Promising Outcomes of Modified ALPPS for Staged Hepatectomy in Cholangiocarcinoma.

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a two-stage procedure that can potentially cure patients with large cholangiocarcinoma. The current study evaluates the impact of modifications on the outcomes of ALPPS in patients with cholangiocarcinoma. In this single-center study, a series of 30 consecutive patients with cholangiocarcinoma (22 extrahepatic and 8 intrahepatic) who underwent ALPPS between 2011 and 2021 was evaluated. The ALPPS procedure in our center was modified in 2016 by minimizing the first stage of the surgical procedure through biliary externalization after the first stage, antibiotic administration during the interstage phase, and performing biliary reconstructions during the second stage. The rate of postoperative major morbidity and 90-day mortality, as well as the one- and three-year disease-free and overall survival rates were calculated and compared between patients operated before and after 2016. The ALPPS risk score before the second stage of the procedure was lower in patients who were operated on after 2016 (before 2016: median 6.4; after 2016: median 4.4; p = 0.010). Major morbidity decreased from 42.9% before 2016 to 31.3% after 2016, and the 90-day mortality rate decreased from 35.7% before 2016 to 12.5% after 2016. The three-year survival rate increased from 40.8% before 2016 to 73.4% after 2016. Our modified ALPPS procedure improved perioperative and postoperative outcomes in patients with extrahepatic and intrahepatic cholangiocarcinoma. Minimizing the first step of the ALPPS procedure was key to these improvements.

JNKs protect from cholestatic liver disease progression by modulating Apelin signalling.

Background & Aims: Cholestatic liver injury is associated with c-Jun N-terminal kinases (JNK) activation in distinct cell types. Its hepatocyte-specific function during cholestasis, however, has not yet been established. Therefore, in our present study, we investigated the role of JNK1/2 during cholestasis and dissected its hepatocyte-specific function. Methods: A cohort of patients with primary biliary cholangitis (n = 29) and primary sclerosing cholangitis (n = 37) was examined. Wild-type, hepatocyte-specific knockout mice for Jnk2 (Jnk2Δhepa) or Jnk1 and Jnk2 (Jnk1Δhepa/2Δhepa) were generated. Mice were subjected to bile duct ligation (BDL) or carbon tetrachloride (CCl4) treatment. Finally, Apelin signalling was blocked using a specific inhibitor. As an interventional approach, Jnk1/2 were silenced in wild-type mice using lipid nanoparticles for small interfering RNA delivery. Results: JNK activation was increased in liver specimens from patients with chronic cholestasis (primary biliary cholangitis and primary sclerosing cholangitis) and in livers of Mdr2-/- and BDL-treated animals. In Jnk1Δhepa/2Δhepa animals, serum transaminases increased after BDL, and liver histology demonstrated enhanced cell death, compensatory proliferation, hepatic fibrogenesis, and inflammation. Furthermore, microarray analysis revealed that hepatocytic Jnk1/2 ablation induces JNK-target genes involved in oxidative stress and Apelin signalling after BDL. Consequently, blocking Apelin signalling attenuated BDL-induced liver injury and fibrosis in Jnk1Δhepa/2Δhepa mice. Finally, we established an interventional small interfering RNA approach of selective Jnk1/2 targeting in hepatocytes in vivo, further demonstrating the essential protective role of Jnk1/2 during cholestasis. Conclusions: Jnk1 and Jnk2 work together to protect hepatocytes from cholestatic liver disease by controlling Apelin signalling. Dual modification of JNK signalling in hepatocytes is feasible, and enhancing its expression might be an attractive therapeutic approach for cholestatic liver disease. Impact and Implications: The cell-specific function of Jnk genes during cholestasis has not been explicitly explored. In this study, we showed that combined Jnk1/2, but not Jnk2 deficiency, in hepatocytes exacerbates liver damage and fibrosis by enhancing Apelin signalling, which contributes to cholestasis progression. Combined cell-specific Jnk targeting may be a new molecular strategy for treating cholestatic liver disease.

Experiences with accreditation for radon measurement laboratories.

The adoption of the Council Directive 2013/59/EURATOM into Austrian national law generated new challenges for businesses, authorities and measurement services. The law defines radon priority regions in which all employers are obliged to hire an authorised radon-monitoring service to determine radon activity concentration at workplaces in basements and on ground floors. In this paper, an overview of our experiences with the process of becoming an accredited and authorised radon-monitoring body using integrating and time-resolved radon measurement equipment is given. The main challenges to overcome, such as determination of measurement uncertainty, conducting metrologically traceable calibration of the track-etch detector system, information not covered by ISO 11665-1, ISO 11665-4 and ISO 11665-5, availability of proficiency tests, etc., are described. This paper aims to be a guideline for laboratories seeking accreditation in the field of radon activity concentration measurements.

PP2A methylesterase PME-1 suppresses anoikis and is associated with therapy relapse of PTEN-deficient prostate cancers.

While organ-confined prostate cancer (PCa) is mostly therapeutically manageable, metastatic progression of PCa remains an unmet clinical challenge. Resistance to anoikis, a form of cell death initiated by cell detachment from the surrounding extracellular matrix, is one of the cellular processes critical for PCa progression towards aggressive disease. Therefore, further understanding of anoikis regulation in PCa might provide therapeutic opportunities. Here, we discover that PCa tumours with concomitant inhibition of two tumour suppressor phosphatases, PP2A and PTEN, are particularly aggressive, having < 50% 5-year secondary-therapy-free patient survival. Functionally, overexpression of PME-1, a methylesterase for the catalytic PP2A-C subunit, inhibits anoikis in PTEN-deficient PCa cells. In vivo, PME-1 inhibition increased apoptosis in in ovo PCa tumour xenografts, and attenuated PCa cell survival in zebrafish circulation. Molecularly, PME-1-deficient PC3 cells display increased trimethylation at lysines 9 and 27 of histone H3 (H3K9me3 and H3K27me3), a phenotype known to correlate with increased apoptosis sensitivity. In summary, our results demonstrate that PME-1 supports anoikis resistance in PTEN-deficient PCa cells. Clinically, these results identify PME-1 as a candidate biomarker for a subset of particularly aggressive PTEN-deficient PCa.

Impact on follow-up strategies in patients with primary sclerosing cholangitis.

BACKGROUND & AIMS: Evidence for the benefit of scheduled imaging for early detection of hepatobiliary malignancies in primary sclerosing cholangitis (PSC) is limited. We aimed to compare different follow-up strategies in PSC with the hypothesis that regular imaging improves survival. METHODS: We collected retrospective data from 2975 PSC patients from 27 centres. Patients were followed from the start of scheduled imaging or in case of clinical follow-up from 1 January 2000, until death or last clinical follow-up alive. The primary endpoint was all-cause mortality. RESULTS: A broad variety of different follow-up strategies were reported. All except one centre used regular imaging, ultrasound (US) and/or magnetic resonance imaging (MRI). Two centres used scheduled endoscopic retrograde cholangiopancreatography (ERCP) in addition to imaging for surveillance purposes. The overall HR (CI95%) for death, adjusted for sex, age and start year of follow-up, was 0.61 (0.47-0.80) for scheduled imaging with and without ERCP; 0.64 (0.48-0.86) for US/MRI and 0.53 (0.37-0.75) for follow-up strategies including scheduled ERCP. The lower risk of death remained for scheduled imaging with and without ERCP after adjustment for cholangiocarcinoma (CCA) or high-grade dysplasia as a time-dependent covariate, HR 0.57 (0.44-0.75). Hepatobiliary malignancy was diagnosed in 175 (5.9%) of the patients at 7.9 years of follow-up. Asymptomatic patients (25%) with CCA had better survival if scheduled imaging had been performed. CONCLUSIONS: Follow-up strategies vary considerably across centres. Scheduled imaging was associated with improved survival. Multiple factors may contribute to this result including early tumour detection and increased endoscopic treatment of asymptomatic benign biliary strictures.

Scheduled endoscopic treatment of biliary anastomotic and nonanastomotic strictures after orthotopic liver transplantation.

BACKGROUND AND AIMS: Biliary strictures after liver transplantation are associated with significant morbidity and mortality. Although various endoscopic treatment strategies are available, consensus on a particular strategy is lacking. Moreover, the influence of endoscopic therapy on overall survival has not been studied. This retrospective study aimed to evaluate the impact of scheduled endoscopic dilatation of biliary strictures after orthotopic liver transplantation on therapeutic success, adverse events, and survival. METHODS: Between 2000 and 2016, patients with post-transplant anastomotic and nonanastomotic strictures were treated with balloon dilatation at defined intervals until morphologic resolution and clinical improvement. The primary clinical endpoint was overall survival, whereas secondary outcomes were technical and sustained clinical success, adverse events, treatment failure, and recurrence. RESULTS: Overall, 165 patients with a mean follow-up of 8 years were included; anastomotic and nonanastomotic strictures were diagnosed in 110 and 55 patients, respectively. Overall survival was significantly higher in patients with anastomotic strictures than in those with nonanastomotic strictures (median, 17.6 vs 13.9 years; log-rank: P < .05). Sustained clinical success could be achieved significantly more frequently in patients with anastomotic strictures (79.1% vs 54.5%, P < .001), and such patients showed significantly superior overall survival (19.7 vs 7.7 years; log-rank: P < .001). Sustained clinical success and the presence of nonanastomotic strictures were independently associated with better and worse outcomes (P < .05), respectively. CONCLUSIONS: Scheduled endoscopic treatment of biliary anastomotic and nonanastomotic strictures after liver transplantation is effective and safe, with high success rates. The implementation of this strategy controls symptoms and significantly improves survival.

Psychosocial Characteristics of Patients Evaluated for Kidney, Liver, or Heart Transplantation.

OBJECTIVE: Psychosocial parameters play a pivotal role in organ recipient evaluation before wait-listing for transplantation because of their impact on organ and patient outcome. Patients in need of heart (HTx), liver (LTx), or kidney transplantation (KTx) face distinct physical and psychological challenges. This study compares the psychosocial characteristics and preferences for additional therapy for patients undergoing assessment for these three types of organ transplantation to optimize patient-tailored psychological, social, and other supportive interventions. METHODS: We conducted a cross-sectional, observational study with 1110 potential transplantation candidates (LTx, n = 544; KTx, n = 330; HTx, n = 236), psychosocial status was determined for depressive symptoms (Patient Health Questionnaire Depression Scale), anxiety symptoms (seven-item Generalized Anxiety Disorder Screener), health-related quality of life (36-Item Short Form Health Survey), perceived social support (Perceived Social Support Questionnaire), sense of coherence (SoC; short form of the Sense of Coherence Scale), self-efficacy (General Self-Efficacy Short Scale), and body image (German Body Image Questionnaire-20). Preferences for additional supportive therapy were assessed dichotomously. Data were analyzed using multivariate analysis of covariance and χ2 tests. RESULTS: Patient groups differed significantly regarding depression ( F (2,1107) = 35.283, p < .001, partial η2 = 0.01), anxiety ( F (2,1107) = 15.027, p < .001, partial η2 = 0.03), health-related quality of life (physical: F (2,1107) = 96.772, p < .001, partial η2 = 0.15; mental: F (2,1107) = 11.442, p < .001, partial η2 = 0.02), perceived social support ( F (2,1107) = 20.813, p < .001, partial η2 = 0.04), SoC ( F (2,1107) = 12.920, p < .001, partial η2 = 0.02), self-efficacy ( F (2,1107) = 17.308, p < .001, partial η2 = 0.03), and body image (rejecting body evaluation: F (2,1107) = 5.006, p = .007, partial η2 = 0.01; vital body dynamics: F (2,1107) = 40.216, p < .001, partial η2 = 0.07). Patients evaluated for HTx showed the highest psychosocial impairment and the highest inclination regarding additional supportive therapy. CONCLUSIONS: Patients evaluated for HTx, LTx, and KTx have distinct psychosocial characteristics and treatment preferences. HTx patients display the highest psychosocial impairment. We suggest psychocardiological treatment structures for optimal outcome.

Prognostic Value of Red Blood Cell Distribution Width (RDW) in the Recurrence of Hepatocellular Carcinoma Following Curative Resection.

Purpose: Although surgery is associated with an acceptable cure rate, tumor recurrence is still a challenging issue in hepatocellular carcinoma (HCC) patients. Red blood cell distribution width (RDW) is considered an inflammatory marker for predicting overall mortality in a wide spectrum of malignancies. In the current study, the prognostic role of pre- and postoperative RDW in HCC recurrence after liver resection (LRx) is investigated. Patients and Methods: In 395 patients, RDW levels were evaluated preoperatively as well as six and twelve months after curative LRx. The RDW cutoff values were determined using receiver operating characteristic curves (ROCs) according to the recurrence-free survival (RFS). Survival analyses were performed using the Kaplan-Meier, and differences were compared using the Log rank test. Results: The RFS was significantly higher among patients with low RDW at the 6th month and 12th month, postoperatively (P < 0.001 and P = 0.028). RDW levels of higher than 16.15% at the 6th (HR: 2.047, P <0.001) and higher than 15.85% at 12th (HR: 3.105, P < 0.002) months after liver resection were independent predictors of RFS. Conclusion: Postoperative RDW values seem to be predictive of tumor recurrence in HCC patients. RDW levels at the 6th and 12th months postoperatively were independent predictors of recurrence after LRx.

Comparative effectiveness of medical treatment vs. metabolic surgery for histologically proven non-alcoholic steatohepatitis and fibrosis: a matched network meta-analysis.

Background: Non-alcoholic steatohepatitis (NASH) comprises a major healthcare problem affecting up to 30% of patients with obesity and the associated risk for cardiovascular and liver-related mortality. Several new drugs for NASH-treatment are currently investigated. No study thus far directly compared surgical and non-surgical therapies for NASH. This network meta-analysis compares for the first time the effectiveness of different therapies for NASH using a novel statistical approach. Methods: The study was conducted according to the PRISMA guidelines for network meta-analysis. PubMed, CENTRAL and Web of Science were searched without restriction of time or language using a validated search strategy. Studies investigating therapies for NASH in adults with liver biopsies at baseline and after at least 12 months were selected. Patients with liver cirrhosis were excluded. Risk of bias was assessed with ROB-2 and ROBINS-I-tools. A novel method for population-adjusted indirect comparison to include and compare single-arm trials was applied. Main outcomes were NASH-resolution and improvement of fibrosis. Results: Out of 7,913 studies, twelve randomized non-surgical studies and twelve non-randomized surgical trials were included. NASH-resolution after non-surgical intervention was 29% [95% confidence interval (CI): 23-40%] and 79% (95% CI: 72-88%) after surgery. The network meta-analysis showed that surgery had a higher chance of NASH-resolution than medication [odds ratio (OR) =2.68; 95% CI: 1.44-4.97] while drug treatment was superior to placebo (OR =2.24; 95% CI: 1.55-3.24). Surgery (OR =2.18; 95% CI: 1.34-3.56) and medication (OR =1.79; 95% CI: 1.39-2.31) were equally effective to treat fibrosis compared to placebo without difference between them. The results did not change when only new drugs specifically developed for the treatment of NASH were included. Conclusions: Metabolic surgery has a higher effectiveness for NASH-therapy than medical therapy while both were equally effective regarding improvement of fibrosis. Trials directly comparing surgery with medication must be urgently conducted. Patients with NASH should be informed about surgical treatment options.

Effect of endoscopic treatment in patients with secondary sclerosing cholangitis.

BACKGROUND AND AIM: Secondary sclerosing cholangitis (SSC) is a progressive disease with high mortality and characterized by chronic inflammation and biliary obstruction. Therapeutic options are limited. The aim of this retrospective study was to evaluate the effects of endoscopic treatment in patients with SSC, the outcome, and association with potential risk factors. METHODS: Data from all patients with SSC from 1996 to April 2021 were included. RESULTS: Eighty patients with SSC were included. Seventy-five patients (93.8%) underwent diagnostic endoscopic retrograde cholangiography; 46 patients (57.5%) could be treated endoscopically. Endoscopic treatment comprised removal of biliary casts (n = 36/75), dilatation of bile ducts (n = 17/75), and intermittent stenting (n = 11/75). Twenty patients underwent orthotopic liver transplantation (25%); 27 patients died (33.8%). Transplantation-free survival was affected neither by endoscopic treatment nor by presence of biliary strictures, but bacteria positive bile culture was associated with better and increased levels of serum alkaline phosphatase and bilirubin levels with poor outcome. CONCLUSIONS: Secondary sclerosing cholangitis is a progressive disease with poor long-term prognosis. Endoscopic treatment options seem to be limited regarding transplantation-free survival but might improve quality of life and prevent local complications such as cholangitis. The observed limited effect of endoscopic treatment might be attributed to the rapid progression of this disease.

Spleen transient elastography predicts actuarial survival after liver transplantation.

Background: Splenic transient elastography (TE) correlates with increased portal pressure. Little data are available in the post liver transplantation (LTx) setting. Methods: Three months after LTx, we performed splenic TE in 125 LTx recipients. Results: Mean splenic TE values were 29.4 (±6.3; range, 21.6-49.2) kPa. Splenic TE correlated with reduced time to development until persistent ascites (30 events, OR =1.082, 95% CI: 1.034-1.133; P=0.001), hepatorenal syndrome (8 events, OR =1.109, 95% CI: 1.015-1.211; P=0.022) and hepatic encephalopathy (16 events, OR =1.136, 95% CI: 1.066-1.211; P=0.000). In Cox univariate analysis, splenic TE served as a predictor of actuarial survival free of liver (OR =1.114, 95% CI: 1.050-1.182; P<0.001) and remained an independent risk factor associated with reduced actuarial survival free of LTx in multivariate analysis (OR =1.103, 95% CI: 1.026-1.186; P=0.008). Conclusions: Splenic TE measurement at 3 months after LTx serves as a robust predictor of survival in LTx recipients.

Repeat liver resection for recurrent intrahepatic cholangiocarcinoma: meta-analysis.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a relatively rare malignancy. The aim of this meta-analysis was to evaluate outcomes of repeat liver resection and non-surgical approaches for treatment of recurrent ICC. METHODS: PubMed, Embase, and Web of Science databases were searched from their inception until March 2021 for studies of patients with recurrent ICC. Studies not published in English were excluded. Two meta-analyses were performed: a single-arm meta-analysis of studies reporting pooled short- and long-term outcomes after repeat liver resection for recurrent ICC (meta-analysis A), and a meta-analysis of studies comparing 1-, 3-, and 5-year overall survival (OS) rates after repeat liver resection and non-surgical approaches for recurrent ICC (meta-analysis B). RESULTS: Of 543 articles retrieved in the search, 28 were eligible for inclusion. Twenty-four studies (390 patients) were included in meta-analysis A and nine studies (591 patients) in meta-analysis B. After repeat liver resection, 1-, 3-, and 5-year OS rates were 87 (95 per cent c.i. 81 to 91), 58 (48 to 68), and 39 (29 to 50) per cent respectively. The 1-, 3-, and 5-year OS rates were higher after repeat liver resection than without surgery: odds ratio 2.70 (95 per cent c.i. 1.28 to 5.68), 2.89 (1.15 to 7.27), and 5.91 (1.59, 21.90) respectively. CONCLUSION: Repeat liver resection is a suitable strategy for recurrent ICC in selected patients. It improves short- and long-term outcomes compared with non-surgical treatments.

Prognostic role of selection criteria for liver transplantation in patients with hepatocellular carcinoma: a network meta-analysis.

BACKGROUND: Patients with hepatocellular carcinoma (HCC) are selected for transplantation if they have a low tumour burden and low risk of recurrence. The morphometric Milan criteria have been the cornerstone for patient selection, but dynamic morphological and biological tumour characteristics surfaced as an encouraging tool to refine the selection of patients with HCC and to support the expansion of the Milan criteria. The outcomes of the most prevalent models that select patients with HCC for liver transplantation were analysed in this study, which aimed to identify the selection model that offered the best recurrence-free and overall survival after transplantation. METHODS: Studies that compared Milan, University of California San Francisco (UCSF), up-to-seven (UPTS), alpha-fetoprotein (AFP), and MetroTicket 2.0 (MT2) models were included. One-year, 3-year, and 5-year recurrence-free and overall survival rates of patients selected for transplantation using different models were analysed. RESULTS: A total of 60 850 adult patients with HCC selected for liver transplantation using Milan, UCSF, UPTS, AFP, or MT2 criteria were included. Patients selected for transplantation using the MT2 model had the highest 1-, 3-, and 5-year recurrence-free survival. In addition, patients selected for transplantation using MT2 criteria had the best 1- and 3-year overall survival, whereas patients selected for transplantation using the Milan criteria had the best 5-year overall survival rates. CONCLUSION: The MT2 model offered the best post-transplant outcomes in patients with HCC, highlighting the importance of considering tumour morphology and biology when selecting patients with HCC for liver transplantation.

Statin use is associated with the reduction in hepatocellular carcinoma recurrence after liver surgery.

BACKGROUND: Hepatocellular carcinoma (HCC) is the sixth most common form of cancer worldwide. Although surgical treatments have an acceptable cure rate, tumor recurrence is still a challenging issue. In this meta-analysis, we investigated whether statins prevent HCC recurrence following liver surgery. METHODS: PubMed, Web of Science, EMBASE and Cochrane Central were searched. The Outcome of interest was the HCC recurrence after hepatic surgery. Pooled estimates were represented as hazard ratios (HRs) and odds ratios (ORs) using a random-effects model. Summary effect measures are presented together with their corresponding 95% confidence intervals (CI). The certainty of evidence was evaluated using the Grades of Research, Assessment, Development and Evaluation (GRADE) approach. RESULTS: The literature search retrieved 1362 studies excluding duplicates. Nine retrospective studies including 44,219 patients (2243 in the statin group and 41,976 in the non-statin group) were included in the qualitative analysis. Patients who received statins had a lower rate of recurrence after liver surgery (HR: 0.53; 95% CI: 0.44-0.63; p < 0.001). Moreover, Statins decreased the recurrence 1 year after surgery (OR: 0.27; 95% CI: 0.16-0.47; P < 0.001), 3 years after surgery (OR: 0.22; 95% CI: 0.15-0.33; P < 0.001), and 5 years after surgery (OR: 0.28; 95% CI: 0.19-0.42; P < 0.001). The certainty of evidence for the outcomes was moderate. CONCLUSION: Statins increase the disease-free survival of patients with HCC after liver surgery. These drugs seem to have chemoprevention effects that decrease the probability of HCC recurrence after liver transplantation or liver resection.

Rapid Development of Cefiderocol Resistance in Carbapenem-resistant Enterobacter cloacae During Therapy Is Associated With Heterogeneous Mutations in the Catecholate Siderophore Receptor cirA.

We report a case of resistance development toward cefiderocol in a patient with intra-abdominal and bloodstream infections caused by carbapenemase-producing Enterobacter cloacae within 21 days of cefiderocol therapy. Whole genome sequencing revealed heterogeneous mutations in the cirA gene, encoding a catecholate siderophore receptor, conferring phenotypic resistance to cefiderocol.

Transcriptomic Cross-Species Analysis of Chronic Liver Disease Reveals Consistent Regulation Between Humans and Mice.

Mouse models are frequently used to study chronic liver diseases (CLDs). To assess their translational relevance, we quantified the similarity of commonly used mouse models to human CLDs based on transcriptome data. Gene-expression data from 372 patients were compared with data from acute and chronic mouse models consisting of 227 mice, and additionally to nine published gene sets of chronic mouse models. Genes consistently altered in humans and mice were mapped to liver cell types based on single-cell RNA-sequencing data and validated by immunostaining. Considering the top differentially expressed genes, the similarity between humans and mice varied among the mouse models and depended on the period of damage induction. The highest recall (0.4) and precision (0.33) were observed for the model with 12-months damage induction by CCl4 and by a Western diet, respectively. Genes consistently up-regulated between the chronic CCl4 model and human CLDs were enriched in inflammatory and developmental processes, and mostly mapped to cholangiocytes, macrophages, and endothelial and mesenchymal cells. Down-regulated genes were enriched in metabolic processes and mapped to hepatocytes. Immunostaining confirmed the regulation of selected genes and their cell type specificity. Genes that were up-regulated in both acute and chronic models showed higher recall and precision with respect to human CLDs than exclusively acute or chronic genes. Conclusion: Similarly regulated genes in human and mouse CLDs were identified. Despite major interspecies differences, mouse models detected 40% of the genes significantly altered in human CLD. The translational relevance of individual genes can be assessed at https://saezlab.shinyapps.io/liverdiseaseatlas/.

Predictors of Jaundice Resolution and Survival After Endoscopic Treatment of Primary Sclerosing Cholangitis.

The benefit of endoscopic retrograde cholangiopancreatography (ERCP) for the treatment of primary sclerosing cholangitis (PSC) remains controversial. To identify predictors of jaundice resolution after ERCP and whether resolution is associated with improved patient outcomes, we conducted a retrospective cohort study of 124 patients with jaundice and PSC. These patients underwent endoscopic biliary balloon dilation and/or stent placement at an American tertiary center, with validation in a separate cohort of 102 patients from European centers. Jaundice resolved after ERCP in 52% of patients. Median follow-up was 4.8 years. Independent predictors of jaundice resolution included older age (P = 0.048; odds ratio [OR], 1.03 for every 1-year increase), shorter duration of jaundice (P = 0.059; OR, 0.59 for every 1-year increase), lower Mayo Risk Score (MRS) (P = 0.025; OR, 0.58 for every 1-point increase), and extrahepatic location of the most advanced biliary stricture (P = 0.011; OR, 3.13). A logistic regression model predicted jaundice resolution with area under the receiver operator characteristic curve of 0.67 (95% confidence interval, 0.5-0.79) in the validation set. Independent predictors of death or transplant during follow-up included higher MRS at the time of ERCP (P < 0.0001; hazard ratio [HR], 2.33 for every 1-point increase), lower total serum bilirubin before ERCP (P = 0.031; HR, 0.91 for every 1 mg/dL increase), and persistence of jaundice after endoscopic therapy (P = 0.003; HR, 2.30). Conclusion: Resolution of jaundice after endoscopic treatment of biliary strictures is associated with longer transplant-free survival of patients with PSC. The likelihood of resolution is affected by demographic, hepatic, and biliary variables and can be predicted using noninvasive data. These findings may refine the use of ERCP in patients with jaundice with PSC.

Obesity surgery in patients with end-stage organ failure: Is it worth it?

BACKGROUND: Little is known about the long-term outcomes of patients with end-stage organ failure (ESOF) undergoing obesity surgery. OBJECTIVE: To investigate the perioperative and mid-term outcomes of patients with ESOF undergoing obesity surgery. SETTING: University hospital, Germany. METHODS: A total of 1 094 patients undergoing obesity surgery from 2006 to 2019 were screened. Inclusion criteria were ejection fraction <30%, continuous oxygen/noninvasive ventilation therapy, liver cirrhosis, or kidney failure stage 4/5. ESOF patients were compared with matched standard (MS) patients without advanced organ failure and matched for age, gender, body mass index (BMI), operation type, diabetes, arterial hypertension, and sleep apnea. RESULTS: Twenty-seven ESOF patients (56% female, age 50.3 ± 8.6, BMI 53.8 ± 8.7 kg/m2) were identified. Eighty-five percent had a sleeve gastrectomy. Mid-term total weight loss was 26.6% ± 9.0% in the ESOF patients versus 17.8% ± 11.1% in MS patients (P = .181). Long-term improvement of type 2 diabetes was comparable (ESOF: HbA1C 8.79 ± 2.06% to 6.25±1.17%, P = .047; MS: HbA1C 7.94 ± 2.02% to 7.2 ± 1.28%; P = .343). Depression scores (Patient Health Questionnaire 9) among ESOF patients improved from 13.0 ± 6.3 to 6.1 ± 5.8 (P = .004) but without significant change in MS patients (9.4 ± 7.3 to 4.3 ± 5.7; P = .082). Lung function improved in all patients although only 15% were off oxygen therapy. Treatment goals were achieved in >50% of the other groups. Major complications occurred in 11% (ESOF) versus 4% (MS) of patients (P = .299) with one death in the ESOF group (4%). CONCLUSION: Both groups had similar outcomes regarding weight loss and co-morbidity improvement. Depression only improved significantly in the ESOF group. Patients with ESOF should not be precluded from obesity surgery. Further investigation is needed to define optimized selection criteria.

Pregnancy with inflammatory bowel disease: Outcomes for mothers and their children at a European tertiary care center.

AIM: The study aimed at investigating pregnancy complications, birth outcomes, and postnatal child development in pregnancies of women with inflammatory bowel diseases (IBDs). METHODS: This is an uncontrolled retrospective single-center study between 2014 and 2019. It is a mixed-method cross-sectional study using data from (1) electronic patient records and (2) questionnaires and copies of mothers' and children's health booklets. Disease activity and IBD medications were analyzed and related to pregnancy complications, birth outcomes, and postnatal child development using mixed models for statistical analyses. RESULTS: Fifty live births from 46 patients were included. Disease activity anytime during pregnancy occurred in 56%. Biologics were applied in ca. 25% of pregnancies, mostly only through the second trimester. Pregnancies of mothers with active disease were slightly shorter than those of mothers with inactive disease (37.4 weeks vs. 38.9 weeks). Adverse pregnancy outcomes were reported in 28% of the live births, including small for gestational age in 6%, low birth weight in 18%, and preterm birth in 20%. Postnatal developmental abnormalities and health problems were reported in 26.8% of the children. Mixed model analyses failed to reveal significant associations between IBD activity and IBD medications during pregnancy and pregnancy complications, perinatal birth outcomes, and postnatal child development. CONCLUSION: Despite a tendency of shorter pregnancies in patients with active IBD and lower birth weight and birth size in patients with IBD-related therapy during pregnancy, disease activity and medications did not significantly influence pregnancy, birth, and developmental outcomes.

Endoscopic Stent Placement Can Successfully Treat Gastric Leak Following Laparoscopic Sleeve Gastrectomy If and Only If an Esophagoduodenal Megastent Is Used.

PURPOSE: Gastric staple line leakage (GL) is a serious complication of laparoscopic sleeve gastrectomy (LSG), with a specific mortality ranging from 0.2 to 3.7%. The current treatment of choice is stent insertion. However, it is unclear whether the type of stent which is inserted affects treatment outcome. Therefore, we aimed not only to determine the effectiveness of stent treatment for GL but also to specifically clarify whether treatment outcome was dependent on the type of stent (small- (SS) or megastent (MS)) which was used. PATIENTS AND METHODS: A single-centre retrospective study of 23 consecutive patients was conducted to compare the outcomes of SS (n = 12) and MS (n = 11) for the treatment of GL following LSG. The primary outcome measure was the success rate of stenting, defined as complete healing of the GL without changing the treatment strategy. Treatment change or death were both coded as failure. RESULTS: The success rate of MS was 91% (10/11) compared to only 50% (6/12) for SS (p = 0.006). An average of 2.3 ± 0.5 and 6.8 ± 3.7 endoscopies were required to achieve healing in the MS and SS groups respectively (p < 0.001). The average time to resumption of oral nutrition was shorter in the MS group (1.4 ± 1.1 days vs. 23.1 ± 33.1 days, p = 0.003). CONCLUSIONS: Stent therapy is only effective and safe for the treatment of GL after LSG if a MS is used. Treatment with a MS may not only increase treatment success rates but may also facilitate earlier resumption of oral nutrition and shorten the duration of hospitalization.