COVID-19-associated secondary sclerosing cholangitis with liver transplantation.

We report on two cases of orthotopic liver transplantation (OLTX) due to SARS-Cov2-associated secondary sclerosing cholangitis (SSC) following long-term artificial respiration and extra-corporal membrane oxygenation in intensive care. Under these conditions, SSC is a rapidly progredient biliary disease featuring degenerative cholangiopathy, loss of bile ducts, ductular and parenchymal cholestasis, biliary fibrosis, and finally cirrhosis. Reduced perfusion and oxygenation of the peribiliary plexus, severe concurrent infections, and secondary medico-toxic effects appear to play a crucial role in the pathogenesis of the disease. A direct cytopathic effect of SARS-Cov2 on endothelial cells followed by thrombosis and fibrosing obliteration in all parts of the vascular bed of the liver may enhance the virus-associated liver disease and particularly SSC.

Premature mortality for patients after completely resected early adenocarcinoma of the esophagus or stomach.

OBJECTIVE: To establish the life expectancy burden of esophago-gastric cancer by analyzing years of life lost (YLL) for a Western patient population after treatment of early esophageal (EAC) or early gastric (GAC) adenocarcinoma. BACKGROUND: For patients with early EAC or GAC, the short-term prognosis after surgical resection is very good. Little data is available regarding long-term prognosis when compared to the general population. METHODS: Two hundred and fourteen patients with pT1 EAC (n = 112) or GAC (n = 102) were included in the study. Patients with EAC underwent transthoracic en-bloc esophagectomy; those with GAC had total or subtotal gastrectomy with D2-lymphadenectomy. Surviving patients had a median follow-up of approximately 14 years. YLL was calculated using average life expectancy data from Germany. RESULTS: Patients with EAC were younger (median age 61 years) than those with GAC (66 years) (p = 0.031). The male:female ratio was 10:1 for EAC and 3:2 for GAC (p < 0.001). Multivariate survival analysis showed the age of the patients ≥60 years and the existence of lymph node metastasis was associated with poor prognosis. The median YLL for all patients who died over follow-up was 8.0 years. For patients under 60 years, it was approximately 20 years, and for older patients, approximately 5 years (p < 0.001) without difference in tumor stage between these age cohorts. YLL did not differ for GAC vs. EAC. CONCLUSION: After surgical resection, the prognostic burden as measured by YLL is relevant for all patients with early esophageal and gastric adenocarcinomas and especially for younger patients. Reasons for YLL need further studies.

Stage of fibrosis is not a predictive determinant of weight loss in patients undergoing bariatric surgery.

BACKGROUND: Obesity and nonalcoholic fatty liver disease (NAFLD) are an increasing health care burden worldwide. Weight loss is currently the best option to alleviate NAFLD and is efficiently achieved by bariatric surgery. Presence of NAFLD seems to be predictive for postoperative weight loss. To date, only few predictive factors for postbariatric weight loss (age, diabetes, psychiatric disorders) are established. OBJECTIVES: Since liver fibrosis is the pathogenic driver for the progression of liver disease, we investigated its role in predicting postoperative weight loss. This study focuses on the correlation between fibrosis stage and weight loss. SETTING: University and university-affiliated cooperation, Germany. METHODS: We used a prospective, single-center cohort study including 164 patients who underwent bariatric surgery with simultaneous liver biopsies. Liver fibrosis was determined histologically according to Kleiner score and noninvasively by APRI and FIB-4 score. Percentage of total body weight loss was calculated at 1-year follow up visit. RESULTS: Thirty-two patients were found without fibrosis, whereas 91 patients showed mild fibrosis (F1), 37 significant fibrosis (F2), and only 4 patients presented advanced fibrosis (F3) at the time of bariatric surgery. Weight loss was similar across different degrees of fibrosis stage. Accordingly, linear regression analysis did not identify predictors of weight loss among fibrosis scores. In multivariable analysis, age and presence of diabetes showed the strongest predictive value. CONCLUSIONS: Baseline presence of fibrosis was not associated with postoperative weight loss, while age and diabetes were independent predictors of weight loss. Bariatric surgery should be applied independently of the fibrosis stage.

Integrative genomic analyses of European intrahepatic cholangiocarcinoma: Novel ROS1 fusion gene and PBX1 as prognostic marker.

BACKGROUND: Cholangiocarcinoma (CCA) is a fatal cancer of the bile duct with a poor prognosis owing to limited therapeutic options. The incidence of intrahepatic CCA (iCCA) is increasing worldwide, and its molecular basis is emerging. Environmental factors may contribute to regional differences in the mutation spectrum of European patients with iCCA, which are underrepresented in systematic genomic and transcriptomic studies of the disease. METHODS: We describe an integrated whole-exome sequencing and transcriptomic study of 37 iCCAs patients in Germany. RESULTS: We observed as most frequently mutated genes ARID1A (14%), IDH1, BAP1, TP53, KRAS, and ATM in 8% of patients. We identified FGFR2::BICC1 fusions in two tumours, and FGFR2::KCTD1 and TMEM106B::ROS1 as novel fusions with potential therapeutic implications in iCCA and confirmed oncogenic properties of TMEM106B::ROS1 in vitro. Using a data integration framework, we identified PBX1 as a novel central regulatory gene in iCCA. We performed extended screening by targeted sequencing of an additional 40 CCAs. In the joint analysis, IDH1 (13%), BAP1 (10%), TP53 (9%), KRAS (7%), ARID1A (7%), NF1 (5%), and ATM (5%) were the most frequently mutated genes, and we found PBX1 to show copy gain in 20% of the tumours. According to other studies, amplifications of PBX1 tend to occur in European iCCAs in contrast to liver fluke-associated Asian iCCAs. CONCLUSIONS: By analyzing an additional European cohort of iCCA patients, we found that PBX1 protein expression was a marker of poor prognosis. Overall, our findings provide insight into key molecular alterations in iCCA, reveal new targetable fusion genes, and suggest that PBX1 is a novel modulator of this disease.