A small intestinal bile acid modulates the gut microbiome to improve host metabolic phenotypes following bariatric surgery.

Bariatric surgical procedures such as sleeve gastrectomy (SG) provide effective type 2 diabetes (T2D) remission in human patients. Previous work demonstrated that gastrointestinal levels of the bacterial metabolite lithocholic acid (LCA) are decreased after SG in mice and humans. Here, we show that LCA worsens glucose tolerance and impairs whole-body metabolism. We also show that taurodeoxycholic acid (TDCA), which is the only bile acid whose concentration increases in the murine small intestine post-SG, suppresses the bacterial bile acid-inducible (bai) operon and production of LCA both in vitro and in vivo. Treatment of diet-induced obese mice with TDCA reduces LCA levels and leads to microbiome-dependent improvements in glucose handling. Moreover, TDCA abundance is decreased in small intestinal tissue from T2D patients. This work reveals that TDCA is an endogenous inhibitor of LCA production and suggests that TDCA may contribute to the glucoregulatory effects of bariatric surgery.

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.

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.

Patient Satisfaction and Healthcare Utilization with the Transition to Virtual Care in a Multidisciplinary Bariatric Program.

BACKGROUND: The COVID-19 pandemic saw an acceleration in virtual-visits (VV) for healthcare delivery. However, the impact of virtual care in metabolic/bariatric surgery (MBS) programs is not well described. METHODS: Appointment data from three time-points: pre-pandemic (1/1/19-3/15/20, n = 19,290), pandemic (3/16/20-10/31/21, n = 29,459) and current-state (11/1/21-12/31/2022, n = 24,270) was retrieved in our multi-hospital ambulatory MBS program. Appointments were grouped by health care provider (HCP) (MD, dietician, and psychologist) and type (VV and in-person). Surveys assessing patient satisfaction were distributed electronically. All pre-op and post-op appointment data was analyzed for the time-points above. Appointment completion rates and patient reported preferences were described. RESULTS: Our data showed an increase in scheduled VV from 0.5% for all HCP visits to 81% during the pandemic and a current VV visit of 77%. The number of completed VV increased for all HCPs, most prominently for dieticians. Parallel to this, the percentage of no-show visits also improved for all HCP, with MDs having the lowest no-show rate currently. Survey data revealed 89% of patients experience added benefits with VV and > 90% reported their VV experience as very good. VV were preferred over in-person visits for psychologists and dietitians (> 61%), but the majority preferred to see MDs in-person (70%). CONCLUSIONS: Our findings reveal significant changes in healthcare utilization trends since the transition to virtual care. While overall satisfaction with virtual care is high, most patients prefer in-person visits with MDs. Thus, multi-disciplinary MBS care can be performed effectively using a hybrid model to ensure efficient distribution of resources.

Accuracy of Conflicts in Interest in General Surgical Journals.

OBJECTIVE: To evaluate the accuracy of self-reported conflicts of interest (COIs) for articles published in prominent minimally invasive and general surgical journals. BACKGROUND: Accurate reporting of industry relationships and COIs is crucial for unbiased assessment of a particular study. Despite the enactment of COI laws, such as the Physician Payments Sunshine Act in 2010, prior work suggests that 40-70% of self-reported COIs have discrepancies. METHODS: We utilized three public databases -- Open Payments (USA), Disclosure UK, and Disclosure Australia -- to assess the accuracy of COI disclosures among authors of 918 published articles from these respective countries. Seven journals were utilized to review the COIs for authors of manuscripts published in 2022 - JAMA Surgery, Annals of Surgery, British Journal of Surgery (BJS), Journal of American College of Surgeons (JACS), Surgical Endoscopy, Obesity Surgery, and Surgery for Obesity and Related Diseases (SOARD). RESULTS: Among the analyzed 6206 authors, 5675 belonged to countries of interest: USA (4282), UK (718), and Australia (213). Of these, 774 authors (12.5%) self-reported a conflict of interest in their papers. Overall, only 4055 researchers (69.1%) reported COIs accurately. Authors from the US had the lowest accuracy of reporting COI at 69% as opposed to UK (93%) and Australia (96%). Inaccurate COI reporting was most common in corresponding/senior authors (39%) and least common amongst first authors (18%). Most payments in excess of $50,000 made to authors by an industry sponsor were not disclosed appropriately. CONCLUSIONS: Our study shows that inaccuracy of self-reported COIs in general surgery journals remains high at 31%. While our findings should encourage authors to overreport any possible COI, journals should consider verifying the authors' COI to facilitate more accurate reporting.

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.

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.

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.

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.

FALCON systematically interrogates free fatty acid biology and identifies a novel mediator of lipotoxicity.

Cellular exposure to free fatty acids (FFAs) is implicated in the pathogenesis of obesity-associated diseases. However, there are no scalable approaches to comprehensively assess the diverse FFAs circulating in human plasma. Furthermore, assessing how FFA-mediated processes interact with genetic risk for disease remains elusive. Here, we report the design and implementation of fatty acid library for comprehensive ontologies (FALCON), an unbiased, scalable, and multimodal interrogation of 61 structurally diverse FFAs. We identified a subset of lipotoxic monounsaturated fatty acids associated with decreased membrane fluidity. Furthermore, we prioritized genes that reflect the combined effects of harmful FFA exposure and genetic risk for type 2 diabetes (T2D). We found that c-MAF-inducing protein (CMIP) protects cells from FFA exposure by modulating Akt signaling. In sum, FALCON empowers the study of fundamental FFA biology and offers an integrative approach to identify much needed targets for diverse diseases associated with disordered FFA metabolism.

FALCON systematically interrogates free fatty acid biology and identifies a novel mediator of lipotoxicity.

Cellular exposure to free fatty acids (FFA) is implicated in the pathogenesis of obesity-associated diseases. However, studies to date have assumed that a few select FFAs are representative of broad structural categories, and there are no scalable approaches to comprehensively assess the biological processes induced by exposure to diverse FFAs circulating in human plasma. Furthermore, assessing how these FFA- mediated processes interact with genetic risk for disease remains elusive. Here we report the design and implementation of FALCON (Fatty Acid Library for Comprehensive ONtologies) as an unbiased, scalable and multimodal interrogation of 61 structurally diverse FFAs. We identified a subset of lipotoxic monounsaturated fatty acids (MUFAs) with a distinct lipidomic profile associated with decreased membrane fluidity. Furthermore, we developed a new approach to prioritize genes that reflect the combined effects of exposure to harmful FFAs and genetic risk for type 2 diabetes (T2D). Importantly, we found that c-MAF inducing protein (CMIP) protects cells from exposure to FFAs by modulating Akt signaling and we validated the role of CMIP in human pancreatic beta cells. In sum, FALCON empowers the study of fundamental FFA biology and offers an integrative approach to identify much needed targets for diverse diseases associated with disordered FFA metabolism. Highlights: FALCON (Fatty Acid Library for Comprehensive ONtologies) enables multimodal profiling of 61 free fatty acids (FFAs) to reveal 5 FFA clusters with distinct biological effectsFALCON is applicable to many and diverse cell typesA subset of monounsaturated FAs (MUFAs) equally or more toxic than canonical lipotoxic saturated FAs (SFAs) leads to decreased membrane fluidityNew approach prioritizes genes that represent the combined effects of environmental (FFA) exposure and genetic risk for diseaseC-Maf inducing protein (CMIP) is identified as a suppressor of FFA-induced lipotoxicity via Akt-mediated signaling.

Safety and effectiveness of 1-stage conversion of adjustable gastric band-to-sleeve gastrectomy: a single-institution case-control study.

BACKGROUND: Patients are increasingly referred for conversion of laparoscopic adjustable gastric band (LAGB) to laparoscopic Roux-en-Y gastric bypass (LRYGB) or sleeve gastrectomy (SG). The safety of a 1- versus 2-stage approach to this revision is debated. OBJECTIVES: We examined the safety and efficacy of 1-stage conversion of LAGB to SG at our institution. SETTING: University hospital. METHODS: An institutional database was used to retrospectively identify patients who underwent single-stage LAGB-to-SG conversion between 2010 and 2018. Patients were matched 1:1 for age, sex, and body mass index with primary SG patients during this same period. Primary endpoints were operative time, complication rate, length of hospital say, and weight loss 12 months from surgery. RESULTS: Two-hundred and twenty-nine patients undergoing conversion of LAGB to SG were identified. Median postoperative length of hospital stay was 2 days. Two patients (.8%) developed surgical site infection. One patient (.4%) developed a postoperative myocardial infarction. There were 4 total readmissions (1.7%) and 1 reoperation within 30 days (.4%). There were no statistically significant differences in 30-day complication rates between groups. Weight loss at 12 months was significantly different: Median body mass index loss for conversion patients was 5.1 kg/m2 compared with 8.85 kg/m2 for patients in the primary SG group (P < .0001). CONCLUSION: Single-stage conversion of LAGB to SG is safe and effective. Patients may not experience the same extent of weight loss as those with primary SG. Our findings represent the largest single-institutional experience to date and support a 1-stage approach whenever feasible.

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.

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.

Restored TDCA and valine levels imitate the effects of bariatric surgery.

Background: Obesity is widespread and linked to various co-morbidities. Bariatric surgery has been identified as the only effective treatment, promoting sustained weight loss and the remission of co-morbidities. Methods: Metabolic profiling was performed on diet-induced obese (DIO) mice, lean mice, and DIO mice that underwent sleeve gastrectomies (SGx). In addition, mice were subjected to intraperitoneal (i.p.) injections with taurodeoxycholic acid (TDCA) and valine. Indirect calorimetry was performed to assess food intake and energy expenditure. Expression of appetite-regulating hormones was assessed through quantification of isolated RNA from dissected hypothalamus tissue. Subsequently, i.p. injections with a melanin-concentrating hormone (MCH) antagonist and intrathecal administration of MCH were performed and weight loss was monitored. Results: Mass spectrometric metabolomic profiling revealed significantly reduced systemic levels of TDCA and L-valine in DIO mice. TDCA and L-valine levels were restored after SGx in both human and mice to levels comparable with lean controls. Systemic treatment with TDCA and valine induced a profound weight loss analogous to effects observed after SGx. Utilizing indirect calorimetry, we confirmed reduced food intake as causal for TDCA/valine-mediated weight loss via a central inhibition of the MCH. Conclusions: In summary, we identified restored TDCA/valine levels as an underlying mechanism of SGx-derived effects on weight loss. Of translational relevance, TDCA and L-valine are presented as novel agents promoting weight loss while reversing obesity-associated metabolic disorders. Funding: This work has been supported in part by a grant from NIH (UO-1 A1 132898 to S.G.T., DP and MA). M.Q. was supported by the IFB Integrated Research and Treatment Centre Adiposity Diseases (Leipzig, Germany) and the German Research Foundation (QU 420/1-1). J.I. was supported by the Biomedical Education Program (BMEP) of the German Academic Exchange Service (DAAD). T.H. (HE 7457/1-1) and F.K. (KR 4362/1-1) were supported by the German Research Foundation (DFG). H.R.C.B. was supported the Swiss Society of Cardiac Surgery. Y.N. was supported by the Chinese Scholarship Council (201606370196) and Central South University. H.U., T.M. and R.M. were supported by the Osaka Medical Foundation. C.S.F. was supported by the German Research Foundation (DFG, SFB738, B3).

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.