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AIM: This multi-centre prospective cohort study aimed to investigate non-inferiority in patients' overall survival when treating potentially resectable colorectal cancer liver metastasis (CRLM) with stereotactic microwave ablation (SMWA) as opposed to hepatic resection (HR).METHODS: Patients with no more than 5 CRLM no larger than 30 mm, deemed eligible for both SMWA and hepatic resection at the local multidisciplinary team meetings, were deliberately treated with SMWA (study group). The contemporary control group consisted of patients with no more than 5 CRLM, none larger than 30 mm, treated with HR, extracted from a prospectively maintained nationwide Swedish database. After propensity-score matching, 3-year overall survival (OS) was compared as the primary outcome using Kaplan-Meier and Cox regression analyses.RESULTS: All patients in the study group (n = 98) were matched to 158 patients from the control group (mean standardised difference in baseline covariates = 0.077). OS rates at 3 years were 78% (Confidence interval [CI] 68-85%) after SMWA versus 76% (CI 69-82%) after HR (stratified Log-rank test p = 0.861). Estimated 5-year OS rates were 56% (CI 45-66%) versus 58% (CI 50-66%). The adjusted hazard ratio for treatment type was 1.020 (CI 0.689-1.510). Overall and major complications were lower after SMWA (percentage decrease 67% and 80%, p < 0.01). Hepatic retreatments were more frequent after SMWA (percentage increase 78%, p < 0.01).CONCLUSION: SMWA is a valid curative-intent treatment alternative to surgical resection for small resectable CRLM. It represents an attractive option in terms of treatment-related morbidity with potentially wider options regarding hepatic retreatments over the future course of disease.

OBJECTIVES: Differentiating benign gallbladder diseases from gallbladder cancer (GBC) remains a radiological challenge because they can appear very similar on imaging. This study aimed at investigating whether CT-based radiomic features of suspicious gallbladder lesions analyzed by machine learning algorithms could adequately discriminate benign gallbladder disease from GBC. In addition, the added value of machine learning models to radiological visual CT-scan interpretation was assessed.METHODS: Patients were retrospectively selected based on confirmed histopathological diagnosis and available contrast-enhanced portal venous phase CT-scan. The radiomic features were extracted from the entire gallbladder, then further analyzed by machine learning classifiers based on Lasso regression, Ridge regression, and XG Boosting. The results of the best-performing classifier were combined with radiological visual CT diagnosis and then compared with radiological visual CT assessment alone.RESULTS: In total, 127 patients were included: 83 patients with benign gallbladder lesions and 44 patients with GBC. Among all machine learning classifiers, XG boosting achieved the best AUC of 0.81 (95% CI 0.72-0.91) and the highest accuracy rate of 73% (95% CI 65-80%). When combining radiological visual interpretation and predictions of the XG boosting classifier, the highest diagnostic performance was achieved with an AUC of 0.98 (95% CI 0.96-1.00), a sensitivity of 91% (95% CI 86-100%), a specificity of 93% (95% CI 90-100%), and an accuracy of 92% (95% CI 90-100%).CONCLUSIONS: Machine learning analysis of CT-based radiomic features shows promising results in discriminating benign from malignant gallbladder disease. Combining CT-based radiomic analysis and radiological visual interpretation provided the most optimal strategy for GBC and benign gallbladder disease differentiation.KEY POINTS: Radiomic-based machine learning algorithms are able to differentiate benign gallbladder disease from gallbladder cancer. Combining machine learning algorithms with a radiological visual interpretation of gallbladder lesions at CT increases the specificity, compared to visual interpretation alone, from 73 to 93% and the accuracy from 85 to 92%. Combined use of machine learning algorithms and radiological visual assessment seems the most optimal strategy for GBC and benign gallbladder disease differentiation.

Solid interfacing biomaterials is a crucial aspect of bionanotechnology and important for applications such as biosensing. Because of their potentially large contact area, flat solenoidal proteins are ideal scaffolds for designing proteins binding to surfaces of man-made solids such as minerals, metals, and plastics. To explore this opportunity, a naturally occurring flat solenoidal protein: the Rhagium inquistor Antifreeze Protein from the insect Rhagium inquisitor is re-designed. By mutating 4, 6, and 10 out of its 4 × 5 arrays of threonines into arginines, it have arrived at the silica-binding proteins RiSiBP-4, RiSiBP-6, and RiSiBP-10. Variants with increasing numbers of arginines bind stronger to silica, but are also less stable and increasingly difficult to produce. It is found that the RiSiBP-6 variant binds strongly to silica yet still has good stability and easy production. It is shown that sfGFP-RiSiBP-6 fusions allow for the functional display of a monolayer of sfGFP cargo on silica surfaces, suggesting the general usefulness of flat solenoidal proteins as scaffolds for designing solid-binding proteins.

Introduction: Doppler ultrasound of the portal vein peak systolic velocity and hepatic artery peak systolic velocity and resistive index in children is often performed during abdominal ultrasound for the assessment of liver and other abdominal pathology. However, evidence-based reference values are not available. We aimed to determine these reference values and to investigate whether they are age-dependent. Methods: Children who underwent abdominal ultrasound between 2020 and 2021 were retrospectively identified. Patients without hepatic or cardiac abnormalities at the time of ultrasound or during at least 3 months follow-up were eligible for the study. Ultrasound without hepatic hilum portal vein peak systolic velocity and/or hepatic artery peak systolic velocity and resistive index measurements were excluded. Age-dependent changes were analyzed using linear regression. Normal range reference values were described using percentiles for all ages, and for age subgroups. Results: One-hundred ultrasound examinations performed in 100 healthy children aged 0–17.9 years (median 7.8 years, interquartile range 1.1–14.1 years) were included. Ninety-nine portal vein peak systolic velocity and 80 hepatic artery peak systolic velocity and resistive index measurements were obtained. There was no significant association between portal vein peak systolic velocity and age (β = −0.056, p = 0.68). There were significant associations between age and hepatic artery peak systolic velocity, and between age and hepatic artery resistive index (β = −0.873, p = 0.04 and β = −0.004, p Conclusion: Reference values for the hepatic hilum portal vein peak systolic velocity, hepatic artery peak systolic velocity, and hepatic artery resistive index in children were established. Portal vein peak systolic velocity is not age-dependent, whereas hepatic artery peak systolic velocity and hepatic artery resistive index decrease when children get older.

Background: Pheochromocytomas and paragangliomas (PPGL) have up to 20% rate of metastatic disease that cannot be reliably predicted. This study prospectively assessed whether the dopamine metabolite, methoxytyramine, might predict metastatic disease, whether predictions might be improved using machine learning models that incorporate other features and how ML-based predictions compare to predictions by specialists in the field. Methods: In this machine learning modelling study we used cross-sectional cohort data from the PMT trial, based in Germany, Poland, and the Netherlands, to prospectively examine the utility of methoxytyramine to predict metastatic disease in 267 patients with pheochromocytomas and paragangliomas and positive biochemical test results at initial screening. Another retrospective dataset from 493 patients with PPGL enrolled under clinical protocols in National Institutes of Health (00-CH-0093) and the Netherlands (PRESCRIPT trial), was used to train and validate machine learningmodels according to selections of additional features. The best performing machine learningmodels were then externally validated using data for all patients in PMT. For comparison, 12 specialists provided predictions of metastatic disease using data from the training and external validation datasets. Findings: Prospective predictions indicated that plasma methoxytyramine could identify metastatic disease at respective sensitivities and specificities of 52% and 85%. The best performing ML model was based on an ensemble tree classifier algorithm that utilized nine features: plasma methoxytyramine, metanephrine and normetanephrine, age, sex, previous history of PPGL, location and size of primary tumors, presence of multifocal disease. This model presented with an area under the receiver-operating characteristic curve of 0·942 (CI:0·894-0·969) that was larger (PSDHB variant data (0·812, CI:0·781-0·854). Sensitivity for prediction of metastatic disease in the external validation cohort reached 83% at a specificity of 92%. Interpretation: Although methoxytyramine has some utility for prediction of metastatic PPGL, sensitivity is limited. Predictive value is considerably enhanced with ML models that incorporate the above mentioned features. Our final model provides a preoperative approach to predict metastases in patients with PPGL, and thereby guide individualized patient management and follow-up.

Objectives Doppler ultrasound (DUS) is the main imaging modality to evaluate vascular complications of pediatric liver transplants (LT). The current study aimed to determine reference values and their change over time. Methods A consecutive cohort of pediatric patients undergoing an LT were retrospectively included between 2015 and 2020. Timepoints for standardized DUS were intra-operative and postoperative (day 0), days 1–7, months 1 and 3, and years 1 and 2. DUS measurements of the hepatic artery (HA), portal vein (PV), and hepatic vein(s) (HV) were included if there were no complications during 2 years follow-up. Measurements consisted of: peak systolic velocity (PSV) and resistive index (RI) for the HA, PSV for the PV, and venous pulsatility index (VPI) for the HV. Generalized estimating equations were used to analyze change over time. Results One hundred twelve pediatric patients with 123 LTs were included (median age 3.3 years, interquartile range 0.7–10.1). Ninety-five HAs, 100 PVs, and 115 HVs without complications were included. Reference values for HA PSV and RI, PV PSV, and HV VPI were obtained for all timepoints (4043 included data points in total) and presented using 5th–95th percentiles and threshold values. All reference values changed significantly over time (p = 0.032 to p < 0.001). Conclusions DUS reference values of hepatic vessels in children after LT are presented, reference values change over time with specific vessel-dependent patterns. Timepoint–specific reference values improve the interpretation of DUS values and may help to better weigh their clinical significance. Key Points • Doppler ultrasound reference values of pediatric liver transplantations are not static but change over time. Applying the correct reference values for the specific timepoint may further improve the interpretation of the measurements. • The pattern of change over time of Doppler ultrasound measurements differs between the hepatic vessel and measurement; knowledge of these patterns may help radiologists to better understand normal postoperative hemodynamic changes.

Contains fulltext : 290866.pdf (Publisher’s version ) (Open Access) BACKGROUND: Management of focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA), is multidisciplinary and subject to practice variation. We aimed to evaluate variation in clinical management of FNH and HCA in Europe. METHODS: We distributed an online survey (November 2021-March 2022) among 294 European experts. The survey included questions on local practice and included eight clinical vignettes. The clinical vignettes focused on FNH or HCA management in the setting of sex, lifestyle modification, and pregnancy. RESULTS: The response rate was 32% and respondents included surgeons (38%), gastroenterologists/hepatologists (25%), radiologists (32%), and pathologists (1.6%) from ten European countries. We observed practice variation with regard to lifestyle modification and imaging follow-up in patients with FNH, and with regard to the management of HCA >5 cm before and during pregnancy. Finally, the management of HCA >5 cm after lifestyle modification deviated from EASL guideline recommendations. CONCLUSION: Our survey illustrates variability in FNH and HCA management in Europe. Several areas were identified for future research and guideline recommendations, including FNH follow-up and the management of HCA >5 cm. We propose the organization of Delphi consensus meetings to prioritize areas of research and update current guidelines to optimize management for all patients with benign liver tumors.

BACKGROUND AND METHODS: Treatment strategies for pancreatic cancer patients are made by a multidisciplinary team (MDT) board. We aimed to assess intra-observer variance at MDT boards. Participating units staged, assessed resectability, and made treatment allocations for the same patients as they did two years earlier. We disseminated clinical information and CT images of pancreatic cancer patients judged by one MDT board to have nonmetastatic pancreatic cancer to the participating units. All units were asked to re-assess the TNM stage, resectability, and treatment allocation for each patient. To assess intra-observer variance, we computed %-agreements for each participating unit, defined as low (75%) agreement.RESULTS: Eighteen patients were re-assessed by six MDT boards. The overall agreement was moderate for TNM-stage (ranging from 50%-70%) and resectability assessment (53%) but low for treatment allocation (46%). Agreement on resectability assessments was low to moderate. Findings were similar but more pronounced for treatment allocation. We observed a shift in treatment strategy towards increasing use of neoadjuvant chemotherapy, particularly in patients with borderline resectable and locally advanced tumors.CONCLUSIONS: We found substantial intra-observer agreement variations across six different MDT boards of 18 pancreatic cancer patients with two years between the first and second assessment.

The Gallbladder Reporting and Data System (GB-RADS) ultrasound (US) risk stratification is proposed to improve consistency in US interpretations, reporting, and assessment of risk of malignancy in gallbladder wall thickening in non-acute setting. It was developed based on a systematic review of the literature and the consensus of an international multidisciplinary committee comprising expert radiologists, gastroenterologists, gastrointestinal surgeons, surgical oncologists, medical oncologists, and pathologists using modified Delphi method. For risk stratification, the GB-RADS system recommends six categories (GB-RADS 0–5) of gallbladder wall thickening with gradually increasing risk of malignancy. GB-RADS is based on gallbladder wall features on US including symmetry and extent (focal vs. circumferential) of involvement, layered appearance, intramural features (including intramural cysts and echogenic foci), and interface with the liver. GB-RADS represents the first collaborative effort at risk stratifying the gallbladder wall thickening. This concept is in line with the other US-based risk stratification systems which have been shown to increase the accuracy of detection of malignant lesions and improve management. Graphical abstract: [Figure not available: see fulltext.].

[This corrects the article DOI: 10.1055/a-1961-9100.].

Computed tomography (CT)-derived body metrics such as skeletal muscle index (SMI), psoas muscle index (PMI), and subcutaneous fat area index (ScFI) are measurable components of sarcopenia, frailty, and nutrition. While these body metrics are advocated in adults for predicting postoperative outcomes after liver transplantation (LT), little is known about their value in pediatric populations. This study assessed the relation between preoperative CT-based body metrics and postoperative short-term outcomes in pediatric LT recipients. Patients aged 0-18 years who underwent a primary LT were retrospectively included (n = 101; median age 0.5 years; range 0.2-17.1). SMI, PMI, and ScFI were derived from preoperative axial CT slices. Postoperative outcomes and complications within 90 days were correlated with the CT-based body metrics. To classify postoperative infections, the Clavien-Dindo (CD) classification was used. Subgroup analyses were performed for age groups ( 10 years old). An optimal threshold for test performance was defined using Youden's J-statistic and receiver operating characteristic curve as appropriate. ScFI was significantly (P = 0.001) correlated with moderate to severe postoperative infections (CD grade 3-5) in children aged

Background Early recognition and management of postoperative complications, before they become clinically relevant, can improve postoperative outcomes for patients, especially for high-risk procedures such as pancreatic resection. Methods We did an open-label, nationwide, stepped-wedge cluster-randomised trial that included all patients having pancreatic resection during a 22-month period in the Netherlands. In this trial design, all 17 centres that did pancreatic surgery were randomly allocated for the timing of the crossover from usual care (the control group) to treatment given in accordance with a multimodal, multidisciplinary algorithm for the early recognition and minimally invasive management of postoperative complications (the intervention group). Randomisation was done by an independent statistician using a computer-generated scheme, stratified to ensure that low-medium-volume centres alternated with high-volume centres. Patients and investigators were not masked to treatment. A smartphone app was designed that incorporated the algorithm and included the daily evaluation of clinical and biochemical markers. The algorithm determined when to do abdominal CT, radiological drainage, start antibiotic treatment, and remove abdominal drains. After crossover, clinicians were trained in how to use the algorithm during a 4-week wash-in period; analyses comparing outcomes between the control group and the intervention group included all patients other than those having pancreatic resection during this wash-in period. The primary outcome was a composite of bleeding that required invasive intervention, organ failure, and 90-day mortality, and was assessed by a masked adjudication committee. This trial was registered in the Netherlands Trial Register, NL6671. Findings From Jan 8, 2018, to Nov 9, 2019, all 1805 patients who had pancreatic resection in the Netherlands were eligible for and included in this study. 57 patients who underwent resection during the wash-in phase were excluded from the primary analysis. 1748 patients (885 receiving usual care and 863 receiving algorithm-centred care) were included. The primary outcome occurred in fewer patients in the algorithm-centred care group than in the usual care group (73 [8%] of 863 patients vs 124 [14%] of 885 patients; adjusted risk ratio [RR] 0middot48, 95% CI 0middot38-0middot61; p

Background: Approximately 26% of esophageal cancer (EC) patients do not respond to neoadjuvant chemoradiotherapy (nCRT), emphasizing the need for pre-treatment selection. The aim of this study was to predict non-response using a radiomic model on baseline 18F-FDG PET. Methods: Retrospectively, 143 18F-FDG PET radiomic features were extracted from 199 EC patients (T1N1-3M0/T2–4aN0-3M0) treated between 2009 and 2019. Non-response (n = 57; 29%) was defined as Mandard Tumor Regression Grade 4–5 (n = 44; 22%) or interval progression (n = 13; 7%). Randomly, 139 patients (70%) were allocated to explore all combinations of 24 feature selection strategies and 6 classification methods towards the cross-validated average precision (AP). The predictive value of the best-performing model, i.e AP and area under the ROC curve analysis (AUC), was evaluated on an independent test subset of 60 patients (30%). Results: The best performing model had an AP (mean ± SD) of 0.47 ± 0.06 on the training subset, achieved by a support vector machine classifier trained on five principal components of relevant clinical and radiomic features. The model was externally validated with an AP of 0.66 and an AUC of 0.67. Conclusion: In the present study, the best-performing model on pre-treatment 18F-FDG PET radiomics and clinical features had a small clinical benefit to identify non-responders to nCRT in EC.

OBJECTIVE. Parastomal hernia (PSH) is a common complication that can occur after end colostomy and may result in considerable morbidity. To select the best candidates for prophylactic measures, knowledge of preoperative PSH predictors is important. This study aimed to determine the value of clinical parameters, preoperative CT-based body metrics, and size of the abdominal wall defect created during end colostomy and measured at postoperative CT for predicting PSH development.MATERIALS AND METHODS. Sixty-five patients who underwent permanent end colostomy with at least 1 year of follow-up were included. On preoperative CT, waist circumference, abdominal wall and psoas muscle indexes, rectus abdominis muscle diameter and diastasis, intra- and extraabdominal fat mass, and presence of other hernias were assessed. On postoperative CT, size of the abdominal wall defect and the presence of PSH were determined. To identify independent predictors of PSH development, univariate analysis with the Kaplan-Meier method and multivariate Cox regression analysis were performed.RESULTS. PSH developed after surgery in 30 patients (46%). Three independent risk factors were identified: chronic obstructive pulmonary disease (COPD) as a comorbidity (hazard ratio [HR], 6.4; 95% CI, 1.9-22.0; p = 0.003), operation time longer than 395 minutes (HR, 3.9; 95% CI, 1.5-10.0; p = 0.005), and maximum aperture diameter of more than 34 mm (HR, 5.2; 95% CI, 2.1-12.7; p CONCLUSION. COPD, longer operation time, and larger abdominal wall defect at the colostomy site can predict PSH development. Intraoperative creation of an abdominal wall ostomy opening that is more than 34 mm in diameter should be avoided.

Background We aimed to determine the anorectal physiological factors associated with rectocele formation. Methods Female patients (N = 32) with severe constipation, fecal incontinence, or suspicion of rectocele, who had undergone magnetic resonance defecography and anorectal function tests between 2015 and 2021, were retrospectively included for analysis. The anorectal function tests were used to measure pressure in the anorectum during defecation. Rectocele characteristics and pelvic floor anatomy were determined with magnetic resonance defecography. Constipation severity was determined with the Agachan score. Information regarding constipation-related symptoms was collected. Results Mean rectocele size during defecation was 2.14 ± 0.88 cm. During defecation, the mean anal sphincter pressure just before defecation was 123.70 ± 67.37 mm Hg and was associated with rectocele size (P = 0.041). The Agachan constipation score was moderately correlated with anal sphincter pressure just before defecation (r = 0.465, P = 0.022), but not with rectocele size (r = 0.276, P = 0.191). During defecation, increased anal sphincter pressure just before defecation correlated moderately and positively with straining maneuvers (r = 0.539, P = 0.007) and defecation blockage (r = 0.532, P = 0.007). Rectocele size correlated moderately and positively with the distance between the pubococcygeal line and perineum (r = 0.446, P = 0.011). Conclusion Increased anal sphincter pressure just before defecation is correlated with the rectocele size. Based on these results, it seems important to first treat the increased anal canal pressure before considering surgical rectocele repair to enhance patient outcomes. Graphical abstract

Hepatocellular adenomas (HCA) are rare benign tumors of the liver, occurring predominantly in females using oral contraceptives. Our case describes a 66-year-old woman presenting with a palpable mass in her upper abdomen. Contrast-enhanced computed tomography and magnetic resonance imaging showed a large exophytic mass protruding from the caudal border of liver segments IV and V, without visible metastases. Laparoscopic resection of the tumor and gallbladder was performed. Histopathological examination showed a hepatocellular carcinoma with areas of HNF1a-HCA (H-HCA). This case shows that malignant transformation is possible in H-HCA. We present our preoperative decision-making process, as well as the role of imaging techniques in this rare case.

Objectives: Biliary atresia (BA) causes neonatal cholestasis that requires hepatoportoenterostomy or liver transplantation (LT) for long-term survival. Nutritional optimization is necessary as sarcopenia and sarcopenic obesity have been associated with adverse clinical outcome. Currently, mid upper arm circumference (MUAC) is considered the most accurate indicator. The aim of the study was to determine computed tomography (CT)-based body metrics in infants with BA and to evaluate its correlation with MUAC.Methods: We retrospectively analyzed all BA infants below 2 years of age who underwent CT as part of LT screening at our hospital between 2006 and 2019. Measured variables were indexed with length and included: MUAC, total psoas muscle surface area (tPMSA), cross-sectional skeletal muscle area (CSMA), and total abdominal fat area. Intraclass correlation coefficients and Pearson coefficients were calculated. CSMA-to-abdominal fat area ratio was divided in quartiles, the lowest quartile group was considered sarcopenic obese.Results: Eighty infants with a median age of 4.6 months at LT screening were included. Intraclass correlation coefficients were: tPMSA = 0.94, CSMA = 0.92, and total abdominal fat area = 0.99. Correlation between MUAC z-score and indices of tPMSA, CSMA, and total abdominal fat area were r = 0.02, r = 0.06, and r = 0.43, respectively. The cut-off for sarcopenic obesity was CSMA-to-abdominal fat area ratio below 0.93.Conclusions: In BA infants, it is possible to determine CT-based body metrics during LT screening with very strong interobserver agreement. Poor correlation between CT-based body metrics and MUAC suggests that CT-based body metrics provide additional information on body composition in BA infants, such as relative muscle mass.

Hepatocellular adenomas (HCAs) are benign liver tumors associated with bleeding or malignant transformation. Data on the indication for surgery are scarce. We analyzed indications and outcome of patients operated for HCAs < 50 mm compared to HCAs ≥ 50 mm. Changes in final postoperative diagnosis were assessed. We performed a retrospective study that included patients who underwent resection for (suspected) HCAs in the Netherlands from 2014 to 2019. Indication for resection was analyzed and stratified for small (50 mm (52%), suspicion of (pre)malignancy (28%), and (previous) bleeding (5.1%). No difference was observed in HCA-subtype distribution between small and large tumors. Ninety-six (43%) patients had a postoperative change in diagnosis. Independent risk factors for change in diagnosis were tumor size

Background: Despite its widespread use, computed tomography (CT) is not perfect for evaluating peritoneal metastases of colorectal origin before cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC). We therefore evaluated the value of adding diagnostic lapamscopy to CT when assessing patient eligibility for CRS + HIPEC.Methods: This was a retrospective study of a consecutive series of 112 patients evaluated systematically by diagnostic laparoscopy and CT between January 2012 and January 2018. Patient eligibility for CRS + HIPEC was assessed by the peritoneal cancer index (PCI) both at the time of initial diagnostic lapamscopy and during the retrospective review of CT images. Two experienced radiologists who were blinded to the PCI result at laparoscopy then independently estimated the PCI based on CT imaging. The primary outcome was the number of patients eligible for CRS + HIPEC by each method.Results: We identified 112 patients, of whom 95 (85%) were eligible for CRS + HIPEC based on diagnostic laparoscopy and 84 underwent CRS + HIPEC. Overall, 14 patients (17%) experienced an "open-and-close" procedure. In contrast to diagnostic lapamscopy, 100 patients (89%) were identified as being eligible for CRS + HIPEC by CT (p = 0.13), which would have resulted in an additional five open-and-close procedures.Conclusions: Adding diagnostic laparoscopy to CT produced a clinically relevant, but statistically non-significant, reduction in the number of patients eligible for CRS + HIPEC. We conclude that diagnostic lapamscopy may be of use in preoperative assessments when systematic analysis by CT scores the PCI as greater than ten. Future research should focus on the cost-effectiveness of this approach.

Objectives Deep learning has been proven to be able to stage liver fibrosis based on contrast-enhanced CT images. However, until now, the algorithm is used as a black box and lacks transparency. This study aimed to provide a visual-based explanation of the diagnostic decisions made by deep learning. Methods The liver fibrosis staging network (LFS network) was developed at contrast-enhanced CT images in the portal venous phase in 252 patients with histologically proven liver fibrosis stage. To give a visual explanation of the diagnostic decisions made by the LFS network, Gradient-weighted Class Activation Mapping (Grad-cam) was used to produce location maps indicating where the LFS network focuses on when predicting liver fibrosis stage. Results The LFS network had areas under the receiver operating characteristic curve of 0.92, 0.89, and 0.88 for staging significant fibrosis (F2–F4), advanced fibrosis (F3–F4), and cirrhosis (F4), respectively, on the test set. The location maps indicated that the LFS network had more focus on the liver surface in patients without liver fibrosis (F0), while it focused more on the parenchyma of the liver and spleen in case of cirrhosis (F4). Conclusions Deep learning methods are able to exploit CT-based information from the liver surface, liver parenchyma, and extrahepatic information to predict liver fibrosis stage. Therefore, we suggest using the entire upper abdomen on CT images when developing deep learning–based liver fibrosis staging algorithms. Key Points • Deep learning algorithms can stage liver fibrosis using contrast-enhanced CT images, but the algorithm is still used as a black box and lacks transparency. • Location maps produced by Gradient-weighted Class Activation Mapping can indicate the focus of the liver fibrosis staging network. • Deep learning methods use CT-based information from the liver surface, liver parenchyma, and extrahepatic information to predict liver fibrosis stage.

Background: Positron emission tomography (PET) with 16α-[18F]-fluoro-17β-estradiol ([18F]-FES) can visualize estrogen receptor (ER) expression, but it is challenging to determine the ER status of liver metastases, due to high physiological [18F]-FES uptake. We evaluated whether [18F]-FES-PET can be used to determine the ER status of liver metastases, using corresponding liver biopsies as the gold standard. Methods: Patients with metastatic breast cancer (n = 23) were included if they had undergone a [18F]-FES-PET, liver metastasis biopsy, CT-scan, and [18F]-FDG-PET. [18F]-FES-PET scans were assessed by visual and quantitative analysis, tracer uptake was correlated with ER expression measured by immunohistochemical staining and the effects of region-of-interest size and background correction were determined. Results: Visual analysis allowed ER assessment of liver metastases with 100% specificity and 18% sensitivity. Quantitative analysis improved the sensitivity. Reduction of the region-of-interest size did not further improve the results, but background correction improved ER assessment, resulting in 83% specificity and 77% sensitivity. Using separate thresholds for ER+ and ER− metastases, positive and negative predictive values of 100% and 75%, respectively, could be obtained, although 30% of metastases remained inconclusive. Conclusion: In the majority of liver metastases, ER status can be determined with [18F]-FES-PET if background correction and separate thresholds are applied.

BACKGROUND AND AIM: Portal vein thrombosis (PVT) is a common complication of cirrhosis. The exact pathophysiology remains largely unknown, and treatment with anticoagulants does not lead to recanalization of the portal vein in all patients. A better insight into the structure and composition of portal vein thrombi may assist in developing strategies for the prevention and treatment of PVT.APPROACH AND RESULTS: Sixteen prospectively and 63 retrospectively collected nonmalignant portal vein thrombi from patients with cirrhosis who underwent liver transplantation were included. Histology, immunohistochemistry, and scanning electron microscopy were used to assess structure and composition of the thrombi. Most recent CT scans were reanalyzed for thrombus characteristics. Clinical characteristics were related to histological and radiological findings. All samples showed a thickened, fibrotic tunica intima. Fibrin-rich thrombi were present on top of the fibrotic intima in 9/16 prospective cases and in 21/63 retrospective cases. A minority of the fibrotic areas stained focally positive for fibrin/fibrinogen (16% of cases), von Willebrand factor (VWF; 10%), and CD61 (platelets, 21%), while most of the fibrin-rich areas stained positive for those markers (fibrin/fibrinogen, 100%; VWF, 77%; CD61, 100%). No associations were found between clinical characteristics including estimated thrombus age and use of anticoagulants and presence of fibrin-rich thrombi.CONCLUSION: We demonstrate that PVT in patients with cirrhosis consists of intimal fibrosis with an additional fibrin-rich thrombus in only one-third of cases. We hypothesize that our observations may explain why not all portal vein thrombi in patients with cirrhosis recanalize by anticoagulant therapy.

Background Radiological differentiation between benign and malignant gallbladder disease is important but remains challenging. Furthermore, the clinical value of diffusion-weighted imaging (DWI) remains unclear. Purpose To determine the value of DWI in discriminating benign from malignant gallbladder disease by conducting a systematic review and meta-analysis. Material and Methods The literature was systematically searched. Studies analyzing diagnostic value of DWI in gallbladder disease with histopathology or follow-up as reference standard were included. Study selection and data extraction were done by two reviewers independently. Methodological quality was assessed using the QUADAS-2 tool. Sensitivity and specificity were calculated and displayed in a forest plot. A sensitivity analysis was performed in case of outliers. Pooled sensitivity and specificity of DWI were plotted on a hierarchical summary receiver operating characteristic curve. If available, the added value of DWI to conventional magnetic resonance imaging (MRI) sequences was analyzed. Results Out of 2456 articles, eight studies fulfilled the inclusion criteria; 592 patients with 221 malignant lesions were included. Pooled sensitivity and specificity rates were 0.87 and 0.84, respectively. In two studies, diagnostic accuracy rates improved after adding DWI to conventional MRI (64% and 75% for conventional MRI vs. 89% and 94% after combining conventional MRI with DWI). In another study, the area under the curve increased from 0.92 to 0.95. Conclusion DWI appears to be an accurate imaging technique in discriminating benign from malignant gallbladder disease. To achieve optimal patient care, it should be part of multiparametric MRI and should be combined with other imaging modalities.

During LT screening, children undergo CTA to determine hepatic artery anatomy. However, CTA imparts radiation, unlike MRA. The aim was to compare MRA to CTA in assessing hepatic artery anatomy in pediatric LT recipients. Twenty-one children (median age 8.9 years) who underwent both CTA and fl3D-ce MRA before LT were retrospectively included. Interreader variability between 2 radiologists, image quality, movement artifacts, and confidence scores, were used to compare MRA to CTA. Subgroup analyses for ages

Purpose: To determine diagnostic performance of preoperative CT in differentiating between benign and malignant suspicious gallbladder lesions and to develop a preoperative risk score.Method: All patients referred between January 2007 and September 2018 for suspicion of gallbladder cancer (GBC) or incidentally found GBC were retrospectively analyzed. Patients were excluded when preoperative CT or histopathologic examination was lacking. Two radiologists, blinded to histopathology results, independently reviewed CT images to differentiate benign disease from GBC. Multivariable analysis and internal validation were used to develop a risk score for GBC. Model discrimination, calibration, and diagnostic performance were assessed.Results: In total, 118 patients with 39 malignant (33 %) and 79 benign (67 %) lesions were included. Sensitivity of CT for diagnosing GBC was 90 % (95 % confidence interval [CI]: 76?97). Specificity rates were 61 % (95 % CI: 49?72) and 59 % (95 % CI: 48?70). Three predictors of GBC (irregular lesion aspect, absence of fat stranding, and locoregional lymphadenopathy) were included in the risk score ranging from -1 to 4. Adequate performance was found (AUC: 0.79, calibration slope: 0.89). In patients allocated >0 points, the model showed higher performance in excluding GBC than the radiologists (sensitivity 92 % [95 % CI: 79?98]). Moreover, when allocated >3 points, the risk score was superior in diagnosing GBC (specificity 99 % [95 % CI: 93?100]). Conclusions: Sensitivity rates of CT for differentiation between benign and malignant gallbladder lesions are high, however specificity rates are relatively low. The proposed risk score may facilitate differentiation between benign and malignant suspicious gallbladder lesions.

Hepatocyte nuclear factor 1A (HNF1A) maturity-onset diabetes of the young (MODY) is a monogenetic, autosomal dominantly inherited form of diabetes. HNF1A-MODY is associated with HNF1A-inactivated hepatocellular adenoma (H-HCA) formation. Hepatocellular adenoma (HCA) are benign liver tumours and related complications are rare but serious: hepatic haemorrhage and malignant transformation. Guidelines recommend resection of all HCA in men and do not take any co-occurring metabolic disorders into account. We report a family with HCA preceding diabetes mellitus. Male index patient presented with numerous, irresectable HCA. After initial diagnostic and aetiologic uncertainty HNF1A germline mutation c.815G>A (p.Arg272His) was confirmed 8 years later. No HCA-related complications occurred. His diabetic mother was diagnosed with HCA after severe hepatic haemorrhage years before. HNF1A-MODY should be considered in (non-)diabetic (male) patients with H-HCA. We advocate liver biopsy and, if necessary, genetic analysis to precede any intervention for HCA in males and screening for HCA in HNF1A-MODY patients.

OBJECTIVE. Local ablation of hepatocellular carcinoma (HCC) before liver transplant has important advantages, such as preventing disease progression, tumor downstaging, and offering a test of time. However, it might render liver transplant more technically demanding Thus far, its potential effect on liver transplant outcomes is still unknown, and, therefore, the current study was performed.MATERIALS AND METHODS. Patients who underwent liver transplant for HCC at a single tertiary referral center between 2008 and 2016 were included and retrospectively analyzed. Patients who underwent liver resection and local ablation before liver transplant were excluded. Patients treated with local ablation before liver transplant were compared with those not treated with local ablation, both before and after propensity score matching In addition, the local ablation group was compared with patients who underwent primary resection before liver transplant. Posttreatment mortality and morbidity were determined, and overall and disease-free survival rates were calculated.RESULTS. In total, 182 patients were included. Twenty-six patients underwent resection but not local ablation before liver transplant. Of the remaining 156 patients, 66 (42%) underwent local ablation before liver transplant and 90 (58%) did not. Perioperative mortality and morbidity were similar in both groups before and after propensity score matching (8% and 74% in the local ablation group vs 10% and 83% in the non-local ablation group, p = 0.60 and 0.17, respectively). In addition, no significant differences in long-term outcomes were observed between the groups before and after propensity score matching Also, no differences were observed in outcomes in the local ablation group versus the liver resection group.CONCLUSION. Local ablation before liver transplant does not have a negative effect on outcomes after liver transplant for HCC.

BACKGROUND & AIMS: Hepatocellular Adenomas (HCA) are rare, hormone driven, benign liver tumors. HCA >50mm are associated with hemorrhage and malignant transformation. Guidelines recommend cessation of oral contraceptive pills (OCP) for size reduction, however, it is currently unknown how HCA respond to cessation of OCP. We sought to investigate the effect of OCP cessation on HCA size.METHODS: A retrospective cohort study was performed including HCA patients who stopped OCP intake within six months of imaging between 2005-2018. Biometrics and hormonal medication use were evaluated with self-designed questionnaires. Response of the largest HCA was evaluated according to Response Evaluation Criteria in Solid Tumors (RECISTv1.1). Cox regression was performed for analysis of factors influencing HCA regression.RESULTS: Seventy-eight HCA patients were included, diagnosed at a median (IQR) age of 32 (26-41) years. Follow-up was 1.6 (0.4-2.9) years. HCA size at diagnosis ranged 10-167mm. After a median time of 1.3 (0.6 - 2.6) years after OCP cessation, 37.2% of HCA showed >30% regression, 5.1% complete regression, 56.4% stability, and 1.3% progression. No HCA induced complications were observed during follow-up. Cox regression analysis demonstrated a significant association of HCA size with rate of regression; 50≤HCA100mm (HR 8.3, 95% CI 3.3-21.6; pCONCLUSIONS: Ninety-eight percent of HCA remained stable or regressed after OCP cessation. A longer wait-and-see period was associated with a larger proportion of regressing HCA, without HCA related complications during follow-up. This article is protected by copyright. All rights reserved.

Introduction: This study aimed to determine the positive predictive value (PPV) of positron emission tomography/computed tomography (PET/CT) with an F-18-fluoro-2-deoxy-D-glucose (FDG)-avid presacral lesion for locally recurrent rectal cancer, and the additional value of magnetic resonance imaging (MRI), including diffusion-weighted imaging (DWI).Materials and methods: This retrospective study included 38 patients who completed primary rectal cancer treatment and who presented with a suspicious FDG-avid presacral lesion on PET/CT. Twenty-seven patients also underwent MRI, of whom 24 with DWI. PPV of FOG-PET/CT and additional value of MRI, including DWI, for the diagnosis of recurrent presacral cancer were determined.Results: The PPV of PET/CT with an FDG-avid presacral lesion for the diagnosis of locally recurrent rectal cancer was 58% (22/38). Air in the FDG-avid presacral lesion, as visible on the a component of the PET/CT examination, favoured the diagnosis of benign presacral tissue with a sensitivity of 56.3% (9/16) and a specificity 81.8% (18/22). Areas under the receiver operating characteristic curve (AUCs) of MRI without DWI for the diagnosis of locally recurrent rectal cancer in FDG-avid presacral tissue were 0.765 and 0.840, for observers 1 and 2. AUCs of MRI with DWI were 0.803 and 0.811, for observers 1 and 2. There were no significant differences among any of these AUCs (P=0.169 to 0.906).Conclusions: FOG-PET/CT has a poor PPV for locally recurrent rectal cancer in the presacral space. The observation of air in the FDG-avid presacral lesion and additional MRI assessment are diagnostically helpful, without a significant additional value of DWI. (C) 2018 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Background Hepatocellular adenomas (HCA) are benign liver tumors at risk of hemorrhage. The influence of pregnancy on HCA growth and potential bleeding remains unclear. This study investigates HCA-associated behavior and bleeding complications during or shortly after pregnancy. Methods (I) Single center retrospective cohort study of HCA during and after pregnancy (II) Systematic literature review. Results The retrospective study included 11 patients, of which 4 with HCA ≥5 cm. In only two patients HCA showed growth during pregnancy. In this local cohort, no HCA-related hemorrhages occurred during median follow-up of 34 months (interquartile range 19–58 months). The systematic review yielded 33 studies, totaling 90 patients with 99 pregnancies. Of 73 pregnancies without prior HCA-related intervention, 39 HCA remained stable (53.4%), 11 regressed (15.1%), and 23 (31.5%) progressed. Fifteen HCA-related hemorrhages occurred in HCA measuring 6.5–17.0 cm. Eight patients experienced bleeding during pregnancy, two during labor and five postpartum. Conclusion Although hemorrhage of HCA during or shortly after pregnancy is rare and only reported in HCA ≥6.5 cm, it can be fatal. Pregnancy in women with HCA, regardless of size, warrant a close surveillance strategy. Observational studies on behavior and management of HCA ≥5 cm during and immediately after pregnancy are needed.

Portal biliopathy refers to biliary tree abnormalities in patients with peribiliary collateral vessels and non-neoplastic extrahepatic portal vein occlusion. These biliary abnormalities are caused by vascular compression and ischemic damage of the biliary tree, which can result in bile duct compression, stenosis, fibrotic strictures, bile duct dilation, and thickening of the bile duct wall. Portal biliopathy is difficult to distinguish from cholangiocarcinoma, IgG4-related disease, and sclerosing cholangitis. Although most patients are asymptomatic, portal biliopathy can lead to serious complications, such as recurrent cholangitis. This case illustrates the importance of including portal biliopathy in the differential diagnosis at an early stage, especially in patients with portal hypertension. With early recognition, the need for additional invasive diagnostic procedures such as biopsies is minimized. Pathogenesis, clinical presentation, diagnostics, and treatment options of portal biliopathy are described in the article.

Background and Aims Recently, we performed a large randomized-controlled trial to assess the effects of the somatostatin analogue lanreotide on kidney function and kidney and liver volume in autosomal dominant polycystic kidney disease (ADPKD), the DIPAK-1 trial. Lanreotide had no effect on rate of kidney function decline, but slowed kidney and especially liver growth and is used for this indication in clinical practice1,2. A higher incidence of gallstones has been suggested with lanreotide use, but the exact size and implications of this problem are unknown. Therefore, we systematically studied the incidence of gallstones with lanreotide in ADPKD patients. Method In the DIPAK-1 trial, 305 ADPKD patients (age 18-60 years and eGFR 30-60 ml/1.73m2/min) were randomized to lanreotide or standard of care. MRIs were performed at baseline and end of study (120 weeks). For this post-hoc study, patients with a medical history of cholecystectomy (n=7) or absence of a MRI at the end of study (n=28) were excluded. For the remaining study population (n=270), all MRIs were assessed for presence of gallstones by two trained investigators blinded for study treatment and study period and in case of disagreeing results, an abdominal radiologist was consulted for a final assessment. For patients with gallstones additional follow up after the end of the trial was obtained. Results In 2 baseline and 8 end-of -study MRIs, it was not possible to identify the gallbladder, due to multiple adjacent liver cysts. Of the remaining 260 patients (age 48.5 years, female 49.6%, eGFR 50.0 ml/min/1.73m2), 14 patients (5,4%) had gallstones at baseline, of whom 5 were randomized to lanreotide and 9 to standard care. At the end of study, 32 patients (12,3%) had gallstones, of whom 21 patients had received lanreotide and 11 standard care. During the 120 week lasting study, new gallstones occurred in 17 out of 128 patients receiving lanreotide (13.3%) and 3 out of 132 patients receiving standard care (2.3%), rendering an adjusted Odds Ratio for gallstone formation with lanreotide use of 6.9 (95% Confidence Interval 1.9-24.7) p Of the 32 patients with gallstones at the end of study, seven experienced gallstone-associated complications. Three experienced a biliary pancreatitis (1 during and 2 after the study). Another one had signs of a chronic pancreatitis as accidental finding on imaging during the study, without having had symptoms. Furthermore, another 3 patients underwent a cholecystectomy for symptomatic gallstones after the study. Importantly, all patients with gallstone-associated complications were part of the subgroup of patients that developed de novo gallstones during lanreotide use in the study. Conclusion Lanreotide increases the risk of gallstone formation in ADPKD sevenfold. Gallstones were associated with severe complications, most occurring after the end of the trial. The benefit of somatostatin analogues to reduce kidney and liver size in ADPKD should therefore be weighed against the higher incidence of these adverse events, and patients and doctors should be aware of the risk of (symptomatic) gallstones with use of these drugs.

Coronavirus disease 2019 (COVID-19) is a contagious life-threatening infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Recent findings indicate an increased risk for acute kidney injury during COVID-19 infection. The pathophysiologic mechanisms leading to acute kidney injury in COVID-19 infection are unclear but may include direct cytopathic effects of the virus on kidney tubular and endothelial cells, indirect damage caused by virus-induced cytokine release, and kidney hypoperfusion due to a restrictive fluid strategy. In this report of 2 cases, we propose an additional pathophysiologic mechanism. We describe 2 cases in which patients with COVID-19 infection developed a decrease in kidney function due to kidney infarction. These patients did not have atrial fibrillation. One of these patients was treated with therapeutic doses of low-molecular-weight heparin, after which no further deterioration in kidney function was observed. Our findings implicate that the differential diagnosis of acute kidney injury in COVID-19–infected patients should include kidney infarction, which may have important preventive and therapeutic implications.