Gastric Bypass Increases Circulating Bile Acids and Activates Hepatic Farnesoid X Receptor (FXR) but Requires Intact Peroxisome Proliferator Activator Receptor Alpha (PPARα) Signaling to Significantly Reduce Liver Fat Content.

BACKGROUND: We interrogate effects of gastric bypass (RYGB), compared with a low-calorie diet, on bile acid (BA), liver fat, and FXR, PPARα, and targets in rats with obesity and non-alcoholic fatty liver disease (NAFLD). METHODS: Male Wistar rats received a high-fat diet (obese/NAFLD, n=24) or standard chow (lean, n=8) for 12 weeks. Obese/NAFLD rats had RYGB (n=11), sham operation pair-fed to RYGB (pair-fed sham, n=8), or sham operation (sham, n=5). Lean rats had sham operation (lean sham, n=8). Post-operatively, five RYGB rats received PPARα antagonist GW6417. Sacrifice occurred at 7 weeks. We measured weight changes, fasting total plasma BA, and liver % steatosis, triglycerides, and mRNA expression of the nuclear receptors FXR, PPARα, and their targets SHP and CPT-I. RESULTS: At sacrifice, obese sham was heavier (p<0.01) than all other groups that had lost similar weight loss. Obese sham had lower BA levels and lower hepatic FXR, SHP, and CPT-I mRNA expression than lean sham (P<0.05, for all comparisons). RYGB had increased BA levels compared with obese and pair-fed sham (P<0.05, for both), while pair-fed sham had BA levels, similar to obese sham. Compared with pair-fed sham, RYGB animals had increased liver FXR and PPARα expression and signaling (P<0.05). Percentage of steatosis was lower in RYGB and lean sham, relative to obese and pair-fed sham (P<0.05, for all comparisons). PPARα inhibition after RYGB resulted in similar weight loss but higher liver triglyceride content (P=0.01) compared with RYGB alone. CONCLUSIONS: RYGB led to greater liver fat loss than low-calorie diet, an effect associated to increased fasting BA levels and increased expression of modulators of liver fat oxidation, FXR, and PPARα. However, intact PPARα signaling was necessary for resolution of NAFLD after RYGB.

Perioperative outcomes and cost of robotic-assisted versus laparoscopic inguinal hernia repair.

BACKGROUND: Utilization of robotic-assisted inguinal hernia repair (IHR) has increased in recent years, but randomized or prospective studies comparing outcomes and cost of laparoscopic and Robotic-IHR are still lacking. With conflicting results from only five retrospective series available in the literature comparing the two approaches, the question remains whether current robotic technology provides any added benefits to treat inguinal hernias. We aimed to compare perioperative outcomes and costs of Robotic-IHR versus laparoscopic totally extraperitoneal IHR (Laparoscopic-IHR). METHODS: Retrospective analysis of consecutive patients who underwent Robotic-IHR or Laparoscopic-IHR at a dedicated MIS unit in the USA from February 2015 to June 2017. Demographics, anthropometrics, the proportion of bilateral and recurrent hernias, operative details, cost, length of stay, 30-day readmissions and reoperations, and rates and severity of complications were compared. RESULTS: 183 patients had surgery: 45 (24.6%) Robotic-IHR and 138 (75.4%) Laparoscopic-IHR. There were no differences between groups in age, gender, BMI, ASA class, the proportion of bilateral hernias and recurrent hernias, and length of stay. Operative time (Robotic-IHR: 116 ± 36 min, vs. Laparoscopic-IHR: 95±44 min, p < 0.01), reoperations (Robotic-IHR: 6.7%, vs. Laparoscopic-IHR: 0%, p = 0.01), and readmissions rates were greater for Robotic-IHR. While the overall perioperative complication rate was similar in between groups (Robotic-IHR: 28.9% vs. Laparoscopic-IHR: 18.1%, p = 0.14), Robotic-IHR was associated with a significantly greater proportion of grades III and IV complications (Robotic-IHR: 6.7% vs. Laparoscopic-IHR: 0%, p = 0.01). Total hospital cost was significantly higher for the Robotic-IHRs ($9993 vs. $5994, p < 0.01). The added cost associated with the robotic device itself was $3106 per case and the total cost of disposable supplies was comparable between the 2 groups. CONCLUSIONS: In the setting in which it was studied, the outcomes of Laparoscopic-IHR were significantly superior to the Robotic-IHR, at lower hospital costs. Laparoscopic-IHR remains the preferred minimally invasive surgical approach to treat inguinal hernias.

Factors Mediating Type 2 Diabetes Remission and Relapse after Gastric Bypass Surgery.

BACKGROUND: Defining factors associated with remission and relapse of type 2 diabetes (T2D) after Roux-en-Y gastric bypass (RYGB) can allow targeting modifiable factors. We investigated factors associated with T2D remission and relapse after RYGB. STUDY DESIGN: We conducted a retrospective review of consecutive patients with T2D who underwent RYGB between 1993 and 2017. T2D remission was defined as medication discontinuation and/or hemoglobin A1c <6.5%. Relapse was defined as recurrence medication use and/or hemoglobin A1c ≥6.5%. Independent correlates of T2D remission and relapse were identified using logistic regression. RESULTS: Six hundred and twenty-one patients (aged 46.7 ± 10.6 years; 30% on insulin; BMI 49.8 ± 8.3 kg/m2) had at least 1-year follow-up. Median follow-up was 4.9 years (range 1 to 23.6 years). Prevalence of T2D remission was 74% at 1 year, 73% from 1 to 3 years, 63% between 3 and 10 years, and 47% beyond 10 years. Ninety-three percent of remissions occurred within 3 years of RYGB, 25% relapsed. Median time to relapse was 5.3 years (interquartile range 3 to 7.8 years) after remission. Higher 1-year percentage total body weight loss, lack of preoperative insulin use, and younger age at operation were independently associated with T2D remission. Preoperative insulin use, lower percentage total body weight loss at 1 year, and greater percentage total body weight regain after 1 year were independently associated with T2D relapse. CONCLUSIONS: This longitudinal retrospective analysis shows that preoperative insulin use and age, 1-year weight loss, and regain after that influence T2D remission and relapse after RYGB. Referring patients at a younger age, before insulin is needed, and optimizing weight loss and preventing weight regain after RYGB can improve the rates and durability of T2D remission.

Changes in Utilization of Bariatric Surgery in the United States From 1993 to 2016.

OBJECTIVE: The aim of this study was to obtain estimates of changes in perioperative outcomes and utilization of bariatric surgery in the United States from 1993 to 2016. BACKGROUND: Bariatric surgery has evolved over the past 2 decades. Nationally representative information on changes of perioperative outcomes and utilization of surgery in the growing eligible population (class III obesity or class II obesity with comorbidities) is lacking. METHODS: Adults with obesity diagnosis who underwent primary bariatric surgery in the United States from 1993 to 2016 were identified in the National Inpatient Sample database. Estimates of the yearly number, types and cost of surgeries, patients' and hospital characteristics, complications and mortality rates were obtained. Prevalence of obesity and comorbidities were obtained from the National Health and Nutrition Examination Survey and changes in utilization of surgery were estimated. RESULTS: An estimated 1,903,273 patients underwent bariatric surgery in the United States between 1993 and 2016. Mean age was 43.9 years (79.9% women, 70.9% white race, 70.7% commercial insurance); these and other characteristics changed over time. Surgeries were exclusively open operations in 1993 (n = 8,631; gastric bypass and vertical banded gastroplasty, 49% each) and 98% laparoscopic (n = 162,969; 69.8% sleeve gastrectomy and 27.8% gastric bypass) in 2016. Complication and mortality rates peaked in 1998 (11.7% and 1%) and progressively decreased to 1.4% and 0.04% in 2016. Utilization increased from 0.07% in 1993 to 0.62% in 2004 and remained low at 0.5% in 2016. CONCLUSIONS: Perioperative safety of bariatric surgery improved over the last quarter-century. Despite growth in number of surgeries, utilization has only marginally increased. Addressing barriers for utilization may allow for greater access to surgical therapy.

Population Diversity Challenge the External Validity of the European Randomized Controlled Trials Comparing Laparoscopic Gastric Bypass and Sleeve Gastrectomy.

INTRODUCTION: Two randomized controlled trials (RCTs) from Europe recently showed similar weight loss and rates of type 2 diabetes (T2D) remission following laparoscopic gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy (LSG). However, results from observational studies in the United States (US) have discordant results. We compared 1-year weight loss and T2D remission between LRYGB and LSG in a heterogeneous patient cohort from the US, albeit with similar inclusion and exclusion criteria to the European RCTs. METHODS: Logistic regression was used to propensity match LSG and LRYGB patients according to age, gender, race, preoperative BMI, and T2D. Inclusion and exclusion criteria were adopted from the two European RCTs. Demographic, anthropometric, weight outcomes, and comorbidities prevalence were compared at baseline and 1-year follow-up. RESULTS: We included 278 patients (139 LSG and 139 RYGB; median age 42 years, 89% female, 57% black race, 22% with public health insurance, and 25% with T2D). One year after surgery, mean %EWL was 77.3 ± 19.5% with LRYGB and 63.1 ± 21% with LSG (P < 0.001). Mean %TWL was 34.2 ± 7.3% after LRYGB and 28.1 ± 8.2% after LSG, (P < 0.001). The proportion of patients who achieved T2D remission was comparable between surgeries (LRGYB: 68.6% vs. LSG: 66.7%, P = 0.89). LSG, older age, black race, and higher preoperative BMI were independently associated with lower %EWL. Independent correlates of weight loss were different for LRYGB and LSG. CONCLUSIONS: Weight loss, but not the likelihood of T2D remission, was greater with LRYGB than LSG in a diverse patient cohort in the US. Further research efforts connecting population diversity to discordant results across studies is needed to better counsel patients with regards to expected postoperative outcomes.

Changes in Bile Acid Metabolism, Transport, and Signaling as Central Drivers for Metabolic Improvements After Bariatric Surgery.

PURPOSE OF REVIEW: We review current evidence regarding changes in bile acid (BA) metabolism, transport, and signaling after bariatric surgery and how these might bolster fat mass loss and energy expenditure to promote improvements in type 2 diabetes (T2D) and nonalcoholic fatty liver disease (NAFLD). RECENT FINDINGS: The two most common bariatric techniques, Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG), increase the size and alter the composition of the circulating BA pool that may then impact energy metabolism through altered activities of BA targets in the many tissues perfused by systemic blood. Recent reports in human patients indicate that gene expression of the major BA target, the farnesoid X receptor (FXR), is increased in the liver but decreased in the small intestine after RYGB. In contrast, intestinal expression of the transmembrane G protein-coupled BA receptor (TGR5) is upregulated after surgery. Despite these apparent conflicting changes in receptor transcription, changes in BAs after both RYGB and VSG are associated with elevated postprandial systemic levels of fibroblast growth factor 19 (from FXR activation) and glucagon-like peptide 1 (from TGR5 activation). These signaling activities are presumed to support fat mass loss and related metabolic benefits of bariatric surgery, and this supposition is in agreement with findings from rodent models of RYGB and VSG. However, inter-species differences in BA physiology limit direct translation and mechanistic understanding of how changes in individual BA species contribute to post-operative improvements of T2D and NAFLD in humans. Thus, details of all these changes and their influences on BAs' biological actions are still under scrutiny. Changes in BA physiology and receptor activities after RYGB and VSG likely support weight loss and promote sustained metabolic improvements.

Concomitant PPARα and FXR Activation as a Putative Mechanism of NASH Improvement after Gastric Bypass Surgery: a GEO Datasets Analysis.

BACKGROUND: Compared to non-surgical weight loss (Diet), weight loss after Roux-en-Y gastric bypass (RYGB) results in greater rates of non-alcoholic steatohepatitis (NASH) resolution. Changes in bile acid physiology and farnesoid X receptor (FXR) signaling are suspected mediators of postoperative NASH improvement. Recent experimental evidence suggests that upregulation of hepatic peroxisome proliferator-activated receptor α (PPARα) activity might also impact NASH improvement. As FXR partly regulates PPARα, we compared resolution of NASH and changes in hepatic PPARα and FXR gene expression following Diet and RYGB. METHODS: We searched the Gene Expression Omnibus database to identify human studies with liver biopsies containing genomic data and histologic NASH features, at baseline and after Diet or RYGB. Microarray data were extracted for PPARα and FXR gene expression analyses using GEOquery R package v.2.42.0. RESULTS: We identified one study (GSE83452) where patients underwent either Diet (n = 29) or RYGB (n = 25). NASH prevalence was similar at baseline (Diet 76% versus RYGB 60%, P = ns). After 1 year, NASH resolved in 93.3% of RYGB but only in 27.3% of Diet (P < 0.001). Hepatic PPARα and FXR gene expression increased only after RYGB (P < 0.001). These changes were also found when analyzing only patients that resolved NASH (P < 0.01), and patients without NASH at baseline and follow-up (P < 0.05). CONCLUSIONS: Compared to Diet, RYGB results in greater NASH resolution with concurrent upregulation of hepatic PPARα and FXR. Our findings point to concurrent PPARα and FXR activation, triggered by RYGB, as a potential mechanism to improve NASH.

LAP-VEGaS Practice Guidelines for Reporting of Educational Videos in Laparoscopic Surgery: A Joint Trainers and Trainees Consensus Statement.

OBJECTIVE: Consensus statement by an international multispecialty trainers and trainees expert committee on guidelines for reporting of educational videos in laparoscopic surgery. SUMMARY OF BACKGROUND DATA: Instructive laparoscopy videos with appropriate exposition could be ideal for initial training in laparoscopic surgery, but there are no guidelines for video annotation or procedural educational and safety evaluation. METHODS: Delphi questionnaire of 45 statements prepared by a steering group and voted on over 2 rounds by committee members using an electronic survey tool. Committee selection design included representative surgical training experts worldwide across different laparoscopic specialties, including general surgery, lower and upper gastrointestinal surgery, gynecology and urology, and a proportion of aligned surgical trainees. RESULTS: All 33 committee members completed both the first and the second round of the Delphi questionnaire related to 7 major domains: Video Introduction/Authors' information; Patient Details; Procedure Description; Procedure Outcome; Associated Educational Content; Peer Review; and Use in Educational Curriculae. The 17 statements that did not reach at least 80% agreement after the first round were revised and returned into the second round. The committee consensus approved 37 statements to at least an 82% agreement. CONCLUSION: Consensus guidelines on how to report laparoscopic surgery videos for educational purposes have been developed. We anticipate that following our guidelines could help to improve video quality.These reporting guidelines may be useful as a standard for reviewing videos submitted for publication or conference presentation.

Blunting of adaptive thermogenesis as a potential additional mechanism to promote weight loss after gastric bypass.

BACKGROUND: Adaptive thermogenesis (AT) is described as a change in resting metabolic rate (RMR) that is greater than would be predicted from changes in lean body mass (LBM) and fat mass (FM) alone during periods of energy imbalance. Whereas an AT-related downregulation of RMR has been implicated in suboptimal weight loss and weight regain after nonsurgical weight loss, defense against AT may underpin the durable weight loss after laparoscopic Roux-en-Y gastric bypass (LRYGB) and other bariatric surgeries. However, methodological differences across the few studies that have evaluated postoperative AT limit interpretation as to the effects of these procedures on RMR. OBJECTIVE: To quantify AT 6 months after LRYGB and laparoscopic adjustable gastric banding (LAGB). SETTING: The study was conducted in a large university hospital in the United States. METHODS: Changes in body composition and RMR were assessed in 13 severely obese adults 6 months after LRYGB (n = 8) and LAGB (n = 5). AT was calculated as the difference between measured RMR and RMR predicted from LBM, FM, age, and sex before and after surgery. RESULTS: RMR significantly decreased after LRYGB (-270±96 kcal/d, P<.01) but not after LAGB. Despite significantly greater reductions in weight, FM, and LBM with LRYGB than LAGB, AT responses after LRYGB (15±110 kcal/d, P = .7) and LAGB (42±97 kcal/d, P = .4) were similar (P = .7). CONCLUSION: Despite significant weight and body composition changes, AT was minimal after LRYGB. A blunting of AT may be an additional mechanism that favors sustainable weight loss with LRYGB.

Assessment of Cardiopulmonary Responses to Treadmill Walking Following Gastric Bypass Surgery.

BACKGROUND: Studies that have evaluated cardiopulmonary responses to exercise within the first few months of bariatric surgery have utilized cycle ergometry. However, walking is the most commonly reported mode of both pre- and post-operative PA. The divergent cardiopulmonary responses and metabolic costs of weight-bearing (walking) and non-weight-bearing (cycling) exercises warrant examination of the effects of bariatric surgery on cardiopulmonary responses during walking. METHODS: Nine women completed a maximal cardiopulmonary exercise test on a treadmill 2 weeks before and 3 months after gastric bypass surgery (GBS). Heart rate (HR), oxygen uptake (VO2), oxygen pulse (O2-p), and time to fatigue were compared before and after surgery and between the GBS group and a comparison group of 12 normal-weight (NW) women who completed the same exercise testing protocol. RESULTS: Time to fatigue increased by ~140 s following GBS (p = 0.018). No other parameter improved during maximal exercise from pre- to post-surgery. Body weight- and fat-free mass-corrected VO2 and O2-p at peak exercise differed between the GBS and NW groups before surgery, while only weight-corrected values were different following surgery. These differences disappeared after controlling for body fat percentage. CONCLUSION: We have demonstrated that weight loss alone was not sufficient to improve select cardiopulmonary fitness measures during treadmill walking in obese females 3 months after GBS. However, we did observe a significant overall improvement in exercise capacity as the GBS group was able to exercise longer, presumably due to significant reductions in body mass and a subsequent reduced metabolic cost of walking.

Changes in Resting Energy Expenditure in Relation to Body Weight and Composition Following Gastric Restriction: A Systematic Review.

In comparison to gastric bypass surgery, gastric restriction without malabsorption more closely simulates dietary adherence while still producing durable weight loss. The latter is achieved despite considerable reductions in resting energy expenditure (REE), and whether REE is adjusted for body weight/composition using ratio- or regression-based methods could influence understanding of how these procedures affect energy balance. This systematic review identified studies that reported REE before and after gastric restriction in order to compare changes using each method. Ratio assessments revealed increases and decreases when REE was expressed per kilogram of body weight and per kilogram of fat-free mass, respectively. In comparison, measured REE tended to be less than predicted from linear regression after surgery. Explanations for these seemingly disparate findings and future directions are discussed.