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Publication Record


Utilizing Untargeted Ion Mobility-Mass Spectrometry To Profile Changes in the Gut Metabolome Following Biliary Diversion Surgery.
Poland JC, Schrimpe-Rutledge AC, Sherrod SD, Flynn CR, McLean JA
(2019) Anal Chem 91: 14417-14423
MeSH Terms: Anastomosis, Surgical, Animals, Bile Acids and Salts, Bile Ducts, Cholesterol, Chromatography, Liquid, Duodenum, Fatty Acids, Volatile, Feces, Gastrointestinal Microbiome, Ileum, Jejunum, Male, Mass Spectrometry, Mice, Inbred C57BL
Show Abstract · Added December 17, 2019
Obesity and obesity-related disorders are a global epidemic affecting over 10% of the world's population. Treatment of these diseases has become increasingly challenging and expensive. The most effective and durable treatment for Class III obesity (body mass index ≥35 kg/m) is bariatric surgery, namely, Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy. These procedures are associated with increased circulating bile acids, molecules that not only facilitate intestinal fat absorption but are also potent hormones regulating numerous metabolic pathways. We recently reported on a novel surgical procedure in mice, termed distal gallbladder bile diversion to the ileum (GB-IL), that emulates the altered bile flow after RYGB without other manipulations of gastrointestinal anatomy. GB-IL improves oral glucose tolerance in mice made obese with high-fat diet. This is accompanied by fat malabsorption and weight loss, which complicates studying the role of elevated circulating bile acids in metabolic control. A less aggressive surgery in which the gallbladder bile is diverted to the proximal ileum, termed GB-IL, also improves glucose control but is not accompanied by fat malabsorption. To better understand the differential effects achieved by these bile diversion procedures, an untargeted ultraperformance liquid chromatography-ion mobility-mass spectrometry (UPLC-IM-MS) method was optimized for fecal samples derived from mice that have undergone bile diversion surgery. Utilizing the UPLC-IM-MS method, we were able to identify dysregulation of bile acids, short-chain fatty acids, and cholesterol derivatives that contribute to the differential metabolism resulting from these surgeries.
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15 MeSH Terms
Role of Bile Acids and GLP-1 in Mediating the Metabolic Improvements of Bariatric Surgery.
Albaugh VL, Banan B, Antoun J, Xiong Y, Guo Y, Ping J, Alikhan M, Clements BA, Abumrad NN, Flynn CR
(2019) Gastroenterology 156: 1041-1051.e4
MeSH Terms: Anastomosis, Surgical, Animals, Anticholesteremic Agents, Bariatric Surgery, Bile Acids and Salts, Blood Glucose, Cholestyramine Resin, Diet, High-Fat, Gallbladder, Glucagon-Like Peptide 1, Glucagon-Like Peptide-1 Receptor, Glucose Tolerance Test, Ileum, Insulin Resistance, Intestines, Lymph, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Receptors, Cytoplasmic and Nuclear, Receptors, G-Protein-Coupled, Signal Transduction, Verrucomicrobia, Weight Loss
Show Abstract · Added January 4, 2019
BACKGROUND & AIMS - Bile diversion to the ileum (GB-IL) has strikingly similar metabolic and satiating effects to Roux-en-Y gastric bypass (RYGB) in rodent obesity models. The metabolic benefits of these procedures are thought to be mediated by increased bile acids, although parallel changes in body weight and other confounding variables limit this interpretation.
METHODS - Global G protein-coupled bile acid receptor-1 null (Tgr5) and intestinal-specific farnesoid X receptor null (Fxr) mice on high-fat diet as well as wild-type C57BL/6 and glucagon-like polypeptide 1 receptor deficient (Glp-1r) mice on chow diet were characterized following GB-IL.
RESULTS - GB-IL induced weight loss and improved oral glucose tolerance in Tgr5, but not Fxr mice fed a high-fat diet, suggesting a role for intestinal Fxr. GB-IL in wild-type, chow-fed mice prompted weight-independent improvements in glycemia and glucose tolerance secondary to augmented insulin responsiveness. Improvements were concomitant with increased levels of lymphatic GLP-1 in the fasted state and increased levels of intestinal Akkermansia muciniphila. Improvements in fasting glycemia after GB-IL were mitigated with exendin-9, a GLP-1 receptor antagonist, or cholestyramine, a bile acid sequestrant. The glucoregulatory effects of GB-IL were lost in whole-body Glp-1r mice.
CONCLUSIONS - Bile diversion to the ileum improves glucose homeostasis via an intestinal Fxr-Glp-1 axis. Altered intestinal bile acid availability, independent of weight loss, and intestinal Akkermansia muciniphila appear to mediate the metabolic changes observed after bariatric surgery and might be manipulated for treatment of obesity and diabetes.
Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.
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2 Members
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25 MeSH Terms
Magnetic Compression Anastomosis (Magnamosis): First-In-Human Trial.
Graves CE, Co C, Hsi RS, Kwiat D, Imamura-Ching J, Harrison MR, Stoller ML
(2017) J Am Coll Surg 225: 676-681.e1
MeSH Terms: Adult, Anastomosis, Surgical, Digestive System Surgical Procedures, Equipment Design, Feasibility Studies, Female, Humans, Intestine, Small, Magnetics, Male, Middle Aged, Pilot Projects, Prospective Studies, Suture Techniques, Time Factors, Treatment Outcome
Show Abstract · Added January 16, 2018
BACKGROUND - Magnetic compression anastomosis (magnamosis) uses a pair of self-centering magnetic Harrison Rings to create an intestinal anastomosis without sutures or staples. We report the first-in-human case series using this unique device.
STUDY DESIGN - We conducted a prospective, single-center, first-in-human pilot trial to evaluate the feasibility and safety of creating an intestinal anastomosis using the Magnamosis device. Adult patients requiring any intestinal anastomosis to restore bowel continuity were eligible for inclusion. For each procedure, 1 Harrison Ring was placed in the lumen of each intestinal segment. The rings were brought together and mated, and left to form a side to side, functional end to end anastomosis. Device movement was monitored with serial x-rays until it was passed in the stool. Patients were monitored for adverse effects with routine clinic appointments, as well as questionnaires.
RESULTS - Five patients have undergone small bowel anastomosis with the Magnamosis device. All 5 patients had severe systemic disease and underwent complex open urinary reconstruction procedures, with the device used to restore small bowel continuity after isolation of an ileal segment. All devices passed without obstruction or pain. No patients have had any complications related to their anastomosis, including anastomotic leaks, bleeding, or stricture at median follow-up of 13 months.
CONCLUSIONS - In this initial case series from the first-in-human trial of the Magnamosis device, the device was successfully placed and effectively formed a side to side, functional end to end small bowel anastomosis in all 5 patients. No patients have had any anastomotic complications at intermediate follow-up.
Copyright © 2017 American College of Surgeons. Published by Elsevier Inc. All rights reserved.
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1 Members
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16 MeSH Terms
Association of Vitamin D Metabolites With Arterial Function in the Hemodialysis Fistula Maturation Study.
van Ballegooijen AJ, Zelnick L, Hoofnagle AN, Hamburg NM, Robinson-Cohen C, Roy-Chaudhury P, Cheung AK, Shiu YT, de Boer IH, Himmelfarb J, Beck G, Imrey PB, Kusek JW, Kestenbaum B, Hemodialysis Fistula Maturation (HFM) Study Group
(2017) Am J Kidney Dis 69: 805-814
MeSH Terms: 25-Hydroxyvitamin D 2, Adult, Aged, Anastomosis, Surgical, Arteries, Brachial Artery, Calcifediol, Carotid Arteries, Chromatography, Liquid, Cohort Studies, Cross-Sectional Studies, Ergocalciferols, Female, Femoral Artery, Humans, Kidney Failure, Chronic, Male, Middle Aged, Nitroglycerin, Prospective Studies, Pulse Wave Analysis, Radial Artery, Renal Dialysis, Tandem Mass Spectrometry, Vascular Stiffness, Vasodilation, Vasodilator Agents, Veins, Vitamin D
Show Abstract · Added September 19, 2017
BACKGROUND - Disturbances in vitamin D metabolism are common in patients with end-stage renal disease and may contribute to vascular dysfunction.
STUDY DESIGN - Cross-sectional.
SETTING & PARTICIPANTS - We evaluated 558 of 602 participants at baseline of the Hemodialysis Fistula Maturation (HFM) Study, a 7-center prospective cohort study of a cohort of patients with chronic kidney disease awaiting arteriovenous fistula (AVF) creation surgery.
FACTOR - 4 vitamin D metabolites measured with liquid chromatography-tandem mass spectroscopy from samples obtained within 4 weeks prior to AVF surgery.
OUTCOMES - Vasodilator functions and measurements of arterial stiffness.
MEASUREMENTS - Trained HFM Study personnel measured brachial artery flow-mediated dilation, nitroglycerin-mediated dilation, and carotid-femoral and carotid-radial pulse wave velocities (PWVs) prior to AVF creation. We evaluated associations after basic adjustment for sex, age, and clinical site and more fully adjusted additionally for baseline education, smoking, body mass index, diabetes, dialysis status, and medication use.
RESULTS - Mean participant age was 55±13 (SD) years and 65% were receiving maintenance dialysis. None of the vitamin D metabolites were significantly associated with flow-mediated dilation, carotid-femoral PWV, or carotid-radial PWV in basic or fully adjusted analyses. Higher serum concentrations of bioavailable vitamin D and 1,25-dihydroxyvitamin D were associated with 0.62% and 0.58% greater nitroglycerin-mediated dilation values, respectively, in basic models; however, these associations were no longer statistically significant with full adjustment. There were no significant associations of vitamin D metabolites with carotid-femoral or carotid-radial PWV in fully adjusted analyses.
LIMITATIONS - Cross-sectional ascertainment of vitamin D metabolites and vascular functions late during the course of kidney disease.
CONCLUSIONS - Serum concentrations of vitamin D metabolites are not associated with vasodilator functions or vascular stiffness at baseline in a cohort study of patients with chronic kidney disease awaiting AVF creation surgery. Laboratory measurements of vitamin D metabolites are unlikely to provide useful information regarding vascular functions in this setting.
Copyright © 2017 National Kidney Foundation, Inc. All rights reserved.
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29 MeSH Terms
Does Diverting Loop Ileostomy Improve Outcomes Following Open Ileo-Colic Anastomoses? A Nationwide Analysis.
Hawkins AT, Dharmarajan S, Wells KK, Krishnamurty DM, Mutch MG, Glasgow SC
(2016) J Gastrointest Surg 20: 1738-43
MeSH Terms: Aged, Aged, 80 and over, Anastomosis, Surgical, Anastomotic Leak, Colon, Digestive System Surgical Procedures, Female, Humans, Ileostomy, Ileum, Male, Middle Aged, Reoperation, Risk Factors, Treatment Outcome
Show Abstract · Added September 27, 2016
BACKGROUND - Anastomotic leak is one of the most feared complications of gastrointestinal surgery. Surgeons routinely perform a diverting loop ileostomy (DLI) to protect high-risk colo-rectal anastomoses.
STUDY DESIGN - The NSQIP database was queried from 2012 to 2013 for patients undergoing open ileo-colic resection with and without a DLI. The primary outcome was the development of any anastomotic leak-including those managed operatively and non-operatively. Secondary outcomes included overall complication rate, return to the OR, readmission, and 30-day mortality.
RESULTS - Four thousand one hundred fifty-nine patients underwent open ileo-colic resection during the study period. One hundred eighty-six (4.5 %) underwent a DLI. Factors associated with the addition of a DLI included emergency surgery, pre-operative sepsis, and IBD. There were 197 anastomotic leaks (4.7 %) with 100 patients requiring reoperation (2.4 %). DLI was associated with a decrease in anastomotic leaks requiring reoperation (DLI vs no DLI: 0 (0 %) vs 100 (2.5 %); p = 0.02) and with increased readmission (OR 1.93; 95 % CI 1.30-2.85; p = 0.001).
CONCLUSION - DLI is rarely used for open ileo-colic resection. There were no serious leaks requiring reoperation in the DLI group. A DLI was associated with an almost two-fold increase in the odds of readmission. Surgeons must weigh the reduction in serious leak rate with postoperative morbidity when considering a DLI for open ileo-colic resection.
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15 MeSH Terms
Bile diversion to the distal small intestine has comparable metabolic benefits to bariatric surgery.
Flynn CR, Albaugh VL, Cai S, Cheung-Flynn J, Williams PE, Brucker RM, Bordenstein SR, Guo Y, Wasserman DH, Abumrad NN
(2015) Nat Commun 6: 7715
MeSH Terms: Adaptation, Biological, Anastomosis, Surgical, Animals, Bariatric Surgery, Bile Acids and Salts, Carrier Proteins, Disease Models, Animal, Energy Metabolism, Fibroblast Growth Factors, Gallbladder, Gastrointestinal Microbiome, Intestine, Small, Liver, Male, Membrane Glycoproteins, Mice, Inbred C57BL, Obesity, Random Allocation
Show Abstract · Added August 26, 2015
Roux-en-Y gastric bypass (RYGB) is highly effective in reversing obesity and associated diabetes. Recent observations in humans suggest a contributing role of increased circulating bile acids in mediating such effects. Here we use a diet-induced obesity (DIO) mouse model and compare metabolic remission when bile flow is diverted through a gallbladder anastomosis to jejunum, ileum or duodenum (sham control). We find that only bile diversion to the ileum results in physiologic changes similar to RYGB, including sustained improvements in weight, glucose tolerance and hepatic steatosis despite differential effects on hepatic gene expression. Circulating free fatty acids and triglycerides decrease while bile acids increase, particularly conjugated tauro-β-muricholic acid, an FXR antagonist. Activity of the hepatic FXR/FGF15 signalling axis is reduced and associated with altered gut microbiota. Thus bile diversion, independent of surgical rearrangement of the gastrointestinal tract, imparts significant weight loss accompanied by improved glucose and lipid homeostasis that are hallmarks of RYGB.
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6 Members
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18 MeSH Terms
Cost benefit analysis of mesh reinforcement of stapled left pancreatectomy.
Idrees K, Edler JR, Linehan DC, Strasberg SM, Jacques D, Hamilton NA, Fields RC, Lambert D, Kymes S, Hawkins WG
(2013) HPB (Oxford) 15: 893-8
MeSH Terms: Anastomosis, Surgical, Anastomotic Leak, Cost of Illness, Cost-Benefit Analysis, Humans, Pancreas, Pancreatectomy, Pancreatic Neoplasms, Reoperation, Retrospective Studies, Single-Blind Method, Surgical Mesh, Surgical Stapling, Suture Techniques, United States
Show Abstract · Added March 28, 2014
OBJECTIVES - Pancreatic leak is a morbid complication following left pancreatectomy, which results in prolonged hospitalization, additional diagnostic testing and invasive procedures. The present authors have previously demonstrated that mesh reinforcement of stapled left pancreatectomy results in fewer pancreatic leaks. This study was conducted to investigate whether mesh reinforcement also results in cost benefits for the health care system.
METHODS - A cost benefit model was developed to estimate net cost savings from the payer's perspective. The model is based on the results of a randomized, single-blinded trial of mesh versus no mesh reinforcement of the pancreatic remnant after left pancreatectomy. A two-way sensitivity analysis was conducted to determine the model's sensitivity to fluctuations in the cost of mesh and the effectiveness of the mesh in reducing clinically significant leaks.
RESULTS - Average total costs for an episode of care were US$13 337 and US$15 505 for patients who did and did not receive mesh, respectively, which indicates savings of US$2168. Two-way sensitivity analysis showed that, given a probability of 1.9% for developing a clinically significant leak in patients in whom mesh reinforcement was used, the strategy would continue to save costs if mesh were priced at ≤US$1804.
CONCLUSIONS - Mesh reinforcement decreases clinically significant pancreatic leaks. Despite the additional cost of mesh reinforcement, the use of mesh reinforcement results in overall cost savings for the health care system because of the resultant decrease in the occurrence of clinically significant leaks.
© 2013 International Hepato-Pancreato-Biliary Association.
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1 Members
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15 MeSH Terms
Ureteroenteric anastomotic strictures after radical cystectomy-does operative approach matter?
Anderson CB, Morgan TM, Kappa S, Moore D, Clark PE, Davis R, Penson DF, Barocas DA, Smith JA, Cookson MS, Chang SS
(2013) J Urol 189: 541-7
MeSH Terms: Aged, Anastomosis, Surgical, Constriction, Pathologic, Cystectomy, Female, Humans, Intestines, Male, Prospective Studies, Urinary Bladder, Urinary Diversion
Show Abstract · Added March 5, 2014
PURPOSE - Robot-assisted laparoscopic radical cystectomy has been increasingly used to decrease the morbidity of radical cystectomy. However, whether it truly lowers the complication rate compared to open radical cystectomy is not well established. We examined the benign ureteroenteric anastomotic stricture rates of open and robot-assisted laparoscopic radical cystectomy.
MATERIALS AND METHODS - In the 478 consecutive patients who underwent radical cystectomy at our institution from December 2007 to December 2011 we examined the proportion diagnosed with benign ureteroenteric anastomotic stricture. Clinicopathological variables were compared by treatment group. Cox multivariable analysis was performed to determine which patient or disease specific factors were independently associated with stricture diagnosis.
RESULTS - A total of 375 patients (78.5%) underwent open radical cystectomy and 103 (21.5%) underwent robot-assisted laparoscopic radical cystectomy. Of the patients 45 (9.4%) were diagnosed with ureteroenteric anastomotic stricture a median of 5.3 months postoperatively. There was no difference in the stricture rate between the open and robot-assisted groups (8.5% vs 12.6%, p = 0.21). On adjusted Cox proportional hazards analysis no patient variable was independently associated with stricture diagnosis, including operative approach.
CONCLUSIONS - Of the patients 9.4% were diagnosed with benign ureteroenteric anastomotic stricture after radical cystectomy with no significant difference in the risk of diagnosis by surgical approach. No patient or disease specific factor was independently associated with an increased risk of stricture diagnosis. Ureteroenteric anastomotic stricture is likely related to surgical technique. Continued efforts are needed to refine the technique of open and robot-assisted laparoscopic radical cystectomy to minimize the occurrence of this critical complication.
Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
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3 Members
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11 MeSH Terms
Operative intervention for complete pancreatic transection in children sustaining blunt abdominal trauma: revisiting an organ salvage technique.
Borkon MJ, Morrow SE, Koehler EA, Shyr Y, Hilmes MA, Miller RS, Neblett WW, Lovvorn HN
(2011) Am Surg 77: 612-20
MeSH Terms: Abdominal Injuries, Adolescent, Age Factors, Analysis of Variance, Anastomosis, Surgical, Child, Child, Preschool, Cohort Studies, Female, Follow-Up Studies, Humans, Infant, Injury Severity Score, Male, Minimally Invasive Surgical Procedures, Pancreas, Pancreatectomy, Postoperative Care, Postoperative Complications, Proportional Hazards Models, Retrospective Studies, Risk Assessment, Salvage Therapy, Statistics, Nonparametric, Survival Rate, Treatment Outcome, Wounds, Nonpenetrating
Show Abstract · Added February 13, 2014
Complete pancreatic transection (CPT) in children is managed commonly with distal pancreatectomy (DP). Alternatively, Roux-en-Y distal pancreaticojejunostomy (RYPJ) may be performed to preserve pancreatic tissue. The purpose of this study was to review our experience using either procedure in the management of children sustaining CPT after blunt abdominal trauma. We retrospectively reviewed the records of all children admitted to our institution during the last 15 years who were confirmed at operation to have CPT after blunt mechanisms. Summary statistics of demographic data were performed to describe children receiving either RYPJ or DP. CPT occurred in 28 children: 15 had DP, 10 had RYPJ, and three had cystogastrostomy. RYPJ children, compared with DP, were younger (7.5 vs. 12.3 years, P = 0.039) and sustained more grade IV pancreatic injuries (70% vs. 14%, P = 0.01). DP patients were 5.63 times more likely to tolerate full enteral feeds (P = 0.009). Nevertheless, when controlling for age, injury severity score, and pancreatic injury grade, procedure type did not statistically affect total and postoperative lengths of stay and postoperative complications. In the operative management algorithm of children sustaining CPT, DP may afford an earlier return to full enteral feeds. RYPJ seems otherwise equivalent to DP and preserves significant pancreatic glandular tissue and the spleen.
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2 Members
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27 MeSH Terms
Robotic liver surgery.
Idrees K, Bartlett DL
(2010) Surg Clin North Am 90: 761-74
MeSH Terms: Anastomosis, Surgical, Hepatectomy, Humans, Jejunum, Liver, Liver Diseases, Robotics
Show Abstract · Added March 28, 2014
Although minimally invasive hepatic resection surgery has shown decreased morbidity in select patients, conventional laparoscopic liver resection has inherent limitations with reduced freedom of movement within the abdominal cavity and 2-dimensional view of the operative field. Robotic liver surgery allows surgeons to perform advanced procedures with a potential for improved precision and ergonomics as well as a 3-dimensional view of the surgical site. However, use of the robot entails a steep learning curve and additional equipment. The purpose of this article is to summarize the emerging field of robotic liver surgery and include the authors' early experience with these operations.
Copyright 2010 Elsevier Inc. All rights reserved.
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7 MeSH Terms