Histological Outcomes of Pharmacological Interventions in Eosinophilic Esophagitis for Adults and Children: A Network Meta-analysis of Randomized Controlled Trials.

INTRODUCTION: Multiple pharmacological interventions have been studied for managing eosinophilic esophagitis (EoE). We performed a comprehensive systematic review and network meta-analysis of all available randomized controlled trials (RCT) to assess the efficacy and safety of these interventions in EoE in adults and children. METHODS: We performed a comprehensive review of Embase, PubMed, MEDLINE OVID, Cochrane CENTRAL, and Web of Science through May 10, 2023. We performed frequentist approach network meta-analysis using random effects model. We calculated the odds ratio (OR) with 95% CI for dichotomous outcomes. RESULTS: Our search yielded 25 RCTs with 25 discrete interventions and 2067 patients. Compared with placebo, the following interventions improved histology (using study definitions) in decreasing order on ranking: orodispersible budesonide (ODB) low dose, ODB high dose, oral viscous budesonide (OVB) high dose, fluticasone tablet 1.5 mg twice daily, fluticasone 3 mg twice daily, esomeprazole, dupilumab every 2 weeks, dupilumab weekly, OVB medium dose, fluticasone 3 mg daily, cendakimab 180 mg, prednisone, swallowed fluticasone, fluticasone tablet 1.5 mg daily, OVB low dose, reslizumab 3 mg/kg, reslizumab 1 mg/kg, and reslizumab 2 mg/kg. CONCLUSIONS: Network meta-analysis demonstrates histological efficacy of multiple medications for EoE. Because of the heterogeneity and large effect size, we recommend more trials comparing pharmacotherapeutic interventions with each other and placebo. An important limitation of this study is absence of clinical efficacy data due to insufficient data. Other limitations include heterogeneity of operator, population, and outcome analysis.

Meta-Analysis of Endoscopic Full-Thickness Resection Versus Endoscopic Submucosal Dissection for Complex Colorectal Lesions.

BACKGROUND: Studies evaluating endoscopic full-thickness resection (EFTR) and endoscopic submucosal dissection (ESD) for complex colorectal lesions have shown variable results. We conducted a meta-analysis of the available data. METHODS: Online databases were searched for studies comparing EFTR versus ESD for complex colorectal lesions. The outcomes of interest were resection rates, procedure time (min), and complications. Pooled odds ratios (OR) and standardized mean difference (SMD) along with 95% CI were calculated. RESULTS: A total of 4 studies with 530 patients (n=215 EFTR, n=315 ESD) were included. The mean follow-up duration was 5 months. The mean age of the patients was 68 years and 64% were men. The EFTR and ESD groups had similar rates of en bloc resection (OR: 1.73, 95% CI: 0.60-4.97, P=0.31) and R0 resection (OR: 1.52, 95% CI: 0.55-4.14, P=0.42). The EFTR group had significantly reduced procedure time (SMD -1.87, 95% CI: -3.13 to -0.61, P=0.004), total complications (OR: 0.24, 95% CI: 0.13-0.44, P<0.00001), perforation (OR: 0.12, 95% CI: 0.03-0.39, P=0.0005) and postresection electrocoagulation syndrome (OR: 0.06, 95% CI: 0.01-0.48, P=0.008). Delayed bleeding was similar in the 2 groups (OR: 0.80, 95% CI: 0.30-2.12, P=0.66). Residual/recurrent lesions were significantly higher in the EFTR group (OR: 4.67, 95% CI: 1.39-15.66, P=0.01). DISCUSSION: This meta-analysis of small studies with high heterogeneity showed that EFTR and ESD have comparable resection rates for complex colorectal lesions. EFTR is faster and has fewer complications, but it increases residual or recurrent lesions.

Trends in mortality from gastrointestinal, hepatic, and pancreatic cancers in the United States: A comprehensive analysis (1999-2020).

Background and Aim: This study investigates temporal trends in gastrointestinal cancer-related mortality in the United States between 1999 and 2020, focusing on differences by sex, age, and race. Methods: We investigated the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research multiple causes of death database (Years 1999-2020) for gastrointestinal cancer-related mortality with a focus on the underlying cause of death. Results: A total of 3 115 243 gastrointestinal cancer-related deaths occurred from 1999 to 2020. The overall age-adjusted mortality rate decreased from 46.7 per 100 000 in 1999 to 38.4 per 100 000 in 2020. The average annual percent change (AAPC) for the study period was -0.9% (95% CI: -1.0%, -0.9%, P < 0.001), with no significant difference in AAPC between the sexes but some difference between races and related to individual cancers. African Americans and Asian Americans, and Pacific Islanders experienced a greater decrease in mortality compared with Whites. Mortality rates for American Indian and Alaskan Native populations also decreased significantly from 1999 to 2020 (P < 0.001). There were significant declines in esophageal, stomach, colon, rectal, and gallbladder cancer-related mortality but increases in the small bowel, anal, pancreatic, and hepatic cancer-related mortality (P < 0.001), with variation across different sexes and racial groups. Conclusion: While overall gastrointestinal cancer-related mortality declined significantly in the United States from 1999 to 2020, mortality from some cancers increased. Furthermore, differences between sexes and racial groups underscore crucial differences in gastrointestinal cancer mortality, highlighting areas for future research.

Comparing EUS-directed Transgastric ERCP (EDGE) Versus Laparoscopic-Assisted ERCP Versus Enteroscopic ERCP: A Network Meta-analysis.

BACKGROUND: Management of choledocholithiasis in patients with Roux-en-Y gastric bypass surgery is challenging. This study aims to compare technical success rates, adverse events, and procedural time between 3 current approaches: endoscopic ultrasound-directed transgastric Endoscopic retrograde cholangiopancreatography (ERCP) (EDGE), enteroscopy-assisted ERCP (E-ERCP), and laparoscopic-assisted ERCP (LA-ERCP). METHODS: A systematic search of 5 databases was conducted. Direct and network meta-analyses were performed to compare interventions using the random effects model. A significance threshold of P < 0.05 was applied. RESULTS: Sixteen studies were included. On direct meta-analysis, technical success rates were comparable between EDGE and LA-ERCP (odds ratio: 0.768, CI: 0.196-3.006, P = 0.704, I2 = 14.13%). However, EDGE and LA-ERCP showed significantly higher success rates than E-ERCP. No significant differences in adverse events were found between EDGE versus LA-ERCP, EDGE versus E-ERCP, and LA-ERCP versus E-ERCP on direct meta-analysis. In terms of procedural time, EDGE was significantly shorter than E-ERCP [mean difference (MD): -31 minutes, 95% CI: -40.748 to -21.217, P < 0.001, I2 = 19.89%), and E-ERCP was shorter than LA-ERCP (MD: -44.567 minutes, 95% CI: -76.018 to -13.116, P = 0.005, I2 = 0%). EDGE also demonstrated a significant time advantage over LA-ERCP (MD: -78.145 minutes, 95% CI: -104.882 to -51.407, P < 0.001, I2 = 0%). All findings were consistent with network meta-analysis on random effects model. The heterogeneity of the model was low. CONCLUSIONS: EDGE and LA-ERCP showed superior technical success rates compared with E-ERCP. Adverse events did not significantly differ among the three approaches. Furthermore, EDGE demonstrated the shortest procedural duration. We recommend considering EDGE as a first-choice procedure.

Hepatic encephalopathy with proton pump inhibitor use in post tips patients: a systematic review and meta-analysis.

INTRODUCTION: Hepatic encephalopathy (HE) after Trans-jugular intrahepatic portosystemic shunt (TIPS) is a common clinical problem. According to recent studies, Proton pump inhibitor (PPI) use can serve as an independent risk factor for HE. We performed a systematic review and meta-analysis to analyze the association between HE with PPI use versus without PPI use in patients undergoing TIPS. EVIDENCE ACQUISITION: We conducted a comprehensive literature search from inception through February 15th, 2022 on MEDLINE, EMBASE, Cochrane Register of Controlled Trials, and Web of Science databases. Odds ratio (OR) was calculated when comparing dichotomous variables of patients with HE vs no HE in PPI use versus no PPI use in post TIPS patients. A 95% confidence interval (CI) and P values (<0.05 considered significant) were also generated. EVIDENCE SYNTHESIS: The search strategy yielded a total of 27 articles. We finalized four studies with a total of 825 patients. There was statistically significant difference in TIPS patients with HE in PPI users versus non-PPI users (OR 3.39 [1.79-6.43], P<0.01, I2=55.5%). Pooled mean average days to hospitalization was 215.2 days to hospitalization for hepatic encephalopathy in non-PPI users compared to 139.5 days in PPI users. CONCLUSIONS: Our study determines that there is a higher risk of post-TIPS HE in patients on PPI therapy vs. patients not receiving PPI therapy. We recommend using PPIs at a lower tolerable dose where necessary. Larger studies are needed to draw stronger conclusions.

Continuous vs. intermittent terlipressin infusion for portal hypertension: a systematic review and meta-analysis.

Background: Portal hypertension, a major complication of chronic liver disease, often leads to life-threatening variceal bleeding, managed effectively with vasoactive drugs like terlipressin. However, the most optimal method of terlipressin administration, continuous versus intermittent infusion, remains a subject of debate, necessitating this systematic review and meta-analysis for evidence-based decision-making in managing this critical condition. Methods: This systematic review and meta-analysis adhered to the PRISMA standards and explored multiple databases until 6 April 2023, such as MEDLINE through PubMed, Scopus, Web of Science, and CENTRAL. Independent reviewers selected randomized controlled trials (RCTs) that met specific inclusion criteria. After assessing study quality and extracting necessary data, statistical analysis was performed using Review Manager (RevMan), with results presented as risk ratios (RR) or mean differences. Results: Five RCTs (n=395 patients) were included. The continuous terlipressin group had a significantly lower risk of rebleeding (RR=0.43, P=0.0004) and treatment failure (RR=0.22, P=0.02) and fewer total adverse effects (RR=0.52, P<0.00001) compared to the intermittent group. However, there were no significant differences between the two groups in mean arterial pressure (P=0.26), length of hospital stays (P=0.78), and mortality rates (P=0.65). Conclusion: This study provides robust evidence suggesting that continuous terlipressin infusion may be superior to intermittent infusions in reducing the risk of rebleeding, treatment failure, and adverse effects in patients with portal hypertension. However, further large-scale, high-quality RCTs are required to confirm these findings and to investigate the potential benefits of continuous terlipressin infusion on mortality and hospital stays.

Safety and efficacy of underwater versus conventional endoscopic mucosal resection for colorectal polyps: Systematic review and meta-analysis of RCTs.

Background and study aims Conventional endoscopic mucosal resection (C-EMR) is limited by low en-bloc resection rates, especially for large (> 20 mm) lesions. Underwater EMR (U-EMR) has emerged as an alternative for colorectal polyps and is being shown to improve en-bloc resection rates. We conducted a systematic review and meta-analysis comparing the two techniques. Methods Multiple databases were searched through November 2022 for randomized controlled trials (RCTs) comparing outcomes of U-EMR and C-EMR for colorectal polyps. Meta-analysis was performed to determine pooled proportions and relative risks (RRs) of R0 and en-bloc resection, polyp recurrence, resection time, and adverse events. Results Seven RCTs with 1458 patients (U-EMR: 739, C-EMR: 719) were included. The pooled rate of en-bloc resection was significantly higher with U-EMR vs C-EMR, 70.17% (confidence interval [CI] 46.68-86.34) vs 58.14% (CI 31.59-80.68), respectively, RR 1.21 (CI 1.01-1.44). R0 resection rates were higher with U-EMR vs C-EMR, 58.1% (CI 29.75-81.9) vs 44.6% (CI 17.4-75.4), RR 1.25 (CI 0.99-1.6). For large polyps (> 20 mm), en-bloc resection rates were comparable between the two techniques, RR 1.24 (CI 0.83-1.84). Resection times were comparable between U-EMR and C-EMR, standardized mean difference -1.21 min (CI -2.57 to -0.16). Overall pooled rates of perforation, and immediate and delayed bleeding were comparable between U-EMR and C-EMR. Pooled rate of polyp recurrence at surveillance colonoscopy was significantly lower with U-EMR than with C-EMR, RR 0.62 (CI 0.41-0.94). Conclusions Colorectal U-EMR results in higher en-bloc resection and lower recurrence rates when compared to C-EMR. Both techniques have comparable resection times and safety profiles.

Risk of post-sphincterotomy bleeding with antiplatelet and anticoagulant use: a propensity-matched analysis of the U.S. Collaborative Network.

BACKGROUND AND AIMS: GI bleeding after ERCP is a serious adverse event and most commonly occurs after endoscopic biliary and/or pancreatic sphincterotomy. Although the strength of available evidence for post-sphincterotomy GI bleeding risk is high for therapeutic warfarin and heparin, it remains unknown for antiplatelet agents like clopidogrel and prasugrel. We conducted a retrospective United States-based, propensity-matched cohort study to assess the risk of post-sphincterotomy bleeding in patients receiving anticoagulant (AC) and antiplatelet (APT) therapy. METHODS: We analyzed the U.S. Collaborative Network in the TriNetX platform through December 27, 2022, to include patients receiving APT and AC therapy who underwent ERCP within 7 days of hospitalization. One-to-one propensity score matching was performed. The primary outcome was the incidence of GI bleeding within 7 days of sphincterotomy. Secondary outcomes included need for blood transfusion, intensive care unit care, and all-cause mortality within 30 days of bleeding. RESULTS: Overall, 2806 patients (1806 in the AC cohort and 1000 in the APT cohort) underwent ERCP with sphincterotomy. One-to-one propensity score matching was performed for age, body mass index ≥30 kg/m2, gender, race, ethnicity, diabetes mellitus, nicotine dependence, presence and severity of chronic kidney disease, cirrhosis, and thrombocytopenia between the cohorts. Patients in both cohorts had an increased risk of post-sphincterotomy bleeding compared with matched control subjects (adjusted odds ratios of 3.6 [95% confidence interval, 2.58-5.06] and 2.2 [95% confidence interval, 1.43-3.56], respectively). Although heparin bridging therapy and concurrent use of aspirin did not further increase the risk of GI bleeding, resumption of AC within 24 hours' postprocedure did. Neither cohort of patients was at an increased risk for blood transfusion, intensive care unit care, or all-cause mortality. CONCLUSIONS: Our database analysis shows that patients receiving AC and APT therapy are at a higher risk of post-sphincterotomy bleeding compared with matched control subjects. An appropriate drug cessation period or alternative biliary decompression modalities may be used in these patients.

The Conundrum of Obesity and Gastroparesis Hospitalizations: A Retrospective Comparative Analysis of Hospitalization Characteristics and Disparities Amongst Socioeconomic and Racial Backgrounds in the United States.

Background/Aims: We aim to assess the influence of obesity on gastroparesis (GP) hospitalizations in the United States (US). Methods: The National Inpatient Sample was analyzed from 2007-2017 to identify all adult hospitalizations with a primary discharge diagnosis of GP. They were subdivided based on the presence or absence of obesity (body mass index > 30). Hospitalization characteristics, procedural differences, all-cause inpatient mortality, mean length of stay (LOS), and mean total hospital charge (THC) were identified and compared. Results: From 2007-2017, there were 140 293 obese GP hospitalizations accounting for 13.75% of all GP hospitalizations in the US. Obese GP hospitalizations were predominantly female (76.11% vs 64.36%, P < 0.001) and slightly older (51.9 years vs 50.8 years, P < 0.001) compared to the non-obese cohort. Racial disparities were noted as Blacks (25.49% vs 22%, P < 0.001) had higher proportions of GP hospitalizations with obesity compared to the non-obese cohort. Furthermore, we noted higher rates of inpatient upper endoscopy utilization (6.05% vs 5.42%, P < 0.001), longer mean LOS (5.71 days vs 5.32 days, P < 0.001), and higher mean THC ($53 373 vs $45 040, P < 0.001) for obese GP hospitalizations compared to the non-obese group. However, obese GP hospitalizations had lower rates of inpatient mortality (0.92% vs 1.33%, P < 0.001), and need for nutritional support with endoscopic jejunostomy (0.25 vs 0.56%, P < 0.001) and total parenteral nutrition (1.46% vs 2.33%, P < 0.001) compared to the non-obese cohort. Conclusions: In the US, compared to non-obese, a higher proportion of obese GP hospitalizations were female and Blacks. Obese GP hospitalizations also had higher THC, LOS, and rates of upper endoscopy.

Obese gastroparesis inpatient admissions: trends and outcomes from 2007-2017 in the United States.

Background: The aim of this study was to investigate obese gastroparesis (GP) hospitalizations in the United States (US). Methods: We analyzed the National Inpatient Sample (NIS) from 2007-2017 to identify all adult obese (body mass index ≥30 kg/m2) GP hospitalizations. These were compared with non-obese GP hospitalizations. The demographic trends, adverse outcomes, and healthcare burden were analyzed. Results: From 2007-2017, obese GP hospitalizations accounted for 13.75% of all GP hospitalizations in the US. There was an increasing trend in obese GP hospitalizations, from 2286 in 2007 to 47,265 in 2017 (P=0.0019), and in the proportion of obese GP hospitalizations, from 6.16% in 2007 to 17.96% in 2017 (P<0.001). Males, Blacks, Hispanics, and Asians showed a rising trend in obese GP hospitalizations. Although rates of upper endoscopy declined from 8.28% in 2007 to 5.36% in 2017 (P<0.001), obese GP hospitalizations had higher rates of upper endoscopy utilization (6.05 vs. 5.42%, P<0.001) compared to the non-obese cohort. Inpatient mortality for obese GP hospitalizations increased from 0.64% in 2007 to 1.10% in 2017 (P<0.001). Furthermore, we noted a rising trend in mean length of stay (LOS), from 4.64 in 2007 to 6.05 days in 2017 (P=0.0029), and mean total hospital charge (THC), from $22,306 in 2007 to $62,220 in 2017 (P<0.001) for obese GP hospitalizations. Conclusions: The prevalence of obese GP hospitalizations along with inpatient mortality, LOS, and THC rose significantly. However, the overall rate of upper endoscopy utilization has decreased for these patients.

Surgical Management of Advanced Achalasia With Sigmoid Esophagus: A Case Report.

The surgical management of achalasia with sigmoid esophagus involves multiple significant challenges due to the difficulty in endoscopic assessment, esophageal motility disorders, and potential complication and recurrence rates. We report a 34-year-old female with worsening dysphagia and malnourishment due to advanced achalasia. An esophagogastroduodenoscopy (EGD) revealed an esophageal dilation, tortuosity, and distal blockage with undigested food. Esophagram demonstrated the typical bird beak appearance with a tortuous dilated esophagus. She underwent a laparoscopic Heller myotomy with Dor fundoplication with no complications. She was discharged on the second postoperative day, tolerating clear liquids, and then a normal diet within six weeks. Several treatment options exist for the surgical management of a sigmoid esophagus with achalasia, but there is no clear gold standard. In our case, Heller myotomy with Dor fundoplication provided favorable results, but treatment should be individualized for each case.

Radiation proctitis: predictors of mortality and inpatient outcomes in the United States.

BACKGROUND: We aimed to evaluate the characteristics of hospitalizations for radiation proctitis (RP). METHODS: The National Inpatient Sample (NIS) was analyzed to identify RP hospitalizations for 2016 and 2017. Outcomes included mortality, predictors of mortality, mean length of stay (LOS), mean total hospital cost (THC), and numerous system-based complications. RESULTS: We identified 16,810 adult hospitalizations for RP. On admission, an initial diagnosis of RP was established for only 27.54% of these patients. The mean age was 72.3±0.5 years and 30.2% of the study population was female. Whites made up 68.7% of the study population. Most hospitalizations for RP were at large (51%), urban (93.6%), and teaching (71.1%) hospitals. The inpatient mortality for RP hospitalizations was 1.7%. After adjusting for biodemographic factors, hospitalization characteristics and comorbidities, older age and protein energy malnutrition (PEM) were associated with higher odds of inpatient mortality. The mean LOS and THC for RP hospitalizations were 5.6 days and $53,800, respectively. Inpatient complications associated with RP included acute renal failure (19.7%), sepsis (4.4%), deep vein thrombosis (3.7%), acute respiratory failure (3.3%), and pulmonary embolism (0.7%). CONCLUSIONS: Inpatient mortality for RP was 1.7%. Older age and PEM were associated with higher odds of inpatient mortality.

Endoscopic Retrograde Cholangiopancreatography (ERCP) in Patients With Liver Cirrhosis: Analysis of Trends and Outcomes From the National Inpatient Sample Database.

GOALS: We aimed to assess outcomes of patients with liver cirrhosis who underwent therapeutic or diagnostic endoscopic retrograde cholangiopancreatography (ERCP) to determine whether these patients had different outcomes relative to patients without cirrhosis. BACKGROUND: ERCP is an important procedure for treatment of biliary and pancreatic disease. However, ERCP is relatively technically difficult to perform when compared with procedures such as esophagogastroduodenoscopy or colonoscopy. Little is known about how ERCP use affects patients with liver cirrhosis. STUDY: Using patient records from the National Inpatient Sample (NIS) database, we identified adult patients who underwent ERCP between 2009 and 2014 using International Classification of Disease, Ninth Revision coding and stratified data into 2 groups: patients with liver cirrhosis and those without liver cirrhosis. We compared baseline characteristics and multiple outcomes between groups and compared outcomes of diagnostic versus therapeutic ERCP in patients with cirrhosis. A multivariate regression model was used to estimate the association of cirrhosis with ERCP outcomes. RESULTS: A total of 1,038,258 hospitalizations of patients who underwent ERCP between 2009 and 2014 were identified, of which 31,294 had cirrhosis and 994,681 did not have cirrhosis. Of the patients with cirrhosis, 21,835 (69.8%) received therapeutic ERCP and 9459 (30.2%) received diagnostic ERCP. Patients with cirrhosis had more ERCP-associated hemorrhages (2.5% vs. 1.2%; P <0.0001) compared with noncirrhosis patients but had lower incidence of perforations (0.1% vs. 0.2%; P <0.0001) and post-ERCP pancreatitis (8.6% vs. 7%; P <0.0001). Cholecystitis was the same between groups (2.3% vs. 2.3%; P <0.0001). In patients with cirrhosis, those who received therapeutic ERCP had higher post-ERCP pancreatitis (7.9% vs. 5.1%; P <0.0001) and ERCP-associated hemorrhage (2.7% vs. 2.1%; P <0.0001) but lower incidences of perforation and cholecystitis (0.1% vs. 0.3%; P <0.0001) and cholecystitis (1.9 vs. 3.1%; P <0.0001) compared with those who received diagnostic ERCP. CONCLUSIONS: Use of therapeutic ERCP in patients with liver cirrhosis may lead to higher risk of complications such as pancreatitis and postprocedure hemorrhage, whereas diagnostic ERCP may increase the risk of pancreatitis and cholecystitis in patients with cirrhosis. Comorbidities in cirrhosis patients may increase the risk of post-ERCP complications and mortality; therefore, use of ERCP in cirrhosis patients should be carefully considered, and further studies on this patient population are needed.

Chest Pain: A Relatively Benign Symptom of Type IV Hiatal Hernia.

Hiatal hernia results from the translocation of intra-abdominal contents from their usual position into the thorax. They can be categorized into type I-IV which implies varying gradations of herniation. The symptomatology can range from just chest pain in the less severe types to respiratory and hemodynamic compromise resulting from strangulation in the advanced hernias. Our patient was an 81-year-old female with a past medical history of gastroesophageal reflux disease (GERD), deep venous thrombosis (DVT), hypertension, hyperlipidemia, coronary artery disease (CAD), and cerebrovascular accident (CVA), who presented to the emergency department (ED) with the chief complaint of chest pain. Assessment of the vitals in the ED revealed a temperature of 37.2 °C, respiratory rate of 18 breaths/minute with an oxygen saturation of 100% on room air, heart rate of 95 beats/min, and blood pressure reading of 132/110 mmHg. Due to significant concern of a possible coronary pathology leading to chest pain, the patient was given 325 mg of aspirin and one tablet of sublingual nitroglycerin. Her electrocardiogram (EKG) was unremarkable but the chest X-ray revealed a large retrocardiac hernia. The finding was corroborated after a review of the computerized tomography (CT) scan performed at the outlying facility. She was treated with omeprazole, a gastroenterologist was consulted, and an esophagogastroduodenoscopy (EGD) performed which revealed significant erosions in the distal esophagus and gastric antrum. She was deemed a high-risk surgical candidate for any intervention and thus managed conservatively with proton pump inhibitor (PPI) therapy. The case highlights the pertinent facts about hiatal hernia. Although the diagnosis of chest pain with the aforementioned comorbidities could be skewed towards coronary pathology, keeping a wide differential is important so that the right diagnosis can be made in a timely fashion and complications avoided.