuracies of MRE for significant fibrosis, severe fibrosis, and cirrhosis were all statistically equivalent to that of liver biopsy (p ≤ 0.017). The proportions of under- and over-diagnosis between liver biopsy and MRE were also statistically comparable. The proportion of precise staging, i.e., not over- and under-staging, was 50-60% overall for both MRE- and liver biopsy-based staging.

              Morisaka et al. set out to prove that MRE can be an alternative to liver biopsy for fibrosis staging; they have successfully done so by demonstrating that the diagnostic accuracy of MRE-based methods for liver fibrosis staging is equivalent to that of liver biopsy.  

              This article is presently one of a kind and its results may reshape current practice –the need for liver biopsy will be alleviated and MRE can make its way to the forefront as the leading method of liver fibrosis staging. It offers a non-invasive, less-costly alternative to liver biopsy sampling for assessing fibrosis in patients with chronic liver disease.

              The article is exceptionally-written, comprehensive, and certainly worth the read.  
              _________________________________________________________________________________________________________________________________________________________________________________

              References
              1.    Castera L, Vergniol J, Foucher J, et al. Prospective comparison of transient elastography, Fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C. Gastroenterology 2005;128: 343–350.
              2.    Venkatesh SK, Yin M, Ehman RL. Magnetic resonance elastography of liver: technique, analysis, and clinical applications. J Magn Reson Imaging 2013;37:544–555.
              3.    Hines CD, Bley TA, Lindstrom MJ, Reeder SB. Repeatability of magnetic resonance elastography for quantification of hepatic stiffness. J Magn Reson Imaging 2010;31:725–731.
              4.    Shire NJ, Yin M, Chen J, et al. Test-retest repeatability of MR elastography for noninvasive liver fibrosis assessment in hepatitis C. J Magn Reson Imaging 2011;34:947–955.
              5.    Venkatesh SK, Wang G, Teo LL, Ang BW. Magnetic resonance elastography of liver in healthy Asians: normal liver stiffness quantification and reproducibility assessment. J Magn Reson Imaging 2014;39:1–8.
              6.    Oudry J, Chen J, Glaser KJ, Miette V, Sandrin L, Ehman RL. Cross-validation of magnetic resonance elastography and ultrasound-based transient elastography: a preliminary phantom study. J Magn Reson Imaging 2009;30:1145–1150.
              7.    Motosugi U, Ichikawa T, Amemiya F, et al. Cross-validation of MR elastography and ultrasound transient elastography in liver stiffness measurement: discrepancy in the results of cirrhotic liver. J Magn Reson Imaging 2012;35:607–610.
              8.    Venkatesh SK, Wang G, Lim SG, Wee A. Magnetic resonance elastography for the detection and staging of liver fibrosis in chronic hepatitis B. Eur Radiol 2014;24:70–78.
              9.    Batheja M, Vargas H, Silva AM, et al. Magnetic resonance elastography (MRE) in assessing hepatic fibrosis: performance in a cohort of patients with histological data. Abdom Imaging 2015;40:760–765.
              10.    Yin M, Glaser KJ, Talwalkar JA, Chen J, Manduca A, Ehman RL. Hepatic MR elastography: clinical performance in a series of 1377 consecutive examinations. Radiology 2015:142141.

              _________________________________________________________________________________________________________________________________________________________________________________

              Dr. Nathania Bonanno is a third year radiology resident at Mater Dei Hospital, Malta. She completed her undergraduate medical degree at the University of Malta in 2011. Her main interests are in diagnostic and interventional abdominal and pelvic radiology, with special regard to oncological imaging. She has presented multiple scientific studies at numerous international and national radiology conferences.
              Comments are to be sent directly to kelvin.cortis@remove-this.gov.mt or nathania.bonanno@remove-this.gov.mt.  

               



              McInnes MD, Hibbert RM, Inácio JR, Schieda N. Focal Nodular Hyperplasia and Hepatocellular Adenoma: Accuracy of Gadoxetic Acid-enhanced MR Imaging-A Systematic Review. Radiology. 2015 Nov; 277(2):413-423.

              Dr. Annalisa Mantarro (Radiology Resident, Pisa University Hospital, Pisa/IT)
              Prof. Emanuele Neri (Associate Professor of Radiology, Pisa University Hospital, Pisa/IT)

              The purposes of this systematic review, published in Radiology by McInnes in November 2015, were: 1) to assess the diagnostic accuracy of hepatobiliary phase (HBP) in gadoxetic acid–enhanced magnetic resonance imaging (MRI) of the liver for the diagnosis of focal nodular hyperplasia (FNH) versus hepatocellular adenoma (HCA); 2) to identify the rate of reported iso- or hyperintense HCAs and hypointense FNHs in HBP.

              Both FNHs and HCAs are benign hepatic neoplasms, which affect similar adult population with overlapped features (such as hypervascularity on enhanced dynamic study) at MR examination. On this ground, accurate imaging differentiation of these lesions is crucial, since the therapeutic management is very different: frequently FNHs are treated conservatively, while HCAs require resection due to its possible complications, such as haemorrhage or malignant degeneration. Based on current knowledge, the HBP of gadoxetic acid-enhanced MRI guides the differential diagnosis between these two hepatic entities with high diagnostic accuracy: FNHs are typically iso/hyperintense owing to abnormal biliary ductules; while HCAs are commonly hypointense, for the lack of biliary ductules1,2,3.

              However, recent studies reported that inflammatory HCAs represent more than half of all HCAs, showing higher rate of iso- or hyperintensity at HBP4.

              This systematic review was written according to PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), and the Cochrane Handbook of Diagnostic Test Accuracy Reviews. The inclusion criteria are summarized in the Table 1.

              The literature search yielded 1286 literature citations. After the review of all records, 61 articles were retrieved in full-text for further evaluation  and  a  total  of 6 studies  (309 patients; 164 with HCA, 233 with FNH) fulfilled  the  inclusion  criteria for the diagnostic accuracy assessment (primary outcome). Moreover, a total of 12 case series and case reports were included, since they reported either the rate of iso- or hyperintense HCAs or hypointense FNHs in the HBP (secondary outcomes, Figure 1).

              The sensitivity in FNH diagnosis based on HBP was high, ranging from 0.91 to 1.00 (lower margin of the 95% confidence interval, CI 0.77). The specificity also was generally high, ranging from 0.87 to 1.00 (lower margin of the 95% CI 0.54, Figure 2). Of note, specificity was lowest among studies in which molecular subtyping of HCA was performed. The rate of iso- or hyperintensity of HCA in HBP ranged considerably from 0% to 70%, occurring more frequently in the inflammatory subtype; while the percentage of hypointense FNHs in HBP were 0%-23% (Figure 3).

              This study pointed out the high diagnostic accuracy of gadoxetic acid–enhanced MRI in differentiating HCAs from FNHs. Among the included studies for the diagnostic accuracy evaluation, it is noteworthy that only one study classified HCA subtypes with molecular imaging, reporting them in a minority of patients (29/71)5, and thus producing the lowest specificity rate (87%; 95% CI 77-94). On the basis of these findings, among the studies in which molecular subtyping was not performed, the detected higher specificity could be the result of inflammatory HCA misclassification (iso- or hyperintense in HBP) as telangectatic FNH. The lack of HCA subtyping potentially produced fewer false-positive results, resulting in overestimation of specificity. This hypothesis was supported by data of the included case series, that provided molecular subtyping and a much higher rate of iso- or hyperintense HCAs in HBP. In this respect, among the included studies for diagnostic accuracy assessment the percentage of iso- or hyperintense HCAs in HBP was much lower (range 0%-13%) than the rate reported in case series (range 9%-70%).

              This study further strengthens the importance of gadoxetic acid–enhanced MRI with liver-specific contrast agents for HCA/FNH differentiation. Nevertheless, additional large studies using molecular imaging are needed to both correctly identify inflammatory HCA and determine the role of HBP in predicting HCA subtype6.

              References
              1. Grazioli L, Bondioni MP, Haradome H et al (2012). Hepatocellular adenoma and focal nodular hyperplasia: value of gadoxetic acid-enhanced MR imaging in differential diagnosis. Radiology 262:520–529.

              2. Neri E, Bali MA, Ba-Ssalamah A et al (2015). ESGAR consensus statement on liver MR imaging and clinical use of liver-specific contrast agents. Eur Radiol [Epub ahead of print].
              3. Bieze M, van den Esschert JW, Nio CY et al (2012) Diagnostic accuracy of MRI in differentiating hepatocellular adenoma from focal nodular hyperplasia: prospective study of the additional value of gadoxetate disodium. AJR Am J Roentgenol 199:26–34.
              4. Shanbhogue AK, Prasad SR, Takahashi N et al (2011). Recent advances in cytogenetics and molecular biology of adult hepatocellular tumors: implications for imaging and management. Radiology 258:673–693.
              5. Grieser C, Steffen IG, Kramme IB et al (2014). Gadoxetic acid enhanced MRI for differenti- ation of FNH and HCA: a single centre expe- rience. Eur Radiol 24:1339–1348.
              6. Merkle EM1, Zech CJ, Bartolozzi C et al (2015). Consensus report from the 7th International Forum for Liver Magnetic Resonance Imaging. Eur Radiol [Epub ahead of print].

              Additional educational material:
              EURORAD Case No: 11885 - Inflammatory hepatocellular adenoma - CT and MRI findings
              Ramos Andrade D, Costa Y, Curvo Semedo L et al.

              ESGAR 2015: SS 14.09 - Focal nodular hyperplasia versus inflammatory adenoma: clues for a confident differential diagnosis during MR imaging with a hepatobiliary (Gd-EOB-DTPA) contrast agent.
              Battaglia V, Turturici L, Mantarro A et al.

              ESGAR 2015: EE-163 - Hepatic adenoma: pictorial review of MRI findings and correlation with new molecular-pathological classification
              Ciresa M, De Gaetano AM, Guerra A et al.


              Dr. Annalisa Mantarrois a final year Resident at University of Pisa, in Italy. Her major field of interest is abdominal radiology, with particular regard to MR liver imaging and CT colonography. She has published in European Journal of Radiology, British Journal of Radiology, Abdominal Imaging, World Journal of Radiology, and Medical Radiology. Has been presenter of scientific papers at ESGAR, ECR, RSNA and SIRM meetings.

              Comments may be sent directly to Dr. Mantarro.


              Raghavan K, Jeffrey RB, Patel BN, DiMaio MA, Willmann JK, Olcott EW. MDCT Diagnosis of Perineural Invasion Involving the Celiac Plexus in Intrahepatic Cholangiocarcinoma: Preliminary Observations and Clinical Implications. AJR. 2015; 205:578-584.

              Ruben Vandenbulcke – Resident, Department of Radiology, AZ Delta Hospital Roeselare & University Hopitals Leuven, Belgium
              Philippe Lefere
              – Department of Radiology, AZ Delta Hospital Roeselare, Belgium

              The purpose of this retrospective study, published in the American Journal of Roentgenology in December 2015 by Raghavan et al., was to test if soft-tissue infiltration along the celiac plexus and delayed enhancement exceeding two-thirds of the tumor area on preoperative Multi Detector Computed Tomography (MDCT) correlate with histologic evidence of perineural invasion in resected intrahepatic cholangiocarcinomas. Both conditions could possibly indicate irresectability of these malignant intrahepatic lesions.
              Intrahepatic cholangiocarcinoma (ICC) is the second cause of primary liver cancer after hepatocellular carcinoma, representing 10-20 % of all primary malignant liver tumors. ICCs have an aggressive tumor biology with 5-year survival rates of 5-10% for unresectable disease and 20-35% for patients where a curative treatment is chosen with radical surgical resection.1  These rates are indicating an unmet need for multimodal treatment strategies to improve current survival and recurrence-free survival rates.

              Twenty patients who underwent resection for intrahepatic cholangiocarcinoma were analyzed in this single centre retrospective study. Preoperative MDCT image sets were reviewed by two radiologists for perineural invasion involving the celiac plexus. Perineural invasion was diagnosed when contiguous soft-tissue infiltration was noted extending from the intrahepatic  tumor directly along the extrahepatic perineural pathways to ultimately involve the fat planes around the celiac artery. The two known extrahepatic pathways include the neural plexus along the common hepatic artery within the hepatoduodenal ligament for right liver lobe tumors and the neural plexus along the left gastric artery within the gastrohepatic ligament for left liver lobe tumors (Figure 1). Also tumor size and delayed enhancement of tumor volume were noted.
              Each resected intrahepatic cholangiocarcinoma specimen was histologically examined with perineural invasion defined as presence of neoplastic cells within the epineurium, perineurium or endoneurial space.
              Preoperative MDCT showed infiltration along the celiac artery in 6 out of 20 patients with in 5 out of these 6 cases histologic examination revealing intratumoral perineural invasion. In this small group, soft-tissue infiltration along the celiac artery on preoperative MDCT was significantly associated with histologic evidence of perineural invasion (Table 1). No significant association was found on perineural infiltration and tumor size or delayed enhancement more than two-thirds of tumor area.

              Despite the small population size, this is the first study comparing histologic findings of perineural invasion with MDCT appearance of soft-tissue infiltration along the perineural celiac axis in the setting of intrahepatic cholangiocarcinomas.

              Only few patients with intrahepatic cholangiocarcinoma present with resectable disease at the time of presentation because of the aggressive behavior of these tumors. Resectability of intrahepatic cholangiocarcinoma is defined as the ability to resect tumor to negative margins while preserving adequate functioning liver. Patients demonstrating intrahepatic metastases, visceral peritoneum perforation, macrovascular or periductal invasion, lymphatic spread and extrahepatic metastases should not undergo resection because of the poor recurrence-free survival.2,3

              In similarity to pancreatic adenocarcinoma where perineural invasion is associated with a poor prognosis, perineural invasion in intrahepatic cholangiocarcinoma is a major factor contributing to the high incidence of local recurrence after resection with curative intent.3,4 This finding on MDCT is a negative prognostic factor and a contraindication for major hepatic resection with curative intent due to distant extrahepatic perineural and lymphovascular tumor spread.4,5
              The high incidence of recurrence is specifically associated with this perineural en lymphovascular invasion, highlighting the need for more effective adjuvant therapies after radical tumor resection with curative intent.5

              Given the relatively poor response to systemic chemotherapy (gemcitabine and cisplatin) for unresectable cholangiocarcinoma, local transarterial therapies are developed such as transarterial chemoembolization (TACE) and selective internal radiotherapy (SIRT). These therapies are showing anti-tumor effects with acceptable toxicities.1,2 Results with SIRT are more pronounced in patients with solitary tumors and absent extrahepatic tumor spread, which could be an effective downstaging method for secondary surgical treatment.6

              More studies with larger sample size are needed to more extensively explore correlations between preoperative MDCT findings and the behavior of intrahepatic cholangiocarcinoma. MDCT diagnosis of perineural invasion of the celiac plexus may assist in determination of prognosis and treatment planning.


               

              References:
              1. Mavros MN, Economopoulos KP, Alexiou VG, Pawlik TM. Treatment and prognosis for patients with intrahepatic cholangiocarcinoma: systematic review and meta-analysis. JAMA Surg. 2014; 149:565-574.
              2. Bridgewater J, Galle PR, Khan SA, et al.: Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma. J Hepatol 2014; 60:1268–1289.
              3. Shirai K, Ebata T, Oda K, et al. Perineural invasion is a prognostic factor in intrahepatic cholangiocarcinoma.World J Surg 2008; 32:2395–2402.
              4. Deshmukh SD, Willmann JK, Jeffrey RB. Pathways of extrapancreatic perineural invasion by pancreatic adenocarcinoma: evaluation with 3D volume-rendered MDCT imaging. AJR 2010; 194:668–674.
              5. Fisher SB, Patel SH, Kooby DA, et al. Lymphovascular and perineural invasion as selection criteria for adjuvant therapy in intrahepatic cholangiocarcinoma: a multi-institution analysis. HPB 2012; 14:514–522.
              6. Mouli S, Memon K, Baker T, et al. Yttrium-90 radioembolization for intrahepatic cholangiocarcinoma: safety, response, and survival analysis. J Vasc Interv Radiol. 2013; 24:1227–1234. 

              Additional educational materials:
              EURORAD Case No:1347 – Cholangiocarcinoma
              Bizimi V, Kailidou E, Katsiva V, Douridas G, Tibishrani M.
              ESGAR 2013: EE-007 – Multimodality assessment of Cholangiocarcinoma. A challenge for the radiologists.
              Sanchez GA, Parrilla JS, Radosevic A, Pedrosa NR, Lopez JCA, Barrera MB.


              Dr. Ruben Vandenbulcke is a second year resident working at the Department of Radiology at AZ Delta Hospital Roeselare, following the radiology training scheme at the University Hospitals Leuven. He completed his undergraduate medical degree at the Catholic University of Leuven in 2014. He  has a main interest in abdominal radiology, with particular regard to interventional abdominal radiology.

              Comments may be sent directly to Dr. Ruben Vandenbulcke.


              Lee YJ, Lee JM, Lee JS et al. Hepatocellular Carcinoma: Diagnostic Performance of Multidetector CT and MR Imaging — A Systematic Review and Meta-Analysis. Radiology. 2015; 275: 97-109

              Dr. Davide Bellini, "Sapienza" - University of Rome, Department of Radiological Sciences, Oncology and Pathology, Italy
              Dr. Riccardo Ferrari, "Sapienza" - University of Rome, Department of Radiological Sciences, Oncology and Pathology, Italy

              This paper published in Radiology by Lee et al in April 2015 (1) aims to provide evidence based advices about which imaging modality to prefer in the setting of hepatocellular carcinoma (HCC).

              Early detection of HCC is extremely important given that the diagnosis of HCC in an early stage allows curative treatment strategies and improves 5-years survival rate by more than 50% (2). Due to the lack of large randomized controlled trial assessing the diagnostic accuracy of different imaging modalities for detection of HCC, the present paper provides the best level of evidence and should be considered the most clinically relevant article on this topic.
              Authors performed a systematic review and meta-analysis of the literature published in the past decade (from January 2000 to December 2012) in the attempt to obtain updated diagnostic performance values of CT and MR imaging for detection of HCCs in patients affected by chronic liver disease, on per patient and per lesion basis. They also evaluated the influence of hepatobiliary contrast agents on diagnostic performance.
              Methods for analysis and inclusion criteria were based on the recommendations established by the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)(3). The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2 tool)(4) was used to evaluate quality of included studies. Heterogeneity was quantified by using the I2, sub-group analysis and meta-regression analysis were used to evaluate factors that could affect heterogeneity.
              Forty studies (six on CT, 22 on MR and 12 on both CT and MR imaging) were included in the quantitative analysis, evaluating 1135 patients and 1332 HCCs with CT, 2489 patients and 2320 HCCs with MR. The mean size of the HCCs was approximately 2 cm (ranging from 0.9 to 4.6 cm), CT scanner used was at least 16 row MDCT in most of the studies (11 of 18), 1.5-Tesla magnetic field and hepatobiliary contrast agents were used in most of the articles on MR.
              As major result, authors suggest that MR imaging should be considered the imaging modality of choice for evaluating HCCs in patients with chronic liver disease due to the higher per-lesion sensitivity compared to CT (80%.vs 68%; P = .0023) (Figure 1). For HCC lesions smaller than 1 cm, sensitivity decrease by 40% (Se = 48 %) for MR and by 54% (Se = 31%) for CT.

              No significant differences were found in cumulative values of Sensitivity and Specificity on per patient basis between MR and CT (CT: Se 88%, Sp 74-100%; MR: Se 94%, Sp 81-100%). Moreover, promising evidences of improved sensitivity using hepatobiliary contrast agent have been reported. In particular, the use of Gadoxetic acid -enhanced MR imaging showed significantly higher per lesion sensitivity than MR imaging performed with other contrast agents (87% vs 74%, P = .03). This result further strengthens the importance of gadoxetic acid–enhanced MR imaging in the evaluation of patients suspected to have HCC.
              Two limitations of the study should be mentioned. Cumulative value of sensitivity could be overestimated due to the retrospective nature of studies included in the analysis. The heterogeneity observed among studies included for per-lesion analysis reduces the strength of results.


              References
              1. Lee YJ, Lee JM, Lee JS, et al. Hepatocellular carcinoma: diagnostic performance of multidetector CT and MR imaging-a systematic review and meta-analysis. Radiology. 2015;275(1):97-109.
              2. Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Lancet. 2012;379(9822):1245-55.
              3. Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Ann Intern Med. 2009;151(4):W65-94.
              4. Whiting PF, Rutjes AW, Westwood ME, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med. 2011;155(8):529-36.


              Dr. Davide Bellini is a final year radiology resident on the “Sapienza, University of Rome” training scheme in Italy. He has a main interest in abdominal radiology, with particular regard to CT colonography. He has a vivid interest in Evidence Based Medicine, in particular meta-analysis and guidelines development. He has presented lectures and scientific talks at a number of international radiology meetings and has published in several radiological and gastroenterological journals.

              Comments may be sent directly to Dr. Davide Bellini.


              Huh J, Kim SY, Yeh BM, Lee SS, Kim KW, Wu EH, Wang ZJ, Zhao LQ, Chang WC.
              Troubleshooting Arterial-Phase MR Images of Gadoxetate Disodium-Enhanced Liver
              Korean J Radiol. 2015 Nov-Dec;16(6):1207-15. doi:10.3348/kjr.2015.16.6.1207. Epub 2015 Oct 2
              6

              Dr. Daniel Ramos Andrade, Resident, Medical Imaging Department, University Hospital of Coimbra, Portugal
              Prof. Dr. Luís Curvo Semedo, Assistant Professor of Radiology, Faculty of Medicine and Medical Imaging Department, University Hospital of Coimbra, Portugal

              Gadoxetate disodium is widely used nowadays for characterization of focal liver lesions, as well as for detection of liver metastases and hepatocellular carcinoma in cirrhotic patients, because of its combined properties of a conventional non-specific extracellular and a hepatocyte-specific contrast agent [1].
              Unfortunately, arterial-phase images are sometimes of very poor quality due to artifacts and weak arterial enhancement.

              The purpose of this review article, published by the Korean Journal of Radiology in late 2015 by Huh et al. was to identify these two challenges and to suggest possible solutions for overcoming them.

              A review of the literature on this subject is very confounding because some authors believe degradation of arterial phase image quality is due to Gibbs phenomenon / ringing / truncation artifacts, related to rapid changes in the contrast concentration during the obtainment of the data in the center of the k-space [2,3,4], while others postulate that transient severe motion / respiratory motion artifact / acute transient dyspnoea is the main culprit [5,6]. It can be very difficult to distinguish both artifacts. Ringing artifacts usually manifest as duplicates of strongly enhanced vessels that are centered on the vessels and fade further away from the vessels, being typically confined to the abdomen, whereas motion artifacts appear as duplicates of all the abdominal organs and abdominal wall and typically extend both anteriorly and posteriorly to the abdomen [7].

              This article ultimately concludes that transient motion is the main source of artifacts in the clinical practice and not the ringing artifacts. After this review was published, another study by Motosugi et al further added that severe artifacts in the arterial phase were mainly associated with breath-hold failure (28 of 33 patients with severe artifacts) [8].
              It is believed that transient severe motion artifacts occur in about 10.7-18% of patients but the pathophysiology and causes remain elusive [9]. While the risk factors are yet to be identified, this article states that we can attempt to decrease these artifacts by using a single-breath-hold multiple arterial-phase acquisition [10] or using motion-insensitive sequences like CAIPIRINHA VIBE and radial-VIBE.

              References:
              [1] Campos JT, Sirlin CB, Choi JY. Focal hepatic lesions in Gd-EOB-DTPA enhanced MRI: the atlas. Insights Imaging. 2012 Oct;3(5):451-74. doi: 10.1007/s13244-012-0179-7. Epub 2012 Jun 15.

              [2] Tanimoto A, Higuchi N, Ueno A. Reduction of ringing artifacts in the arterial phase of gadoxetic acid-enhanced dynamic MR imaging. Magn Reson Med Sci. 2012;11(2):91-7.

              [3] Motosugi U, Ichikawa T, Sou H, Sano K, Ichikawa S, Tominaga L, Araki T. Dilution method of gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI). J Magn Reson Imaging. 2009 Oct;30(4):849-54. doi: 10.1002/jmri.21913.

              [4] Haradome H, Grazioli L, Tsunoo M, Tinti R, Frittoli B, Gambarini S, Morone M, Motosugi U, Colagrande S. Can MR fluoroscopic triggering technique and slow rate injection provide appropriate arterial phase images with reducing artifacts on gadoxetic acid-DTPA (Gd-EOB-DTPA)-enhanced hepatic MR imaging? J Magn Reson Imaging. 2010 Aug;32(2):334-40. doi: 10.1002/jmri.22241.

              [5] Davenport MS, Viglianti BL, Al-Hawary MM, Caoili EM, Kaza RK, Liu PS, Maturen KE, Chenevert TL, Hussain HK. Comparison of acute transient dyspnea after intravenous administration of gadoxetate disodium and gadobenate dimeglumine: effect on arterial phase image quality. Radiology. 2013 Feb;266(2):452-61. doi: 10.1148/radiol.12120826. Epub 2012 Nov 28.

              [6] Ringe KI, Husarik DB, Sirlin CB, Merkle EM. Gadoxetate disodium-enhanced MRI of the liver: part 1, protocol optimization and lesion appearance in the noncir