Co-inhibition of Aurora A and Haspin kinases enhances survivin blockage and p53 induction for mitotic catastrophe and apoptosis in human colorectal cancer.

Colorectal cancer (CRC) is a leading cause and mortality worldwide. Aurora A and haspin kinases act pivotal roles in mitotic progression. However, the blockage of Aurora A and Haspin for CRC therapy is still unclear. Here we show that the Haspin and p-H3T3 protein levels were highly expressed in CRC tumor tissues of clinical patients. Overexpression of Haspin increased the protein levels of p-H3T3 and survivin in human CRC cells; conversely, the protein levels of p-H3T3 and survivin were decreased by the Haspin gene knockdown. Moreover, the gene knockdown of Aurora A induced abnormal chromosome segregation, mitotic catastrophe, and cell growth inhibition. Combined targeted by co-treatment of CHR6494, a Haspin inhibitor, and MLN8237, an Aurora A inhibitor, enhanced apoptosis and CRC tumor inhibition. MLN8237 and CHR6494 induced abnormal chromosome segregation and mitotic catastrophe. Meanwhile, MLN8237 and CHR6494 inhibited survivin protein levels but conversely induced p53 protein expression. Ectopic survivin expression by transfection with a survivin-expressed vector resisted the cell death in the MLN8237- and CHR6494-treated cells. In contrast, the existence of functional p53 increased the apoptotic levels by treatment with MLN8237 and CHR6494. Co-treatment of CHR6494 and MLN8237 enhanced the blockage of human CRC xenograft tumors in nude mice. Taken together, co-inhibition of Aurora A and Haspin enhances survivin inhibition, p53 pathway induction, mitotic catastrophe, apoptosis and tumor inhibition that may provide a potential strategy for CRC therapy.

Intragastric injection of botulinum toxin A for weight loss: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: Intragastric botulinum toxin A (BTA) injection is a potential treatment for weight reduction in obese patients. Current studies yielded conflicting results. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the efficacy of intragastric BTA injection for weight management. METHODS: We searched several databases to identify RCTs evaluating intragastric BTA injections for obesity. We applied random-effects models for all meta-analyses due to heterogeneity in the included studies. The mean difference (MD) and 95% confidence interval (CI) were calculated for continuous outcomes. RESULTS: A total of 6 RCTs including 192 subjects met the inclusion criteria and were included for the meta-analysis. Although the pooled data from six studies showed no difference in the absolute weight loss between intragastric BTA injection and control, subgroup analysis showed a significantly decreased absolute weight after a BTA injection dose ≥ 200 U (MD, -2.04 kg; 95% CI, -3.96 to -0.12) and after multiple injection regions in the stomach combined with diet control (MD, -4.44 kg; 95% CI, -6.54 to -2.33 kg) compared with the control. Regarding absolute weight loss, the impact of endoscopic ultrasound-guided injection and follow-up duration showed no difference. Intragastric BTA injection had a significant change in body mass index (MD, -1.25 kg/m2 ; 95% CI, -2.18 to -0.32 kg/m2 ) and prolonged gastric half-emptying time (MD, 11.37 min; 95% CI, -3.69 to 19.06 min). CONCLUSION: Intragastric BTA injection is effective for obesity treatment, and adequate doses (≥ 200 U), multiple gastric injection regions, and combined diet control are crucial. However, given the small sample size and limited power, caution should be exercised.

The effect of coffee/caffeine on postoperative ileus following elective colorectal surgery: a meta-analysis of randomized controlled trials.

PURPOSE: Postoperative ileus (POI) is the most common complication of elective colon resection. Coffee or caffeine has been reported to be useful in improving gastrointestinal function after abdominal surgery. This study aimed to investigate the effect of coffee/caffeine on POI in patients undergoing elective colorectal surgery. METHODS: We searched Cochrane library, Embase, PubMed, and ClinicalTrials.gov (until July 2021) to identify randomized controlled trials (RCTs) evaluating the effect of coffee or caffeine on bowel movements and POI in patients undergoing elective colorectal surgery. The mean difference (MD) for continuous outcomes and risk ratio (RR) for dichotomous outcomes were calculated and are presented with 95% confidence intervals (CIs). A random effects model was used in all meta-analyses. RESULTS: A total of four RCTs including 312 subjects met the inclusion criteria and were included in the meta-analysis. Postoperative coffee or caffeine consumption decreased the time to first bowel movement (MD, - 10.36 h; 95% CI, - 14.61 to - 6.11), shortened the length of hospital stay (MD, - 0.95 days; 95% CI, - 1.57 to - 0.34), and was associated with a decreased risk of the use of any laxatives after the procedure (RR, 0.64; 95% CI, 0.44 to 0.92). The time to first flatus, time to tolerance of solid food, risk of any postoperative complication, postoperative reinsertion of a nasogastric (NG) tube, and anastomotic leakage showed no statistical differences between groups. CONCLUSION: Postoperative coffee or caffeine consumption improved bowel movement and decreased the duration of hospital stay in patients undergoing elective colorectal surgery. This method is safe and can prevent or treat POI.

Neochlorogenic Acid Attenuates Hepatic Lipid Accumulation and Inflammation via Regulating miR-34a In Vitro.

Neochlorogenic acid (5-Caffeoylquinic acid; 5-CQA), a major phenolic compound isolated from mulberry leaves, possesses anti-oxidative and anti-inflammatory effects. Although it modulates lipid metabolism, the molecular mechanism is unknown. Using an in-vitro model of nonalcoholic fatty liver disease (NAFLD) in which oleic acid (OA) induced lipid accumulation in HepG2 cells, we evaluated the alleviation effect of 5-CQA. We observed that 5-CQA improved OA-induced intracellular lipid accumulation by downregulating sterol regulatory element-binding protein 1 (SREBP1) and fatty acid synthase (FASN) expression, which regulates the fatty acid synthesis, as well as SREBP2 and HMG-CoA reductases (HMG-CoR) expressions, which regulate cholesterol synthesis. Treatment with 5-CQA also increased the expression of fatty acid ß-oxidation enzymes. Remarkably, 5-CQA attenuated OA-induced miR-34a expression. A transfection assay with an miR-34a mimic or miR-34a inhibitor revealed that miR-34a suppressed Moreover, Sirtuin 1 (SIRT1) expression and inactivated 5' adenosine monophosphate-activated protein kinase (AMPK). Our results suggest that 5-CQA alleviates lipid accumulation by downregulating miR-34a, leading to activation of the SIRT1/AMPK pathway.

Improvement in the Mortality-to-Incidence Ratios for Gastric Cancer in Developed Countries With High Health Expenditures.

The mortality-to-incidence ratio (MIR) is widely used to evaluate the efficacy of cancer management outcomes for individual countries. However, the association among health care expenditure, human development index (HDI), and changes in MIR over time (δMIR) remains unknown. We aimed to elucidate the significance between these indicators and gastric cancer outcomes in different countries. Among the regions, Asia had the highest number of new gastric cancer cases, gastric cancer-related deaths, age-standardized ratio of incidence, and mortality. Chile had the highest age-standardized ratio (ASR) for gastric cancer incidence and the highest ASR for mortality. Moreover, MIR was highest in Africa (0.91) and lowest in North America (0.43). Of note, MIR was negatively associated with HDI, current health expenditure (CHE) per capita, and CHE/GDP % and δMIR was positively associated with CHE/GDP % in countries with very high HDI. However, δMIR showed no significant associations with these indicators in the countries analyzed. In conclusion, increased HDI, CHE per capita, and CHE/GDP are associated with improved gastric cancer outcomes. In addition, the δMIR could be an indicator that can be used to evaluate the improvement in cancer management outcomes over time.

A Deep Learning Model for Classification of Endoscopic Gastroesophageal Reflux Disease.

Gastroesophageal reflux disease (GERD) is a common disease with high prevalence, and its endoscopic severity can be evaluated using the Los Angeles classification (LA grade). This paper proposes a deep learning model (i.e., GERD-VGGNet) that employs convolutional neural networks for automatic classification and interpretation of routine GERD LA grade. The proposed model employs a data augmentation technique, a two-stage no-freezing fine-tuning policy, and an early stopping criterion. As a result, the proposed model exhibits high generalizability. A dataset of images from 464 patients was used for model training and validation. An additional 32 patients served as a test set to evaluate the accuracy of both the model and our trainees. Experimental results demonstrate that the best model for the development set exhibited an overall accuracy of 99.2% (grade A-B), 100% (grade C-D), and 100% (normal group) using narrow-band image (NBI) endoscopy. On the test set, the proposed model resulted in an accuracy of 87.9%, which was significantly higher than the results of the trainees (75.0% and 65.6%). The proposed GERD-VGGNet model can assist automatic classification of GERD in conventional and NBI environments and thereby increase the accuracy of interpretation of the results by inexperienced endoscopists.

The Role of Series Cholecystectomy in High Risk Acute Cholecystitis Patients Who Underwent Gallbladder Drainage.

Background: Cholecystectomy (CCY) is the only definitive therapy for acute cholecystitis. We conducted this study to evaluate which patients may not benefit from further CCY after percutaneous transhepatic gallbladder drainage (PTGBD) has been performed in acute cholecystitis patients. Methods: Acute cholecystitis patients with PTGBD treatment were selected from one million random samples from the National Health Insurance Research Database obtained between January 2004 and December 2010. Recurrent biliary events (RBEs), RBE-related medical costs, RBE-related mortality rate and an RBE-free survival curve were compared in patients who accepted CCY within 2 months and patients without CCY within 2 months after the index admission. Results: Three hundred and sixty-five acute cholecystitis patients underwent PTGBD at the index admission. A total of 190 patients underwent further CCY within 2 months after the index admission. The other 175 patients did not accept further CCY within 2 months after the index admission. RBE-free survival was significantly better in the CCY within 2 months group (60 vs. 42%, p < 0.001). The RBE-free survival of the CCY within 2 months group was similar to that of the no CCY within 2 months group in patients ≥ 80 years old and patients with a Charlson Comorbidity Index (CCI) score ≥ 9. Conclusions: We confirmed CCY after PTGBD reduced RBEs, RBE-related medical expenses, and the RBE-related mortality rate in patients with acute cholecystitis. In patients who accepted PTGBD, the RBE and survival benefits of subsequent CCY within 2 months became insignificant in patients ≥ 80 years old or with a CCI score ≥ 9.

Gallic Acid Improves Diabetic Steatosis by Downregulating MicroRNA-34a-5p through Targeting NFE2L2 Expression in High-Fat Diet-Fed db/db Mice.

Type 2 diabetes mellitus (T2DM) has become epidemic worldwide and is strongly associated with nonalcoholic fatty liver disease (NAFLD). The molecular mechanisms of microRNAs in NAFLD and T2DM development and the corresponding therapies remain unclear. We performed microRNA microarray validation to determine whether hepatic miR-34a-5p was significantly upregulated in db/db mice fed with a high-fat diet (HFD), a mouse model of T2DM with steatohepatitis. The potential role of miR-34a-5p and gallic acid (GA) in regulating hepatic lipid metabolism and diabetic steatosis was explored. GA improved the activities of antioxidant enzymes and suppressed lipid accumulation in the HFD-induced steatotic liver of db/db mice. In vitro, the silencing of miR-34a-5p in hepatocyte HepG2 cells ameliorated high glucose + oleic acid/palmitic acid mixture-induced accumulation of cellular triglycerides. We identified nuclear factor erythroid-derived 2-like 2 (NFE2L2) as a direct target of miR-34a-5p. Reduction in intracellular triglyceride and the expression levels of sterol regulatory element-binding protein 1 and fatty acid synthase by GA were mediated by the inhibition of miR-34a-5p expression in HepG2 cells. The findings suggest that GA improves hepatic lipogenesis by downregulating miR-34a-5p by suppressing NFE2L2 expression, indicating the potential therapeutic role of GA or an NFE2L2-activating agent in diabetic fatty liver disease.

Symptomatic cholelithiasis patients have an increased risk of pancreatic cancer: A population-based study.

BACKGROUND AND AIM: Pancreatic cancer is a fatal disease; currently, the risk factor survey is not suitable for sporadic pancreatic cancer, which has neither family history nor the genetic analysis data. The aim of the present study was to evaluate the roles of cholelithiasis and cholelithiasis treatments on pancreatic cancer risk. METHODS: Symptomatic adult patients with an index admission of cholelithiasis were selected from one million random samples obtained between January 2005 and December 2009. The control group was matched with a 1:1 ratio for sex, age, chronic pancreatitis, and pancreatic cystic disease. Subsequent pancreatic cancer, which we defined as pancreatic cancer that occurred ≥ 6 months later, and total pancreatic cancer events were calculated in the cholelithiasis and control groups. The cholelithiasis group was further divided into endoscopic sphincterotomy/endoscopic papillary balloon dilatation, cholecystectomy, endoscopic sphincterotomy/endoscopic papillary balloon dilatation and cholecystectomy, and no-intervention groups for evaluation. RESULTS: The cholelithiasis group and the matched control group included 8265 adults. The cholelithiasis group contained 86 cases of diagnosed pancreatic cancer, and the control group contained 8 cases (P < 0.001). The incidence rate ratio (IRR) of subsequent pancreatic cancer was significantly higher in the cholelithiasis group than in the control group (IRR: 5.28, P < 0.001). The IRR of subsequent pancreatic cancer was higher in the no-intervention group comparing with cholecystectomy group (IRR = 3.21, P = 0.039) but was similar in other management subgroups. CONCLUSION: Symptomatic cholelithiasis is a risk factor for pancreatic cancer; the risk is similar regardless of the intervention chosen for cholelithiasis.

Cholecystectomy reduces subsequent cholangiocarcinoma risk in choledocholithiasis patients undergoing endoscopic intervention.

BACKGROUND: Cholangiocarcinoma is a disease with a high mortality rate. Our previous study revealed that cholelithiasis patients who undergo endoscopic sphincterotomy (ES)/endoscopic papillary balloon dilatation are at a higher risk for subsequent cholangiocarcinoma than cholelithiasis patients who undergo cholecystectomy. AIM: To clarify the relationship between recurrent biliary events and subsequent cholangiocarcinoma risk in choledocholithiasis patients. METHODS: From one million random cases in the Taiwan National Health Insurance Research Database 2004-2011, we selected symptomatic choledocholithiasis patients older than 18 years who were admitted from January 2005 to December 2009 (study group). Cases for a control group were defined as individuals who had never been diagnosed with cholelithiasis, matched by sex and age in a 1:3 ratio. The study group was further divided into ES/endoscopic papillary balloon dilatation, both ES/endoscopic papillary balloon dilatation and cholecystectomy, and no intervention groups. RESULTS: We included 2096 choledocholithiasis patients without previous intervention or cholangiocarcinoma. A total of 12 (2.35%), 11 (0.74%), and 1 (1.00%) subsequent cholangiocarcinoma cases were diagnosed among 511 ES/endoscopic papillary balloon dilatation patients, 1485 patients with no intervention, and 100 ES/endoscopic papillary balloon dilatation and cholecystectomy patients, respectively. The incidence rates of recurrent biliary event were 527.79/1000 person-years and 286.69/1000 person-years in the subsequent cholangiocarcinoma and no cholangiocarcinoma group, showing a high correlation between subsequent cholangiocarcinoma risk and recurrent biliary events. CONCLUSION: Choledocholithiasis patients who undergo further cholecystectomy after ES/endoscopic papillary balloon dilatation have decreased subsequent cholangiocarcinoma risk due to reduced recurrent biliary events.

Comorbidities and Outcome of Alcoholic and Non-Alcoholic Liver Cirrhosis in Taiwan: A Population-Based Study.

The prognosis of different etiologies of liver cirrhosis (LC) is not well understood. Previous studies performed on alcoholic LC-dominated cohorts have demonstrated a few conflicting results. We aimed to compare the outcome and the effect of comorbidities on survival between alcoholic and non-alcoholic LC in a viral hepatitis-dominated LC cohort. We identified newly diagnosed alcoholic and non-alcoholic LC patients, aged ≥40 years old, between 2006 and 2011, by using the Longitudinal Health Insurance Database. The hazard ratios (HRs) were calculated using the Cox proportional hazards model and the Kaplan-Meier method. A total of 472 alcoholic LC and 4313 non-alcoholic LC patients were identified in our study cohort. We found that alcoholic LC patients were predominantly male (94.7% of alcoholic LC and 62.6% of non-alcoholic LC patients were male) and younger (78.8% of alcoholic LC and 37.4% of non-alcoholic LC patients were less than 60 years old) compared with non-alcoholic LC patients. Non-alcoholic LC patients had a higher rate of concomitant comorbidities than alcoholic LC patients (79.6% vs. 68.6%, p < 0.001). LC patients with chronic kidney disease demonstrated the highest adjusted HRs of 2.762 in alcoholic LC and 1.751 in non-alcoholic LC (all p < 0.001). In contrast, LC patients with hypertension and hyperlipidemia had a decreased risk of mortality. The six-year survival rates showed no difference between both study groups (p = 0.312). In conclusion, alcoholic LC patients were younger and had lower rates of concomitant comorbidities compared with non-alcoholic LC patients. However, all-cause mortality was not different between alcoholic and non-alcoholic LC patients.

Current Endoscopic Management of Malignant Biliary Stricture.

Biliary and pancreatic cancers occur silently in the initial stage and become unresectable within a short time. When these diseases become symptomatic, biliary obstruction, either with or without infection, occurs frequently due to the anatomy associated with these cancers. The endoscopic management of these patients has changed, both with time and with improvements in medical devices. In this review, we present updated and integrated concepts for the endoscopic management of malignant biliary stricture. Endoscopic biliary drainage had been indicated in malignant biliary obstruction, but the concept of endoscopic management has changed with time. Although routine endoscopic stenting should not be performed in resectable malignant distal biliary obstruction (MDBO) patients, endoscopic biliary drainage is the treatment of choice for palliation in unresectable MDBO patients. Self-expanding metal stents (SEMS) have better stent patency and lower costs compared with plastic stents (PS). For malignant hilum obstruction, PS and uncovered SEMS yield similar short-term outcomes, while a covered stent is not usually used due to a potential unintentional obstruction of contralateral ducts.

Favorable gallbladder cancer mortality-to-incidence ratios of countries with good ranking of world's health system and high expenditures on health.

BACKGROUND: The mortality-to-incidence ratio (MIR) is a marker that reflects the clinical outcome of cancer treatment. MIR as a prognostic marker is more accessible when compared with long-term follow-up survival surveys. Theoretically, countries with good health care systems would have favorable outcomes for cancer; however, no report has yet demonstrated an association between gallbladder cancer MIR and the World's Health System ranking. METHODS: We used linear regression to analyze the correlation of MIRs with the World Health Organization (WHO) rankings and total expenditures on health/gross domestic product (e/GDP) in 57 countries selected according to the data quality. RESULTS: The results showed high crude rates of incidence/mortality but low MIR in more developed regions. Among continents, Europe had the highest crude rates of incidence/mortality, whereas the highest age-standardized rates (ASR) of incidence/mortality were in Asia. The MIR was lowest in North America and highest in Africa (0.40 and 1.00, respectively). Furthermore, favorable MIRs were correlated with good WHO rankings and high e/GDP (p = 0.01 and p = 0.030, respectively). CONCLUSIONS: The MIR variation for gallbladder cancer is therefore associated with the ranking of the health system and the expenditure on health.

Enterotype-based Analysis of Gut Microbiota along the Conventional Adenoma-Carcinoma Colorectal Cancer Pathway.

The dysbiosis of human gut microbiota is strongly associated with the development of colorectal cancer (CRC). The dysbiotic features of the transition from advanced polyp to early-stage CRC are largely unknown. We performed a 16S rRNA gene sequencing and enterotype-based gut microbiota analysis study. In addition to Bacteroides- and Prevotella-dominated enterotypes, we identified an Escherichia-dominated enterotype. We found that the dysbiotic features of CRC were dissimilar in overall samples and especially Escherichia-dominated enterotype. Besides a higher abundance of Fusobacterium, Enterococcus, and Aeromonas in all CRC faecal microbiota, we found that the most notable characteristic of CRC faecal microbiota was a decreased abundance of potential beneficial butyrate-producing bacteria. Notably, Oscillospira was depleted in the transition from advanced adenoma to stage 0 CRC, whereas Haemophilus was depleted in the transition from stage 0 to early-stage CRC. We further identified 7 different CAGs by analysing bacterial clusters. The abundance of microbiota in cluster 3 significantly increased in the CRC group, whereas that of cluster 5 decreased. The abundance of both cluster 5 and cluster 7 decreased in the Escherichia-dominated enterotype of the CRC group. We present the first enterotype-based faecal microbiota analysis. The gut microbiota of colorectal neoplasms can be influenced by its enterotype.

Risk of cholangiocarcinoma in patients undergoing therapeutic endoscopic retrograde cholangiopancreatography or cholecystectomy: A population based study.

BACKGROUND: Cholangiocarcinoma is a highly lethal disease that had been underestimated in the past two decades. Many risk factors are well documented for in cholangiocarcinoma, but the impacts of advanced biliary interventions, like endoscopic sphincterotomy (ES), endoscopic papillary balloon dilatation (EPBD), and cholecystectomy, are inconsistent in the previous literature. AIM: To clarify the risks of cholangiocarcinoma after ES/EPBD, cholecystectomy or no intervention for cholelithiasis using the National Health Insurance Research Database (NHIRD). METHODS: From data of NHIRD 2004-2011 in Taiwan, we selected 7938 cholelithiasis cases as well as 23814 control group cases (matched by sex and age in a 1:3 ratio). We compared the previous risk factors of cholangiocarcinoma and cholangiocarcinoma rate in the cholelithiasis and control groups. The incidences of total and subsequent cholangiocarcinoma were calculated in ES/EPBD patients, cholecystectomy patients, cholelithiasis patients without intervention, and groups from the normal population. RESULTS: In total, 537 cases underwent ES/EPBD, 1743 cases underwent cholecystectomy, and 5658 cholelithiasis cases had no intervention. Eleven (2.05%), 37 (0.65%), and 7 (0.40%) subsequent cholangiocarcinoma cases were diagnosed in the ES/EPBD, no intervention, and cholecystectomy groups, respectively, and the odds ratio for subsequent cholangiocarcinoma was 3.13 in the ES/EPBD group and 0.61 in the cholecystectomy group when compared with the no intervention group. CONCLUSION: In conclusion, symptomatic cholelithiasis patients who undergo cholecystectomy can reduce the incidence of subsequent cholangiocarcinoma, while cholelithiasis patients who undergo ES/EPBD are at a great risk of subsequent cholangiocarcinoma according to our findings.

Role of Cholecystectomy in Choledocholithiasis Patients Underwent Endoscopic Retrograde Cholangiopancreatography.

There are no clinical guidelines for the timing of cholecystectomy (CCY) after performing therapeutic endoscopic retrograde cholangiopancreatography (ERCP) for choledocholithiasis. We tried to analyze the clinical practice patterns, medical expenses, and subsequent outcomes between the early CCY, delayed CCY, and no CCY groups of patients. 1827 choledocholithiasis patients who underwent therapeutic ERCP were selected from the nationwide population databases of two million random samples. These patients were further divided into early CCY, delayed CCY, and no CCY performed. In our analysis, 1440 (78.8%) of the 1827 patients did not undergo CCY within 60 days of therapeutic ERCP, and only 239 (13.1%) patients underwent CCY during their index admission. The proportion of laparoscopic CCY increased from 37.2% to 73.6% in the delayed CCY group. There were no significant differences (p = 0.934) between recurrent biliary event (RBE) rates with or without early CCY within 60 days of ERCP. RBE event-free survival rates were significantly different in the early CCY (85.04%), delayed CCY (89.54%), and no CCY (64.45%) groups within 360 days of ERCP. The method of delayed CCY can reduce subsequent RBEs and increase the proportion of laparoscopic CCY with similar medical expenses to early CCY in Taiwan's general practice environment.

Major bleeding risk of endoscopic sphincterotomy versus endoscopic papillary balloon dilatation in hemodialysis patients.

BACKGROUND/AIMS: Endoscopic sphincterotomy (EST) and endoscopic papillary balloon dilatation (EPBD) are used for therapeutic endoscopic retrograde cholangiopancreatography (ERCP). The postprocedure bleeding rate for EPBD is low in the normal population; however, this bleeding rate in a group of patients prone to bleeding, such as patients with end-stage renal disease, is not well-established. We therefore evaluated the post-EST and post-EPBD bleeding rate among hemodialysis (HD) patients based on data from Taiwan's National Health Insurance Research Database (NHIRD). PATIENTS AND METHODS: The NHIRD entries for a population of 2 million were screened for patients who had a catastrophic illness card for HD between 1st January 2004 and 31st December 2011 and these patients were enrolled as research subjects. The rates of major gastrointestinal tract bleeding events appearing within 14 days after EST or EPBD were compared between HD and non-HD patients. RESULTS: A total of 3561 patients, over 18 years of age and without liver cirrhosis or hematologic diseases, underwent 3826 EST and 280 EPBD procedures during the 8 calendar years selected for our analysis. The total post-ERCP major bleeding rate was much higher in HD than in non-HD patients (8.64% vs. 2.16%, P < 0.0001). The rate of postprocedure major bleeding events was lower for non-HD patients who underwent EPBD than those who underwent EST (0.75% vs. 2.26%; P = 0.049), whereas the postprocedure major bleeding event rates were similar in HD patients who underwent either EPBD or EST (8.70% vs. 8.33%; P = 0.484). CONCLUSION: Post-ERCP, post-EST, and post-EPBD major bleeding rates were all higher in HD patients in this study. EPBD resulted in lower postprocedure major bleeding events than EST in the non-HD population, but it failed to provide the reduction in bleeding events needed to perform endoscopic hemostasis in HD patients.