Clinical outcomes and learning curve for ERCP during advanced endoscopy training: a comparison of supine versus prone positioning.

BACKGROUND AND AIMS: No studies have evaluated trainees' outcomes when learning ERCP with patients in the supine and prone positions simultaneously. We aimed to assess whether patient position impacts procedural outcomes and learning curve. METHODS: We prospectively evaluated patients undergoing ERCP by a supervised advanced endoscopy trainee (AET) at a tertiary care center. Adult patients with native papillae were included. The AET was universally given 5 attempts per cannulation. Outcomes were evaluated quarterly. RESULTS: Successful cannulation was achieved in 44 supine (69%) and 17 prone (68%) patients (P = .95). Although mean time to reach the papilla was shorter in the supine patient position, time to biliary cannulation (7.8 vs 9.4 minutes, P = .53) and number of attempts were similar. A stepwise increase was seen in cannulation rates throughout the academic year (P < .01) and increased more in supine patients (P = .01). Procedure and total room times were shorter in supine patients. CONCLUSIONS: Shorter procedure and room turnover times and a comparable cannulation rate were found for supine versus prone ERCP.

Nonalcoholic Steatohepatitis (NASH) and Hepatic Fibrosis: Emerging Therapies.

Nonalcoholic fatty liver disease remains a major cause of liver-related morbidity and mortality worldwide. It is a complex disease associated with obesity, diabetes, and dyslipidemia but is increasingly recognized in normal-weight individuals. Its progressive inflammatory phenotype, nonalcoholic steatohepatitis (NASH), currently has no effective treatment apart from lifestyle interventions. Multiple pathogenic pathways are involved in disease progression, and targets for intervention have been identified. These targets mediate glucose, lipid, and bile acid metabolism; inflammation; apoptosis; and fibrosis. Novel therapeutic agents are being developed in each of these pathways, and several have shown promise in early phase testing. Given the complexity of the disease, intervention trials are large and long and require histologic confirmation as a primary endpoint for disease improvement or regression. We highlight active Phase 2 and 3 therapeutic trials for NASH as this field rapidly expands in development.

Endoscopic ultrasound-guided gallbladder drainage as a rescue therapy for unresectable malignant biliary obstruction: a multicenter experience.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is often unsuccessful in patients with duodenal stenosis or malignant ampullary infiltration. While endoscopic ultrasound-guided biliary drainage (EUS-BD) has been proposed as an alternative, EUS-guided gallbladder drainage (EUS-GBD) is an attractive option when both approaches fail. We aimed to assess the effectiveness and safety of EUS-GBD as rescue therapy for malignant distal bile duct obstruction. METHODS: A multicenter retrospective study was performed on patients with unresectable malignant distal bile duct obstruction who underwent EUS-GBD between 2014 and 2019 after unsuccessful ERCP and EUS-BD. Clinical success was defined as a decrease in serum bilirubin of > 50 % within 2 weeks. RESULTS: 28 patients were included, with a lumen-apposing metal stent used in 26 (93 %) and a self-expandable metal stent in two (7 %). The technical success rate was 100 %. The clinical success rate was 93 %, with an improvement in bilirubin (7.3 [SD 5.4] pre-procedure vs. 2.8 [SD 1.1] post-procedure; P = 0.001). Delayed adverse events included food impaction of the stent (n = 3), with a further two patients developing cholecystitis and bleeding. CONCLUSION: This study demonstrates the feasibility of gallbladder drainage to relieve malignant distal bile duct obstruction in patients with failed ERCP and EUS-BD.

Future therapy for non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease is a leading cause of chronic liver disease and can lead to cirrhosis, hepatocellular cancer and end stage liver disease. It is also associated with increased cardiovascular and cancer related morbidity and mortality. The pathogenesis of non-alcoholic fatty liver disease includes metabolic stress to the liver associated with insulin resistance with downstream cell stress from reactive oxygen species and unfolded protein response with activation of inflammatory and fibrotic pathways. There are currently no approved therapies for non-alcoholic fatty liver disease. This review summarizes ongoing efforts to establish the treatment of non-alcoholic steatohepatitis the progressive form of non-alcoholic fatty liver disease. Therapies are currently directed towards improving the metabolic status of the liver, cell stress, apoptosis, inflammation or fibrosis. Several agents are now in pivotal trials and it is expected that the first therapies will be approved in 2-3 years.

Nonalcoholic Steatohepatitis is the Most Rapidly Increasing Indication for Liver Transplantation in Young Adults in the United States.

GOALS: To analyze the frequency and trend of liver transplantation (LT) for nonalcoholic steatohepatitis (NASH) cirrhosis in young adults aged 18 to 40 years and to assess post-LT outcomes in this age group. BACKGROUND: NASH is currently the fastest-growing indication for LT in US adults. It is believed that NASH is a rare indication for LT among young adults. STUDY: Using the United Network for Organ Sharing database, we performed a retrospective cohort analysis of all LTs in young adults between 2002 and 2012. Incidence rate ratio was calculated for each indication. RESULTS: A total of 5157 young adults underwent LT over the study period-54% were male, 23% obese. Mean (±SD) age and body mass index were 31.6±6.7 years and 26.3±6.1 kg/m, respectively. The incidence of LTs performed for NASH cirrhosis increased from 0.53% in 2002 to 4.46% in 2012. NASH was the most rapidly growing indication for LT among all other etiologies with a 14% increment per year (incidence rate ratio, 1.14; 95% confidence interval, 1.09-1.20, P<0.001). The 5-year post-LT outcomes were comparable between NASH and non-NASH recipients, but graft survival was lower and retransplantation cumulative rates were higher in NASH recipients compared with those with other metabolic liver diseases (63.5% vs. 81.4%, P=0.003 and 12.7% vs. 4.2%, P=0.046, respectively). CONCLUSIONS: NASH is the fastest-growing indication for LT among young US adults aged 18 to 40 years and now accounts for almost 5% of all LTs in this age group.

Similar Risk of Cardiopulmonary Adverse Events Between Propofol and Traditional Anesthesia for Gastrointestinal Endoscopy: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Even though propofol use for gastrointestinal endoscopic procedures has increased over the past decade, there is a perception that it causes a higher rate of cardiopulmonary adverse events. The aim of this study was to compare the sedation-related adverse events associated with use of propofol vs nonpropofol agents for endoscopic procedures. We also wanted to determine the influence of duration or complexity of the procedures and endoscopist-directed (gastroenterologist) vs non-gastroenterologist-directed sedation on the outcomes. METHODS: A search was conducted using Medline, EMBASE, and the Cochrane controlled trials registry. The following cardiopulmonary adverse events were assessed: hypoxia, hypotension, and arrhythmias. The procedures were divided into 2 groups based on the procedure length: a nonadvanced endoscopic procedure group consisting of esophagogastroduodenoscopy, colonoscopy, and sigmoidoscopy, and an advanced endoscopic procedures group including endoscopic retrograde cholangiopancreatography, endoscopic ultrasonography, balloon enteroscopy, and endoscopic submucosal dissection. Pooled odds ratios for complications were calculated for all the procedures combined and then separately for the 2 groups. Random-effects models were used for 2-proportion comparisons. RESULTS: Of the 2117 citations identified, 27 original studies qualified for this meta-analysis and included 2518 patients. Of these, 1324 received propofol, and 1194 received midazolam, meperidine, pethidine, remifentanil, and/or fentanyl. Most of the included studies were randomized trials of moderate quality and nonsignificant heterogeneity (Cochran Q, 26.07; P = .13). Compared with traditional sedative agents, the pooled odds ratio with the use of propofol for developing hypoxia for all the procedures combined was 0.82 (95% confidence interval [CI], 0.63-1.07), and for developing hypotension was 0.92 (95% CI, 0.64-1.32). In the nonadvanced endoscopic procedure group, those who received propofol were 39% less likely to develop complications than those receiving traditional sedative agents (odds ratio, 0.61; 95% CI, 0.38-0.99). There was no difference in the complication rate for the advanced endoscopic procedure group (odds ratio, 0.86; 95% CI, 0.56-1.34). A subgroup analysis did not show any difference in adverse events when propofol was administered by gastroenterologists or nongastroenterologists. CONCLUSIONS: Propofol sedation has a similar risk of cardiopulmonary adverse events compared with traditional agents for gastrointestinal endoscopic procedures. Propofol use in simple endoscopic procedures was associated with a decreased number of complications. When used for gastrointestinal endoscopic procedures of a complex nature and longer duration, propofol was not associated with increased rates of hypoxemia, hypotension, or arrhythmias. Administration of propofol by gastroenterologists does not appear to increase the complication rates.

The development of a non-invasive model to predict the presence of non-alcoholic steatohepatitis in patients with non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is an advanced and aggressive form of non-alcoholic fatty liver disease (NAFLD), which remains difficult to diagnose without a liver biopsy. Hyperferritinemia has increasingly been associated with the presence of NASH. Hence, we sought to explore the relationship between ferritin and NASH and to develop a composite model based on ferritin to predict the presence of NASH. METHODS: A total of 405 patients with biopsy-proven NAFLD were enrolled in the study. Comparison was explored to assess differences between patients with and without NASH, upon which a scoring model was established using variables found to be independent predictors of NASH. RESULTS: Among all patients with NAFLD, 291 (72%) had biopsy-proven NASH, and 114 (28%) had non-NASH. Mean age was 48 ± 12 years, and 56% were female. Ferritin was significantly higher in NASH compared with non-NASH patients (184 vs 126, respectively; P < 0.001) but lacked diagnostic accuracy for predicting NASH alone (area under the curve [AUC 0.62]). The addition of other significant variables such as aspartate aminotransferase, body mass index, platelet count, diabetes, and hypertension to ferritin improved the prediction of NASH with an AUC 0.81 (95% confidence interval: 0.76-0.86). Internal validation of the model using imputed data sets demonstrated that AUC did not change materially. CONCLUSIONS: While higher ferritin was significantly associated with NASH, ferritin alone lacked diagnostic accuracy to predict NASH. However, incorporating several easily obtainable variables with ferritin allowed the construction of a novel scoring system that can be easily applied in the clinical setting to guide management of NAFLD.

Analyzing TCGA Data to Identify Gene Mutations Linked to Hepatocellular Carcinoma in Asians.

Introduction: Liver cancer is the sixth most common and second most fatal type of cancer worldwide. Few treatment options are available as patients with liver cancer are often diagnosed in an advanced stage due to a lack of clinical symptoms. Effectively preventing and treating liver cancer relies heavily on early diagnosis; early diagnosis results from identifying and monitoring high-risk patients. Epigenetic risk factors, such as hepatitis B, hepatitis C, cirrhosis, nonalcoholic fatty liver disease, and alcohol/tobacco abuse, are highly prevalent in Asia and likely cause Asians to have a higher incidence and mortality rate of liver cancer. While these acquired risk factors are relatively well understood, the underlying genetic background of liver cancer in Asians has not been well established or correlated with clinical outcomes. Methods: In this study, we accessed The Cancer Genome Atlas (TCGA) hepatocellular carcinoma clinical and mutation data through TCGAbiolinksGUI. Results: We found that mutations in five genes (TP53, TTN, OBSCN, MUC5B, CSMD1) were statistically linked with increased mortality in Asians compared to non-Asians, four of which (TTN, OBSCN, MUC5B, CSMD1) were also more prevalent in the Asian population. Within the Asian cohort, two gene mutations (TTN, HMCN1) were statistically linked with worse outcomes. We also found that the TP53 mutation predicts worse outcomes within the non-Asian cohort but not within the Asian cohort. Discussion/Conclusion: Our findings can improve cancer care in the Asian population through better disease prognostication, evaluations for potential targeted therapy, and a deeper understanding of liver cancer pathogenesis.

Azithromycin versus erythromycin infusions prior to endoscopy in upper gastrointestinal bleeding.

Background: Intravenous erythromycin prior to endoscopy for upper gastrointestinal bleeding (GIB) improves outcomes but requires immediate preparation delaying administration in emergency cases. Azithromycin is readily available and does not require prolonged preparation. The aim of the study was to assess the effect of azithromycin in improving the quality of endoscopic visualization in upper GIB compared to erythromycin. Methods: Patients admitted with upper GIB who received erythromycin or azithromycin before urgent endoscopy were included. Primary outcome of the quality of visualization was assessed by two gastroenterologists, blinded to the choice of infusion, using a scoring system ranging from 0 to 8, with a maximum of 2 points assigned to the fundus, body, antrum and bulb. Results: Sixty-six patients were included; 25 received azithromycin and 41 received erythromycin. Mean total visualization score was significantly higher with azithromycin compared to that with erythromycin (6.8±1.4 vs. 5.5±2.2, respectively; P=0.01) and remained significant after adjusting for confounders (Diff: 0.01, 1.88; P=0.05). Secondary outcomes analyses showed a shorter LOS when given azithromycin compared to erythromycin [6 (3 to 9) vs. 8 (7 to 16) days, respectively, 95% CI: 1.03, 3.89; P=0.04]. Time between initiating the infusion and endoscopy was longer with azithromycin (Diff: 40.64 min; 95% CI: 7.23, 74.05; P=0.02). Need for second look endoscopy, procedure time, blood transfusion requirements and procedure-related complications did not differ between the groups. Conclusions: Azithromycin infusion before endoscopy for upper GIB was associated with better visualization than that of erythromycin. Randomized trials are needed to validate these findings.

EUS-guided stent placement for afferent limb and gastrojejunal obstruction in a patient with pancreatic cancer.

Video 1EUS-guided stent placement for afferent limb and gastrojejunal obstruction in a patient with pancreatic cancer.