Sleeve gastrectomy (SG) has become the most common bariatric operation performed in the United States, but the relationship between gastroesophageal reflux (GERD) and SG remains poorly understood. Altieri and Pryor authored a comprehensive analysis of literature studying GERD after bariatric surgery. They found articles outlining 16 potential mechanisms for reflux after SG and the same number of operative techniques that can minimize reflux after SG [ [1] Altieri M. Pryor A. Gastroesophageal reflux disease after bariatric procedures. Surg Clin North Am. 2015; 95: 579-591 Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar ]. Studies attempting to define this relationship are few, with mostly level III and IV evidence. Even fewer studies have evaluated the impact of hiatal hernia repair (HHR) during SG on GERD symptoms. The goal of this study was “to determine the nature of reflux symptoms after SG and if hiatal hernia repair has any effect on said symptoms.”

OBJECTIVE This study assessed all-cause and specific-cause mortality after Roux-en-Y gastric bypass (RYGB) and in matched control subjects, stratified by diabetes status. RESEARCH DESIGN AND METHODS RYGB patients were matched by age, BMI, sex, and diabetes status at time of surgery to nonsurgical control subjects using data from the electronic health record. Kaplan-Meier curves and Cox regression were used to assess differences in all-cause and specific-cause mortality between RYGB patients and control subjects with and without diabetes. RESULTS Of the 3,242 eligible RYGB patients enrolled from January 2004 to December 2015, control subjects were identified for 2,428 (n = 625 with diabetes and n = 1,803 without diabetes). Median postoperative follow-up was 5.8 years for patients with diabetes and 6.7 years for patients without diabetes. All-cause mortality was reduced in RYGB patients compared with control subjects only for those with diabetes at the time of surgery (adjusted hazard ratio 0.44; P < 0.0001). Mortality was not significantly improved in RYGB patients without diabetes compared with control subjects without diabetes (adjusted hazard ratio 0.84; P = 0.37). Deaths from cardiovascular diseases (P = 0.011), respiratory conditions (P = 0.017), and diabetes P = 0.011) were more frequent in control subjects with diabetes than in RYGB patients with diabetes. RYGB patients without diabetes were less likely to die of cancer (P = 0.0038) and respiratory diseases (P = 0.046) than control subjects without diabetes but were at higher risk of death from external causes (P = 0.012), including intentional self-harm (P = 0.025), than control subjects without diabetes. CONCLUSIONS All-cause mortality benefits of RYGB are driven predominantly by patients with diabetes at the time of surgery. RYGB patients with diabetes were less likely to die of cardiovascular diseases, diabetes, and respiratory conditions than their counterparts without RYGB.

Nonalcoholic fatty liver disease (NAFLD) is common in adults with extreme obesity and can impact long-term health and survival. Liver biopsy is the only accurate test for diagnosis and staging, but is invasive and costly. Non-invasive testing offers an attractive alternate, but the overall accuracy remains a significant issue. This study was conducted to determine the accuracy and clinical utility of pre-operative ultrasound and liver transaminase levels, as well as intra-operative hepatic visual inspection, for assessing presence of NAFLD as confirmed by hepatic histology.Data was collected prospectively from 580 morbidly obese adult patients who underwent Roux-en-Y gastric bypass surgery with intraoperative wedge biopsy between January 2004 and February 2009. Complete data for ultrasound, ALT and AST levels, and documented visual inspection was available for 513 patients.The prevalence of NAFLD was 69 % and that of NASH was 32 %. The individual non-invasive clinical assessments demonstrated low sensitivity, specificity, and accuracy for detecting the presence of steatosis, steatohepatitis, or fibrosis. The combination of normal or abnormal results for all tests improved predictive utility. Abnormal tests with all three assessments had a sensitivity of 95-98 % and a specificity of 28-48 % for major histologic findings in NAFLD/NASH. Normal tests with all three assessments had a sensitivity of 12-22 % and a specificity of 89-97 % for major histologic findings in NAFLD/NASH.Although individual clinical tests for NAFLD have limited accuracy, the use of combined clinical tests may prove useful.

BACKGROUND: Health care in the United States is expensive and quality is variable. The aim of this study was to investigate whether our integrated health system, composed of academic hospitals, a practice plan, and a managed care payer, could reliably implement an evidence-based program for gastric bypass surgery. A secondary aim was to evaluate the impact of the program on clinical outcomes.STUDY DESIGN: A standardized program for delivery of clinical best-practice elements for patients undergoing initial open or laparoscopic Roux-en-Y gastric bypass was implemented in 2008. Best-practice elements were embedded into the workflow. The best-practice elements were refined after reviewing failures observed during the early implementation period. The study period was divided into 3 groups: group alpha = year preceding program implementation (control), group beta = first year of implementation (unreliable), and group Omega = 2 nd to 4th years of implementation (reliable). Outcomes data were collected for all patients who had undergone Roux-en-Y gastric bypass between May 2008 and April 2012 and were compared with a control group from the preceding year using multiple logistic regression analysis.RESULTS: Two thousand and sixty-one patients were studied, with no significant demographic differences between study groups. Best-practice elements delivery was 40% in group beta, but was > 90% for group U (p < 0.001). Length of stay for group alpha was 3.5 days and improved to 2.2 days (p < 0.001) for group Omega. Complications and readmission rates improved considerably with reliable delivery of best-practice elements.CONCLUSIONS: Standardization of evidence-based care delivery for Roux-en-Y gastric bypass was feasible and reliable delivery of this pathway improved clinical outcomes. (C) 2015 by the American College of Surgeons

Bozorghadad, Sayeh; Scholtis, Leah MEd; Sherman, Chung-Yin; Dove, James T.; Blansfield, Joseph A. MD, FACS; Hunsinger, Marie A. RN; Petrick, Anthony T. MD, FACS; Strodel, William E. III MD, FACS; Shabahang, Mohsen MD, FACS Author Information

We read with interest the video case report from Kedia et al1Kedia P. et al.Gastroenterology. 2014; 147: 566-568Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar regarding a new approach to facilitate ERCP in patients who have had Roux-en-Y gastric bypass (RYGB) surgery. Device-assisted enteroscopy has an unacceptable failure rate for successfully accomplishing ERCP when there is a long Roux limb,2Schreiner M.A. et al.Gastrointest Endosc. 2012; 75: 748-756Abstract Full Text Full Text PDF PubMed Scopus (176) Google Scholar and as a result several approaches have been described in recent years to allow access to the remnant stomach through which a “regular” ERCP can be done. Although this well-documented presentation does provide a proof of concept, we feel that it is premature to declare “game over” from a single case report. A RYGB operation is a major undertaking, and creation of a gastrogastric fistula (which may persist) cannot be undertaken lightly. Follow-up on this patient is not provided, so it is not certain that the OverStitch closure will lead to complete and permanent closure. There is at present insufficient published experience with OverStitch in fistula closure to ensure that this approach will work all of the time. Failure of complete closure even in a small percentage of patients who have a working/successful RYGB could necessitate repeat surgery for gastrogastric fistulas. The fistula is created typically with an oblique echoendoscope, whereas the OverStitch closure is done with a forward-viewing, double-channel endoscope. Because of this, it is possible that achieving a closure may be challenging technically in some cases. In some situations, a transjejunal puncture might be required for gastric remnant access, introducing another source of variability for the endoscopic closure. The Axios stent is a wonderful advance for lumen apposition, but the 1-cm length may be too short in some patients. With the divided RYGB, there may be commonly >1 cm between the remnant and pouch. An increasingly utilized laparoscopic surgical technique for bypass involves omental interposition between the gastric pouch and gastric remnant. This may also create a tract that is >1 cm long, in which case the current Axios stent will not properly work. We also take issue with the characterization that lap assisted ERCP “carries significant risk of complications.” It is a straightforward procedure, and unless the patient has a “hostile abdomen,” is the easiest way at present to access the gastric remnant. Laparoscopic-assisted ERCP can typically be done completely in 1 procedure as an outpatient through a few small incisions, most of which are <1 cm in size. Several studies have confirmed high success and low complication rates.3Grover B.T. et al.Surg Clinic N Am. 2014; 94: 413-425Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar Patients have no gastrogastric fistula and only have a temporary gastrostomy tube if repeat access is necessary. It is anticipated that more ERCP procedures will be required in RYGB patients. Great advances have been made that allow a high degree of safety and success. We anticipate even more advances. However, intentional violation of the postoperative anatomy should not be considered “ready for prime time” right now. Internal EUS-Directed Transgastric ERCP (EDGE): Game OverGastroenterologyVol. 147Issue 3PreviewAs the prevalence of obesity in the United States exceeds 30%, the number of bariatric procedures being performed, including Roux-en-Y gastric bypass (RYGB), is steadily increasing.1 Therefore, gastroenterologists will inevitably be required to manage pancreaticobiliary diseases in more patients with altered anatomy. Various techniques including deep enteroscopy-assisted endoscopic retrograde cholangiopancreatography (ERCP) and laparoscopy-assisted ERCP have been developed to address the anatomic challenges of these patients. Full-Text PDF ReplyGastroenterologyVol. 148Issue 4PreviewWe thank the authors for taking interest in our publication and appreciate their time to raise some insightful arguments regarding the internal endoscopic ultrasonography (EUS)-directed transgastric endoscopic retrograde cholangiopancreatography (EDGE) procedure as a novel method for performing endoscopic retrograde cholangiopancreatography (ERCP) in Roux-n-Y gastric bypass (RYGB) patients. Full-Text PDF

Fibroblast growth factors 19 and 21 (FGF19 and FGF21) have been implicated, independently, in type 2 diabetes (T2D) but it is not known if their circulating levels correlate with each other or whether the associated hepatic signaling mechanisms that play a role in glucose metabolism are dysregulated in diabetes. We used a cross-sectional, case/control, experimental design involving Class III obese patients undergoing Roux-en-Y bariatric surgery (RYGB), and measured FGF19 and FGF21 serum levels and hepatic gene expression (mRNA) in perioperative liver wedge biopsies. We found that T2D patients had lower FGF19 and higher FGF21 serum levels. The latter was corroborated transcriptionally, whereby, FGF21, as well as CYP7A1, β-Klotho, FGFR4, HNF4α, and glycogen synthase, but not of SHP or FXR mRNA levels in liver biopsies were higher in T2D patients that did not remit diabetes after RYGB surgery, compared to T2D patients that remitted diabetes after RYGB surgery or did not have diabetes. In a Phenome-wide association analysis using 205 clinical variables, higher FGF21 serum levels were associated with higher glucose levels and various cardiometabolic disease phenotypes. When serum levels of FGF19 were < 200 mg/mL and FGF21 > 500 mg/mL, 91% of patients had diabetes. These data suggest that FGF19/FGF21 circulating levels and hepatic gene expression of the associated signaling pathway are significantly dysregulated in type 2 diabetes.

Objective: Themain goal of this studywas to determine the effects of incretins on type 2 diabetes (T2D) remission after Roux-en-Y gastric bypass (RYGB) surgery for patients taking insulin.Background: Type 2 diabetes is a chronic diseasewith potentially debilitating consequences. RYGB surgery is one of the few interventions that can remit T2D. Preoperative use of insulin, however, predisposes to significantly lower T2D remission rates.Methods: A retrospective cohort of 690 T2D patients with at least 12 months follow-up and available electronic medical records was used to identify 37 T2D patients who were actively using a Glucagon-like peptide 1 (GLP-1) agonist in addition to another antidiabetic medication, during the preoperative period.Results: Here, we report that use of insulin, along with other antidiabetic medications, significantly diminished overall T2D remission rates 14 months after RYGB surgery (9%) compared with patients not taking insulin (56%). Addition of the GLP-1 agonist, however, increased significantly T2D early remission rates (22%), compared with patients not taking the GLP-1 agonist (4%). Moreover, the 6-year remission rates were also significantly higher for the former group of patients. The GLP-1 agonist did not improve the remission rates of diabetic patients not taking insulin as part of their pharmacotherapy.Conclusions: Preoperative use of antidiabetic medication, coupled with an incretin agonist, could significantly improve the odds of T2D remission after RYGB surgery in patients also using insulin.

Background About 60% of patients with type 2 diabetes achieve remission after Roux-en-Y gastric bypass (RYGB) surgery. No accurate method is available to preoperatively predict the probability of remission. Our goal was to develop a way to predict probability of diabetes remission after RYGB surgery on the basis of preoperative clinical criteria.Methods In a retrospective cohort study, we identified individuals with type 2 diabetes for whom electronic medical records were available from a primary cohort of 2300 patients who underwent RYGB surgery at the Geisinger Health System (Danville, PA, USA) between Jan 1, 2004, and Feb 15, 2011. Partial and complete remission were defined according to the American Diabetes Association criteria. We examined 259 clinical variables for our algorithm and used multiple logistic regression models to identify independent predictors of early remission (beginning within first 2 months after surgery and lasting at least 12 months) or late remission (beginning more than 2 months after surgery and lasting at least 12 months). We assessed a final Cox regression model with a consistent subset of variables that predicted remission, and used the resulting hazard ratios (HRs) to guide creation of a weighting system to produce a score (DiaRem) to predict probability of diabetes remission within 5 years. We assessed the validity of the DiaRem score with data from two additional cohorts.Findings Electronic medical records were available for 690 patients in the primary cohort, of whom 463 (63%) had achieved partial or complete remission. Four preoperative clinical variables were included in the final Cox regression model: insulin use, age, HbA(1c) concentration, and type of antidiabetic drugs. We developed a DiaRem score that ranges from 0 to 22, with the greatest weight given to insulin use before surgery (adding ten to the score; HR 5.90, 95% CI 4.41-7.90; p<0.0001). Kaplan-Meier analysis showed that 88% (95% CI 83-92%) of patients who scored 0-2, 64% (58-71%) of those who scored 3-7, 23% (13-33%) of those who scored 8-12, 11% (6-16%) of those who scored 13-17, and 2% (0-5%) of those who scored 18-22 achieved early remission (partial or complete). As in the primary cohort, the proportion of patients achieving remission in the replication cohorts was highest for the lowest scores, and lowest for the highest scores.Interpretation The DiaRem score is a novel preoperative method to predict the probability of remission of type 2 diabetes after RYGB surgery.

Objectives. The accumulation of lipids stored as excess triglycerides in the liver (steatosis) is highly prevalent in obesity and has been associated with several clinical characteristics, but most studies have been based on relatively small sample sizes using a limited set of variables. We sought to identify clinical factors associated with liver fat accumulation in a large cohort of patients with extreme obesity. Methods. We analyzed 2929 patients undergoing intraoperative liver biopsy during a primary bariatric surgery. Univariate and multivariate regression modeling was used to identify associations with over 200 clinical variables with the presence of any fat in the liver and with moderate to severe versus mild fat accumulation. Results. A total of 19 data elements were associated with the presence of liver fat and 11 with severity of liver fat including ALT and AST, plasma lipid, glucose, and iron metabolism variables, several medications and laboratory measures, and sleep apnea. The accuracy of a multiple logistic regression model for presence of liver fat was 81% and for severity of liver fat accumulation was 77%. Conclusions. A limited set of clinical factors can be used to model hepatic fat accumulation with moderate accuracy and may provide potential mechanistic insights in the setting of extreme obesity.

Objectives: Genome-wide association studies (GWAS) have led to the identification of single nucleotide polymorphisms in or near several loci that are associated with the risk of obesity and nonalcoholic fatty liver disease (NAFLD). We hypothesized that missense variants in GWAS and related candidate genes may underlie cases of extreme obesity and NAFLD-related cirrhosis, an extreme manifestation of NAFLD. Methods: We performed whole-exome sequencing on 6 Caucasian patients with extreme obesity [mean body mass index (BMI) 84.4] and 4 obese Caucasian patients (mean BMI 57.0) with NAFLD-related cirrhosis. Results: Sequence analysis was performed on 24 replicated GWAS and selected candidate obesity genes and 5 loci associated with NAFLD. No missense variants were identified in 19 of the 29 genes analyzed, although all patients carried at least 2 missense variants in the remaining genes without excess homozygosity. One patient with extreme obesity carried 2 novel damaging mutations in BBS1 and was homozygous for benign and damaging MC3R variants. In addition, 1 patient with NAFLD-related cirrhosis was compound heterozygous for rare damaging mutations in PNPLA3. Conclusions: These results indicate that analyzing candidate loci previously identified by GWAS analyses using whole-exome sequencing is an effective strategy to identify potentially causative missense variants underlying extreme obesity and NAFLD-related cirrhosis.

OBJECTIVE Roux-en-Y gastric bypass (RYGB) in humans can remit type 2 diabetes, but the operative mechanism is not completely understood. In mice, fibroblast growth factor (FGF) 15 (FGF19 in humans) regulates hepatic bile acid (BA) production and can also resolve diabetes. In this study, we tested the hypothesis that the FGF19–BA pathway plays a role in the remission of human diabetes after RYGB surgery. RESEARCH DESIGN AND METHODS Cohorts of diabetic and nondiabetic individuals of various body weights were used. In addition, RYGB patients without diabetes (No-Diabetes), RYGB patients with diabetes who experienced remission for at least 12 months after surgery (Diabetes-R), and RYGB patients with diabetes who did not go into remission after surgery (Diabetes-NoR) were studied. Circulating FGF19 and BA levels, hepatic glycogen content, and expression levels of genes regulating the FGF19–BA pathway were compared among these groups of patients using pre- and postoperative serum samples and intraoperative liver biopsies. RESULTS Preoperatively, patients with diabetes had lower FGF19 and higher BA levels than nondiabetic patients, irrespective of body weight. In diabetic patients undergoing RYGB, lower FGF19 levels were significantly correlated with increased hepatic expression of the cholesterol 7alpha-hydroxylase 1 (CYP7A1) gene, which modulates BA production. Following RYGB surgery, however, FGF19 and BA levels (particularly cholic and deoxycholic acids) exhibited larger increases in Diabetic-R patients compared with nondiabetic and Diabetic-NoR patients. CONCLUSIONS Taken together, the baseline and postoperative data implicate the FGF19–CYP7A1–BA pathway in the etiology and remission of type 2 diabetes following RYGB surgery.

Background: Evidences have proved that LRYGB is able to induce T2DM remission. Multiple studies have showed different predictors in the remission of T2DM after this procedure. Our objective is to determine the predictors of diabetes remission in T2DM patients that has undergone LRYGB in Asian. Methods: Data was collected on T2DM patients who underwent LRYGB from December 2005 to April 2012. Patients with T2DM who underwent LRYGB were included irrespective of the BMI and age. Data collected were gender, age, body height (BH) and body weight (BW), BMI, waist-hip ratio (WHR), FPG, HbA1c, c-peptide, duration of T2DM, oral hypoglycemic agent (OGHA) and/or insulin used and associated co morbidities. Patients were divided into three groups: total patients (group A), patients with BMI >35 (group B) and those with BMI < 35 (group C). Remission is defined as “FPG <100 mg/dL and HbA1c <6% without the use of OGHA or insulin therapy”. Glycemic control HbA1c of 7% despite no use of anti-diabetic medications. Data were collected prospectively and analyzed retrospectively. Results were analyzed to determine the remission of T2DM and its predictors. Results: Total patients included were 384 patients with BMI >35 were 260 and those with BMI < 35 were 124. In group A, mean age was 41.26yo, baseline mean BMI was 38.91kg/m2, FPG 165.63mg/dl, HbA1c 8.54%, cpeptide 3.58mg/dl. In group B, mean age was 38.97yo, baseline mean BMI 43.98kg/m2 FPG 155.64mg/dl, HbA1c 8.27%, c-peptide 4.13mg/dl. In group c, mean age was 46.06yo, baseline mean BMI was 29.33kg/m2 FPG 184.78mg/dl, HbA1c 9.02%, cpeptide 2.75mg/dl. The duration of the diabetes was range from newly diagnosed up to 20 years. Using univariate analysis the significant factors in predicting T2DM remission at 1 year were, age (p=0.000), BH (p=0.008), BW (p=0.000), WHR (p=0.035), BMI (p=0.000), FPG p=(0.030), HbA1C (p=0.000), cpeptide (p=0.000), duration of DM(p=0.000) and OGHA user (p=0.000), insulin user (p=0.030), and combination of OGHA and insulin user (p=0.000) in group A patients; in group B patients, significant factors were FPG (p=0.009) and fatty liver (p0.022), while in group C patients BW (p=0.000), BMI (p=0.000), OGHA usage (p=0.043) were significant. Using multivariate regression analysis, the significant predictors in group A were HbA1c (p=0.000) and cpeptide (p=0.031), in group B FPG (p=0.034) was the only significant predictors and C patients BW (p=0.000) was significant predictor. Conclusions: This study demonstrates the significant predictors of T2DM remission in total patients were HbA1c and cpeptide. In patients with BMI > 35 was FPG the only predictors, whereas in patient with BMI < 35 body weight is the significant predictor.

Genome-wide association and linkage studies have identified multiple susceptibility loci for obesity. We hypothesized that such loci may affect weight loss outcomes following dietary or surgical weight loss interventions. A total of 1,001 white individuals with extreme obesity (BMI >35 kg/m(2)) who underwent a preoperative diet/behavioral weight loss intervention and Roux-en-Y gastric bypass surgery were genotyped for single-nucleotide polymorphisms (SNPs) in or near the fat mass and obesity-associated (FTO), insulin induced gene 2 (INSIG2), melanocortin 4 receptor (MC4R), and proprotein convertase subtilisin/kexin type 1 (PCSK1) obesity genes. Association analysis was performed using recessive and additive models with pre- and postoperative weight loss data. An increasing number of obesity SNP alleles or homozygous SNP genotypes was associated with increased BMI (P < 0.0006) and excess body weight (P < 0.0004). No association between the amounts of weight lost from a short-term dietary intervention and any individual obesity SNP or cumulative number of obesity SNP alleles or homozygous SNP genotypes was observed. Linear mixed regression analysis revealed significant differences in postoperative weight loss trajectories across groups with low, intermediate, and high numbers of obesity SNP alleles or numbers of homozygous SNP genotypes (P < 0.0001). Initial BMI interacted with genotype to influence weight loss with initial BMI < 50 kg/m(2), with evidence of a dosage effect, which was not present in individuals with initial BMI <50 kg/m(2). Differences in metabolic rate, binge eating behavior, and other clinical parameters were not associated with genotype. These data suggest that response to a surgical weight loss intervention is influenced by genetic susceptibility and BMI.

Evidence-based health care delivery in the US has been problematic. Pay-for-performance (P4P) has emerged as a strategy to control cost and reward quality. Our goal was to test whether an integrated health care delivery system could successfully implement an evidence-based P4P program for gastric bypass surgery.