Intestinal epigenomic alterations are associated with a dysregulated nutrient absorption phenotype in obesity.

Obesity is an epidemic with myriad health effects, but little is understood regarding individual obese phenotypes and how they may respond to therapy. Epigenetic changes associated with obesity have been detected in blood, liver, pancreas, and adipose tissues. Previous work found that dietary glucose hyperabsorption occurs in some obese subjects, but detailed transcriptional or epigenomic features of the intestine associated with this phenotype are unknown. This study evaluated differentially expressed genes and relative chromatin accessibility in intestinal organoids established from donors classified as lean, obese, or obese hyperabsorptive by body mass index and glucose transport assays. Transcriptomic analysis indicated that obese hyperabsorptive subjects have significantly upregulated dietary nutrient absorption proteins and downregulated type I interferon targets. Chromatin accessibility and transcription factor footprinting suggested that enhanced binding of HNF4G promotes the obese hyperabsorption phenotype. Quantitative PCR assessment in a larger subject cohort suggested that intestinal epithelial expression of CUBN, GIP, and SLC2A5 have high correlation with hyperabsorption. The obese hyperabsorption phenotype is characterized by transcriptional changes that support increased nutrient uptake and may be driven by differentially accessible chromatin. Recognizing unique intestinal phenotypes in obesity provides new perspective in considering therapeutic targets and options to manage the disease.

Acute Pancreatitis Review.

Acute pancreatitis, a prevalent illness with devastating consequences, poses a grave threat to those affected. There has been a steady increase in the occurrence of acute pancreatitis at about 3% per year from 1961 to 2016. There are 3 main guidelines on acute pancreatitis, including the American College of Gastroenterology, the International Association of Pancreatology/American Pancreatic Association guideline in 2013, and the American Gastroenterological Association guideline in 2018. However, several milestone studies have been published since then. We hereby reviewed the current acute pancreatitis guidelines with an update on clinical practicechanging literature. The aggressive or moderate fluid resuscitation in acute pancreatitis (WATERFALL) trial recommended fluid resuscitation with lactated Ringer's solution at a moderate aggressive rate. All guidelines did not recommend prophylactic antibiotics use. Early enteral feeding reduces morbidity. A clear liquid diet is no longer recommended. Nutrition with nasogastric or nasojejunal feeding does not have a difference. The upcoming high vs. low-energy administration in the early phase of acute pancreatitis (GOULASH) trial will provide more information on the impact of calorie intake. Pain management should be individualized based on the degree of pain and severity of pancreatitis. In patients with moderate to severe and severe acute pancreatitis, a step-down approach with epidural analgesia can be considered for moderate to severe pain. The management of acute pancreatitis has evolved. New research on the impact of electrolytes, pharmacologic agents, the role of anticoagulants, and nutrition support will provide scientific and clinical evidence to improve patient care and decrease morbidity and mortality.

Challenges of developing and executing a multi-site registry for a novel device with evolving indications for use.

BACKGROUND: The introduction of new technologies in endoscopy has been met with uncertainty, skepticism, and lack of standardization or training parameters, particularly when disruptive devices or techniques are involved. The widespread availability of a novel endoscopic suturing device (OverStitch™) for tissue apposition has enabled the development of applications of endoscopic suturing. METHODS: The American Gastroenterological Association partnered with Apollo Endosurgery to develop a registry to capture in a pragmatic non-randomized study the safety, effectiveness, and durability of endoscopic suturing in approximating tissue in the setting of bariatric revision and fixation of endoprosthetic devices. RESULTS: We highlight the challenges of the adoption of novel techniques by examining the process of developing and executing this multicenter registry to assess real-world use of this endoscopic suturing device. We also present our preliminary data on the safety and effectiveness of the novel device as it is applied in the treatment of obesity. CONCLUSIONS: The Prospective Registry for Trans-Orifice Endoscopic Suturing Applications (ES Registry) was an effective Phase 4, postmarketing registry aimed at capturing pragmatic, real-world use of a novel device. These findings serve to solidify the role of endoscopic suturing in clinical practice.

Gastric Per-Oral Endoscopic Myotomy (G-POEM) for the Treatment of Gastric Stenosis Post-Laparoscopic Sleeve Gastrectomy (LSG).

Laparoscopic sleeve gastrectomy (LSG) has become the most common form of bariatric surgery performed worldwide. However, it is associated with potentially debilitating adverse events such as post-operative stenosis. Finding effective and minimally invasive treatments for such complications is of paramount importance. Gastric per-oral endoscopic myotomy (G-POEM) is a novel procedure developed over the past decade to treat conditions that delay gastric emptying. We present a case demonstrating the use of G-POEM in the successful endoscopic management of post-LSG gastric stenosis.

Endoscopic sleeve gastroplasty versus intragastric balloon insertion: efficacy, durability, and safety.

BACKGROUND: Intragastric balloon (IGB) placement and endoscopic sleeve gastroplasty (ESG) are reported to be safe and effective endoscopic bariatric therapies. This study aimed to compare the patient demographics and therapeutic outcomes between the IGB and ESG procedures. METHODS: This was a retrospective review of prospectively collected data from consecutive patients between December 2015 and October 2017 who underwent IGB or ESG at a single academic center. Fluid-filled IGBs implanted for a 6-month duration were used. IGB and ESG patients were subjected to identical post-procedure dietary instructions and follow-up protocols. Body weight was recorded at 1, 3, 6, and 12 months post-procedure. RESULTS: A total of 47 patients underwent IGB insertion and 58 underwent ESG. The IGB cohort had a lower baseline body mass index (BMI) than the ESG (34.5 vs. 41.5 kg/m2; P < 0.001) and a significantly lower proportion of men (2.1 % vs. 41.4 %; P < 0.001). IGB patients showed a mean (standard deviation [SD]) percentage total body weight loss (%TBWL) that was significantly lower than ESG patients at 1 month (6.6 % [2.6 %] vs. 9.9 % [2.4 %]; P < 0.001), 3 months (11.1 % [4.4 %] vs. 14.3 % [4.6 %]; P = 0.004), 6 months (15.0 % [7.6 %] vs. 19.5 % [5.7 %]; P = 0.01), and 12 months (13.9 % [9.0 %] vs. 21.3 % [6.6 %]; P = 0.005). The IGB cohort also experienced significantly more adverse events compared with the ESG (17 % vs. 5.2 %; P = 0.048). CONCLUSIONS: IGB placement and ESG result in clinically meaningful weight loss. However, ESG appears to provide clinically superior and more enduring weight loss with fewer adverse events compared with an IGB.

Endoscopic sleeve gastroplasty versus laparoscopic sleeve gastrectomy: a case-matched study.

BACKGROUND AND AIMS: Endoscopic sleeve gastroplasty (ESG) reduces the gastric lumen to a size comparable with that of laparoscopic sleeve gastrectomy (LSG). However, there is a paucity of research comparing outcomes between the 2 procedures. Our study compared the 6-month weight loss outcomes and adverse events of ESG with LSG in a case-matched cohort. METHODS: We retrospectively reviewed prospectively collected data for patients undergoing ESG or LSG at a single academic center. Weight was recorded at 1 and 6 months postprocedure, and percent total body weight loss (%TBWL) was calculated. Adverse events and new-onset Gastroesophageal Reflux Disease (GERD) were also recorded. RESULTS: A total of 54 ESG patients were matched with 83 LSG patients by age, sex, and body mass index. The proportion of patients with GERD at baseline was similar in the 2 groups (16.7% in ESG group vs 25.3% in LSG group, P = .27). At the 6-month follow-up, %TBWL (compared with baseline) was significantly lower in the ESG group compared with the LSG group (17.1% ± 6.5% vs 23.6% ± 7.6%, P < .01). ESG patients had significantly lower rates of adverse events compared with LSG patients (5.2% vs 16.9%, P < .05). New-onset GERD was also significantly lower in the ESG group compared with the LSG group (1.9% vs 14.5%, P < .05). CONCLUSIONS: ESG, a minimally invasive same-day procedure, achieved less weight loss at 6 months than LSG, with the caveat that LSG caused more adverse events and new-onset GERD than ESG.

Endoscopic sleeve gastroplasty and its application to China.

Obesity is a burgeoning problem in China with potential for significant adverse economic and health consequences if not addressed. Unfortunately, the body mass index (BMI) targets used in the West are not applicable to China as Asians have visceral adiposity and thus develop complications of obesity at a lower BMI. Recent studies suggest using lower BMI targets for defining overweight and obesity and to qualify patients for bariatric surgery. Diet, exercise and pharmacology have been the foundation for treatment in those not meeting criteria for bariatric surgery, despite modest weight loss that is poorly sustained over time. The large majority in China are averse to bariatric surgery and thus endoscopic bariatric therapy is emerging as an illustrious remedy to fill this gap. Of the current procedures available endoscopic sleeve gastroplasty has shown the most promise due to the significant and sustained weight loss it produces coupled with the ease of execution and lower cost. The procedure is performed under general anesthesia using a full-thickness endoscopic suturing device and patients are discharged the same day. The mean procedure time in experienced hands is 60 minutes. Due to the repetitive nature of the procedure, the learning curve is steep. Data thus far demonstrate total body weight loss to be 16-20% at 12 months. The safety profile is excellent with a low morbidity rate seen in the 3 000 procedures performed worldwide. Therefore, widespread dissemination in China is expected with the potential to help millions of obese patients.

Timing of procedure and compliance with outpatient endoscopy among an underserved population in an inner-city tertiary institution.

PURPOSE: Anecdotal evidence suggests that patient compliance with colonoscopy is poorer with Monday procedures and better during the winter months because "there is not much else to do." We examined patients' compliance with scheduled outpatient endoscopy by time of the day, days of the week, and seasons of the year. METHODS: We included 2873 patients who were scheduled for endoscopy from September 2009 to August 2010. Compliant patients were those who showed up for their procedures whereas noncompliant patients were those who did not show up without canceling or rescheduling their procedures up to 24 hours before their scheduled procedures. We used logistic regression models to evaluate the association between the timing of the scheduled procedure and compliance. RESULTS: A total of 574 (20%) patients did not show up. There was no difference in compliance by time of day of the procedures. However, when compared with patients scheduled for procedures on Monday, there was a trend towards improved compliance as the week progressed, becoming significant on Friday (odds ratio 1.46; 95% confidence interval 1.06-2.00). There was also better compliance in the warmer months. CONCLUSIONS: Noncompliance with outpatient endoscopy is substantial among underserved populations with limited predictive pattern of compliance by the timing of the procedures.

Likelihood of missed and recurrent adenomas in the proximal versus the distal colon.

BACKGROUND: Colonoscopy may be less efficacious in reducing colorectal cancer mortality in the proximal compared with the distal colon. A greater likelihood for missed and recurrent adenomas in the proximal colon may contribute to this phenomenon. OBJECTIVE: To examine whether a proximal adenoma is associated with the risk and location of missed and recurrent adenomas. DESIGN: Prospective. SETTING: Polyp Prevention Trial. PARTICIPANTS: A total of 1864 patients with an adenoma at baseline underwent a follow-up colonoscopy 4 years later (adenoma recurrence). Of these, 1731 underwent a clearing colonoscopy 1 year after the baseline examination (missed adenoma). MAIN OUTCOME MEASUREMENTS: Association of baseline adenoma location with the risk and location of adenomas found at colonoscopy performed 1 year and 4 years later. RESULTS: At the year 1 colonoscopy, 598 patients (34.6%) had an adenoma (missed adenoma). Compared with those with a distal-only adenoma at baseline, patients with a proximal-only adenoma at baseline were more likely to have any missed adenomas (relative risk [RR] 1.28; 95% CI, 1.09-1.49) and a proximal-only missed adenoma (RR 2.05; 95% CI, 1.49-2.80). At the year 4 colonoscopy, 733 patients (39.3%) had adenoma recurrence. Patients with a baseline proximal-only adenoma were more likely to have any adenoma recurrence (RR 1.14; 95% CI, 1.00-1.31) and a proximal-only adenoma recurrence (RR 1.52; 95% CI, 1.15-2.02). Sensitivity analyses involving missed adenomas did not materially affect the risk or location of recurrent adenomas at year 4 colonoscopy. LIMITATION: Lesions may still be missed on repeated colonoscopies. CONCLUSIONS: Missed and recurrent adenomas are more likely to be in the proximal colon.