Sharma, Prateek

Background Methods: The question prompt list content was derived through a modified Delphi process consisting of 3 rounds. In round 1, experts provided 5 answers to the prompts “What general questions should patients ask when given a new diagnosis of Barrett’s esophagus” and “What questions do I not hear patients asking, but given my expertise, I believe they should be asking?” Questions were reviewed and categorized into themes. In round 2, experts rated questions on a 5-point Likert scale. In round 3, experts rerated questions modified or reduced after the previous rounds. Only questions rated as “essential” or “important” were included in Barrett’s esophagus question prompt list (BE-QPL). To improve usability, questions were reduced to minimize redundancy and simplified to use language at an eighth-grade level (Fig. 1). Results: Twenty-one esophageal medical and surgical experts participated in both rounds (91% males; median age 52 years). The expert panel comprised of 33% esophagologists, 24% foregut surgeons, and 24% advanced endoscopists, with a median of 15 years in clinical practice. Most (81%), worked in an academic tertiary referral hospital. In this 3-round Delphi technique, 220 questions were proposed in round 1, 122 (55.5%) were accepted into the BE-QPL and reduced down to 76 questions (round 2), and 67 questions (round 3). These 67 questions reached a Flesch Reading Ease of 68.8, interpreted as easily understood by 13 to 15 years olds. Conclusions: With multidisciplinary input, we have developed a physician-derived BE-QPL to optimize patient-physician communication. Future directions will seek patient feedback to distill the questions further to a smaller number and then assess their usability.

Background The long-term outcomes of esophageal peroral endoscopic myotomy (POEM) are still unknown. Methods We searched electronic databases (MEDLINE/PubMed, EMBASE, Scopus) for studies assessing outcomes after POEM for esophageal achalasia with a minimum median follow-up duration of 36 months. Pooled rates of clinical success and postoperative reflux were calculated and compared with the same values at 12/24/36 months when available. Subgroup analyses were performed to explore the interstudy heterogeneity. Results From 1528 initial records, 11 studies (2017–2021) were included. A total of 2342 patients (age 48.1 [SD 6.8] years; 50.1 % males) with a median follow-up of 48 months (interquartile range 45–60) were analyzed. The pooled clinical success rate was 87.3 % (95 %CI 83.6 %–91.0 %; I2 = 73.1 %). The symptomatic reflux pooled rate was 22.0 % (95 %CI 14.4 %–29.5 %; I2 = 92.7 %). Three cases of peptic strictures and one Barrett’s esophagus were reported. The pooled rate of severe adverse events was 1.5 % (95 %CI 0.5 %–2.5 %; I2 = 52.8 %). Conclusions Long-term clinical efficacy of POEM persisted in 87 % of patients with achalasia. Post-POEM symptomatic reflux remained stable over time. The risk for Barrett’s esophagus and peptic strictures appeared minimal.

In the last decade, flexible endoscopic septotomy has been reported as a well-tolerated and effective treatment for Zenker’s diverticulum. More recently, novel endoscopic submucosal tunneling techniques, namely Zenker-PerOral Endoscopic Myotomy (Z-POEM) and PerOral Endoscopic Septotomy (POES) have been proposed to obtain complete muscular septum exposure and deeper myotomy. The aim of this study is to provide a systematic review with a meta-analysis of the first experiences of third space approaches for Zenker’s diverticulum. Electronic databases (Medline, Scopus, EMBASE) were searched up to October 2020. Studies including patients with symptomatic Zenker’s diverticulum who underwent endoscopic treatment by submucosal tunneling technique were eligible. Procedural, clinical and safety outcomes were assessed by pooling data with a random-effect model to obtain a proportion with a 95% confidence interval. Nine retrospective studies were eligible for inclusion (196 patients). Five studies were performed in the USA, two in Europe and two in Asia. Endoscopic treatment was feasible in 96.9% (I 2 = 0%) of patients. The mean procedure duration was 36.4 ± 14.3 minutes. Clinical success was achieved after 93.4% (I 2 = 0%) of procedures. The overall adverse events rate was 4.9% (I 2 = 0%). No differences between the two approaches (Z-POEM vs POES) have been shown in terms of both efficacy and safety. Submucosal tunneling techniques appear to be feasible for symptomatic Zenker’s diverticulum, with promising results in terms of efficacy and safety outcomes.

AbstractBackgroundThe novel Coronavirus (SARS‐CoV‐2) has caused almost 2 million deaths worldwide. Both Food and Drug Administration and European Medicines Agency have recently approved the first COVID‐19 vaccines, and a few more are going to be approved soon.MethodsSeveral different approaches have been used to stimulate the immune system in mounting a humoral response. As more traditional approaches are under investigation (inactivated virus vaccines, protein subunit vaccines, recombinant virus vaccines), more recent and innovative strategies have been tried (non‐replicating viral vector vaccines, RNA based vaccines, DNA based vaccines).ResultsSince vaccinations campaigns started in December 2020 in both the US and Europe, gastroenterologists will be one of the main sources of information regarding SARS‐CoV 2 vaccination for patients in their practice, including vulnerable patients such as those with Inflammatory Bowel Disease (IBD), patients with chronic liver disease, and GI cancer patients.ConclusionsThus, we must ourselves be well educated and updated in order to provide unambiguous counseling to these categories of vulnerable patients. In this commentary, we aim to provide a comprehensive review of both approved COVID‐19 vaccines and the ones still under development, and explore potential risks, benefits and prioritization of vaccination.

The COVID-19 pandemic has had a profound impact on provision of endoscopy services globally as staff and real estate were repurposed. As we begin to recover from the pandemic, a cohesive international approach is needed, and guidance on how to resume endoscopy services safely to avoid unintended harm from diagnostic delays. The aim of these guidelines is to provide consensus recommendations that clinicians can use to facilitate the swift and safe resumption of endoscopy services. An evidence-based literature review was carried out on the various strategies used globally to manage endoscopy during the COVID-19 pandemic and control infection. A modified Delphi process involving international endoscopy experts was used to agree on the consensus statements. A threshold of 80% agreement was used to establish consensus for each statement. 27 of 30 statements achieved consensus after two rounds of voting by 34 experts. The statements were categorised as pre-endoscopy, during endoscopy and postendoscopy addressing relevant areas of practice, such as screening, personal protective equipment, appropriate environments for endoscopy and infection control precautions, particularly in areas of high disease prevalence. Recommendations for testing of patients and for healthcare workers, appropriate locations of donning and doffing areas and social distancing measures before endoscopy are unique and not dealt with by any other guidelines. This international consensus using a modified Delphi method to produce a series of best practice recommendations to aid the safe resumption of endoscopy services globally in the era of COVID-19.

Abstract Background: In patients with Barrett's esophagus, chronic reflux injury and inflammation are associated with esophageal adenocarcinoma, one of the most rapidly increasing lethal cancers. Epidemiological and preclinical studies support decreased risk of esophageal adenocarcinoma with NSAID use. Gastroesophageal refluxate contents can promote carcinogenesis in Barrett's metaplasia by activating AKT, which up regulates COX-2 expression and prostaglandin biosynthesis. We recently noted that neoplastic transformation in Barrett's esophagus is associated with increased AKT expression, particularly isoform AKT1. The AIM of this study is to investigate the effect of NSAID (Aspirin) use in patients with Barrett's esophagus on AKT1 expression using frozen tissue from the randomized, phase II trial of aspirin and esomeprazole for esophageal cancer chemoprevention in Barrett's esophagus patients and to assess the functional consequences of AKT1 expression in-vitro. Methods and Results: In a subset of patients (12 of 120 patients) with Barrett's esophagus who were randomized to placebo, lower dose (81 mg) or higher dose (325 mg) Aspirin for 4 weeks, both PCR and Western blot revealed marked reduction in AKT1 expression in patients who received 325 mg of Aspirin daily compared to patients who received placebo. Our in-vitro experiments support that AKT1 expression is functionally relevant to the process of carcinogenesis in Barrett's epithelial cells. Using adenovirus to induce AKT1 expression, we show that increased AKT1 expression increases Barrett's epithelial cell growth, facilitates RAS-mediated transformation of pre-neoplastic epithelial cells and promotes colony formation. Since AKT1 is known as Warburg kinase and regulates cellular glucose uptake to support aerobic glycolysis during growth de-regulation and neoplasia, we examined the uptake of fluorescent deoxyglucose analog (2-NBDG) in Barrett's epithelial cells transduced with AKT1 adenovirus. At 48 hrs, compared to control, AKT1 overexpression resulted in increased glucose uptake both by metaplastic and neoplastic Barrett's epithelial cells. Transcriptional repression of AKT1 abrogated the 2-NBDG uptake by these cells. Finally, we did pathway specific qPCRs and noted that use of Aspirin is associated with altered expression of chromatin remodelers that could down-regulate AKT1 expression. Conclusion: Collectively, our results demonstrate that Aspirin mediated down-regulation of Warburg kinase AKT1 in patients with Barrett?s esophagus is a novel mechanism for the regulation of Barrett?s epithelial cell growth. The in-depth characterization of molecular mechanisms is currently underway. This abstract is also presented as Poster A82. Citation Format: Navtej S. Buttar, Gary W. Falk, Cathrine J. DeMars, Sonia Chowdhury, Ahmed Elebiary, Anamay Sharma, Sidhartha Chaudhry, Nathan R. Foster, Katie L. Allen Ziegler, Yvonne Romero, Norman E. Marcon, Thomas Schnell, Douglas A. Corley, Prateek Sharma, Marcia R. Cruz-Correa, Chin Hur, David E. Fleischer, Amitabh Chak, Kenneth R. DeVault, David S. Weinberg, Gary Della’Zanna, Ellen Richmond, Thomas C. Smyrk, Sumithra Mandrekar, Paul J. Limburg. Aspirin mediated downregulation of Warburg kinase AKT1 in patients with Barrett's esophagus: Implications in neoplastic transformation. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr PR-03.