Malondialdehyde-Acetaldehyde Extracellular Matrix Protein Adducts Attenuate Unfolded Protein Response During Alcohol and Smoking-Induced Pancreatitis.

BACKGROUND & AIMS: Epidemiological studies have established alcohol and smoking as independent risk factors for recurrent acute pancreatitis and chronic pancreatitis. However, the molecular players responsible for the progressive loss of pancreatic parenchyma and fibroinflammatory response are poorly characterized. METHODS: Tandem mass tag-based proteomic and bioinformatics analyses were performed on the pancreata of mice exposed to alcohol, cigarette smoke, or a combination of alcohol and cigarette smoke. Biochemical, immunohistochemistry, and transcriptome analyses were performed on the pancreatic tissues and primary acinar cells treated with cerulein in combination with ethanol (50 mmol/L) and cigarette smoke extract (40 µg/mL) for the mechanistic studies. RESULTS: A unique alteration in the pancreatic proteome was observed in mice exposed chronically to the combination of alcohol and cigarette smoke (56.5%) compared with cigarette smoke (21%) or alcohol (17%) alone. The formation of toxic metabolites (P < .001) and attenuated unfolded protein response (P < .04) were the significantly altered pathways on combined exposure. The extracellular matrix (ECM) proteins showed stable malondialdehyde-acetaldehyde (MAA) adducts in the pancreata of the combination group and chronic pancreatitis patients with a history of smoking and alcohol consumption. Interestingly, MAA-ECM adducts significantly suppressed expression of X-box-binding protein-1, leading to acinar cell death in the presence of alcohol and smoking. The stable MAA-ECM adducts persist even after alcohol and smoking cessation, and significantly delay pancreatic regeneration by abrogating the expression of cyclin-dependent kinases (CDK7 and CDK5) and regeneration markers. CONCLUSIONS: The combined alcohol and smoking generate stable MAA-ECM adducts that increase endoplasmic reticulum stress and acinar cell death due to attenuated unfolded protein response and suppress expression of cell cycle regulators. Targeting aldehyde adducts might provide a novel therapeutic strategy for the management of recurrent acute pancreatitis and chronic pancreatitis.

Adenoma and polyp detection rates during insertion versus withdrawal phase of colonoscopy: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Colonoscopy is the preferred modality for colorectal cancer screening because it has both diagnostic and therapeutic capabilities. Current consensus states that colonoscopy should be performed with initial rapid passage of the instrument to the cecum, followed by thorough evaluation for and removal of all polyps during a deliberate slow withdrawal. Reports have suggested that polyps that are seen but not removed during insertion are sometimes quite difficult to find during withdrawal. METHODS: We performed a comprehensive literature search of several major databases (from inception to March 2020) to identify randomized controlled trials comparing inspection and polypectomy during the insertion phase as opposed to the traditional practice of inspection and polypectomy performed entirely during the withdrawal phase. We examined differences in terms of adenoma detection rate (ADR), polyps detected per patient (PDPP), cecal intubation time (CIT), withdrawal time, and total procedure time. RESULTS: Seven randomized controlled trials, including 3834 patients, were included in our final analysis. The insertion/withdrawal cohort had 1951 patients and the withdrawal-only cohort 1883 patients. Pooled odds of adenoma detection in the insertion/withdrawal cohort was .99 (P = .8). ADR was 47.2% in the insertion/withdrawal cohort and 48.6% in the withdrawal-only cohort. Although total procedure and withdrawal times were shorter in the insertion/withdrawal cohort, PDPP in both cohorts were not statistically significant (1.4 vs 1.5, P = .7). CONCLUSIONS: Additional inspection and polypectomy during the insertion and withdrawal phases of colonoscopy offer no additional benefit in terms of ADR or PDPP.

Clinical efficacy of per-oral endoscopic myotomy (POEM) for spastic esophageal disorders: a systematic review and meta-analysis.

BACKGROUND: POEM has been successfully performed in patients with spastic esophageal disorders (SED), such as diffuse esophageal spasm, jackhammer esophagus, and type 3 achalasia. We performed a systematic review and meta-analysis to evaluate its efficacy in these patients and if total average myotomy length and prior medical or endoscopic treatments affected clinical success. METHODS: PubMed, EMBASE, Google-Scholar, Scopus, and Cochrane Review were searched for studies on POEM in SED from 2008 to September 2018. Clinical success was determined by Eckardt score (≤ 3) at follow-up. Sub-group analysis was performed based on myotomy length and evaluates the effect of prior treatments on clinical success. RESULTS: 9 studies with 210 patients were included in the final analysis. We found that the pooled rate of clinical success for POEM was 89.6% (95% CI 83.5-93.1, 95% PI 83.4-93.7, I2 = 0%). In three studies (50 patients), where total myotomy length was < 10 cm, the pooled rate of clinical success was 91.1% (95% CI 79.5-96.4, I2 = 0%). In six studies (160 patients), the length was > 10 cms and the pooled rate of clinical success was 89.1% (95% CI 83.0-93.2, I2 = 0%). The difference between these results was not statistically significant (p = 0.69). Additionally, a meta-regression analysis showed that prior treatment status did not significantly affect the primary outcome (p = 0.43). CONCLUSIONS: While it is well known that POEM is a safe and effective treatment for spastic esophageal disorders, we conclude that variation in total myotomy length and prior endoscopic or medical treatments did not have a significant effect on clinical success.

Lumen-apposing Metal Stents, Fully Covered Self-expanding Metal Stents, and Biodegradable Stents in the Management of Benign of GI Strictures: A Systematic Review and Meta-Analysis.

BACKGROUND: Refractory benign gastrointestinal (GI) strictures are difficult to treat and placement of a stent is a commonly sought resort. Stents used for this purpose are fully covered self-expanding metal stent (FCSEMS), a biodegradable stent (BDS) and recently, a lumen-apposing metal stent (LAMS). There is no data comparing these stents to this end. METHODS: We conducted a comprehensive search of multiple electronic databases and conference proceedings (from inception through October 2018) to identify studies that reported on the performance of FCSEMS, BDS, and LAMS in the treatment of refractory benign GI strictures. Our goals were to evaluate the pooled rate of technical success, clinical success, and adverse events with these stents and compare the outcomes between them. RESULTS: A total of 31 studies were analyzed. In total, 14 (342 patients), 11 (226 patients), and 8 studies (192 patients) reported the use of FCSEMS, BDS, and LAMS, respectively. The pooled rate of technical success was 96.5% [95% confidence interval (CI): 93.5-98.1], 91.9% (95% CI: 85.6-95.6), and 97.6% (95% CI: 94.0-99.0) with FCSEMS, BDS, and LAMS respectively. No statistical significance to the difference was noted. The pooled rate of clinical success was 48.4% (95% CI: 37.1-59.8), 34.9% (95% CI: 23.6-48.1), and 78.8% (95% CI: 65.8-87.8) with FCSEMS, BDS, and LAMS, respectively. Statistical significance was noted in LAMS versus FCSEMS (P=0.001) and LAMS versus BDS (P=0.001). LAMS demonstrated statistically better outcomes in regards to stent migration and postprocedure pain when compared with FCSEMS and BDS. CONCLUSION: Our study demonstrates that LAMS gives better clinical outcomes in the treatment of refractory benign GI strictures when compared with FCSEMS and BDS. Variability in the site, as well as the length of stricture, indirect comparison, and heterogeneity, were the limitations of our study.

Periampullary Diverticula and ERCP Outcomes: A Systematic Review and Meta-Analysis.

INTRODUCTION: Periampullary diverticulum (PAD) is most often asymptomatically found in elderly population. ERCP in the presence of PAD is technically challenging since the location and orientation of the ampulla could be altered. Various studies have reported differing results on the technical success and safety outcomes of ERCP in the presence of PAD. We aimed at a meta-analysis of such studies to assess the technical success and the occurrence of complications during ERCP in patients with PAD. METHODS: We conducted a comprehensive search of several databases and conference proceedings including PubMed, EMBASE, and Web of Science databases (earliest inception to October 2017). The search was done in accordance with PRISMA guidelines to identify studies. Studies that reported on the ERCP outcomes based on the presence of PAD were included. Both prospective and retrospective studies, manuscripts and abstracts were included. Only articles in English literature were included. The primary analysis focused on the overall technical success of ERCP in the presence of PAD, and the secondary analysis was to estimate the risk of occurrence of complications. RESULTS: Our search resulted in 16 studies that were included for final analysis. These 16 studies reported on 2794 patients, who had PAD, and the control group included 13,032 patients, who did not have a PAD during ERCP. Our meta-analysis of this data showed an Odd's ratio estimate of having a successful ERCP procedure in patients with PAD to be 0.51 [95% C.I. (0.35-0.72)] when compared to patients without it. This was statistically significant, with a p value 0.00. Considerable heterogeneity was noted among the studies. The heterogeneity proportion was quantified at 74.6% based on I2 statistic. The secondary outcomes measured were complications. We analyzed the pooled Post-ERCP Pancreatitis (PEP), cholangitis, perforation, and bleeding. Only those studies that had the data for these complications in both the study and the control groups were selected. PEP: The pooled Odd's estimate of having PEP was 1.28, [95% C.I (0.88-1.87)] from 12 studies reporting on 1863 patients with PAD in comparison with 7803 patients without it. The risk of PEP occurrence tended to be more in the group without PAD, though it was not statistically significant, with a p value 0.20. There was some heterogeneity observed between the studies, with the quantification I2 statistic being 28.6%. Our analysis shows that having PAD does not put a patient at increased risk for PEP. Bleeding: The pooled Odds estimate was 1.69, 95% C.I. 0.88-3.25 from nine studies reporting on 1816 patients with PAD in comparison with 5327 patients without it. This was not statistically significant, p value 0.11. Considerable heterogeneity was noted, with I2 being 55.7%. The risk of having a bleed was noted to be more in control group, and having PAD did not put patients at increased risk for bleeding during an ERCP procedure. Perforation: Patients with PAD undergoing ERCP were not at increased risk for perforation. Seven studies reported on this complication. This was noted in seven patients out of 1245 in study group, and 19 patients out of 4912 in control group. The pooled Odd's estimate was 1.24, 95% C.I. 0.54-2.87. There was no statistical significance, p value 0.61. No heterogeneity was noted among the studies included in this analysis. Cholangitis: Only four studies reported on this complication. In a total of 778 patients in study group, four had cholangitis and eight had this complication out of 3886 patients in the control group. The pooled Odd's was 2.12, 95% C.I. 0.61-7.33. There was no statistical significance, p value 0.24. No heterogeneity was noted. CONCLUSION: ERCP is technically feasible and increasingly successful when performed by experts in the presence of PAD. The risk of complications such as PEP, bleeding, perforation and cholangitis does not differ between ERCP done in patients with and without PAD.

Effects of the 2009 Medical Cannabinoid Legalization Policy on Hospital Use for Cannabinoid Dependency and Persistent Vomiting.

BACKGROUND & AIMS: In 2009, the U.S. Department of Justice issued a memo stating that it would not prosecute users and sellers who complied with the state laws allowing for medical use of marijuana. There are growing concerns about legalization of marijuana use and its related public health effects. We performed an interrupted time series analysis to evaluate these effects. METHODS: We collected a representative sample of hospital discharge data from the Healthcare Cost and Utilization Project, from January 1993 to December 2014. We divided the data in to 3 groups: the prelegalization period (1993-2008), the legalization period (2009), and the postlegalization period (2010-2014). The disease variables were International Classification of Disease-Ninth Revision-Clinical Modification 304.30 cannabinoid dependency unspecified (CDU), 536.2 persistent vomiting, and an aggregate of CDU and persistent vomiting. We performed interrupted time series and Poisson-Gamma regression analysis to calculate each year's incidence rate of unspecified and persistent vomiting and CDU per 100,000 hospital discharges. CDU, persistent vomiting, and aggregate of CDU and persistent vomiting were modeled separately to estimate average incidence rate ratio and 95% confidence interval for each study phase. RESULTS: We observed an increasing trend of CDU or an aggregate of CDU and persistent vomiting during the prelegalization period. The legalization of marijuana significantly increased the incidence rate during the legalization period (by 17.9%) and the yearly average increase in rate by 6% after policy implementation, compared to the prelegalization period. The increase in rate of persistent vomiting after policy implementation increased significantly (by about 8%), although there were no significant trends in increase prior to or during marijuana legalization in 2009. CONCLUSIONS: In an interrupted time series analysis of before, during, and after medical marijuana legalization, we estimated levels and rate changes in CDU and persistent vomiting. We found persistent increases in rates of CDU and persistent vomiting during and after legalization of marijuana.

Efficacy of EUS-guided needle-based confocal laser endomicroscopy in the diagnosis of pancreatic lesions: A systematic review and meta-analysis.

Background and Objectives: Needle-based confocal laser endomicroscopy (nCLE) is a procedure in which an AQ-Flex nCLE mini-probe is passed through an EUS-FNA needle into a pancreatic lesion to enable subsurface in vivo tissue analysis. In this study, we conducted a systematic review and meta-analysis of nCLE for the diagnosis of pancreatic lesions. Materials and Methods: We conducted a comprehensive search of several databases and conference proceedings, including PubMed, EMBASE, Google-Scholar, MEDLINE, SCOPUS, and Web of Science databases (earliest inception to March 2020). The primary outcomes assessed the pooled rate of diagnostic accuracy for nCLE and the secondary outcomes assessed the pooled rate of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and adverse events (AE) of nCLE to diagnose premalignant/malignant pancreatic lesions. Results: Eleven studies on 443 patients were included in our analysis. The pooled rate of diagnostic accuracy of EUS nCLE was 83% (95 confidence interval [CI] = 79-87; I 2 = 0). The pooled rate of sensitivity, specificity, PPV and NPV of EUS nCLE was 85.29% (95% CI = 76.9-93.68; I 2 = 85%), 90.49% (95% CI = 82.24-98.74; I 2 = 64%), 94.15% (95% CI = 88.55-99.76; I 2 = 68%), and 73.44% (95% CI = 60.16-86.72; I 2 = 93%), respectively. The total AE rate was 5.41% (±5.92) with postprocedure pancreatitis being the most common AE at 2.28% (±3.73). Conclusion: In summary, this study highlights the rate of diagnostic accuracy, sensitivity, specificity, and PPV for distinguishing premalignant/malignant lesions. Pancreatic lesions need to be further defined with more validation studies to characterize CLE diagnosis criteria and to evaluate its use as an adjunct to EUS-FNA.

Safety and efficacy of EUS-guided ablation of pancreatic lesions with ethanol versus ethanol with paclitaxel: A systematic review and meta-analysis.

Background and Objectives: EUS-guided ethanol ablation has emerged as an alternative method for pancreatic lesions. Recently, paclitaxel was added to ethanol to assess ablative effects in pancreatic lesions. We performed a systematic review and meta-analysis on EUS-guided ethanol ablation (EUS E) versus EUS-guided ethanol with paclitaxel (EUS EP) ablation for the management of pancreatic lesions. Methods: Comprehensive search of multiple electronic databases and conference proceedings including PubMed, EMBASE, Google Scholar, and Web of Science databases (from inception to May 2020). The primary outcome evaluated complete ablation of the lesions radiologically and the secondary outcome evaluated adverse events (AEs). Results: Fifteen studies on 524 patients were included in our analysis. The pooled complete ablation rate was 58.89% (95% confidence interval (CI) = 38.72-77.80, I2 = 91.76%) and 55.99% (95% CI = 44.66-67.05, I2 = 0) in the EUS E and EUS EP groups (P = 0.796), respectively. The pooled AE rates were 13.92% (95% CI = 4.71-26.01, I2 = 83.43%) and 31.62% (95% CI = 3.36-68.95, I2 = 87.9%) in the EUS E and EUS EP groups (P = 0.299), respectively. The most common AE was abdominal pain at 7.27% (95% CI = 1.97-14.6, I2 = 68.2%) and 12.44% (95% CI = 0.00-39.24, I2 = 81.1%) in the EUS E and EUS EP groups (P = 0.583), respectively. Correlation coefficient (r) was ‒0.719 (P = 0.008) between complete ablation and lesion size. Conclusion: Complete ablation rates were comparable among both groups. AE rates were higher in the EUS EP group. Further randomized controlled trials are needed to validate our findings.

Endoscopic cryotherapy: Indications, techniques, and outcomes involving the gastrointestinal tract.

Endoscopic cryotherapy is a technique utilized for the ablation of target tissue within the gastrointestinal tract. A cryotherapy system utilizes the endoscopic application of cryogen such as liquid nitrogen, carbon dioxide or liquid nitrous oxide. This leads to disruption of cell membranes, apoptosis, and thrombosis of local blood vessels within the target tissue. Several trials utilizing cryotherapy for Barrett's esophagus (BE) with variable dysplasia, gastric antral vascular ectasia (GAVE), esophageal carcinoma, radiation proctitis, and metastatic esophageal carcinomas have shown safety and efficacy. More recently, liquid nitrogen cryotherapy (cryodilation) was shown to be safe and effective for the treatment of a benign esophageal stricture which was refractory to dilations, steroid injections, and stenting. Moreover, liquid nitrogen cryotherapy is associated with less post procedure pain as compared to radiofrequency ablation in BE with comparable ablation rates. In patients with GAVE, cryotherapy was found to be less tedious as compared to argon plasma coagulation. Adverse events from cryotherapy most commonly include chest pain, esophageal strictures, and bleeding. Gastric perforations did occur as well, but less often. In summary, endoscopic cryotherapy is a promising and growing field, which was first demonstrated in BE, but the use now spans for several other disease processes. Larger randomized controlled trials are needed before its role can be established for these different diseases.

Endo-sponge in management of anastomotic colorectal leaks: a systematic review and meta-analysis.

Background and study aims Following colorectal surgery, anastomotic dehiscence and leak formation has an incidence of 2 % to 7 %. Endo-SPONGE has been applied in the management of anastomatic leaks (ALs) after colorectal surgery. This is the first systematic review and meta analysis to evaluate the efficacy and safety of Endo-SPONGE in the management of colorectal ALs. Patients and methods The primary outcomes assessed were the technical and clinical success of Endo-SPONGE placement in colorectal ALs. The secondary outcomes assessed were the overall adverse events (AEs) and the AE subtypes. Pooled estimates were calculated using random-effects models with 95 % confidence interval (C. I.). The statistical analysis was done using STATA v16.1 software (StataCorp, LLC College Station, Texas, United States). Results The analysis included 17 independent cohort studies with a total of 384 patients. The rate of technical success was 99.86 % (95 % CI: 99.2 %, 100 %; P  = 0.00; I 2  = 70.69 %) and the calculated pooled rate of clinical success was 84.99 % (95 % CI: 77.4 %, 91.41 %; P  = 0.00; I 2  = 68.02 %). The calculated pooled rate of adverse events was 7.6 % (95 % CI: 3.99 %, 12.21 %; P  = 0.03; I 2  = 42.5 %) with recurrent abscess formation and bleeding being the most common AEs. Moderate to substantial heterogeneity was noted in our meta-analysis. Conclusions Endoscopic vacuum therapy appears to be a minimally invasive, safe, and effective treatment modality for patients with a significant colorectal leak without any generalized peritonitis with high clinical and technical success rates and a low rate of adverse events. Further prospective or randomized controlled trials are needed to validate our findings.

Choice of sedation in endoscopic retrograde cholangiopancreatography: is monitored anesthesia care as safe as general anesthesia? A systematic review and meta-analysis.

BACKGROUND: Monitored anesthesia care (MAC) and general anesthesia (GA) are the 2 most common methods of sedation used for endoscopic retrograde cholangiopancreatography (ERCP). We performed a systematic review and meta-analysis to compare the overall safety between MAC vs. GA in ERCP. METHODS: We conducted a comprehensive search of electronic databases to identify studies reporting the use of MAC or GA as a choice of sedation for ERCP. The primary outcome was to compare the overall rate of sedation-related adverse events in MAC vs. GA groups. The secondary endpoint was to investigate the total duration of the procedure, recovery time, ERCP cannulation rates, and conversion rate of MAC to GA. The meta-analysis was performed using a Der Simonian and Laird random-effects model. RESULTS: A total of 21 studies reporting on 11,592 patients were included. The overall sedation-related side-effects were similar in the GA (12.76%, 95% confidence interval [CI] 5.80-21.73; I2=95%) and MAC (12.08%, 95%CI 5.38-20.89; I2=99%) groups (P=0.956). Hypoxia, arrhythmias, hypotension, aspiration and other sedation-related side-effects were similar between the 2 groups. The mean duration of the procedure was longer in the MAC group, but the mean recovery time was shorter. Significant heterogeneity was noted in our meta-analysis. CONCLUSIONS: In our meta-analysis, the overall sedation-related side-effects were similar between the MAC and GA groups. MAC could be used as a safer alternative to GA when performing ERCP. However, large multicenter randomized control trials are needed to further validate our findings.

Reversal of anti-drug antibodies against tumor necrosis factor inhibitors with addition of immunomodulators: A systematic review and meta-analysis.

BACKGROUND: The development of anti-drug antibodies (ADA) to tumor necrosis factor (TNF-α) inhibitors is a significant result contributing to the loss of clinical response in inflammatory bowel disease (IBD). AIMS: We performed a systematic review and meta-analysis to assess whether the addition of immunomodulators to TNF-α inhibitors lead to reversal of antibody formation in TNF-α inhibitor-treated IBD patients. METHODS: We conducted a comprehensive search of electronic databases from inception through October 2018 in order to identify specific studies describing clinical response in IBD patients following the addition of immunomodulators (methotrexate or thiopurines) to TNF-α inhibitors. Clinical response was expressed as an improvement of symptoms, with a noted decrease or complete elimination of ADA against TNF-α inhibitors. The meta-analysis was performed using the DerSimonian and Laird random-effect model. RESULTS: Four studies were included in our final meta-analysis, which reported outcomes in 72 patients receiving TNF-α inhibitors. Forty-nine of the seventy-two (68%) patients received either methotrexate (19) or thiopurines (30). The average follow up period was 13.5 months. The overall pooled clinical response was 73.86% (95% confidence interval [CI] = 47.36-94.38, I2 = 60.77%). CONCLUSION: In our meta-analysis, addition of immunomodulators to TNF-α inhibitors was shown to restore the clinical response in 74% of the patients by either decreasing or completely eliminating anti-drug antibody levels. Further long-term multicenter studies are needed to validate these findings.

Diagnostic yield of deep biopsy via endoscopic submucosal dissection for the diagnosis of upper gastrointestinal subepithelial tumors: a systematic review and meta-analysis.

BACKGROUND: Conventionally, endoscopic ultrasound-guided fine-needle aspiration and biopsy (EUS-FNA)/EUS-FNB) has been used for tissue diagnosis of upper gastrointestinal (GI) subepithelial tumors (SETs). However, deep biopsy (DB) via endoscopic submucosal dissection (ESD) is emerging as an alternative technique, given the inadequate tissue sampling with EUS-FNA/EUS-FNB. Our aim was to conduct a systematic review and meta-analysis to report the overall diagnostic yield of DB via ESD for upper GI SETs. METHODS: PubMed, Cochrane Library and Web of Science databases were searched to identify studies (from commencement to Oct 2017) that reported the DB via ESD technique for diagnosis of upper GI SETs. The primary outcome of interest was the method's overall diagnostic yield and the secondary outcome was to the occurrence of complications. The meta-analysis was performed using the DerSimonian and Laird random-effects model. RESULTS: A total of 7 studies, comprising 209 patients with a mean age of 57.3 years, were included in the final meta-analysis. The overall pooled diagnostic yield of DB via ESD for upper GI SETs was 95% (95% confidence interval [CI] 84.91-99.98, I2=78.2%). Overall, pooled outcomes of major bleeding and perforation in our meta-analysis was noted in 0.07% (95%CI 0.00-2.32, I2=0%) and 0% (95%CI 0.00-1.70, I2=0%) respectively. Data regarding major bleeding and perforation rates were not reported in 2 studies. Substantial heterogeneity was observed in our meta-analysis. CONCLUSION: DB via ESD is an effective and safe procedure for diagnosing upper GI SETs. Further multicenter randomized controlled trials are needed to validate these findings.

Efficacy of pancreatoscopy for pancreatic duct stones: A systematic review and meta-analysis.

BACKGROUND: Pancreatic duct stones can lead to significant abdominal pain for patients. Per oral pancreatoscopy (POP)-guided intracorporal lithotripsy is being increasingly used for the management of main pancreatic duct calculi (PDC) in chronic pancreatitis. POP uses two techniques: Electrohydraulic lithotripsy (EHL) and laser lithotripsy (LL). Data on the safety and efficacy are limited for this procedure. We performed a systematic review and meta-analysis with a primary aim to calculate the pooled technical and clinical success rates of POP. The secondary aim was to assess pooled rates of technical success, clinical success for the two individual techniques, and adverse event rates. AIM: To perform a systematic review and meta-analysis of POP, EHL and LL for management of PDC in chronic pancreatitis. METHODS: We conducted a comprehensive search of multiple electronic databases and conference proceedings including PubMed, EMBASE, Cochrane, Google Scholar and Web of Science databases (from 1999 to October 2019) to identify studies with patient age greater than 17 and any gender that reported on outcomes of POP, EHL and LL. The primary outcome assessed involved the pooled technical success and clinical success rate of POP. The secondary outcome included the pooled technical success and clinical success rate for EHL and LL. We also assessed the pooled rate of adverse events for POP, EHL and LL including a subgroup analysis for the rate of adverse event subtypes for POP: Hemorrhage, post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP), perforation, abdominal pain, fever and infections. Technical success was defined as the rate of clearing pancreatic duct stones and clinical success as the improvement in pain. Random-effects model was used for analysis. Heterogeneity between study-specific estimates was calculated using the Cochran Q statistical test and I 2 statistics. Publication bias was ascertained, qualitatively by visual inspection of funnel plot and quantitatively by the Egger test. RESULTS: A total of 16 studies including 383 patients met the inclusion criteria. The technical success rate of POP was 76.4% (95%CI: 65.9-84.5; I 2 = 64%) and clinical success rate was 76.8% (95%CI: 65.2-85.4; I 2 = 66%). The technical success rate of EHL was 70.3% (95%CI: 57.8-80.3; I 2 = 36%) and clinical success rate of EHL was 66.5% (95%CI: 55.2-76.2; I 2 = 19%). The technical success rate of LL was 89.3% (95%CI: 70.5-96.7; I 2 = 70%) and clinical success rate of LL was 88.2% (95%CI: 66.4-96.6; I 2 = 77%). The incidence of pooled adverse events for POP was 14.9% (95%CI: 9.2-23.2; I 2 = 49%), for EHL was 11.2% (95%CI: 5.9-20.3; I 2 = 15%) and for LL was 13.1% (95%CI: 6.3-25.4; I 2 = 31%). Subgroup analysis of adverse events showed rates of PEP at 7% (95%CI: 3.5-13.6; I 2 = 38%), fever at 3.7% (95%CI: 2-6.9; I 2 = 0), abdominal pain at 4.7% (95%CI: 2.7-7.8; I 2 = 0), perforation at 4.3% (95%CI: 2.1-8.4; I 2 = 0), hemorrhage at 3.4% (95%CI: 1.7-6.6; I 2 = 0) and no mortality. There was evidence of publication bias based on funnel plot analysis and Egger's test. CONCLUSION: Our study highlights the high technical and clinical success rates for POP, EHL and LL. POP-guided lithotripsy could be a viable option for management of chronic pancreatitis with PDC.

Efficacy of EUS-RFA in pancreatic tumors: Is it ready for prime time? A systematic review and meta-analysis.

Background and study aims Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) can be used in patients with unresectable pancreatic ductal adenocarcinoma (PDAC). We performed a systematic review and meta-analysis to evaluate the efficacy of EUS-RFA in treatment of locally advanced unresectable PDAC and other pancreatic tumors. Patients and methods A comprehensive search was done of multiple electronic databases and conference proceedings including PubMed, EMBASE, Web of Science databases, Google Scholar and manual search of references (from inception through May 2019) to identify the studies reporting use of EUS-RFA for pancreatic lesions. The primary outcome was to evaluate technical and clinical success of the procedure. The secondary outcome was to study overall adverse events (AEs). Results Thirteen studies reporting 165 EUS-RFA procedures on 134 patients were included. Of 134 patients, 27.94 % (38) had unresectable locally advanced PDAC, 40 % (53) had PNETs, 3 % (4) had metastasis to the pancreas and 30 % (41) had other lesions. The pooled technical success rate calculated out of the total number of procedures was 100 % (95 % CI [99.18 - 100], I2 = 0 %). The pooled clinical success rate calculated out of the total number of patients was 91.58 % (95 % CI [82.5 - 98.08], I2 = 21.5 %). The pooled overall AE rates were 14.67 % (95 % CI [4.77 - 27.46], I2 = 56.19 %) out of which abdominal pain was the most common with 9.82 % (95 % CI [3.34 - 18.24], I2 = 23.76 %). Low to moderate heterogeneity was noted. Conclusion EUS-RFA has high technical (100 %) and clinical success (91.5 %) rates. Further multicenter trials are needed to further validate our findings.

EUS-guided biliary drainage: A systematic review and meta-analysis.

ERCP is the current procedure of choice for patients with jaundice caused by biliary obstruction. EUS-guided biliary drainage (EUS-BD) has emerged as an alternative to ERCP in patients requiring biliary drainage. The aim of the study was to conduct a systematic review and meta-analysis to report the overall efficacy and safety of EUS-BD. We conducted a comprehensive search of several databases including PubMed, EMBASE, Web of Science, Google Scholar, and LILACS databases (earliest inception to June 2018) to identify studies that reported EUS-BD in patients. The primary outcome was to look at the technical and clinical success of the procedure. The secondary analysis focused on calculating the pooled rate of re-interventions and all adverse-events, along with the commonly reported adverse-event subtypes. Twenty-three studies reporting on 1437 patients were identified undergoing 1444 procedures. Majority of the patient population were male (53.86%), with an average age of 67.22 years. The pooled technical success rates and clinical success rates were 91.5% (95% confidence interval [CI]: 87.7-94.2, I[2] = 76.5) and 87% (95% CI: 82.3-90.6, I[2] = 72.4), respectively. The total adverse event rates were 17.9% (95% CI: 14.3-22.2, I[2] = 69.1). Subgroup analysis of three major individual adverse events was bile leak: 4.1% (2.7-6.2, I[2] = 46.7), stent migration: 3.9% (2.5-6.2, I[2] = 43.5), and infection: 3.8% (2.8-5.1, I[2] = 0) Substantial heterogeneity was noted in the analysis. EUS-BD has high technical and clinical success rate and hence a very effective procedure. Concerns about publication bias exist. Careful consideration should be given to the adverse events and weighing the risks and benefits of the alternative nonsurgical/surgical approaches.

Clinical efficacy and safety of palliative esophageal stenting without fluoroscopy: a systematic review and meta-analysis.

Background and study aims Despite advances in curative treatments for esophageal cancer, many patients often present with advanced disease. Dysphagia resulting in significant weight loss and malnutrition leads to poor quality of life. Palliative esophageal stenting with self-expanding metal stents (SEMS) helps alleviate symptoms and prolongs survival. However, access to fluoroscopy may be limited at certain centers causing delay in patient care. Methods We searched multiple databases from inception to November 2019 to identify studies evaluating the efficacy and safety of endoscopic palliative esophageal stenting and selected only those studies where fluoroscopic guidance was not used. Our primary aim was to calculate the overall technical as well as clinical success. Using meta-regression analysis, we also evaluated the effect of tumor location and obstruction length on overall technical and clinical success. Results A total of 1778 patients from 17 studies were analyzed. A total of 2036 stents were placed without the aid of fluoroscopy. The pooled rate of technical success was 94.7 % (CI 89.9-97.3, PI 55-99; I 2  = 85) and clinical success was 82.1 % (CI 67.1-91.2, PI 24-99; I 2  = 87). Based on meta-regression analysis both the length of obstruction and tumor location did not have any statistically significant effect on technical and clinical success. The pooled rate of adverse events was 4.1 % (CI 2.4-7.2; I 2  = 72) for stent migration, 8.1 % (CI 4.1-15.4; I 2  = 89) for tumor overgrowth and 1.2 % (CI 0.7-2; I 2  = 0) for perforation. The most frequent clinical adverse event was retro-sternal chest pain. Conclusion Palliative esophageal stenting without fluoroscopy using SEMS is both safe and effective in patients with advanced esophageal cancer.

EDGE in Roux-en-Y gastric bypass: How does it compare to laparoscopy-assisted and balloon enteroscopy ERCP: a systematic review and meta-analysis.

Background and study aims Endoscopic ultrasound-directed transgastric ERCP (EDGE) is a new endoscopic procedure to perform ERCP in Roux-en-y gastric bypass (RYGB) patients. The aim of this study was to conduct a systematic review and meta-analysis to evaluate technical success, clinical success and adverse effects of EDGE and compare it to laparoscopic ERCP (LA-ERCP) and balloon ERCP (BE-ERCP). Patients and methods We conducted a comprehensive search of several databases and conference proceedings including PubMed, EMBASE, Google-Scholar, LILACS, SCOPUS, and Web of Science databases to identify studies reporting on EDGE, LA-ERCP, and BE-ERCP. The primary outcome was to evaluate technical and clinical success of all three procedures and the secondary analysis focused on calculating the pooled rate of all adverse events (AEs), along with the commonly reported AE subtypes. Results Twenty-four studies on 1268 patients were included in our analysis with the majority of the population being males with mean age 53.72 years. Pooled rates of technical and clinical success with EDGE wer 95.5 % and 95.9 %, with LA-ERCP were 95.3 % and 92.9 % and were BE-ERCP were 71.4 % and 58.7 %, respectively. Pooled rates of all AEs with EDGE were 21.9 %, with LA-ERCP 17.4 % and with BE-ERCP 8.4 %. Stent migration was the most common AE with EDGE with 13.3 % followed by bleeding with 6.6 %. Conclusion Our meta-analysis demonstrated that the technical and clinical success of EDGE procedure is better than BE-ERCP and comparable to that of LA-ERCP in RYGB patients. EDGE also has a similar safety profile as compared to LA-ERCP but has higher AE rate as compared to BE-ERCP.

Comparison of EUS-guided conventional smear and liquid-based cytology in pancreatic lesions: A systematic review and meta-analysis.

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.

Safety and efficacy of combined antegrade and retrograde endoscopic dilation for complete esophageal obstruction: a systematic review and meta-analysis.

BACKGROUND: Complete esophageal obstruction (CEO) due to occlusive proximal stricture occurs after chemoradiation for head and neck cancers. A combined antegrade and retrograde endoscopic technique with controlled recanalization and dilation (CARD) has been shown to be an effective and safe method for regaining and maintaining esophageal luminal patency in the short term. METHODS: We conducted a comprehensive search of multiple electronic databases and conference proceedings, including PubMed, EMBASE, and Web of Science databases (from inception through November 2018), to identify studies that reported the outcomes of CARD. The primary outcomes were the pooled rates of technical and clinical success, specifically improvement in dysphagia and independence from percutaneous endoscopic gastrostomy (PEG)-tube feeds. The secondary outcomes were the need for repeat dilations and the risks of complications, such as pneumomediastinum, perforation, and death. RESULTS: From a total of 19 studies (229 cases and 251 procedures) the calculated technical success rate was 88.9% (95% confidence interval [CI] 83.9-92.5, I 2=0). The rates of improvement in dysphagia and being PEG-tube free were 58.4% (95%CI 50-66.3, I 2=12.6) and 43.5% (95%CI 34.1-53.4, I 2=30.6), respectively. The pooled rate of repeat dilatations was 78.9% (95%CI 69.7-85.8, I 2=15.2). The risks of pneumomediastinum, perforation and death were 9.9% (95%CI 6.2-15.6, I 2=0), 8% (95%CI 4.8-13, I 2=0), and 6.8% (95%CI 3.4-13.1, I 2=0), respectively. Minimal heterogeneity was noted in the analysis. CONCLUSIONS: The CARD procedure for CEO has a high technical success rate, but also a high rate of repeat dilations. Given its complexity and associated adverse events, this procedure should be restricted to centers with a high level of expertise.