National trends in utilization and safety of gastric bypass, sleeve gastrectomy and conversion surgery in patients with GERD.

BACKGROUND: While some studies have reported improvement in gastro-esophageal reflux disease (GERD) symptoms after sleeve gastrectomy (SG), others have reported higher incidence of de-novo GERD, worsening of prior GERD symptoms and erosive esophagitis post SG. Furthermore, GERD unresponsive to medical management is one of the most common indications for conversion of SG to Roux-en-Y gastric bypass (RYGB). Real-world data on safety of primary SG, primary RYGB and SG to RYGB conversion for obese patients with GERD would be helpful for informing surgeons and patient procedure selection. We sought to evaluate the trends in utilization and safety of primary RYGB and primary SG for patients with GERD requiring medications, and compare the peri-operative outcomes between primary RYGB and conversion surgery from SG to RYGB for GERD using the MBSAQIP database. METHODS: A comparative analysis of post-operative outcomes within 30 days was performed for primary RYGB and primary SG after 1:1 nearest neighbor propensity score matching for patient demographics and preoperative comorbidities using the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) registry from 2015 to 2021. This was followed by comparison of peri-operative outcomes between conversion surgery from SG to RYGB for GERD and primary RYGB using MBSAQIP 2020-2021 data. RESULTS: Utilization of primary RYGB increased from 38% in 2015 to 45% in 2021, while primary SG decreased from 62% in 2015 to 55% in 2021 for bariatric patients with GERD. Post-operative outcomes including reoperation, reintervention, readmission, major complications, and death within 30 days were significantly higher for patients undergoing primary RYGB compared to primary SG. Increased readmissions and ED visits were seen with conversion surgery. However, there was no difference in rates of reoperation, reintervention, major complications, or death between primary RYGB and SG conversion to RYGB cohorts. CONCLUSIONS: This data suggests that a strategy of performing a primary SG and subsequent SG-RYGB conversion for those with recalcitrant GERD symptoms is not riskier than a primary RYGB. Thus, it may be reasonable to perform SG in patients who are well informed of the risk of worsening GERD requiring additional surgical interventions. However, the impact of such staged approach (SG followed by conversion to RYGB) on long-term outcomes remains unknown.

Bariatric surgery reveals a gut-restricted TGR5 agonist with anti-diabetic effects.

Bariatric surgery, the most effective treatment for obesity and type 2 diabetes, is associated with increased levels of the incretin hormone glucagon-like peptide-1 (GLP-1) and changes in levels of circulating bile acids. The levels of individual bile acids in the gastrointestinal (GI) tract after surgery have, however, remained largely unstudied. Using ultra-high performance liquid chromatography-mass spectrometry-based quantification, we observed an increase in an endogenous bile acid, cholic acid-7-sulfate (CA7S), in the GI tract of both mice and humans after sleeve gastrectomy. We show that CA7S is a Takeda G-protein receptor 5 (TGR5) agonist that increases Tgr5 expression and induces GLP-1 secretion. Furthermore, CA7S administration increases glucose tolerance in insulin-resistant mice in a TGR5-dependent manner. CA7S remains gut restricted, minimizing off-target effects previously observed for TGR5 agonists absorbed into the circulation. By studying changes in individual metabolites after surgery, the present study has revealed a naturally occurring TGR5 agonist that exerts systemic glucoregulatory effects while remaining confined to the gut.

Fellowship training influences learning curves for laparoscopic sleeve gastrectomy.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is the most commonly performed bariatric surgical procedure. Little is known about how surgeon training background influences the learning curve of this procedure. We examined operating times (OT), weight loss outcomes, and 30-day complications between surgeons with and without fellowship training in LSG. We hypothesize that post-residency training specific to LSG influences learning curves. METHODS: Surgeons from a single institution were split into two groups: those who had not completed fellowship training in LSG (NF, n = 3), and those who had completed LSG specific training in fellowship (SGF, n = 3). OTs, BMI changes at 1 year, and 30-day readmissions, reoperations, and complications were extracted for the first 100 LSG cases of each surgeon. Data were analyzed in bins of 20 cases. Comparisons were made between cohorts within a bin and between adjacent bins of the same surgeon cohort. Logistic regression analyses were performed of OT and weight loss outcomes. RESULTS: SGF surgeons showed no difference in OTs over their first 100 cases. NF surgeons had statistically significant increased OTs compared to SGF surgeons during their first 60 cases and progressively shortened OTs during that interval (109 min to 78 min, p < 0.001 for NF surgeons vs. 73 min to 69 min, SGF surgeons). NF surgeons had a significantly steeper slope for improvement in OT over case number. There was no correlation between case number and weight loss outcomes in either group, and no differences in 30-day outcomes between groups. CONCLUSION: Surgeons who trained to perform LSG in fellowship demonstrate faster and consistent OR times on their initial independent LSG cases compared to surgeons who did not, with no correlation between case number and weight loss outcomes or safety profiles for either group. This suggests that learning curves for LSG are achieved during formal case-specific fellowship training.

Sleeve gastrectomy enhances glucose utilization and remodels adipose tissue independent of weight loss.

Sleeve gastrectomy (SG) induces weight loss-independent improvements in glucose homeostasis by unknown mechanisms. We sought to identify the metabolic adaptations responsible for these improvements. Nonobese C57BL/6J mice on standard chow underwent SG or sham surgery. Functional testing and indirect calorimetry were used to capture metabolic phenotypes. Tissue-specific glucose uptake was assessed by 18-fluorodeoxyglucose (18-FDG) PET/computed tomography, and RNA sequencing was used for gene-expression analysis. In this model, SG induced durable improvements in glucose tolerance in the absence of changes in weight, body composition, or food intake. Indirect calorimetry revealed that SG increased the average respiratory exchange ratio toward 1.0, indicating a weight-independent, systemic shift to carbohydrate utilization. Following SG, orally administered 18-FDG preferentially localized to white adipose depots, showing tissue-specific increases in glucose utilization induced by surgery. Transcriptional analysis with RNA sequencing demonstrated that increased glucose uptake in the visceral adipose tissue was associated with upregulation in transcriptional pathways involved in energy metabolism, adipocyte maturation, and adaptive and innate immune cell chemotaxis and differentiation. SG induces a rapid, weight loss-independent shift toward glucose utilization and transcriptional remodeling of metabolic and immune pathways in visceral adipose tissue. Continued study of this early post-SG physiology may lead to a better understanding of the anti-diabetic mechanisms of bariatric surgery.

The impact of lipomatous tumors on type 2 diabetes: are adipose-derived tumors metabolically active?

BACKGROUND: The metabolic and immunologic properties of adipose tissue are linked to the pathogenesis of type 2 diabetes mellitus. Lipomatous tumors, such as liposarcomas, are rare but can reach significant size. We hypothesized that some lipomatous tumors are metabolically active and can alter systemic glucose homeostasis. METHODS: We performed a retrospective study of patients who underwent resection of a lipomatous tumor at a tertiary cancer referral center (2004-2015). We divided patients into nondiabetics, well-controlled diabetics (hemoglobin A1c [HbA1c] < 7), and poorly controlled diabetics (HbA1c ≥ 7). We compared patient demographics, tumor characteristics, and measures of glycemic control among these groups before and after tumor resection. RESULTS: We reviewed 217 operations for lipomatous tumors. No differences were observed in tumor characteristics in patients with and without diabetes. However, tumor characteristics differed significantly between the well-controlled and poorly controlled diabetics groups. Patients with poorly controlled diabetes had larger tumors that were more likely to be malignant, retroperitoneal, and well-differentiated. Tumor resection had no detectable impact on diabetes, as assessed by HbA1c, and requirement for diabetic medications. CONCLUSIONS: Poorly controlled diabetes was linked to the presence of large, malignant, and retroperitoneal lipomatous tumors. However, in limited follow-up, no detectable impact of tumor resection was apparent on glycemic control. These data suggest that most lipomatous tumors do not exert a clinically relevant impact on glucose homeostasis.

An appraisal of the learning curve in robotic general surgery.

BACKGROUND: Robotic-assisted surgery is used with increasing frequency in general surgery for a variety of applications. In spite of this increase in usage, the learning curve is not yet defined. This study reviews the literature on the learning curve in robotic general surgery to inform adopters of the technology. METHODS: PubMed and EMBASE searches yielded 3690 abstracts published between July 1986 and March 2016. The abstracts were evaluated based on the following inclusion criteria: written in English, reporting original work, focus on general surgery operations, and with explicit statistical methods. RESULTS: Twenty-six full-length articles were included in final analysis. The articles described the learning curves in colorectal (9 articles, 35%), foregut/bariatric (8, 31%), biliary (5, 19%), and solid organ (4, 15%) surgery. Eighteen of 26 (69%) articles report single-surgeon experiences. Time was used as a measure of the learning curve in all studies (100%); outcomes were examined in 10 (38%). In 12 studies (46%), the authors identified three phases of the learning curve. Numbers of cases needed to achieve plateau performance were wide-ranging but overlapping for different kinds of operations: 19-128 cases for colorectal, 8-95 for foregut/bariatric, 20-48 for biliary, and 10-80 for solid organ surgery. CONCLUSION: Although robotic surgery is increasingly utilized in general surgery, the literature provides few guidelines on the learning curve for adoption. In this heterogeneous sample of reviewed articles, the number of cases needed to achieve plateau performance varies by case type and the learning curve may have multiple phases as surgeons add more complex cases to their case mix with growing experience. Time is the most common determinant for the learning curve. The literature lacks a uniform assessment of outcomes and complications, which would arguably reflect expertise in a more meaningful way than time to perform the operation alone.

Improvement in severe pulmonary hypertension in obese patients after laparoscopic gastric bypass or sleeve gastrectomy.

BACKGROUND: Case reports have suggested that bariatric surgery improves pulmonary hypertension. We performed a retrospective, case-control study to evaluate the safety and efficacy of bariatric surgery in obese patients with severe pulmonary hypertension. METHODS: Morbidly obese patients followed in a specialty pulmonary hypertension clinic who underwent laparoscopic gastric bypass or sleeve gastrectomy between 2008 and 2013 (n = 10) were compared to a BMI-matched cohort managed with maximal medical therapy (n = 10). Patients with advanced malignancy, prior heart/lung transplantation, and pulmonary hypertension from thromboembolism were excluded. Primary outcomes assessed were changes in use of pulmonary vasodilatory and diuretic medications, need for home oxygen therapy, and mean pulmonary arterial pressures. Secondary outcomes measured were excess body weight loss, perioperative mortality and morbidity, and hospital length of stay. RESULTS: More patients who underwent bariatric surgery experienced improvements in pulmonary arterial pressures (75 vs. 0%, p = 0.02), reduction in or discontinuation of pulmonary vasodilatory therapy (67 vs. 0%, p = 0.01), and decreased diuretic requirements (86 vs. 13%, p = 0.01) than the control cohort. Seventy-five percent of patients previously on home oxygen discontinued therapy after surgery, while oxygen requirements increased in 50% of the control cohort. Excess body weight loss was greater in the surgical group (EWL 68 vs. 19%, p < 0.001). Seven significant complications in five patients occurred in the first postoperative year, but there were no mortalities. Mean inpatient length of stay was 5 days. CONCLUSIONS: Laparoscopic gastric bypass and sleeve gastrectomy in obese patients improves pulmonary hypertension in the short term.

Evaluation of the LINX antireflux procedure.

PURPOSE OF REVIEW: To evaluate the current data on the safety, efficacy, and indications for magnetic sphincter augmentation (MSA) using the LINX device to treat gastroesophageal reflux disease (GERD). RECENT FINDINGS: The LINX device has demonstrated excellent safety and GERD efficacy in several recent nonblinded, single arm studies with strict inclusion criteria and up to 3 years follow-up. Dysphagia has been the most common adverse effect occurring after LINX. Other gastrointestinal side-effects seen after laparoscopic fundoplication (bloating, gas, and inability to belch) may be less common after LINX. SUMMARY: The LINX device is a safe, well tolerated, and effective therapy for GERD in the short term. MSA should be considered for selected GERD patients without significant anatomic or motility defects. However, the long-term safety and efficacy of LINX - both alone and in comparison to current GERD therapies - remains to be determined.

A comparative trial of laparoscopic magnetic sphincter augmentation and Nissen fundoplication.

BACKGROUND: Laparoscopic magnetic sphincter augmentation (MSA) with the LINX device is a promising new therapy for the treatment of gastroesophageal reflux disease (GERD). Initial studies have demonstrated MSA to be safe and effective. However, no direct comparison between MSA and laparoscopic Nissen fundoplication (LNF), the gold standard surgical therapy for GERD, has been performed. METHODS: A single institution, case-control study was conducted of MSA performed from 2012 to 2013 and a cohort of LNF matched for age, gender, and hiatal hernia size. RESULTS: MSA and LNF were both effective treatments for reflux with 75 and 83 % of patients, respectively, reporting resolution of GERD at short-term follow-up. Dysphagia was common following both MSA and LNF, but severe dysphagia requiring endoscopic dilation was more frequent after MSA (50 vs. 0 %, p = 0.01). Need for dilation did not correlate with size of the LINX device or any other examined patient factors. A trend toward decreased adverse GI symptoms of bloating, flatulence, and diarrhea was seen after MSA compared to LNF (0 vs. 33 %). MSA had a shorter operative time (64 vs. 90 min, p < 0.01) but other peri-operative outcomes, including pain, morbidity, and re-admissions were equivalent to LNF. MSA patients were more likely to be self-referred (58 vs. 0 %, p < 0.001). CONCLUSIONS: MSA and LNF are both effective and safe treatments for GERD; however, severe dysphagia requiring endoscopic intervention is more common with MSA. Other adverse GI side effects may be less frequent after MSA. Consideration should be paid to these distinct post-operative symptom profiles when selecting a surgical therapy for reflux disease.

From Bands to Bypasses: Navigating Safety of Band Conversions to Roux-en-Y Gastric Bypass and Single Anastomosis Duodenoileostomy Versus Sleeve Gastrectomy.

INTRODUCTION: Revisional bariatric surgery is associated with higher perioperative complications over primary procedures. Adjustable gastric bands (AGB) continue to be the most frequently converted bariatric configuration. This study examines trends in current clinical indication and safety profile of the most frequently pursued AGB conversions. MATERIALS AND METHODS: MBSAQIP data from 2020 to 2022 was retrospectively analyzed in a cohort study examining 30-day postoperative outcomes after AGB conversion to sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), or single anastomosis duodenoileostomy (SADI). Descriptive statistics were used, including multivariable and 2:1 nearest neighbor matching analysis. RESULTS: This study included 19,335 AGB conversions, of which most were to SG (n = 11,736) followed by RYGB (n = 7442) and SADI (n = 157). While a majority were completed for weight loss, there were differences in distribution of primary indication for each conversion cohort, such as higher proportion of RYGB conversion for gastroesophageal reflux disease (18.7%) compared to SG (7.92%) and SADI (5.10%). Multivariable analysis demonstrates conversion to RYGB has significantly higher odds of 30-day major complications (OR 1.75, p < 0.001), reoperation (OR 2.08; p = 0.001), readmission (OR 1.69; p = 0.001), and emergency department visits (OR 1.50; p = 0.001) over SG. These risks and odds of reintervention (OR 1.75; p < 0.001) remained significantly higher after conversion to RYGB versus SG on matched analysis. None of these risks is significantly different between conversions to SADI versus SG in either multivariable or matched analysis. CONCLUSIONS: Compared to AGB conversion to SG, single-stage conversion to RYGB had increased odds of perioperative complications while risks of conversion to SADI were not significantly different.

Safety of Same-Day Discharge after Bariatric Surgery: Retrospective 6-Year North American Analysis.

BACKGROUND: With increasing implementation of Enhanced Recovery After Surgery protocols and rising demand for inpatient hospital beds accentuated by COVID-19, there has been interest in same-day discharge (SDD) for bariatric surgery. The aim of this study was to determine the national trends, safety profile, and risk factors for complications of SDD for minimally invasive bariatric surgery. STUDY DESIGN: We analyzed the MBSAQIP database from 2016 to 2021 to characterize trends in SDD for minimally invasive bariatric operation. Multivariate logistic regression was performed on preoperative patient characteristics predictive of increased complications associated with SDD. A comparative analysis of postoperative outcomes within 30 days was performed for SDD and admission after 1:1 nearest neighbor propensity score matching for patient demographics and preoperative comorbidities. RESULTS: SDD increased from 2.4% in 2016 to 7.4% in 2021. Major preoperative factors associated with increased complications for SDD included Black race, history of MI, renal insufficiency, deep vein thrombosis, and smoking. SDD for Roux-en-Y gastric bypass had 72% increased risk of postoperative complications compared with sleeve gastrectomy. The overall major complications were lower in SDD cohort vs admission cohort (odds ratio [OR] 0.62, p < 0.01). However, there was a significant increase in deaths within 30 days (OR 2.11, p = 0.01), cardiac arrest (OR 2.73; p < 0.01), and dehydration requiring treatment (OR 1.33; p < 0.01) in SDD cohort compared with admission cohort. CONCLUSIONS: Nationally, there has been a rise in SDD for bariatric operation from 2016 to 2021. Matched analysis demonstrates that SDD is associated with a significantly higher mortality rate. Additionally, the risk of complications with SDD is higher for RYGB compared with sleeve gastrectomy. Therefore, further studies are required to appropriately select patients for whom bariatric surgery can be safely performed as an outpatient.

Sleeve Gastrectomy is Associated with Longitudinal Improvements in Lung Function and Patient-Reported Respiratory Outcomes.

PURPOSE: Obesity exerts negative effects on pulmonary function through proven mechanical and biochemical pathways. Multiple studies have suggested that bariatric surgery can improve lung function. However, the timing of these effects on lung function and its association with patient reported outcomes is not known. MATERIALS AND METHODS: A prospective cohort study of patients undergoing laparoscopic sleeve gastrectomy (LSG) at a tertiary care hospital was undertaken. Spirometry tests, laboratory tests, and self-reported questionnaires on asthma symptoms and asthma control (ACQ and ACT) were administered. All data were recorded pre-operatively (T0) and every 3 months post-operatively for 1 year (T3, T6, T9, T12) and were compared using a mixed-models approach for repeated measures. RESULTS: For the 23 participants, mean age was 44.2 ± 12.3 years, mean BMI was 45.2 ± 7.2 kg/m2, 18(78%) were female, 9(39%) self-reported as non-white and 6(26%) reported to have asthma. Following LSG, % total body weight loss was significant at all follow-up points (P < 0.0001). Rapid improvement in forced expiratory volume (FEV)% predicted and forced vital capacity (FVC)% predicted was seen at T3. Although the overall ACQ and ACT score remained within normal range throughout the study, shortness of breath declined significantly at 3 months post-op (P < 0.05) and wheezing resolved for all patients by twelve months. Patients also reported reduced frequency of sleep interruption and inability to exercise by the end of the study (P < 0.05). CONCLUSION: Improvements in objective lung function assessments and patient-reported respiratory outcomes begin as early as 3 months and continue until 12 months after sleeve gastrectomy.

Outcomes and Management of Re-Establishing Bariatric Patients.

BACKGROUND: Lifelong follow-up after metabolic and bariatric surgery (MBS) is necessary to monitor for patient outcomes and nutritional status. However, many patients do not routinely follow-up with their MBS team. We studied what prompted MBS patients to seek bariatric care after being lost to follow-up and the subsequent treatments they received. STUDY DESIGN: A retrospective cohort study of patients after MBS who had discontinued regular MBS follow-up but represented to the MBS clinic between July 2018 and December 2022 to re-establish care. Patients with a history of a sleeve gastrectomy (SG), Roux-En-Y gastric bypass (RYGB), and adjustable gastric banding (AGB) were included. RESULTS: We identified 400 patients (83.5% women, mean age 50.3 ± 12.2 years at the time of re-establishment of bariatric care), of whom 177 (44.3%) had RYGB, 154 (38.5%) had SG, and 69 (17.2%) had AGB. Overall, recurrent weight gain was the most common reason for presentation for all three procedures (81.2% in SG, 62.7% in RYGB, and 65.2% in AGB; p < 0.001). Patients who underwent SG were more likely to undergo a revision MBS compared with patients who underwent RYGB (16.9% vs 5.8%, p < 0.001), whereas patients who underwent RYGB were more likely to undergo an endoscopic intervention than patients who underwent SG (17.5% vs 7.8%, p < 0.001). The response to antiobesity medication agents, specifically glucagon-like peptide-1 receptor agonists drugs, was better in patients who underwent RYGB, than that in patients who underwent SG. CONCLUSIONS: This study highlights recurrent weight gain as the most common reason for patients after MBS seeking to re-establish care with the MBS team. SG had a higher rate of revision MBS than RYGB, whereas endoscopic interventions were performed more frequently in the RYGB group. Antiobesity medication agents, especially glucagon-like peptide-1 receptor agonists drugs, were more effective in patients who underwent RYGB.

Procedure Matters in Gender-Associated Outcomes following Metabolic-Bariatric Surgery: Five Year North American Matched Cohort Analysis.

PURPOSE: Eighty percent of patients who undergo metabolic-bariatric surgery self-identify as female. It is unclear why there is a disparate use of metabolic-bariatric surgery by men compared to women given the widely accepted safety of weight loss surgical procedures. One possible explanation is that post-operative outcomes of metabolic-bariatric surgery have been shown to be worse for men compared to women in prior studies. The purpose of this study was to characterize the impact of gender on outcomes of metabolic-bariatric surgery using the most recent MBSAQIP data registry from 2017-2021. MATERIALS AND METHODS: Data entered into the MBSAQIP registry from 2017-2021 for patients who underwent primary metabolic-bariatric surgery procedures was identified. The data was then matched for multiple pre-operative factors and comorbidities, and outcomes were assessed and compared for men and women. RESULTS: No significant difference was observed in anastomotic leak, wound complications, and bleeding between men and women. However, men were at 0.15% (p < 0.01) higher risk of major complications (encompassing unplanned ICU admission, deep organ space infection, unplanned intubation, bleeding, anastomotic leak, sepsis, pneumonia, myocardial infarction, cardiac arrest, cerebrovascular accident, pulmonary embolism, reoperation, and death) compared to women. While men had higher major complications compared to women for SG, there was no significant difference between the two cohorts for RYGB, BPD and LAGB. CONCLUSION: While there are some differences in outcomes between male and female patients, the difference is modest. Male gender should not be considered a high-risk factor for all bariatric procedures and cannot explain the difference in utilization of metabolic-bariatric surgery by men compared to women.

Early Changes in Immune Cell Count, Metabolism, and Function Following Sleeve Gastrectomy: A Prospective Human Study.

OBJECTIVE: To characterize longitudinal changes in blood biomarkers, leukocyte composition, and gene expression following laparoscopic sleeve gastrectomy (LSG). BACKGROUND: LSG is an effective treatment for obesity, leading to sustainable weight loss and improvements in obesity-related comorbidities and inflammatory profiles. However, the effects of LSG on immune function and metabolism remain uncertain. METHODS: Prospective data were collected from 23 enrolled human subjects from a single institution. Parameters of weight, comorbidities, and trends in blood biomarkers and leukocyte subsets were observed from preoperative baseline to 1 year postsurgery in 3-month follow-up intervals. RNA sequencing was performed on pairs of whole blood samples from the first 6 subjects of the study (baseline and 3 months postsurgery) to identify genome-wide gene expression changes associated with undergoing LSG. RESULTS: LSG led to a significant decrease in mean total body weight loss (18.1%) at 3 months and among diabetic subjects a reduction in hemoglobin A1c. Improvements in clinical inflammatory and hormonal biomarkers were demonstrated as early as 3 months after LSG. A reduction in neutrophil-lymphocyte ratio was observed, driven by a reduction in absolute neutrophil counts. Gene set enrichment analyses of differential whole blood gene expression demonstrated that after 3 months LSG induced transcriptomic changes not only in inflammatory cytokine pathways but also in several key metabolic pathways related to energy metabolism. CONCLUSIONS: LSG induces significant changes in the composition and metabolism of immune cells as early as 3 months postoperatively. Further evaluation is required of bariatric surgery's effects on immunometabolism and the consequences for host defense and metabolic disease.

Impact of Bariatric Surgery on Endometrial Cancer Tumor Pathology.

INTRODUCTION: Obesity is a well-established risk factor for endometrial cancer and is thought to adversely affect outcomes. The impact of significant and sustained weight loss as achieved by bariatric surgery for women with endometrial cancer is not well understood. METHODS: We performed an institutional retrospective review of patients who underwent bariatric surgery and were diagnosed with premalignant or malignant uterine disease from 1989 to 2019 (n=171). We compared tumor characteristics and cancer-specific outcomes in patients diagnosed with uterine disease before ("PRE" group) or after ("POST" group) undergoing bariatric surgery and in a BMI- and age-matched cohort who did not undergo bariatric surgery. RESULTS: Of the 171 patients, 120 were in the PRE group and 51 in the POST group. The POST group was more likely to have adenocarcinoma (68.6 vs 45.0%, p=0.012) and more likely to have a minimally invasive hysterectomy (80.9 vs 46.2%, p<0.001). Post-bariatric surgery weight loss was similar between the two groups. In women with malignant disease, tumor grade and pathology were similar in the PRE and POST groups. The 5-year overall survival was 98% in the PRE group and 77.8% in the POST group (p=0.016). However, 5-year overall survival was statistically similar in both PRE and POST groups compared to a matched cohort who did not undergo bariatric surgery. CONCLUSIONS: In this study, we did not detect an impact of bariatric surgery on endometrial cancer pathology or disease survival. Larger, multi-center studies are needed to investigate the relationship between bariatric surgery status and cancer outcomes.

Weight and organ specific immune cell profiling of sleeve gastrectomy in mice.

OBJECTIVE: Sleeve gastrectomy (SG) has profound, immediate weight-loss independent effects on obesity related diabetes (T2D). Our prior studies have shown that immunologic remodeling may play a part in this metabolic improvement. However, to date, little is known about how the major immune cell populations change following SG and whether these are weight loss dependent. METHODS: Using mass cytometry with time of flight analysis (CyTOF), we broadly quantified the organ-specific immune cell repertoire induced by SG from splenic, jejunal, ileal, colonic, and hepatic lymphocyte fractions. Surgeries were performed in both diet-induced obese (DIO), insulin resistant mice and lean mice, which leads to sustained and non-sustained weight loss in SG animals compared to shams, respectively. Intergroup comparisons allow understanding of the relative contribution of diet, weight-loss, and surgery on immune profiling. Conserved immune changes represent surgery-specific, weight-independent, and diet-independent phenotypic changes. RESULTS: Initial analysis by way of visualization of t-distributed stochastic neighbor embedding analysis revealed changes in the B cell compartment following SG in both DIO and lean mice compared to Sham animals. In depth, traditional gating showed a shift within the splenic B cell compartment toward innate-like phenotype. There was a 1.3-fold reduction in follicular B cells within DIO SG (14% absolute reduction; p = 0.009) and lean SG (15% absolute reduction; p = 0.031) animals with a significant increase in innate-like B cell subsets in DIO SG mice(2.2 to 4.3-fold increase; p < 0.05). There was a similar trend toward increased innate B cell subsets in lean SG mice. There was a concomitant increase in multiple circulating immunoglobulin classes in both models. Further, lean (p = 0.009) and DIO SG animals (p = 0.015) had a conserved 5.5-fold and 5.7-fold increase, respectively, in splenic neutrophils and tendency toward M2 macrophage polarization. CONCLUSIONS: SG induces surgery-specific, weight-loss independent immune cells changes that have been previously linked to improved glucose metabolism. This immune phenotype may be a major contributor to post SG physiology. Characterizing the complex immune milieu following SG is an important step toward understanding the physiology of SG and the potential therapies therein.

A microbial metabolite remodels the gut-liver axis following bariatric surgery.

Bariatric surgery is the most effective treatment for type 2 diabetes and is associated with changes in gut metabolites. Previous work uncovered a gut-restricted TGR5 agonist with anti-diabetic properties-cholic acid-7-sulfate (CA7S)-that is elevated following sleeve gastrectomy (SG). Here, we elucidate a microbiome-dependent pathway by which SG increases CA7S production. We show that a microbial metabolite, lithocholic acid (LCA), is increased in murine portal veins post-SG and by activating the vitamin D receptor, induces hepatic mSult2A1/hSULT2A expression to drive CA7S production. An SG-induced shift in the microbiome increases gut expression of the bile acid transporters Asbt and Ostα, which in turn facilitate selective transport of LCA across the gut epithelium. Cecal microbiota transplant from SG animals is sufficient to recreate the pathway in germ-free (GF) animals. Activation of this gut-liver pathway leads to CA7S synthesis and GLP-1 secretion, causally connecting a microbial metabolite with the improvement of diabetic phenotypes.

Inhibition of rat gut reperfusion injury with an agent developed for the mouse. Evidence that amplification of injury by innate immunity is conserved between two animal species.

Murine reperfusion injury follows binding of specific IgM natural antibodies to neo-antigens exposed in ischemic tissue. Peptides that mimic the site of antibody binding in the injury prevent IgM binding when administered intravenously before reperfusion. To determine whether this pathogenic sequence is restricted to mice, we have tested the ability of the peptide to prevent reperfusion injury in a dissimilar species, the rat. Sprague-Dawley rats were subjected to 40 min of mesenteric ischemia followed by 180 min of reperfusion. The peptide mimic was administered intravenously prior to reperfusion. Gut injury was quantified using a scoring system based on the hematoxylin-and-eosin section. (125)I-labeled albumin was used to assess local (gut) and remote (lung) injury. The macroscopic appearance of bowel from peptide-treated animals was less edematous and hemorrhagic. Microscopic analysis showed a significantly reduced injury score in peptide-treated animals. Permeability data indicated a significant reduction in local and remote injury in peptide-treated animals. The data demonstrate attenuation of rat gut microvillus injury, of gut edema, and of remote injury following mesenteric ischemia-reperfusion due to administration of an intravenous peptide mimic of a murine ischemia neo-antigen, indicating a second species uses a similar ischemia neo-antigen and corresponding natural antibody specificity to amplify reperfusion injury to the point of necrosis. This mechanism of inflammation is potentially applicable to higher species.