Association between single and mixed exposure to polycyclic aromatic hydrocarbons and biological aging.

Background: Aging is one of the most important public health issues. Previous studies on the factors affecting aging focused on genetics and lifestyle, but the association between polycyclic aromatic hydrocarbons (PAHs) and aging is still unclear. Methods: This study utilized data from the National Health and Nutrition Examination Survey (NHANES) 2003-2010. A total of 8,100 participants was used to construct the biological age predictors by using recent advanced algorithms Klemera-Doubal method (KDM) and Mahalanobis distance. Two biological aging indexes, recorded as KDM-BA acceleration and PhenoAge acceleration, were used to investigate the relationship between single PAHs and biological age using a multiple linear regression analysis, and a weighted quantile sum (WQS) model was constructed to explore the mixed effects of PAHs on biological age. Finally, we constructed the restricted cubic spline (RCS) model to assess the non-linear relationship between PAHs and biological age. Results: Exposure to PAHs was associated with PhenoAge acceleration. Each unit increase in the log10-transformed level of 1-naphthol, 2-naphthol, and 2-fluorene was associated with a 0.173 (95% CI: 0.085, 0.261), 0.310 (95% CI: 0.182, 0.438), and 0.454 (95% CI: 0.309, 0.598) -year increase in PhenoAge acceleration, respectively (all corrected P < 0.05). The urinary PAH mixture was relevant to KDM-BA acceleration (ß = 0.13, 95% CI: 0, 0.26, P = 0.048) and PhenoAge acceleration (ß = 0.59, 95% CI: 0.47, 0.70, P < 0.001), and 2-naphthol had the highest weight in the weighted quantile sum (WQS) regression. The RCS analyses showed a non-linear association between 2-naphthol and 2-fluorene with KDM-BA acceleration (all P < 0.05) in addition to a non-linear association between 1-naphthol, 2-naphthol, 3-fluorene, 2-fluorene, and 1-pyrene with PhenoAge acceleration (all P < 0.05). Conclusion: Exposure to mixed PAHs is associated with increased aging, with 2-naphthol being a key component of PAHs associated with aging. This study has identified risk factors in terms of PAH components for aging.

GNAS mutations suppress cell invasion by activating MEG3 in growth hormone-secreting pituitary adenoma.

Approximately 30%-40% of growth hormone-secreting pituitary adenomas (GHPAs) harbor somatic activating mutations in GNAS (α subunit of stimulatory G protein). Mutations in GNAS are associated with clinical features of smaller and less invasive tumors. However, the role of GNAS mutations in the invasiveness of GHPAs is unclear. GNAS mutations were detected in GHPAs using a standard polymerase chain reaction (PCR) sequencing procedure. The expression of mutation-associated maternally expressed gene 3 (MEG3) was evaluated with RT-qPCR. MEG3 was manipulated in GH3 cells using a lentiviral expression system. Cell invasion ability was measured using a Transwell assay, and epithelial-mesenchymal transition (EMT)-associated proteins were quantified by immunofluorescence and western blotting. Finally, a tumor cell xenograft mouse model was used to verify the effect of MEG3 on tumor growth and invasiveness. The invasiveness of GHPAs was significantly decreased in mice with mutated GNAS compared with that in mice with wild-type GNAS. Consistently, the invasiveness of mutant GNAS-expressing GH3 cells decreased. MEG3 is uniquely expressed at high levels in GHPAs harboring mutated GNAS. Accordingly, MEG3 upregulation inhibited tumor cell invasion, and conversely, MEG3 downregulation increased tumor cell invasion. Mechanistically, GNAS mutations inhibit EMT in GHPAs. MEG3 in mutated GNAS cells prevented cell invasion through the inactivation of the Wnt/ß-catenin signaling pathway, which was further validated in vivo. Our data suggest that GNAS mutations may suppress cell invasion in GHPAs by regulating EMT through the activation of the MEG3/Wnt/ß-catenin signaling pathway.

The association between polychlorinated dibenzo-p-dioxin exposure and cancer mortality in the general population: a cohort study.

Introduction: Earlier research has indicated that being exposed to polychlorinated dibenzo-p-dioxins (PCDDs) in the workplace can heighten the likelihood of cancer-related deaths. Nevertheless, there is limited information available regarding the connection between PCDD exposure and the risk of cancer mortality in the general population (i.e., individuals not exposed to these substances through their occupation). Methods: The National Health and Nutrition Examination Survey (NHANES) detected PCDDs in the general population, and the death data were recently updated as of December 31, 2019. We conducted Cox regression analysis and controlled for covariates including age, gender, ethnicity, educational attainment, physical activity, alcohol intake, NHANES survey period, BMI category, cotinine concentration, and household earnings. Results: After accounting for confounding factors, the findings indicated that for each incremental rise of 1 log unit in 1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin, there was a 76% rise in the likelihood of death from any cause, with a p value of 0.003. An increase of 1 log unit in the concentration of 1,2,3,4,6,7,8-heptachlorodibenzofuran could potentially lead to a 90% higher risk of cancer mortality, as indicated by a p value of 0.034 and a 95% confidence interval of 0.05-2.43. As the concentrations of 1,2,3,4,6,7,8-heptachlorodibenzofuran increased, the dose-response curve indicated a proportional rise in the risk of cancer mortality, accompanied by a linear p value of 0.044. The sensitivity analysis demonstrated that our findings were resilient. Discussion: In the general population, an elevated risk of cancer mortality was observed in PCDDs due to the presence of 1,2,3,4,6,7,8-heptachlorodibenzofuran. Mechanistic research is required to further confirm it.

Association of organophosphate flame retardants with all-cause and cause-specific mortality among adults aged 40 years and older.

The longitudinal associations of urinary concentrations of diphenyl phosphate (DPHP), bis(2-chloroethyl) phosphate (BCEP), and bis(1,3-dichloro-2-propyl) phosphate (BDCPP) with all-cause, cardiovascular, and cancer mortality in a population of adults aged 40 years and older are still unclear. A total of 3238 participants were included in this cohort study. Urinary BCEP levels were positively associated with all-cause mortality and cardiovascular mortality. Specifically, a logarithmic increase in BCEP concentration was related to a 26 % higher risk of all-cause mortality and a 32 % higher risk of cardiovascular mortality. No significant associations were observed for DPHP and BDCPP in relation to mortality. Doseresponse analysis confirmed the linear associations of BCEP with all-cause and cardiovascular mortality and the nonlinear inverted U-shaped association between DPHP exposure and all-cause mortality. Notably, the economic burden associated with BCEP exposure was estimated, and it was shown that concentrations in the third tertile of BCEP exposure incurred approximately 507 billion dollars of financial burden for all-cause mortality and approximately 717 billion dollars for cardiovascular mortality. These results highlight the importance of addressing exposure to BCEP and its potential health impacts on the population. More research is warranted to explore the underlying mechanisms and develop strategies for reducing exposure to this harmful chemical.

Mediation analysis of urinary metals and stroke risk by inflammatory markers.

BACKGROUND: The association between metals and stroke has been reported, but the mediating role of inflammation between metals and stroke remains unclear. METHODS: We included 9326 adults from the National Health and Nutrition Examination Survey in this study. Through least absolute selection and shrinkage operator (LASSO) regression, weighted quantile sum (WQS) regression, logistic regression, linear regression, restricted cubic spline analysis, and mediation analysis, we explored the association between metals and stroke, as well as the association between metals and inflammatory indicators, and further evaluated the mediating effect of inflammatory indicators on the association between selected metals and stroke risk. RESULTS: The results of the present study suggested positive associations between mixed metals, cadmium and uranium and stroke risk. There is a positive correlation and dose‒response relationship between cadmium and C-reactive protein (CRP). Moreover, CRP mediates 10.1% of the association between cadmium and stroke. CONCLUSIONS: At the epidemiological level, CRP mediates the association between cadmium and stroke risk, suggesting that inflammation may be a potential mechanism for metal-induced stroke.

The role of polyglycolic acid sheets in the management of post-endoscopic submucosal dissection gastrointestinal bleeding and esophageal stricture: A PRISMA compliant systematic review and meta-analysis.

BACKGROUND: As a relatively minimally invasive technique, endoscopic submucosal dissection (ESD) is widely used for the treatment of gastrointestinal lesions. However, it is associated with complications, such as postoperative bleeding, stricture, and perforation. A covering method using polyglycolic acid (PGA) sheets for ESD-induced ulcers has been reported to be effective in reducing the risk of post-ESD bleeding and esophageal stricture. Herein, we conducted a systematic review and meta-analysis to evaluate the role of PGA sheets in the prevention of gastrointestinal bleeding and esophageal stricture after ESD. METHODS: We searched PubMed, Web of Science, and the Cochrane Library databases on October 15, 2019. All eligible articles were selected based on the predefined inclusion and exclusion criteria. The main outcomes were the rates of post-ESD gastrointestinal bleeding and esophageal stricture. Cochrane's Q statistic and I2 test were used to identify heterogeneity between the studies. When there was no obvious heterogeneity (I2 < 50%, P > .1), a fixed-effect model was used. When there was obvious heterogeneity (I2 > 50%, P < .1), a random effect model was used. Funnel plots and the Egger regression test were used to assess publication bias. RESULTS: Fifteen articles were included in the meta-analysis, of which 7 were exclusively about the use of PGA sheets to prevent postoperative gastrointestinal bleeding, and the remaining reported the use of PGA sheets to prevent postoperative esophageal stenosis. Our analysis showed that preventive therapy with PGA sheets decreased the rates of post-ESD gastrointestinal bleeding (risk ratio [RR] = 0.35, 95% confidential interval [CI]: 0.19-0.64, P < .001) and esophageal stricture (RR = 0.46, 95% CI: 0.27-0.79, P = .005), and the gastrointestinal bleeding and esophageal stricture rates after preventive treatment with PGA sheets were 5.7% (95% CI: 3.6%-8.8%) and 20.6% (95% CI: 14.5%-28.4%), respectively. CONCLUSION: The utilization of PGA sheets after ESD has an excellent outcome in reducing the risk of postoperative gastrointestinal bleeding and esophageal stricture.

The Landscape of Acute Pancreatitis Trials Registered in ClinicalTrials.gov: A Cross-sectional Study.

OBJECTIVES: Clinical studies are important in informing evidence-based practice for patients with acute pancreatitis (AP). To determine whether registered studies adequately meet this need, we leveraged the ClinicalTrials.gov database to provide an overview of studies pertaining to AP. METHODS: ClinicalTrials.gov was searched and the search term used was AP. Analysis was restricted to studies registered before January 12, 2021. RESULTS: Of 363,632 trials overall, 234 (0.06%) were eventually included for analysis. Interventional studies and observational studies comprised 67.5% and 32.5% of these studies respectively. Most studies were initiated 2007 or later. Endoscopic retrograde cholangiopancreatography was the single most frequent cause of AP specified in these studies (16.7%). Nearly 72% of these studies had a sample size greater than 50. With respect to study design, 87.3% of interventional studies were randomized, 53.5% were blinded. The top 3 countries with the largest number of registered studies were China (n = 59), followed by the United States (n = 53) and India (n = 12). CONCLUSIONS: Our results indicate that the research activity falls short of what is needed in terms of the burden of AP. The distribution of these AP-related studies by global regions indicates that there exists regional disparities.

The Top-Cited Articles With a Focus on Barrett's Esophagus: A Bibliometric Analysis.

BACKGROUND: Because the number of published literatures with a focus on Barrett's esophagus (BE) that researchers must be familiar with has quickly increased in recent years, the significance of selective searching and summarization of bibliometrics is also increasing. It is, thus, very important to find a method that can quickly and effectively search the most influential medical science articles. Therefore, the objective of this study was to use bibliometric analysis to assess and characterize the most influential articles involving BE research. METHODS: Publications on BE research were retrieved from the Web of Science Core Collection using the term "Barrett's esophagus." Microsoft Excel 2016 and VOSviewer were used to further analyzed each article's citation number, title, journal, country, organization, category, and authorship. RESULTS: On 14 June 2020, 5,389 records of BE research published until 2020 were retrieved. The citation number of the top 100 most-cited articles ranged from 208 to 824. Gastroenterology published 29 articles, which accounted for the largest number of top 100 articles (29%); however, among the top 500 most-cited articles, the American Journal of Gastroenterology published the largest number. Of the top-cited articles, the USA was by far the leading country in BE research and contributed most of the articles (n = 72). Among the academic institutions that produced the top 100 most-cited articles, the University of Washington (n = 12) was dominant. Sharma Prateek (n = 6) authored the largest number of most-cited articles. The USA contributed the most articles per year, and the time trend of the number of top 500 articles increased by 38-fold between 1987 and 2000. "Adenocarcinoma," "high-grade dysplasia," "cancer," "diagnosis," and "dysplasia" were the most influential keywords. CONCLUSIONS: This study not only presents a historical perspective but also facilitated the recognition of the significant advances in this area by researchers. Furthermore, the current study serves as a guide in decision clinical practice decision-making and provides a valuable reference for further research.

Role of Peroral Endoscopic Myotomy in Geriatric Patients with Achalasia: A Systematic Review and Meta-Analysis.

BACKGROUND: Peroral endoscopic myotomy (POEM) is a particularly attractive intervention for achalasia. Presently, POEM has been reported to be effective and safe for achalasia in geriatric patients. Herein, this systematic review was conducted to explore the role of POEM in geriatric patients with achalasia. METHOD: PubMed, Embase, and Cochrane Library were searched to identify studies evaluating the clinical outcome of POEM in geriatric patients with achalasia during January 2009 to October 2020. The primary outcomes were technical and clinical success. Secondary outcomes included postoperative Eckardt score, lower esophageal sphincter (LES) pressure, adverse events, and clinical reflux. RESULTS: There were 7 studies with a total of 469 geriatric patients, and the pooled technical success of POEM treatment was 98.1% (95% confidence interval [CI], 95.1-99.3%), and the pooled clinical success was 92.5% (95% CI, 89.3-94.8%). After POEM, the Eckardt score significantly decreased by 6.09 points (95% CI, 5.44-6.74, p < 0.00001), and the LES pressure significantly reduced by 13.53 mm Hg (95% CI, 5.14-21.91, p = 0.002). The pooled adverse events rate was 9.0% (95% CI, 4.3-17.9%), and the post-POEM clinical reflux rate was 17.4% (95% CI, 12.9-23.2%). CONCLUSION: Our current study demonstrated that POEM was an effective and safe technique for achalasia in geriatric patients.

Efficacy and Safety of Peroral Endoscopic Myotomy for Sigmoid-Type Achalasia: A Systematic Review and Meta-Analysis.

Background: The efficacy and safety of peroral endoscopic myotomy (POEM) in the treatment of sigmoid-type achalasia is unknown. This meta-analysis aims to explore the clinical outcomes of POEM for sigmoid-type achalasia. Method: We searched all relevant studies published up to September 2020 in PubMed, Embase, and Cochrane library databases. Meta-analyses for clinical success, Eckardt score, angle of esophageal tortuosity, diameter of esophagus, lower esophageal sphincter (LES) pressure, integrated relaxation pressure (IRP), adverse events, and gastroesophageal reflux diseases were performed based on random or fixed-effects models as needed. Results: We found a total of eight studies that provided data on 248 patients. Overall, the pooled clinical success was achieved in 211 sigmoid-type achalasia patients [90.4%; 95% confidence interval (CI), 85.5%-93.8%]. The pre- and post-POEM Eckardt scores, angle of esophageal tortuosity, diameter of esophageal, LES pressure, and IRP were significantly improved (All p < 0.05). The pooled adverse events rate was 13.0% (95% CI, 3.6%-37.4%). The pooled objective confirmation of reflux rate was 41.5% (95% CI, 26.5%-58.3%), and symptomatic reflux rate was 12.5% (95% CI, 8.3%-18.4%). Conclusions: Our current evidence indicated that POEM is an effective and safe therapeutic modality for the treatment of sigmoid-type achalasia.

Scoping Review and Bibliometric Analysis of the Most Influential Publications in Achalasia Research from 1995 to 2020.

OBJECTIVE: To identify and evaluate characteristics of the most influential articles in achalasia research during the period 1995-2020. METHODS: Articles in Scopus, Web of Science Core Collection (WoSCC), and PubMed were scanned from 1995 to 2020 with achalasia as the keyword. We retrieved the articles that met all criteria by descending order after using EndNote to remove the duplicated references. Our bibliometric analysis highlighted publication year, country, journals, and networks of keywords. RESULTS: Fifteen percent of the top 100 most-cited articles were published in Annals of Surgery. They were performed in 15 countries, and most (n = 55) were from the USA. The number of citations of the 482 articles ranged from 30 to 953, 38 of which had been published in American Journal of Gastroenterology. Those articles were from 31 countries, and most of the studies (n = 217) had been performed in the USA. Most of articles (n = 335) were clinical research. Treatments were hotspots in the field of achalasia in the past years. The most influential title words were "achalasia," "esophagomyotomy," "pneumatic dilation," and "lower esophageal sphincter." CONCLUSION: Our study offers a historical perspective on the progress of achalasia research and identified the most significant evolution in this field. Results showed treatment was the most influence aspect in achalasia.

The Effect of Peroral Endoscopic Myotomy in Achalasia Patients with Prior Endoscopic Intervention: A Systematic Review and Meta-Analysis.

BACKGROUND: Peroral endoscopic myotomy (POEM) has been reported to be effective in achalasia patients with prior failed endoscopic intervention (PFI). We performed this meta-analysis to compare and summarize the clinical outcome of POEM in patients with or without prior endoscopic intervention. METHOD: We searched relevant studies published up to March 2020. Meta-analysis for technical success, clinical success, Eckardt score, lower esophageal sphincter (LES) pressure, clinical reflux, and adverse event were conducted based on a random-effects model. RESULTS: Eight studies enrolling 1,797 patients who underwent POEM were enrolled, including 1,128 naïve achalasia patients and 669 patients with PFI. In the PFI group, the pooled estimated rate of technical success was 97.7% (95% confidence interval [CI], 95.8-98.8%), the pooled clinical success rate was 91.0% (95% CI, 88.0-93.4%), and the pooled adverse events rate was 23.5% (95% CI, 10.6-44.1%). The Eckardt score significantly decreased by 5.95 points (95% CI, 5.50-6.40, p < 0.00001) and the LES pressure significantly reduced by 19.74 mm Hg (95% CI, 14.10-25.39, p < 0.00001) in the PFI group. There were no difference in the technical success, clinical success, and adverse events rate between the treatment-naïve group and PFI group, with a risk ratio of 1.0 (95% CI, 0.99-1.01, p = 0.89), 1.02 (95% CI, 0.98-1.06, p = 0.36), and 0.88 (95% CI, 0.67-1.16, p = 0.38), respectively. CONCLUSIONS: POEM is an effective and safe treatment for achalasia patients with prior endoscopic intervention. Randomized clinical trials are needed to further verify the efficiency and safety of the POEM in those patients.

Evaluation of Surgical Freedom for One-and-a-Half Nostril, Mononostril, and Binostril Endoscopic Endonasal Transsphenoidal Approaches.

Objective This article determines which of the one-and-a-half nostril, mononostril, and binostril endoscopic endonasal transsphenoidal approaches provide a superior manipulation during surgery. Methods The three approaches were orderly performed on 10 silicon-injected cadaveric heads to quantitatively assess surgical freedom and attack angle for sella. Measurements were determined with a standardized method under neuronavigation system using data of computed tomography. Results The one-and-a-half nostril endoscopic transsphenoidal approach (OETA) offered superior exposed area than that of the mononostril approach (META), and similar to that of the binostril approach (BETA). For surgical freedom at anatomic targets, the OETA showed greater surgical flexibility at pituitary center, the right medial optic carotid recess (R-mOCR), the left mOCR, the medial intersection of the right cavernous internal carotid artery, and extension line of upper margin of the clivus (R-mICC) than those of the META, and similar to those of the BETA. For sagittal angle of attack to the R-mOCR, R-mICC, and L-mOCR, the OETA can provide better angular freedom for surgeon than that of the META, and similar to that of the BETA. The OETA had the same axial attack to the pituitary center with the BETA. The OETA and the META had limited surgical freedom at L-mICC, and both inferior to the BETA. Conclusion The OETA has similar exposed area, surgical freedom, and attack angle for most anatomic targets to the BETA without resecting contralateral nasal septal mucosa, and obviously superior to the META.

Clinical outcomes of peroral endoscopic myotomy for achalasia in children: a systematic review and meta-analysis.

Peroral endoscopic myotomy (POEM) is a novel minimally invasive intervention, which has shown to be effective and safe for treating achalasia in adults. Presently, POEM was also reported to be effective for achalasia in children. So we conducted this study to explore the clinical outcomes of POEM for pediatric achalasia. A systematic literature search in PubMed, Embase, and Cochrane databases was performed, which covered the period from January 2009 to June 2020. Selecting studies and collecting data was independently by two reviewers according to predefined criteria. The statistical analysis was carried out using Comprehensive Meta-Analysis software version 2 and Review Manager 5.3. A total of 11 studies with 389 children were identified in the final analysis. Pooled technical success of POEM treatment achalasia was achieved in 385 children (97.4%; 95% confidence interval [CI], 94.7%-98.7%), and the pooled clinical success was achieved in 348 children (92.4%; 95% CI, 89.0%-94.8%). After POEM, the Eckardt score was significantly decreased by 6.76 points (95% CI, 6.18-7.34, P < 0.00001), and the lower esophageal sphincter pressure was significantly reduced by 19.38 mmHg (95% CI, 17.54-21.22, P < 0.00001). The pooled major adverse events rate related to POEM was 12.8% (95% CI, 4.5%-31.5%) and the gastroesophageal reflux rate was 17.8% (95% CI, 14.2%-22.0%). Our current study demonstrated that the POEM was an effective and safe technique for treating achalasia in children. Further randomized comparative studies of POEM and other therapeutic methods are warranted to determine the most effective treatment modality for achalasia in children.

Olfactory outcomes after endonasal skull base surgery: a systematic review.

For the last two decades, endonasal approach has been regularly applied to treat skull base lesions. However, postoperative olfactory dysfunction remains an unsolved problem. This systematic review aimed to identify factors that might affect postoperative olfactory prognosis of patients undergoing endonasal surgery for resection of sellar/parasellar lesions. The literature search was conducted comprehensively to exhaust studies which focused on patients' olfaction with objective olfactory assessments after endonasal skull base surgery. We sought to characterize the potential factors that might affect postoperative olfactory outcomes. Nineteen articles met inclusion criteria. We found that (1) endoscopic surgery was beneficial to patients' olfactory prognosis than microscopic surgery (incidence of postoperative decreased olfactory function: 18.48% (39/211) for the endoscopic group and 36.88% (52/141) for the microscopic group, P < 0.01); meta-analysis for single rate, 20% (95% CI 9-30%) for the endoscopic group and 35% (95% CI 0-72%) for the microscopic group); (2) harvesting septal flaps was an unfavorable factor for olfactory recovery and the rescue flap technique should be preferred compared with the HB flap; (3) no evidence showed that resection of the middle turbinate was detrimental to recovery of olfaction. Patients undergoing endoscopic endonasal surgery may have better olfactory outcomes than those undergoing microscopic endonasal surgery for resection of sellar/parasellar lesions. Special attention should be paid when using septal flaps is planned and the rescue flap technique should be the preferred choice. After resecting the middle turbinate, patients' olfaction still has a great chance of returning to the baseline. More homogeneous and high-quality studies are needed for further assessment.

Endoscopic management of iatrogenic gastrointestinal defects with the over-the-scope clip (OTSC) system: an updated systematic review.

BACKGROUND: Management of iatrogenic gastrointestinal (GI) defects traditionally required surgical interventions. Recently, the over-the-scope-clip system (OTSC) has been reported to be effective for GI defects. So we aimed to conduct an updated systematic review to evaluate the clinical safety and efficacy of the OTSC system for the management of iatrogenic GI defects. MATERIAL AND METHODS: Studies published in PubMed, Embase and Cochrane library from January 2006 to December 2018 were searched. The literature was selected independently by two reviewers according to inclusion and exclusion criteria. The statistical analysis was carried out using Comprehensive Meta-Analysis software version 3.0. RESULTS: A total of 12 studies including 191 patients with iatrogenic GI defects were identified. The major causes for iatrogenic GI defects were endoscopic submucosal dissection (n = 79) and endoscopic mucosal resection (n = 31). Pooled technical success was achieved in 182 patients (89.1%; 95% confidence interval (CI), 81.6%-93.8%, I2 =41.06%), and the pooled clinical success was achieved in 170 patients (85.2%; 95% CI, 71.9%-92.8%, I2=58.92%). Two patients (1%) suffered complications after OTSC system procedures. CONCLUSIONS: Our study revealed that endoscopic closure of iatrogenic GI defects by the OTSC system was a safe and effective approach. Further randomized controlled trials are warranted to compare the OTSC system to other treatment modalities.

Characteristics and publication status of gastrointestinal endoscopy clinical trials registered in ClinicalTrials.gov.

BACKGROUND AND AIMS: This study aimed to examine the fundamental characteristics of gastrointestinal (GI) endoscopy trials and evaluate their publication status. METHODS: A cross-sectional analysis was performed in the ClinicalTrials.gov database, and then the PubMed, Medline, Google Scholar, and Embase databases were searched. A dataset containing GI endoscopy clinical studies from ClinicalTrials.gov registered until November 24, 2017, was downloaded. Data of observational and interventional studies were extracted and analyzed. Publications in peer-reviewed journals were examined for completed trials, and factors associated with publication were identified. RESULTS: A total of 1338 of 253,777 clinical trials were assigned into GI endoscopy, of which 1018 were interventional and 320 were observational studies. Of all the trials, those from the USA comprised the largest percentage (n = 377, 28.18%). The most common field for registered trials was gastroscopy (n = 436, 32.6%), followed by colonoscopy (n = 215, 16.1%), endoscopic ultrasound (n = 186, 13.9%), endoscopic retrograde cholangiopancreatography (n = 176, 13.1%), and novel endoscopic procedure (n = 103, 7.7%). A total of 501 trials were completed before November 25, 2015, 281 (56.1%) of which were published. The median time from study completion to publication was 21 months (interquartile range, 12-32 months). Trials that were comprised of medium sample sizes (150-1000 subjects), conducted in Europe or Asia and other countries, and single or quadruple blinded were more likely to be published. CONCLUSIONS: GI endoscopy is rapidly evolving in clinical applications. Most clinical trials in GI endoscopy are published promptly. These findings demonstrated that investigators are active in performing and communicating the results of clinical trials in the field of GI endoscopy. In the future, the sample size calculation should be presented in detail in the registration system to maintain trial reporting transparency.

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.

The safety and efficacy of endoscopic ultrasound-guided ablation therapy for solid pancreatic tumors: a systematic review.

BACKGROUND AND AIMS: Recently, endoscopic ultrasound (EUS)-guided ablation therapy, as a minimally invasive technique, has shown its potential to substitute surgery in treating solid pancreatic tumors, such as small potential malignant pancreatic tumors, small insulinomas and locally advanced pancreatic ductal adenocarcinoma (LAPDAC). Therefore, we conducted this systematic review to assess the safety and efficacy of EUS-guided ablation therapy for solid pancreatic tumors. METHODS: We conducted a comprehensive search of PubMed, Embase, Cochrane library and Web of Science databases from inception to February 2020. The endpoints were clinical success and complications rates. The pooled event rate was calculated using Comprehensive Meta Analysis software. RESULTS: Fourteen studies with a total of 158 patients were included in our final analysis. The major types of solid pancreatic tumors were nonfunction pancreatic neuroendocrine tumors (n = 78, 49.4%), LAPDAC (n = 48, 30.4%) and insulinomas (n = 26, 16.5%). Overall, the pooled clinical success rate was 85.9% (95% confidence interval (CI): 75.4-92.4%, I 2 = 25.18%), pooled complications rate was 29.1% (95% CI: 18.6-42.3%, I 2 = 50.40%). Subgroup analysis was performed based on ablation methods, which showed clinical success rate for radiofrequency ablation (RFA) was 83.5% (95% CI: 67.9-92.4%), and 87.9% (95% CI: 66.2-96.4%) for ethanol ablation (EA). In terms of complications rate, it was 32.2% (95% CI: 19.4-48.4%) for RFA, and 21.2% (95% CI: 6.8-49.9%) for EA. CONCLUSIONS: EUS-guided ablation therapy is a promising alternative treatment for solid pancreatic tumors, especially for p-NETs and insulinomas < 2 cm, with rarely severe complications. Further prospective studies with long-term follow-up are warranted in future.

Peroral endoscopic myotomy versus pneumatic dilation for achalasia: a systematic review and meta-analysis.

Presently, the primary endoscopic options for the treatment of achalasia are peroral endoscopic myotomy (POEM) and pneumatic dilation. But the clinical outcomes of POEM and pneumatic dilation for achalasia have not yet to be fully evaluated. So, we aimed to compare the clinical outcomes between the two treatment modalities. We searched all the relevant studies published up to September 2019 examining the comparative efficacy between POEM and pneumatic dilation. Outcomes included success rate, Eckardt score, lower esophageal sphincter pressure and adverse events. Outcomes were documented by pooled risk ratios and mean difference with 95% confidence interval (CI) using Review Manager 5.3. Seven studies with a total of 619 patients were identified. There were 298 patients underwent POEM treatment and 321 patients underwent pneumatic dilation treatment. The clinical success rate was higher in the POEM group than that in the pneumatic dilation group at 6, 12 and 24 months' follow-up, with a risk ratio of 1.14 (95% CI, 1.06-1.22, P = 0.0002, I= 0%), 1.34 (95% CI, 1.24-1.45, P < 0.00001, I= 17%) and 1.35 (95% CI, 1.10-1.65, P = 0.004, I= 70%), respectively. The change of Eckardt scores was more obvious in the POEM group than in the pneumatic dilation group, with a mean difference of 1.19 (95% CI, 0.78-1.60, P < 0.00001, I= 70%). The rate of gastroesophageal reflux and other complications for POEM was significantly higher than for pneumatic dilation, with a risk ratio of 4.17 (95% CI, 1.52-11.45, P = 0.006, I= 61%) and 3.78 (95% CI, 1.41-10.16, P = 0.008, I= 0%). Our current evidence suggests that the long-term efficacy of POEM was superior to that of pneumatic dilation, but accompanied by higher complications.