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Best of foregut: esophagus, stomach, and duodenum

Published:October 13, 2016DOI:https://doi.org/10.1016/j.gie.2016.10.005

      Abbreviations:

      BE (Barrett’s esophagus), EAC (esophageal adenocarcinoma), EoE (eosinophilic esophagitis), ESD (endoscopic submucosal dissection), POEM (peroral endoscopic myotomy), PPI (proton pump inhibitor), RFA (radiofrequency ablation), VCE (video capsule endoscopy)
      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.

      Esophagus

       Barrett’s esophagus

      The premise of an ideal esophageal adenocarcinoma (EAC) screening program lies in the ability to detect early cancer and improve patient outcomes.
      • Shaheen N.J.
      • Falk G.W.
      • Iyer P.G.
      • et al.
      ACG clinical guideline: diagnosis and management of Barrett's esophagus.
      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%).
      • Bhat S.K.
      • McManus D.T.
      • Coleman H.G.
      • et al.
      Oesophageal adenocarcinoma and prior diagnosis of Barrett's oesophagus: a population-based study.
      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.
      • Sami 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.
      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%.
      • Ross-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.
      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.
      • Thota 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.
      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.
      • Duits 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.
      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.
      • di 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.
      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.
      • Wolfsen H.C.
      • Sharma P.
      • Wallace M.B.
      • et al.
      Safety and feasibility of volumetric laser endomicroscopy in patients with Barrett's esophagus (with videos).
      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).
      • Leggett 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.
      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.
      • Qumseya 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.
      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.
      • Chevaux J.B.
      • Piessevaux H.
      • Jouret-Mourin A.
      • et al.
      Clinical outcome in patients treated with endoscopic submucosal dissection for superficial Barrett's neoplasia.
      • Terheggen G.
      • Horn E.M.
      • Vieth M.
      • et al.
      A randomised trial of endoscopic submucosal dissection versus endoscopic mucosal resection for early Barrett's neoplasia.
      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).
      • Wolf W.A.
      • Pasricha S.
      • Cotton C.
      • et al.
      Incidence of esophageal adenocarcinoma and causes of mortality after radiofrequency ablation of Barrett’s esophagus.
      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.
      • Fudman D.I.
      • Lightdale C.J.
      • Poneros J.M.
      • et al.
      Positive correlation between endoscopist radiofrequency ablation volume and response rates in Barrett's esophagus.
      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.
      • Haidry 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.
      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.
      • Krishnamoorthi R.
      • Singh S.
      • Ragunathan K.
      • et al.
      Risk of recurrence of Barrett's esophagus after successful endoscopic therapy.
      In another study, with the exception of those associated with endoscopic findings (60%), all remaining recurrences occurred within 1 cm of the gastroesophageal junction.
      • Cotton C.C.
      • Wolf W.A.
      • Pasricha S.
      • et al.
      Recurrent intestinal metaplasia after radiofrequency ablation for Barrett's esophagus: endoscopic findings and anatomic location.
      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.

       Eosinophilic esophagitis

      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.
      • Dellon 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.
      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.
      • Jensen E.T.
      • Shah N.D.
      • Hoffman K.
      • et al.
      Seasonal variation in detection of oesophageal eosinophilia and eosinophilic oesophagitis.
      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.
      • Lucendo 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.
      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.
      • Moawad 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.
      Eotaxin-3 levels (P = .02) also independently predicted response to steroids in another study.
      • Wolf W.A.
      • Cotton C.C.
      • Green D.J.
      • et al.
      Evaluation of histologic cutpoints for treatment response in eosinophilic esophagitis.
      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.
      • Dellon E.S.
      • Speck O.
      • Woodward K.
      • et al.
      Distribution and variability of esophageal eosinophilia in patients undergoing upper endoscopy.
      • Salek J.
      • Clayton F.
      • Vinson L.
      • et al.
      Endoscopic appearance and location dictate diagnostic yield of biopsies in eosinophilic oesophagitis.
      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).
      • Dellon 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).
      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.
      • van 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.
      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.
      • Katzka 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.
      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.
      • Rothenberg M.E.
      • Wen T.
      • Greenberg A.
      • et al.
      Intravenous anti-IL-13 mAb QAX576 for the treatment of eosinophilic esophagitis.

       Motility and POEM

      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.
      • Kahrilas P.J.
      • Bredenoord A.J.
      • Fox M.
      • et al.
      The Chicago Classification of esophageal motility disorders, v3.0.
      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.
      • Talukdar R.
      • Inoue H.
      • Nageshwar Reddy D.
      Efficacy of peroral endoscopic myotomy (POEM) in the treatment of achalasia: a systematic review and meta-analysis.
      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.
      • Orenstein 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.
      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.
      • Patel 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.
      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.
      • Khashab 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).
      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.
      • Bechara R.
      • Onimaru M.
      • Ikeda H.
      • et al.
      Per-oral endoscopic myotomy, 1000 cases later: pearls, pitfalls, and practical considerations.

       GERD and transoral incisionless fundoplication

      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).
      • Ates F.
      • Yuksel E.S.
      • Higginbotham T.
      • et al.
      Mucosal impedance discriminates GERD from non-GERD conditions.
      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.
      • Hunter 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.
      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).
      • Trad 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.
      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.
      • Witteman 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.

       Esophageal stents

      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.
      • Philips 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.
      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.
      • Repici A.
      • Small A.J.
      • Mendelson A.
      • et al.
      Natural history and management of refractory benign esophageal strictures.

      Gastric

       Gastric antral vascular ectasias

      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.
      • Zepeda-Gomez S.
      • Sultanian R.
      • Teshima C.
      • et al.
      Gastric antral vascular ectasia: a prospective study of treatment with endoscopic band ligation.
      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.
      • Raza N.
      • Diehl D.L.
      Radiofrequency ablation of treatment-refractory gastric antral vascular ectasia (GAVE).
      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.
      • Zepeda-Gomez S.
      • Sultanian R.
      • Teshima C.
      • et al.
      Gastric antral vascular ectasia: a prospective study of treatment with endoscopic band ligation.

       Gastric varices

      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.
      • Rios 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.
      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.
      • Bhat 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).

       Endobariatrics

      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.
      • Ponce 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.
      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 events.
      • Kumar N.
      • Thompson C.C.
      Transoral outlet reduction for weight regain after gastric bypass: long-term follow-up.

       Gastric cancer and ESD

      ESD is currently the standard of care for the treatment of early gastric cancers.
      • Bhatt A.
      • Abe S.
      • Kumaravel A.
      • et al.
      Indications and techniques for endoscopic submucosal dissection.
      Previously limited to “conventional indications,” an expanded list of indications has recently been defined including smaller ulcerated intramucosal and superficially invasive submucosal cancers. A meta-analysis compared the outcomes of ESD in expanded list of indications compared with conventional indications in 1241 patients from 13 nonrandomized trials. The study revealed similar long-term survival (gastric cancer mortality, P = .22; all-cause mortality, P = .37) but lower rates of en-bloc resection, complete and curative resection, and unfavorable short-term outcomes (delayed bleeding and perforation) in expanded list of indication cancers (all P < .001). Moreover, survival rates in both groups were comparable with gastrectomy with lymph node dissection.
      • Peng L.J.
      • Tian S.N.
      • Lu L.
      • et al.
      Outcome of endoscopic submucosal dissection for early gastric cancer of conventional and expanded indications: systematic review and meta-analysis.
      Bleeding (3.1%) and perforation (1.2%-5.2%) are the most common adverse events after gastric ESD.
      • Wolfsen H.C.
      • Sharma P.
      • Wallace M.B.
      • et al.
      Safety and feasibility of volumetric laser endomicroscopy in patients with Barrett's esophagus (with videos).
      A nonrandomized trial evaluated the efficacy and safety of covering the resection site in 41 high-risk patients with a protective polyglycolic acid sheet (absorbent suture material fixed with fibrin glue). There was a significant drop in bleeding rate (6.7% vs 22.0%, P = .041) when compared with historical control subjects.
      • Tsuji Y.
      • Fujishiro M.
      • Kodashima S.
      • et al.
      Polyglycolic acid sheets and fibrin glue decrease the risk of bleeding after endoscopic submucosal dissection of gastric neoplasms (with video).
      Second-look endoscopy is a common practice after ESD. A noninferiority multicenter prospective trial (n = 262, 1:1 randomization) assessed the value of second-look endoscopy 1 day after ESD and found it reduced bleeding risk with a difference of –1.6% (95% confidence interval, –6.7 to 3.5; P noninferiority < .001). Second-look endoscopy in ESD was noninferior even when prophylactic coagulation was undertaken. The authors concluded that in most patients second-look endoscopy is not indicated, which could represent a significant cost-saving practice.
      • Mochizuki S.
      • Uedo N.
      • Oda I.
      • et al.
      Scheduled second-look endoscopy is not recommended after endoscopic submucosal dissection for gastric neoplasms (the SAFE trial): a multicentre prospective randomised controlled non-inferiority trial.
      Patient quality of life is a less discussed aspect of care in gastric cancer. Although ESD is comparable in curative resections with surgery in early gastric cancers, it preserves the function of the stomach, likely leading to improved quality of life, counterbalanced by worry regarding residual or recurrent cancer. A cross-sectional study of 565 patients with early gastric cancers undergoing ESD and surgery evaluated quality of life questionnaires and anxiety and depression scales. Although surgery was associated with impaired quality of life, the ESD group had a higher worry of cancer recurrence despite adjusting for covariates. There were no differences in anxiety and depression scales. This study emphasizes the importance of physician-directed evaluation of quality of life in patients receiving treatment for gastric cancer.
      • Choi J.H.
      • Kim E.S.
      • Lee Y.J.
      • et al.
      Comparison of quality of life and worry of cancer recurrence between endoscopic and surgical treatment for early gastric cancer.

      Duodenum

       Capsule endoscopy

      Indications for VCE continue to expand. In Crohn’s disease, VCE has been shown to be helpful in diagnosing small-bowel disease, determining the extent and degree of inflammation, and evaluating response to therapy. The Lewis Score is a composite of small-bowel edema, ulceration, and stenosis and was standardized using an online calculator in a retrospective blinded study of 70 patients. There was high correlation within the individual tertiles, various stages of inflammatory activity, and for the global score (r = .745-.928, P < .0001). Studies were evaluated by 3 investigators with a central reader in a retrospective blinded single-center study.
      • Cotter J.
      • Dias de Castro F.
      • Magalhaes J.
      • et al.
      Validation of the Lewis score for the evaluation of small-bowel Crohn's disease activity.
      Although the quality of VCE images has dramatically improved, identifying subtle aphthous ulcers, their clinical impact in Crohn’s is questionable. In a retrospective evaluation of 187 patients, VCE changed management in 52% of cases, despite the VCE findings not correlating with noninvasive inflammatory markers (C-reactive protein and fecal calprotectin).
      • Kopylov U.
      • Nemeth A.
      • Koulaouzidis A.
      • et al.
      Small bowel capsule endoscopy in the management of established Crohn's disease: clinical impact, safety, and correlation with inflammatory biomarkers.
      Capsule retention remains a concerning adverse event in Crohn’s patients undergoing VCE. The incidence of retention (lack of capsule expulsion after 2 weeks of ingestion) remains unclear. A retrospective review from a large tertiary care center identified a risk of .3%. The cohort was managed surgically, endoscopically, and conservatively in 10, 2, and 4 patients, respectively. In the conservative management group, 3 had capsule expulsion after control of inflammation. High-risk features included surgical small-bowel anastomoses and evidence of partial obstruction on CT.
      • Al-Bawardy B.
      • Locke G.
      • Huprich J.E.
      • et al.
      Retained capsule endoscopy in a large tertiary care academic practice and radiologic predictors of retention.
      VCE is a valuable tool in the workup of obscure GI bleeding. In a prospective trial of acute hemodynamically significant GI bleeding without hematochezia, 20 of 88 patients had a negative EGD. Immediately placed duodenal VCE after duodenal infusion of polyethylene glycol (500 mL) correctly guided further management in 85% patients (95% confidence interval, 62%-97%). Completion rate of VCE was 95%, whereas diagnostic yield was 75%. Duodenally placed VCE, although diagnostic only, may guide clinicians to the precise location of bleeding without a colonoscopy because images are not limited to the small bowel alone; in fact, 20% of bleeding lesions were detected in the cecum.
      • Schlag C.
      • Menzel C.
      • Nennstiel S.
      • et al.
      Emergency video capsule endoscopy in patients with acute severe GI bleeding and negative upper endoscopy results.
      The role of emergency double-balloon endoscopy in the evaluation of acute obscure GI bleeding is unclear. Emergency double-balloon endoscopy was able to achieve hemostasis in 78% of patients when performed within 24 hours from symptom onset, in a retrospective study of 24 patients. Lesion detection rate was significantly higher when compared with routine double-balloon endoscopy (>24 hour) (40.7% vs .9%, P < .001); 67% of lesions were vascular in nature. Addition of VCE to the evaluation altered the direction of double-balloon endoscopy in 25% of patients.
      • Perez-Cuadrado Robles E.
      • Bebia Conesa P.
      • Esteban Delgado P.
      • et al.
      Emergency double-balloon enteroscopy combined with real-time viewing of capsule endoscopy: a feasible combined approach in acute overt-obscure gastrointestinal bleeding?.
      VCE may assist in small-bowel surveillance for neoplasms in hereditary syndromes that predispose to small-bowel tumors. A small-bowel tumor prevalence of 1.5% was observed in a study of 200 asymptomatic carriers of gene mutations, associated with small-bowel tumors. However, false-negative assessments can occur as demonstrated by 3 carcinomas missed by VCE, all of which were duodenal and within reach of an upper endoscope.
      • Haanstra J.F.
      • Al-Toma A.
      • Dekker E.
      • et al.
      Prevalence of small-bowel neoplasia in Lynch syndrome assessed by video capsule endoscopy.
      A proprietary motility capsule (Smart pill, Covidien, Minneapolis, Minn) has been developed that monitors pH, temperature, and pressure parameters and is capable of diagnosing GI dysmotility. A retrospective study of 161 patients aimed to determine clinical utility and diagnostic yield of this capsule; 67.7% of patients had abnormal testing and nearly half of them had simultaneous multiregional dysmotility, whereas 16%, 12%, and 23% had isolated gastroparesis, small-bowel dysmotility, and large-bowel dysmotility, respectively. There was poor correlation with both upper and lower GI symptoms. Nearly half of the patients had normal testing, reflecting a subset of functional diseases. The diagnostic and prognostic utility of this promising capsule device remains to be established.
      • Arora Z.
      • Parungao J.M.
      • Lopez R.
      • et al.
      Clinical utility of wireless motility capsule in patients with suspected multiregional gastrointestinal dysmotility.

       Duodenal tumor surveillance and therapy

      The lifetime incidence of duodenal adenomas in familial adenomatous polyposis approaches 100%, with a carcinoma risk of 3% to 10%. The optimal approach to surveillance and treatment in this population is unclear. In a single-center study of 80 patients with familial adenomatous polyposis followed for 7.2 years, a surveillance protocol was able to prevent development of any carcinomas. The protocol used annual forward and/or side-viewing endoscopy with EUS evaluation for all ampullary adenomas. EUS allowed more accurate size measurements, with advanced adenomas (>10 mm) undergoing ampullectomy. Thirty-eight patients had ampullary adenomas, 10 of whom had advanced adenomas; an additional 9 patients were upstaged as advanced based EUS measurements and the absence of other criteria. Ampullectomies were endoscopically performed in 15 patients, of whom 10 had recurrences. Two ultimately required surgery, and 3 underwent repeat ampullectomy. Twenty-three patients had advanced nonampullary adenomas, and all were treated endoscopically.
      • Gluck N.
      • Strul H.
      • Rozner G.
      • et al.
      Endoscopy and EUS are key for effective surveillance and management of duodenal adenomas in familial adenomatous polyposis.
      Equally unclear are recommendations for resection of GI stromal tumors of the upper GI tract. Endoscopic options for the management of these lesions are expanding. A retrospective review of 130 patients who underwent resection of foregut GI stromal tumors (70% endoscopic, 30% surgical) found notable differences between the 2 approaches. When compared with the surgical group, endoscopic resections were more likely to involve gastric lesions (P = .001), smaller lesions (2.3 vs 5.1 cm, P < .001), shorter procedure times (51.8 ± 36.2 vs 124.6 ± 74.7 minutes; P < .001), and shorter hospital stays (3.3 ± 2.4 vs 8.3 ± 5.4 days; P < .001). Although rate of R0 resection was lower (25.6% vs 85.0%, P = .001) in the endoscopic group, there were no significant differences in recurrence despite a mean follow-up of 45.5 months (2.2% vs 5.0%, P = .586).
      • Joo M.K.
      • Park J.J.
      • Kim H.
      • et al.
      Endoscopic versus surgical resection of GI stromal tumors in the upper GI tract.

       Stents

      Malignant gastroduodenal obstructions are seen in advanced foregut GI malignancies and are associated with poor quality of life in the setting of dehydration, malnutrition, and anorexia. Surgical bypass has good outcomes but has associated significant morbidity and mortality. Self-expandable metal stents are capable of providing immediate palliative relief and are less invasive. Distal duodenal lesions were previously deemed challenging. Fifty-one patients who underwent endoscopic self-expandable metal stent placement (using standard proximal duodenal equipment and technique) for malignant distal duodenal obstructions were evaluated. The somewhat lower 89% technical success rate was attributed to a learning curve. Although the clinical score improved (gastric outlet obstruction score, .62-2.57; P < .0001), evaluating long-term outcomes was challenging because patients had short life expectancy. Four patients died within 30 days, none attributed to the stent. Re-establishing luminal patency leads to a key improvement in quality of life because it allows for enteral feeding. Self-expandable metal stent placement beyond the bulb is technically possible without added equipment and achieving luminal patency in patients previously destined for surgery.
      • Chiu K.W.
      • Razack A.
      • Maraveyas A.
      Self-expandable metal stent placement for malignant duodenal obstruction distal to the bulb.

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