The genetic regulation of the gastric transcriptome is associated with metabolic and obesity-related traits and diseases.

Tissue-specific gene expression and gene regulation lead to a better understanding of tissue-specific physiology and pathophysiology. We analyzed the transcriptome and genetic regulatory profiles of two distinct gastric sites, corpus and antrum, to identify tissue-specific gene expression and its regulation. Gastric corpus and antrum mucosa biopsies were collected during routine gastroscopies from up to 431 healthy individuals. We obtained genotype and transcriptome data and performed transcriptome profiling and expression quantitative trait locus (eQTL) studies. We further used data from genome-wide association studies (GWAS) of various diseases and traits to partition their heritability and to perform transcriptome-wide association studies (TWAS). The transcriptome data from corpus and antral mucosa highlights the heterogeneity of gene expression in the stomach. We identified enriched pathways revealing distinct and common physiological processes in gastric corpus and antrum. Furthermore, we found an enrichment of the single nucleotide polymorphism (SNP)-based heritability of metabolic, obesity-related, and cardiovascular traits and diseases by considering corpus- and antrum-specifically expressed genes. Particularly, we could prioritize gastric-specific candidate genes for multiple metabolic traits, like NQO1 which is involved in glucose metabolism, MUC1 which contributes to purine and protein metabolism or RAB27B being a regulator of weight and body composition. Our findings show that gastric corpus and antrum vary in their transcriptome and genetic regulatory profiles indicating physiological differences which are mostly related to digestion and epithelial protection. Moreover, our findings demonstrate that the genetic regulation of the gastric transcriptome is linked to biological mechanisms associated with metabolic, obesity-related, and cardiovascular traits and diseases. NEW & NOTEWORTHY We analyzed the transcriptomes and genetic regulatory profiles of gastric corpus and for the first time also of antrum mucosa in 431 healthy individuals. Through tissue-specific gene expression and eQTL analyses, we uncovered unique and common physiological processes across both primary gastric sites. Notably, our findings reveal that stomach-specific eQTLs are enriched in loci associated with metabolic traits and diseases, highlighting the pivotal role of gene expression regulation in gastric physiology and potential pathophysiology.

Prevention of Rebleeding From Esophageal Varices in Patients With Cirrhosis Receiving Small-Diameter Stents Versus Hemodynamically Controlled Medical Therapy.

BACKGROUND & AIMS: Patients with cirrhosis and variceal hemorrhage have a high risk of rebleeding. We performed a prospective randomized trial to compare the prevention of rebleeding in patients given a small-diameter covered stent vs those given hepatic venous pressure gradient (HVPG)-based medical therapy prophylaxis. METHODS: We performed an open-label study of patients with cirrhosis (92% Child class A or B, 70% alcoholic) treated at 10 medical centers in Germany. Patients were assigned randomly more than 5 days after variceal hemorrhage to groups given a small covered transjugular intrahepatic portosystemic stent-shunt (TIPS) (8 mm; n = 90), or medical reduction of portal pressure (propranolol and isosorbide-5-mononitrate; n = 95). HVPG was determined at the time patients were assigned to groups (baseline) and 2 weeks later. In the medical group, patients with an adequate reduction in HVPG (responders) remained on the drugs whereas nonresponders underwent only variceal band ligation. The study was closed 10 months after the last patient was assigned to a group. The primary end point was variceal rebleeding. Survival, safety (adverse events), and quality of life (based on the Short Form-36 health survey) were secondary outcome measures. RESULTS: A significantly smaller proportion of patients in the TIPS group had rebleeding within 2 years (7%) than in the medical group (26%) (P = .002). A slightly higher proportion of patients in the TIPS group experienced adverse events, including encephalopathy (18% vs 8% for medical treatment; P = .05). Rebleeding occurred in 6 of 23 patients (26%) receiving medical treatment before hemodynamic control was possible. Per-protocol analysis showed that rebleeding occurred in a smaller proportion of the 32 responders (18%) than in nonresponders who received variceal band ligation (31%) (P = .06). Fifteen patients from the medical group (16%) underwent TIPS placement during follow-up evaluation, mainly for refractory ascites. Survival time and quality of life did not differ between both randomized groups. CONCLUSIONS: Placement of a small-diameter, covered TIPS was straightforward and prevented variceal rebleeding in patients with Child A or B cirrhosis more effectively than drugs, which often required step-by-step therapy. However, TIPS did not increase survival time or quality of life and produced slightly more adverse events. Clinical Trial no: ISRCTN 16334693.

Novel endocuff-assisted colonoscopy significantly increases the polyp detection rate: a randomized controlled trial.

GOALS AND BACKGROUND: Screening colonoscopy for colorectal cancer has proven to reduce mortality rates. Recently the Endocuff (EC), an attachment to the distal tip of the colonoscope, was introduced. The aim of our study was to compare EC-assisted colonoscopies with standard colonoscopies for the detection of colonic polyps. STUDY: This study is a randomized prospective 2-center trial. The study was conducted at 2 tertiary care centers. PARTICIPANTS: A total of 498 patients [249 males; median age 67 y; interquartile range (IQR), 56-75 y] for colon adenoma screening purposes were included. All patients underwent standard colonoscopy with or without the use of EC. Overall polyp detection rate, the number of colonic polyps, and the polyp distribution in the colon were measured. Difference in recognition of polyps with or without the use of EC was assessed. Statistical analysis was applied. RESULTS: In the EC group, the number of polyps detected per patient was 63% higher [2.00 (IQR, 1.00-4.00) vs. 1.00 (IQR, 1.00-2.25), P<0.0001]. The polyp detection rate in patients increased by 14% with the use of EC (56% vs. 42%, P=0.001). For polyp detection, superiority by use of EC could be observed in the sigmoid (P=0.001) and cecum (P=0.002) for polyps <1 cm in diameter. In the EC group, the number of adenomas detected per patient significantly increased by 86% (P=0.002). No major complications occurred in both groups. CONCLUSIONS: The use of the EC is feasible and safe with significantly higher polyp detection rates, especially for those located in the sigmoid region. The cuff system has the potential to improve the accuracy of screening colonoscopies.

Improving primary prophylaxis of variceal bleeding by adapting therapy to the clinical stage of cirrhosis. A competing-risk meta-analysis of individual participant data.

BACKGROUND & AIMS: Non-selective ß-blockers (NSBBs) and endoscopic variceal-ligation (EVL) have similar efficacy preventing first variceal bleeding. Compensated and decompensated cirrhosis are markedly different stages, which may impact treatment outcomes. We aimed to assess the efficacy of NSBBs vs EVL on survival in patients with high-risk varices without previous bleeding, stratifying risk according to compensated/decompensated stage of cirrhosis. METHODS: By systematic review, we identified RCTs comparing NSBBs vs EVL, in monotherapy or combined, for primary bleeding prevention. We performed a competing-risk, time-to-event meta-analysis, using individual patient data (IPD) obtained from principal investigators of RCTs. Analyses were stratified according to previous decompensation of cirrhosis. RESULTS: Of 25 RCTs eligible, 14 failed to provide IPD and 11 were included, comprising 1400 patients (656 compensated, 744 decompensated), treated with NSBBs (N = 625), EVL (N = 546) or NSBB+EVL (N = 229). Baseline characteristics were similar between groups. Overall, mortality risk was similar with EVL vs. NSBBs (subdistribution hazard-ratio (sHR) = 1.05, 95% CI = 0.75-1.49) and with EVL + NSBBs vs either monotherapy, with low heterogeneity (I2 = 28.7%). In compensated patients, mortality risk was higher with EVL vs NSBBs (sHR = 1.76, 95% CI = 1.11-2.77) and not significantly lower with NSBBs+EVL vs NSBBs, without heterogeneity (I2 = 0%). In decompensated patients, mortality risk was similar with EVL vs. NSBBs and with NSBBs+EVL vs. either monotherapy. CONCLUSIONS: In patients with compensated cirrhosis and high-risk varices on primary prophylaxis, NSBBs significantly improved survival vs EVL, with no additional benefit noted adding EVL to NSBBs. In decompensated patients, survival was similar with both therapies. The study suggests that NSBBs are preferable when advising preventive therapy in compensated patients.

Intrahepatic IL-8 producing Foxp3⁺CD4⁺ regulatory T cells and fibrogenesis in chronic hepatitis C.

BACKGROUND & AIMS: Regulatory CD4(+) T cells (Tregs) are considered to affect outcomes of HCV infection, because they increase in number during chronic hepatitis C and can suppress T-cell functions. METHODS: Using microarray analysis, in situ immunofluorescence, ELISA, and flowcytometry, we characterised functional differentiation and localisation of adaptive Tregs in patients with chronic hepatitis C. RESULTS: We found substantial upregulation of IL-8 in Foxp3(+)CD4(+) Tregs from chronic hepatitis C. Activated GARP-positive IL-8(+) Tregs were particularly enriched in livers of patients with chronic hepatitis C in close proximity to areas of fibrosis and their numbers were correlated with the stage of fibrosis. Moreover, Tregs induced upregulation of profibrogenic markers TIMP1, MMP2, TGF-beta1, alpha-SMA, collagen, and CCL2 in primary human hepatic stellate cells (HSC). HSC activation, but not Treg suppressor function, was blocked by adding a neutralizing IL-8 antibody. CONCLUSIONS: Our studies identified Foxp3(+)CD4(+) Tregs as an additional intrahepatic source of IL-8 in chronic hepatitis C acting on HSC. Thus, Foxp3(+)CD4(+) Tregs in chronic hepatitis C have acquired differentiation as regulators of fibrogenesis in addition to suppressing local immune responses.

Standard versus Endocuff versus cap-assisted colonoscopy for adenoma detection: A randomised controlled clinical trial.

BACKGROUND AND AIMS: Adenoma detection rate (ADR) in colon cancer screening is most important for cancer prophylaxis. This work is the first three-armed randomised controlled clinical trial aimed at comparing a head-to-head setting standard colonoscopy (SC) with Endocuff-assisted colonoscopy (EC) and cap-assisted colonoscopy (CAC) for improvement of ADR. METHODS: Patients from Poland and Germany with independent indication for colonoscopy were randomised into three arms of this trial: EC, CAC and SC. Exclusion criteria were age <18 years, active Crohn's disease or ulcerative colitis, known stenosis and post-colonic resection status. RESULTS: A total of 585 patients (195 SC, 189 EC and 186 CAC) were enrolled in this study. Indications were not different between the groups (colorectal cancer screening 51%, diagnostic colonoscopy in 31% and post-polypectomy follow-up in 18%; p = 0.94). Withdrawal time was a mean of 7 min in all groups (p = 0.658), and bowel preparation did not differ between the groups. The time to reach the caecum was significantly reduced when using the cap (a mean of 6 min for CAC vs. 7 min for SC; p = 0.0001). There was no significant difference in the primary outcome of the ADR between the groups (EC 32%, CAC 30%, SC 30%; p = 0.815). EC proved to be superior (EC vs. SC) in the sigmoid colon and transverse colon for polyp detection. CONCLUSION: The use of EC increased the total number of polyps seen during colonoscopy. In contrast to recent studies, no significant improvement of the ADR was detected.

Coexisting gastric varices should not preclude prophylactic ligation of large esophageal varices in cirrhosis.

BACKGROUND/AIMS: Coexisting gastric varices at baseline or the risk of their formation during treatment could alter the approach for primary bleeding prophylaxis in patients with large esophageal varices. METHODS: Data analysis of 152 patients with cirrhosis and large esophageal varices included in the German multicenter trial on primary prevention of variceal bleeding. RESULTS: 20 patients (13.6%) had coexisting gastric varices at baseline (GOV+). 10 of those each received either band ligation or propranolol, respectively. During follow-up (34.4 +/- 18.9 months) new gastric varices occurred in 2/75 (2.7%, ligation) and 4/77 (5.2%, propranolol) patients, respectively. One patient with newly developed gastric varices bled (propranolol group). GOV+ patients had a better baseline liver function and overall survival. Bleeding incidence did not differ significantly between GOV+ and GOV- patients (3-year actuarial risk: 20.0 +/- 10.6% (GOV+), 38.1 +/- 4.4% (GOV-), p = 0.195). Among GOV+ patients, bleeding occurred in 3/10 patients of the propranolol group and in 0/10 in the ligation group (p = 0.038). CONCLUSION: Prophylactic band ligation of large esophageal varices is safe and effective also in patients with coexisting gastric varices. Band ligation did not increase the risk of secondary gastric varices compared to propranolol.

Irbesartan plus low-dose propranolol versus low-dose propranolol alone in cirrhosis: a placebo-controlled, double-blind study.

OBJECTIVES: Angiotensin II receptor antagonists have been shown to moderately lower portal pressure in some patients with cirrhosis but may have adverse effects on kidney function. This study aimed at comparing the effects of a combined treatment using irbesartan plus propranolol with propranolol monotherapy on portal pressure and kidney function in patients with cirrhosis. METHODS: Thirty-two patients were included (Child A/B/C: 13/18/1, etiology: 16 alcohol, 13 viral, 3 other; bilirubin 1.4 +/- 1.1 mg/dL, creatinine 0.86 +/- 0.20 mg/dL, baseline hepatic venous pressure gradient 18.7 +/- 5.3 mmHg). All patients received 20 mg propranolol b.i.d. Additionally, they randomly received either placebo (N = 15) or irbesartan (step-up dosage titration up to 300 mg/d, N = 17). Patients were followed at weekly intervals, re-evaluation of hepatic venous pressure gradient (HVPG) was performed after 8 wk. RESULTS: One patient in the propranolol/irbesartan group was excluded due to variceal bleeding. No other adverse events occurred. Portal pressure declined in both groups (propranolol/irbesartan group 19.6 +/- 1.5 mmHg to 16.6 +/- 1.2 mmHg, P= 0.037, propranolol/placebo group 17.8 +/- 1.1 mmHg to 15.1 +/- 1.2 mmHg, P= 0.019). Sodium excretion significantly increased in the propranolol/irbesartan group (from 122 +/- 20 mmol/d to 230 +/- 23 mmol/d, P= 0.045), but not in the propranolol/placebo group. CONCLUSIONS: Combination treatment of propranolol plus irbesartan is well tolerated in cirrhotic patients when titrating the angiotensin II antagonist in a step-up manner, and it increases sodium excretion in patients with compensated or moderately decompensated cirrhosis. Addition of irbesartan has no effect on portal pressure.

Prevention of paracentesis-induced circulatory dysfunction: midodrine vs albumin. A randomized pilot study.

BACKGROUND/AIMS: Large-volume paracentesis in patients with cirrhosis and ascites induces arterial vasodilatation and decreases effective arterial blood volume, termed paracentesis-induced circulatory dysfunction (PICD), which can be prevented by costly intravenous albumin. Vasoconstrictors, e.g. terlipressin, may also prevent PICD. The aim was to compare the less expensive vasoconstrictor midodrine, an alpha-adrenoceptor agonist, with albumin in preventing PICD. METHODS: Twenty-four patients with cirrhosis and ascites were randomly assigned to be treated with either midodrine (n=11) (12.5 mg three times per day; over 2 days) or albumin (n=13) (8 g/L of removed ascites) after large-volume paracentesis. Effective arterial blood volume was assessed indirectly by measuring plasma renin and aldosterone concentration on days 0 and 6 after paracentesis; renal function and haemodynamic changes were also measured. PICD was defined as an increase in plasma renin concentration on day 6 by more than 50% of the baseline value. RESULTS: PICD developed in six patients of the midodrine group (60%) and in only four patients (31%) of the albumin group. Six days after paracentesis, the aldosterone concentration increased significantly in the midodrine group, but not in the albumin group. CONCLUSIONS: This pilot study suggests that midodrine is not as effective as albumin in preventing circulatory dysfunction after large-volume paracentesis in patients with cirrhosis and ascites.

Prognostic role of the initial portal pressure gradient reduction after TIPS in patients with cirrhosis.

BACKGROUND: The aim of this study was to determine the prognostic relevance of the portal pressure gradient (PPG) before and after transjugular intrahepatic portosystemic stent shunt (TIPS) insertion in patients with liver cirrhosis and recurrent oesophageal variceal bleeding. METHODS: 118 cirrhotic patients (Child A/B/C, 41/56/21; Child score, 7.7+/-2.0; baseline PPG, 21.8+/-4.7 mmHg) underwent TIPS for the prevention of variceal rebleeding. A multivariate logistic regression analysis was applied to identify the independent determinants of rebleeding and survival. The estimated rebleeding rate and the estimated survival were compared by log-rank testing. RESULTS: TIPS insertion reduced the PPG by 53.2+/-17.7%. During follow-up 21 patients suffered significant rebleeding (17.8%); bleeding-related mortality was 3.4% (four patients). The median survival [95% confidence intervals (CI)] was 48.2 (39.8; 60.8) months. The multivariate Cox model identified creatinine as the only independent predictor of survival, and the initial decrease of the PPG after TIPS as the only independent predictor of rebleeding. PPG before TIPS (21.8+/-4.7 mmHg) and the gradient at the time of rebleeding (22.0+/-2.9 mmHg) did not differ significantly. Patients with an initial decrease of the PPG after TIPS <30% were at the highest risk for rebleeding. Patients with an initial decrease of the PPG >60% rarely suffered from rebleeding. CONCLUSIONS: The initial decrease in the PPG after TIPS is a predictor for the risk of rebleeding but not for survival after TIPS. For that reason, in patients undergoing TIPS placement for the prevention of recurrent bleeding from oesophageal varices, an initial reduction of the PPG of 30-50% should be attempted.

Cholecystitis in neutropenic patients: retrospective study and systematic review.

Abdominal infections are life-threatening complications in neutropenic patients. Among these, neutropenic cholecystitis is relatively rare. Nevertheless, its actual relevance is only investigated by anecdotal reports. We present a consecutive retrospective series of nine patients over a 12-year period. We calculated a frequency of 0.4% among all neutropenic episodes in patients with acute leukemia or aggressive lymphoma undergoing myelosuppressive chemotherapy. Only three of these patients had gallstones. Four patients died during the course of cholecystitis but in none of them cholecystitis was the primary cause of death. Systematic review of the literature revealed 45 patients with neutropenic cholecystitis of whom 26.7% died.

Total ascitic fluid leukocyte count for reliable exclusion of spontaneous bacterial peritonitis in patients with ascites.

BACKGROUND AND AIMS: The diagnosis of spontaneous bacterial peritonitis (SBP) in patients with ascites is established by definition with a polymorphonuclear (PMN) cell count in the ascitic fluid greater than 0.250 g/l determined via cytological (microscopic) examination. In this study, we correlated the automatically assessed total ascitic nucleated cell count with PMN and determined its predictive value for diagnosis of SBP. METHODS: Six hundred and eleven consecutive paracenteses of 179 patients with ascites of various aetiologies (liver cirrhosis, hepatocellular carcinoma, peritoneal carcinomatosis, and ascites of other aetiology) were studied retrospectively. RESULTS: The most reliable diagnostic cut-off level was determined for differentiation between SBP and non-SBP via receiver operating characteristics analysis. A total ascitic nucleated cell count less than 1.0 g/l is unlikely to represent SBP (negative predictive value, 95.5%). CONCLUSIONS: If ascitic fluid samples with machine-made total ascitic nucleated cell count below 1.0 g/l are not followed by additional laboratory tests, the risk of missing the diagnosis of SBP is low. Applying these criteria we would have classified 51 samples of 611 samples (20 of 179 patients) wrongly using the cut-off value of 1 g/l. On the other hand we would have spared cytologic evaluation in about 63% of paracentesis performed in our hospital. Nevertheless, to insure patient safety, standard laboratory analysis is recommended in circumstances of clinical uncertainty. Thus, patients with first manifestation of ascites should always receive cytologic examination and full diagnostic investigation to exclude other causes of ascites.

C-reactive protein is a prognostic indicator in patients with perihilar cholangiocarcinoma.

AIM: To evaluate prognostic indicators for the outcome of patients with perihilar extrahepatic cholangiocarcinoma in an unselected cohort. METHODS: We retrospectively analyzed 98 patients with perihilar cholangiocarcinoma. Twenty-three patients (23.5%) underwent tumor resection. Patients with non-resectable tumors underwent either transpapillary or percutaneous transhepatic biliary drainage. Additionally, 32 patients (32.7%) received photodynamic therapy (PDT) and 18 patients (18.4%) systemic chemotherapy. Predefined variables at the time of diagnosis and characteristics considering the mode of treatment were entered into a Cox's proportional hazards model. Included in the analysis were age, tumor stage following the modified Bismuth-Corlette classification, bilirubin, prothrombin time (PT), C-reactive protein (CRP), carbohydrate antigen 19-9 (CA19-9), history of weight loss, surgical resection, chemotherapy and PDT. RESULTS: The Kaplan-Meier estimate of overall median survival was 10.5 (95%CI: 8.4-12.6) mo. In the univariate analysis, low Bismuth stage, low CRP and surgical resection correlated significantly with better survival. In the multivariate analysis, only CRP (P = 0.005) and surgical resection (P = 0.029) were found to be independently predictive of survival in the cohort. Receiver operating characteristic (ROC) analysis identified a CRP level of 11.75 mg/L as the value associated with the highest sensitivity and specificity predicting a survival > 5 mo. Applying Kaplan-Meier analysis, patients with a CRP < 12 mg/L at the time of diagnosis had a significantly longer median survival than patients with higher values (16.2 vs 7.6 mo; P = 0.009). CONCLUSION: This retrospective analysis identified CRP level at the time of diagnosis as a novel indicator for the prognosis of patients with perihilar cholangiocarcinoma. It should be evaluated in future prospective trials on this entity.

Prospective evaluation of a clinical score for 60-day mortality after transjugular intrahepatic portosystemic stent-shunt: Bonn TIPSS early mortality analysis.

OBJECTIVE: Transjugular intrahepatic portosystemic stent-shunt (TIPSS) is increasingly used to treat complications of portal hypertension, but proven tools for risk assessment of early mortality are lacking. DESIGN: The prospective evaluation of a new 60-day mortality score. PATIENTS AND METHODS: In a tertiary medical centre, 30 consecutive TIPSS patients were analysed for early mortality predictors, such as Child-Pugh score, TIPSS urgency (elective: > or = 36 h or emergency: < 36 h after variceal bleeding), comorbidity (Acute Physiology and Chronic Health Evaluation [APACHE]-II) and clinical data. Main predictors (P< 0.01) in this group (group-1: Child-Pugh score 10A, 10B, 10C) were graded (1, 2 or 3 points representing low, medium and high risk, respectively) and summarized as a Bonn TIPSS early mortality (BOTEM) score. This score was then tested prospectively in the next 73 TIPSS patients (group-2: Child-Pugh score 14A, 42B, 17C). RESULTS: Group 1 early mortality (30%) depended primarily on bilirubin (P< 0.005), APACHE-II (P < 0.001) and TIPSS urgency (P< 0.001). Added risk points (1, 2, 3) for bilirubin (< 3 mg/dl, 3-6 mg/dl, > 6 mg/dl, respectively), APACHE-II (< 10, 10-20, > 20 points, respectively) and urgency (elective, emergency, active bleeding, respectively) represented individual BOTEM score points. BOTEM was the best mortality predictor (P< 0.001); < or = / > 6 score points was the optimal cut-off, with 56% sensitivity, 100% specificity, 100% positive predictive value, 84% negative predictive value and 87% accuracy. In group 2, early mortality (8.2%) was again best predicted by BOTEM (P < 0.01) with the same cut-off and 67% sensitivity, 99% specificity, 80% positive predictive value, 97% negative predictive value and 96% accuracy. CONCLUSION: BOTEM score based on bilirubin, comorbidity and TIPSS-urgency predicts rather reliably post-TIPSS 60-day mortality and might optimize TIPSS treatment.

Higher adenoma detection rates with endocuff-assisted colonoscopy - a randomized controlled multicenter trial.

OBJECTIVES: The Endocuff is a device mounted on the tip of the colonoscope to help flatten the colonic folds during withdrawal. This study aimed to compare the adenoma detection rates between Endocuff-assisted (EC) colonoscopy and standard colonoscopy (SC). METHODS: This randomized prospective multicenter trial was conducted at four academic endoscopy units in Germany. PARTICIPANTS: 500 patients (235 males, median age 64[IQR 54-73]) for colon adenoma detection purposes were included in the study. All patients were either allocated to EC or SC. The primary outcome measure was the determination of the adenoma detection rates (ADR). RESULTS: The ADR significantly increased with the use of the Endocuff compared to standard colonoscopy (35.4%[95% confidence interval{CI} 29-41%] vs. 20.7%[95%CI 15-26%], p<0.0001). Significantly more sessile polyps were detected by EC. Overall procedure time and withdrawal time did not differ. Caecal and ileum intubation rates were similar. No major adverse events occurred in both groups. In multivariate analysis, age (odds ratio [OR] 1.03; 95%[CI] 1.01-1.05), male sex (OR 1.74; 95%CI 1.10-2.73), withdrawal time (OR 1.16; 95%CI 1.05-1.30), procedure time (OR 1.07; 95%CI 1.04-1.10), colon cleanliness (OR 0.60; 95%CI 0.39-0.94) and use of Endocuff (OR 2.09; 95%CI 1.34-3.27) were independent predictors of adenoma detection rates. CONCLUSIONS: EC increases the adenoma detection rate by 14.7%(95%CI 6.9-22.5%). EC is safe, effective, easy to handle and might reduce colorectal interval carcinomas. TRIAL REGISTRATION: ClinicalTrials.gov NCT02034929.

Fulminant sepsis after liver biopsy: A long forgotten complication?

We report on a 74-year-old patient with recurrent cholangitis and a large juxtapapillary duodenal diverticulum. Despite drainage of the common bile duct by an endoscopically placed stent, the elevated liver enzymes normalized only partially. To rule out other possible causes of liver injury, a percutaneous liver biopsy was done. After the liver biopsy the patient developed fulminant septic shock and died within 24 h. We discuss the possible causes of the septic shock following percutaneous liver biopsy in our patient and give a concise overview of the literature.

Nodular regenerative hyperplasia and portal hypertension in a patient with coeliac disease.

Nodular regenerative hyperplasia (NRH) of the liver is often associated with rheumatologic or lymphoproliferative disorders and a cause of portal hypertension in some patients. We report the case of a 71-year-old patient with celiac disease and unexplained portal hypertension. Biopsy of the liver revealed NRH as the underlying cause. The patient did not suffer from an autoimmune, rheumatologic or lymphoproliferative disease. A thrombophilic disorder that might cause NRH was ruled out. Celiac disease is often associated with mild elevation of liver enzymes and steatosis of the liver, but the association with NRH was described in only a few patients. We discuss the possible relationship of celiac disease and NRH.

Does therapy of oesophageal varices influences the progression of varices?

BACKGROUND: Aim of this study was to determine the progression time of oesophageal varices in patients with cirrhosis and to study whether therapy of varices has an impact on the progression time. Parameters associated with the progression of oesophageal varices were analyzed as well. METHODS: One hundred and eighty-one cirrhotic patients (Child A/B/C: 105/69/15; Child score 7.6+/-2.0, initial variceal grade 1.7+/-0.9) undergoing repeated endoscopy for follow-up and/or treatment of oesophageal varices were retrospectively analyzed. A multivariate logistic regression analysis was applied to identify independent determinants of progression of oesophageal varices. RESULTS: Of the 189 patients, 26 patients were on beta-blocker therapy only, 52 patients underwent ligation therapy only, and 37 patients received a combination of ligation and beta-blocker therapy of varices. The mean time of progression of oesophageal varices by one grade was 384+/-364 days. This interval did not vary significantly between patients who underwent no treatment or were on a beta-blocker and/or ligation therapy. The serum bilirubin (hazard ratio 1.030; 95% confidence interval, 1.004, 1.055; P<0.03) was the only parameter independently associated with the progression of varices. Initial eradication of varices was achieved after 2.2+/-1.5 ligation sessions. Rings of 6.1+/-2.5 were used in the first banding session and 11.5+/-8.9 rings were needed to achieve eradication of varices. CONCLUSION: Therapy of oesophageal varices does not influence the progression time of oesophageal varices in patients with cirrhosis of the liver.