Faculty Bibliography

Background: Lifestyle and behavioral interventions remain the foundation for obesity management. However, as standalone therapies, the rates of success are limited with marked heterogeneity in response. We aimed to determine the efficacy and safety of the 32 weeks adjustable fluid-filled intragastric balloon system (Spatz 3, Spatz FGIA, Great Neck, NY)for weight loss.
Method(s): This was an open-label randomized-controlled trial of an 8 months adjustable intragastric balloon system plus lifestyle therapy compared with lifestyle therapy alone for weight loss in 288 participants (187 device and 101 control), aged 22-64, BMI 30-40 kg/m², across 8 sites in the US. Primary weight loss endpoints included difference in percent total body weight loss (%TBL)in treatment group (TG)vs control group (CG)greater than 4.5% at 32 weeks, and a responder rate > 35% in the TG. Weight maintenance secondary endpoint was defined as maintenance of > 40% of the weight loss in at least 50% of the TG at 56 weeks.
Result(s): Percent total weight loss in the TG utilizing intention to treat analysis (ITT)at 32 weeks was 14.9+/-7.2% compared to 3.6+/-5.8% in the control group for a difference of 11.3% [97.5% lower confidence bound (LCB)9.1%]. TG responder rate was 90.7% [97.5% LCB 86.1%]with 72% of subjects achieving >= 10%TBL compared to 13% in the CG (figure). Seventy five percent of the TG maintained > 40% of the weight loss at 56 weeks. The downward adjustability feature of the balloon was useful in minimizing intolerance and early removal rates; 28 subjects (15%)required downward adjustment of which 23 (82%)continued therapy. The upward adjustability feature of the balloon was effective for management of weight loss plateau; an additional 4.7% TBL was observed after upward adjustment between weeks 18 and 32. Serious adverse events rate was 5.3% and mostly related to persistent accommodative GI symptoms. Uncomplicated gastric ulcer rate with the balloon was 4%. All adverse events fully recovered. No mortality, perforation, pancreatitis, or balloon hyperinflation reported.
Conclusion(s): The adjustable intragastric balloon systems enabled patients to achieved significant weight loss and maintenance after balloon removal with a good safety profile. The adjustability feature of the balloon offers significant advantages to maximize tolerance and manage weight loss plateaus [Figure presented]
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The increased hepatic gluconeogenesis in type 2 diabetes mellitus has often been ascribed to increased transcription of phosphoenolpyruvate carboxykinase 1, cystolic form (PEPCK1), although recent evidence has questioned this attribution. To assess the metabolic role of PEPCK1, we treated regular chow fed and high-fat fed (HFF) male Sprague-Dawley rats with a 2'-O-methoxyethyl chimeric antisense oligonucleotide (ASO) against PEPCK1 and compared them with control ASO-treated rats. PEPCK1 ASO effectively decreased PEPCK1 expression in the liver and white adipose tissue. In chow fed rats, PEPCK1 ASO did not alter adiposity, plasma glucose, or insulin. In contrast, PEPCK1 ASO decreased the white adipose tissue mass in HFF rats but without altering basal rates of lipolysis, de novo lipogenesis, or glyceroneogenesis in vivo. Despite the protection from adiposity, hepatic insulin sensitivity was impaired in HFF PEPCK1 ASO-treated rats. PEPCK1 ASO worsened hepatic steatosis, although without additional impairments in hepatic insulin signaling or activation of inflammatory signals in the liver. Instead, the development of hepatic insulin resistance and the decrease in hepatic glycogen synthesis during a hyperglycemic clamp was attributed to a decrease in hepatic glucokinase (GCK) expression and decreased synthesis of glycogen via the direct pathway. The decrease in GCK expression was associated with increased expression of activating transcription factor 3, a negative regulator of GCK transcription. These studies have demonstrated that PEPCK1 is integral to coordinating cellular metabolism in the liver and adipose tissue, although it does not directly effect hepatic glucose production or adipose glyceroneogenesis.

BACKGROUND:Bariatric surgery is endorsed by multiple societies as the most effective treatment for obesity. Psychosocial functioning has also been noted to improve for most patients after bariatric surgery. However, some studies have shown an increase in post-operative suicide risk. The aim of this study was to review the published literature and evaluate the association of bariatric surgery with suicide events and suicide/self-harm attempts in patients who have undergone weight loss surgery. METHODS:MEDLINE and Embase were searched from inception through January 2018 for retrospective or prospective studies reporting mortality outcomes and self-harm or suicide rates after bariatric procedures. The primary outcome was the pooled event rate with 95% confidence interval (95% CI) for suicide. Secondary outcomes were suicide/self-harm attempts after bariatric surgery compared to same population prior to surgery and to matched control subjects, with the respective calculated odds ratios (OR) and 95% CI. RESULTS:From 227 citations, 32 studies with 148,643 subjects were eligible for inclusion. The patients were predominantly females (76.9%). Roux-en-Y gastric bypass (RYGB) was the most commonly performed procedure (58.9%). The post-bariatric suicide event rate was 2.7/1000 patients (95% CI 0.0019-0.0038), while the suicide/self-harm attempt event rate was 17/1000 patients (95% CI 0.01-0.03). The self-harm/suicide attempt risk was higher after bariatric surgery within the same population with OR of 1.9 (95% CI 1.23-2.95), and compared to matched control subjects, OR 3.8 (95% CI, 2.19-6.59). CONCLUSIONS:Post-bariatric surgery patients had higher self-harm/suicide attempt risk compared to age-, sex-, and BMI-matched controls. Various pre- and post-surgical psychosocial, pharmacokinetic, physiologic, and medical factors may be involved.

BACKGROUND AND AIMS/OBJECTIVE:The need to increase the adenoma detection rate (ADR) for colorectal cancer screening has ushered in devices that mechanically or optically improve conventional colonoscopy. Recently, new technology devices (NTDs) have become available. We aimed to compare the ADR, polyp detection rate (PDR), and adenoma miss rate (AMR) between NTDs and conventional colonoscopy and between mechanical and optical NTDs. METHODS:MEDLINE and Embase databases were searched from inception through September 2017 for articles or abstracts reporting ADR, PDR, and AMR with NTDs. Randomized controlled trials and case-control studies with >10 subjects were included. Primary outcomes included ADR, PDR, and AMR odds ratio (OR) between conventional colonoscopy and NTDs. Secondary outcomes included cecal intubation rates, adverse events, cecal intubation time, and total colonoscopy time. RESULTS:From 141 citations, 45 studies with 20,887 subjects were eligible for ≥1 analyses. Overall, the ORs for ADR (1.35; 95% confidence interval [CI] 1.24-1.47; P < .01) and PDR (1.51; 95% CI, 1.37-1.67; P < .01) were higher with NTDs. Higher ADR (OR, 1.52 vs 1.25; P = .035) and PDR (OR, 1.63 vs 1.10; P ≤ .01) were observed with mechanical NTDs. The overall AMR with NTDs was lower compared with conventional colonoscopy (OR, .19; 95% CI, .14-.26; P < .01). Mechanical NTDs had lower AMRs compared with optical NTDs (OR, .10 vs .33; P < .01). No differences in cecal intubation rates, cecal intubation time, or total colonoscopy time were found. CONCLUSIONS:Newer endoscopic technologies are an effective option to improve ADR and PDR and decrease AMR, particularly with mechanical NTDs. No differences in operability and safety were found.

Background: New technology devices (NTDs) - including Endocuff, Endoring, and Full Spectrum Endoscopy (FUSE) have recently been described as having increased performance in adenoma detection rate as compared to conventional colonoscopy by means of improving colonic mucosal visualization. An increasing awareness of the significant risk of sessile-serrated adenoma progression to malignancy has ushered a need for increased detection of these characteristically flat lesions. Two prior studies evaluating the Endocuff technology and sessile-serrated adenoma detection rate have been published. This is the first meta-analysis comparing the sessile-serrated adenoma detection rate of NTDs and conventional colonoscopy. Methods: Embase and PubMed/MEDLINE databases were searched from inception through November 2017 for published manuscripts or major conference abstracts reporting sessile-serrated adenoma detection rate (SSADR) with Endocuff, EndoRing, G-Eye, FUSE, Third-Eye and conventional colonoscopy. Randomized controlled trials and high-quality case-control studies in adults with >10 subjects were included. Studies excluded were those with overlap in data collection site or time frame. The primary outcome was pooled sessile-serrated adenoma detection rate odds ratio (OR) with 95% confidence interval (95% CI) between conventional colonoscopy and new technology devices. A sub-analysis between Endocuff technology and conventional colonoscopy was performed. Results: Of 163 citations identified, 15 studies with 14,546 subjects were eligible. Four studies were excluded for overlapping collection site or time frame, and two additional studies were excluded for incomplete data reporting within the abstract. A total of nine studies with 5,667 subjects were included in our analysis (2,658 subjects with NTDs and 3,009 with conventional colonoscopy). Seven studies included Endocuff, one with EndoRing, and one with FUSE technology. Mean age was 61.5 (range 59-65), and 60.5% were males. Calculated SSADR with NTDs was 12.6 as compared to 6.5 with conventional colonoscopy, with an increased OR 2.57 (95% CI: 2.09-3.16, p<0.01; I2: 69%)(Figure 1). On Endocuff sub-analysis, seven studies with 4,655 patients were included (2,153 with Endocuff and 2,502 in conventional colonoscopy). Mean age in the sub-analysis was 62.1 (59.8-65), and 62.8% were males. Endocuff sub-analysis of SSADR was 14.0 as compared with 7.3 in conventional colonoscopy, with an increased OR 2.64 (95% CI: 2.12-3.28, p<0.01; I2: 76%). Conclusion: New technology devices, including Endocuff, are an effective option to increase sessileserrated adenoma detection rate. Further studies are needed to evaluate other new technology devices, as well as the long-term impact of increased sessile-serrated adenoma detection rate in colon malignancy. (Table Presented)

Introduction: Intragastric balloons (IGB) are a safe and effective endoscopic weight loss procedure that has recently been approved for use in the U.S. The Manhattan VA initiated the first bariatric endoscopy program in the country, which works in conjunction with the MOVEprogram. We report an interesting case of an obese man with dramatic weight loss and obstructive symptoms after IGB. Case report: Patient is a 45-year-old veteran with BMI of 38 kg/m2, hypertension, and obstructive sleep apnea, who presented for IGB. Physical exam and labs were unremarkable, with initial weight of 233 lbs. An Orbera IGB (Apollo Endosurgery, Austin, TX) was implanted and filled with 650 mL of saline mixed with methylene blue. At 4 months after implantation, the patient had lost an impressive 46 lbs, with active participation in the MOVEprogram. At 4 months, he presented with new-onset nausea and vomiting. He denied abdominal pain, or changes in color of stool and urine. Initial abdominal x-ray(AXR) was unremarkable (Fig. 2a). The patient improved temporarily with dietary changes and anti-emetics, but vomiting after solid meals resumed and he was admitted. On admission, his weight was 169 lbs, with K of 3.1 mEq/L, BUN 32, creatinine of 2.0, normal liver tests and lipase. Hyperinflation of balloon, small bowel obstruction, gastric ulceration and gastroparesis were considered. Repeat AXR showed air-fluid levels (Fig. 2b). Upper endoscopy revealed intact freely movable IGB, located in antrum. IGB was removed, and the patient's symptoms resolved. Four months later, the patient has maintained the weight loss, with weight of 174 lbs (BMI 27 kg/m2) and a total excess weight loss of 68%. Discussion: We present a patient with BMI of 38 kg/m2 status post IGB therapy with 59-lb total weight loss, later complicated by persistent gastric outlet obstructive symptoms with no evidence of mechanical obstruction. This functional dynamic gastric outlet obstruction may be attributed to the patient's sudden weight loss, especially since typical rate of weight loss after IGB is lower. The patient had no diabetes history, underlying infiltrative process, or medications use that could explain the functional gastroparesis. This study highlights an unexpected phenomenon that physicians should be aware of when monitoring effects of acute weight loss and consider in the presentation of late nausea and vomiting (after 3 months of implantation) in patients with IGB

Background: Duodenal-jejunal bypass liner (DJBL) is a fluoropolymer sleeve endoscopically placed at the duodenum, extending to the proximal jejunum. It prevents ingested nutrients from contacting duodenal mucosa. Previous studies have reported its efficacy at treating obesity. Aim: To assess effect of DJBL on weight outcomes at time of explant and after device removal. Methods Study Design: A meta-Analysis. Data Sources: MEDLINE, EMBASE and Web of Science through Nov 2016. Study Selection, Data Extraction and Synthesis: Published randomized controlled trials (RCTs) and cohort studies assessing weight outcomes of DJBL. Authors were contacted for additional data if needed. Data were pooled using fixed-effects or randomeffects model if there was heterogeneity. Main Outcomes and Measures: Primary outcome was change in weight (kg) and body mass index (BMI) (kg/m2) at time of explant. Secondary predefined outcomes included changes in weight and BMI post-explant. Outcomes were reported using difference in means+/-SEM. Results: Of 593 potentially eligible records, 14 studies were included in the qualitative and quantitative analyses. Primary Outcome: Thirteen of 14 studies (4 RCTs with 182 patients (97 in DJBS vs 85 in control) and 9 cohort studies with 378 patients) reported the effect of DJBL on weight loss at time of explant. Mean baseline age, weight and BMI ranged from 36-54 years, 82.1-142.5 kg, and 30.0-48.9 kg/m2. Compared to control, DJBL induced more weight loss by 6.0+/-0.8 kg (po0.0001) (I2=0) and 12.9+/-2.4% TBWL (po0.0001) (I2=56) at time of explant (4.2+/-1.6 months from implant). For the 9 cohort studies, the amount of weight loss from baseline weight was 13.1+/-1.8 kg (po0.0001) (I2=93), which corresponded to a decrease in BMI of 4.6+/-0.6 kg/m (po0.0001) (I2=96). Pooled %TBWL and %EWL at time of explant was 14.6+/-6.5% and 44.3+/-24.5%. Secondary Outcomes: Three studies including 166 patients reported weight outcome after DJBL removal. On average, the DJBL was implanted for 7.3+/-2.3 months and follow-up weight was performed at 14.3+/-3.2 months (7.0+/-4.6 months after device removal). Effect of DJBL on weight loss persisted after device removal with weight remaining significantly lower than baseline weight by 7.2+/-0.9 kg (po0.0001) (I2=0) (Figure 1). Similarly, BMI and %TBWL were lower than baseline BMI and %TBWL by 2.4 +/-0.2 kg/m (po0.0001) (I2=7) and 6.6+/-0.7% (po0.0001) (I2=0). Conclusion: DJBL is effective at inducing weight loss with the effect persisting at least 7 months after device removal. Considering the minimal invasive and reversible features, DJBL will likely have a role in the multidisciplinary management of obesity

Introduction: Rapid weight loss after bariatric surgery (BS) has been associated with the formation of gallstones, and subsequent acute cholecystitis and cholangitis (AC). However, the complex post-surgical anatomy limits the possibility of performing an ERCP as part of AC treatment. Therefore, the aim of this study was to assess the impact of bariatric surgery on mortality and resource utilization among patients with AC using a national database. Aims & Methods: This was a case-control study using the National Inpatient Sample 2013, the largest publically available inpatient database in the United States. All patients with an ICD-9 CM code for a principal diagnosis of AC were included. There were no exclusion criteria. Patients with a past history of BS were identified using the appropriate ICD-9CM codes. The primary outcome was all cause mortality. The secondary outcome was resource utilization: use of ERCP, cholecystectomy, length of hospital stay (LOS), total hospitalization charges and costs. Multivariate regression analyses were used to adjust for the following confounders: Age, sex, race, income in patients' zip code, Charlson Comorbidity Index, hospital region, location, size and teaching status. Results: A total of 274,775 patients with AC were included in the study, of which 4,240 (1.7%) had undergone BS. The mean patient age was 51 years and 48% were female. After adjusting for confounders, patients with and without history of bariatric surgery had similar adjusted odds of mortality (adjusted Odds Ratio (aOR): 1.37, 95% CI: 0.51-3.65, p=0.52). As far as resource utilization, patients with bariatric surgery had lower adjusted odds of ERCP (aOR: 0.28, 95% CI: 0.09-0.83, p=0.02), but higher odds of cholecystectomy (aOR: 3.18, 95% CI: 1.00-10.05, p=0.04). Both patient groups had similar adjusted length of stay (adjusted mean difference: 1.19 days, 95% CI: 0.09-0.83, p=0.16) total hospitalization costs (adjusted mean difference: $2237, 95% CI: -$2308 - $6782, p=0.49), and total hospitalization charges (adjusted mean difference: $7477, 95% CI: -$9595-$24549, p=0.39) Conclusion: Bariatric surgery has no impact on inpatient all-cause mortality among patients who develop acute cholangitis, despite its association gallstone acute pancreatitis and limited ERCP performance. In addition, bariatric surgery does not affect resource utilization in this patient population as measured by length of stay and total hospitalization costs and charges