Best of foregut: esophagus, stomach, and duodenum

Abstract

Several major advances have occurred in endoscopic research focused on the foregut (encompassing the esophagus, stomach, and small bowel) in 2015 and 2016. In this review we attempt to briefly describe some of the research with the most impact pertaining to the foregut published in this time frame. In addition to the anatomic subdivisions, the information is subsequently categorized according to disease states. Advances in this field include new methods for Barrett’s esophagus (BE) screening, additional data on progression rates and endoscopic therapy in BE with low-grade dysplasia, and estimates of recurrence after endoscopic therapy. The role of the esophageal epithelial barrier was further defined in eosinophilic esophagitis (EoE) along with potential biomarkers for diagnosing and defining the clinical course of EoE. Several reports describing the efficacy and durability of peroral endoscopic myotomy (POEM) were published along with encouraging data on the endoscopic treatment of obesity. The utility of endoscopic submucosal dissection (ESD) in the management of early gastric cancer was further defined along with novel endoscopic methods to treat gastric varices. Additional data on the utility of video capsule endoscopy (VCE) in the management of obscure GI bleeding and small-bowel neoplastic surveillance in genetic cancer syndromes were also published. The premise of an ideal esophageal adenocarcinoma (EAC) screening program lies in the ability to detect early cancer and improve patient outcomes.1Shaheen N.J. Falk G.W. Iyer P.G. et al.ACG clinical guideline: diagnosis and management of Barrett's esophagus.Am J Gastroenterol. 2016; 111: 30-50Google Scholar Unfortunately, in a Northern Ireland study only 7.3% of EAC had a prior diagnosis of BE. However, a 23% survival benefit for patients in surveillance was reported, after accounting for lead and length time biases, likely accounted by earlier stage at diagnosis (44.2% vs 11.1%) and greater likelihood of undergoing a resection (50.0% vs 25.5%).2Bhat S.K. McManus D.T. Coleman H.G. et al.Oesophageal adenocarcinoma and prior diagnosis of Barrett's oesophagus: a population-based study.Gut. 2015; 64: 20-25Google Scholar Minimally invasive or nonendoscopic interventions are redefining current BE screening paradigms. Unsedated transnasal endoscopy, in a mobile van or hospital setting, allowed for comparable evaluation (P = .080, study completion) and yield for BE (P = .37) compared with conventional endoscopy (EGD) in a randomized community trial. Unsedated transnasal endoscopy had shorter recovery times (P < .01) but, although less tolerable (1.9 and 2.2 vs .4 on a visual analogue scale), had comparable participation rates.3Sami S.S. Dunagan K.T. Johnson M.L. et al.A randomized comparative effectiveness trial of novel endoscopic techniques and approaches for Barrett's esophagus screening in the community.Am J Gastroenterol. 2015; 110: 148-158Google Scholar Findings of an earlier study documenting the utility of a sponge capsule with a protein marker were replicated in a case-control study of 1110 individuals, reporting a sensitivity of 79.9% and a specificity of 92%.4Ross-Innes C.S. Debiram-Beecham I. O'Donovan M. et al.Evaluation of a minimally invasive cell sampling device coupled with assessment of trefoil factor 3 expression for diagnosing Barrett's esophagus: a multi-center case-control study.PLoS Med. 2015; 12: e1001780Google Scholar Annual progression rates in low-grade dysplasia (defined as development of EAC or high-grade dysplasia) were reported to be 2.7% per year in a natural history study from Cleveland. Prevalent cases, male gender, multifocality, and nodules were associated with the higher rates of progression.5Thota P.N. Lee H.J. Goldblum J.R. et al.Risk stratification of patients with Barrett’s esophagus and low-grade dysplasia or indefinite for dysplasia.Clin Gastroenterol Hepatol. 2015; 13: 459-465Google Scholar Confirmation of diagnosis further enhanced progression rates. In a Dutch study, a low-grade dysplasia diagnosis was confirmed in only 27% of initial community diagnoses, and the progression risk in this group was substantially higher (9.1%) compared with .6% in those whose diagnosis was downgraded to no dysplasia.6Duits L.C. Phoa K.N. Curvers W.L. et al.Barrett's oesophagus patients with low-grade dysplasia can be accurately risk-stratified after histological review by an expert pathology panel.Gut. 2015; 64: 700-706Google Scholar Enhanced detection of dysplasia was demonstrated to be feasible by combining autofluorescence imaging with biomarkers such as p53, aneuploidy, and cyclin A, leading to an area under the curve of .97 for detection of high-grade dysplasia/EAC.7di Pietro M. Boerwinkel D.F. Shariff M.K. et al.The combination of autofluorescence endoscopy and molecular biomarkers is a novel diagnostic tool for dysplasia in Barrett's oesophagus.Gut. 2015; : 49-56Google Scholar Volumetric laser endomicroscopy is emerging as a broad-field imaging technology by providing high-resolution cross-sectional surface evaluation of 6-cm BE segments. It was demonstrated to be safe and feasible in a multicenter study.8Wolfsen H.C. Sharma P. Wallace M.B. et al.Safety and feasibility of volumetric laser endomicroscopy in patients with Barrett's esophagus (with videos).Gastrointest Endosc. 2015; 82: 631-640Google Scholar A new scoring system for detection of dysplasia in BE improved sensitivity, specificity, and accuracy to 86%, 88%, and 87%, respectively, when evaluated on dysplasia-enriched EMR specimens, with moderately high κ values (.8).9Leggett C.L. Gorospe E.C. Chan D.K. et al.Comparative diagnostic performance of volumetric laser endomicroscopy and confocal laser endomicroscopy in the detection of dysplasia associated with Barrett's esophagus.Gastrointest Endosc. 2016; 83: 880-888Google Scholar The utility of EUS in the evaluation of early cancer in BE has been debated. In a meta-analysis of 13 studies, EUS correctly identified submucosal invasion (in the absence of visible nodules) in 4% and advanced disease in 14% overall. Additionally, EUS also was highly specific (94%) with a high negative predictive value (96%) in evaluating nodal disease.10Qumseya B.J. Brown J. Abraham M. et al.Diagnostic performance of EUS in predicting advanced cancer among patients with Barrett's esophagus and high-grade dysplasia/early adenocarcinoma: systematic review and meta-analysis.Gastrointest Endosc. 2015; 81: 865-874Google Scholar ESD allows en-bloc removal of neoplastic lesions as an alternative to piecemeal EMR, and its role in BE remains unclear. In a randomized controlled trial comparing ESD (n = 20) with EMR (n = 20) in BE high-grade dysplasia or intramucosal cancer (<3 cm), ESD was able to achieve greater R0 resection, but there were no differences in complete remission of intestinal metaplasia at 3 months. Paradoxically, the only recurrence was noted in the ESD group after a mean follow-up of 23.1 months. The need for curative surgery was also not different between the 2 groups. Two severe adverse events were noted in the ESD but none in the EMR groups. This study underscores the need for additional studies to define the role of ESD in BE endotherapy.11Chevaux J.B. Piessevaux H. Jouret-Mourin A. et al.Clinical outcome in patients treated with endoscopic submucosal dissection for superficial Barrett's neoplasia.Endoscopy. 2015; 47: 103-112Google Scholar, 12Terheggen G. Horn E.M. Vieth M. et al.A randomised trial of endoscopic submucosal dissection versus endoscopic mucosal resection for early Barrett's neoplasia.Gut. 2016; Google Scholar Despite its efficacy in reducing progression and eliminating metaplasia, radiofrequency ablation (RFA) is not a Barrett’s panacea. In a U.S. RFA registry, among 4982 patients, 2% developed EAC (incidence of 7.8 per 1000 person-years) after initiation of RFA, with baseline BE length and histology predicting incidence. The most common causes of death after RFA were cardiovascular and extraesophageal cancers (both 15% individually).13Wolf W.A. Pasricha S. Cotton C. et al.Incidence of esophageal adenocarcinoma and causes of mortality after radiofrequency ablation of Barrett’s esophagus.Gastroenterology. 2015; 149: 1752-1761Google Scholar A strong correlation between the volume of RFA performed by the endoscopist and rates of complete remission of intestinal metaplasia (ρ = .85, P = .014) was reported in a multicenter cohort study.14Fudman D.I. Lightdale C.J. Poneros J.M. et al.Positive correlation between endoscopist radiofrequency ablation volume and response rates in Barrett's esophagus.Gastrointest Endosc. 2014; 80: 71-77Google Scholar A U.K. RFA registry assessed time trends on results with RFA, and reported an improvement in clearance of all dysplasia and clearance of all intestinal metaplasia (77% and 56% to 92% and 83%, P < .0001) between 2008 to 2010 and 2011 to 2013. This was associated with increase in pre-RFA EMR while requiring less “rescue” EMR. This study further supports the hypothesis of improved results with increasing RFA experience.15Haidry R.J. Butt M.A. Dunn J.M. et al.Improvement over time in outcomes for patients undergoing endoscopic therapy for Barrett's oesophagus-related neoplasia: 6-year experience from the first 500 patients treated in the UK patient registry.Gut. 2015; 64: 1192-1199Google Scholar New data on the incidence of recurrence after successful endotherapy and its location were reported. A meta-analysis of 41 studies identified an annual incidence of recurrent intestinal metaplasia, dysplasia, and high-grade dysplasia/EAC of 7.1%, 1.3%, and .8%, respectively. This study confirmed increasing age and length of the BE segment as predictors of recurrence. Most recurrences (>90%) were endoscopically treatable.16Krishnamoorthi R. Singh S. Ragunathan K. et al.Risk of recurrence of Barrett's esophagus after successful endoscopic therapy.Gastrointest Endosc. 2016; 83: 1090-1106Google Scholar In another study, with the exception of those associated with endoscopic findings (60%), all remaining recurrences occurred within 1 cm of the gastroesophageal junction.17Cotton C.C. Wolf W.A. Pasricha S. et al.Recurrent intestinal metaplasia after radiofrequency ablation for Barrett's esophagus: endoscopic findings and anatomic location.Gastrointest Endosc. 2015; 81: 1362-1369Google Scholar Hence, although RFA is an effective treatment modality, post-treatment surveillance remains essential. Cost-effective practices might limit histologic acquisition to areas of highest yield. The prevalence of EoE is currently estimated at 50 to 100 per 100,000 persons in the Western world. The rising incidence of EoE has been variably attributed to greater disease awareness, revised histologic criteria, and a true rising incidence. A study from the Danish National Registry reported that the rising incidence of EoE outweighed the increased frequency of biopsy sampling by 20- to 25-fold.18Dellon E.S. Erichsen R. Baron J.A. et al.The increasing incidence and prevalence of eosinophilic esophagitis outpaces changes in endoscopic and biopsy practice: National population-based estimates from Denmark.Aliment Pharmacol Ther. 2015; 41: 662-670Google Scholar Analysis of a cross-sectional pathology database confirmed seasonal and geographic variations in EoE, with the highest incidence in July (adjusted odds ratio, 1.13) and in temperate and cold climates.19Jensen E.T. Shah N.D. Hoffman K. et al.Seasonal variation in detection of oesophageal eosinophilia and eosinophilic oesophagitis.Aliment Pharmacol Ther. 2015; 42: 461-469Google Scholar The overlap between EoE and GERD extends from esophageal eosinophilia to proton pump inhibitor (PPI) response. PPI-responsive eosinophilia has emerged as a distinct entity. A meta-analysis of studies on PPI-responsive eosinophilia identified clinical response and histologic remission rates of 60.8% and 50.05%, respectively. There was a trend toward increased PPI efficacy in prospective trials, pH-confirmed GERD, and twice a day administration.20Lucendo A.J. Arias A. Molina-Infante J. Efficacy of proton pump inhibitor drugs for inducing clinical and histologic remission in patients with symptomatic esophageal eosinophilia: a systematic review and meta-analysis.Clin Gastroenterol Hepatol. 2016; 14: 13-22Google Scholar In an attempt to explore the role of biomarkers in predicting EoE course, histologic specimens from patients with EoE, PPI-responsive eosinophilia, and GERD with dense eosinophilia were stained for eotaxin-3 (a protein implicated in activation, recruitment, and degranulation of eosinophils). Staining scores and intensity were higher in EoE compared with GERD (P = .002 and P < .001, respectively), with a trend toward significance between EoE and PPI-responsive eosinophilia (P = .054). The histologic evaluation was limited by the lack of a validated scoring method for eotaxin-3 staining intensity.21Moawad F.J. Schoepfer A.M. Safroneeva E. et al.Eosinophilic oesophagitis and proton pump inhibitor-responsive oesophageal eosinophilia have similar clinical, endoscopic and histological findings.Aliment Pharmacol Ther. 2014; 39: 603-608Google Scholar Eotaxin-3 levels (P = .02) also independently predicted response to steroids in another study.22Wolf W.A. Cotton C.C. Green D.J. et al.Evaluation of histologic cutpoints for treatment response in eosinophilic esophagitis.J Gastroenterol Hepatol Res. 2015; 4: 1780-1787Google Scholar Endoscopic biopsy sampling remains the criterion standard diagnostic tool for EoE. Guidelines have advocated for a threshold 15 eosinophils per high-power field. Investigators at University of North Carolina found that although a threshold of 15 eosinophils per high-power field had excellent sensitivity of 100% and specificity of 96%, marked variability in eosinophil counts existed within individual patients and between collected specimens. Inflammatory endoscopic findings (exudative plaques and furrows) also correlated with a higher yield of eosinophilia in 2 studies.23Dellon E.S. Speck O. Woodward K. et al.Distribution and variability of esophageal eosinophilia in patients undergoing upper endoscopy.Mod Pathol. 2015; 28: 383-390Google Scholar, 24Salek J. Clayton F. Vinson L. et al.Endoscopic appearance and location dictate diagnostic yield of biopsies in eosinophilic oesophagitis.Aliment Pharmacol Ther. 2015; 41: 1288-1295Google Scholar Firmness during tissue biopsy acquisition (“pull sign”) performed by a single endoscopist had a specificity of 98% for EoE (area under the curve = .871), resolved with therapy, but had no correlation to predicted histology of lamina propria fibrosis (P = .72).25Dellon E.S. Gebhart J.H. Higgins L.L. et al.The esophageal biopsy “pull” sign: a highly specific and treatment-responsive endoscopic finding in eosinophilic esophagitis (with video).Gastrointest Endosc. 2016; 83: 92-100Google Scholar Functional parameters to diagnose and monitor treatment effect have been recently described in EoE. In a prospective trial, treatment effects of swallowed fluticasone on the esophageal epithelial barrier were measured. In vivo (transepithelial electrical resistance) and ex vivo (transepithelial molecule flux) measures of mucosal integrity were analyzed. Increased impedance (P < .01) and reduced molecular flux (P < .05) suggestive of restitution of the epithelial barrier were noted on steroids.26van Rhijn B.D. Verheij J. van den Bergh Weerman M.A. et al.Histological response to fluticasone propionate in patients with eosinophilic esophagitis is associated with improved functional esophageal mucosal integrity.Am J Gastroenterol. 2015; 110: 1289-1297Google Scholar Endoscopy is used to monitor response in EoE. The capsule sponge (discussed in detail above) offers a promising alternative along with the added advantage of consistent pan-esophageal cellular sampling. Accuracy, safety, and tolerability were evaluated in a pilot study of 20 patients. Eosinophilia correlated with histologic samples on EGD (r = .50, P = .025). In addition to eosinophils, the authors also evaluated degranulation protein that strongly correlated with eosinophils per high-power field (P = .0223). The sponge was safe across a range of esophageal diameters, and except for 1 patient, there were only minimal abrasions on tandem endoscopies.27Katzka D.A. Geno D.M. Ravi A. et al.Accuracy, safety, and tolerability of tissue collection by Cytosponge vs endoscopy for evaluation of eosinophilic esophagitis.Clin Gastroenterol Hepatol. 2015; 13: 77-83Google Scholar None of the available treatments for EoE is approved by the U.S. Food and Drug Administration. Moreover, response rates to steroid therapy and/or dietary eliminations vary. Previous work has identified IL-13 as a likely tailored therapeutic target because it was significantly induced in ex vivo epithelial transcripts from EoE patients. QAX576, a fully human monoclonal anti-IL13 antibody, was studied in 23 patients in a pilot trial. Despite a sustained 6-month reversal in the transcriptome and reduction in intraepithelial eosinophil count, it was only able to achieve a trend toward clinical improvement.28Rothenberg M.E. Wen T. Greenberg A. et al.Intravenous anti-IL-13 mAb QAX576 for the treatment of eosinophilic esophagitis.J Allergy Clin Immunol. 2015; 135: 500-507Google Scholar The Chicago classification has provided consensus definitions and pathologic diagnostic thresholds in high-resolution manometry for the evaluation of esophageal motility disorders. In its third iteration, it has aggregated prior entities (occasionally seen in asymptomatic individuals) into minor disorders. It has also prioritized others through a hierarchical approach. Major disorders of peristalsis include absent peristalsis, distal esophageal spasm, and jackhammer esophagus, whereas disorders of esophagogastric junction outflow include the 3 subtypes of achalasia.29Kahrilas P.J. Bredenoord A.J. Fox M. et al.The Chicago Classification of esophageal motility disorders, v3.0.Neurogastroenterol Motil. 2015; 27: 160-174Google Scholar POEM has emerged as a novel treatment option for achalasia. A meta-analysis of 19 studies noted a significant reduction in Eckardt’s dysphagia scores and reduction in lower esophageal sphincter pressure.30Talukdar R. Inoue H. Nageshwar Reddy D. Efficacy of peroral endoscopic myotomy (POEM) in the treatment of achalasia: a systematic review and meta-analysis.Surg Endosc. 2015; 29: 3030-3046Google Scholar In another study of 40 achalasia patients, POEM in treatment-naive subjects (n = 16) tended to be quicker (P = .07) and had no significant difference in adverse events, clinical dysphagia, and reflux scores compared with patients with prior treatment.31Orenstein S.B. Raigani S. Wu Y.V. et al.Peroral endoscopic myotomy (POEM) leads to similar results in patients with and without prior endoscopic or surgical therapy.Surg Endosc. 2015; 29: 1064-1070Google Scholar Although such excellent outcomes can be achieved by expert endoscopists, they could also be achieved after 40 to 60 cases based on a learning curve analysis study from a single-operator experience of 93 consecutive POEMs.32Patel K.S. Calixte R. Modayil R.J. et al.The light at the end of the tunnel: a single-operator learning curve analysis for per oral endoscopic myotomy.Gastrointest Endosc. 2015; 81: 1181-1187Google Scholar In addition to achalasia, an extended myotomy POEM that includes the esophageal body (average length, 16 cm) was shown to be 93% clinically effective in spastic esophageal disorders in 73 “difficult-to-treat” patients from 11 international centers without serious adverse events.33Khashab M.A. Messallam A.A. Onimaru M. et al.International multicenter experience with peroral endoscopic myotomy for the treatment of spastic esophageal disorders refractory to medical therapy (with video).Gastrointest Endosc. 2015; 81: 1170-1177Google Scholar Continued refinement of the procedure was described in a report of a 1000-case experience. Aspects discussed included equipment, technique, adverse event management, and procedural training.34Bechara R. Onimaru M. Ikeda H. et al.Per-oral endoscopic myotomy, 1000 cases later: pearls, pitfalls, and practical considerations.Gastrointest Endosc. 2016; 84: 330-338Google Scholar The enormity of the health economics of reflux disease is daunting; improving our diagnostic accuracy while reducing costs is essential. In a prospective longitudinal study of 268 patients with mixed diagnoses, a novel mucosal impedance catheter was compared with wireless pH testing on and off PPIs. Mucosal impedance was significantly lower in untreated GERD and EoE compared with control subjects without reflux (including achalasia). The pattern of mucosal impedance was different in reflux esophagitis compared with EoE, and it normalized with PPIs. Compared with wireless pH testing, mucosal impedance had a higher degree of specificity and positive predictive value (95% vs 64% and 96% vs 40%, respectively).35Ates F. Yuksel E.S. Higginbotham T. et al.Mucosal impedance discriminates GERD from non-GERD conditions.Gastroenterology. 2015; 148: 334-343Google Scholar Challenges in GERD also extend into treatment. In addition to an expanding population desiring to discontinue PPIs, many patients are symptomatic despite optimal PPI therapy. This has reinvigorated interest in nonpharmacologic therapy. Because fundoplications are invasive, endoscopic alternatives have been explored. One hundred twenty-nine patients were randomized to transoral incisionless fundoplication and placebo versus sham endoscopy and PPIs (∼2:1). Transoral incisionless fundoplication eliminated troublesome regurgitation (67% vs 45%, P = .023) and achieved greater pH control (9.3% vs 6.3%, P < .001). However, both groups had similar improvement in symptom score and adverse event profiles.36Hunter J.G. Kahrilas P.J. Bell R.C. et al.Efficacy of transoral fundoplication vs omeprazole for treatment of regurgitation in a randomized controlled trial.Gastroenterology. 2015; 148: 324-333Google Scholar This was supported in another randomized controlled trial that found a global difference in troublesome regurgitation and extraesophageal symptoms at 6 months (62% vs 5%, P = .009).37Trad K.S. Barnes W.E. Simoni G. et al.Transoral incisionless fundoplication effective in eliminating GERD symptoms in partial responders to proton pump inhibitor therapy at 6 months: the TEMPO Randomized Clinical Trial.Surg Innov. 2015; 22: 26-40Google Scholar However, long-term efficacy was questioned in a similar trial of 60 patients randomized to transoral incisionless fundoplication versus optimal PPIs (2:1 ratio). Although all patients opted to cross over into the transoral incisionless fundoplication group, which had improved distal esophageal acid exposure at 6 months, no improvement was noted at 12 months. Moreover, 71% had worsened lower esophageal sphincter function and 61% resumed PPIs at the end of the study.38Witteman B.P. Conchillo J.M. Rinsma N.F. et al.Randomized controlled trial of transoral incisionless fundoplication vs. proton pump inhibitors for treatment of gastroesophageal reflux disease.Am J Gastroenterol. 2015; 110: 531-542Google Scholar Esophageal stents remain the optimal therapy for palliation of dysphagia in esophageal malignancy given developments in stent materials, delivery mechanisms, and greater endoscopic experience. Careful selection of patients is necessary to improve outcomes. In a prospective single-center trial of 40 consecutive patients with stage 2/3 gastroesophageal junction tumors, esophageal stents were associated with improved dysphagia score (P = .01) with associated improvement in quality of life score, sustained over 10 weeks of follow-up. Of note, 85% completed chemotherapy and/or radiation. Although increased reflux was adequately controlled with lifestyle modifications and PPIs in most patients, stent migration was seen in 63% of patients.39Philips P. North D.A. Scoggins C. et al.Gastric-esophageal stenting for malignant dysphagia: results of prospective clinical trial evaluation of long-term gastroesophageal reflux and quality of life-related symptoms.J Am Coll Surg. 2015; 221: 165-173Google Scholar The role of stents in the management of refractory benign esophageal strictures is unclear. Seventy consecutive patients with refractory benign esophageal strictures from 2 tertiary referral centers were retrospectively studied. Clinical success across heterogeneous etiologies was hampered when stents (various types) were used (odds ratio, 3.7; 95% confidence interval, 1.01-19.0). The authors concluded that stents were not helpful in most patients with refractory benign esophageal strictures.40Repici A. Small A.J. Mendelson A. et al.Natural history and management of refractory benign esophageal strictures.Gastrointest Endosc. 2016; 84: 222-228Google Scholar Although gastric antral vascular ectasias are an uncommon source of upper GI bleeding and are adequately controlled by various endoscopic thermal therapies, a 14% failure rate has been observed, and refractory presentations can occur.41Zepeda-Gomez S. Sultanian R. Teshima C. et al.Gastric antral vascular ectasia: a prospective study of treatment with endoscopic band ligation.Endoscopy. 2015; 47: 538-540Google Scholar Nine patients with refractory gastric antral vascular ectasias were enrolled in a study of RFA using the focal RFA device. Eradication (complete transfusion independence) was achieved in 2 to 6 sessions (median, 3), without adverse events. There was sustained response in 78% over a median 11 months of follow-up. RFA may provide a broad area of uniform coaptive coagulation.42Raza N. Diehl D.L. Radiofrequency ablation of treatment-refractory gastric antral vascular ectasia (GAVE).Surg Laparosc Endosc Percutan Tech. 2015; 25: 79-82Google Scholar An alternative approach is endoscopic band ligation. Twenty-one patients with gastric antral vascular ectasias were treated with serial endoscopic band ligation at 2-month intervals, and 91% achieved clinical response without any adverse events.41Zepeda-Gomez S. Sultanian R. Teshima C. et al.Gastric antral vascular ectasia: a prospective study of treatment with endoscopic band ligation.Endoscopy. 2015; 47: 538-540Google Scholar Gastric variceal bleeds are associated with higher mortality than esophageal variceal bleeds. Although definitive treatment is lacking, cyanoacrylate glue injection is currently considered the best hemostatic approach. A Cochrane meta-analysis of 6 trials found poor level of evidence with significant heterogeneity. Of note, the follow-up period varied (6-26 months), and the comparators were different (other endoscopic therapy, alcohol-based sclerotherapy, and endoscopic band ligation). The authors concluded that although cyanoacrylate injection was the most effective modality, uncertainty remains regarding mortality, frequency of success, and adverse events.43Rios Castellanos E. Seron P. Gisbert J.P. et al.Endoscopic injection of cyanoacrylate glue versus other endoscopic procedures for acute bleeding gastric varices in people with portal hypertension.Cochrane Database Syst Rev. 2015; : Cd010180Google Scholar Prophylactic treatment of gastric varices has been proposed. In a retrospective chart review of 152 patients with gastric fundal varices treated with EUS-guided coiling and sclerosant injection, primary prophylaxis was the indication for intervention in 26%, whereas the remaining 69% and 5% were for recent bleeding and active hemorrhage, respectively. Complete obliteration (verified on Doppler study) was achieved in 93%, but post-treatment bleeding occurred in 3%. Obliteration occurred after 1 session in most patients, but 10% required 2 procedures, whereas 4% needed 3 to 4 procedures. Ninety-six percent of the primary prophylaxis group had sustained obliteration on follow-up endoscopy. Adverse events included 1 patient with possible pulmonary embolization and 4 with mild postprocedural abdominal pain. The authors proposed primary and secondary prophylactic therapy of gastric varices based on size, location, and dominance.44Bhat Y.M. Weilert F. Fredrick R.T. et al.EUS-guided treatment of gastric fundal varices with combined injection of coils and cyanoacrylate glue: a large U.S. experience over 6 years (with video).Gastrointest Endosc. 2016; 83: 1164-1172Google Scholar Endoscopic bariatric interventions may offer an attractive alternative to current options. Space-occupying balloons that resembled restrictive surgeries are 1 of the options. A dual-balloon device was designed to minimize adverse events, notably migration. Three hundred twenty-six patients (body mass indices, 30-40 kg/m2) were randomized in a blinded sham trial to diet and exercise alone versus an additional dual-balloon system; 11.3% versus 25.1% achieved the primary endpoint of excess body weight reduction at 24 weeks. Expected abdominal pain symptoms abated with supportive measures, but 35% developed gastric ulcers (reduced to 10% after minor device adjustment) and 9% of balloons had to be retrieved for other reasons. All balloons were retrieved after 6 months of treatment per protocol.45Ponce J. Woodman G. Swain J. et al.The REDUCE pivotal trial: a prospective, randomized controlled pivotal trial of a dual intragastric balloon for the treatment of obesity.Surg Obes Relat Dis. 2015; 11: 874-881Google Scholar Roux-en-Y gastric bypass has been limited by a 30% loss of efficacy because of widening of the gastrojejunal anastomosis aperture. Endoscopic suturing has been developed to perform transoral outlet reduction of the widened aperture. In a prospective study of 150 patients with weight gain after Roux-en-Y gastric bypass, transoral outlet reduction achieved durable weight loss in 24.9%, 20.0%, and 19.2% excess weight loss at 1, 2, and 3 years, respectively, without adverse event