Comparative analysis of SEC61A1 mutant R236C in two patient-derived cellular platforms.

SEC61A1 encodes a central protein of the mammalian translocon and dysfunction results in severe disease. Recently, mutation R236C was identified in patients having autosomal dominant polycystic liver disease (ADPLD). The molecular phenotype of R236C was assessed in two cellular platforms. Cells were immortalized by retroviral transduction of an oncogene (UCi) or reprogrammed to induced pluripotent stem cells (iPSC) that were differentiated to cholangiocyte progenitor-like cells (CPLC). UCi and CPLC were subjected to analyses of molecular pathways that were associated with development of disease. UCi displayed markers of epithelial cells, while CPLCs expressed typical markers of both cholangiocytes and hepatocytes. Cells encoding R236C showed a stable, continuous proliferation in both platforms, however growth rates were reduced as compared to wildtype control. Autophagy, cAMP synthesis, and secretion of important marker proteins were reduced in R236C-expressing cells. In addition, R236C induced increased calcium leakiness from the ER to the cytoplasm. Upon oxidative stress, R236C led to a high induction of apoptosis and necrosis. Although the grade of aberrant cellular functions differed between the two platforms, the molecular phenotype of R236C was shared suggesting that the mutation, regardless of the cell type, has a dominant impact on disease-associated pathways.

Elevated Liver Fibrosis Progression in Isolated PSC Patients and Increased Malignancy Risk in a PSC-IBD Cohort: A Retrospective Study.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease often associated with inflammatory bowel disease (IBD), particularly ulcerative colitis (CU), and rarely with Crohn's disease (CD). Various long-term analyses show different rates of cancer and the need for orthotopic liver transplantation (OLT) in patients with isolated PSC and with concomitant IBD, respectively. However, data on the detailed course of PSC with or without IBD are limited. We aimed to analyze the clinical disease course of PSC patients without IBD compared to PSC patients with UC and CD, respectively. A retrospective data analysis of patients with isolated PSC (n = 41) and of patients with concomitant IBD (n = 115) was performed. In detail, PSC disease characteristics including occurrence of dominant stenoses, liver cirrhosis, OLT and malignancy, as well as the temporal course of PSC activity and disease progression, were analyzed. A multivariable Cox regression model and a Fine-Gray competing risk model were further used for the independent risk factor analysis of cirrhosis development and OLT. Patients with isolated PSC were significantly older at first diagnosis than patients with PSC-IBD (39 vs. 28 years, p = 0.02). A detailed analysis of the course of PSC revealed a faster PSC progression after initial diagnosis in isolated PSC patients compared to PSC-IBD including significantly earlier diagnosis of dominant stenoses (29 vs. 74 months, p = 0.021) and faster progression to liver cirrhosis (38 vs. 103 months, p = 0.027). Patients with isolated PSC have a higher risk of developing cirrhosis than patients with PSC-IBD (Gray's test p = 0.03). OLT was more frequently performed in male patients with isolated PSC compared to males with coincident IBD (48% (n = 13) vs. 33% (n = 25), p = 0.003). Colorectal carcinoma was significantly more often diagnosed in patients with PSC-IBD than in isolated PSC (8.7% vs. 0%, p = 0.042). Patients with isolated PSC seem to have a different clinical course of disease than PSC patients with concomitant IBD characterized by a more pro-fibrotic disease course with earlier onset of liver cirrhosis and dominant stenosis but with less malignancy. These data may be interpreted as either a more progressive disease course of isolated PSC or a later diagnosis of the disease at an advanced disease stage. The different clinical courses of PSC and the underlying mechanisms of the gut-liver axis need further attention.

Enhanced monitoring and detection of recent genotype 3 hepatitis E virus infection through urine antigen testing.

Hepatitis E virus (HEV) is the leading cause of acute viral hepatitis. Numerous studies have investigated the dynamics of HEV infection markers, but the most suitable marker for diagnosing ongoing or recent HEV infection remains to be determined. Recent evidence suggests that serum antigen testing is superior to serum IgM and RNA quantification. Moreover, it has been found that infected individuals excrete HEV antigen in significant quantities through urine. To address this question, we conducted a longitudinal analysis involving 16 patients with acute or chronic HEV infection in an area where genotype 3 HEV is prevalent. Our findings indicate that the diagnostic and monitoring capabilities of antigen testing for HEV infection can be further enhanced by measuring it in urine. Additionally, we were able to demonstrate that this enhancement is likely due to the presence of HEV-reactive IgG in blood plasma, which hampers efficient detection of HEV antigen through sandwich ELISA. In conclusion, urine-based antigen testing appears to be superior to measuring anti-HEV antibodies or viral RNA for diagnosing suspected HEV infection and monitoring ongoing infections.

Utility of Digital Single-operator Video Cholangioscopy for the Endoscopic Management of Biliary Complications After Liver Transplantation-A Single-center Experience.

BACKGROUND: Liver transplant recipients (LTRs) frequently develop biliary complications, and endoscopy is crucial for their subsequent management. Recently, single-operator video cholangioscopy (SOVC) with digital imaging quality was introduced. This study evaluated the utility of digital SOVC for the management of biliary complications in LTRs. METHODS: This observational study retrospectively analyzed all LTRs undergoing digital SOVC between 2015 and 2019 at a tertiary referral center. Endpoints included the assessment of biliary strictures, performance of selective guidewire passage across biliary strictures, and diagnosis and treatment of biliary stone disease. RESULTS: In total, 79 digital SOVCs performed in 50 LTRs were identified. Fifty-eight percent of the procedures were performed for biliary stricture assessment, and using visual signs or guided biopsies, SOVC excluded malignancy in all cases (100%). Of all the examinations, 29.1% (23/79) were performed solely because of a previous failure of conventional endoscopic methods to pass a guidewire across a biliary stricture. Using SOVC, guidewire passage was successfully performed in 73.9% of these examinations, enabling subsequent endoscopic therapy. Furthermore, biliary stones were found in 16.5% (13/79) of the examinations. In 38.5% of these cases, standard fluoroscopy failed to detect stones, which were only visualized using digital SOVC. Biliary stone treatment was successful in 92% (12/13) of the examinations. Complications occurred in 11.4% of all SOVCs. No procedure-associated mortalities were observed. CONCLUSIONS: Digital SOVC is effective and safe for the endoscopic management of biliary complications in LTRs and offers unique diagnostic and therapeutic opportunities that strongly impact the clinical course in selected cases.

Balloon enteroscopy-assisted endoscopic retrograde cholangiography and rendezvous procedures in patients with altered gastrointestinal anatomy.

BACKGROUND: Standard endoscopic retrograde cholangiography (ERC) frequently fails to treat biliary obstruction in patients with altered gastrointestinal anatomy. Balloon enteroscopy-assisted ERC (BE-ERC) and combined percutaneous transhepatic endoscopic rendezvous procedures (PTE-RVs) may offer effective rescue approaches. OBJECTIVE: This study aimed to evaluate the efficacy and safety of BE-ERC and PTE-RV for the treatment of biliary obstruction in patients with altered gastrointestinal anatomy. METHODS: In this observational study, all patients with altered gastrointestinal anatomy underwent BE-ERC between 2003 and 2016 at a tertiary referral center. In case of procedural failure, a combined PTE-RV was performed in selected cases. Endpoints included the success and safety of the procedures. RESULTS: A total of 180 BE-ERC performed in 106 patients with altered gastrointestinal anatomy were included. Of the procedures, 76.7% were performed due to benign and 23.3% due to malignant biliary obstruction. BE-ERC was successful in 53% (96/180) of cases. In case of failure, in 23/32 cases a combined PTE-RV was successfully performed, improving the overall success rate of BE-ERC, including PTE-RV, to 66% (119/180). Benign biliary obstruction and repeated procedures were positive predictors of successful BE-ERC (odds ratio 6.8 (95% CI 2.7-17.0), p < .001 and odds ratio 4.1 (2.1-8.2), p < .001). Complications were significantly more frequent in combined PTE-RVs than in BE-ERC procedures alone (34.4% vs. 7.4%; p < .001). CONCLUSIONS: BE-ERC is effective and safe for the endoscopic management of patients with altered gastrointestinal anatomy and percutaneous transhepatic rendezvous procedures can substantially increase success rates in selected cases.

Unmasking of Metamizole-induced Liver Injury by Simult aneous Development of Characteristic Agranulocytosis.

BACKGROUND: Metamizole is one of the most used analgesic, antipyretic, and spasmolytic agents in many countries worldwide. While metamizole-induced agranulocytosis is an, albeit seldom, well-known adverse event, metamizole-associated drug-induced liver injury has been reported rarely in the literature and hence often remains unconsidered. Here, we present a unique case where metamizole-induced hepatotoxicity got unmasked by the simultaneous development of characteristic agranulocytosis. CASE REPORT: A 22-year-old woman without known conditions presented with a new onset of fever, jaundice, and maculopapular rash and explicitly denied intake of any new substances. Laboratory tests showed liver injury, granulopenia, and positive anti-nuclear and anti-mitochondrial (AMA-M2) antibodies. Liver biopsy revealed a histological pattern characteristic of drug-induced liver injury and bone marrow biopsy, the classical picture of metamizole-induced agranulocytosis. Indeed the in-depth interview of the patient unveiled metamizole consumption over the last two months. Therefore, we could diagnose metamizole-induced hepato- and myelotoxicity. Accordingly, steroid therapy led to normalization of liver parameters and stimulation with granulocyte colony- stimulating factor to leukocyte recovery. CONCLUSION: This case report is intended to increase the awareness of metamizole-associated druginduced liver injury which should always be kept in mind due to its occasionally life-threatening course. Diagnosis can be difficult particularly if anamnesis and written records are without hints for prior metamizole intake.

Digital single-operator video cholangioscopy improves endoscopic management in patients with primary sclerosing cholangitis-a retrospective observational study.

BACKGROUND: Patients with primary sclerosing cholangitis (PSC) are at a high risk of developing cholestatic liver disease and biliary cancer, and endoscopy is crucial for the complex management of these patients. AIM: To clarify the utility of recently introduced digital single-operator video cholangioscopy (SOVC) for the endoscopic management of PSC patients. METHODS: In this observational study, all patients with a history of PSC and in whom digital SOVC (using the SpyGlass DS System) was performed between 2015 and 2019 were included and retrospectively analysed. Examinations were performed at a tertiary referral centre in Germany. In total, 46 SOVCs performed in 38 patients with a history of PSC were identified. The primary endpoint was the evaluation of dominant biliary strictures using digital SOVC, and the secondary endpoints were the performance of selective guidewire passage across biliary strictures and the diagnosis and treatment of biliary stone disease in PSC patients. RESULTS: The 22 of 38 patients had a dominant biliary stricture (57.9%). In 4 of these 22 patients, a cholangiocellular carcinoma was diagnosed within the stricture (18.2%). Diagnostic evaluation of dominant biliary strictures using optical signs showed a sensitivity of 75% and a specificity of 94.4% to detect malignant strictures, whereas SOVC-guided biopsies to gain tissue for histopathological analysis showed a sensitivity of 50% and a specificity of 100%. In 13% of examinations, SOVC was helpful for guidewire passage across biliary strictures that could not be passed by conventional methods (technical success rate 100%). Biliary stone disease was observed in 17.4% of examinations; of these, in 37.5% of examinations, biliary stones could only be visualized by SOVC and not by standard fluoroscopy. Biliary stone treatment was successful in all cases (100%); 25% required SOVC-assisted electrohydraulic lithotripsy. Complications, such as postinterventional cholangitis and pancreatitis, occurred in 13% of examinations; however, no procedure-associated mortality occurred. CONCLUSION: Digital SOVC is effective and safe for the endoscopic management of PSC patients and may be regularly considered an additive tool for the complex endoscopic management of these patients.

Indications of Persistent Glycocalyx Damage in Convalescent COVID-19 Patients: A Prospective Multicenter Study and Hypothesis.

The COVID-19 pandemic is caused by the SARS CoV-2 virus and can lead to severe lung damage and hyperinflammation. In the context of COVID-19 infection, inflammation-induced degradation of the glycocalyx layer in endothelial cells has been demonstrated. Syndecan-1 (SDC-1) is an established parameter for measuring glycocalyx injury. This prospective, multicenter, observational, cross-sectional study analyzed SDC-1 levels in 24 convalescent patients that had been infected with SARS-CoV-2 with mild disease course without need of hospitalization. We included 13 age-matched healthy individuals and 10 age-matched hospitalized COVID-19 patients with acute mild disease course as controls. In convalescent COVID-19 patients, significantly elevated SDC-1 levels were detected after a median of 88 days after symptom onset compared to healthy controls, whereas no difference was found when compared to SDC-1 levels of hospitalized patients undergoing acute disease. This study is the first to demonstrate signs of endothelial damage in non-pre-diseased, convalescent COVID-19 patients after mild disease progression without hospitalization. The data are consistent with studies showing evidence of persistent endothelial damage after severe or critical disease progression. Further work to investigate endothelial damage in convalescent COVID-19 patients should follow.

Prediction of late allograft dysfunction following liver transplantation by immunological blood biomarkers.

BACKGROUND: An accelerated course of hepatic fibrosis may occur in liver transplantation (LT) patients despite normal or slightly abnormal liver blood tests. AIM: To identify screening tools based on blood biomarkers to predict late allograft dysfunction in LT recipients. METHODS: 174 LT recipients were enrolled. Liver biopsy, liver functional tests, cytokine quantitation in serum, as well as soluble MHC class I polypeptide-related sequence A and B (sMICA/sMICB) and soluble UL16 binding protein 2 (sULBP2) were performed. RESULTS: Patients with late graft dysfunction had a significantly higher donor age, lower albumin level, higher alanine (ALT) and aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), total bilirubin and alkaline phosphatase (ALP), higher sMICA, sULBP2, higher interleukin (IL) 6, interferon γ and lower IL10 in serum as compared to recipients without allograft dysfunction. In order to provide a better statistical accuracy for discriminating 5-year allograft dysfunction from other less progressive subtype of allograft injury, we established a predictive model, based on 7 parameters (serum ALP, ALT, AST, GGT, sMICA, IL6 and albumin) which provided an Area Under the Receiver Operating Characteristics (AUROC) curve of 0.905. CONCLUSIONS: Blood-based biomarkers can significantly improve prediction of late liver allograft outcome in LT patients. The new developed score comprising serum parameters, with an excellent AUROC, can be reliably used for diagnosing late allograft dysfunction in transplanted patients.

Vitamin A Plasma Levels in COVID-19 Patients: A Prospective Multicenter Study and Hypothesis.

COVID-19 is a pandemic disease that causes severe pulmonary damage and hyperinflammation. Vitamin A is a crucial factor in the development of immune functions and is known to be reduced in cases of acute inflammation. This prospective, multicenter observational cross-sectional study analyzed vitamin A plasma levels in SARS-CoV-2 infected individuals, and 40 hospitalized patients were included. Of these, 22 developed critical disease (Acute Respiratory Distress Syndrome [ARDS]/Extracorporeal membrane oxygenation [ECMO]), 9 developed severe disease (oxygen supplementation), and 9 developed moderate disease (no oxygen supplementation). A total of 47 age-matched convalescent persons that had been earlier infected with SARS-CoV-2 were included as the control group. Vitamin A plasma levels were determined by high-performance liquid chromatography. Reduced vitamin A plasma levels correlated significantly with increased levels of inflammatory markers (CRP, ferritin) and with markers of acute SARS-CoV-2 infection (reduced lymphocyte count, LDH). Vitamin A levels were significantly lower in hospitalized patients than in convalescent persons (p < 0.01). Of the hospitalized patients, those who were critically ill showed significantly lower vitamin A levels than those who were moderately ill (p < 0.05). Vitamin A plasma levels below 0.2 mg/L were significantly associated with the development of ARDS (OR = 5.54 [1.01-30.26]; p = 0.048) and mortality (OR 5.21 [1.06-25.5], p = 0.042). Taken together, we conclude that vitamin A plasma levels in COVID-19 patients are reduced during acute inflammation and that severely reduced plasma levels of vitamin A are significantly associated with ARDS and mortality.

Postoperative pancreatic fistula affects recurrence-free survival of pancreatic cancer patients.

PURPOSE: Postoperative pancreatic fistula (POPF) with reported incidence rates up to 45% contributes substantially to overall morbidity. In this study, we conducted a retrospective evaluation of POPF along with its potential perioperative clinical risk factors and its effect on tumor recurrence. METHODS: Clinical data on patients who had received pancreatoduodenectomy (PD), distal pancreatectomy (DP), or duodenum-preserving pancreatic head resection (DPPHR) were prospectively collected between 2007 and 2016. A Picrosirius red staining score was developed to enable morphological classification of the resection margin of the pancreatic stump. The primary end point was the development of major complications. The secondary end points were overall and recurrence-free survival. RESULTS: 340 patients underwent pancreatic resection including 222 (65.3%) PD, 87 (25.6%) DP, and 31 (9.1%) DPPHR. Postoperative major complications were observed in 74 patients (21.8%). In multivariable logistic regression analysis, POPF correlated with body mass index (BMI) (p = 0.025), prolonged stay in hospital (p<0.001), high Picrosirius red staining score (p = 0.049), and elevated postoperative levels of amylase or lipase in drain fluid (p≤0.001). Multivariable Cox regression analysis identified UICC stage (p<0.001), tumor differentiation (p<0.001), depth of invasion (p = 0.001), nodal invasion (p = 0.001), and the incidence of POPF grades B and C (p = 0.006) as independent prognostic markers of recurrence-free survival. CONCLUSION: Besides the known clinicopathological risk factors BMI and amylase in the drain fluid, the incidence of POPF correlates with high Picrosirius red staining score in the resection margins of the pancreatic stumps of curatively resected pancreatic ductal adenocarcinoma (PDAC). Furthermore, clinically relevant POPF seems to be a prognostic factor for tumor recurrence in PDAC.

Symptom Diary-Based Analysis of Disease Course among Patients with Mild Coronavirus Disease, Germany, 2020.

Limited information is available on the clinical course of outpatients with mild coronavirus disease (COVID-19). This information is critically important to inform public health prevention strategies and to provide anticipatory guidance to patients, primary care providers, and employers. We retrospectively assessed the daily prevalence of symptoms in 313 COVID-19 outpatients for the first 20 days of illness. Generalized estimating equations were used to assess the probability of symptom occurrence over time. Fatigue (91%), cough (85%), and headache (78%) were the most common symptoms and occurred a median of 1 day from symptom onset. Neurologic symptoms, such as loss of taste (66%) and anosmia (62%), and dyspnea (51%) occurred considerably later (median 3-4 days after symptom onset). Symptoms of COVID-19 are similar to those of other respiratory pathogens, so symptomatic patients should be tested more frequently for severe acute respiratory syndrome coronavirus 2 during influenza season to prevent further spread of COVID-19.

Four weeks of high-intensity interval training (HIIT) improve the cardiometabolic risk profile of overweight patients with type 1 diabetes mellitus (T1DM).

This study investigated the effects of a four-week HIIT intervention on the cardiometabolic risk profile, liver fat content, insulin requirement, hypoglycaemia, physical fitness, and health-related quality of life in patients with T1DM. A supervised exercise intervention with baseline to follow-up comparison between overweight (BMI = 28.6 ± 2.1 kg/m2) and normal weight (BMI = 23.2 ± 1.40 kg/m2) T1DM patients was performed. Eleven overweight (age = 40.7 ± 14.3 years) and 11 normal weight (age = 42.2 ± 15.5 years) T1DM patients performed a four-week, low-volume, all-out cycling HIIT (4-6 bouts, work/relief ratio 1:1) twice weekly. HIIT lowered low-density lipoprotein and uric acid levels in overweight patients by up to 10.5% (vs. normal weight, p≤0.0312). HbA1c, high-density lipoprotein, and triglyceride levels did not change in any of the groups. Participants' maximal exercise capacity and power output at individual anaerobic lactate threshold increased to an equal extend of up to 10% (p≤0.0002) in both groups. During the intervention, participants used fewer daily bolus insulin (-5.22 ± 12.80%) and less total units of insulin (-4.42 ± 10.20%, p≤0.023) compared to the pre-intervention period with no between-group difference. Overall, the average daily number of hypoglycaemias increased from 0.90 ± 0.56-1.08 ± 0.63 during the intervention (p = 0.033). SF-36 subscales showed higher scores after the intervention, with a significant improvement of "role limitations due to physical problems" (p<0.05) for both groups. We conclude that in T1DM, HIIT may exert beneficial effects on physical fitness, insulin requirement and health-related quality of life. Of note, beneficial HIIT effects on the cardiometabolic risk profile in T1DM may be larger in overweight T1DM patients.

Conversion from Standard-Release Tacrolimus to MeltDose® Tacrolimus (LCPT) Improves Renal Function after Liver Transplantation.

Renal impairment is a typical side effect of tacrolimus (Tac) treatment in liver transplant (LT) recipients. One strategy to avoid renal dysfunction is to increase the concentration/dose (C/D) ratio by improving drug bioavailability. LT recipients converted from standard-release Tac to MeltDose® Tac (LCPT), a novel technological formulation, were able to reduce the required Tac dose due to higher bioavailability. Hence, we hypothesize that such a conversion increases the C/D ratio, resulting in a preservation of renal function. In the intervention group, patients were switched from standard-release Tac to LCPT. Clinical data were collected for 12 months after conversion. Patients maintained on standard-release Tac were enrolled as a control group. Twelve months after conversion to LCPT, median C/D ratio had increased significantly by 50% (p < 0.001), with the first significant increase seen 3 months after conversion (p = 0.008). In contrast, C/D ratio in the control group was unchanged after 12 months (1.75 vs. 1.76; p = 0.847). Estimated glomerular filtration rate (eGFR) had already significantly deteriorated in the control group at 9 months (65.6 vs. 70.6 mL/min/1.73 m2 at study onset; p = 0.006). Notably, patients converted to LCPT already had significant recovery of mean eGFR 6 months after conversion (67.5 vs. 65.3 mL/min/1.73 m2 at study onset; p = 0.029). In summary, conversion of LT recipients to LCPT increased C/D ratio associated with renal function improvement.

Serum levels of ferritin and transferrin serve as prognostic factors for mortality and survival in patients with end-stage liver disease: A propensity score-matched cohort study.

BACKGROUND: Patients with end-stage liver disease are known to suffer from a significantly high risk of mortality, but accurate prediction of the course of disease is challenging. OBJECTIVE: The study aim was to evaluate the independent prognostic and clinical importance of serum levels of ferritin and transferrin for 90-day survival of patients with liver disease. METHODS: Patients with end-stage liver disease treated during a 2-year period were enrolled retrospectively in a single-centre study. Unmatched and propensity score matching (PSM) analyses were applied. RESULTS: The study cohort comprised 286 patients with end-stage liver disease, of which 22.9% died during the observational period. High serum ferritin levels and low serum transferrin levels were associated significantly with increased 90-day mortality in the unmatched (p < 0.001) and PSM study population (p = 0.017). Serum levels of ferritin and transferrin had high prognostic capability to predict 90-day survival similar to the Model for End-stage Liver Disease. Patients with serum ferritin values >1030.5 µg/l had a 50% risk of dying within 11 days after measurement, which translated up to a 90-day mortality of 83%. CONCLUSION: Serum levels of ferritin and transferrin have independent and excellent capabilities to determine prognosis in patients with end-stage liver disease. Ferritin measurements can reliably identify those with high mortality in daily practice.

Digital single-operator video cholangioscopy in treating refractory biliary stones: a multicenter observational study.

BACKGROUND: Standard endoscopic treatment might fail to treat biliary stone disease. Here, we investigated the efficacy and safety of recently introduced digital single-operator video cholangioscopy (SOVC) for the treatment of difficult biliary stones. METHODS: Digital SOVC procedures, performed in two tertiary referral centers between 2015 and 2018, were retrospectively analyzed. Only patients with a previous failure of endoscopic standard treatment and a SOVC-based biliary stone treatment using electrohydraulic lithotripsy (EHL) or laser lithotripsy (LL) were included. The primary endpoint was to evaluate the stone removal rate per procedure and per patient. RESULTS: In total, 75 examinations with a digital SOVC-assisted biliary stone treatment, performed in 60 patients, were identified. Biliary stones were mainly located extrahepatic (64%) and less frequently intrahepatic (36%). The median stone size was 20 mm (interquartile range [IQR]: 10-25 mm) and the median stone number was 1 (IQR: 1-2). Digital SOVC-based treatment of biliary stone disease was successful in 95% of patients and 15% needed at least two treatment sessions. Evaluated per procedure, a complete stone removal was accomplished in 67% of all examinations (including initial and repeated procedures), while an incomplete stone removal was observed in 33% of cases. The per procedure analyzes revealed that the success rates for a complete stone removal were similar between LL and EHL (66% vs. 68%; p = 0.87). Complications, such as postinterventional cholangitis and pancreatitis occurred in 16% of examinations; however, except from one case, all were mild or moderate and no procedure-associated mortality occurred. CONCLUSIONS: Digital SOVC-assisted biliary stone treatment is highly effective even in cases with difficult biliary stones and might be considered the new standard of care for these patients. Furthermore, mild up to moderate complications were intermittently observed which might document the complexity of our included cases.

Endoscopic Radiofrequency Ablation Prolongs Survival of Patients with Unresectable Hilar Cholangiocellular Carcinoma - A Case-Control Study.

The life expectancy of unresectable hilar cholangiocellular carcinomas (CCCs) is very limited and endoscopic radiofrequency ablation (ERFA) of the biliary tract may prolong survival. Our single-center-study retrospectively analysed all CCC cases, in whom ERFAs of the biliary tract were performed between 2012 and 2017 and compared these to historical control cases who received the standard treatment of sole stent application. ERFA was performed in 32 patients with malignant biliary strictures that were mainly caused by Bismuth III and IV hilar CCCs (66%). 14 of these patients received repeated ERFAs, for an overall performance of 54 ERFAs. Stents were applied after examination of all patients (100%). Adverse events occurred in 18.5% of examinations. Case-control analysis revealed that the survival time of cases with unresectable Bismuth type III and IV hilar CCCs (n = 20) treated with combined ERFA and stent application significantly increased compared to controls (n = 22) treated with sole stent application (342 +/- 57 vs. 221 +/- 26 days; p = 0.046). In conclusion, ERFA therapy significantly prolonged survival in patients with unresectable Bismuth type III and IV hilar CCC. As an effective and safe method, ERFA should be considered as a palliative treatment for all these patients.

Impact of nighttime procedures on outcomes after liver transplantation.

BACKGROUND: Sleep deprivation is a well-known risk factor for the performance of medical professionals. Solid organ transplantation (especially orthotopic liver transplantation (oLT)) appears to be vulnerable since it combines technically challenging operative procedures with an often unpredictable start time, frequently during the night. Aim of this study was to analyze whether night time oLT has an impact on one-year graft and patient survival. MATERIAL AND METHODS: Deceased donor oLTs between 2006 and 2017 were retrospectively analyzed and stratified for recipients with a start time at day (8 a.m. and 6 p.m.) or at night (6 p.m. to 8 a.m.). We examined donor as well as recipient demographics and primary outcome measure was one-year patient and graft survival. RESULTS: 350 oLTs were conducted in the study period, 154 (44%) during daytime and 196 (56%) during nighttime. Donor and recipient variables were comparable. One-year patient survival (daytime 75.3% vs nighttime 76.5%, p = 0.85) as well as graft survival (daytime 69.5% vs nighttime 73.5%, p = 0.46) were similar between the two groups. Frequencies of reoperation (daytime 53.2% vs nighttime 55.1%, p = 0.74) were also not significantly different. CONCLUSION: Our retrospective single center data derived from a German transplant center within the Eurotransplant region provides evidence that oLT is a safe procedure irrespective of the starting time. Our data demonstrate that compared to daytime surgery nighttime liver transplantation is not associated with a greater risk of surgical complications. In addition, one-year graft and patient survival do not display inferior results in patients undergoing nighttime transplantation.

Chronic liver disease promotes lesions of the colorectal adenoma-carcinoma sequence, independent of liver cirrhosis.

Background: Research increasingly focuses on identifying individuals at greater risk of colorectal cancer (CRC) to enhance colonoscopy screening efficacy. Objective: The objective of this article is to determine associations between chronic liver disease and lesions along the colorectal adenoma-carcinoma sequence. Methods: This retrospective study encompasses consecutive liver disease patients (LDPs) of all etiologies evaluated for liver transplantation at a single institution and a control group of liver-healthy patients (LHPs) undergoing colonoscopy as part of the German CRC screening program.Rates of polyps, adenomas, high-risk situations (HRS) and CRC were analyzed in univariable and multivariable settings adjusting for age, gender, body mass index and number of colonoscopies. Differences between LHPs and LDPs and between cirrhotic and noncirrhotic hepatopathy were assessed. Results: In total, 1046 patients (52.6% male, median age 59.6 years) were included, of whom 38.9% had liver disease. A total of 41.0% of all patients showed polyps, 23.2% adenomas, 10.0% HRS, and 0.5% CRC. LDPs were more likely to develop polyps, adenomas and HRS than LHPs, both in univariable and multivariable analysis. There were no significant differences between cirrhotic and noncirrhotic patients. Conclusion: Chronic liver disease of any etiology is associated with colonic lesions of the colorectal adenoma-carcinoma sequence, independent of cirrhosis. LDPs should receive intensified, and earlier, colonoscopy screening.