Ponnada, Suresh

Background: Pouchitis is the most common long-term complication after ileal pouch-anal anastomosis in patients with ulcerative colitis. Those with ≥3 episodes of pouchitis/year and symptoms despite antibiotics are considered to have chronic antibiotic refractory pouchitis (CARP). While several agents including probiotics, steroids and immunomodulators have been used, treatment of CARP remains challenging. We conducted a systematic review and meta-analysis evaluating the safety and efficacy of various biological agents in treatment of CARP. Methods: Multiple databases were searched through June 2020 for studies that reported the efficacy and safety of biological therapy including antitumor necrosis factor-alpha agents [infliximab (IFX) and adalimumab (ADA)], vedolizumab (VDZ), and ustekinumab in CARP. We excluded studies on Crohn’s like and/or other inflammatory complications of the pouch. Meta-analysis was performed to calculate pooled rates of clinical as well as endoscopic improvement and remission. Results: We included 15 studies with 311 patients in our final analysis. Ninety-two patients were treated with IFX, 42 with ADA, 144 with VDZ and 33 with ustekinumab. Pooled rate of clinical improvement was 71.4%, 58.2%, 47.9% and clinical remission was 65.7%, 31%, 47.4% with IFX, ADA, and VDZ, respectively. Pooled rate of endoscopic improvement was achieved in 61.2% patients treated with VDZ while endoscopic remission was achieved in 70.3% patients treated with IFX. Adverse events were reported in 3.9% patients. Conclusion: Biologic therapy is safe and effective in the treatment of CARP.

Abstract Background and study aims Proton pump inhibitors (PPI) are effective medical therapy options for gastro-esophageal reflux disease (GERD). However, 20 % to 40 % of patients report symptoms despite taking daily PPI. Transoral incisionless fundoplication (TIF2) and magnetic sphincter augmentation (MSA) are less invasive options for the treatment of refractory GERD and are increasingly gaining popularity. Methods We conducted a comprehensive search of several databases to identify relevant studies. Our primary aim was to compare the efficacy of both interventions reported as improvement in Gastroesophageal Reflux Disease-Health Related Quality of Life (GERD-HRQL) score, overall patient satisfaction, improvement in post-procedure regurgitation, and fraction of patients completely off PPI therapy at follow up. Results Twenty-four studies with 1942 patients were included in the final analysis. Both MSA and TIF2 had comparable technical success and clinical success based on improvement in GERD-HRQL scores i. e. 98.8 % (CI 95.6,99.7) vs 98.5 % (CI 95.7,99.5) and 80.4 % (CI 66,89.6) vs 77.7 % (CI 64.1,87.2), respectively. A significantly greater proportion of patients reported improvement in regurgitation, i. e. 91.1 % (CI 83.8,95.3) vs 73.1 % (CI 62.5,81.7) and were able to completely discontinue PPI therapy with MSA compared to TIF2 i. e. 91.3 % (CI 81.5,96.2) vs 63.8 % (CI 51.6,74.4). Patients’ BMI and presence of a hiatal hernia did not have any effect on procedural outcomes. Conclusion Both procedures performed at par when comparing clinical success in terms of improvement in GERD-HRQL scores. In terms of overall patient satisfaction, post procedure regurgitation and cumulative number of patients off PPI therapy, MSA outperforms TIF2.

Background: Mucinous pancreatic cysts are well reported to transform into pancreatic adenocarcinoma, whereas nonmucinous cysts are mostly benign with low risk for malignant transformation. Nonsurgical methods of differentiating mucinous and nonmucinous pancreatic cysts are challenging and entail a multi investigational approach. Low intracystic glucose levels have been evaluated in multiple studies for its accuracy in differentiating mucinous from nonmucinous cysts of the pancreas. Methods: Multiple databases were searched and studies that reported on the utility of intracystic glucose levels in diagnosing mucinous pancreatic cysts were analyzed. Meta-analysis was conducted using the random-effects model, heterogeneity was assessed by I 2%, and pooled diagnostic test accuracy values were calculated. Results: Seven studies were included in the analysis from an initial total of 375 citations. The pooled sensitivity of low glucose in differentiating mucinous pancreatic cyst was 90.5% [95% confidence interval (CI): 88.1-92.5; I 2=0%] and the pooled specificity was 88% (95% CI: 80.8-92.7; I 2=79%). The sensitivity at a glucose cut-off of 50 was 90.1% (95% CI: 87.2-92.5; I 2=0%) and the specificity was 85.3% (95% CI: 76.8-91.1; I 2=76%). The sensitivity of glucose levels in pancreatic cyst fluid taken by endoscopic ultrasound guided fine-needle aspiration was 90.8% (95% CI: 87.9-93.1; I 2=0%) and the specificity was 90.5% (95% CI: 81.7-95.3; I 2=83%). The sensitivity of point-of-care glucometers was 89.5% (95% CI: 87.9-93.1; I 2=0%) and specificity was 83.9% (95% CI: 68.5-92.6; I 2=43%). Conclusions: Low glucose level at a cut-off of 50 mg/dL on fluid samples collected by endoscopic ultrasound guided fine-needle aspiration and analyzed by point-of-care glucometer achieves excellent diagnostic accuracy in differentiating mucinous pancreatic cysts.

Abtract Background and study aims Endoscopic and surgical techniques have been utilized for palliation of gastric outlet obstruction (GOO). Enteral stenting (ES) is an established technique with high clinical success and low morbidity rate. Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) is a novel approach that aims to provide sustained palliation of GOO. We conducted a comprehensive review and meta-analysis to evaluate the effectiveness in terms of clinical and technical success, as well as the safety profile of EUS-GE and ES. Methods We searched multiple databases from inception through July 2020 to identify studies that reported on safety and effectiveness of EUS-GE in comparison to ES. Pooled rates of technical success, clinical success, and adverse events (AEs) were calculated. Study heterogeneity was assessed using I2% and 95 % confidence interval. Results Five studies including 659 patients were included in our final analysis. Pooled rate of technical and clinical success for EUS-GE was 95.2 % (CI 87.2-.98.3, I2 = 42) and 93.3 % (CI 84.4–97.3, I2 = 59) while for ES it was 96.9 % (CI 90.9–99, I2 = 64) and 85.6 % (CI 73–92.9, I2 = 85), respectively. Pooled rate of re-intervention was significantly lower with EUS-GE i. e. 4 % (CI 1.8–8.7, I2 = 35) compared to ES, where it was 23.6 % (CI 17.5–31, I2 = 35), p = 0.001. Pooled rates of overall and major AEs were comparable between the two techniques. Conclusion EUS-GE is comparable in terms of technical and clinical effectiveness and has a similar safety profile when compared to ES for palliation of GOO.

Abstract Background Data on efficacy of hepatitis-B vaccine (HBV) in patients with inflammatory bowel disease (IBD) is limited. Our aim was to review the literature and perform meta-analysis of available studies to quantify efficacy of HBV in patients with IBD. Methods We conducted a comprehensive search of several databases (inception to July 2020) to identify studies evaluating efficacy of HBV in patients with IBD. Random effects model was used to calculate the pooled rates and I2 percentage values were used to assess the heterogeneity. Results A total of 14 studies (2375 patients) were included. Four data sets were available from 2 studies that compared HBV response in patients with IBD against healthy controls. The pooled odds ratio of HBV response in IBD patients was 0.13 (95% CI, 0.05–0.33, P = 0.001). The pooled proportion of adequate immune response (AIR) was 64% (95% CI, 55–72.1, P = 0.003) from 13 data sets, and effective immune response (EIR) was 39.7% (95% CI, 30.7–49.5, P = 0.04) from 10 data sets. Conclusion Patients with IBD on immunosuppression demonstrated significantly reduced HBV response as compared with general population.

Abstract Background and study aims Endoscopic ultrasound (EUS)-guided fine-needle aspiration (EUS-FNA) has limitations of inadequate sampling and false-negative results for malignancy. It has been performed using conventional smear (CS) cytology with rapid on-site evaluation (ROSE) with reasonable diagnostic accuracy. An alternative to ROSE is liquid-based cytology (LBC). Commonly used LBC techniques include precipitation-based (SurePath™) and filtration-based (ThinPrep®, CellPrep®). Data regarding the diagnostic efficacy of LBC compared with CS are limited. Methods Multiple databases were searched through March 2020 to identify studies reporting diagnostic yield of EUS-guided CS and LBC in pancreatic lesions. Pooled diagnostic odds and rates of performance for the cytologic diagnoses of benign, suspicious, and malignant lesions were calculated. Diagnostic efficacy was evaluated by pooled rates of accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Results Nine studies with a total of 1308 patients were included in our final analysis. Pooled diagnostic odds of CS cytology were 1.69 (CI 1.02–2.79) and 0.39 (CI 0.19–0.8) for malignant lesions when compared to filtration-based and precipitation-based LBC techniques, respectively. For CS, precipitation-based and filtration-based LBC, pooled diagnostic accuracy was 79.7 %, 85.2 %, 77.3 %, sensitivity was 79.2 %, 83.6 %, 68.3 %, and specificity was 99.4 %, 99.5 %, 99.5 %, respectively. Conclusions The precipitation-based LBC technique (SurePath™) had superior diagnostic odds for malignant pancreatic lesions compared with CS cytology in the absence of ROSE. It showed superior accuracy and sensitivity, but comparable specificity and PPV. Diagnostic odds of CS cytology in the absence of ROSE were superior to the filtration-based LBC technique (ThinPrep®, Cellprep®) for diagnosing malignant pancreatic lesions.

Abstract Background and study aims Recently, a growing body of evidence has been amassed on evaluation of artificial intelligence (AI) known as deep learning in computer-aided diagnosis of gastrointestinal lesions by means of convolutional neural networks (CNN). We conducted this meta-analysis to study pooled rates of performance for CNN-based AI in diagnosis of gastrointestinal neoplasia from endoscopic images. Methods Multiple databases were searched (from inception to November 2019) and studies that reported on the performance of AI by means of CNN in the diagnosis of gastrointestinal tumors were selected. A random effects model was used and pooled accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. Pooled rates were categorized based on the gastrointestinal location of lesion (esophagus, stomach and colorectum). Results Nineteen studies were included in our final analysis. The pooled accuracy of CNN in esophageal neoplasia was 87.2 % (76–93.6) and NPV was 92.1 % (85.9–95.7); the accuracy in lesions of stomach was 85.8 % (79.8–90.3) and NPV was 92.1 % (85.9–95.7); and in colorectal neoplasia the accuracy was 89.9 % (82–94.7) and NPV was 94.3 % (86.4–97.7). Conclusions Based on our meta-analysis, CNN-based AI achieved high accuracy in diagnosis of lesions in esophagus, stomach, and colorectum.

Abstract Background and study aims Endoscopic ultrasound guided pancreatic duct drainage (EUS-PDD) is a minimal-invasive therapeutic option to surgery and in patients with failed endoscopic retrograde pancreatography (ERP). The aim of this review was to quantitatively appraise the clinical outcomes of EUS-PDD by meta-analysis methods. Methods We searched multiple databases from inception through March 2020 to identify studies that reported on EUS-PDD. Pooled rates of technical success, successful drainage of pancreatic duct, clinical success, and adverse events were calculated. Study heterogeneity was assessed using I2% and 95 % prediction interval. Results A total of 22 studies (714 patients) were included. The pooled rate of technical success in EUS-PDD was 84.8 % (95 % CI 79.1–89.2). The pooled rate of successful PD drained by EUS-PDD was 77.5 % (95 % CI 63.1–87.4). The pooled rate of clinical success of EUS-PDD was 89.2 % (95 % CI 82.1–93.7). The pooled rate of all adverse events was 18.1 % (95 % CI 14.2–22.9). On sub-group analysis, the pooled technical success and clinical success of EUS-PDD from Japanese data were considerably superior (91.2 %, 83–95.6 & 92.5 %, 83.9–96.7, respectively). The pooled rate of post EUS-PDD acute pancreatitis was 6.6 % (95 % CI 4.5–9.4), bleeding was 4.1 % (95 % CI 2.7–6.2), perforation and/or pneumoperitoneum was 3.1 % (95 % CI 1.9–5), pancreatic leak and/or pancreatic fluid collection was 2.3 % (95 % CI 1.4–4), and infection was 2.8 % (95 % CI 1.7–4.6). Conclusion EUS-PDD demonstrates high technical success and clinical success rates with acceptable adverse events. Technical success was especially high for anastomotic strictures.

Abstract Background and study aims Refractory and recurrent esophageal variceal (EV) bleeding can be life threatening. Self-expanding metal stents (SEMS) have been used as a “bridge” therapy. However, their role in the treatment protocol is not established due to paucity in data. Methods We searched multiple databases from inception through May 2019 to identify studies that reported on SEMS and TIPS in refractory EV hemorrhage. Our primary goals were to analyze and compare the pooled all-cause mortality, immediate bleeding control and rebleeding rates. Results Five hundred forty-seven patients from 21 studies were analyzed (SEMS: 12 studies, 176 patients; TIPS: 9 studies, 398 patients). The pooled rate of all-cause mortality with SEMS was 43.6 % (95 % CI 28.6–59.8, I2 = 38) and with TIPS was 27.9 % (95 % CI 16.3–43.6, I2 = 91). The pooled rate of immediate bleeding control with SEMS was 84.5 % (95 % CI 74–91.2, I2 = 40) and with TIPS was 97.9 % (95 % CI 87.7–99.7, I2 = 0). The pooled rate of rebleeding with SEMS was 19.4 % (95 % CI 11.9–30.4, I2 = 32) and with TIPS was 8.8 % (95 % CI 4.8–15.7, I2 = 40). Conclusion Use of SEMS in refractory EV hemorrhage demonstrates acceptable immediate bleeding control with good technical success rate. Mortality and rebleeding rates were lesser with TIPS, however, its superiority and/ or inferiority cannot be validated due to limitations in the comparison methodology.