Pooled Event Rates Research Articles

Discordant reporting of VTE in pancreatic cancer: A systematic review and meta‐analysis of thromboprophylaxis versus chemotherapeutic trials

BackgroundDespite the frequency of venous thromboembolism (VTE) in pancreatic cancer, it is inconsistently reported as an adverse event in clinical trials. We hypothesized that reported rates of VTE in pancreatic cancer clinical trials are influenced by the objectives of the trial, with higher rates reported in thromboprophylaxis compared with chemotherapeutic trials. We performed a systematic review and meta‐analysis of randomized, controlled trials (RCT) in pancreatic cancer to quantify differences in reported rates of VTE in thromboprophylaxis and chemotherapeutic trials. MethodsWe systematically searched MEDLINE, EMBASE, and Clinicaltrials.gov. Eligible thromboprophylaxis RCTs were required to report rates of thrombosis in non‐anticoagulant pancreatic cancer cohorts. Eligible chemotherapy studies were RCTs evaluating chemotherapy regimens in advanced pancreatic cancer and reported thrombosis as adverse events. Pooled event rates of VTE and arterial thrombosis were calculated using a random‐effects model. ResultsThe pooled VTE rate in 13 chemotherapy studies (5694 patients) was 5.9% (95% confidence interval [CI], 3.9‐9.0%) compared with 16.5% (95% CI, 11.7%‐23.3%; P < .001) in 9 thromboprophylaxis studies (631 patients). The pooled symptomatic VTE rate from chemotherapy studies was 5.4% (95% CI, 3.5%‐8.3%), which was significantly lower than the pooled rate from thromboprophylaxis studies of 10.5% (95% CI, 7.3%‐14.9%; P = .02). ConclusionThe VTE incidence reported in chemotherapy RCTs in pancreatic cancer is significantly lower than reported in thromboprophylaxis studies. This finding highlights the underrecognition of VTE in chemotherapeutic trials and emphasizes the need to standardize approaches towards monitoring and reporting of VTE in clinical trials.

Association of Arrhythmia and Acute Cardiac Injury with COVID-19 Severity

Background: Our study evaluates the published litera-ture of the overall contribution of COVID-19 in the oc-currence cardiac arrhythmia and acute cardiac injury in addition to their relation to COVID-19 severity. Methods: The international web databases, including PubMed, Science Direct, and Scopus, were electroni-cally searched between January 1, 2020, and August 18, 2020, to identify studies describing subjects with cardiac complications in COVID-19 infection in partic-ular arrhythmia and acute cardiac injury. Studies that provided adequate details on cardiac arrhythmia and acute cardiac injury as outcomes complication in posi-tively diagnosed COVID-19 were included. The Joanna Briggs Institute (JBI) critical appraisal checklist for case series to assess the risk of bias. Random-effect mod-els were used to estimate the pooled event rates of arrhythmia and acute cardiac injury. Results: Relevant data regarding the event rate of car-diac manifestations particularly arrhythmia and acute cardiac injury in 4,355 patients with COVID-19 were collected from 13 studies. The pooled prevalence of arrhythmia as a complication of COVID-19 was 19% (95%CI: 12% to 29%), while the pooled prevalence of acute cardiac injury as a complication of COVID-19 was 9% (95%CI: 5% to 18%). Arrhythmia was found to in-crease the severity of COVID-19 about ten-folds signifi-cantly. In contrast, acute cardiac injury significantly in-creased the severity of COVID-19 with nearly 15-folds. No significant publication bias was indicated by either the visual symmetry or the Egger's test. Conclusion: In conclusion, cardiac arrhythmias and acute cardiac injury are highly associated with the se-verity and the mortality rate of COVID-19.

The efficacy of meniscus posterior root tears repair: A systematic review and meta-analysis.

To report of efficacy repair treatment for meniscus posterior root tears repair. We systematically searched databases including PubMed, Embase, and Cochrane Library for relevant articles. Coleman Methodology Score was used for a quality assessment of the included studies. A meta-analysis was performed to analyze for efficacy of MMPRTs repair. Twenty-two studies, 14 level III and 8 level IV, were included in this systematic review, with a total of 926 cases. Studies comparing repair with either meniscectomy or conservative treatment found greater improvement and slower progression of Kellgrene-Lawrence grade with meniscal repair. Decreased meniscus extrusion is beneficial to the prognosis of patients undergoing MMPRTs repair. As treatment efficacy, the Lysholm score increased 28.87 (P < 0.001), IKDC score increased 31.73. The overall pooled event rates of progression of K-L grade is 0.200. Difference of Lysholm score and IKDC score between repair and meniscectomy were 8.72 and 9.67. The clinical subjective score after MMPRT repair was significantly improved compared with the preoperative status. Considering the progression of joint K-L grade, it can prevent the progression of arthrosis to some extent, but not completely. Decreased meniscus extrusion is beneficial to the prognosis of patients undergoing MMPRTs repair. Based on these results, MMPRTs repair cloud result favorable outcomes.

Incidence of Pediatric Perforated Appendicitis during the COVID-19 Pandemic; a Systematic Review and Meta-Analysis.

Introduction:COVID-19 has affected the pattern of referral to medical centers and quarantine against COVID-19 might delay referral and management of surgical emergencies. This study aimed to compare the pooled event rate of pediatric perforated appendicitis before and during the COVID-19 pandemic. Methods:This was a systematic review and meta-analysis study based on the PRISMA guidelines. Scopus, Web of Sciences, and PubMed databases were searched for studies reporting the rate of perforated appendicitis based on the post-appendectomy observations or imaging methods. The Egger bias test and funnel plot were used to detect and depict publication bias. Statistical analysis was performed in Comprehensive Meta-analysis package version 3. Results: Twelve studies were eligible for inclusion in our study. The pooled prevalence of pediatric perforated appendicitis in the pre-COVID era was 28.5% (CI95%: 28.3 to 28.7%) with a heterogeneity of 99%. In the COVID era, the event rate proportion was 39.4% (CI95%: 36.6 to 42.3%) with a heterogeneity of 99%. There was a significant difference in the subgroup analysis within the pre-COVID and COVID era (P<0.001), showing a higher perforation rate in the COVID era.Conclusion:Our study showed that during the COVID-19 pandemic, the rate of perforated appendicitis has significantly increased in comparison to before the COVID-19 pandemic.

Pharmacologic Thromboprophylaxis and Thrombosis in Hospitalized Patients with COVID-19: A Pooled Analysis.

Background Coronavirus disease 2019 (COVID-19) increases thrombosis in hospitalized patients prompting adoption of different thromboprophylaxis strategies. Safety and efficacy of escalated-dose pharmacologic thromboprophylaxis are not established. Objectives To determine the pooled incidence of thrombosis/bleeding in hospitalized patients with COVID-19 for standard-dose, intermediate-dose, therapeutic anticoagulation, and no pharmacologic thromboprophylaxis. Methods MEDLINE, EMBASE, and Cochrane CENTRAL were searched up to August 29, 2020 for studies reporting pharmacologic thromboprophylaxis and thrombosis or bleeding. Pooled event rates were calculated using a random-effects model. Results Thirty-five observational studies were included. The pooled incidence rates of total venous thromboembolism ( N = 4,685) were: no prophylaxis 41.9% (95% confidence interval [CI]: 28.1–57.2, I 2 = 76%), standard-dose prophylaxis 19.8% (95% CI: 13.2–28.6, I 2 = 95%), intermediate-dose prophylaxis 11.9% (95% CI: 4.3–28.6, I 2 = 91%), and therapeutic-dose anticoagulants 10.5% (95% CI: 4.2–23.8, I 2 = 82%, p = 0.003). The pooled incidence rates of arterial thrombosis ( N = 1,464) were: no prophylaxis 11.3% (95% CI: 5.2–23.0, I 2 = 0%), standard-dose prophylaxis 2.5% (95% CI: 1.4–4.3, I 2 = 45%), intermediate-dose prophylaxis 2.1% (95% CI: 0.5–7.7, I 2 = 45%), and therapeutic-dose anticoagulants 1.3% (95% CI: 0.2–8.8, I 2 = 0, p = 0.009). The pooled bleeding event rates ( N = 6,393) were nonsignificantly higher in therapeutic-dose anticoagulants compared with standard-dose prophylaxis, (6.3 vs. 1.7%, p = 0.083). Conclusion Thrombosis rates were lower in hospitalized COVID-19 patients who received pharmacologic thromboprophylaxis. Thrombosis and bleeding rates for patients receiving intermediate-dose thromboprophylaxis or therapeutic anticoagulation were similar to those who received standard-dose pharmacologic thromboprophylaxis.

Malignant Progression of Monoclonal Gammopathy of Undetermined Significance: A Systematic Review and Meta-Analysis

Introduction: Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic premalignant plasma cell dyscrasia that occurs in 3-5% of patients above the age of 50. In addition to its known progression to multiple myeloma (MM), MGUS is associated with higher risks of second malignancies. The progression from MGUS to more advanced diseases has a significant impact on overall survival. This systematic review and meta-analysis therefore aimed to comprehensively evaluate the incidence of malignant progression and the development of second malignancies in patients with MGUS. Methods: The protocol of our study was registered in PROSPERO with ID(CRD42018092067). Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a comprehensive electronic search in nine electronic databases, including PubMed, Google Scholar, POPLINE, WHO health library, System for Information on Grey Literature in Europe, Scopus, Web of Science, Virtual Health Library, and The New York Academy of Medicine. The following predetermined search terms were used: (monoclonal gammopathy of undetermined significance or MGUS); (incidence or progression or transformation); (myeloma or lymphoma or amyloidosis or macroglobulinemia or leukemia or plasmacytoma or malignancy or malignant). Risk of bias was assessed using the National Institute of Health (NIH) study quality assessment tool. Random-effects model was used to synthesize the pooled event rates of MGUS progression and development of second malignancies. Statistical heterogeneity was evaluated using Cochran's Q statistics and I² tests, with p-value≤0.10 or I² value&amp;gt;50% considered as statistically significant. Sub-group analysis based on the duration of follow-up was conducted to obtain rates of progression in patients who were followed-up for 0-5 years, 5-10 years, and more than 10 years. Meta-regression based on age, gender, immunoglobulin subtype of MGUS, and publication year was performed to explore any statistically significant heterogeneity if there were more than 10 studies. Publication bias was assessed using Begg's funnel plot and Egger's regression test if the number of studies was more than 10. Results: A total of 4690 articles were identified. Of those, 315 articles were found eligible for full-text screening. We finally included 48 studies for analysis including a total of 20945 patients with a mean age of 64.1 years. The mean duration of follow-up was 7.43 (1.8-34.1) years. The overall cumulative rate of MGUS progression and development of second malignancies was 8.6% (95% CI, 7.2-10.2%). The rates stratified based on years of follow-up were 6.9% (95% CI, 5.3-8.9%) at 0-5 years, 8.8% (95% CI, 6.4-11.8%) at 5-10 years, and 14.9% (95% CI, 10.8-20.2%) beyond 10 years. Rates of progression to MM, Waldenstrom macroglobulinemia, and amyloidosis were 5.8% (95% CI, 4.7-7.2%), 2.1% (95% CI, 1.1-4.0%), and 0.7% (95% CI, 0.3-1.5%) respectively. The rates of development of non-Hodgkin lymphoma and leukemia were 2.5% (95% CI, 1.5-4.3%) and 1.4% (95% CI, 0.4-4.4%) respectively. The rate of development of solid tumors was 6.4% (95% CI, 2.5-15.4%). Meta-regression for evaluation of statistical heterogeneity was performed for most outcomes, except for those with less than 10 studies (leukemia, amyloidosis, solid tumors, and follow-up beyond 10 years). Age and publication year were the source of heterogeneity in most. Overall risk of progression does not vary with MGUS subtypes. There was no publication bias based on Begg's funnel plot and Egger's regression test. Conclusions: The risks of MGUS malignant progression and development of other hematological/solid malignancies remain significant, approximating 15% after 10 years of diagnosis. Future efforts could be directed toward better cancer surveillance and deferral of malignant progression among patients with MGUS. Disclosures No relevant conflicts of interest to declare.

Reirradiation Using Stereotactic Body Radiotherapy in the Management of Recurrent or Second Primary Head and Neck Cancer: A Meta-Analysis and Systematic Review

We conducted a meta-analysis and systematic review of stereotactic body radiotherapy (SBRT)-based reirradiation efficacy in patients with recurrent or second primary head and neck cancer (RSHNC). We systematically reviewed PubMed/Medline, Embase, and Cochrane Library. The primary endpoint was 2-year overall survival (OS); secondary endpoints were grade ≥ 3 complications and response rate. We included 10 studies involving 575 patients (only 12% of whom underwent salvage surgery post-recurrence) with RSHNC who underwent SBRT; median SBRT reirradiation doses ranged from 24 to 44 Gy (median, 30 Gy) delivered with 3 to 6 fractions (median, 5 fractions). Median target volume of SBRT reirradiation was measured from 19 to 103 cm3. The pooled event rate of 2-year OS following SBRT reirradiation for RSHNC was 30.0% (95% confidence interval [CI] 24.5–36.1). The pooled rates of late grade ≥ 3 and grade 5 toxicity were 9.6% (95% CI 5.0–17.6) and 4.6% (95% CI 2.4–8.6), respectively. Grade 5 toxicity was not observed in five studies (range: 0% to 10.7%). The pooled rates of clinical response and complete response were 61.7% (95% CI 51.1–71.3) and 31.3% (95% CI 23.3–40.5), respectively, and the 2-year local control rate was 47.3% (95% CI 3.1–62.1). SBRT with median 30 Gy in 5 fractions is a feasible therapy showing good responses for patients with RSHNC not suitable for salvage surgery. However, to improve OS, SBRT reirradiation strategy should be investigated in terms of dose escalation for sustained control and combined systemic therapy.

Tacrolimus and mycophenolate mofetil as second-line treatment in autoimmune hepatitis: Is the evidence of sufficient quality to develop recommendations?

BACKGROUNDThe standard management of autoimmune hepatitis (AIH) is based on corticosteroids, alone or in combination with azathioprine. Second-line treatments are needed for patients who have refractory disease. However, high-quality data on the alternative management of AIH are scarce.AIMTo evaluate the efficacy and safety of tacrolimus and mycophenolate mofetil (MMF) and the quality of evidence by using the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE).METHODSA systematic review and meta-analysis of the available data were performed. We calculated pooled event rates for three outcome measures: Biochemical remission, adverse events, and mortality, with their corresponding 95% confidence intervals (CI).RESULTSThe pooled biochemical remission rate was 68.9% (95%CI: 60.4-76.2) for tacrolimus, and 59.6% (95%CI: 54.8-64.2) for MMF, and rates of adverse events were 25.5% (95%CI: 12.4-45.3) for tacrolimus and 24.1% (95%CI: 15.4-35.7) for MMF. The pooled mortality rate was estimated at 11.5% (95%CI: 7.1-18.1) for tacrolimus and 9.01% (95%CI: 6.2-12.8) for MMF. Pooled biochemical remission rates for tacrolimus and MMF in patients with intolerance to standard therapy were 56.6% (CI: 43.4-56.6) vs 73.5% (CI: 58.1-84.7), and among non-responders were 59.1% (CI: 48.7-68.8) vs 40.8% (CI: 32.3-50.0), respectively. Moreover, the overall quality assessments using GRADE proved to be very low for all our outcomes in both treatment groups.CONCLUSIONTacrolimus and MMF are in practice considered effective for patients with AIH who are non-responders or intolerant to first-line treatment, but we found no high-quality evidence to support this statement.

A 5-Decade Analysis of Incidence Trends of Ischemic Stroke After Transient Ischemic Attack

Management of transient ischemic attack (TIA) has gained significant attention during the past 25 years after several landmark studies indicated the high incidence of a subsequent stroke. To calculate the pooled event rate of subsequent ischemic stroke within 2, 7, 30, and 90 days of a TIA and compare this incidence among the population with TIA recruited before 1999 (group A), from 1999 to 2007 (group B), and after 2007 (group C). All published studies of TIA outcomes were obtained by searching PubMed from 1996, to the last update on January 31, 2020, irrespective of the study design, document type, or language. Of 11 516 identified citations, 175 articles were relevant to this review. Both the classic time-based definition of TIA and the new tissue-based definition were accepted. Studies with a combined record of patients with TIA and ischemic stroke, without clinical evaluation for the index TIA, with diagnosis of index TIA event after ischemic stroke occurrence, with low suspicion for TIA, or duplicate reports of the same database were excluded. The study was conducted and reported according to the PRISMA, MOOSE, and EQUATOR guidelines. Critical appraisal and methodological quality assessment used the Quality in Prognosis Studies tool. Publication bias was visualized by funnel plots and measured by the Begg-Mazumdar rank correlation Kendall τ2 statistic and Egger bias test. Data were pooled using double arcsine transformations, DerSimonian-Laird estimator, and random-effects models. The proportion of the early ischemic stroke after TIA within 4 evaluation intervals (2, 7, 30, and 90 days) was considered as effect size. Systematic review yielded 68 unique studies with 223 866 unique patients from 1971 to 2019. The meta-analysis included 206 455 patients (58% women) during a span of 4 decades. The overall subsequent ischemic stroke incidence rates were estimated as 2.4% (95% CI, 1.8%-3.2%) within 2 days, 3.8% (95% CI, 2.5%-5.4%) within 7 days, 4.1% (95% CI, 2.4%-6.3%) within 30 days, and 4.7% (95% CI, 3.3%-6.4%) within 90 days. There was a recurrence risk of 3.4% among group A in comparison with 2.1% in group B or 2.1% in group C within 2 days; 5.5% in group A vs 2.9% in group B or 3.2% in group C within 7 days; 6.3% in group A vs 2.9% in group B or 3.4% in group C within 30 days, and 7.4% in group A vs 3.9% in group B or 3.9% in group C within 90 days. These findings suggest that TIA continues to be associated with a high risk of early stroke; however, the rate of post-TIA stroke might have decreased slightly during the past 2 decades.

S3272 Prevalence of Colonic Adenomas in Cirrhotic Patients Undergoing Pre-Transplant Evaluation: A Meta-Analysis and Systematic Review

INTRODUCTION: Multiple studies have suggested that the risk of advanced adenomas and colorectal cancer is not only higher in liver transplant patients, but also significantly increases post transplantation, particularly due to their immunocompromised state. As it stands, CRC screening recommendations in low to moderate risk liver transplant candidates are the same for those of the general population. This study aims to analyze the literature on the prevalence of adenomas in liver cirrhosis patients undergoing colonoscopy screening as part of their pre-transplant evaluation. METHODS: A systemic review was conducted in PUBMED, Embase, PubMed Central and ScienceDirect databases from inception through May 2020. Effect estimates from the individual studies were extracted and combined using the random effect, generic inverse variance method of DerSimonian and Laird and pooled event rates were calculated. Forest plots were generated, and publication bias was assessed for using conventional techniques. RESULTS: Eleven studies with a total of 4223 patients with cirrhosis undergoing liver transplant evaluation were included in this analysis. The pooled event rate for any adenoma was 21.2% (95% CI, 16.9%–26.2%), whereas the pooled event rate for advanced adenoma was 5.6% (95% CI, 2.7%–11.4%). The pooled event rate for adenocarcinoma was 0.7% (95% CI, 0.03%–1.7%), most of which were successfully resected endoscopically. CONCLUSION: This study suggests a considerable prevalence of adenomatous polyps and advanced lesions in this high-risk patient population, and hence, colonoscopy should be performed for every transplant candidate within the frame of the current ACG recommendations. Additionally, our results call for further risk-matched prospective studies to examine the need for earlier endoscopic surveillance in this cohort of patients.Figure 1.: Forrest plot, pooled event rate of any adenoma in cirrhotic patients undergoing transplant evaluation.Figure 2.: Forrest plot, pooled event rate of advanced adenomas in cirrhotic patients undergoing transplant evaluation.Figure 3.: Forrest plot, pooled event rate of adenocarcinoma in cirrhotic patients undergoing transplant evaluation.

S0226 The Association Between Microscopic Colitis and Celiac Disease: A Systematic Review and Meta-Analysis

INTRODUCTION: Multiple studies have suggested that Celiac disease (CD) may be associated with microscopic colitis (MC); however, most of these studies were limited by their small sample size or the main scope of interest. Hence, we aimed to analyze the previously published literature on this association to determine the extent and significance of this relationship. METHODS: A systemic review was conducted in PUBMED, Embase, PubMed Central and ScienceDirect databases from inception through May 2020. Effect estimates from the individual studies were extracted and combined using the random effect, generic inverse variance method of DerSimonian and Laird and a pooled odds ratio (OR) and event rates were calculated. Forest plots were generated, and publication bias was assessed for using conventional techniques. RESULTS: Fifteen studies with a total of 4640 patients with MC were included in this Analysis. CD was significantly associated with MC (OR 6.221, 95% CI, 3.828–10.108, P < 0.005). The pooled event rate for MC in patients with CD was 6.7% (4.4%–10.0%, P < 0.005), while the pooled event rate for celiac disease in patients with MC was 7.7% (4.6%–12.6%, P < 0.005). CD was prevalent in both types of MC; 5.4% (1.3%–20%, P < 0.005) in collagenous colitis and 9.1% (4.5%–17.3%, P < 005) in lymphocytic colitis. We found no publication bias as assessed by the funnel plots and Egger’s regression asymmetry test. CONCLUSION: Our meta-analysis confirms a statistically significant association between CD and MC, with a high prevalence of CD in both types of MC. Gastroenterologists should be wary of this association when evaluating patients with either disease, particularly in patients with a sub-optimal response to first line therapy.Figure 1.: Forrest plot, pooled OR for the association between celiac disease and microscopic colitis.

S0911 Self-Expanding Metal Stents for Palliation of Malignant Gastric Outlet Obstruction: Does Cover Material Matter? A Meta-Analysis

INTRODUCTION: Knowledge regarding the optimal cover material for fully or partially covered self-expanding metal stents (CSEMS) deployed for palliation of malignant gastric outlet obstruction (MGOO) is lacking. METHODS: A comprehensive literature search was performed of Medline (Ovid) and Embase from inception-July 2019. All studies were screened by two authors to identify studies reporting the safety and efficacy of CSEMS for palliation of MGOO with information on CSEMS cover material. A logistic-normal random-effects model was applied while pooling data to account for effect sizes close or equal to zero and one. Pooled data was reported as proportions with 95% confidence interval (CI). RESULTS: Screening of 3553 articles yielded 13 studies (5 on silicone CSEMS, 8 on Polytetrafluoroethylene (PTFE)-CSEMS) enrolling 646 patients (484 with PTFE-CSEMS, 162 with silicone CSEMS). Technical success rate was 99% (95–100%) and 100% (98%–100%) for silicone CSEMS and PTFE-CSEMS. Clinical success of PTFE-CSEMS was 94% (86–97%) which was higher than the clinical success of silicone CSEMS (90%; 82–94%). The pooled adverse event rate for silicone CSEMS and PTFE-CSEMS was 26% (20–32%) and 62% (32–85%), respectively. Stent migration occurred in 17% (11–24%) and 23% (10–36%) of PTFE-CSEMS and silicone CSEMS. Stent collapse/fracture rate was 4% (0–8%) and 5% (1–9%) for PTFE-CSEMS and silicone CSEMS. Tumor ingrowth occurred in 2% (0–4%) and 31% (24–39%) of PTFE-CSEMS and silicone CSEMS. Tumor overgrowth occurred in 4% (1–7%) and 5% (0–9%) of PTFE-CSEMS and silicone CSEMS. Luminal perforation rate was 2% (1–4%) and 1% (0–4%) with PTFE-CSEMS and Silicone CSEMS. Post-procedural bleeding rate was 2% (0–5%) and 1% (0–4%) with PTFE-CSEMS and Silicone CSEMS. Endoscopic reintervention rate was 24% (10–37%) and 29% (0–59%) with PTFE-CSEMS and silicone CSEMS. Surgical intervention rate was 2% (0–5%) and 1% (0–4%) for PTFE-CSEMS and silicone CSEMS. CONCLUSION: A trend towards higher rate of adverse events, particularly stent migration and tumor ingrowth was observed with Silicone CSEMS use upon indirect comparison with PTFE-CSEMS; this may translate into a higher reintervention rate. Further well-designed studies are needed to validate and build upon our findings. The standard of care for MGOO in the US remains uncovered SEMS; we anticipate our findings can aide investigators as well as policy makers when considering expanded access to CSEMS in the US.Table and Figure 1.: Safety and Efficacy Outcomes of Covered Self-Expanding Metal Stent Insertion for the Palliation of Malignant Gastric Outlet Obstruction Stratified by Cover Type

S3307 Partially Covered Self-Expanding Metal Stents for Palliation of Malignant Gastric Outlet Obstruction; A Meta-Analysis of Observational Studies

INTRODUCTION: Enteral covered and partially covered self-expanding metal stents (CSEMS, pCSEMS) were designed to improve stent patency and reduce stent migration and are widely used for the palliation of malignant gastric outlet obstruction (MGOO). However, knowledge regarding the safety and efficacy profile of pCSEMS is lacking. METHODS: A comprehensive literature search was performed of Medline(Ovid) and Embase from inception to July 2019. All studies were screened by two authors to identify studies reporting the safety and efficacy of pCSEMS for palliation of MGOO. A logistic-normal random-effects model was applied while pooling data to account for effect sizes close or equal to zero and one. Pooled data was reported as proportions with 95% confidence interval (CI). RESULTS: Screening of 3553 articles yielded 4 studies on pCSEMS enrolling 167 patients. Three studies reported using silicone covered pCSEMS whereas one study did not report cover material type. Technical success rate was 100% (71%–100%) whereas clinical success of was of pCSEMS placement was 90% (84–96%). The pooled adverse event rate was 54% (29%–77%). Stent migration occurred in 8% (5–13%) of patients. Stent collapse/fracture rate was 4% (1–20%). Tumor ingrowth occurred in 0% (0–64%) of pCSEMS, whereas tumor overgrowth occurred in 7% (2–26%) of pCSEMS. Luminal perforation rate was 1% (0–5%). Post–procedural bleeding was reported in 1% (0–5%) of patients. Endoscopic reintervention rate was 23% (10–44%) due to 71% (16–97%) of the reported adverse events. Surgical intervention rate was 2% (1–6%) due to 4% (1–21%) of the adverse events. No adverse event–associated mortality was reported. CONCLUSION: pCSEMS carry a clinical success rate of 90%, making them an efficacious alternative to fully-covered SEMS. The migration rate of pCSEMS was 8%, along with an endoscopic reintervention rate of 23%, a finding that warrants further query. Well-designed studies are needed to validate and build upon our findings. The standard of care for malignant gastric outlet obstruction (MGOO) in the US remains uncovered SEMS; we anticipate our findings can aide investigators as well as policy makers when considering expanded access to CSEMS in the US.Table and Figure 1.: Safety and Efficacy Outcomes of Partially Covered Self-Expanding Metal Stents for Palliation of Malignant Gastric Outlet Obstruction

Efficacy and Safety of Digital Single-Operator Cholangioscopy in the Diagnosis of Indeterminate Biliary Strictures by Targeted Biopsies: A Systematic Review and Meta-Analysis.

Background: Biliary strictures are frequently encountered in clinical practice. The determination of their nature is often difficult. This study aims to systematically evaluate the efficacy and safety of the second generation of digital single-operator cholangioscopy (SpyGlass DS, DSOC) in indeterminate biliary strictures (IBDS) through biopsies. Methods: All relative studies published in Medline, the Cochrane Library, Web of Science, and EMBASE were included. The diagnostic tests for IBDS were compared to the surgical histology, autopsy, or long-term clinical follow-up. The methodological quality of the included studies was evaluated by the Quality Assessment of Studies of Diagnostic Accuracy Included in Systematic Reviews (QUADAS-2). Results: A total of 11 studies, which involved 356 patients diagnosed through biopsies, were included. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio were 0.74 (95% CI: 0.67–0.80), 0.98 (95% CI: 0.95–1.00), 10.52 (95% CI: 5.45–20.32), 0.31 (95% CI: 0.23–0.41), and 65.18 (95% CI: 26.79–158.61), respectively. The area under the curve (AUC) was 0.9479, and the pooled adverse event rate was 7%. The sensitivity and specificity in the heterogeneity analysis were I2 = 48.1% and I2 = 25.4%, respectively. Conclusion: SpyGlass DS is a safe and effective technique for IBDS. However, future randomized trials are needed to determine optimal number of biopsies.

Comparing the efficacy and safety of Q-switched and picosecond lasers in the treatment of nevus of Ota: a systematic review and meta-analysis.

Nevus of Ota is cosmetically burdensome and often prompts patients to seek treatment. Lasers are commonly used in removing these lesions; however, no systemic analysis has been conducted to support a gold standard laser. To conduct a meta-analysis of the efficacy and safety of Q-switched Nd:YAG lasers (QSNL), Q-switched ruby lasers (QSRL), Q-switched alexandrite lasers (QSAL), and picosecond alexandrite lasers (PSAL) in removing nevus of Ota. Inclusion criteria were nevus of Ota patients treated with QSNL, QSRL, QSAL, or PSAL and documentation of percent clearance and the rate of at least one adverse event. Articles in English, Chinese, or Japanese were included. The prespecified outcome measures were efficacy (percent clearance) and safety (rates of hyperpigmentation, hypopigmentation, scarring, and recurrence). The review included 57 studies and 13,417 patients. The pooled success rate was 64% for QSNL (95% CI 52-76%), 54% for QSRL (95% CI 39-69%), 58% for QSAL (95% CI 44-72%), and 100% for PSAL (95% CI 98-102%). The pooled adverse event rate was 5% for QSNL (95% CI 4-6%), 14% for QSRL (95% CI 9-19%), 9% for QSAL (95% CI 6-12%), and 44% (95% CI 31-57%) for PSAL. QSNL has the most evidence for effectively and safely treating nevus of Ota. PSAL potentially has a superior efficacy; however, further studies are needed to elucidate its side effect profile when treating nevus of Ota.

Efficacy and Safety of Peroral Endoscopic Myotomy in Achalasia Patients with Failed Previous Intervention: A Systematic Review and Meta-Analysis.

Peroral endoscopic myotomy (POEM) has emerged as a rescue treatment for recurrent or persistent achalasia after failed initial management. Therefore, we aimed to investigate the efficacy and safety of POEM in achalasia patients with failed previous intervention. We searched the MEDLINE, Embase, Cochrane, and PubMed databases using the queries “achalasia,” “peroral endoscopic myotomy,” and related terms in March 2019. Data on technical and clinical success, adverse events, Eckardt score and lower esophageal sphincter (LES) pressure were collected. The pooled event rates, mean differences (MDs) and risk ratios (RR) were calculated. A total of 15 studies with 2,276 achalasia patients were included. Overall, the pooled technical success, clinical success and adverse events rate of rescue POEM were 98.0% (95% confidence interval [CI], 96.6% to 98.8%), 90.8% (95% CI, 88.8% to 92.4%) and 10.3% (95% CI, 6.6% to 15.8%), respectively. Seven studies compared the clinical outcomes of POEM between previous failed treatment and the treatment naïve patients. The RR for technical success, clinical success, and adverse events were 1.00 (95% CI, 0.98 to 1.01), 0.98 (95% CI, 0.92 to 1.04), and 1.17 (95% CI, 0.78 to 1.76), respectively. Overall, there was significant reduction in the pre- and post-Eckardt score (MD, 5.77; p<0.001) and LES pressure (MD, 18.3 mm Hg; p<0.001) for achalasia patients with failed previous intervention after POEM. POEM appears to be a safe, effective and feasible treatment for individuals who have undergone previous failed intervention. It has similar outcomes in previously treated and treatment-naïve achalasia patients.

A Systematic Review and Meta-Analysis of Transcarotid Artery Revascularization with Dynamic Flow Reversal Versus Transfemoral Carotid Artery Stenting and Carotid Endarterectomy

Transfemoral carotid artery stenting (TFCAS) was introduced as a less invasive option for carotid revascularization in patients at high risk for complications from carotid endarterectomy (CEA). The increased perioperative stroke and death risk of TFCAS has however prevented TFCAS from widespread acceptance as an alternative to CEA in high-risk patients. Recent research suggests that transcarotid artery revascularization (TCAR) may be associated with a low stroke and death risk and potentially meet the needs of patients at high surgical risk. We aimed to estimate the 30-day risk of stroke or death of TCAR and compare it to TFCAS and CEA. We searched PubMed, Cochrane, Embase, and Scopus for studies of patients treated with TCAR. Meta-analysis was conducted when appropriate. A logistic-normal random-effects model with logit transformation was used to estimate the pooled event rates after TCAR. Pooled Mantel-Haenszel odds ratios (ORs) of events comparing TCAR to TFCAS and CEA were calculated using a fixed-effects model. Heterogeneity among studies was quantified with the chi-squared statistic of the likelihood ratio (LR) test that compares the random-effects and fixed-effects models. Nine nonrandomized studies evaluating 4012 patients who underwent TCAR were included. The overall 30-day risks after TCAR were stroke/death, 1.89% (95% confidence interval [CI]: 1.50, 2.37); stroke, 1.34% (95% CI: 1.02,1.75); death, 0.76% (95% CI: 0.56, 1.08); myocardial infarction (MI), 0.60% (95% CI: 0.23, 1.59); stroke/death/MI, 2.20% (95% CI: 1.31, 3.69); cranial nerve injury (CNI), 0.31% (95% CI: 0.12, 0.83). The failure rate of TCAR was 1.27% (95% CI: 0.32, 4.92). Two nonrandomized studies suggested that TCAR was associated with lower risk of stroke and death as compared with TFCAS (1.33% vs. 2.55%, OR: 0.52, 95% CI: 0.36, 0.74 and 0.76% vs. 1.46%, OR: 0.52, 95% CI: 0.32, 0.84, respectively). Four nonrandomized studies suggested that TCAR was associated with a lower risk of CNI (0.54% and 1.84%, OR: 0.52, 95% CI: 0.36, 0.74) than CEA, but no statistically significant difference in the 30-day risk of stroke, stroke/death, or stroke/death/MI. Among patients undergoing TCAR with dynamic flow reversal for carotid stenosis the 30-day risk of stroke or death was low. The perioperative stroke/death rate of TCAR was similar to that of CEA while CNI risk was lower. Larger prospective studies are needed to account for confounding factors and provide higher certainty.

Systematic review: medical therapy for fibrostenosing Crohn's disease.

Medical therapy and/or endoscopic balloon dilation with intralesional therapies are options for the treatment of small bowel fibrostenotic Crohn's disease (CD). To perform a systematic review summarising evidence for efficacy of systemic and endoscopic intralesional medical therapy in established small bowel strictures in adult CD patients. A systematic search of MEDLINE, EMBASE, CENTRAL and Scopus was conducted. Primary outcomes were rates of surgical resection and repeat endoscopic dilation. Pooled event rates from random effects models across studies with 95% confidence intervals were reported. Ten studies describing systemic medical therapy and eight studies of intralesional injection were included. One randomised controlled trial each for systemic therapy and intrastricture injection were identified. Only observational studies were found for systemic biologic therapies, which exclusively included tumour necrosis factor (TNF) antagonists, while intralesional therapies all involved corticosteroids except for one study that evaluated infliximab. Pooled event rates for surgical resection after systemic and intralesional therapy were 28.3% (95% CI: 18.2%-41.3%) and 18.5% (95% CI: 8.3%-36.2%), respectively over a median follow-up of 23months (range 5.5-105.8), and 21.8months (range 5-47). Risk of repeat endoscopic balloon dilation in those with intralesional therapy was 58.3% (95% CI: 36.6%-77.3%) over a median follow-up of 21.8months (range 5-47). There are no favoured therapies for patients with stricturing small bowel CD. Data are lacking for ustekinumab and vedolizumab. No endoscopic intralesional medications provided a clear benefit for prevention of repeat EBD or surgery.

Reirradiation using stereotactic body radiotherapy in the management of recurrent or second primary head and neck cancer: A meta-analysis and systematic review.

We conducted a meta-analysis and systematic review of stereotactic body radiotherapy (SBRT)-based reirradiation efficacy in patients with recurrent or second primary head and neck cancer (RSHNC). We systematically reviewed PubMed/MEDLINE, Embase, and Cochrane Library. The primary endpoint was 2-year overall survival (OS); secondary endpoints were grade >3 complications and response rate. We included 10 studies involving 575 patients (only 12% of whom underwent salvage surgery post-recurrence) with RSHNC who underwent SBRT; median SBRT reirradiation doses ranged from 24 to 44Gy (median, 30Gy) delivered with 3-6 fractions (median, 5 fractions). Median target volume of SBRT reirradiation was measured from 19 to 103cm3. The pooled event rate of 2-year OS following SBRT reirradiation for RSHNC was 30.0% (95% confidence interval [CI] 24.5-36.1). The pooled rates of late grade ≥3 and grade 5 toxicity were 9.6% (95% CI 5.0-17.6) and 4.6% (95% CI 2.4-8.6), respectively. Grade 5 toxicity was not observed in five studies (range: 0-10.7%). The pooled rates of clinical response and complete response were 61.7% (95% CI 51.1-71.3) and 31.3% (95% CI 23.3-40.5), respectively, and the 2-year local control rate was 47.3% (95% CI 3.1-62.1). SBRT with median 30Gy in 5 fractions is a feasible therapy showing good responses for patients with RSHNC not suitable for salvage surgery. However, to improve OS, SBRT reirradiation strategy should be investigated in terms of dose escalation for sustained control and combined systemic therapy.

Diagnostic yield of EUS-guided through-the-needle microforceps biopsy versus EUS-FNA of pancreatic cystic lesions: a systematic review and meta-analysis.

Background and study aims Accurate diagnosis and risk stratification of pancreatic cysts (PCs) is challenging. The aim of this study was to perform a systematic review and meta-analysis to assess the feasibility, safety, and diagnostic yield of endoscopic ultrasound-guided through-the-needle biopsy (TTNB) versus fine-needle aspiration (FNA) in PCs. Methods Comprehensive search of databases (PubMed, EMBASE, Cochrane, Web of Science) for relevant studies on TTNB of PCs (from inception to June 2019). The primary outcome was to compare the pooled diagnostic yield and concordance rate with surgical pathology of TTNB histology and FNA cytology of PCs. The secondary outcome was to estimate the safety profile of TTNB. Results: Eight studies (426 patients) were included. The diagnostic yield was significantly higher with TTNB over FNA for a specific cyst type (OR: 9.4; 95 % CI: [5.7–15.4]; I 2 = 48) or a mucinous cyst (MC) (OR: 3.9; 95 % CI: [2.0–7.4], I 2 = 72 %). The concordance rate with surgical pathology was significantly higher with TTNB over FNA for a specific cyst type (OR: 13.5; 95 % CI: [3.5–52.3]; I 2 = 48), for a MC (OR: 8.9; 95 % [CI: 1.9–40.8]; I 2 = 29), and for MC histologic severity (OR: 10.4; 95 % CI: [2.9–36.9]; I 2 = 0). The pooled sensitivity and specificity of TTNB for MCs were 90.1 % (95 % CI: [78.4–97.6]; I 2 = 36.5 %) and 94 % (95 % CI: [81.5–99.7]; I 2 = 0), respectively. The pooled adverse event rate was 7.0 % (95 % CI: [2.3–14.1]; I 2 = 82.9). Conclusions TTNB is safe, has a high sensitivity and specificity for MCs and may be superior to FNA cytology in risk-stratifying MCs and providing a specific cyst diagnosis.