Seven cases of hereditary haemorrhagic telangiectasia-like hepatic vascular abnormalities associated with EPHB4 pathogenic variants.

BACKGROUND: EPHB4 loss of function is associated with type 2 capillary malformation-arteriovenous malformation syndrome, an autosomal dominant vascular disorder. The phenotype partially overlaps with hereditary haemorrhagic telangiectasia (HHT) due to epistaxis, telangiectases and cerebral arteriovenous malformations, but a similar liver involvement has never been described. METHODS: Members of the French HHT network reported their cases of EPHB4 mutation identified after an initial suspicion of HHT. Clinical, radiological and genetic characteristics were analysed. RESULTS: Among 21 patients with EPHB4, 15 had a liver imaging, including 7 with HHT-like abnormalities (2 female patients and 5 male patients, ages 43-69 years). Atypical epistaxis and telangiectases were noted in two cases each. They were significantly older than the eight patients with normal imaging (median: 51 vs 20 years, p<0.0006).The main hepatic artery was dilated in all the cases (diameter: 8-11 mm). Six patients had hepatic telangiectases. All kind of shunts were described (arteriosystemic: five patients, arterioportal: two patients, portosystemic: three patients). The overall liver appearance was considered as typical of HHT in six cases.Six EPHB4 variants were classified as pathogenic and one as likely pathogenic, with no specific hot spot. CONCLUSION: EPHB4 loss-of-function variants can be associated with HHT-like hepatic abnormalities and should be tested for atypical HHT presentations.

Synthetic MR image generation of macrotrabecular-massive hepatocellular carcinoma using generative adversarial networks.

PURPOSE: The purpose of this study was to develop a method for generating synthetic MR images of macrotrabecular-massive hepatocellular carcinoma (MTM-HCC). MATERIALS AND METHODS: A set of abdominal MR images including fat-saturated T1-weighted images obtained during the arterial and portal venous phases of enhancement and T2-weighted images of 91 patients with MTM-HCC, and another set of MR abdominal images from 67 other patients were used. Synthetic images were obtained using a 3-step pipeline that consisted in: (i), generating a synthetic MTM-HCC tumor on a neutral background; (ii), randomly selecting a background among the 67 patients and a position inside the liver; and (iii), merging the generated tumor in the background at the specified location. Synthetic images were qualitatively evaluated by three radiologists and quantitatively assessed using a mix of 1-nearest neighbor classifier metric and Fréchet inception distance. RESULTS: A set of 1000 triplets of synthetic MTM-HCC images with consistent contrasts were successfully generated. Evaluation of selected synthetic images by three radiologists showed that the method gave realistic, consistent and diversified images. Qualitative and quantitative evaluation led to an overall score of 0.64. CONCLUSION: This study shows the feasibility of generating realistic synthetic MR images with very few training data, by leveraging the wide availability of liver backgrounds. Further studies are needed to assess the added value of those synthetic images for automatic diagnosis of MTM-HCC.

Prophylactic sequential antibiotic therapy for recurrent liver/biliary sepsis.

BACKGROUND AND AIMS: Recurrent liver/biliary sepsis are rare and can occur in different situations. Curative treatment of acute septic episodes is based on antibiotics. Nevertheless, recurrent sepsis can be life-threatening, and the treatment of the underlying disease could be complex, and eventually not possible. The aim of the present study was to report our experience on prophylactic sequential antibiotic therapy for recurrent liver/biliary sepsis in a large cohort of patients with long follow-up. METHODS: All patients who received a prophylactic sequential antibiotic therapy for recurrent liver/biliary sepsis in our institution from 2005 to 2020 were included. Prophylactic sequential antibiotic therapy was based on per os antibiotics with expected antibacterial activity on digestive bacteria, mainly Gram-negative bacilli. The primary end-point was the reduction of the number of septic episodes to 1 or less episode per year, and not severe (not requiring hospitalization). RESULTS: Were included 33 adult patients and the main initial disease/condition leading to prophylaxis was history of hepaticojejunostomy (78.8%). The majority of septic episodes required hospitalization (57.6%). First line prophylactic sequential antibiotic therapy was weekly ciprofloxacin in all cases. First line therapy was successful in the long-term in 19 patients (57.6%), with a median follow-up of 92 months (range: 25-206). Global efficacy (first-second-third lines) was 28/33 (84.8%). CONCLUSIONS: The results of the present study with very long follow-up suggest that prophylactic sequential antibiotic therapy can successfully prevent recurrent liver/biliary sepsis with good tolerance.

Digestive perforations related to endoscopy procedures: a local management charter based on local evidence and experts' opinion.

Background and study aims Perforations are a known adverse event of endoscopy procedures; a proposal for appropriate management should be available in each center as recommended by the European Society of Gastrointestinal Endoscopy. The objective of this study was to establish a charter for the management of endoscopic perforations, based on local evidence. Patients and methods Patients were included if they experienced partial or complete perforation during an endoscopic procedure between 2008 and 2018 (retrospectively until 2016, then prospectively). Perforations (size, location, closure) and management (imagery, antibiotics, surgery) were analyzed. Using these results, a panel of experts was asked to propose a consensual management charter. Results A total of 105 patients were included. Perforations occurred mainly during therapeutic procedures (91, 86.7%). Of the perforations, 78 (74.3 %) were diagnosed immediately and managed during the procedure; 69 of 78 (88.5 %) were successfully closed. Closures were more effective during therapeutic procedures (60 of 66, 90.9 %) than during diagnostic procedures (9 of 12, 75.0 %, P  = 0.06). Endoscopic closure was effective for 37 of 38 perforations (97.4 %) < 0.5 cm, and for 26 of 34 perforations (76.5 %) ≥ 0.5 cm ( P  < 0.05). For perforations < 0.5 cm, systematic computed tomography (CT) scan, antibiotics, or surgical evaluation did not improve the outcome. Four of 105 deaths (3.8 %) occurred after perforation, one of which was attributable to the perforation itself. Conclusions Detection and closure of perforations during endoscopic procedure had a better outcome compared to delayed perforations; perforations < 0.5 cm had a very good prognosis and CT scan, surgeon evaluation, or antibiotics are probably not necessary when the endoscopic closure is confidently performed. This work led to proposal of a local management charter.

Polycystic liver: automatic segmentation using deep learning on CT is faster and as accurate compared to manual segmentation.

OBJECTIVE: This study aimed to develop and investigate the performance of a deep learning model based on a convolutional neural network (CNN) for the automatic segmentation of polycystic livers at CT imaging. METHOD: This retrospective study used CT images of polycystic livers. To develop the CNN, supervised training and validation phases were performed using 190 CT series. To assess performance, the test phase was performed using 41 CT series. Manual segmentation by an expert radiologist (Rad1a) served as reference for all comparisons. Intra-observer variability was determined by the same reader after 12 weeks (Rad1b), and inter-observer variability by a second reader (Rad2). The Dice similarity coefficient (DSC) evaluated overlap between segmentations. CNN performance was assessed using the concordance correlation coefficient (CCC) and the two-by-two difference between the CCCs; their confidence interval was estimated with bootstrap and Bland-Altman analyses. Liver segmentation time was automatically recorded for each method. RESULTS: A total of 231 series from 129 CT examinations on 88 consecutive patients were collected. For the CNN, the DSC was 0.95 ± 0.03 and volume analyses yielded a CCC of 0.995 compared with reference. No statistical difference was observed in the CCC between CNN automatic segmentation and manual segmentations performed to evaluate inter-observer and intra-observer variability. While manual segmentation required 22.4 ± 10.4 min, central and graphics processing units took an average of 5.0 ± 2.1 s and 2.0 ± 1.4 s, respectively. CONCLUSION: Compared with manual segmentation, automated segmentation of polycystic livers using a deep learning method achieved much faster segmentation with similar performance. KEY POINTS: • Automatic volumetry of polycystic livers using artificial intelligence method allows much faster segmentation than expert manual segmentation with similar performance. • No statistical difference was observed between automatic segmentation, inter-observer variability, or intra-observer variability.

Diffuse Versus Localized Caroli Disease: A Comparative MRCP Study.

OBJECTIVE. The purpose of this multicenter retrospective study was to assess the MRCP features of Caroli disease (CD). MATERIALS AND METHODS. Sixty-six patients were identified from 2000 to 2019. The inclusion criteria were diagnosis of diffuse or localized CD mentioned in an imaging report, presence of intrahepatic bile duct (IHBD) dilatation, and having undergone an MRCP examination. The exclusion criteria included presence of obstructive proximal biliary stricture and having undergone hepatobiliary surgery other than cholecystectomy. Histopathology records were available for 53 of the 66 (80%) patients. Diffuse and localized diseases were compared by chi-square and t tests and Kaplan-Meier model. RESULTS. Forty-five patients had diffuse bilobar CD ((five pediatric patients [three girls and two boys] with a mean [± SD] age of 8 ± 5 years [range, 1-15 years] and 40 adult patients [26 men and 14 women] with a mean age of 35 ± 11 years [range, 20-62 years]) and 21 patients had localized disease (12 men and 9 women; mean age, 54 ± 14 years). Congenital hepatic fibrosis was found only in patients with diffuse CD (35/45 [78%]), as was a "central dot" sign (15/35 [43%]). IHBD dilatation with both saccular and fusiform features was found in 43 (96%) and the peripheral "funnel-shaped" sign in 41 (91%) of the 45 patients with diffuse CD but in none of the patients with localized disease (p < .001). Intrahepatic biliary calculi were found in all patients with localized disease but in only 16 of the 45 (36%) patients with diffuse CD (p < .001). Left liver atrophy was found in 18 of the 21 (86%) patients with localized disease and in none of the patients with diffuse CD (p < .001). The overall survival rate among patients with diffuse CD was significantly lower than that among patients with localized disease (p = .03). CONCLUSION. Diffuse IHBD dilatation with both saccular and fusiform features associated with the peripheral funnel-shaped sign can be used for the diagnosis of CD on MRCP. Localized IHBD dilatation seems to be mainly related to primary intrahepatic lithiasis.

Partial major hepatectomy with cyst fenestration for polycystic liver disease: Indications, short and long-term outcomes.

BACKGROUND AND OBJECTIVE: Symptomatic polycystic liver disease (PLD) with massive hepatomegaly represents a challenging surgical issue. In this work, we focused on early and long term outcomes after partial hepatectomy with cyst fenestration (PHCF) in selected patients. METHODS: All patients who had PHCF for treatment of PLD between January 2003 and December 2019 in our center were included in this study. PHCF was undertaken if at least one hepatic section was relatively spared from PLD, afferent and efferent hepatic vasculature was patent, and liver function was maintained. RESULTS: Twenty nine patients (25 women) with a mean age of 54.6 ±â€¯9 years underwent PHCF. Major hepatectomy was performed in all cases with 4.3 ±â€¯0.8 resected segments. Overall perioperative morbidity (Clavien ≥ II) and mortality rates were 41.4.6% and 13.8% respectively. Significant postoperative liver volume reduction was 52.8% within the first year and 55.5% thereafter. From preoperative evaluation, performance status (PS) normalized or improved in 84% of patients. After a mean follow-up time of 70.8 ±â€¯65 months, overall patient survival was 82.7%. In univariate analysis, PS, initial liver volume, operative time and transfusion were associated with post-operative complications and PS, preoperative cyst infection, portal hypertension, transfusion, postoperative sepsis and persistent ascites were associated with mortality. CONCLUSIONS: Our study confirms that in spite of significant morbidity rate, PHCF allows a massive reduction of liver volume in selected patients with symptomatic PLD and is highly and durably effective for the reduction of liver volume and improvement of quality of life.

Management and Prognosis of Localized Duodenal Neuroendocrine Neoplasms.

INTRODUCTION: The characteristics, prognostic factors, and management of duodenal neuroendocrine neoplasms (dNEN) are ill-defined, given their rarity. Whether nonsurgical management might be appropriate for patients with nonmetastatic dNEN and a good prognosis, as is the case for pancreatic NEN (pNEN), is unknown. We aimed to describe the management and prognosis of nonmetastatic dNEN patients. METHODS: All consecutive patients with nonmetastatic dNEN managed between 1981 and 2018 in 2 expert centers were included. Recurrence-free survival (RFS) and factors associated with recurrence were estimated. RESULTS: A total of 145 patients with dNEN were included. Twenty-eight patients with sporadic, nonfunctioning, small (median 7 mm) dNEN underwent endoscopic resection, with a 5-year RFS rate of 89.4%. Local recurrence occurred in 2 patients, who underwent surgery with no new events. The 5-year RFS rate was 87.9% in patients who underwent surgery. Upon univariate analysis, age, size, Ki67 index, and lymph node involvement (LN+) were significantly associated with worse RFS for all dNEN treated (endoscopy/surgery); multivariate analysis found that age, size, and LN+ were associated with worse RFS. CONCLUSION: Selected nonmetastatic dNEN had a favorable outcome, and a less invasive therapeutic strategy appeared more suitable than oncological surgery.

Anastomotic bilio-biliary stricture after adult liver transplantation: A retrospective study over 20 years in a single center.

BACKGROUND: Biliary complications are the main surgical complication after liver transplantation (LT). The aims of the present retrospective single center study were to describe anastomotic bilio-biliary strictures (ABS) in a large cohort of liver transplant recipients with long follow-up. METHODS: All adult LT recipients who underwent a LT, with bilio-biliary anastomosis, between 1990 and 2010 in Edouard Herriot hospital, Lyon, France were included in the study. RESULTS: The study population consisted in 783 patients (70.0% males), median age 50.5 years; main indication was alcohol-related liver disease (46.8%). The median follow-up after LT was 11.9 years (range 0-27 years). The overall incidence of anastomotic biliary complications was 9.7%: 50 patients developed an ABS (6.6%), after a median delay of 4.4 months (range 0.1-245.2) after LT and 32 (4.1%) developed biliary leakage after a median delay of 25 days (range 1-179). The actuarial risk of developing an ABS was 1.6% at 1-month, 2.7% at 3-months, 4.1% at 6-months, and 5.1%, 6.0%, 6.4%, 6.6%, 7.3% at 1-, 2-, 5-, 10- and 15-years, respectively. Univariate analysis disclosed that post-reperfusion syndrome and liver graft steatosis (≥30%) were significant risk factors for ABS. Multivariate analysis disclosed that graft steatosis (OR=6.262, 95%CI 1.936-20.257, P=0.002) and MELD score (OR=1.071, 95%CI 1.018-1.128, P=0.008) were significant risk factors for ABS. The first-line treatment of ABS consisted in endoscopic stenting for 44 patients (88.0%) and immediate success rate was 75.0%. Delayed recurrence of ABS occurred in 8/33 patients (24.0%). CONCLUSION: Our results suggest that steatotic grafts should be used for recipients without severe liver failure to avoid ABS, and that endoscopic stenting of post-LT ABS leads to a high success rate, but is associated with a significant risk of recurrence.