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Background: Apraglutide is a novel long-acting GLP-2 analog in development for short bowel syndrome with intestinal failure (SBS-IF). This multicenter, open-label, phase 2 study in SBS-IF and colon-in-continuity (CiC) investigates the safety and efficacy of apraglutide., Methods: This was a 52-week phase 2 metabolic balance study (MBS) in 9 adult patients with SBS-IF-CiC receiving once-weekly subcutaneous apraglutide injections. Safety was the primary endpoint. Secondary endpoints included changes in absorption parameters (MBS at baseline, after 4 weeks with stable parenteral support (PS), and 48 weeks), PS needs (48-week PS adjustment period based on monthly 48-h fluid balances) and intestinal morphology and motility (static and cine MRI at baseline and 4, 24 and 48 weeks)., Results: PS volume decreased by -4702 mL/week (-52 %; p < 0.001) at week 52. Seven patients (78 %) achieved ≥1 day off PS at week 52. At 4 weeks, fecal output was reduced by 253 g/day (p = 0.013). At 48 weeks, increases in wet weight absorption by 316 g/day (p = 0.039), energy absorption by 1134 kJ/day (p = 0.041) and carbohydrate absorption by 56.1 g/day (p = 0.024) were observed. Moreover, small bowel length increased from 29.7 to 40.7 cm (p = 0.012), duodenal wall thickness increased by 0.8 mm (p = 0.02) and motility in the proximal colon was reduced (p = 0.031). A total of 127 adverse events was reported, which were mostly mild to moderate., Conclusion: Apraglutide had an acceptable safety profile and was associated with significant reductions in PS needs and days off PS, improvements in intestinal absorption, and structural and functional intestinal changes in patients with SBS-IF-CiC., Clinicaltrials: gov, Number NCT04964986., Competing Interests: Declaration of competing interest Astrid Verbiest: nothing to declare. Mark Krogh Hvistendahl: full time employee at Zealand Pharma A/S as per 01/Jun2024. Federico Bolognani: FB was an employee of VectivBio, now part of Ironwood Pharmaceuticals, Inc., at the time of the conduct of the study. Carrie Li: CL was an employee of VectivBio, now part of Ironwood Pharmaceuticals, Inc., at the time of the conduct of the study and data analysis. Nader N. Youssef: NNY was an employee of VectivBio, now part of Ironwood Pharmaceuticals, Inc., at the time of the conduct of the study. Susanna Huh: Employee of Ironwood Pharmaceuticals. Alex Menys: CEO of Motilent. Gauraang Bhatnagar: Clinical Imaging Lead at Motilent. Ragna Vanslembrouck: nothing to declare. Ronald Peeters: nothing to declare. Ricardo Sartoris: nothing to declare. Pieter Vermeersch: nothing to declare. Lucas Wauters: nothing to declare. Kristin Verbeke: nothing to declare. Palle Bekker Jeppesen: Albumedix A/S, ArTara Therapeutics, Bainan Biotech, Baxter, Coloplast A/S, Ferring Pharmaceuticals, Fresenius Kabi, GlyPharma Therapeutic, Hanmi Pharmaceuticals, Ironwood, Naia Pharmaceuticals, NPS Pharmaceuticals, Protara Therapeutics, Shire, Takeda, The Novo Nordisk Foundation, Therachon, VectiveBio AG, Zealand Pharma A/S Francisca Joly: has received grants/research support/honoraria or consultation fees from Agomab, Baxter, Fresenius Kabi, Nestlé Health Sciences, BBraun, Theradial, Mayoli, Biocodex, mobile3e Consulting, Carembouche, NPS Pharmaceuticals, NorthSea Therapeutics, Shire, Takeda, Therachon, VectivBio and Zealand Pharma. Tim Vanuytsel: has served as a speaker for Baxter, Fresenius Kabi, Ironwood, VectivBio, Zealand Pharma and consultant for Agomab, Baxter, Hanmi Pharmaceuticals, Ironwood, NorthSea Therapeutics, VectivBio, Zealand Pharma., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background The clinicopathologic-radiologic and prognostic characteristics of intratumoral fat in hepatocellular carcinoma (HCC) are critical for personalized treatment but remain understudied. Purpose To investigate the clinicopathologic-radiologic associations and prognostic implications of MRI-assessed intratumoral fat in HCCs. Materials and Methods This retrospective cohort study included consecutive adult patients who underwent resection for solitary HCCs and preoperative contrast-enhanced MRI from two tertiary-care hospitals in East Asia (March 2011 to December 2021) and Western Europe (September 2012 to December 2019). MRI scans were independently evaluated by three radiologists at each hospital. Based on Liver Imaging Reporting and Data System (LI-RADS) version 2018, intratumoral fat was defined as "fat in mass more than adjacent liver," and the homogeneous subtype was defined as intratumoral fat "in absence of mosaic and nodule-in-nodule architecture." Recurrence-free survival (RFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared using the log-rank test. Cox regression analyses were conducted to identify factors associated with RFS and OS. Results A total of 933 patients were included in the Asian ( n = 736; median age, 53 years [IQR, 45-62 years]; 626 male) and European ( n = 207; median age, 64 years [IQR, 55-70 years]; 161 male) cohorts. MRI-assessed intratumoral fat was detected in 30% (215 of 726) and 31% (64 of 207) of patients in the Asian and European cohorts, respectively ( P = .72). In both cohorts, the steatohepatitic subtype, nonperipheral washout, enhancing capsule, and mosaic architecture were more frequent in tumors with intratumoral fat ( P value range, <.001 to .04). Intratumoral fat in general was not associated with RFS or OS in either cohort ( P value range, .48-.97). However, in the Asian cohort, homogeneous intratumoral fat was associated with longer RFS (hazard ratio [HR], 0.60; P = .009) and OS (HR, 0.33; P = .008) in multivariable Cox regression analyses. Conclusion MRI-assessed intratumoral fat was more frequent in steatohepatitic HCCs and associated with nonperipheral washout, enhancing capsule, and mosaic architecture. Although intratumoral fat was generally nonprognostic, homogeneous intratumoral fat was associated with longer RFS and OS in the Asian cohort. Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Harmath in this issue.

Background and Aims: Deterioration of liver function is a leading cause of death in patients with advanced hepatocellular carcinoma (HCC). We evaluated the impact of immune checkpoint inhibitor (ICI)-treatment on liver function and outcomes., Method: HCC patients receiving ICIs or sorafenib between 04/2003 and 05/2024 were included. Liver function (assessed by Child-Pugh score [CPS]) was evaluated at the start of ICI-treatment (baseline, BL) and 3 and 6 months thereafter. A ≥1 point change in CPS was defined as deterioration (-) or improvement (+), while equal CPS points were defined as stable (=)., Results: Overall, 182 ICI-treated patients (66.8 ± 11.8 years; cirrhosis: n = 134, 74%) were included. At BL, median CPS was 5 (IQR: 5-6; CPS-A: 147, 81%). After 3 months, liver function improved/stabilized in 102 (56%) and deteriorated in 61 (34%) patients, while 19 (10%) patients deceased/had missing follow-up (d/noFU). Comparable results were observed at 6 months (+/=: n = 82, 45%; -: n = 55, 30%; d/noFU: n = 45, 25%). In contrast, 54 (34%) and 33 (21%) out of 160 sorafenib patients achieved improvement/stabilization at 3 and 6 months, respectively. Radiological response was linked to CPS improvement/stabilization at 6 months (responders vs. non-responders, 73% vs. 50%; p = 0.007). CPS improvement/stabilization at 6 months was associated with better overall survival following landmark analysis (6 months: +/=: 28.4 [95% CI: 18.7-38.1] versus -: 14.2 [95% CI: 10.3-18.2] months; p < 0.001). Of 35 ICI-patients with CPS-B at BL, improvement/stabilization occurred in 16 (46%) patients, while 19 (54%) patients deteriorated/d/noFU at 3 months. Comparable results were observed at 6 months (CPS +/=: 14, 40%, -: 8, 23%). Importantly, 6/35 (17%) and 9/35 (26%) patients improved from CPS-B to CPS-A at 3 and 6 months., Conclusion: Radiological response to ICI-treatment was associated with stabilization or improvement in liver function, which correlated with improved survival, even in patients with Child-Pugh class B at baseline., (© 2024 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

The discontinuous peripheral enhancement is a pattern of enhancement usually attributed to typical cavernous hemangioma, that is the most common benign solid lesion of the liver. The discontinuous peripheral enhancement, however, may be encountered in many other benign and malignant focal liver lesions as an atypical presentation or evolution, and hemangiomas with discontinuous peripheral hyperenhancement on hepatic arterial phase may not always have the typical post-contrast pattern on portal venous and delayed phases. Therefore, abdominal radiologists may be challenged in their practice by lesions with discontinuous peripheral enhancement. This pictorial essay aims to review the spectrum of benign and malignant focal liver lesions that may show discontinuous peripheral enhancement. A particular point of interest is the diagnostic tree pathway that may guide the radiologists in the differential diagnosis., (© 2024. The Author(s).)

Objectives: To develop and evaluate a deep convolutional neural network (DCNN) for automated liver segmentation, volumetry, and radiomic feature extraction on contrast-enhanced portal venous phase magnetic resonance imaging (MRI)., Materials and Methods: This retrospective study included hepatocellular carcinoma patients from an institutional database with portal venous MRI. After manual segmentation, the data was randomly split into independent training, validation, and internal testing sets. From a collaborating institution, de-identified scans were used for external testing. The public LiverHccSeg dataset was used for further external validation. A 3D DCNN was trained to automatically segment the liver. Segmentation accuracy was quantified by the Dice similarity coefficient (DSC) with respect to manual segmentation. A Mann-Whitney U test was used to compare the internal and external test sets. Agreement of volumetry and radiomic features was assessed using the intraclass correlation coefficient (ICC)., Results: In total, 470 patients met the inclusion criteria (63.9±8.2 years; 376 males) and 20 patients were used for external validation (41±12 years; 13 males). DSC segmentation accuracy of the DCNN was similarly high between the internal (0.97±0.01) and external (0.96±0.03) test sets (p=0.28) and demonstrated robust segmentation performance on public testing (0.93±0.03). Agreement of liver volumetry was satisfactory in the internal (ICC, 0.99), external (ICC, 0.97), and public (ICC, 0.85) test sets. Radiomic features demonstrated excellent agreement in the internal (mean ICC, 0.98±0.04), external (mean ICC, 0.94±0.10), and public (mean ICC, 0.91±0.09) datasets., Conclusion: Automated liver segmentation yields robust and generalizable segmentation performance on MRI data and can be used for volumetry and radiomic feature extraction., Clinical Relevance Statement: Liver volumetry, anatomic localization, and extraction of quantitative imaging biomarkers require accurate segmentation, but manual segmentation is time-consuming. A deep convolutional neural network demonstrates fast and accurate segmentation performance on T1-weighted portal venous MRI., Key Points: • This deep convolutional neural network yields robust and generalizable liver segmentation performance on internal, external, and public testing data. • Automated liver volumetry demonstrated excellent agreement with manual volumetry. • Automated liver segmentations can be used for robust and reproducible radiomic feature extraction., (© 2024. The Author(s).)

Rim arterial phase hyperenhancement is an imaging feature commonly encountered on contrast-enhanced CT and MRI in focal liver lesions. Rim arterial phase hyperenhancement is a subtype of arterial phase hyperenhancement mainly present at the periphery of lesions on the arterial phase. It is caused by a relative arterialization of the periphery compared with the center of the lesion and needs to be differentiated from other patterns of peripheral enhancement, including the peripheral discontinuous nodular enhancement and the corona enhancement. Rim arterial phase hyperenhancement may be a typical or an atypical imaging presentation of many benign and malignant focal liver lesions, challenging the radiologists during imaging interpretation. Benign focal liver lesions that may show rim arterial phase hyperenhancement may have a vascular, infectious, or inflammatory origin. Malignant focal liver lesions displaying rim arterial phase hyperenhancement may have a vascular, hepatocellular, biliary, lymphoid, or secondary origin. The differences in imaging characteristics on contrast-enhanced CT may be subtle, and a multiparametric approach on MRI may be helpful to narrow the list of differentials. This article aims to review the broad spectrum of focal liver lesions that may show rim arterial phase hyperenhancement, using an approach based on the benign and malignant nature of lesions and their histologic origin. CRITICAL RELEVANCE STATEMENT: Rim arterial phase hyperenhancement may be an imaging feature encountered in benign and malignant focal liver lesions and the diagnostic algorithm approach provided in this educational review may guide toward the final diagnosis. KEY POINTS: Several focal liver lesions may demonstrate rim arterial phase hyperenhancement. Rim arterial phase hyperenhancement may occur in vascular, inflammatory, and neoplastic lesions. Rim arterial phase hyperenhancement may challenge radiologists during image interpretation., (© 2024. The Author(s).)

Background & Aims: Similarly to the controlled attenuation parameter (CAP), the ultrasound-based attenuation imaging (ATI) can quantify hepatic steatosis. We prospectively compared the performance of ATI and CAP for the diagnosis of hepatic steatosis in patients with type 2 diabetes and nonalcoholic fatty liver disease using histology and magnetic resonance imaging-proton density fat fraction (MRI-PDFF) as references., Methods: Patients underwent ATI and CAP measurement, MRI, and biopsy on the same day. Steatosis was classified as S0, S1, S2, and S3 on histology (<5%, 5%-33%, 33%-66%, and >66%, respectively) while the thresholds of 6.4%, 17.4%, and 22.1%, respectively, were used for MRI-PDFF. The area under the curve (AUC) of ATI and CAP was compared using a DeLong test., Results: Steatosis could be evaluated in 191 and 187 patients with MRI-PDFF and liver biopsy, respectively. For MRI-PDFF steatosis, the AUC of ATI and CAP were 0.86 (95% confidence interval [CI], 0.81-0.91) vs 0.69 (95% CI, 0.62-0.75) for S0 vs S1-S3 (P = .02) and 0.71 (95% CI, 0.64-0.77) vs 0.69 (95% CI, 0.61-0.75) for S0-S1 vs S2-S3 (P = .60), respectively. For histological steatosis, the AUC of ATI and CAP were 0.92 (95% CI, 0.87-0.95) vs 0.95 (95% CI, 0.91-0.98) for S0 vs S1-S3 (P = .64) and 0.79 (95% CI, 0.72-0.84) vs 0.76 (95% CI, 0.69-0.82) for S0-S1 vs S2-S3 (P = .61), respectively., Conclusion: ATI may be used as an alternative to CAP for the diagnosis and quantification of steatosis, in patients with type 2 diabetes and nonalcoholic fatty liver disease., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Purpose: Steatohepatitic hepatocellular carcinoma (SH-HCC) is characterized by intratumoral fat with > 50% inflammatory changes. However, intratumoral fat (with or without inflammation) can also be found in not-otherwise specified HCC (NOS-HCC). We compared the imaging features and outcome of resected HCC containing fat on pathology including SH-HCC (> 50% steatohepatitic component), NOS-HCC with < 50% steatohepatitic component (SH-NOS-HCC), and fatty NOS-HCC (no steatohepatitic component)., Material and Methods: From September 2012 to June 2021, 94 patients underwent hepatic resection for fat-containing HCC on pathology. Imaging features and categories were assessed using LIRADS v2018. Fat quantification was performed on chemical-shift MRI. Recurrence-free and overall survival were estimated., Results: Twenty-one patients (26%) had nonalcoholic steatohepatitis (NASH). The median intra-tumoral fat fraction was 8%, with differences between SH-HCC and SH-NOS-HCC (9.5% vs. 5% p = 0.03). There was no difference in major LI-RADS features between all groups; most tumors were classified as LR-4/5. A mosaic architecture on MRI was rare (7%) in SH-HCC, a fat in mass on CT was more frequently depicted (48%) in SH-HCC. A combination of NASH with no mosaic architecture on MRI or NASH with fat in mass on CT yielded excellent specificity for diagnosing SH-HCC (97.6% and 97.7%, respectively). The median recurrence-free and overall survival were 58 and 87 months, with no difference between groups (p = 0.18 and p = 0.69)., Conclusion: In patients with NASH, an SH-HCC may be suspected in L4/LR-5 observations with no mosaic architecture at MRI or with fat in mass on CT. Oncological outcomes appear similar between fat-containing HCC subtypes., (© 2024. Italian Society of Medical Radiology.)

Background Both Liver Imaging Reporting and Data System (LI-RADS) and histopathologic features provide prognostic information in patients with hepatocellular carcinoma (HCC), but whether LI-RADS is independently associated with survival is uncertain. Purpose To assess the association of LI-RADS categories and features with survival outcomes in patients with solitary resected HCC. Materials and Methods This retrospective study included patients with solitary resected HCC from three institutions examined with preoperative contrast-enhanced CT and/or MRI between January 2008 and December 2019. Three independent readers evaluated the LI-RADS version 2018 categories and features. Histopathologic features including World Health Organization tumor grade, microvascular and macrovascular invasion, satellite nodules, and tumor capsule were recorded. Overall survival and disease-free survival were assessed with Cox regression models. Marginal effects of nontargetoid features on survival were estimated using propensity score matching. Results A total of 360 patients (median age, 64 years [IQR, 56-70 years]; 280 male patients) were included. At CT and MRI, the LI-RADS LR-M category was associated with increased risk of recurrence (CT: hazard ratio [HR] = 1.83 [95% CI: 1.26, 2.66], P = .001; MRI: HR = 2.22 [95% CI: 1.56, 3.16], P < .001) and death (CT: HR = 2.47 [95% CI: 1.72, 3.55], P < .001; MRI: HR = 1.80 [95% CI: 1.32, 2.46], P < .001) independently of histopathologic features. The presence of at least one nontargetoid feature was associated with an increased risk of recurrence (CT: HR = 1.80 [95% CI: 1.36, 2.38], P < .001; MRI: HR = 1.93 [95% CI: 1.81, 2.06], P < .001) and death (CT: HR = 1.51 [95% CI: 1.10, 2.07], P < .010) independently of histopathologic features. In matched samples, recurrence was associated with the presence of at least one nontargetoid feature at CT (HR = 2.06 [95% CI: 1.15, 3.66]; P = .02) or MRI (HR = 1.79 [95% CI: 1.01, 3.20]; P = .048). Conclusion In patients with solitary resected HCC, LR-M category and nontargetoid features were negatively associated with survival independently of histopathologic characteristics. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Kartalis and Grigoriadis in this issue.

Objectives: To measure the performance and variability of a radiomics-based model for the prediction of microvascular invasion (MVI) and survival in patients with resected hepatocellular carcinoma (HCC), simulating its sequential development and application., Methods: This study included 230 patients with 242 surgically resected HCCs who underwent preoperative CT, of which 73/230 (31.7%) were scanned in external centres. The study cohort was split into training set (158 patients, 165 HCCs) and held-out test set (72 patients, 77 HCCs), stratified by random partitioning, which was repeated 100 times, and by a temporal partitioning to simulate the sequential development and clinical use of the radiomics model. A machine learning model for the prediction of MVI was developed with least absolute shrinkage and selection operator (LASSO). The concordance index (C-index) was used to assess the value to predict the recurrence-free (RFS) and overall survivals (OS)., Results: In the 100-repetition random partitioning cohorts, the radiomics model demonstrated a mean AUC of 0.54 (range 0.44-0.68) for the prediction of MVI, mean C-index of 0.59 (range 0.44-0.73) for RFS, and 0.65 (range 0.46-0.86) for OS in the held-out test set. In the temporal partitioning cohort, the radiomics model yielded an AUC of 0.50 for the prediction of MVI, a C-index of 0.61 for RFS, and 0.61 for OS, in the held-out test set., Conclusions: The radiomics models had a poor performance for the prediction of MVI with a large variability in the model performance depending on the random partitioning. Radiomics models demonstrated good performance in the prediction of patient outcomes., Clinical Relevance Statement: Patient selection within the training set strongly influenced the performance of the radiomics models for predicting microvascular invasion; therefore, a random approach to partitioning a retrospective cohort into a training set and a held-out set seems inappropriate., Key Points: • The performance of the radiomics models for the prediction of microvascular invasion and survival widely ranged (AUC range 0.44-0.68) in the randomly partitioned cohorts. • The radiomics model for the prediction of microvascular invasion was unsatisfying when trying to simulate its sequential development and clinical use in a temporal partitioned cohort imaged with a variety of CT scanners. • The performance of the radiomics models for the prediction of survival was good with similar performances in the 100-repetition random partitioning and temporal partitioning cohorts., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

We report the synthesis, crystal structure, and characterisation of a dinuclear Co(II) compound with thiodiacetate (tda) and phenanthroline (phen) as ligands (1), and of a series of metal complexes isomorphous to 1 with different Co : Zn ratios (2, 4 : 1; 3, 1 : 1; 4, 1 : 4; 5, 1 : 10). General characterisation methodologies and X-ray data showed that all the synthesised complexes are isomorphous to Zn(II) and Cu(II) analogues (CSD codes: DUHXEL and BEBQII). 1 consists of centrosymmetric Co(II) ion dimers in which the ions are 3.214 Å apart, linked by two μ-O bridges. Each cobalt atom is in a distorted octahedral environment of the N 2 O 3 S type. UV-vis spectra of 1 and 5 are in line with high spin ( S = 3/2) Co(II) ions in octahedral coordination and indicate that the electronic structure of both Co(II) ions in the dinuclear unit does not significantly change relative to that of the magnetically isolated Co(II) ion. EPR spectra of powder samples of 5 (Co : Zn ratio of 1 : 10) together with spectral simulation indicated high spin Co(II) ions with high rhombic distortion of the zfs [ E / D = 0.31(1), D > 0]. DC magnetic susceptibility experiments on 1 and analysis of the data constraining the E / D value obtained by EPR yielded g = 2.595(7), | D | = 61(1) cm -1 , and an intradimer ferromagnetic exchange coupling of J = 1.39(4) cm -1 . EPR spectra as a function of Co : Zn ratio for both powder and single crystal samples confirmed that they result from two effective S ' = 1/2 spins that interact through dipolar and isotropic exchange interactions to yield magnetically isolated S ' = 1 centres and that interdimeric exchange interactions, putatively mediated by hydrophobic interactions between phen moieties, are negligible. The latter observation contrasts with that observed in the Cu(II) analogue, where a transition from S = 1 to S ' = 1/2 was observed. Computational calculations indicated that the absence of the interdimeric exchange interaction in 1 is due to a lower Co(II) ion spin density delocalisation towards the metal ligands.

Background: Sarcopenia is a common problem in patients with HCC. We aimed to evaluate the prognostic and predictive value of baseline transversal psoas muscle thickness (TPMT) measurement in patients with HCC undergoing immunotherapy., Methods: HCC patients treated with programmed death ligand 1-based therapies between June 2016 and October 2022 at the Vienna General Hospital (n = 80) and the Hôpital Beaujon Clichy (n = 96) were included and followed until April 2023. TPMT at the level of the third lumbar vertebra was measured independently by 2 radiologists to evaluate interreader reliability. TPMT <12 mm/m in men and <8 mm/m in women indicated sarcopenia., Results: Overall, 176 patients (age: 66.3±11.7 y; male: n=143, 81%, Barcelona-Clinic Liver Cancer C: n=121, 69%) were included, of which 131 (74%) exhibited cirrhosis. Interreader agreement for the diagnosis of sarcopenia based on TPMT was 92.6%, and Cohen κ showed a "strong agreement" [κ = 0.84 (95% CI: 0.75-0.92)]. Sarcopenia, present in 58 patients (33%), was associated with shorter median overall survival [7.2 (95% CI: 5.0-9.5) vs. 22.6 (95% CI: 16.4-28.8 months); p < 0.001] and median progression-free survival [3.4 (95% CI: 0.2-6.8) vs. 7.9 (95% CI: 5.8-9.9 months), p = 0.001], and an independent predictor of overall [adjusted HR: 1.63 (95% CI: 1.07-2.48)] and progression-free mortality [adjusted HR: 1.54 (95% CI: 1.06-2.23)] in multivariable analyses. The objective response rate [evaluable in 162 subjects (92.0%)] per modified Response Evaluation Criteria In Solid Tumors (mRECIST) in patients with and without sarcopenia was 22% and 39%, respectively (p = 0.029). Survival and radiological responses were worse in patients with sarcopenia and systemic inflammation [median overall survival: 6.1 (95% CI: 3.6-8.6) mo; median progression-free survival: 2.8 (95% CI: 2.1-3.4) mo; objective response rate=16%; disease control rate=39%]., Conclusions: Evaluation of sarcopenia using TPMT measurement is reliable and identifies HCC patients with a dismal prognosis and response to immunotherapy., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Background & Aims: Assessment of computed tomography (CT)/magnetic resonance imaging Liver Imaging Reporting and Data System (LI-RADS) v2018 major features leads to substantial inter-reader variability and potential decrease in hepatocellular carcinoma diagnostic accuracy. We assessed the performance and added-value of a machine learning (ML)-based algorithm in assessing CT LI-RADS major features and categorisation of liver observations compared with qualitative assessment performed by a panel of radiologists., Methods: High-risk patients as per LI-RADS v2018 with pathologically proven liver lesions who underwent multiphase contrast-enhanced CT at diagnosis between January 2015 and March 2019 in seven centres in five countries were retrospectively included and randomly divided into a training set (n = 84 lesions) and a test set (n = 345 lesions). An ML algorithm was trained to classify non-rim arterial phase hyperenhancement, washout, and enhancing capsule as present, absent, or of uncertain presence. LI-RADS major features and categories were compared with qualitative assessment of two independent readers. The performance of a sequential use of the ML algorithm and independent readers were also evaluated in a triage and an add-on scenario in LR-3/4 lesions. The combined evaluation of three other senior readers was used as reference standard., Results: A total of 318 patients bearing 429 lesions were included. Sensitivity and specificity for LR-5 in the test set were 0.67 (95% CI, 0.62-0.72) and 0.91 (95% CI, 0.87-0.96) respectively, with 242 (70.1%) lesions accurately categorised. Using the ML algorithm in a triage scenario improved the overall performance for LR-5. (0.86 and 0.93 sensitivity, 0.82 and 0.76 specificity, 78% and 82.3% accuracy for the two independent readers)., Conclusions: Quantitative assessment of CT LI-RADS v2018 major features is feasible and diagnoses LR-5 observations with high performance especially in combination with the radiologist's visual analysis in patients at high-risk for HCC., Impact and Implications: Assessment of CT/MRI LI-RADS v2018 major features leads to substantial inter-reader variability and potential decrease in hepatocellular carcinoma diagnostic accuracy. Rather than replacing radiologists, our results highlight the potential benefit from the radiologist-artificial intelligence interaction in improving focal liver lesions characterisation by using the developed algorithm as a triage tool to the radiologist's visual analysis. Such an AI-enriched diagnostic pathway may help standardise and improve the quality of analysis of liver lesions in patients at high risk for HCC, especially in non-expert centres in liver imaging. It may also impact the clinical decision-making and guide the clinician in identifying the lesions to be biopsied, for instance in patients with multiple liver focal lesions., Competing Interests: Five authors (VM, RQ, LD, JHL and NC) are GE Healthcare France employees. The remaining authors, who are not employees of or consultants for GE Healthcare, had control of inclusion of all data and information that might present a conflict of interest for authors who are employees for GE Healthcare. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2023 The Author(s).)

Purpose: The purpose of this study was to assess the performance of quantitative computed tomography (CT) imaging for detecting pancreatic fatty infiltration, using the results of histopathological analysis as reference., Materials and Methods: Sixty patients who underwent pancreatic surgery for a pancreatic tumor between 2016 and 2019 were retrospectively included. There were 33 women and 27 men with a mean age of 56 ± 12 (SD) years (age range: 18-79 years). Patients with dilatation of the main pancreatic duct, chronic pancreatitis, or preoperative treatment were excluded to prevent any bias in the radiological-pathological correlation. Pancreatic fatty infiltration was recorded at pathology. Pancreatic surface lobularity, pancreatic attenuation, visceral fat area, and subcutaneous fat area were derived from preoperative CT images. The performance for the prediction of fatty infiltration was assessed using area under receiver operating characteristic curve (AUC) and backward binary logistic regression analysis. Results were validated in a separate cohort of 34 patients (17 women; mean age, 50 ± 14 [SD] years; age range: 18-73)., Results: A total of 28/60 (47%) and 17/34 (50%) patients had pancreatic fatty infiltration in the derivation and validation cohorts, respectively. In the derivation cohort, patients with pancreatic fatty infiltration had a significantly higher PSL (P < 0.001) and a lower pancreatic attenuation on both precontrast and portal venous phase images (P = 0.011 and 0.003, respectively), and higher subcutaneous fat area and visceral fat area (P = 0.010 and 0.007, respectively). Multivariable analysis identified pancreatic surface lobularity > 7.6 and pancreatic attenuation on portal venous phase images < 83.5 Hounsfield units as independently associated with fatty infiltration. The combination of these variables resulted in an AUC of 0.85 (95% CI: 0.74-0.95) and 0.83 (95% CI: 0.67-0.99) in the derivation and validation cohorts, respectively., Conclusion: CT-based quantitative imaging accurately predicts pancreatic fatty infiltration., Competing Interests: Disclosure of interest All authors declare no actual or potential conflict of interest related to the submitted study., (Copyright © 2023 Société française de radiologie. Published by Elsevier Masson SAS. All rights reserved.)

Background and Aims: The Liver Imaging Reporting and Data System (LI-RADS) and European Association for the Study of the Liver (EASL) diagnostic criteria for noninvasive diagnosis of HCC can only be applied to patients at a high risk of HCC. This systematic review assesses adherence to the LI-RADS and EASL high-risk population criteria in published studies., Approach and Results: PubMed was searched for original research, published between January 2012 and December 2021, reporting LI-RADS and EASL diagnostic criteria on contrast-enhanced ultrasound, CT, or MRI. The algorithm version, publication year, risk status, and etiologies of chronic liver disease were recorded for each study. Adherence to high-risk population criteria was evaluated as optimal (unequivocal adherence), suboptimal (equivocal), or inadequate (clear violation). A total of 219 original studies were included, with 215 that used the LI-RADS criteria, 4 EASL only, and 15 that evaluated both LI-RADS and EASL criteria. Optimal, suboptimal, or inadequate adherence to high-risk population criteria was observed in 111/215 (51.6%), 86/215 (40.0%), and 18/215 (8.4%) LI-RADS and 6/19 (31.6%), 5/19 (26.3%), and 8/19 (42.1%) EASL studies ( p < 0.001) regardless of the imaging modality. Adherence to high-risk population criteria significantly improved according to the CT/MRI LI-RADS versions (optimal in v2018 in 64.5% of studies; v2017, 45.8%; v2014, 24.4%; v2013.1, 33.3%; p < 0.001) and the publication year (2020-2021, 62.5%; 2018-2019, 33.9%; 2014-2017, 39.3% of all LI-RADS studies; p = 0.002). No significant differences in adherence to high-risk population criteria were observed in the versions of contrast-enhanced ultrasound LI-RADS ( p = 0.388) or EASL ( p = 0.293)., Conclusion: Adherence to high-risk population criteria was optimal or suboptimal in about 90% and 60% of LI-RADS and EASL studies, respectively., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Background and Aims: Porto-sinusoidal vascular disorder (PSVD) is a rare and commonly overlooked cause of portal hypertension. The interest of CT analysis, including quantification of liver surface nodularity (LSN) for PSVD diagnosis has not been established. This study aimed at assessing the performance of LSN and CT features for a PSVD diagnosis in patients with signs of portal hypertension., Approach and Results: This retrospective case-control study included a learning cohort consisting of 50 patients with histologically proven PSVD, according to VALDIG criteria, and 100 control patients with histologically proven cirrhosis, matched on ascites. All patients and controls had at least one sign of portal hypertension and CT available within 1 year of liver biopsy. Principal component analysis of CT features separated patients with PSVD from patients with cirrhosis. Patients with PSVD had lower median LSN than those with cirrhosis (2.4 vs. 3.1, p < 0.001). Multivariate analysis identified LSN < 2.5 and normal-sized or enlarged segment IV as independently associated with PSVD. Combination of these two features had a specificity of 90% for PSVD and a diagnostic accuracy of 84%. Even better results were obtained in an independent multicenter validation cohort including 53 patients with PSVD and 106 control patients with cirrhosis (specificity 94%, diagnostic accuracy 87%)., Conclusions: This study that included a total of 103 patients with PSVD and 206 patients with cirrhosis demonstrates that LSN < 2.5 combined with normal-sized or enlarged segment IV strongly suggests PSVD in patients with signs of portal hypertension., (© 2022 American Association for the Study of Liver Diseases.)

Background: To investigate whether fractal analysis of perfusion differentiates hepatocellular adenoma (HCA) subtypes and hepatocellular carcinoma (HCC) in non-cirrhotic liver by quantifying perfusion chaos using four-dimensional dynamic contrast-enhanced magnetic resonance imaging (4D-DCE-MRI)., Results: A retrospective population of 63 patients (47 female) with histopathologically characterized HCA and HCC in non-cirrhotic livers was investigated. Our population consisted of 13 hepatocyte nuclear factor (HNF)-1α-inactivated (H-HCAs), 7 β-catenin-exon-3-mutated (b ex3 -HCAs), 27 inflammatory HCAs (I-HCAs), and 16 HCCs. Four-dimensional fractal analysis was applied to arterial, portal venous, and delayed phases of 4D-DCE-MRI and was performed in lesions as well as remote liver tissue. Diagnostic accuracy of fractal analysis was compared to qualitative MRI features alone and their combination using multi-class diagnostic accuracy testing including kappa-statistics and area under the receiver operating characteristic curve (AUC). Fractal analysis allowed quantification of perfusion chaos, which was significantly different between lesion subtypes (multi-class AUC = 0.90, p < 0.001), except between I-HCA and HCC. Qualitative MRI features alone did not allow reliable differentiation between HCA subtypes and HCC (κ = 0.35). However, combining qualitative MRI features and fractal analysis reliably predicted the histopathological diagnosis (κ = 0.89) and improved differentiation of high-risk lesions (i.e., HCCs, b ex3 -HCAs) and low-risk lesions (H-HCAs, I-HCAs) from sensitivity and specificity of 43% (95% confidence interval [CI] 23-66%) and 47% (CI 32-64%) for qualitative MRI features to 96% (CI 78-100%) and 68% (CI 51-81%), respectively, when adding fractal analysis., Conclusions: Combining qualitative MRI features with fractal analysis allows identification of HCA subtypes and HCCs in patients with non-cirrhotic livers and improves differentiation of lesions with high and low risk for malignant transformation., (© 2022. The Author(s).)

Background: Posthepatectomy liver failure (PHLF) is a rare but dreaded complication. The aim was to test whether a combination of non-invasive biomarkers (NIBs) and CT data could predict the risk of PHLF in patients who underwent resection of hepatocellular carcinoma (HCC)., Methods: Patients with HCC who had liver resection between 2012 and 2020 were included. A relevant combination of NIBs (NIB model) to model PHLF risk was identified using a doubly robust estimator (inverse probability weighting combined with logistic regression). The adjustment variables were body surface area, ASA fitness grade, male sex, future liver remnant (FLR) ratio, difficulty of liver resection, and blood loss. The reference invasive biomarker (IB) model comprised a combination of pathological analysis of the underlying liver and hepatic venous pressure gradient (HVPG) measurement. Various NIB and IB models for prediction of PHLF were fitted and compared. NIB model performances were validated externally. Areas under the curve (AUCs) were corrected using bootstrapping., Results: Overall 323 patients were included. The doubly robust estimator showed that hepatitis C infection (odds ratio (OR) 4.33, 95 per cent c.i. 1.29 to 9.20; P = 0.001), MELD score (OR 1.26, 1.04 to 1.66; P = 0.001), fibrosis-4 score (OR 1.36, 1.06 to 1.85; P = 0.001), liver surface nodularity score (OR 1.55, 1.28 to 4.29; P = 0.031), and FLR volume ratio (OR 0.99, 0.97 to 1.00; P = 0.014) were associated with PHLF. Their combination (NIB model) was fitted externally (2-centre cohort, 165 patients) to model PHLF risk (AUC 0.867). Among 129 of 323 patients who underwent preoperative HVPG measurement, NIB and IB models had similar performances (AUC 0.753 versus 0.732; P = 0.940). A well calibrated nomogram was drawn based on the NIB model (AUC 0.740). The risk of grade B/C PHLF could be ruled out in patients with a cumulative score of less than 160 points., Conclusion: The NIB model provides reliable preoperative evaluation with performance at least similar to that of invasive methods for PHLF risk prediction., (© The Author(s) 2022. Published by Oxford University Press on behalf of BJS Society Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Laparoscopic resection of the inferior vena cava (IVC) during laparoscopic pancreatoduodenectomy (LPD) has never been described. A 32-year-old male with large solid pseudopapillary neoplasm underwent LPD with resection of the IVC and reconstruction by a peritoneal patch (PP)., Methods: In this indication, the dissection is achieved by resection of the IVC. Kocher maneuver is difficult owing to the caval invasion, and section of the retroportal lamina tissue, before Kocher maneuver, is needed to control the left side of the IVC. Extended lymphadenectomy is not needed because the risk of lymph node invasion is low, and venous resection may be required for severe tumor adhesions without necessary histological invasion, to avoid tumor rupture at high risk of recurrence. 1,2 The IVC was clamped by a laparoscopic vascular clamp and reconstructed (5-6 cm) with a PP., Results: The operative duration was 430 min, including IVC clamping for 27 min. The outcome was marked by biliary fistula and 24 days of hospital stay. Histology showed 6 cm tumor without histological invasion of the IVC wall. After 15 months of follow-up, there was no recurrence and no stenosis of the IVC. In our experience, reconstruction of the IVC with a PP is a safe procedure, with no PP-related complications and high patency rate (> 90%). 3 CONCLUSION: Laparoscopic resection of the IVC is feasible in highly selected centers. The harvesting of the PP is easier than that of other autologous venous grafts, especially when done by the laparoscopic approach., (© 2022. Society of Surgical Oncology.)

Objectives: To evaluate the diagnostic performance of liver surface nodularity (LSN) for the assessment of advanced fibrosis in patients with non-alcoholic fatty liver disease (NAFLD)., Methods: We retrospectively analysed patients with pathologically proven NAFLD who underwent liver MRI. Demographic, clinical, and laboratory data (including FIB-4 scores) were gathered. The SAF score was used to assess NAFLD. MRI-proton density fat fraction (PDFF) and LSN were determined on pre-contrast MR sequences. ROC curve analysis was performed to evaluate the diagnostic performance of MRI-LSN for the diagnosis of advanced (F3-F4) liver fibrosis., Results: The final population included 142 patients. Sixty-seven (47%) patients had non-alcoholic steatohepatitis (NASH), and 52 (37%) had advanced fibrosis. The median MRI-PDFF increased with the grades of steatosis: 8.1%, 18.1%, and 31% in S1, S2, and S3 patients, respectively (p < 0.001). The area under the ROC curve (AUC) of MRI-LSN ≥ 2.50 was 0.838 (95%CI 0.767-0.894, sensitivity 67.3%, specificity 88.9%, positive and negative predictive values 77.8% and 82.5%, respectively) for the diagnosis of advanced fibrosis. Combining FIB-4 and MRI-LSN correctly classified 103/142 (73%) patients. This was validated in an external cohort of 75 patients., Conclusions: MRI-LSN has good diagnostic performance in diagnosis of advanced fibrosis in NAFLD patients. A combination of FIB-4 and MRI-LSN derived from pre-contrast MRI could be helpful to detect advanced fibrosis., Key Points: • MRI-LSN ≥ 2.5 was accurate for the diagnosis of advanced hepatic fibrosis in NAFLD patients. • The combination of FIB-4 and MRI-LSN improved the detection of advanced fibrosis. • MRI-LSN can be easily derived by unenhanced MRI sequences that are routinely acquired., (© 2021. European Society of Radiology.)

Purpose: To compare the magnetic resonance imaging (MRI) features of benign liver lesions developed on Budd-Chiari syndrome (BCS) with those on Fontan-associated liver disease (FALD) and to describe their long-term progression., Materials and Methods: Patients with BCS or FALD who underwent MRI between 2010 and 2020 were retrospectively included. MRI features of nodules (≥ 5 mm) at baseline and at final follow-up were reviewed. The final diagnosis of benign lesion was based on a combination of clinical and biological data and findings at follow-up MRI examination., Results: Two-hundred and thirty benign liver lesions in 39 patients with BCS (10 men, 29 women; mean age, 36 ± 11 [SD] years; age range: 15-66 years) and 84 benign lesions in 14 patients with FALD (2 men, 12 women; mean age, 31 ± 10 [SD] years; age range: 20-48 years) were evaluated. On baseline MRI, BCS nodules were more frequently hyperintense on T1-weighted (183/230, 80%) and hypointense on T2-weighted (142/230; 62%) images, while FALD nodules were usually isointense on both T1- (70/84; 83%) and T2-weighted (64/84; 76%) images (all P< 0.01). Most lesions showed arterial phase hyperenhancement (222/230 [97%] vs. 80/84 [95%] in BCS and FALD, respectively; P = 0.28) but wash-out was more common in BCS (64/230 [28%] vs. 9/84 [11%]; P < 0.01). At follow-up, changes were more frequent in BCS nodules with more frequent disappearance (P < 0.01), changes in size, signal intensity on T2-weighted, portal, and delayed phase, and in the depiction of washout and capsule (all P ≤ 0.03)., Conclusion: MRI features of benign lesions are different at diagnosis and during the course of the disease between BCS and FALD. Changes in size and MRI features are more frequent in benign lesions developed in BCS., (Copyright © 2021 Société française de radiologie. Published by Elsevier Masson SAS. All rights reserved.)

Background & Aims: Recent non-malignant non-cirrhotic portal venous system thrombosis (PVT) is a rare condition. Among risk factors for PVT, cytomegalovirus (CMV) disease is usually listed based on a small number of reported cases. The aim of this study was to determine the characteristics and outcomes of PVT associated with CMV disease., Methods: We conducted a French multicenter retrospective study comparing patients with recent PVT and CMV disease ("CMV positive"; n = 23) to patients with recent PVT for whom CMV testing was negative ("CMV negative"; n = 53) or unavailable ("CMV unknown"; n = 297)., Results: Compared to patients from the "CMV negative" and "CMV unknown" groups, patients from the "CMV positive" group were younger, more frequently had fever, and had higher heart rate, lymphocyte count and serum ALT levels (p ≤0.01 for all). The prevalence of immunosuppression did not differ between the 3 groups (4%, 4% and 6%, respectively). Extension of PVT was similar between the 3 groups. Thirteen out of 23 "CMV positive" patients had another risk factor for thrombosis. Besides CMV disease, the number of risk factors for thrombosis was similar between the 3 groups. Heterozygosity for the prothrombin G20210A gene variant was more frequent in "CMV positive" patients (22%) than in the "CMV negative" (4%, p = 0.01) and "CMV unknown" (8%, p = 0.03) groups. Recanalization rate was not influenced by CMV status., Conclusions: In patients with recent PVT, features of mononucleosis syndrome should raise suspicion of CMV disease. CMV disease does not influence thrombosis extension nor recanalization. More than half of "CMV positive" patients have another risk factor for thrombosis, with a particular link to the prothrombin G20210A gene variant., Lay Summary: Patients with cytomegalovirus (CMV)-associated portal venous system thrombosis have similar thrombosis extension and evolution as patients without CMV disease. However, patients with CMV-associated portal venous system thrombosis more frequently have the prothrombin G20210A gene variant, suggesting that these entities act synergistically to promote thrombosis., Competing Interests: Conflict of interest Authors declare no conflict of interest related to the present study. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Purpose: The purpose of this study was to compare the value of contrast-enhanced computed tomography (CT) to that of magnetic resonance imaging obtained with extracellular contrast agent (ECA-MRI) for the diagnosis of a tumor capsule in hepatocellular carcinoma (HCC) using histopathologic findings as the standard of reference., Materials and Methods: This retrospective study included patients with pathologically-proven resected HCCs with available preoperative contrast-enhanced CT and ECA-MRI examinations. Two blinded radiologists independently reviewed contrast-enhanced CT and ECA-MRI examinations to assess the presence of an enhancing capsule. The histopathological analysis of resected specimens was used as reference for the diagnosis of a tumor capsule. The sensitivity and specificity of CT and ECA-MRI for the diagnosis of a tumor capsule were determined, and an intra-individual comparison of imaging modalities was performed using McNemar test. Inter-reader agreement was assessed using Kappa test., Results: The study population included 199 patients (157 men, 42 women; mean age: 61.3 ± 13.0 [SD] years) with 210 HCCs (mean size 56.7 ± 43.7 [SD] mm). A tumor capsule was present in 157/210 (74.8%) HCCs at histopathologic analysis. Capsule enhancement was more frequently visualized on ECA-MRI (R1, 68.6%; R2, 71.9%) than on CT (R1, 44.3%, P < 0.001; R2, 47.6%, P < 0.001). The sensitivity of ECA-MRI was better for the diagnosis of histopathological tumor capsule (R1, 76.4%; R2, 79.6%; P < 0.001), while CT had a greater specificity (R1, 84.9%; R2, 83.0%; P < 0.001). Inter-reader agreement was moderate both on CT (kappa = 0.55; 95% confidence interval [CI]: 0.43-0.66) and ECA-MRI (kappa = 0.57; 95% CI: 0.45-0.70)., Conclusion: Capsule enhancement was more frequently visualized on ECA-MRI than on CT. The sensitivity of ECA-MRI was greater than that of CT, but the specificity of CT was better than that of ECA-MRI., (Copyright © 2021 Société française de radiologie. Published by Elsevier Masson SAS. All rights reserved.)

Background: The factors affecting intra-operator variability of two-dimensional shear wave elastography (2D-SWE) have not been clearly established. We evaluated 2D-SWE variability according to the number of measurements, clinical and laboratory features, and liver stiffness measurements (LSM)., Methods: At least three LSM were performed in 452 patients who underwent LSM by 2D-SWE (supersonic shear imaging) out of an initial database of 1650 patients. The mean value of the three LSM was our best measurement method. Bland-Altman plots were used to evaluate intra-operator variability when considering only one, or the first two measurements. Variability was assessed by taking the absolute value of the difference between the first LSM and the mean of the three LSM. Logistic regression was used to assess the factors associated with the highest tertile of variability., Results: The limit of agreement was narrower with the mean of the first and second measurements than with each measurement taken separately (- 2.83 to 2.99 kPa vs. - 5.86 to 6.21 kPa and - 5.77 to 5.73 kPa for the first and second measurement, respectively). A BMI ≥ 25 kg/m 2 and a first LSM by 2D-SWE ≥ 7.1 kPa increased the odds of higher variability by 3.4 and 3.9, respectively. Adding a second LSM didn't change the variability in patients with BMI < 25 and a first LSM by 2D-SWE < 7.1 kPa., Conclusions: Intra-operator variability of LSM by 2D-SWE increases with both a high BMI and high LSM value. In patients with BMI < 25 kg/m 2 and a first LSM < 7.1 kPa we recommend performing only one LSM., (© 2021. The Author(s).)

Background & Aims: The histopathological subtypes of hepatocellular carcinoma (HCC) are associated with distinct clinical features and prognoses. This study aims to report Liver Imaging Reporting and Data System (LI-RADS)-defined imaging features of different HCC subtypes in a cohort of resected tumours and to assess the influence of HCC subtypes on computed tomography (CT)/magnetic resonance imaging (MRI) LI-RADS categorisation in the subgroup of high-risk patients., Methods: This retrospective institutional review board-approved study included patients with resected HCCs and available histopathological classification. Three radiologists independently reviewed preoperative CT and MRI exams. The readers evaluated the presence of imaging features according to LI-RADS v2018 definitions and provided a LI-RADS category in patients at high risk of HCC. Differences in LI-RADS features and categorisations were assessed for not otherwise specified (NOS-HCC), steatohepatitic (SH-HCC), and macrotrabecular-massive (MTM-HCC) types of HCCs., Results: Two hundred and seventy-seven patients (median age 64.0 years, 215 [77.6%] men) were analysed, which involved 295 HCCs. There were 197 (66.7%) NOS-HCCs, 62 (21.0%) SH-HCCs, 23 (7.8%) MTM-HCCs, and 13 (4.5%) other rare subtypes. The following features were more frequent in MTM-HCC: elevated α-foetoprotein serum levels ( p <0.001), tumour-in-vein ( p <0.001 on CT, p ≤0.052 on MRI), presence of at least 1 LR-M feature ( p ≤0.010 on CT), infiltrative appearance ( p ≤0.032 on CT), necrosis or severe ischaemia ( p ≤0.038 on CT), and larger size ( p ≤0.006 on CT, p ≤0.011 on MRI). SH-HCC was associated with fat in mass ( p <0.001 on CT, p ≤0.002 on MRI). The distribution of the LI-RADS major features and categories in high-risk patients did not significantly differ among the 3 main HCC subtypes., Conclusions: The distribution of LI-RADS major features and categories is not different among the HCC subtypes. Nevertheless, careful analysis of tumour-in-vein, LR-M, and ancillary features as well as clinico-biological data can provide information for the non-invasive diagnosis of HCC subtypes., Lay Summary: In high-risk patients, the overall distribution of LI-RADS major features and categories is not different among the histological subtypes of hepatocellular carcinoma, but tumour-in-vein, presence of LR-M features, and ancillary features can provide information for the non-invasive diagnosis of hepatocellular carcinoma subtypes., Competing Interests: The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2021 The Authors.)

Objective: To assess the feasibility and reproducibility of pancreatic surface lobularity (PSL) quantification derived from abdominal computed tomography (CT) in a population of patients free from pancreatic disease., Materials and Methods: This retrospective study included 265 patients free from pancreatic disease who underwent contrast-enhanced abdominal CT between 2017 and 2019. A maximum of 11 individual PSL measurements were performed by two abdominal radiologists (head [5 measurements], body, and tail [3 measurements each]) using dedicated software. The influence of age, body mass index (BMI), and sex on PSL was assessed using the Pearson correlation and repeated measurements. Inter-reader agreement was assessed using the intraclass correlation coefficient (ICC) and Bland Altman (BA) plots., Results: CT images of 15 (6%) patients could not be analyzed. A total of 2750 measurements were performed in the remaining 250 patients (143 male [57%], mean age 45 years [range, 18-91]), and 2237 (81%) values were obtained in the head 951/1250 (76%), body 609/750 (81%), and tail 677/750 (90%). The mean ± standard deviation PSL was 6.53 ± 1.37. The mean PSL was significantly higher in male than in female (6.89 ± 1.30 vs. 6.06 ± 1.31, respectively, p < 0.001). PSL gradually increased with age ( r = 0.32, p < 0.001) and BMI ( r = 0.32, p < 0.001). Inter-reader agreement was excellent (ICC 0.82 [95% confidence interval 0.72-0.85], with a BA bias of 0.30 and 95% limits of agreement of -1.29 and 1.89)., Conclusion: CT-based PSL quantification is feasible with a high success rate and inter-reader agreement in subjects free from pancreatic disease. Significant variations were observed according to sex, age, and BMI. This study provides a reference for future studies., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2021 The Korean Society of Radiology.)

Objectives: The goal of this study was to assess the relationship between liver surface nodularity (LSN), chemotherapy-associated liver injury (CALI), and clinically relevant post-hepatectomy liver failure (CR-PHLF) (i.e., ≥ grade B) in patients undergoing hepatectomy for colorectal liver metastases (CLM)., Methods: Preoperative CT scans of patients who underwent chemotherapy followed by hepatectomy for CLM between 2010 and 2017 were retrospectively analyzed. LSN was measured using semi-automated CT software CT images in patients who had available preoperative CT scans within 6 weeks before hepatectomy, and was computed based on the means of one to 10 measurements by two abdominal radiologists consensually. The association of LSN, CALI, and CR-PHLF was analyzed., Results: Two hundred fifty-six patients were analyzed (149 men and 107 women; overall median age, 61 [range, 29-88 years]). A total of 26 patients (10.2%) developed CR-PHLF. The optimal LSN cut-off value for detecting CR-PHLF was 2.5, as determined by receiver operative characteristic analysis (p < 0.001). LSN ≥ 2.5 was associated with prolonged chemotherapy (> 6 cycles, p = 0.018), but not with CALIs. After propensity score matching, LSN remained significantly associated with CR-PHLF (p = 0.031). Furthermore, multivariate analysis identified LSN ≥ 2.50 and future liver remnant (FLR) < 30% as significant preoperative predictors of CR-PHLF in 102 patients undergoing major hepatectomy. LSN ≥ 2.50 was more frequent in patients undergoing major hepatectomy despite FLR ≥ 30% (p = 0.008)., Conclusion: LSN quantified on CT is an independent surrogate of CR-PHLF in patients who undergo chemotherapy followed by hepatectomy for CLM and may provide a valuable additional tool in the preoperative assessment of these patients., Key Points: • LSN was not associated with chemotherapy- associated liver injury but high LSN (defined ≥ 2.5) was associated with prolonged chemotherapy (> 6 cycles). • High LSN was an independent predictor of clinically relevant postoperative liver failure in patients undergoing hepatectomy for CRLM. • LSN ≥ 2.50 was more frequent in patients with PHLF after major hepatectomy despite a future liver remnant ≥ 30%., (© 2021. European Society of Radiology.)

Magnetic resonance imaging (MRI) is highly important for the detection, characterization, and follow-up of focal liver lesions. Several quantitative MRI-based methods have been proposed in addition to qualitative imaging interpretation to improve the diagnostic work-up and prognostics in patients with focal liver lesions. This includes DWI with apparent diffusion coefficient measurements, intravoxel incoherent motion, perfusion imaging, MR elastography, and radiomics. Multiple research studies have reported promising results with quantitative MRI methods in various clinical settings. Nevertheless, applications in everyday clinical practice are limited. This review describes the basic principles of quantitative MRI-based techniques and discusses the main current applications and limitations for the assessment of focal liver lesions.

Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide. Understanding of the pathogenesis of HCC has significantly improved in the past few years due to advances in genetics, molecular biology and pathology. Several subtypes have been identified with different backgrounds and outcomes, leading to possible changes in disease management and challenging the role of imaging. Indeed, despite its pivotal role in the diagnostic workup, prognosis, and the decision-making process in patients with HCC, these recent developments are progressively redefining the role of imaging. First and most important, liver imaging is shifting from a purely qualitative to a quantitative paradigm, integrating quantitative imaging and radiomics in a digital era. Second, to improve patient management, imaging has gradually moved beyond tumor-centered assessment to include a broader evaluation of the liver and its function. This review describes and discusses these advances in the imaging for the diagnosis and prognosis of HCC., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: The aim of this study was to assess the prognostic value of liver surface nodularity (LSN) and sarcopenia from preoperative computed tomography (CT) in patients with resectable metabolic syndrome (MS)-related hepatocellular carcinoma (HCC)., Methods: Patients with MS undergoing hepatectomy for HCC between 2006 and 2018 at a single center were retrospectively analyzed. LSN and sarcopenia were assessed on preoperative CT scans, and their association with severe (Clavien-Dindo grade 3-5) postoperative complications was analyzed on multivariate analysis. The influence of LSN and sarcopenia on overall survival (OS) and recurrence-free survival (RFS) was assessed., Results: Overall, 110 patients (92 men [84%], mean 67.7 ± 7.7 years of age) were analyzed. Severe postoperative complications occurred in 34/110 (31%) patients. Patients with severe complications had a significantly higher LSN score (area under the receiver operating characteristic curve 0.68 ± 0.05, optimal cut-off > 2.50) and were more frequently sarcopenic (47% vs. 13% without major complications, p < 0.001). Multivariate analysis identified sarcopenia (odds ratio [OR] 6.51, 95% confidence interval [CI] 2.08-20.39; p < 0.001), LSN > 2.50 (OR 7.05, 95% CI 2.13-23.35; p < 0.001), and preoperative portal vein embolization (PVE; OR 6.06, 95% CI 1.71-21.48; p = 0.005) as independent predictors of severe complications. LSN and sarcopenia had no influence on OS. Stratification according to a combination of LSN > 2.50 and sarcopenia predicted the risk of severe postoperative complications from 7% (no sarcopenia and LSN ≤2.50) to 71% (sarcopenia and LSN > 2.50; p < 0.001), as well as RFS from 61 months (95% CI 40-82) to 17 months (95% CI 9-25; p = 0.033). Results remained significant in 52 patients without advanced fibrosis., Conclusions: The combination of LSN and sarcopenia derived from routine preoperative CT seems to help predict severe postoperative complications and stratification of RFS in patients with MS and resectable HCC.

To assess the performance of CT-based radiomics analysis in differentiating benign from malignant intraductal papillary mucinous neoplasms of the pancreas (IPMN), preoperative scans of 408 resected patients with IPMN were retrospectively analyzed. IPMNs were classified as benign (low-grade dysplasia, n = 181), or malignant (high grade, n = 128, and invasive, n = 99). Clinicobiological data were reported. Patients were divided into a training cohort (TC) of 296 patients and an external validation cohort (EVC) of 112 patients. After semi-automatic tumor segmentation, PyRadiomics was used to extract radiomics features. A multivariate model was developed using a logistic regression approach. In the training cohort, 85/107 radiomics features were significantly different between patients with benign and malignant IPMNs. Unsupervised clustering analysis revealed four distinct clusters of patients with similar radiomics features patterns with malignancy as the most significant association. The multivariate model differentiated benign from malignant tumors in TC with an area under the ROC curve (AUC) of 0.84, sensitivity (Se) of 0.82, specificity (Spe) of 0.74, and in EVC with an AUC of 0.71, Se of 0.69, Spe of 0.57. This large study confirms the high diagnostic performance of preoperative CT-based radiomics analysis to differentiate between benign from malignant IPMNs.

Purpose: To establish measurement quality criteria for the noninvasive assessment of clinically significant portal hypertension (CSPH) in patients with cirrhosis using CT-based liver surface nodularity (LSN) measurements., Methods: Seventy-four consecutive patients with cirrhosis (mean 62 ± 13 years), including 30 with CSPH (41%), underwent CT and hepatic venous pressure gradient measurements. Three independent readers performed 15 LSN measurements/patient using dedicated software. LSN was computed based on the median and means of one to 15 measurements. Accuracy for diagnosing CSPH was assessed using receiver operating characteristic (ROC) curve analysis. Variability was assessed by the intra-class correlation coefficient (ICC) and the Bland-Altman plot (BA). Quality criteria were identified to maximize the accuracy of LSN and minimize variability., Results: The area under the (AU) ROCs of mean and median LSN measurements based on one to 15 measurements ranged from 0.79 ± 0.05 to 0.91 ± 0.04 and 0.86 ± 0.04 to 0.91 ± 0.03, respectively, with no difference on pair-wise comparisons (all p > 0.05). AUROCs of LSN increased from one to eight and leveled off between eight and 15 measurements. Inter- and intra-reader variability decreased from one to 15 measurements, with only slight improvement after more than eight measurements. Intra- and inter-observer agreements were excellent with eight measurements (ICC = 0.90 [95%CI 0.84-0.94], and ICC = 0.93 [95%CI 0.89-0.95], respectively), and variability for intra-observer and inter-observer agreement was low (BA bias 4.2% (95% limits of agreement [LoA] [- 15.3; + 23.7%]) and 4.8% LoA [ - 17.5; + 27.1%], respectively)., Conclusions: CT-based LSN measurement is highly reproducible and accurate. We suggest using at least 8 valid measurements to determine the mean LSN value for the detection of CSPH.

With the development of chemotherapy regimens, targeted therapies, and hepatic surgery, the survival of patients with colorectal liver metastases (CRLM) has dramatically improved. Imaging plays a central role for the diagnosis, staging, and treatment allocation in these patients. To interpret CRLM on imaging, radiologists must be familiar with the main imaging features of untreated tumors as well as the modifications induced by systemic therapies, and their meaning in relation to pathological tumor response and tumor biology. CRLM have the same histological features as the primary tumor. Most are "non-otherwise specified" (NOS) adenocarcinomas. The mucinous tumor is the most common of the rare subtypes. In NOS tumors, imaging usually differentiates central areas of necrosis from peripheral proliferating tumors and desmoplastic reaction. Areas of mucin mixed with fibrosis are seen in mucinous subtypes to help differentiate the metastases from other tumors cysts or hemangiomas. After treatment, the viable tumor is gradually replaced by ischemic-like necrosis and fibrosis, and remnants cells are mainly located on the periphery of tumors. Imaging can help predict the degree of tumor response, but changes can be difficult to differentiate from the pretherapeutic appearance. When chemotherapy is interrupted or in case of resistance to treatment, a peripheral infiltrating halo of tumor growth may appear. The purpose of the article is to illustrate the significance of the imaging features of colorectal liver metastases during systemic therapy, using radiopathological correlations.

Background & Aims: We compare the performance of liver surface nodularity (LSN) and liver stiffness measurements (LSM) using transient elastography (TE) for the detection of clinically significant portal hypertension (CSPH) in patients with cirrhosis and hepatocellular carcinoma (HCC)., Methods: All patients with cirrhosis and HCC who underwent computed tomography, LSM and hepatic venous pressure gradient (HVPG) measurements within 30 days between 2015 and 2018 were included. The estimation of CSPH by LSN and LSM, and the LSM-spleen-size-to-platelet ratio score (LSPS) were evaluated and compared., Results: In total, 140 patients were included (109 men [78%], mean age 63 ± 9 years old), including 39 (28%) with CSPH. LSN measurements were valid in 130 patients (93%) and significantly correlated with HVPG (r = 0.68; p <0.001). Patients with CSPH had higher LSN measurements compared with those without [3.1 ± 0.4 vs . 2.5 ± 0.3, p <0.001; area under the receiver operating characteristic (AUROC): 0.87 ± 0.31]. LSM and LSPS were valid in 132 patients (94%) and significantly correlated with HVPG (r = 0.75, p <0.001; AUROC 0.87 ± 0.04 and r = 0.68, p <0.001; AUROC 0.851 ± 0.04, respectively). There was no significant difference in the diagnostic performance between LSN and LSM-LSPS (DeLong, p  = 0.28, 0.37, and 0.65, respectively) in patients with both valid tests (n = 122). LSN <2.50 had a 100% negative predictive value for CSPH. A 2-step algorithm combining LSN and LSPS for the diagnosis of CSPH classified 108/140 patients (77%) with an 8% error., Conclusions: The diagnostic performance and feasibility of LSN measurements were similar to those of LSM for the detection of CSPH in patients with compensated cirrhosis and HCC. Combining LSN and LSPS accurately detected CSPH in >75% of patients. Such a combination could be useful in centres where the HVPG measurement is unavailable., Lay Summary: The diagnostic performance and feasibility of liver surface nodularity was similar to that of liver stiffness measurement (LSM) for the detection of clinically significant portal hypertension in patients with compensated cirrhosis. Thus, liver surface nodularity could be an option for the preoperative detection of clinically significant portal hypertension in patients with hepatocellular carcinoma. Combining liver surface nodularity with LSM-spleen-size-to-platelet ratio score resulted in the accurate detection of clinically significant portal hypertension in >75% of patients, thus limiting the need for HVPG measurements., Competing Interests: The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2020 The Author(s).)

Purpose: To assess and compare the performance of liver surface nodularity (LSN) quantification using Gd-BOPTA-enhanced MRI and contrast-enhanced CT for the diagnosis of clinically significant portal hypertension (CSPH) in patients with cirrhosis., Methods: This retrospective study included 30 patients with compensated histologically proven cirrhosis who underwent hepatic venous pressure gradient (HVPG), abdominal CT and Gd-BOPTA-MRI within a 60-day interval during pre-surgery workup for hepatocellular carcinoma (HCC) between January 2016 and August 2018. LSN score was derived from CT portal venous phase (PVP), axial T2- and T1-weighted PVP and hepatobiliary phase (HBP). Accuracy for the detection of CSPH was evaluated for each set of images by ROC curve analysis. Intra-observer, inter-observer and inter-method reproducibilities were assessed by the intraclass correlation coefficient (ICC) and coefficient of variation (CV)., Results: Thirty patients were analysed (23 men [77%], mean age 60 ± 11 years old), including 15 (50%) with CSPH. All CT- and MRI-derived LSN quantifications were correlated to HVPG (CT-PVP: r = 0.63, p = 0.001, AUROC = 0.908 ± 0.06; T1-w-PVP: r = 0.43, p = 0.028, AUROC = 0.876 ± 0.07; T1-w-HBP: r = 0.50, p = 0.012, AUROC = 0.823 ± 0.08; T2-w: r = 0.51, p = 0.007, AUROC = 0.801 ± 0.09). There was no significant difference in AUROC pairwise comparisons (p = 0.12-0.88). Patients with CSPH had higher LSN than those without (CT-PVP: 3.2 ± 0.6 vs 2.4 ± 0.5, p < 0.001; T1-w-PVP: 2.7 ± 0.4 vs 2.2 ± 0.4, p = 0.002; T1-w-HBP: 3.0 ± 0.6 vs 2.3 ± 0.3, p < 0.001; T2-w: 3.0 ± 0.6 vs 2.2 ± 0.3, p = 0.001) and 86%, 82%, 85% and 82% of patients were correctly classified, respectively. Reproducibility of inter-image set comparisons was excellent (ICC = 0.84-0.96 and CV = 8.3-14.2%)., Conclusion: The diagnostic performance of MRI-based LSN for detecting CSPH is strong and similar to that of CT-based LSN.

Background and Aim: The study aims to assess the influence of pretreatment tumor growth rate (TGR) on modified response evaluation criteria in solid tumors (mRECIST) objective response (OR) after a first session of selective transarterial chemoembolization (TACE) for the treatment of hepatocellular carcinoma (HCC)., Methods: One hundred fifteen patients (101 men [88%], mean 65.1 ± 10.5 years [range 26-87]) with 169 tumors (mean 34.2 ± 29.3 mm [10-160]), undergoing a first session of selective TACE for the treatment of HCC between 2011 and 2016, were included. TGR was calculated as the percentage change in tumor volume per month (%/month) on imaging before treatment. TGR cut-off for prediction of OR was identified by receiver operating characteristic curve analysis., Results: Overall 88/189 (52%) and 46/189 (27%) tumors showed complete response (CR) and partial response (PR) (OR rate 79%), while 32/189 (19%) showed stable disease (SD), and 3/189 (2%) were progressive disease (PD) on computed tomography at 1-month post-TACE. The mean pretreatment TGR was 12.0 ± 15.4 (-3.2-90.4) %/month. TGR of tumors showing CR, PR, SD, and PD was a mean 13.2 ± 16.4%, 12.1 ± 15.1%, 5.3 ± 4.5%, and 44.8 ± 20.4%, respectively (P < 0.001). The three tumors showing PD had TGR values > 20%/month. TGR was significantly higher in tumors with OR (12.8 ± 15.9% vs 5.3 ± 4.5% in SD, P = 0.009). A cut-off value of 6.5%/month had the highest predictive value of OR (AUROC 0.65 ± 0.05, P = 0.009)., Conclusion: Pretreatment TGR is highly variable in HCC before TACE with a U-shaped distribution for the prediction of tumor response. It provides insight into tumor biology that may be used during pretreatment workup to help stratify patients., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: To evaluate the predictive value of the lipiodol retention pattern for local progression of HCC with a complete response (CR) on CT according to mRECIST criteria after a first session of conventional chemoembolization (cTACE)., Methods: From January 2014 to May 2016 all consecutive patients undergoing a first cTACE session for HCC were identified. Inclusion criteria were the presence of ≤3 HCCs and available pre- and post-cTACE CT. Tumor response was classified according to mRECIST criteria. The analysis focused on tumors with a CR. The lipiodol retention pattern in these tumors was classified as complete (C-Lip, covering the entire tumor volume), or incomplete (I-Lip). Local progression was defined as the reappearance of areas of enhancement on arterial-phase images with washout on portal/delayed phase images within 2 cm from treated tumors on follow-up CT., Results: The final population included 50 patients with 82 HCCs. A total of 46 (56%) HCCs were classified with a CR, including 16 (35%) with I-Lip, and 30 (65%) with C-Lip. After a median follow-up of 14 months (3.2-35.9 months), 15/16 (94%) and 10/30 (30%) of I-Lip and C-Lip HCCs showed local progression on CT, respectively (p < 0.001), with no significant difference in the time to progression (mean 11.1 ± 2 vs. 13.4 ± 3 months for I-Lip and C-Lip, respectively p = 0.51)., Conclusions: HCCs with incomplete lipiodol retention after a first cTACE session have a high risk of local progression even when there is a CR according to mRECIST, and should be considered to be incompletely treated.

Purpose To determine whether quantification of liver surface nodularity (LSN) provides an estimate of the presence of clinically significant portal hypertension (CSPH) in patients with cirrhosis. Materials and Methods This retrospective study included a training cohort (n = 189) and separate external validation cohort (n = 78), both composed of patients with cirrhosis who underwent abdominal CT and hepatic venous pressure gradient (HVPG) measurement between 2010 and 2016. The LSN score, liver and spleen volumes, liver-to-spleen volume ratio, platelet count to spleen diameter ratio, Iranmanesh score, aspartate amino transferase-to-platelet ratio index, and Fibrosis-4 index were derived from CT images and serum laboratories. The accuracy of the various tests for predicting CSPH was evaluated with area under the receiver operating characteristic curve (AUROC) and compared by using the DeLong test. Student t test and Pearson correlation coefficient were used. Results One hundred eighty-nine patients were analyzed (119 men [mean age ± standard deviation, 57 years ± 11; range, 29-81 years] and 70 women [mean age, 61 years ± 10; range, 34-83 years]; overall mean age, 58 years ± 10; range, 29-83 years). A total of 102 patients (54%) had CSPH. LSN score correlated with HVPG (r = 0.75; P < .001). Patients with CSPH had a higher LSN score than did those without CSPH (3.2 ± 0.6 vs 2.4 ± 0.3; P < .001). A cutoff value of 2.8 had a positive predictive value of 88% for CSPH; the AUROC of LSN was 0.88 ± 0.03. This was higher than that of other available noninvasive tests (DeLong, all P < .001). In the validation cohort, LSN score of 2.8 had a positive predictive value of 86% for CSPH; the AUROC was 0.87 ± 0.04. Conclusion The CT-based liver surface nodularity score demonstrated high diagnostic performance for detecting clinically significant portal hypertension and outperformed multiple other noninvasive tests. © RSNA, 2018 Online supplemental material is available for this article.