Publications by authors named "J Christopher Eagon"

75 Publications

The Risks of Stone Diagnosis and Stone Removal Procedure After Different Bariatric Surgeries.

J Endourol 2021 Jan 13. Epub 2021 Jan 13.

Division of Urologic Surgery, Washington University School of Medicine, St. Louis, Missouri, USA.

Nephrolithiasis is common after malabsorptive bariatric surgery; however, the comparative risk of stone formation after different bariatric surgeries remains unclear. We seek to compare the risk of stone diagnosis and stone procedure after gastric banding (GB), sleeve gastrectomy (SG), short-limb Roux-en-Y (SLRY), long-limb Roux-en-Y (LLRY), and biliopancreatic diversion with duodenal switch (BPDDS). Using an administrative database, we retrospectively identified 116,304 patients in the United States, who received bariatric surgery between 2007 and 2014, did not have a known kidney stone diagnosis before surgery, and were enrolled in the database for at least 1 year before and after their bariatric surgery. We used diagnosis and procedural codes to identify comorbidities and events of interest. Our primary analysis was performed with extended Cox proportional hazards models using time to stone diagnosis and time to stone procedure as outcomes. The adjusted hazard ratio of new stone diagnosis from 1 to 36 months, compared to GB, was 4.54 for BPDDS (95% confidence interval [CI] 3.66-5.62), 2.12 for LLRY (95% CI 1.74-2.58), 2.15 for SLRY (95% CI 2.02-2.29), and 1.35 for SG (95% CI 1.25-1.46). Similar results were observed for risk of stone diagnosis from 36 to 60 months, and for risk of stone removal procedure. Male sex was associated with an overall 1.63-fold increased risk of new stone diagnosis (95% CI 1.55-1.72). BPDDS was associated with a greater risk of stone diagnosis and stone procedures than SLRY and LLRY, which were associated with a greater risk than restrictive procedures. Nephrolithiasis is more common after more malabsorptive bariatric surgeries, with a much greater risk observed after BPDDS and for male patients.
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http://dx.doi.org/10.1089/end.2020.0817DOI Listing
January 2021

Initial Experience with a Virtual Platform for Advanced Gastrointestinal Minimally Invasive Surgery Fellowship Interviews.

J Am Coll Surg 2020 12 17;231(6):670-678. Epub 2020 Sep 17.

Section of Minimally Invasive Surgery, Department of Surgery, Washington University School of Medicine, St Louis, MO. Electronic address:

Background: The COVID-19 pandemic travel restrictions triggered a rapid alteration in the interview process for fellowships this spring. We describe our initial experience with virtual interviews for Advanced Gastrointestinal (GI) Minimally Invasive Surgery Fellowships and assess the value and limitations via a post-interview applicant survey.

Study Design: Twenty candidates were interviewed via Zoom teleconferencing during March and April 2020 using combined group and breakout rooms. An anonymous post-interview Likert and free text survey was sent to candidates with questions regarding feasibility, appropriateness, and acceptability of this method.

Results: Seventeen of 20 candidates (85%) responded to the survey. The candidates rated ease of interaction with the program director, faculty surgeons, and the current fellow highly: 94%, 83%, and 89%, respectively. The majority (53%) stated the virtual interviews exceeded or met expectations. Only a minority, 12%, reported the virtual platform was short of expectations. Approximately 70% noted little to no impact of not being able to conduct these interviews in-person and not being able to physically see the program institution. Overall, 94% were satisfied with their experience, and only 6% were neutral, with no respondents reporting dissatisfaction. Finally, 76% would recommend a virtual interview in the future. Most negative open response comments were secondary to issues with software rather than the lack of the in-person traditional interviews.

Conclusions: The use of a remote teleconferencing platform provides a favorable method for conducting fellowship interviews and results in a high degree of candidate satisfaction. Virtual interviews will likely be increasingly substituted for in-person interviews across the spectrum of medical training.
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http://dx.doi.org/10.1016/j.jamcollsurg.2020.08.768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7497742PMC
December 2020

Effects of Diet versus Gastric Bypass on Metabolic Function in Diabetes.

N Engl J Med 2020 08;383(8):721-732

From the Center for Human Nutrition (M.Y., B.D.K., J.Y., R.I.S., D.R., K.S., B.W.P., S.K.) and the Department of Surgery (J.C.E., S.R.E.), Washington University School of Medicine, St. Louis; and the Departments of Medicine (J.D.W., M.J.), Pharmacology (J.D.W., M.J.), Pediatrics (R.K.), and Computer Science and Engineering (R.K.), University of California San Diego, San Diego.

Background: Some studies have suggested that in people with type 2 diabetes, Roux-en-Y gastric bypass has therapeutic effects on metabolic function that are independent of weight loss.

Methods: We evaluated metabolic regulators of glucose homeostasis before and after matched (approximately 18%) weight loss induced by gastric bypass (surgery group) or diet alone (diet group) in 22 patients with obesity and diabetes. The primary outcome was the change in hepatic insulin sensitivity, assessed by infusion of insulin at low rates (stages 1 and 2 of a 3-stage hyperinsulinemic euglycemic pancreatic clamp). Secondary outcomes were changes in muscle insulin sensitivity, beta-cell function, and 24-hour plasma glucose and insulin profiles.

Results: Weight loss was associated with increases in mean suppression of glucose production from baseline, by 7.04 μmol per kilogram of fat-free mass per minute (95% confidence interval [CI], 4.74 to 9.33) in the diet group and by 7.02 μmol per kilogram of fat-free mass per minute (95% CI, 3.21 to 10.84) in the surgery group during clamp stage 1, and by 5.39 (95% CI, 2.44 to 8.34) and 5.37 (95% CI, 2.41 to 8.33) μmol per kilogram of fat-free mass per minute in the two groups, respectively, during clamp stage 2; there were no significant differences between the groups. Weight loss was associated with increased insulin-stimulated glucose disposal, from 30.5±15.9 to 61.6±13.0 μmol per kilogram of fat-free mass per minute in the diet group and from 29.4±12.6 to 54.5±10.4 μmol per kilogram of fat-free mass per minute in the surgery group; there was no significant difference between the groups. Weight loss increased beta-cell function (insulin secretion relative to insulin sensitivity) by 1.83 units (95% CI, 1.22 to 2.44) in the diet group and by 1.11 units (95% CI, 0.08 to 2.15) in the surgery group, with no significant difference between the groups, and it decreased the areas under the curve for 24-hour plasma glucose and insulin levels in both groups, with no significant difference between the groups. No major complications occurred in either group.

Conclusions: In this study involving patients with obesity and type 2 diabetes, the metabolic benefits of gastric bypass surgery and diet were similar and were apparently related to weight loss itself, with no evident clinically important effects independent of weight loss. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT02207777.).
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http://dx.doi.org/10.1056/NEJMoa2003697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456610PMC
August 2020

Assessment of postoperative nausea and vomiting after bariatric surgery using a validated questionnaire.

Surg Obes Relat Dis 2020 Oct 28;16(10):1505-1513. Epub 2020 May 28.

Section of Minimally Invasive Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri.

Background: Postoperative nausea and vomiting (PONV) is known to occur after bariatric surgery, with over two thirds of patients affected. However, variability exists in how to objectively measure PONV.

Objectives: The goals of the present study were to use a validated, patient-centered scoring tool, the Rhodes Index of Nausea, Vomiting, and Retching to measure the severity of PONV after bariatric surgery, to directly compare PONV between patients who underwent laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB), and to identify risk factors for the development of PONV after bariatric surgery.

Setting: Barnes-Jewish Hospital/Washington University School of Medicine, St. Louis, Missouri, United States of America.

Methods: The Washington University Weight Loss Surgery team prospectively surveyed patients from January 1, 2017 to December 1, 2018 at the following 6 different timepoints: postoperative day (POD) 0, POD 1, POD 2, POD 3 to 4, the first postoperative outpatient visit (POV 1: POD 5-25), and the second postoperative visit (POV 2: POD 25-50). At each timepoint, a cumulative Rhodes score was calculated from the sum of 8 questions. The American Society for Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database was used to collect patient demographic characteristics and perioperative clinical data.

Results: A total of 274 patients met study criteria and completed 605 Rhodes questionnaires. Two hundred fifty Rhodes questionnaires were completed by patients after SG and 355 were completed by patients after LRYGB. Total Rhodes scores are statistically higher in LSG patients compared with patients who underwent LRYGB (LSG = 5.45 ± 6.27; LRYGB = 3.08 ± 4.19, P = .0002). Additionally, at the earlier timepoints, scores were higher among patients who underwent LSG than those who had undergone LRYGB as follows: POD 0 (LSG = 6.96 ± 6.50; LRYGB = 2.89 ± 2.90, P = .0115), POD 1 (LSG = 8.20 ± 6.76; LRYGB = 2.88 ± 3.44, P < .0001), and POD 2 (LSG = 4.05 ± 4.88; LRYGB = 2.06 ± 3.43, P = .05). On subset analysis, examining patients who either underwent an LSG or LRYGB, both procedures had a statistically significant PONV peak emerge on POV 2. Last, overall Rhodes scores were statistically higher in female patients compared with male patients (female: 4.43 ± 5.46; male: 2.35 ± 3.90, P = .021). Although the magnitude of the difference varied somewhat across POD time intervals, the difference was most pronounced at POV 2.

Conclusions: This is the largest study using a validated nausea and vomiting questionnaire to objectively measure PONV after bariatric surgery. The factors found to be most associated with increased PONV were LSG and female sex. Ultimately, these data can help bariatric surgery programs, including Washington University Weight Loss Surgery, identify patients who may require more intensive treatment of PONV, particularly POD 0 to 2, and help to identify patients that continue to struggle with PONV in the later surgical recovery phase.
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http://dx.doi.org/10.1016/j.soard.2020.05.017DOI Listing
October 2020

Alcohol sensitivity in women after undergoing bariatric surgery: a cross-sectional study.

Surg Obes Relat Dis 2020 Apr 23;16(4):536-544. Epub 2020 Jan 23.

Department of Food Science and Human Nutrition, College of Agricultural, Consumer and Environmental Sciences, University of Illinois Urbana-Champaign, Urbana, Illinois; Division of Nutritional Sciences, University of Illinois Urbana-Champaign, Urbana, Illinois. Electronic address:

Background: Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), the most common bariatric surgeries performed worldwide, increase the risk to develop an alcohol use disorder. This might be due, in part, to surgery-related changes in alcohol pharmacokinetics. Another risk factor, unexplored within this population, is having a reduced subjective response to alcohol's sedative effects.

Objectives: To assess whether the alcohol sensitivity questionnaire (ASQ), a simple self-report measure, could pinpoint reduced alcohol sensitivity in the bariatric population.

Setting: University medical centers in Missouri and Illinois.

Methods: Women who had RYGB (n = 16), SG (n = 28), or laparoscopic adjustable gastric banding surgery (n = 11) within the last 5 years completed the ASQ for both pre- and postsurgical timeframes, and 45 of them participated in oral alcohol challenge testing postsurgery. Blood alcohol concentration (BAC) and subjective stimulation and sedation were measured before and for 3.5 hours after drinking.

Results: In line with faster and higher peak BACs after RYGB and SG than laparoscopic adjustable gastric banding surgery (P < .001), postsurgery ASQ scores were more reduced from presurgery scores after RYGB/SG than after laparoscopic adjustable gastric banding surgery (-2.3 ± .3 versus -1.2 ± .2; P < .05). However, despite the dramatic changes in BAC observed when ingesting alcohol after RYGB/SG surgeries, which resulted in peak BAC that were approximately 50% above the legal driving limit, a third of these women felt almost no alcohol-related sedative effects.

Conclusions: Although RYGB/SG dramatically increased sensitivity to alcohol in all participants, meaningful interindividual differences remained. The ASQ might help identify patients at increased risk to develop an alcohol use disorder after surgery.
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http://dx.doi.org/10.1016/j.soard.2020.01.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141947PMC
April 2020

Sengstaken-Blakemore Tube as a Rescue Treatment for Hemorrhagic Shock Secondary to Laparoscopic Adjustable Gastric Banding Erosion.

ACG Case Rep J 2019 Dec 25;6(12):e00296. Epub 2019 Dec 25.

Division of Gastroenterology, Washington University School of Medicine, St. Louis, MO.

Gastrointestinal bleeding is an uncommon but potentially life-threatening complication of laparoscopic adjustable gastric banding (LAGB) erosion. We present the use of a Sengstaken-Blakemore tube as a treatment device for severe gastrointestinal bleeding secondary to persistent LAGB erosion. A 72-year-old woman post-LAGB placement presented with hemorrhagic shock from gastric band erosion that was not responsive to endoscopic and angiographic interventions. A salvage attempt to tamponade with a Sengstaken-Blakemore tube resulted in successful resuscitation of the patient. When used judiciously, balloon tamponade serves as a replicable technique to control severe gastric band erosion refractory to standard management.
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http://dx.doi.org/10.14309/crj.0000000000000296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946207PMC
December 2019

Testing a model of body image in the bariatric surgery patient.

Appl Nurs Res 2020 04 7;52:151228. Epub 2020 Jan 7.

Washington University School of Medicine, 4921 Parkview Place, Suite C, Floor 8, St. Louis, MO 63110, United States of America. Electronic address:

Purpose: The purpose was to test a published model of body image in the bariatric surgery patient in the clinical office setting.

Background: A model was created based on clinical observations during field work and the literature. It focuses on five concepts of body image: body attitude, body checking, appearance orientation, perceived body size, and perceived body space. Testing this model 3 months after surgery is important because morphology changes rapidly influencing early changes in body image, yet there is a paucity of research at this time point.

Methods: For this study of 67 bariatric surgery patients, sequential sampling was used. Body image and anthropometric measures (body mass index and other weight loss indicators) were obtained at baseline and 3-months postoperatively. Established model testing criteria were used.

Results: Over 3 months, mean body mass index was significantly reduced. Mean body image was significantly improved regarding all concepts in the model, except body checking. Body image improvement varied widely when individual responses were examined.

Conclusions: The model was successfully tested. Data on the five concepts in the model provided a body image profile at 3 months indicating individuals' degree of improvement. Areas of non-improvement in the early postoperative phase may signal the need for interventions, like support or psychological counseling, for patients who might be struggling with views of themselves after surgery. Preliminary recommendations are made regarding several of the instruments and their use clinically. Researchers should take into consideration the study's short 3-month time frame when designing future studies.
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http://dx.doi.org/10.1016/j.apnr.2019.151228DOI Listing
April 2020

Biliopancreatic Diversion Induces Greater Metabolic Improvement Than Roux-en-Y Gastric Bypass.

Cell Metab 2019 11 3;30(5):855-864.e3. Epub 2019 Oct 3.

Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO, USA; Departments of Medicine and Pharmacology, University of California, San Diego, San Diego, CA, USA. Electronic address:

Diabetes remission is greater after biliopancreatic diversion (BPD) than Roux-en-Y gastric bypass (RYGB) surgery. We used a mixed-meal test with ingested and infused glucose tracers and the hyperinsulinemic-euglycemic clamp procedure with glucose tracer infusion to assess the effect of 20% weight loss induced by either RYGB or BPD on glucoregulation in people with obesity (ClinicalTrials.gov number: NCT03111953). The rate of appearance of ingested glucose into the circulation was much slower, and the postprandial increases in plasma glucose and insulin concentrations were markedly blunted after BPD compared to after RYGB. Insulin sensitivity, assessed as glucose disposal rate during insulin infusion, was ∼45% greater after BPD than RYGB, whereas β cell function was not different between groups. These results demonstrate that compared with matched-percentage weight loss induced by RYGB, BPD has unique beneficial effects on glycemic control, manifested by slower postprandial glucose absorption, blunted postprandial plasma glucose and insulin excursions, and greater improvement in insulin sensitivity.
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http://dx.doi.org/10.1016/j.cmet.2019.09.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6876863PMC
November 2019

Effect of alcohol ingestion on plasma glucose kinetics after Roux-en-Y gastric bypass surgery.

Surg Obes Relat Dis 2019 01 2;15(1):36-42. Epub 2018 Nov 2.

Department of Food Science and Human Nutrition, College of Agricultural, Consumer and Environmental Sciences, University of Illinois, Urbana-Champaign, Illinois; Division of Nutritional Sciences, College of Agricultural, Consumer and Environmental Sciences, University of Illinois, Urbana-Champaign, Illinois. Electronic address:

Background: Roux-en-Y gastric bypass surgery (RYGB) increases the rate of alcohol absorption so that peak blood alcohol concentration is 2-fold higher after surgery compared with concentrations reached after consuming the same amount presurgery. Because high doses of alcohol can lead to hypoglycemia, patients may be at increased risk of developing hypoglycemia after alcohol ingestion.

Objectives: We conducted 2 studies to test the hypothesis that the consumption of approximately 2 standard drinks of alcohol would decrease glycemia more after RYGB than before surgery.

Setting: Single-center prospective randomized trial.

Methods: We evaluated plasma glucose concentrations and glucose kinetics (assessed by infusing a stable isotopically labelled glucose tracer) after ingestion of a nonalcoholic drink (placebo) or an alcoholic drink in the following groups: (1) 5 women before RYGB (body mass index = 43 ± 5 kg/m) and 10 ± 2 months after RYGB (body mass index = 31 ± 7 kg/m; study 1), and (2) 8 women who had undergone RYGB surgery 2.2 ± 1.2 years earlier (body mass index = 30 ± 5 kg/m; study 2) RESULTS: Compared with the placebo drink, alcohol ingestion decreased plasma glucose both before and after surgery, but the reduction was greater before (glucose nadir placebo = -.4 ± 1.0 mg/dL versus alcohol = -9.6 ± 1.5 mg/dL) than after (glucose nadir placebo = -1.0 ± 1.6 mg/dL versus alcohol = -5.5 ± 2.6 mg/dL; P < .001) surgery. This difference was primarily due to an alcohol-induced early increase followed by a subsequent decrease in the rate of glucose appearance into systemic circulation.

Conclusion: RYGB does not increase the risk of hypoglycemia after consumption of a moderate dose of alcohol.
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http://dx.doi.org/10.1016/j.soard.2018.10.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6441624PMC
January 2019

Conceptualization of body image in the bariatric surgery patient.

Appl Nurs Res 2018 06 26;41:52-58. Epub 2018 Mar 26.

Washington University School of Medicine, 4921 Parkview Place, Suite C, Floor 8, St. Louis, MO 63110, United States. Electronic address:

Bariatric (weight loss) surgery is more popular than ever. The American Society for Metabolic and Bariatric Surgery in 2016 reported that 216,000 bariatric procedures were performed in the United States. Bariatric surgery has major physiological benefits; its use is expected to increase globally. However, patients may not anticipate the profound impact that rapid and massive weight loss may have on their body image after bariatric surgery. The construct of body image in this population needs to be explicated to facilitate continued research regarding this increasingly prevalent healthcare procedure. This article describes the formulation of a model of relevant concepts and dimensions within the construct of body image in the bariatric surgery patient. In the process of creating the model, we identified many factors influencing body image in patients before and after bariatric surgery, summarized eight measures, and developed a new definition based on prior work. Theoretical considerations are discussed. The long-term objective of this model building approach is to encourage researchers and clinicians to test the feasibility of systematic clinical measurement of body image at office visits before as well as multiple times after bariatric surgery.
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http://dx.doi.org/10.1016/j.apnr.2018.03.008DOI Listing
June 2018

Opioid Medication Use in the Surgical Patient: An Assessment of Prescribing Patterns and Use.

J Am Coll Surg 2018 08 7;227(2):203-211. Epub 2018 May 7.

Section of Minimally Invasive Surgery, Department of Surgery, Washington University in St Louis School of Medicine, St Louis, MO.

Background: With the epidemic of prescription opioid abuse in the US, rates of opioid-related unintentional deaths have risen dramatically. However, few data exist comparing postoperative opioid prescriptions with patient use. We sought to better elucidate this relationship in surgical patients.

Study Design: A prospective cohort study was conducted of narcotic-naïve patients undergoing open and laparoscopic abdominal procedures on a minimally invasive surgery service. During the first 14 post-discharge days and at their first postoperative clinic visit, patients recorded pain scores and number of opioid pills taken. Clinical data were extracted from the medical record. Descriptive statistics were used in data analysis.

Results: From 2014 through 2017, one hundred and seventy-six patients completed postoperative pain surveys. Mean age was 60.4 ± 14.9 years and sex was distributed equally. Most patients (69.9%) underwent laparoscopic procedures. Hydrocodone-acetaminophen was the most commonly prescribed postoperative pain medication (118 patients [67.0%]), followed by oxycodone-acetaminophen (26 patients [14.8%]). Patients were prescribed a median of 150 morphine milligram equivalents (MME) (interquartile range [IQR] 150 to 225 MME), equivalent to twenty 5-mg oral oxycodone pills (IQR 20 to 30 pills). However, by their first postoperative visit, they had only taken a median 30 MME (IQR 10 to 90 MME), or 4 pills (IQR 1.3 to 12 pills). Eight (4.5%) patients received a refill or an additional prescription for pain medications. At the first postoperative visit, 76.7% of respondents were satisfied or very satisfied with their overall postoperative pain management.

Conclusions: Postoperative patients might consume less than half of the opioid pills they are prescribed. More research is needed to standardize opioid prescriptions for postoperative pain management while reducing opioid diversion.
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http://dx.doi.org/10.1016/j.jamcollsurg.2018.04.032DOI Listing
August 2018

Sleeve gastrectomy surgery: when 2 alcoholic drinks are converted to 4.

Surg Obes Relat Dis 2018 03 10;14(3):277-283. Epub 2017 Nov 10.

Department of Food Science and Human Nutrition, College of Agricultural, Consumer and Environmental Sciences, University of Illinois, Urbana-Champaign, Illinois; Division of Nutritional Sciences, College of Agricultural, Consumer and Environmental Sciences, University of Illinois, Urbana-Champaign, Illinois. Electronic address:

Background: While it is well established that Roux-en-Y gastric bypass (RYGB) causes a rapid and heightened peak blood alcohol concentration (BAC), results from previous studies on the effects of sleeve gastrectomy (SG) on alcohol pharmacokinetics are conflicting. Data from 2 studies found SG did not affect BAC, whereas another study found SG caused a heightened peak BAC after alcohol ingestion. Moreover, these 3 studies estimated BAC from breathalyzers, which might not reliably estimate peak BAC.

Objectives: The aims of this study were to evaluate (1) the effect of SG, relative to RYGB and a presurgery group, on alcohol pharmacokinetics and subjective effects, and (2) whether breathalyzers are reliable in this population.

Setting: Single-center prospective nonrandomized trial.

Methods: We performed alcohol challenge tests in 11 women who had SG surgery 1.9 ± .1 years ago (body mass index = 35.1 ± 6.6 kg/m), 8 women who had RYGB surgery 2.2 ± .4 years ago (body mass index = 30.0 ± 5.2 kg/m), and 9 women who were scheduled for bariatric surgery (body mass index = 44.1 ± 4.0 kg/m). BACs were estimated from breath samples and measured by gas chromatography at various times after consuming approximately 2 standard drinks.

Results: BAC increased faster, peak BAC was approximately 2-fold higher, and feelings of drunkenness were heightened in both SG and RYGB groups relative to the presurgery group (P values<.001). BAC estimated from breath samples underestimated BAC by 27% (standard deviation = 13%) and missed peak BACs postsurgery.

Conclusions: SG, similar to RYGB, causes marked alterations in the response to alcohol ingestion manifested by a faster and higher peak BAC. The breathalyzer is invalid to assess effects of gastric surgeries on pharmacokinetics of ingested alcohol.
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http://dx.doi.org/10.1016/j.soard.2017.11.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5844810PMC
March 2018

Effects of Sleeve Gastrectomy vs. Roux-en-Y Gastric Bypass on Eating Behavior and Sweet Taste Perception in Subjects with Obesity.

Nutrients 2017 Dec 24;10(1). Epub 2017 Dec 24.

Department of Food Science and Human Nutrition, College of Agricultural, Consumer and Environmental Sciences, University of Illinois, Urbana-Champaign, Champaign, IL 61801, USA.

The goal of this study was to test the hypothesis that weight loss induced by Roux-en-Y gastric bypass (RYGB) has greater effects on taste perception and eating behavior than comparable weight loss induced by sleeve gastrectomy (SG). We evaluated the following outcomes in 31 subjects both before and after ~20% weight loss induced by RYGB ( = 23) or SG ( = 8): (1) sweet, savory, and salty taste sensitivity; (2) the most preferred concentrations of sucrose and monosodium glutamate; (3) sweetness palatability, by using validated sensory testing techniques; and (4) eating behavior, by using the Food Craving Inventory and the Dutch Eating Behavior Questionnaire. We found that neither RYGB nor SG affected sweetness or saltiness sensitivity. However, weight loss induced by either RYGB or SG caused the same decrease in: (1) frequency of cravings for foods; (2) influence of emotions and external food cues on eating behavior; and (3) shifted sweetness palatability from pleasant to unpleasant when repetitively tasting sucrose (all -values ≤ 0.01). Therefore, when matched on weight loss, SG and RYGB cause the same beneficial effects on key factors involved in the regulation of eating behavior and hedonic component of taste perception.
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http://dx.doi.org/10.3390/nu10010018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5793246PMC
December 2017

Early major complications after bariatric surgery in the USA, 2003-2014: a systematic review and meta-analysis.

Obes Rev 2018 04 20;19(4):529-537. Epub 2017 Dec 20.

Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA.

The effectiveness of bariatric surgery has been well-studied. However, complications after bariatric surgery have been understudied. This review assesses <30-d major complications associated with bariatric procedures, including anastomotic leak, myocardial infarction and pulmonary embolism. This review included 71 studies conducted in the USA between 2003 and 2014 and 107,874 patients undergoing either gastric bypass, adjustable gastric banding or sleeve gastrectomy, with mean age of 44 years and pre-surgery body mass index of 46.5 kg m . Less than 30-d anastomotic leak rate was 1.15%; myocardial infarction rate was 0.37%; pulmonary embolism rate was 1.17%. Among all patients, mortality rate following anastomotic leak, myocardial infarction and pulmonary embolism was 0.12%, 0.37% and 0.18%, respectively. Among surgical procedures, <30-d after surgery, sleeve gastrectomy (1.21% [95% confidence interval, 0.23-2.19%]) had higher anastomotic leak rate than gastric bypass (1.14% [95% confidence interval, 0.84-1.43%]); gastric bypass had higher rates of myocardial infarction and pulmonary embolism than adjustable gastric banding or sleeve gastrectomy. During the review, we found that the quality of complication reporting is lower than the reporting of other outcomes. In summary, <30-d rates of the three major complications after either one of the procedures range from 0% to 1.55%. Mortality following these complications ranges from 0% to 0.64%. Future studies reporting complications after bariatric surgery should improve their reporting quality.
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http://dx.doi.org/10.1111/obr.12647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5880318PMC
April 2018

Bariatric Surgery-Induced Cardiac and Lipidomic Changes in Obesity-Related Heart Failure with Preserved Ejection Fraction.

Obesity (Silver Spring) 2018 02 15;26(2):284-290. Epub 2017 Dec 15.

Cardiovascular Division, Department of Medicine, School of Medicine, Washington University, St Louis, Missouri, USA.

Objective: To determine the effects of gastric bypass on myocardial lipid deposition and function and the plasma lipidome in women with obesity and heart failure with preserved ejection fraction (HFpEF).

Methods: A primary cohort (N = 12) with HFpEF and obesity underwent echocardiography and magnetic resonance spectroscopy both before and 3 months and 6 months after bariatric surgery. Plasma lipidomic analysis was performed before surgery and 3 months after surgery in the primary cohort and were confirmed in a validation cohort (N = 22).

Results: After surgery-induced weight loss, Minnesota Living with Heart Failure questionnaire scores, cardiac mass, and liver fat decreased (P < 0.02, P < 0.001, and P = 0.007, respectively); echo-derived e' increased (P = 0.03), but cardiac fat was unchanged. Although weight loss was associated with decreases in many plasma ceramide and sphingolipid species, plasma lipid and cardiac function changes did not correlate.

Conclusions: Surgery-induced weight loss in women with HFpEF and obesity was associated with improved symptoms, reverse cardiac remodeling, and improved relaxation. Although weight loss was associated with plasma sphingolipidome changes, cardiac function improvement was not associated with lipidomic or myocardial triglyceride changes. The results of this study suggest that gastric bypass ameliorates obesity-related HFpEF and that cardiac fat deposition and lipidomic changes may not be critical to its pathogenesis.
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http://dx.doi.org/10.1002/oby.22038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5783730PMC
February 2018

Roux-en-Y Gastric Bypass Surgery Has Unique Effects on Postprandial FGF21 but Not FGF19 Secretion.

J Clin Endocrinol Metab 2017 10;102(10):3858-3864

Center for Human Nutrition, Washington University School of Medicine, St. Louis, Missouri 63110.

Context: Fibroblast growth factor (FGF)19 and FGF21 are secreted by the intestine and liver in response to macronutrient intake. Intestinal resection and reconstruction via bariatric surgery may alter their regulation.

Objective: We tested the hypothesis that weight loss induced by Roux-en-Y gastric bypass (RYGB) surgery, but not matched weight loss induced by laparoscopic adjustable gastric banding (LAGB), increases postprandial plasma FGF19 and FGF21 concentrations.

Design: Glucose kinetics and plasma FGF19 and FGF21 responses to mixed meal ingestion and to glucose-insulin infusion during a hyperinsulinemic-euglycemic clamp procedure, with stable isotope tracer methods, were evaluated in 28 adults with obesity before and after 20% weight loss induced by RYGB (n = 16) or LAGB (n = 12).

Results: LAGB- and RYGB-induced weight loss increased postprandial plasma FGF19 concentrations (P < 0.05). However, weight loss after RYGB, but not LAGB, increased postprandial plasma FGF21 concentrations (1875 ± 330 to 2976 ± 682 vs 2150 ± 310 and 1572 ± 265 pg/mL × 6 hours, respectively). The increase in plasma FGF21 occurred ∼2 hours after the peak in delivery of ingested glucose into systemic circulation. Glucose-insulin infusion increased plasma FGF21, but not FGF19, concentrations. The increase in plasma FGF21 during glucose-insulin infusion was greater after than before weight loss in both surgery groups without a difference between groups, whereas plasma FGF19 was not affected by either procedure.

Conclusions: RYGB-induced weight loss has unique effects on postprandial FGF21 metabolism, presumably due to rapid delivery of ingested macronutrients to the small intestine and delivery of glucose to the liver.
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http://dx.doi.org/10.1210/jc.2017-01295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5630246PMC
October 2017

Randomized sham-controlled trial evaluating efficacy and safety of endoscopic gastric plication for primary obesity: The ESSENTIAL trial.

Obesity (Silver Spring) 2017 02 21;25(2):294-301. Epub 2016 Dec 21.

Gastroenterology, Brigham and Women's Hospital, Boston, Massachusetts, USA.

Objective: Evaluate safety and efficacy of the pose™ procedure for obesity treatment.

Methods: Subjects with Class I to II obesity were randomized (2:1) to receive active or sham procedure, after each investigator performed unblinded lead-in cases. All subjects were provided low-intensity lifestyle therapy. Efficacy end points were the mean difference in percent total body weight loss (%TBWL) at 12 months between randomized groups, and responder rate achieving ≥5% TBWL. The primary safety end point was incidence of reported adverse events.

Results: Three hundred thirty-two subjects were randomized (active, n = 221; sham, n = 111); thirty-four subjects were included in the unblinded lead-in cohort. Twelve-month results were mean TBWL 7.0 ± 7.4% in lead-in, 4.95 ± 7.04% in active, and 1.38 ± 5.58% in sham groups, respectively. Responder rate was 41.55% in active and 22.11% in sham groups, respectively (P < 0.0001); mean responder result was 11.5% TBWL. The differences observed between active and sham groups for co-primary end points were statistically significant (P < 0.0001); however, super superiority margin as set forth in the study design was not met. No unanticipated adverse events or deaths occurred. Procedure-related serious adverse event rates were 5.0% (active) and 0.9% (sham), P = 0.068.

Conclusions: The pose procedure was safe and resulted in statistically significant and clinically meaningful weight loss over sham through 1 year.
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http://dx.doi.org/10.1002/oby.21702DOI Listing
February 2017

Effect of Roux-en-Y gastric bypass and laparoscopic adjustable gastric banding on gastrointestinal metabolism of ingested glucose.

Am J Clin Nutr 2016 Jan 25;103(1):61-5. Epub 2015 Nov 25.

Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, MO;

Background: Data from studies conducted in animal models suggest that intestinal glucose uptake and metabolism are upregulated after Roux-en-Y gastric bypass (RYGB) surgery, which contributes to a weight-loss-independent improvement in glycemic control.

Objective: We conducted a cohort study to evaluate whether an increase in gastrointestinal metabolism of ingested glucose occurs in obese people who underwent RYGB compared with those who underwent laparoscopic adjustable gastric banding (LAGB).

Design: A mixed meal containing stable isotope-labeled glucose was used to determine the gastrointestinal (small intestine and liver) retention, and presumably metabolism, of ingested glucose in obese subjects before and after matched weight loss (∼21%) induced by RYGB (n = 16) or LAGB (n = 9).

Results: The total percentage of ingested glucose that appeared in the systemic circulation was slightly lower after than before RYGB (85% ± 9% and 90% ± 8%, respectively) but was slightly higher after than before LAGB (89% ± 3% and 85% ± 4%, respectively) (P-interaction < 0.05). Accordingly, gastrointestinal clearance of ingested glucose (cumulative percentage cleared over 6 h postprandially) increased after RYGB (from 10% ± 8% before to 15% ± 9% after surgery) but decreased after LAGB (from 15% ± 4% before to 11% ± 3% after surgery) (P < 0.05). Surgery-induced weight loss caused a similar decrease in the 6-h postprandial plasma glucose area under the curve in both RYGB and LAGB groups (-4% ± 9% and -6% ± 5%, respectively; P = 0.475).

Conclusions: These data support the notion that intestinal glucose disposal increases after RYGB surgery. However, the magnitude of the effect was small and did not result in weight-loss-independent therapeutic effects on postprandial glycemic control. This trial was registered at clinicaltrials.gov as NCT00981500.
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http://dx.doi.org/10.3945/ajcn.115.116111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4691669PMC
January 2016

Effect of Roux-en-Y Gastric Bypass Surgery: Converting 2 Alcoholic Drinks to 4.

JAMA Surg 2015 Nov;150(11):1096-8

Center for Human Nutrition, Washington University School of Medicine, St Louis, Missouri2Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St Louis, Missouri.

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http://dx.doi.org/10.1001/jamasurg.2015.1884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4886858PMC
November 2015

Adipose tissue monomethyl branched-chain fatty acids and insulin sensitivity: Effects of obesity and weight loss.

Obesity (Silver Spring) 2015 Feb 18;23(2):329-34. Epub 2014 Oct 18.

Department of Biochemistry and Molecular Biology, Soochow University Medical College, Suzhou, China; Center for Human Nutrition, Washington University School of Medicine, St. Louis, Missouri, USA.

Objectives: An increase in circulating branched-chain amino acids (BCAA) is associated with insulin resistance. Adipose tissue is a potentially important site for BCAA metabolism. It was evaluated whether monomethyl branched-chain fatty acids (mmBCFA) in adipose tissue, which are likely derived from BCAA catabolism, are associated with insulin sensitivity.

Methods: Insulin-stimulated glucose disposal was determined by using the hyperinsulinemic-euglycemic clamp procedure with stable isotope glucose tracer infusion in nine lean and nine obese subjects, and in a separate group of nine obese subjects before and 1 year after Roux-en-Y gastric bypass (RYGB) surgery (38% weight loss). Adipose tissue mmBCFA content was measured in tissue biopsies taken in the basal state.

Results: Total adipose tissue mmBCFA content was ∼30% lower in obese than lean subjects (P=0.02) and increased by ∼65% after weight loss in the RYGB group (P=0.01). Adipose tissue mmBCFA content correlated positively with skeletal muscle insulin sensitivity (R(2) =35%, P=0.01, n=18).

Conclusions: These results demonstrate a novel association between adipose tissue mmBCFA content and obesity-related insulin resistance. Additional studies are needed to determine whether the association between adipose tissue mmBCFA and muscle insulin sensitivity is causal or a simple association.
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http://dx.doi.org/10.1002/oby.20923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4310778PMC
February 2015

Perioperative risk and complications of revisional bariatric surgery compared to primary Roux-en-Y gastric bypass.

Surg Endosc 2015 Jun 8;29(6):1316-20. Epub 2014 Oct 8.

Department of Surgery and Section of Minimally Invasive Surgery, Washington University School of Medicine, 660 S. Euclid Ave, Box 8109, St Louis, MO, 63110, USA,

Introduction: Growing number of patients requires revisional bariatric surgery. This study compares perioperative course and outcomes of revisional versus primary bariatric surgery.

Methods: Patients who underwent revisional bariatric surgery from Jan 1997 to Sept 2012 were reviewed retrospectively. Every revisional patient with BMI >35 and age <70 was matched with a primary Roux-en-Y gastric bypass control patient based on preoperative BMI, age, sex, and year of surgery. Patients' preoperative indications, intraoperative/postoperative course, and complications were analyzed.

Results: Two hundred and fifty five patients underwent revisional bariatric surgery with resulting Roux-en-Y gastric bypass anatomy while 1,674 patients underwent primary gastric bypass in the same time interval. Of 255 patients, 172 patients were paired with 172 primary gastric bypass patients. Revisional bariatric group had preoperative BMI 48 ± 9, age 52 ± 9 years, 93 % female, 44 % laparoscopic, 30 % diabetic, 60 % hypertensive. Primary bypass patients had preoperative BMI 49 ± 8, age 52 ± 9 years, 93 % female, 97 % laparoscopic, 49 % diabetic, 67 % hypertensive. Compared to primary bypass patients, revisional patients had significantly higher estimated blood loss (463.7 vs. 113.3 mL), longer operative time (272.5 vs. 175.5 min), greater risk for ICU stay (N = 24, 14 % vs. N = 2, 1 %), and longer hospital stay (5.6 vs. 2.5 days). There were significantly more intraoperative liver (N = 13, 8 % vs. N = 1, 1 %) and spleen (N = 18, 10 % vs. N = 0) injuries, and more enterotomies (N = 9, 5 % vs. N = 0) in the revisional group. There were also significantly more postoperative complications (N = 94, 55 % vs. N = 48, 28 %), readmissions (N = 27, 16 % vs. N = 12, 7 %), and reoperations (N = 16, 9 % vs. N = 3, 2 %) within 30 days of surgery. Mean percentage weight loss at 1 year was significantly less for revisional patients (27 vs. 37 %). There was no significant difference in 30 day mortality between the two groups (N = 6 vs. 0).

Conclusion: Even in experienced hands, complex revisional bariatric surgery should be approached with significant caution, especially given that weight loss is less substantial.
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http://dx.doi.org/10.1007/s00464-014-3848-4DOI Listing
June 2015

Peroral endoscopic extraction of an eroded laparoscopic gastric band.

Gastrointest Endosc 2015 Feb 28;81(2):456-7. Epub 2014 Jun 28.

Division of Gastroenterology and Hepatology, Washington University School of Medicine, St. Louis, Missouri, USA.

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http://dx.doi.org/10.1016/j.gie.2014.05.314DOI Listing
February 2015

Matched weight loss induced by sleeve gastrectomy or gastric bypass similarly improves metabolic function in obese subjects.

Obesity (Silver Spring) 2014 Sep 28;22(9):2026-31. Epub 2014 May 28.

Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, Missouri, USA; Division of Endocrinology, Diabetes and Metabolism, The Ohio State University Medical Center, Columbus, Ohio, USA.

Objective: The effects of marked weight loss, induced by Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) surgeries, on insulin sensitivity, β-cell function and the metabolic response to a mixed meal were evaluated.

Methods: Fourteen nondiabetic insulin-resistant patients who were scheduled to undergo SG (n = 7) or RYGB (n = 7) procedures completed a hyperinsulinemic-euglycemic clamp procedure and a mixed-meal tolerance test before surgery and after losing ∼20% of their initial body weight.

Results: Insulin sensitivity (insulin-stimulated glucose disposal during a clamp procedure), oral glucose tolerance (postprandial plasma glucose area under the curve), and β-cell function (insulin secretion in relationship to insulin sensitivity) improved after weight loss, and were not different between surgical groups. The metabolic response to meal ingestion was similar after RYGB or SG, manifested by rapid delivery of ingested glucose into the systemic circulation and a large early postprandial increase in plasma glucose, insulin, and C-peptide concentrations in both groups.

Conclusions: When matched on weight loss, RYGB and SG surgeries result in similar improvements in the two major factors involved in regulating plasma glucose homeostasis, insulin sensitivity and β-cell function in obese people without diabetes.
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http://dx.doi.org/10.1002/oby.20803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149594PMC
September 2014

Bariatric surgery-induced weight loss causes remission of food addiction in extreme obesity.

Obesity (Silver Spring) 2014 Aug 23;22(8):1792-8. Epub 2014 May 23.

Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, Missouri, 63110, USA.

Objective: To test the hypotheses that bariatric surgery-induced weight loss: induces remission of food addiction (FA), and normalizes other eating behaviors associated with FA.

Methods: Forty-four obese subjects (BMI= 48 ± 8 kg/m(2) ) were studied before and after ∼20% weight loss induced by bariatric surgery (25 Roux-en-Y gastric bypass, 11 laparoscopic adjustable gastric banding, and eight sleeve gastrectomy). We assessed: FA (Yale Food Addiction Scale), food cravings (Food Craving Inventory), and restrictive, emotional and external eating behaviors (Dutch Eating Behavior Questionnaire).

Results: FA was identified in 32% of subjects before surgery. Compared with non-FA subjects, those with FA craved foods more frequently, and had higher scores for emotional and external eating behaviors (all P-values <0.01; all Cohen's d >0.8). Surgery-induced weight loss resulted in remission of FA in 93% of FA subjects; no new cases of FA developed after surgery. Surgery-induced weight loss decreased food cravings, and emotional and external eating behaviors in both groups (all P-values < 0.001; all Cohen's d ≥ 0.8). Restrictive eating behavior did not change in non-FA subjects but increased in FA subjects (P < 0.01; Cohen's d>1.1).

Conclusion: Bariatric surgery-induced weight loss induces remission of FA and improves several eating behaviors that are associated with FA.
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http://dx.doi.org/10.1002/oby.20797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4115048PMC
August 2014

Changes in taste perception and eating behavior after bariatric surgery-induced weight loss in women.

Obesity (Silver Spring) 2014 May 6;22(5):E13-20. Epub 2013 Dec 6.

Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, Missouri, 63110, USA.

Objective: Roux-en-Y gastric bypass (RYGB) surgery causes greater weight loss than laparoscopic adjustable gastric banding (LAGB). We tested the hypothesis that RYGB has weight loss-independent effects on taste perception, which influence eating behavior and contribute to the greater weight loss.

Methods: Subjects were studied before and after ∼20% weight loss induced by RYGB (n = 17) or LAGB (n = 10). The following have been evaluated: taste sensitivity for sweet, salty and savory stimuli, sucrose and monosodium glutamate (MSG) preferences, sweetness palatability, eating behavior, and expression of taste-related genes in biopsies of fungiform papillae.

Results: Weight loss induced by both procedures caused the same decrease in: preferred sucrose concentration (-12 ± 10%), perceived sweetness of sucrose (-7 ± 5%), cravings for sweets and fast-foods (-22 ± 5%), influence of emotions (-27 ± 5%), and external food cues (-30 ± 4%) on eating behavior, and expression of α-gustducin in fungiform papillae (all P values <0.05). RYGB, but not LAGB, shifted sweetness palatability from pleasant to unpleasant when repetitively tasting sucrose (P = 0.05). Neither procedure affected taste detection thresholds nor MSG preferences.

Conclusions: LAGB and RYGB cause similar alterations in eating behaviors, when weight loss is matched. These changes in eating behavior were not associated with changes in taste sensitivity, suggesting other, as yet unknown, mechanisms are involved.
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http://dx.doi.org/10.1002/oby.20649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4000290PMC
May 2014

Incidence, mechanisms, and outcomes of esophageal and gastric perforation during laparoscopic foregut surgery: a retrospective review of 1,223 foregut cases.

Surg Endosc 2014 Jan 7;28(1):85-90. Epub 2013 Sep 7.

Section of Minimally Invasive Surgery, Department of Surgery, Washington University School of Medicine, 660 S Euclid Avenue, Box 8109, St. Louis, MO, 63110, USA,

Background: Intraoperative perforation is a potentially major complication of laparoscopic (lap) foregut surgery. This study analyzed the incidence, mechanism, and outcomes of intraoperative perforations during these procedures in a large institutional experience.

Methods: All patients who underwent lap foregut surgery including laparoscopic antireflux surgery (LARS), paraesophageal hernia (PEH) repair, Heller myotomy, and reoperative hiatal hernia (redo HH) repair at the authors' institution from August 2004 to September 2012 were reviewed retrospectively. Perforation events and postoperative outcomes were analyzed, and complications were graded by the modified Clavien system. All data are expressed as means ± standard deviations or as medians. Statistical analysis was performed using Fisher's exact test and the Mann-Whitney U test.

Results: In this study, the repairs for 1,223 patients were analyzed (381 LARS procedures, 379 PEH repairs, 313 Heller myotomies, 150 redo HH repairs). Overall, 51 patients (4.2 %) had 56 perforations resulting from LARS (n = 4, 1 %), PEH repair (n = 7, 1.8 %), Heller myotomy (n = 18, 5.8 %), and redo HH repair (n = 22, 14.6 %). Redo HH was significantly more likely to result in perforations than LARS or PEH repair (p < 0.001). The locations of the perforations were esophageal in 13 patients (23.6 %), gastric in 40 patients (72.7 %), and indeterminate in 2 patients (3.6 %). The most common mechanisms of perforations were suture placement for LARS (75 %) and traction for PEH repair (43 %) and for Heller myotomy during the myotomy (72 %). The most redo HH perforations resulted from dissection/wrap takedown (73 %) and traction (14 %). Perforations were recognized and repaired intraoperatively in 43 cases (84 %) and postoperatively in eight cases (16 %). Perforations discovered postoperatively were more likely to require reoperation (75 vs 2 %; p < 0.001), to require more gastrointestinal and radiologic interventions (50 vs 2 %; p = 0.004), and to have higher morbidity (88 vs 26 %; p = 0.004) than perforations recognized intraoperatively.

Conclusions: In a high-volume center, intraoperative perforations are the most frequent with reoperative HH repair. If perforations are recognized and repaired intraoperatively, they require minimal postoperative intervention. Unrecognized perforations usually require reoperation and result in significantly greater morbidity.
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http://dx.doi.org/10.1007/s00464-013-3167-1DOI Listing
January 2014

Effect of Roux-en-Y gastric bypass and laparoscopic adjustable gastric banding on branched-chain amino acid metabolism.

Diabetes 2013 Aug 22;62(8):2757-61. Epub 2013 Apr 22.

Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine,Washington University School of Medicine, St Louis, Missouri, USA.

It has been hypothesized that a greater decline in circulating branched-chain amino acids (BCAAs) after weight loss induced by Roux-en-Y gastric bypass (RYGB) surgery than after calorie restriction alone has independent effects on glucose homeostasis, possibly by decreased signaling through the mammalian target of rapamycin (mTOR). We evaluated plasma BCAAs and their C3 and C5 acylcarnitine metabolites, muscle mTOR phosphorylation, and insulin sensitivity (insulin-stimulated glucose Rd) in obese subjects before and after ~20% weight loss induced by RYGB (n = 10, BMI 45.6 ± 6.7 kg/m(2)) or laparoscopic adjustable gastric banding (LAGB) (n = 10, BMI 46.5 ± 8.8 kg/m(2)). Weight loss increased insulin-stimulated glucose Rd by ~55%, decreased total plasma BCAA and C3 and C5 acylcarnitine concentrations by 20-35%, and did not alter mTOR phosphorylation; no differences were detected between surgical groups (all P values for interaction >0.05). Insulin-stimulated glucose Rd correlated negatively with plasma BCAAs and with C3 and C5 acylcarnitine concentrations (r values -0.56 to -0.75, P < 0.05). These data demonstrate that weight loss induced by either LAGB or RYGB causes the same decline in circulating BCAAs and their C3 and C5 acylcarnitine metabolites. Plasma BCAA concentration is negatively associated with skeletal muscle insulin sensitivity, but the mechanism(s) responsible for this relationship is not known.
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http://dx.doi.org/10.2337/db13-0185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3717831PMC
August 2013

Association between specific adipose tissue CD4+ T-cell populations and insulin resistance in obese individuals.

Gastroenterology 2013 Aug 15;145(2):366-74.e1-3. Epub 2013 Apr 15.

Center for Human Nutrition, Washington University School of Medicine, St Louis, Missouri 63110, USA.

Background & Aims: An increased number of macrophages in adipose tissue is associated with insulin resistance and metabolic dysfunction in obese people. However, little is known about other immune cells in adipose tissue from obese people, and whether they contribute to insulin resistance. We investigated the characteristics of T cells in adipose tissue from metabolically abnormal insulin-resistant obese (MAO) subjects, metabolically normal insulin-sensitive obese (MNO) subjects, and lean subjects. Insulin sensitivity was determined by using the hyperinsulinemic euglycemic clamp procedure.

Methods: We assessed plasma cytokine concentrations and subcutaneous adipose tissue CD4(+) T-cell populations in 9 lean, 12 MNO, and 13 MAO subjects. Skeletal muscle and liver samples were collected from 19 additional obese patients undergoing bariatric surgery to determine the presence of selected cytokine receptors.

Results: Adipose tissue from MAO subjects had 3- to 10-fold increases in numbers of CD4(+) T cells that produce interleukin (IL)-22 and IL-17 (a T-helper [Th] 17 and Th22 phenotype) compared with MNO and lean subjects. MAO subjects also had increased plasma concentrations of IL-22 and IL-6. Receptors for IL-17 and IL-22 were expressed in human liver and skeletal muscle samples. IL-17 and IL-22 inhibited uptake of glucose in skeletal muscle isolated from rats and reduced insulin sensitivity in cultured human hepatocytes.

Conclusions: Adipose tissue from MAO individuals contains increased numbers of Th17 and Th22 cells, which produce cytokines that cause metabolic dysfunction in liver and muscle in vitro. Additional studies are needed to determine whether these alterations in adipose tissue T cells contribute to the pathogenesis of insulin resistance in obese people.
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http://dx.doi.org/10.1053/j.gastro.2013.04.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3756481PMC
August 2013

Weight loss induced by Roux-en-Y gastric bypass but not laparoscopic adjustable gastric banding increases circulating bile acids.

J Clin Endocrinol Metab 2013 Apr 1;98(4):E708-12. Epub 2013 Mar 1.

Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA.

Context: It has been hypothesized that increased plasma bile acids (BAs) contribute to metabolic improvements after Roux-en-Y gastric bypass (RYGB) surgery by the G protein-coupled receptor TGR5-mediated effects on glucagon-like peptide-1 secretion and thyroid hormones.

Objective: The objective of this study was to evaluate the importance of bariatric surgery-induced alterations in BA physiology on factors that regulate glucose homeostasis (insulin secretion and sensitivity) and energy metabolism (resting energy expenditure and thyroid hormone axis). DESIGN, PARTICIPANTS, INTERVENTION, AND MAIN OUTCOME MEASURE: Eighteen extremely obese subjects were studied before and after 20% weight loss, induced by either laparoscopic adjustable gastric banding (LAGB) (n = 10) or RYGB surgery (n = 8).

Results: Plasma BAs more than doubled after RYGB [fasting: 1.08 (0.26-1.42) to 2.28 (1.59-3.28) μmol/L, P = .03; postprandial: 2.46 ± 1.59 to 6.00 ± 2.75 μmol/L, P = .01] but were either lower or did not change after LAGB [fasting: 1.80 (1.49-2.19) to 0.92 (0.73-1.15) μmol/L, P = .02; postprandial: 3.71 ± 2.61 to 2.82 ± 1.75 μmol/L, P = .14]. Skeletal muscle expression of TGR5 targets, Kir6.2 and cyclooxygenase IV, increased after RYGB but not LAGB. Surgery-induced changes in BAs were associated with increased peak postprandial plasma glucagon-like peptide-1 (r(2) = 0.509, P = .001) and decreased serum TSH (r(2) = 0.562, P < .001) but did not correlate with the change in insulin response to a meal (r(2) = 0.013, P = .658), insulin sensitivity (assessed as insulin stimulated glucose disposal during a hyperinsulinemic-euglycemic clamp procedure) (r(2) = 0.001, P = .995), or resting energy expenditure (r(2) = 0.004, P = .807).

Conclusions: Compared with LAGB, RYGB increases circulating BAs and TGR5 signaling, but this increase in BAs is not a significant predictor of changes in glucose homeostasis or energy metabolism.
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http://dx.doi.org/10.1210/jc.2012-3736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3615197PMC
April 2013

Gastric bypass and banding equally improve insulin sensitivity and β cell function.

J Clin Invest 2012 Dec 26;122(12):4667-74. Epub 2012 Nov 26.

Center for Human Nutrition, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

Bariatric surgery in obese patients is a highly effective method of preventing or resolving type 2 diabetes mellitus (T2DM); however, the remission rate is not the same among different surgical procedures. We compared the effects of 20% weight loss induced by laparoscopic adjustable gastric banding (LAGB) or Roux-en-Y gastric bypass (RYGB) surgery on the metabolic response to a mixed meal, insulin sensitivity, and β cell function in nondiabetic obese adults. The metabolic response to meal ingestion was markedly different after RYGB than after LAGB surgery, manifested by rapid delivery of ingested glucose into the systemic circulation, by an increase in the dynamic insulin secretion rate, and by large, early postprandial increases in plasma glucose, insulin, and glucagon-like peptide-1 concentrations in the RYGB group. However, the improvement in oral glucose tolerance, insulin sensitivity, and overall β cell function after weight loss were not different between surgical groups. Additionally, both surgical procedures resulted in a similar decrease in adipose tissue markers of inflammation. We conclude that marked weight loss itself is primarily responsible for the therapeutic effects of RYGB and LAGB on insulin sensitivity, β cell function, and oral glucose tolerance in nondiabetic obese adults.
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http://dx.doi.org/10.1172/JCI64895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3512168PMC
December 2012