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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.

Colorectal cancer (CRC) remains the third leading cause of cancer death in the United States with an alarming rise among young (1 Epidemiologically, obesity appears to be a risk factor for CRC.1 Although bariatric surgery has been shown to be associated with decreased risk for most cancers, studies to date on bariatric surgery and CRC continue to yield conflicting results.2 One possible explanation for this seeming irreconcilability is the inherent heterogeneity of CRC with its varied mechanisms. This is likely compounded by the differing bariatric operations currently employed. Here, we sharpen our focus and investigate how the most performed bariatric operation, sleeve gastrectomy (SG), affects colitis-associated CRC. Using a murine model, we found that SG significantly exacerbates both colitis and colitis-associated CRC. Using a germ-free (GF) microbiota transplant model, we found that the post-SG microbiota, when transplanted into GF mice, is capable of independently recapitulating the tumor-promoting phenotype of SG. Our results suggest that the postsurgical microbiome plays a key causal role in the increased risk for CRC after SG. This finding represents the first step in our understanding of this complex relationship that is at the intersection of two rising public health threats.

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. 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. 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

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.

There are currently few pre-operative predictors of initial and long-term weight loss following bariatric surgery. We evaluated the role of pre-operative patient characteristics and baseline gut and adipose-derived hormones in predicting maximal total body weight loss (WLmax) and risk of weight regain (WR) after Roux-en-Y gastric bypass (RYGB) surgery. One hundred five adult patients undergoing primary RYGB were prospectively recruited. Baseline demographics were recorded and fasting plasma glucose, glycosylated hemoglobin (A1C), insulin, glucagon, leptin, active ghrelin, glucagon-like peptide 1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) levels were measured on day of surgery. Our cohort had a mean age of 44.4 ± 13.0 years, and initial BMI (body mass index) of 45.1 ± 6.7 kg/m2 with mean post-operative follow-up of 40 months. Eighty patients were female and 26 had type 2 diabetes mellitus (T2D). Average WLmax was 35.3 ± 7.4%. On univariate analysis, higher baseline fasting ghrelin, lower age, lower CRP (C-reactive protein), lower A1C, and negative T2D status were associated with greater WLmax (p

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).

Bariatric surgery rapidly induces improvements in type 2 diabetes (T2D) in concert with reduction in systemic markers of inflammation. The impact of bariatric surgery on local intestinal immunity is not known. We hypothesize that sleeve gastrectomy (SG) and gastric bypass (RYGB) surgeries resolve obesity-induced intestinal inflammation, thereby promoting T2D resolution. SG and RYGB, or control surgery was performed in SD rats (n = 4–6/group). Key cytokines involved in insulin resistance (TNF-α, IFN-γ), inflammasome activation (IL-1β, IL-18), inflammation resolution (IL-10, IL-33), and Th17 cell responses (IL-17, IL-23) were measured by qPCR in mucosal scrapings of jejunum at 4 weeks post-surgery. Intestinal cytokine expressions were correlated with weight change, systemic and portal glucose, and insulin levels in response to an enteral glucose load. SG downregulated IL-17 and IL-23 in both proximal and distal jejunum, and IFN-γ was reduced only in distal jejunum (p

Bariatric surgery is associated with a reduced risk of developing certain malignancies, particularly in women. However, the impact of bariatric surgery on tumor characteristics, cancer treatment, and oncologic outcomes is unknown. In a retrospective cohort study, 42 subjects diagnosed with breast cancer after bariatric surgery (1989–2014) were matched to 84 subjects with breast cancer (1984–2012) who did not undergo bariatric surgery, based on age, body mass index (BMI), and menopausal status at the time of breast cancer diagnosis, as well as the date of cancer diagnosis. Medical records were reviewed for cancer and bariatric endpoints. Statistical analysis was performed using mixed effects regression models, generalized estimating equation, conditional logistic regression, and Fisher’s exact tests. Women who developed breast cancer after bariatric surgery presented at an earlier stage compared to non-operated, obese controls. In the bariatric surgery group, there were fewer tumors with human epidermal growth factor receptor 2 overexpression (HER2+) (OR 0.16 (0.03–0.76); p = 0.02), with no significant differences seen in estrogen and progesterone receptor positivity. No HER2+ cancers were found in patients who underwent Roux-en-Y gastric bypass (OR 0.00 (0.00–0.43); p = 0.002). On multivariate analysis, bariatric surgery status remained associated with reduced HER2+ breast cancers (OR 0.18 (0.03–0.99); p

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.We performed sleeve-gastrectomies (SGx) in a pre-clinical mouse model of diet-induced obesity (DIO), delineating the effects on long-term remission from obesity. SGx resulted in sustained weight loss and improved glucose tolerance. Mass-spectrometric metabolomic profiling revealed significantly reduced systemic levels of taurodeoxycholic acid (TDCA) and L-valine in DIO mice. Notably, TDCA and L-Valine levels were restored after SGx in both human and mice to levels comparable with lean controls.Strikingly, combined systemic treatment with TDCA and valine induced a profound weight loss in DIO mice 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 melanin-concentrating hormone.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.

The use of magnets has been a part of human civilization since antiquity. The ancient Greeks and Chinese civilizations were among the first to harness the usefulness of magnetic properties. While magnets played an important role in these early civilizations, their usefulness in the modern society is even more significant. Early industrial magnets were transition metal-based, which, while useful, had many inherent chemical flaws. The incorporation of rare-earth elements (REE) allowed them to become stronger and more resistant to demagnetization. The most abundantly used magnet in both industrial and medical applications is neodymium-iron-boron (Nd-Fe-B). This compound has high energy product and coercivity. While elemental neodymium is cytotoxic and, if untreated, vulnerable to environmental corrosion, properly coated Nd-Fe-B magnets can be extremely useful in the medical and surgical world. As with any new technology, fully understanding its properties and potential side effects is crucial for safe usage in patients. This chapter provides an introductory overview of the properties, toxicity, and potential adverse effects of magnets in surgery.

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.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.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%, p0.001). 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.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.

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.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.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.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.

ObjectiveTo characterize longitudinal changes in blood biomarkers, leukocyte composition, and gene expression following laparoscopic sleeve gastrectomy (LSG).BackgroundLSG is an effective treatment for obesity, leading to sustainable weight loss and improvements in obesity-related co-morbidities and inflammatory profiles. However, the effects of LSG on immune function and metabolism remain uncertain.MethodsProspective data was collected from 23 enrolled human subjects from a single institution. Parameters of weight, co-morbidities, and trends in blood biomarkers and leukocyte subsets were observed from pre-operative baseline to one year in three-month follow-up intervals. RNA-sequencing was performed on pairs of whole blood samples from the first six subjects of the study (baseline and three months post-surgery) to identify genome-wide gene expression changes associated with undergoing LSG.ResultsLSG led to a significant decrease in mean total body weight loss (18.1%) at three months and among diabetic subjects a reduction in HbA1c. Improvements in clinical inflammatory and hormonal biomarkers were demonstrated as early as three 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 three months, LSG induced transcriptomic changes not only in inflammatory cytokine pathways but also in several key metabolic pathways related to energy metabolism.ConclusionsLSG induces significant changes in the composition and metabolism of immune cells as early as three months post-operatively. Further evaluation is required of bariatric surgery’s effects on immunometabolism and consequences for host defense and metabolic disease.

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. Using mass cytometry with time of flight analysis (CyTOF) we aimed to broadly explore the organ-specific immune cell repertoire induced by SG. Surgery was performed on obese, insulin resistant and lean mice in order to understand surgery-specific phenotypes. We identified a shift within the splenic B cell compartment with a reduction in follicular and an increase in innate-like B cell subsets in SG animals. There was a concomitant increase in multiple circulating immunoglobulin classes. Further, SG animals had a conserved increase in splenic neutrophils and a tendency toward M2 macrophage polarization. Others have shown that these, weight-loss independent, surgery-specific changes are linked to improved glucose metabolism and thus, 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.

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.

There are currently few pre-operative predictors of initial and long-term weight loss following bariatric surgery.We evaluated the role of pre-operative patient characteristics and baseline gut and adipose-derived hormones in predicting maximal total body weight loss (WLOne hundred five adult patients undergoing primary RYGB were prospectively recruited. Baseline demographics were recorded and fasting plasma glucose, glycosylated hemoglobin (A1C), insulin, glucagon, leptin, active ghrelin, glucagon-like peptide 1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) levels were measured on day of surgery.Our cohort had a mean age of 44.4 ± 13.0 years, and initial BMI (body mass index) of 45.1 ± 6.7 kg/mIncorporation of baseline biological and hormonal markers may help in developing more accurate predictive models for weight loss following bariatric surgery that help inform patient counseling and decision-making.

Bariatric surgery, the most effective treatment for obesity and type 2 diabetes, is consistently associated with increased levels of the incretin hormone GLP-1 and changes in overall levels of circulating bile acids. The levels of individual bile acids in the GI tract following surgery, however, have remained largely unstudied. Using UPLC-MS-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 TGR5 agonist that induces GLP-1 secretion in vitro and in vivo and that CA7S administration increases glucose tolerance in insulin-resistant mice in a GLP-1 receptor-dependent manner. CA7S remains gut-restricted, minimizing off-target effects previously observed for TGR5 agonists absorbed into circulation. By studying changes in individual metabolites following surgery, this study has revealed a naturally occurring TGR5 agonist that exerts systemic glucoregulatory effects while remaining confined to the gut.

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.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.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.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.

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.

ObjectiveSleeve gastrectomy (SG) induces weight-loss independent improvements in glucose homeostasis by unknown mechanisms. We sought to identify the metabolic adaptations responsible for these improvements.MethodsNon-obese C57Bl6/J 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-FDG PET/CT and RNA sequencing was used for gene expression analysis.ResultsIn this model, SG induced durable improvements in glucose tolerance despite not causing lasting changes in weight, fat/lean mass, or food intake. Indirect calorimetry revealed post-SG animals had respiratory exchange ratios (RER) nearing 1.0 on average and had daily RER excursions above 1.0, indicating preferential glucose utilization and increased energy demand, respectively. Sham operated mice demonstrate normal RER feeding/fasting excursions. PET/CT showed increased avidity within white adipose depots. Finally, SG led to an upregulation in the transcriptional pathways involved in energy metabolism, adipocyte maturation, and adaptive and innate immune cell chemotaxis and differentiation within the visceral adipose tissue.ConclusionsSG induces a rapid, weight-loss independent shift towards glucose utilization and transcriptional remodeling of metabolic and immune pathways in visceral adipose tissue.

Gastroparesis is a chronic and often debilitating disorder of the stomach characterized by delayed emptying without mechanical obstruction. It is an underrecognized and often undertreated disease often presenting with nausea, vomiting, bloating, and/or abdominal pain. The pathophysiology involves derangements of normal gastric motor function. The most common etiologies include idiopathic, diabetes, and postsurgical. In approximately one-half of gastroparetics, there is no identifiable cause. After ruling out mechanical obstruction with cross-sectional imaging and endoscopy, the diagnosis of gastroparesis is made with gastric emptying scintigraphy. This is a noninvasive and quantitative measurement of gastric emptying and is considered the gold standard for diagnosis. In this chapter we discuss the evaluation, workup, and classification of gastroparesis.

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.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.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.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.

Ischemia-reperfusion injury (I/R) is an inflammatory response to hypoxia that is dependent on antibodies. We have previously shown that the N2 peptide blocks binding of autoreactive antibody to ischemic tissue and reduces I/R injury in rodents. Whether these same antibodies exist and target the same antigen in humans is unknown. In this study, we create a novel "humanized" mice model of intestinal I/R and test the efficacy of N2.Humanized mice were generated by transplanting human lymphocytes into immunodeficient mice. Human T- and B-cell engraftment in the spleen and peritoneum was confirmed using flow cytometry, and circulating human antibody in mouse serum was measured with ELISA. Injury in the small intestine and lung after intestinal I/R was measured in the presence or absence of N2. Immunohistochemistry was used to assess for human antibody deposition in the small intestine.Humanized mice engrafted with functional CD20+ B cells generated high circulating serum levels of human antibody. N2 treatment significantly reduced intestinal injury severity scores after I/R (control: 28 ± 1.5, N2: 9.1 ± 3.4; P .05). N2 also attenuated remote lung inflammation after I/R (control: 28 ± 4, N2: 5.4 ± 1.3; P .05). Protection from I/R injury correlated with blockade of human antibody deposition on small intestine.N2 is an effective therapy for I/R injury in the presence of human immunity, supporting a conserved target of inflammatory attack in human reperfusion injury.

Although weight loss-dependent type 2 diabetes (T2D) improvement after sleeve gastrectomy (SG) is well documented, whether SG has a weight-independent impact on T2D is less studied.To evaluate early, weight-independent T2D improvement after SG and Roux-en-Y gastric bypass (RYGB) and its relationship to longer-term T2D outcomes.University Hospital, United States.We completed a retrospective cohort study of patients with T2D who underwent SG (n = 187) or RYGB (n = 246) from 2010 to 2015. Pre- and postoperative parameters, including demographic characteristics, T2D characteristics, and T2D medication requirements, blood glucose, glycosylated hemoglobin, weight, and body mass index, were reviewed.T2D improved within days after both SG and RYGB, with more patients off T2D medications after SG than RYGB (39% versus 25%, respectively; P.01) at the time of discharge (2.5 ± .8 versus 2.7 ± 1 d; P = .04). Over the initial postoperative 12 months, T2D medication cessation rates remained relatively stable after SG but continued to improve after RYGB (at 12 mo: 52% versus 68%, respectively; P.05). T2D medication cessation at discharge predicts 12-month T2D medication cessation (92% [RYGB] and 78% [SG] positive predictive value). In a mixed-effects regression model adjusting for weight loss and severity of diabetes, discharge T2D medication cessation remained a significant predictor of T2D outcomes after both RYGB (odds ratio, 51; 95% confidence interval, 16.1-161; P.0001) and SG (6.4; 95% confidence interval, 2.8-14.7; P.0001).Both SG and RYGB lead to high rates of T2D medication cessation within days of surgery, suggesting both operations activate weight loss-independent anti-T2D pathways. T2D medication cessation at discharge is predictive of 12-month T2D outcomes, particularly in noninsulin requiring patients. By 1 year after the surgery, RYGB leads to more weight loss and higher rates of T2D medication cessation than SG.

Background Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are the most effective therapies for obesity and may have beneficial effects on the immune system. Therefore, we compared RYGB vs SG outcomes in patients with inflammatory bowel disease (IBD). Study Design In this retrospective cohort study, we identified 54 patients with either Crohn's disease (CD; n = 31) or ulcerative colitis (UC; n = 23), diagnosed before bariatric surgery, between 2000 and 2017. Nineteen patients underwent RYGB and 35 patients underwent SG. Results Patients presenting for RYGB and SG were of similar age (46.2 ± 9.5 years vs 47.2 ± 12.3 years), preoperative BMI (48.5 ± 7.7 kg/m2 vs 44.9 ± 7.3 kg/m2) and IBD status, as measured by medications. Both operations led to significant weight loss at 1 year. After RYGB and SG, there were no significant differences in the proportion of patients with UC who had improved (27% vs 8%), unchanged (64% vs 92%), or worse (9% vs 0%) IBD medication requirements, respectively. Similar analysis in the patients with CD showed no significant differences in the proportion who had improved (37.5% vs 44%), or unchanged (25% vs 52%) IBD-medication requirements after RYGB and SG, respectively. However, there was a significant difference in the proportion of patients who had worsened CD after RYGB compared with SG (37.5% vs 4%; p = 0.016). There was a greater rate of surgical complications after RYGB compared to SG (26% vs. 3%; p = 0.02). Conclusions A sizable proportion of patients experienced improvements in IBD post-bariatric surgery. However, in CD patients, RYGB was associated with a significantly greater number of patients with increased IBD-medication requirements. Sleeve gastrectomy led to less weight loss, but had a lower rate of severe complications compared with RYGB. In patients with IBD, and particularly CD, SG may be the safer surgery.

Bariatric surgery has proven to be the most effective and durable treatment for obesity and obesity-related diseases. As such, the number of bariatric procedures performed has dramatically increased over the past several decades. Although multiple bariatric procedures have been performed, the sleeve gastrectomy, Roux-en-Y[H1] gastric bypass, and gastric band have been by far the most common operations in the United States in the last decade. Given the prevalence of bariatric surgery and increased push to short-track postoperative hospital stays, emergency department (ED) visits are common in this patient cohort. This review covers the pathophysiology, diagnosis, and treatment of complications that ED providers are likely to see in patients after bariatric surgery. Although many complications are shared between all bariatric procedures, there are unique surgery-specific complications. To address the needs of these patients, providers must understand the surgery that their patients have had and how the postoperative timing and nature of their complaints inform the likely etiology of their presentation. This review contains 6 figures, 4 tables, and 83 references. Key words: anastomotic leak, bariatric surgery, cholelithiasis, complications, dehydration, dumping syndrome, gastric banding, gastrogastric fistula, internal hernia, malnutrition, mesenteric vein thrombosis, Roux-en-Y gastric bypass, sleeve gastrectomy, stricture, ulcer, vitamin deficiency

Gastroesophageal reflux disease (GERD) and hiatal hernia (HH) are common problems more frequently found in the obese. Growing experience indicates that bariatric surgery can lead to significant weight loss and, in many cases, improvement in GERD. Laparoscopic Roux-en-Y gastric bypass in particular is a highly effective therapy for GERD and can be safely performed in conjunction with repair of an HH. Laparoscopic sleeve gastrectomy (LSG) has rapidly become the most commonly performed bariatric procedure; however, one major drawback of LSG is the potential for development of GERD postoperatively. The indications for LSG in the setting of GERD and HH remain incompletely defined. This chapter highlights aspects of evaluation and management of the obese pre- or postop bariatric surgery patient with GERD and/or HH, including areas of controversy.

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. 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. 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. 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.

A little more than a decade after the first report of natural orifice transluminal endoscopic surgery (NOTES) in a preclinical model, NOTES has entered human clinical practice. Thousands of pure and hybrid NOTES procedures, including esophageal myotomy, cholecystectomy, and colectomy, are being performed around the globe. This chapter provides an overview of the history, current status, and future challenges in the field of natural orifice surgery.