ω-3PUFA supplementation ameliorates adipose tissue inflammation and insulin-stimulated glucose disposal in subjects with obesity: a potential role for apolipoprotein E.

BACKGROUND: Long chain omega-3 polyunsaturated fatty acids (ω-3PUFA) supplementation in animal models of diet-induced obesity has consistently shown to improve insulin sensitivity. The same is not always reported in human studies with insulin resistant (IR) subjects with obesity. OBJECTIVE: We studied whether high-dose ω-3PUFA supplementation for 3 months improves insulin sensitivity and adipose tissue (AT) inflammation in IR subjects with obesity. METHODS: Thirteen subjects (BMI = 39.3 ± 1.6 kg/m2) underwent 80 mU/m2·min euglycemic-hyperinsulinemic clamp with subcutaneous (Sc) AT biopsy before and after 3 months of ω-3PUFA (DHA and EPA, 4 g/daily) supplementation. Cytoadipokine plasma profiles were assessed before and after ω-3PUFA. AT-specific inflammatory gene expression was evaluated on Sc fat biopsies. Microarray analysis was performed on the fat biopsies collected during the program. RESULTS: Palmitic and stearic acid plasma levels were significantly reduced (P < 0.05) after ω-3PUFA. Gene expression of pro-inflammatory markers and adipokines were improved after ω-3PUFA (P < 0.05). Systemic inflammation was decreased after ω-3PUFA, as shown by cytokine assessment (P < 0.05). These changes were associated with a 25% increase in insulin-stimulated glucose disposal (4.7 ± 0.6 mg/kg ffm•min vs. 5.9 ± 0.9 mg/kg ffm•min) despite no change in body weight. Microarray analysis identified 53 probe sets significantly altered post- ω-3PUFA, with Apolipoprotein E (APOE) being one of the most upregulated genes. CONCLUSION: High dose of long chain ω-3PUFA supplementation modulates significant changes in plasma fatty acid profile, AT, and systemic inflammation. These findings are associated with significant improvement of insulin-stimulated glucose disposal. Unbiased microarray analysis of Sc fat biopsy identified APOE as among the most differentially regulated gene after ω-3PUFA supplementation. We speculate that ω-3PUFA increases macrophage-derived APOE mRNA levels with anti-inflammatory properties.

Intraoperative musculoskeletal discomfort and risk for surgeons during open and laparoscopic surgery.

BACKGROUND: Surgeon workload is significant both mentally and physically and may differ by procedure type. When comparing laparoscopic surgery and open surgery, studies have reported contrasting results on the physical and mental workload assessed. METHODS: Wearable posture sensors and pre-/post-surgical questionnaires were employed to assess intraoperative workload and to identify risk factors for surgeons using objective and subjective measures. RESULTS: Data from 49 cases (27 open and 22 laparoscopic surgeries performed by 13 male and 11 female surgeons) were assessed. More than half the surgeons reported a clinically relevant post-surgical fatigue score. The surgeons also self-reported a significant increase in pain for the neck, upper back, and lower back during/after surgery. Procedural time had significant impacts on fatigue, body part pain, and subjective (NASA-TLX) workload. The objectively assessed intraoperative work postures using wearable sensors showed a high musculoskeletal risk for neck and lower back based on their posture overall. Open surgeries had significantly larger neck angles (median [IQR]: 40 [28-47]°) compared with laparoscopic surgeries (median [IQR]: 23 [16-29]°), p < 0.001) and torso (median [IQR]: 17 [14-22]° vs. 13 [10-17]°, p = 0.006). CONCLUSION: Surgeons reported significantly higher levels of fatigue and pain in the neck and lower back during or after performing a surgical case. Longer procedural time resulted in more self-rated fatigue, pain, and subjective workload. Open surgery had higher postural risk. Overall, surgeons spent a disturbingly high percentage of time during surgery in high-risk musculoskeletal postures, especially the neck. These results show that intraoperative postural risk is very high and that interventions are necessary to protect surgeon musculoskeletal health for optimal surgeon performance and career longevity.

High-precision isotopic analysis of serum and whole blood Cu, Fe and Zn to assess possible homeostasis alterations due to bariatric surgery.

Bariatric surgery is an effective procedure to achieve weight loss in obese patients. However, homeostasis of essential metals may be disrupted as the main absorption site is bypassed. In this study, we determined Cu, Fe and Zn isotopic compositions in paired serum and whole blood samples of patients who underwent Roux-en-Y gastric bypass (RYGB) surgery for evaluation of longitudinal changes and their potential relation to mineral element concentrations and relevant clinical parameters used for monitoring the patient's condition. Samples from eight patients were collected pre-surgery and at 3, 6 and 12 months post-surgery. Multi-collector inductively coupled plasma-mass spectrometry (MC-ICP-MS) was used for high-precision isotope ratio measurements. Alterations in metal homeostasis related to bariatric surgery were reflected in the serum and whole blood Cu, Fe and Zn isotopic compositions. The serum and whole blood Cu became isotopically lighter (lower δ65Cu values) after bariatric surgery, reaching statistical significance at 6 months post-surgery (p < 0.05). The difference between the serum and the whole blood Zn isotopic composition increased after surgery, reaching significance from 6 months post-surgery onwards (p < 0.05). Those changes in Cu, Fe and Zn isotopic compositions were not accompanied by similar changes in their respective concentrations, making isotopic analysis more sensitive to physiological changes than elemental content. Furthermore, the Zn isotopic composition correlates with blood glycaemic and lipid parameters, while the Fe isotopic composition correlates with glycaemic parameters. Graphical Abstract.

Infectious Surgical Complications are Not Dichotomous: Characterizing Discordance Between Administrative Data and Registry Data.

OBJECTIVE: To characterize reasons for discordance between administrative data and registry data in the determination of postoperative infectious complications. BACKGROUND: Data regarding the occurrence of postoperative surgical complications are identified through either administrative or registry data. Rates of complications vary significantly between these two types of data; the reasons for this are not well-understood. METHODS: The occurrence of 30-day inpatient infectious complications (pneumonia, sepsis, surgical site infection, and urinary tract infection) was compared between the NSQIP and administrative mechanisms at 4 academic hospitals between 2012 and 2014. In each situation where the NSQIP and administrative data were discordant regarding the occurrence of a specific complication, a 2-clinician chart abstraction was performed to characterize the reasons for discordance as (i) administrative coding error, (ii) NSQIP coding error, (iii) "question of criteria", where the discordance was the result of differences in criteria, or (iv) "dually incorrect", where both data sources coded the complication incorrectly. RESULTS: The cohort included 19,163 patients undergoing surgery in 4 different academic hospitals. Rates of infectious complications varied up to 5-fold between the two data sources. A total of 717 discordant complications were identified. Of these, the greatest portion (43%) was due to "question of criteria," followed by administrative coding error (37%), NSQIP error (15%), and dually incorrect (5%). CONCLUSIONS: With a goal of improving existing mechanisms for measuring surgical quality, definitions for the occurrence of a postoperative complication need to be developed and applied consistently. Progress toward this goal will enable patients and payers to better take advantage of recent advances in healthcare data transparency.

"Metabolic Bridge Therapy Prior to Microvascular Breast Reconstruction in the Morbidly Obese: A Proof-of-Concept Risk Analysis".

BACKGROUND: Obese patients experience more complications after autologous breast reconstruction. This study evaluates how bariatric surgery modulates risk of complications in the setting of microvascular breast reconstruction. METHODS: Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) databases were queried for patients with body mass index (BMI) ≥35 kg/m2 undergoing bariatric surgery from 2017-2022. Outcomes included BMI and obesity-related comorbidities before and 1 year after bariatric surgery. Paired Breast Reconstruction Risk Assessment (BRA) scores were analyzed to evaluate risk modulation before and after bariatric surgery in the setting of microvascular breast reconstruction. RESULTS: A total of 1,026 patients were included with an average age of 47 and BMI of 44.7 kg/m2. Comorbidities included hypertension (601, 59%), type 2 diabetes (291, 28%), and cardiovascular disease (10, 1%). One-year outcomes after bariatric surgery included an average BMI of 32.7 kg/m2, with remission of type 2 diabetes in 29% of patients. Paired BRA risk analysis for microvascular breast reconstruction before and after bariatric surgery showed reduction in 30-day surgical complications (40.4% vs. 24.8%, P<0.0001), with an absolute risk reduction (ARR) of 15%, relative risk reduction (RRR) of 36%, and a number needed to treat (NNT) of 7. Each 1 kg/m2 reduction in preoperative BMI was associated with a 3.4% reduction in surgical complications (P<0.0001). CONCLUSIONS: There is potential efficacy for metabolic bridge therapy in reducing complications for obese patients undergoing microvascular breast reconstruction.

Linking adipose tissue eosinophils, IL-4, and leptin in human obesity and insulin resistance.

BACKGROUNDObesity is a multifactorial disease with adverse health implications including insulin resistance (IR). In patients with obesity, the presence of high circulating levels of leptin, deemed hyperleptinemia, is associated with IR. Recent data in mice with diet-induced obesity (DIO) show that a partial reduction in leptin levels improves IR. Additional animal studies demonstrate that IL-4 decreases leptin levels. In rodents, resident adipose tissue eosinophils (AT-EOS) are the main source of IL-4 and are instrumental in maintaining metabolic homeostasis. A marked reduction in AT-EOS content is observed in animal models of DIO. These observations have not been explored in humans.METHODSWe analyzed AT from individuals with obesity and age-matched lean counterparts for AT-EOS content, IL-4, circulating leptin levels, and measures of IR.RESULTSOur results show that individuals with obesity (n = 15) had a significant reduction in AT-EOS content (P < 0.01), decreased AT-IL-4 gene expression (P = 0.02), and decreased IL-4 plasma levels (P < 0.05) in addition to expected IR (P < 0.001) and hyperleptinemia (P < 0.01) compared with lean subjects (n = 15). AT-EOS content inversely correlated with BMI (P = 0.002) and IR (P = 0.005). Ex vivo AT explants and in vitro cell culture of primary human mature adipocytes exposed to either IL-4 or EOS conditioned media produced less leptin (P < 0.05).CONCLUSIONOur results suggest that IL-4 acts as a link between EOS, AT, and leptin production. Future studies exploring this interaction may identify an avenue for the treatment of obesity and its complications through amelioration of hyperleptinemia.TRIAL REGISTRATIONClinicaltrials.gov NCT02378077 & NCT04234295.

Bariatric Surgery and Longitudinal Cancer Risk: A Review.

Importance: Cancer is one of the leading causes of death in the United States, with the obesity epidemic contributing to its steady increase every year. Recent cohort studies find an association between bariatric surgery and reduced longitudinal cancer risk, but with heterogeneous findings. Observations: This review summarizes how obesity leads to an increased risk of developing cancer and synthesizes current evidence behind the potential for bariatric surgery to reduce longitudinal cancer risk. Overall, bariatric surgery appears to have the strongest and most consistent association with decreased incidence of developing breast, ovarian, and endometrial cancers. The association of bariatric surgery and the development of esophageal, gastric, liver, and pancreas cancer is heterogenous with studies showing either no association or decreased longitudinal incidences. Conversely, there have been preclinical and cohort studies implying an increased risk of developing colon and rectal cancer after bariatric surgery. A review and synthesis of the existing literature reveals epidemiologic shortcomings of cohort studies that potentially explain incongruencies observed between studies. Conclusions and Relevance: Studies examining the association of bariatric surgery and longitudinal cancer risk remain heterogeneous and could be explained by certain epidemiologic considerations. This review provides a framework to better define subgroups of patients at higher risk of developing cancer who would potentially benefit more from bariatric surgery, as well as subgroups where more caution should be exercised.

Defining Biliary Hyperkinesia and the Role of Cholecystectomy.

BACKGROUND: Functional gallbladder disorder is most commonly defined by biliary colic and low ejection fraction (EF) on cholescintigraphy. Biliary hyperkinesia is a controversial type of functional gallbladder disorder, and its definition and the role of cholecystectomy in treating functional gallbladder disorder remains unclear. STUDY DESIGN: We conducted a retrospective review of patients who underwent cholecystokinin-stimulated cholescintigraphy and cholecystectomy at 3 Mayo Clinic sites between 2007 and 2020. Eligible patients were 18 years or older, presented with symptoms of biliary disease, had an EF greater than 50%, underwent cholecystectomy, and had no evidence of acute cholecystitis or cholelithiasis on imaging. We used receiver operating characteristics curve analysis to identify the optimal cutoff value that predicted symptom resolution within 30 days of cholecystectomy. RESULTS: A total of 2,929 cholecystokinin-stimulated cholescintigraphy scans were performed during the study period; the average EF was 67.5% and the median EF was 77%. Analyzing those with EFs greater than or equal to 50% yielded 1,596 patients with 141 (8.8%) going on to have cholecystectomy. No significant differences were found in age, sex, BMI, final pathology between patients with and without pain resolution. Using a cutoff EF of 81% was significantly associated with pain resolution after cholecystectomy (78.2% for EF greater than or equal to 81% vs 60.0% for EF less than 81%, p = 0.03). Chronic cholecystitis was found in 61.7% of the patients on final pathology. CONCLUSIONS: We determined that an EF cutoff of 81% is a reasonable upper limit of normal gallbladder EF. Patients with biliary symptoms and an EF greater than 81% but no evidence of biliary disease on ultrasound or scintigraphy can be classified as having biliary hyperkinesia. Based on our findings, we recommend cholecystectomy for this patient population.

Current trends in U.S. general surgery practice consolidation.

BACKGROUND: Consolidation of physician practices is well-documented in recent years, yet minimal data exist regarding consolidation in general surgery. This study evaluates current trends in general surgery practice consolidation. METHODS: Data were obtained through the CMS Physician Compare database. Surgeons and practices were categorized by size, and trends were analyzed using the Cochran-Armitage test. Data were stratified by US region. RESULTS: From 2012 to 2020, practicing general surgeons increased from 20,044 to 20,637 (+3%). Unique general surgery practices declined from 8178 to 6489 (-21%). The percentage of surgeons in practices of 1 or 2 declined from 19% to 12%, while surgeons in groups of 500 or more grew from 20% to 31%. Tests for trends towards consolidation at both the individual surgeon and unique practice levels were significant (p < .001). The Midwest region demonstrated the highest degree of consolidation. CONCLUSION: Consistent with trends in medicine overall, general surgery is experiencing substantial practice consolidation.

Weight loss after Roux-En-Y gastric bypass surgery reveals skeletal muscle DNA methylation changes.

BACKGROUND: The mechanisms of weight loss and metabolic improvements following bariatric surgery in skeletal muscle are not well known; however, epigenetic modifications are likely to contribute. The aim of our study was to investigate skeletal muscle DNA methylation after weight loss induced by Roux-en-Y gastric bypass (RYGB) surgery. Muscle biopsies were obtained basally from seven insulin-resistant obese (BMI > 40 kg/m2) female subjects (45.1 ± 3.6 years) pre- and 3-month post-surgery with euglycemic hyperinsulinemic clamps to assess insulin sensitivity. Four lean (BMI < 25 kg/m2) females (38.5 ± 5.8 years) served as controls. We performed reduced representation bisulfite sequencing next generation methylation on DNA isolated from the vastus lateralis muscle biopsies. RESULTS: Global methylation was significantly higher in the pre- (32.97 ± 0.02%) and post-surgery (33.31 ± 0.02%) compared to the lean (30.46 ± 0.02%), P < 0.05. MethylSig analysis identified 117 differentially methylated cytosines (DMCs) that were significantly altered in the post- versus pre-surgery (Benjamini-Hochberg q < 0.05). In addition, 2978 DMCs were significantly altered in the pre-surgery obese versus the lean controls (Benjamini-Hochberg q < 0.05). For the post-surgery obese versus the lean controls, 2885 DMCs were altered (Benjamini-Hochberg q < 0.05). Seven post-surgery obese DMCs were normalized to levels similar to those observed in lean controls. Of these, 5 were within intergenic regions (chr11.68,968,018, chr16.73,100,688, chr5.174,115,531, chr5.1,831,958 and chr9.98,547,011) and the remaining two DMCs chr17.45,330,989 and chr14.105,353,824 were within in the integrin beta 3 (ITGB3) promoter and KIAA0284 exon, respectively. ITGB3 methylation was significantly decreased in the post-surgery (0.5 ± 0.5%) and lean controls (0 ± 0%) versus pre-surgery (13.6 ± 2.7%, P < 0.05). This decreased methylation post-surgery was associated with an increase in ITGB3 gene expression (fold change + 1.52, P = 0.0087). In addition, we showed that ITGB3 promoter methylation in vitro significantly suppressed transcriptional activity (P < 0.05). Transcription factor binding analysis for ITGB3 chr17.45,330,989 identified three putative transcription factor binding motifs; PAX-5, p53 and AP-2alphaA. CONCLUSIONS: These results demonstrate that weight loss after RYGB alters the epigenome through DNA methylation. In particular, this study highlights ITGB3 as a novel gene that may contribute to the metabolic improvements observed post-surgery. Future additional studies are warranted to address the exact mechanism of ITGB3 in skeletal muscle.

Low-Dose Ketamine Infusion for Perioperative Pain Management in Patients Undergoing Laparoscopic Gastric Bypass: A Prospective Randomized Controlled Trial.

INTRODUCTION: Obesity is a common comorbidity seen in the perioperative setting and is associated with many diseases including cardiovascular disease and obstructive sleep apnea. Laparoscopic Roux-en-Y gastric bypass is the gold standard surgical treatment for patients whose weight is refractory to diet and exercise. Caring for these patients perioperatively presents unique challenges to anesthesiologists and is associated with an increased risk of adverse respiratory events. In our study, we hypothesize that a low-dose perioperative ketamine infusion will reduce opioid consumption and improve analgesia when compared to standard therapy. METHODS: This is a single-center, prospective randomized controlled study enrolling 35 patients in total. Patients were randomized equally into the ketamine and control group. Preop, intraop, and postop management regimens were standardized. The ketamine group received a 0.3 mg/kg ideal body weight ketamine bolus after induction followed by a 0.2 mg/kg/hr ketamine infusion continued into the postop setting for up to 24 hours. Data collected included total perioperative opioids used converted to oral morphine equivalents (ME), pain scores, side effects, hospital length of stay, and patient satisfaction captured via postoperative questionnaires. RESULTS: The use of perioperative opioid consumption was significantly lower in the ketamine group when compared with the control group (179.9 ME versus 248.7 ME, P=0.03). There was no statistically significant difference in pain scores or hospital length of stay postoperatively between the two groups. There were also no reported adverse respiratory events, prolonged sedation, agitation, or other side effects reported in either group. The patient satisfaction questionnaires showed a significant difference with the ketamine group reporting lower maximum pain scores, a decrease in how pain limited activities of daily living once discharged, and increased hospital pain management satisfaction scores. CONCLUSIONS: Perioperative low-dose ketamine infusions significantly reduced opioid consumption in morbidly obese patients undergoing laparoscopic gastric bypass surgery.

A technique to address peritoneal dialysis catheter malfunction.

BACKGROUND: A 66-year-old male with a history of severe ischemic myopathy and renal failure underwent a combined heart and kidney transplant. Postoperative failure of the transplanted kidney eventually led to the need for peritoneal dialysis (PD). METHODS: After one month, the PD catheter was laparoscopically repositioned after it was found to have migrated from its correct position in the pelvis and twisted and clogged in the omentum. After one more month, the same complication recurred. Laparoscopy was again used to clear the clogged catheter and reposition it. This time, a testicular prosthesis was sewn to the catheter and used as an anchoring weight for the proper position in the pelvis. RESULTS: Six months after anchoring with the testicular prosthesis, the peritoneal dialysis catheter continues to function appropriately, and the patient has no complaints. CONCLUSIONS: Mal-positioned peritoneal dialysis catheters may be repositioned and anchored by using a testicular prosthesis in the event that weighted catheters are not available.

Is There an Upper Age Limit for Bariatric Surgery? Laparoscopic Gastric Bypass Outcomes in Septuagenarians.

PURPOSE: Upper age limits for bariatric surgery are questioned on the merits of increased complication rates in the elderly and questionable efficacy. This study evaluates outcomes of bariatric surgery in patients ≥ 70 years of age. MATERIALS AND METHODS: Retrospective review was performed of patients ≥ 70 years of age who underwent laparoscopic Roux-en-Y gastric bypass (RYGB) between 2001 and 2018. Primary endpoints were 30-day readmission, Clavien-Dindo grade III-V (CD III-IV) complications, and mortality. Secondary data included were weight loss, long-term outcomes, comorbidity resolution, hemoglobin A1C, and lipid panels. RESULTS: A total of 23 patients with an average age of 72 years (range 70-80 years) and mean BMI of 43.3 (range 37.3-56.0) were reviewed. Average length-of-stay was 2.4 days (range 1-6 days), with the only acute complication being aspiration pneumonia in one patient. Median follow-up was 69.3 weeks (range 9-875 weeks). One-year follow-up rate was 96%, during which no deaths or CD III-IV complications occurred. Subsequently, one patient experienced failure-to-thrive requiring temporary enteral nutrition. Average 1 year percent total weight loss (%TWL) was 29%, and this was maintained on subsequent follow-ups. Average 1 year percent excess weight loss (%EWL) was 60%, maintained long-term at 61%. Significant serum biochemical improvements included hemoglobin A1C (6.9 ± 1.4% to 5.6 ± 1.3%, p = 0.001), triglycerides (155 ± 49 mg/dL to 102 ± 41 mg/dL, p = 0.0003), and high-density lipoprotein cholesterol (48 ± 14 mg/dL to 58 ± 22 mg/dL, p = 0.004). CONCLUSION: Laparoscopic RYGB is a safe and effective treatment for obesity and obesity-related comorbidities in septuagenarians.

A FACS-based approach to obtain viable eosinophils from human adipose tissue.

Eosinophils have been widely investigated in asthma and allergic diseases. More recently, new insights into the biology of these cells has illustrated eosinophils contribute to homeostatic functions in health such as regulation of adipose tissue glucose metabolism. Human translational studies are limited by the difficulty of obtaining cells taken directly from their tissue environment, relying instead on eosinophils isolated from peripheral blood. Isolation techniques for tissue-derived eosinophils can result in unwanted cell or ribonuclease activation, leading to poor cell viability or RNA quality, which may impair analysis of effector activities of these cells. Here we demonstrate a technique to obtain eosinophils from human adipose tissue samples for the purpose of downstream molecular analysis. From as little as 2 g of intact human adipose tissue, greater than 104 eosinophils were purified by fluorescence-activated cell sorting (FACS) protocol resulting in ≥ 99% purity and ≥ 95% viable eosinophils. We demonstrated that the isolated eosinophils could undergo epigenetic analysis to determine differences in DNA methylation in various settings. Here we focused on comparing eosinophils isolated from human peripheral blood vs human adipose tissue. Our results open the door to future mechanistic investigations to better understand the role of tissue resident eosinophils in different context.

The role of minimally invasive treatments in surgical oncology.

This article reviews the use of minimally invasive surgical and endoscopic techniques in the field of surgical oncology. It reviews the indications and techniques of the use of minimally invasive surgery for several oncologic indications in general surgery. In particular, it reviews the currently published literature discussing the oncologic outcomes of these techniques.

Total pancreatectomy (R0 resection) improves survival over subtotal pancreatectomy in isolated neck margin positive pancreatic adenocarcinoma.

UNLABELLED: In patients undergoing pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma (PC), conversion to total pancreatectomy (TP) may be necessary to achieve R0 resection. HYPOTHESIS: We sought to examine the oncologic benefit of conversion of PD to TP to achieve an R0 resection in patients with an isolated positive neck margin. METHODS: We conducted a retrospective analysis of prospectively collected data at Indiana University and Johns Hopkins Medical Institutions. A review of 1,579 patients who underwent PD or TP for PC at these institutions between 1992 and 2006 was performed. Sixty-one patients were eligible. RESULTS: Twenty-eight patients underwent PD with an isolated positive neck margin found on pathologic examination; 33 patients had conversion to TP for isolated neck margin involvement to achieve R0 resection. Patients undergoing TP versus PD had a greater median survival (18 vs 10 months; P = .04). Mortality (6% vs 7%) and morbidity (36% vs 54%; P = .20) for TP versus PD were comparable. Multivariate analysis revealed PD and greater tumor size as the only independent predictors of poor long-term survival (hazard ratio [HR], 2.2; P = .01 and HR, 1.3; P = .005). CONCLUSIONS: Conversion of PD to TP to achieve an R0 resection in patients with pancreatic adenocarcinoma is associated with a survival benefit.

Diagnosis and management of sphincter of Oddi dysfunction and pancreas divisum.

Sphincter of Oddi dysfunction and pancreas divisum are very distinct anatomic abnormalities, yet are diagnosed in similar clinical situations. While both entities are uncommon, they are most often discovered during the evaluation of postcholecystectomy syndrome, recurrent idiopathic pancreatitis, and biliary or pancreatic pain when first line studies are normal. Treatment consists of surgical sphincteroplasty or endoscopic sphincterotomy for both diagnoses, which result in reliable relief of symptoms for most sphincter of Oddi dysfunction patients but less predictable response in pancreas divisum.

Alterations of sorbin and SH3 domain containing 3 (SORBS3) in human skeletal muscle following Roux-en-Y gastric bypass surgery.

BACKGROUND: Obesity is a disease that is caused by genetic and environmental factors. However, epigenetic mechanisms of obesity are less well known. DNA methylation provides a mechanism whereby environmental factors can influence gene transcription. The aim of our study was to investigate skeletal muscle DNA methylation of sorbin and SH3 domain containing 3 (SORBS3) with weight loss induced by Roux-en-Y gastric bypass (RYGB). RESULTS: Previously, we had shown increased methylation (5.0 to 24.4%) and decreased gene expression (fold change - 1.9) of SORBS3 with obesity (BMI > 30 kg/m2) compared to lean controls. In the present study, basal muscle biopsies were obtained from seven morbidly obese (BMI > 40 kg/m2) female subjects pre- and 3 months post-RYGB surgery, in combination with euglycemic-hyperinsulinemic clamps to assess insulin sensitivity. We identified 30 significantly altered promoter and untranslated region methylation sites in SORBS3 using reduced representation bisulfite sequencing (RRBS). Twenty-nine of these sites were decreased (- 5.6 to - 24.2%) post-RYGB compared to pre-RYGB. We confirmed the methylation in 2 (Chr.8:22,423,690 and Chr.8:22,423,702) of the 29 decreased SORBS3 sites using pyrosequencing. This decreased methylation was associated with an increase in SORBS3 gene expression (fold change + 1.7) post-surgery. In addition, we demonstrated that SORBS3 promoter methylation in vitro significantly alters reporter gene expression (P < 0.0001). Two of the SORBS3 methylation sites (Chr.8:22,423,111 and Chr.8:22,423,205) were strongly correlated with fasting plasma glucose levels (r = 0.9, P = 0.00009 and r = 0.8, P = 0.0010). Changes in SORBS3 gene expression post-surgery were correlated with obesity measures and fasting insulin levels (r = 0.5 to 0.8; P < 0.05). CONCLUSIONS: These results demonstrate that SORBS3 methylation and gene expression are altered in obesity and restored to normal levels through weight loss induced by RYGB surgery.

Influence of bactibilia after preoperative biliary stenting on postoperative infectious complications.

The aim of this study was to correlate the bactibilia found after preoperative biliary stenting with that of the bacteriology of postoperative infectious complications in patients with obstructive jaundice. One hundred thirty-eight patients (83% malignant and 17% benign etiologies) with obstructive jaundice had both their bile and all postoperative infectious complications cultured. Eighty-six (62%) had preoperative biliary stents (stent group) and 52 (38%) did not (no-stent group). There were no differences for age, sex, incidence of malignancy, type of operation, estimated blood loss, transfusion requirements, hospital length of stay, morbidity, or mortality rates between the two groups. Of 31 infectious complications, 23 were in the stent group and eight were in the no-stent group (P > 0.05), but only 13 (42%) infectious complications had bacteria that were also cultured from the bile. Only wound infection (P = 0.03) and bacteremia (P = 0.04) were more likely to occur in stented patients. Taken together, these data show that preoperative biliary stenting increases the incidence of bactibilia, bacteremia, and wound infection rates but does not increase morbidity, mortality, or hospital length of stay. Jaundiced patients can undergo preoperative biliary stenting while maintaining an acceptable postoperative morbidity rate.