Publications by authors named "W Scott Melvin"

278 Publications

Inhibition of macrophage histone demethylase JMJD3 protects against abdominal aortic aneurysms.

J Exp Med 2021 Jun;218(6)

Section of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI.

Abdominal aortic aneurysms (AAAs) are a life-threatening disease for which there is a lack of effective therapy preventing aortic rupture. During AAA formation, pathological vascular remodeling is driven by macrophage infiltration, and the mechanisms regulating macrophage-mediated inflammation remain undefined. Recent evidence suggests that an epigenetic enzyme, JMJD3, plays a critical role in establishing macrophage phenotype. Using single-cell RNA sequencing of human AAA tissues, we identified increased JMJD3 in aortic monocyte/macrophages resulting in up-regulation of an inflammatory immune response. Mechanistically, we report that interferon-β regulates Jmjd3 expression via JAK/STAT and that JMJD3 induces NF-κB-mediated inflammatory gene transcription in infiltrating aortic macrophages. In vivo targeted inhibition of JMJD3 with myeloid-specific genetic depletion (JMJD3f/fLyz2Cre+) or pharmacological inhibition in the elastase or angiotensin II-induced AAA model preserved the repressive H3K27me3 on inflammatory gene promoters and markedly reduced AAA expansion and attenuated macrophage-mediated inflammation. Together, our findings suggest that cell-specific pharmacologic therapy targeting JMJD3 may be an effective intervention for AAA expansion.
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http://dx.doi.org/10.1084/jem.20201839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008365PMC
June 2021

International Delphi Expert Consensus on Safe Return to Surgical and Endoscopic Practice: from the Coronavirus Global Surgical Collaborative.

Ann Surg 2020 Dec 29. Epub 2020 Dec 29.

*Hepatobiliary and Pancreas Surgery, Miami Cancer Institute, Miami, FL, USA †Department of Surgery, Istituto Fondazione Poliambulanza, Brescia, Italy ‡Department of Surgery, Southampton University Hospital., 1. Division of Hepatobiliary and Pancreas Surgery, Miami Cancer Institute, Miami, FL, USA §Department of Surgery, University of California San Francisco Fresno, Fresno, CA, USA ¶Department of Surgery, Amsterdam University Medical Center, Amsterdam, The Netherlands ||Department of Surgery, Trinity College Dublin, and St. Vincent's University Hospital, Dublin, Ireland **Department of Visceral Surgery, Lausanne University Hospital (CHUV), University of Lausanne, Lausanne, Switzerland ††Edward W. Archibald Professor and Chair, Department of Surgery McGill University Surgeon-in-chief, McGill University Health Centre Montreal, Quebec, Canada ‡‡University Hospital Virgen del Rocio, Sevilla, Spain §§Dipartimento di Scienze Clinico Chirurgiche, Diagnostiche e Pediatriche, Università Degli Studi Di Pavia, Pavia, Italy. Fondazione IRCCS Policlinico San Matteo, Pavia ¶¶Stony Brook University Department of Surgery, Stony Brook, NY, USA ||||Department of Surgery, Schulich School of Medicine and Dentistry, Western University, London, Canada ***Icahn School Medicine at Mount Sinai, New York, NY, USA †††Division of Colorectal Surgery, Department of Surgery, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain ‡‡‡Ministry of Health, Madrid, Spain §§§Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA ¶¶¶Department of Surgery, Mayo Clinic, Rochester, MN, USA ||||||Department of Anesthesia at Baptist Hospital of Miami, Miami, FL, USA. Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA ****General Management, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland ††††BA Wake Forest University, Reno, NV, USA ‡‡‡‡Department of Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seoul, Korea. 16. Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA §§§§Department of Anesthesiology, Stony Brook University Renaissance School of Medicine, Stony Brook, NY, USA ¶¶¶¶Communicable Diseases Division, Swiss Federal Office of Public Health, Bern, Switzerland ||||||||Department of Surgery, Massachusetts General Hospital, Boston, USA *****Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore †††††Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, OH, USA ‡‡‡‡‡Divisions of General and Gastrointestinal Surgery, Department of Surgery, Atrium Health Carolinas Medical Center, Charlotte, NC, USA §§§§§Southern Illinois University School of Medicine, Departments of Surgery and Medical Education, Springfield, IL, USA ¶¶¶¶¶Division of General Surgery, Department of Surgery, Montefiore Medical Center, New York, NY, USA ||||||||||Department of Surgery, ABC Medical Center, Mexico City, Mexico ******Servicio de Cirugía Endoscópica Hospital San Borja Arriarán de Santiago. Departamento de Cirugía, Clinica Santa Maria, Santiago, Chile ††††††Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA ‡‡‡‡‡‡Department of Digestive Surgery, Nouvel Hôpital Civil, Université de Strasbourg, IHU Institute of Image-Guided Surgery of Strasbourg and U1110 Inserm, Institute of Viral and Liver Disease, Strasbourg, France §§§§§§Section of Hygiene, University Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, Rome, Italy. Department of Woman and Child Health and Public Health - Public Health Area Fondazione Policlinico Universitario A. Gemelli IRCCS Rome, Italy ¶¶¶¶¶¶Department of Surgery, University at Buffalo, Buffalo, NY, USA ||||||||||||Department of Surgery, NYU Langone Health, New York, NY, USA *******Department of Anesthesiology, NorthShore University HealthSystem, University of Chicago Pritzker School of Medicine, Evanston, IL, USA †††††††Departments of Surgery, State University of New York, Stony Brook, NY, USA ‡‡‡‡‡‡‡Departamento of Surgery, Hospital Escuela "José de San Martín", Corrientes, Argentina.**, 2. Department of Surgery, Istituto Fondazione Poliambulanza, Brescia, Italy §§§§§§§Department of Surgery, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand ¶¶¶¶¶¶¶Fondazione Nadia Valsecchi Onlus, Palazzolo Sull'Oglio, Brescia, Italy ||||||||||||||Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA ********Department of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA ††††††††Department of Colorectal Surgery, Cleveland Clinic Florida, Weston, FL, USA ‡‡‡‡‡‡‡‡Miami Cancer Institute, Miami, FL, USA §§§§§§§§Department of General Surgery, Yeovil District Hospital National Health Service Foundation Trust, Yeovil, England. Division of Surgery and Interventional Science, University College London. The Griffin Institute at Northwick Park Institute for Medical Research, Norwich Park London. Enhanced-Recovery After Surgery - UK (ERAS-UK).

Objective: The aim of this work is to formulate recommendations based on global expert consensus to guide the surgical community on the safe resumption of surgical and endoscopic activities.

Background: The COVID-19 pandemic has caused marked disruptions in the delivery of surgical care worldwide. A thoughtful, structured approach to resuming surgical services is necessary as the impact of COVID-19 becomes better controlled. The Coronavirus Global Surgical Collaborative (CVGSC) sought to formulate, through rigorous scientific methodology, a consensus-based recommendations in collaboration with a multidisciplinary group of international experts and policy makers.

Methods: Recommendations were developed following a Delphi process. Domain topics were formulated and subsequently subdivided into questions pertinent to different aspects of surgical care in the COVID-19 crisis. Forty-four experts from 15 countries across four continents drafted statements based on the specific questions. Anonymous Delphi voting on the statements was performed in two rounds, as well as in a telepresence meeting.

Results: One hundred statements were formulated across 10 domains. The statements addressed terminology, impact on procedural services, patient/staff safety, managing a backlog of surgeries, methods to restart and sustain surgical services, education, and research. Eightythree of the statements were approved during the first round of Delphi voting, and 11 during the second round. A final telepresence meeting and discussion yielded acceptance of five other statements.

Conclusions: The Delphi process resulted in 99 recommendations. These consensus statements provide expert guidance, based on scientific methodology, for the safe resumption of surgical activities during the COVID-19 pandemic.
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http://dx.doi.org/10.1097/SLA.0000000000004674DOI Listing
December 2020

Epigenetic regulation of the PGE2 pathway modulates macrophage phenotype in normal and pathologic wound repair.

JCI Insight 2020 09 3;5(17). Epub 2020 Sep 3.

Section of Vascular Surgery, Department of Surgery.

Macrophages are a primary immune cell involved in inflammation, and their cell plasticity allows for transition from an inflammatory to a reparative phenotype and is critical for normal tissue repair following injury. Evidence suggests that epigenetic alterations play a critical role in establishing macrophage phenotype and function during normal and pathologic wound repair. Here, we find in human and murine wound macrophages that cyclooxygenase 2/prostaglandin E2 (COX-2/PGE2) is elevated in diabetes and regulates downstream macrophage-mediated inflammation and host defense. Using single-cell RNA sequencing of human wound tissue, we identify increased NF-κB-mediated inflammation in diabetic wounds and show increased COX-2/PGE2 in diabetic macrophages. Further, we identify that COX-2/PGE2 production in wound macrophages requires epigenetic regulation of 2 key enzymes in the cytosolic phospholipase A2/COX-2/PGE2 (cPLA2/COX-2/PGE2) pathway. We demonstrate that TGF-β-induced miRNA29b increases COX-2/PGE2 production via inhibition of DNA methyltransferase 3b-mediated hypermethylation of the Cox-2 promoter. Further, we find mixed-lineage leukemia 1 (MLL1) upregulates cPLA2 expression and drives COX-2/PGE2. Inhibition of the COX-2/PGE2 pathway genetically (Cox2fl/fl Lyz2Cre+) or with a macrophage-specific nanotherapy targeting COX-2 in tissue macrophages reverses the inflammatory macrophage phenotype and improves diabetic tissue repair. Our results indicate the epigenetically regulated PGE2 pathway controls wound macrophage function, and cell-targeted manipulation of this pathway is feasible to improve diabetic wound repair.
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http://dx.doi.org/10.1172/jci.insight.138443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526451PMC
September 2020

Palmitate-TLR4 signaling regulates the histone demethylase, JMJD3, in macrophages and impairs diabetic wound healing.

Eur J Immunol 2020 12 20;50(12):1929-1940. Epub 2020 Jul 20.

Section of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, USA.

Chronic macrophage inflammation is a hallmark of type 2 diabetes (T2D) and linked to the development of secondary diabetic complications. T2D is characterized by excess concentrations of saturated fatty acids (SFA) that activate innate immune inflammatory responses, however, mechanism(s) by which SFAs control inflammation is unknown. Using monocyte-macrophages isolated from human blood and murine models, we demonstrate that palmitate (C16:0), the most abundant circulating SFA in T2D, increases expression of the histone demethylase, Jmjd3. Upregulation of Jmjd3 results in removal of the repressive histone methylation (H3K27me3) mark on NFκB-mediated inflammatory gene promoters driving macrophage-mediated inflammation. We identify that the effects of palmitate are fatty acid specific, as laurate (C12:0) does not regulate Jmjd3 and the associated inflammatory profile. Further, palmitate-induced Jmjd3 expression is controlled via TLR4/MyD88-dependent signaling mechanism, where genetic depletion of TLR4 (Tlr4 ) or MyD88 (MyD88 ) negated the palmitate-induced changes in Jmjd3 and downstream NFκB-induced inflammation. Pharmacological inhibition of Jmjd3 using a small molecule inhibitor (GSK-J4) reduced macrophage inflammation and improved diabetic wound healing. Together, we conclude that palmitate contributes to the chronic Jmjd3-mediated activation of macrophages in diabetic peripheral tissue and a histone demethylase inhibitor-based therapy may represent a novel treatment for nonhealing diabetic wounds.
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http://dx.doi.org/10.1002/eji.202048651DOI Listing
December 2020

Reflections on the coronavirus disease 2019 (COVID-19) epidemic: The first 30 days in one of New York's largest academic departments of surgery.

Surgery 2020 08 20;168(2):212-214. Epub 2020 May 20.

Department of Surgery, Montefiore Medical Center, New York, NY; Department of Epidemiology & Population Health, Albert Einstein College of Medicine, New York, NY.

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http://dx.doi.org/10.1016/j.surg.2020.05.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237892PMC
August 2020

Epigenetic Regulation of TLR4 in Diabetic Macrophages Modulates Immunometabolism and Wound Repair.

J Immunol 2020 05 23;204(9):2503-2513. Epub 2020 Mar 23.

Section of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI 48109;

Macrophages are critical for the initiation and resolution of the inflammatory phase of wound healing. In diabetes, macrophages display a prolonged inflammatory phenotype preventing tissue repair. TLRs, particularly TLR4, have been shown to regulate myeloid-mediated inflammation in wounds. We examined macrophages isolated from wounds of patients afflicted with diabetes and healthy controls as well as a murine diabetic model demonstrating dynamic expression of TLR4 results in altered metabolic pathways in diabetic macrophages. Further, using a myeloid-specific mixed-lineage leukemia 1 (MLL1) knockout ( ), we determined that MLL1 drives expression in diabetic macrophages by regulating levels of histone H3 lysine 4 trimethylation on the promoter. Mechanistically, MLL1-mediated epigenetic alterations influence diabetic macrophage responsiveness to TLR4 stimulation and inhibit tissue repair. Pharmacological inhibition of the TLR4 pathway using a small molecule inhibitor (TAK-242) as well as genetic depletion of either ( ) or myeloid-specific resulted in improved diabetic wound healing. These results define an important role for MLL1-mediated epigenetic regulation of TLR4 in pathologic diabetic wound repair and suggest a target for therapeutic manipulation.
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http://dx.doi.org/10.4049/jimmunol.1901263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443363PMC
May 2020

Feasibility and efficacy of gamification in general surgery residency: Preliminary outcomes of residency teams.

Am J Surg 2020 02 6;219(2):283-288. Epub 2019 Nov 6.

Department of Surgery, Montefiore Medical Center, 1865 Eastchester Rd, Bronx, NY, 10461, USA. Electronic address:

Background: Comprehensive studies evaluating the efficacy of team-based competition ("Gamification") in surgery have not been performed. Board pass rates and resident satisfaction may improve if surgical residents are involved in competition.

Methods: Residents at Montefiore Medical Center (Bronx, New York) were surveyed and separated into teams during a draft. Each resident's performance was converted into a point system. Resident scores were combined into a team score and presented as a leaderboard. Awards were given. ABSITE, ACGME residency satisfaction, and ABS qualifying exam pass rates were compared.

Results: Sixty percent of residents are inspired to improve their performance during gamification. ABSITE average percentile score improved from 28 to 43. ABS qualifying exam pass rates improved from 73% to 100%. Resident satisfaction improved from 65% to 88%. The point system allowed for establishing "growth curves" for each resident enabling enhanced assessment of residents.

Conclusions: A comprehensive team-based competition inspires performance, is feasible, and seems to improve ABSITE scores, ABS pass rates, and satisfaction while being a tool for assessment of performance.
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http://dx.doi.org/10.1016/j.amjsurg.2019.10.051DOI Listing
February 2020

Sepsis Induces Prolonged Epigenetic Modifications in Bone Marrow and Peripheral Macrophages Impairing Inflammation and Wound Healing.

Arterioscler Thromb Vasc Biol 2019 11 5;39(11):2353-2366. Epub 2019 Sep 5.

From the Section of Vascular Surgery, Department of Surgery (F.M.D., A.D., A.D.J., A.S.K., A.T.O., W.J.M., K.A.G.), University of Michigan, Ann Arbor.

Objective: Sepsis represents an acute life-threatening disorder resulting from a dysregulated host response. For patients who survive sepsis, there remains long-term consequences, including impaired inflammation, as a result of profound immunosuppression. The mechanisms involved in this long-lasting deficient immune response are poorly defined. Approach and Results: Sepsis was induced using the murine model of cecal ligation and puncture. Following a full recovery period from sepsis physiology, mice were subjected to our wound healing model and wound macrophages (CD11b+, CD3-, CD19-, Ly6G-) were sorted. Post-sepsis mice demonstrated impaired wound healing and decreased reepithelization in comparison to controls. Further, post-sepsis bone marrow-derived macrophages and wound macrophages exhibited decreased expression of inflammatory cytokines vital for wound repair (IL [interleukin]-1β, IL-12, and IL-23). To evaluate if decreased inflammatory gene expression was secondary to epigenetic modification, we conducted chromatin immunoprecipitation on post-sepsis bone marrow-derived macrophages and wound macrophages. This demonstrated decreased expression of , an epigenetic enzyme, and impaired histone 3 lysine 4 trimethylation (activation mark) at NFκB (nuclear factor kappa-light-chain-enhancer of activated B cells)-binding sites on inflammatory gene promoters in bone marrow-derived macrophages and wound macrophages from postcecal ligation and puncture mice. Bone marrow transplantation studies demonstrated epigenetic modifications initiate in bone marrow progenitor/stem cells following sepsis resulting in lasting impairment in peripheral macrophage function. Importantly, human peripheral blood leukocytes from post-septic patients demonstrate a significant reduction in compared with nonseptic controls.

Conclusions: These data demonstrate that severe sepsis induces stable mixed-lineage leukemia 1-mediated epigenetic modifications in the bone marrow, which are passed to peripheral macrophages resulting in impaired macrophage function and deficient wound healing persisting long after sepsis recovery.
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http://dx.doi.org/10.1161/ATVBAHA.119.312754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6818743PMC
November 2019

Long-term reported outcomes of transoral incisionless fundoplication: an 8-year cohort study.

Surg Endosc 2019 04 27;33(4):1304-1309. Epub 2018 Aug 27.

Department of Surgery, The Ohio State University, Columbus, OH, USA.

Background: Transoral incisionless fundoplication (TIF) offers an endoscopic approach to the treatment of gastroesophageal reflux disease (GERD). Controlled trials have demonstrated the short-term efficacy of this procedure, but long-term follow-up studies are lacking. The objective of this study was to evaluate the long-term impact of TIF on disease-specific quality of life and antisecretory medication use.

Methods: We performed retrospective cohort study of all patients undergoing TIF between 2007 and 2014 in a large academic medical center. Reflux symptoms and quality of life were assessed using the gastroesophageal reflux disease health-related quality of life (GERD-HRQL) questionnaire at baseline, short-term, and long-term follow-up.

Results: Fifty-seven patients with a median age of 46 (37-59) years and an average BMI of 28.8 ± 4.9 kg/m underwent TIF during the study period. Sixty percent of the patients were female, and all were taking a PPI at least daily. At a median follow-up interval of 97 months, twelve patients had undergone subsequent laparoscopic antireflux surgery (LARS). Of those who had not, 23 had complete long-term follow-up data for analysis and were included in the study. Seventy-three percent reported daily acid-reducing medication use, and the median GERD-HRQL score was 10 (6-14) compared to 24 (15-28) at baseline (p < 0.01). Seventy-eight percent of these patients expressed satisfaction or neutral feelings about their GERD management. There were no significant differences in the baseline characteristics of patients who underwent LARS during the study period and those who did not.

Conclusions: This study demonstrates that TIF can produce durable improvements in disease-specific quality of life in some patients with symptomatic GERD. The majority of patients resumed daily PPI therapy during the study period, but with significantly improved GERD-HRQL scores compared to baseline and increased satisfaction with their medical condition.
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http://dx.doi.org/10.1007/s00464-018-6403-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6461469PMC
April 2019

Protracted Hypocalcemia following 3.5 Parathyroidectomy in a Kidney Pancreas Recipient with a History of Robotic-Assisted Roux-en-Y Gastric Bypass.

Case Rep Transplant 2018 24;2018:2182083. Epub 2018 Jul 24.

Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.

Background: Hypocalcemia is a frequent complication of parathyroidectomy for secondary/tertiary hyperparathyroidism. In patients with a history of prior Roux-en-Y gastric bypass (RYGBP), changes in nutritional absorption make management of hypocalcemia after parathyroidectomy difficult.

Case Report: A 41-old-year morbidly obese female with c-peptide negative diabetes mellitus and renal failure had RYGBP. Following significant weight loss she underwent simultaneous pancreas-kidney transplantation. She had excellent transplant graft function but developed tertiary hyperparathyroidism with calciphylaxis. She underwent resection of 3.5 glands leaving a small, physiologic remnant remaining in situ at the left inferior position. She was discharged on postoperative day one in good condition, asymptomatic with serum calcium of 7.6 mg/dL and intact PTH of 12 pg/mL. The patient had to be readmitted on postoperative day #14 for severe hypocalcemia of 5.0 mg/dl and ionized calcium 2.4 mg/dl. She required intravenous calcium infusion to achieve calcium levels of >6.5 mg/dl. Long-term treatment includes 5 g of elemental oral calcium TID, vitamin D, and hydrochlorothiazide. She remains in the long term on high-dose medical therapy with normal serum calcium levels and PTH levels around 100 pg/mL.

Discussion: Our patient's protracted hypocalcemia originates from a combination of 3.5 gland parathyroidectomy, altered intestinal anatomy post-RYGBP, and potentially her pancreas transplant causing additional metabolic derangement. Alternative bariatric procedures such as sleeve gastrectomy may be more suitable for patients with renal failure or organ transplants in whom adequate absorption of vitamins, minerals, and drugs such as immunosuppressants is essential.
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http://dx.doi.org/10.1155/2018/2182083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6081600PMC
July 2018

Commentary on Gomez et al.

Authors:
W Scott Melvin

Ann Surg 2018 05;267(5):e89

Albert Einstein School of Medicine, Bronx, NY.

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http://dx.doi.org/10.1097/SLA.0000000000002715DOI Listing
May 2018

Anatomy of change: a Kodak moment.

Authors:
W Scott Melvin

Surgery 2018 03 10;163(3):485-487. Epub 2018 Jan 10.

Montefiore Medical Center, The Albert Einstein College of Medicine, Bronx, NY. Electronic address:

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http://dx.doi.org/10.1016/j.surg.2017.11.001DOI Listing
March 2018

Impact of minimally invasive surgery on healthcare utilization, cost, and workplace absenteeism in patients with Incisional/Ventral Hernia (IVH).

Surg Endosc 2017 11 31;31(11):4412-4418. Epub 2017 Mar 31.

Department of Surgery, The University of Hawaii John A. Burns School of Medicine, Honolulu, HI, 96813, USA.

Background: Incisional hernia repair is one of the most common general surgery operations being performed today. With the advancement of laparoscopy since the 1990s, we have seen vast improvements in faster return to normal activity, shorter hospital stays and less post-operative narcotic use, to name a few.

Objective: The key aims of this review were to measure the impact of minimally invasive surgery versus open surgery on health care utilization, cost, and work place absenteeism in the patients undergoing inpatient incisional/ventral hernia (IVH) repair.

Methods: We analyzed data from the Truven Health Analytics MarketScan Commercial Claims and Encounters Database. Total of 2557 patients were included in the analysis.

Results: Of the patient that underwent IVH surgery, 24.5% (n = 626) were done utilizing minimally invasive surgical (MIS) techniques and 75.5% (n = 1931) were done open. Ninety-day post-surgery outcomes were significantly lower in the MIS group compared to the open group for total payment ($19,288.97 vs. $21,708.12), inpatient length of stay (3.12 vs. 4.24 days), number of outpatient visit (5.48 vs. 7.35), and estimated days off (11.3 vs. 14.64), respectively. At 365 days post-surgery, the total payment ($27,497.96 vs. $30,157.29), inpatient length of stay (3.70 vs. 5.04 days), outpatient visits (19.75 vs. 23.42), and estimated days off (35.71 vs. 41.58) were significantly lower for MIS group versus the open group, respectively.

Conclusion: When surgical repair of IVH is performed, there is a clear advantage in the MIS approach versus the open approach in regard to cost, length of stay, number of outpatient visits, and estimated days off.
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http://dx.doi.org/10.1007/s00464-017-5488-yDOI Listing
November 2017

Outcomes of bariatric surgery in the young: a single-institution experience caring for patients under 21 years old.

Surg Endosc 2016 11 11;30(11):5015-5022. Epub 2016 Mar 11.

Montefiore Institute for Minimally Invasive Surgery, Montefiore Medical Center, 3400 Bainbridge Avenue, MAP 4, Bronx, NY, 104647, USA.

Background: Medical weight loss options are rarely successful long term in young patients. Bariatric surgery has been shown to be safe and effective in this population.

Methods: Patients ≤21 years old who had bariatric surgery at our institution between January 2009 and December 2013 were evaluated to determine the safety and efficacy of bariatric surgery in this population. The primary end point was excess weight loss (EWL). Secondary end points included surgical morbidity, improvement in obesity-related metabolic parameters, and subjective obesity-related symptoms at 1 year.

Results: Fifty-four patients were identified who had a laparoscopic Roux-en-Y gastric bypass (LGBP) or laparoscopic sleeve gastrectomy (LSG). Fourteen patients were male (25.9 %), and 40 patients were female (74.1 %). Thirty-seven patients (68.5 %) underwent LGBP, and 17 patients (31.5 %) underwent LSG. Median follow-up was 13.3 months. The baseline BMI was 51.7 kg/m for the LGBP group and 51.0 kg/m for the LSG group. EWL was 35.2, 47.6, 62.4, 58.1, and 61.8 % for the LGBP group; 29.7, 44.7, 57.4, 60.3, and 59.0 % for the LSG group at 3, 6, 12, 24, and 36 months, respectively. Our complications included 1 anastomotic bleed, 1 postoperative stricture, and 1 patient who developed vitamin deficiency that manifested as a peripheral neuropathy in the LGBP group. LGBP was more successful than LSG in improving lipid panel parameters and HbA1c at 1 year, and it also seemed to offer better subjective improvement in obesity-related symptoms.

Conclusions: LGBP and LSG seem to confer comparable weight loss benefit in patients ≤21 years old with acceptable surgical morbidity.
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http://dx.doi.org/10.1007/s00464-016-4849-2DOI Listing
November 2016

Excess Weight Loss and Cardiometabolic Parameter Reduction Diminished among Hispanics Undergoing Bariatric Surgery: Outcomes in More than 2,000 Consecutive Hispanic Patients at a Single Institution.

J Am Coll Surg 2016 Feb 24;222(2):166-73. Epub 2015 Oct 24.

Montefiore Institute for Minimally Invasive Surgery, Montefiore Medical Center, New York, NY; Albert Einstein College of Medicine, Department of Surgery, New York, NY.

Background: Bariatric surgery has been established as the most effective long-term treatment for morbid obesity and obesity-related comorbidities. Despite its success, there is a paucity of data on the outcomes of bariatric surgery on Hispanic patients.

Study Design: We performed a retrospective review of obese patients treated at our institute between 2008 and 2014. We identified self-reported Hispanic patients who underwent a laparoscopic gastric bypass (LGBP), sleeve gastrectomy (LSG), or gastric band (LGB) procedure. The primary end point was excess weight loss (EWL) at 6, 12, 24, and 36 months. Secondary end points included improvement of obesity-related metabolic parameters at 1 year. We performed a repeated measures analysis of variance to calculate statistical significance throughout our study time period.

Results: We identified 2002 Hispanic patients who underwent bariatric surgery (1,235 LGBP, 600 LSG, 167 LGB) at our institute from 2008 to 2014. Follow-ups at 6, 12, 24, and 36 months were 62.2%, 54.5%, 36.2%, and 19.8%, respectively. Mean preoperative BMIs were 47.0 ± 7.2 kg/m2, 46.1 ± 7.8 kg/m2, and 44.9 ± 6.0 kg/m2 for the LGBP, LSG, and LGB cohorts, respectively. Excess weight loss was significantly more pronounced in the LGBP and the LSG groups than in the LGB group; this difference was accentuated over time (p < 0.0001). Obesity-related metabolic parameters and the need for comorbidity medical therapy decreased in all 3 surgical groups.

Conclusions: Bariatric surgery is highly successful in Hispanic obese patients. In the largest series to date, LGBP and LSG seem to yield more effective EWL and reduction of cardiometabolic parameters than LGB among Hispanics; however, outcomes are still markedly reduced when compared with those in non-Hispanic populations.
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http://dx.doi.org/10.1016/j.jamcollsurg.2015.10.009DOI Listing
February 2016

IFITMs from Mycobacteria Confer Resistance to Influenza Virus When Expressed in Human Cells.

Viruses 2015 Jun 12;7(6):3035-52. Epub 2015 Jun 12.

Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, the Ohio State University, Columbus, OH 43210, USA.

Interferon induced transmembrane proteins (IFITMs) found in vertebrates restrict infections by specific viruses. IFITM3 is known to be essential for restriction of influenza virus infections in both mice and humans. Vertebrate IFITMs are hypothesized to have derived from a horizontal gene transfer from bacteria to a primitive unicellular eukaryote. Since bacterial IFITMs share minimal amino acid identity with human IFITM3, we hypothesized that examination of bacterial IFITMs in human cells would provide insight into the essential characteristics necessary for antiviral activity of IFITMs. We examined IFITMs from Mycobacterium avium and Mycobacterium abscessus for potential antiviral activity. Both of these IFITMs conferred a moderate level of resistance to influenza virus in human cells, identifying them as functional homologues of IFITM3. Analysis of sequence elements shared by bacterial IFITMs and IFITM3 identified two hydrophobic domains, putative S-palmitoylation sites, and conserved phenylalanine residues associated with IFITM3 interactions, which are all necessary for IFITM3 antiviral activity. We observed that, like IFITM3, bacterial IFITMs were S-palmitoylated, albeit to a lesser degree. We also demonstrated the ability of a bacterial IFITM to co-immunoprecipitate with IFITM3 suggesting formation of a complex, and also visualized strong co-localization of bacterial IFITMs with IFITM3. However, the mycobacterial IFITMs lack the endocytic-targeting motif conserved in vertebrate IFITM3. As such, these bacterial proteins, when expressed alone, had diminished colocalization with cathepsin B-positive endolysosomal compartments that are the primary site of IFITM3-dependent influenza virus restriction. Though the precise evolutionary origin of vertebrate IFITMs is not known, our results support a model whereby transfer of a bacterial IFITM gene to eukaryotic cells may have provided a selective advantage against viral infection that was refined through the course of vertebrate evolution to include more robust signals for S-palmitoylation and localization to sites of endocytic virus trafficking.
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http://dx.doi.org/10.3390/v7062759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4488726PMC
June 2015

Outcomes of Laparoscopic Sleeve Gastrectomy and Roux-en-Y Gastric Bypass in Patients Older than 60.

Obes Surg 2015 Dec;25(12):2251-6

Montefiore Institute for Minimally Invasive Surgery, Montefiore Medical Center, 3400 Bainbridge Avenue, MAP 4, Bronx, NY, 104647, USA.

Background: The proportion of population older than 60 years is rapidly increasing. The majority of this older population suffers from multiple comorbid conditions including obesity. Non-surgical means of weight loss do not offer a predictable solution. Surgical interventions seem to be the most promising solution for the obesity problem, but there is a relative lack of data in literature regarding bariatric procedures in older populations.

Objectives: Our study aims to evaluate the safety and efficacy of bariatric surgery in patients older than 60 years of age, to determine the weight loss, rate of operation-related complications, and impacts of surgery on comorbid conditions, and to compare the effectiveness of bariatric surgery in older patients to the effectiveness of bariatric surgery for the general population at Montefiore Medical Center.

Methods: A retrospective review of patients' medical records were used to collect data to create databases to identify patients older than 60 years age who underwent bariatric surgery procedures spanning a 4-year period between January 2009 and October 2013. Data reviewed included age, sex, height, pre-operative weight, and body mass index (BMI), presence of obesity-related comorbid conditions, procedures performed, mortality, immediate or delayed complications, length of follow-up, excess weight lost, BMI points lost, percent of excess weight loss (%EWL), hemoglobin Alc (HgbA1c), and effects on obesity-related comorbid conditions. The percent of excess weight loss and number of complications within the older patient group were compared to the general population, which consists of patients between the ages of 22 and 59.

Results: Ninety-eight patients were identified. Seven patients did not follow up at any time period, and the eight patients who had laparoscopic adjustable gastric band (LAGB) were also excluded due to insufficient data. Overall, 83 patients who were above the age of 60 were examined; 30 patients had laparoscopic sleeve gastrectomy (LSG), and 53 patients underwent laparoscopic Roux-en-Y gastric bypass (LRYGB). The average patient age was 63.4 years, the average pre-operative weight was 122.3 kg, and the average excess body weight was 54.8 kg. The pre-existing comorbid conditions included 90.4 % hypertension (HTN), 63.9 % diabetes mellitus (DM), 50.6 % hyperlipidemia (HL), 34.9 % obstructive sleep apnea (OSA), and 30.1 % asthma. The average %EWL at 3 months, 6 months, and 12 months was 37.0, 51.3, and 65.2 %, respectively. A significant proportion of patients reported resolution or improvement in comorbid conditions. When results were compared to the general, population there was no significant difference in the number of complications that occurred within each of the two groups. The difference in %EWL at the 12-month follow-up was not statistically significant between the general population and the older patients, which suggests that both groups lost a similar amount of weight and that bariatric surgery on patients who are above the age of 60 is effective.

Conclusions: Bariatric surgery can be safe and effective for patients older than 60 years of age with a low morbidity and mortality; the weight loss and improvement in comorbidities in older patients were clinically significant. When compared to the general population, there was no statistically significant difference in the average %EWL at 12 months or the number of complications due to surgery. Long-term effects of such interventions will need further studies and investigations.
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http://dx.doi.org/10.1007/s11695-015-1712-9DOI Listing
December 2015

Biomarkers of NAFLD progression: a lipidomics approach to an epidemic.

J Lipid Res 2015 Mar 17;56(3):722-736. Epub 2015 Jan 17.

Pharmacology, Vanderbilt University Medical Center, Nashville, TN; Biochemistry, and the Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical Center, Nashville, TN. Electronic address:

The spectrum of nonalcoholic fatty liver disease (NAFLD) includes steatosis, nonalcoholic steatohepatitis (NASH), and cirrhosis. Recognition and timely diagnosis of these different stages, particularly NASH, is important for both potential reversibility and limitation of complications. Liver biopsy remains the clinical standard for definitive diagnosis. Diagnostic tools minimizing the need for invasive procedures or that add information to histologic data are important in novel management strategies for the growing epidemic of NAFLD. We describe an "omics" approach to detecting a reproducible signature of lipid metabolites, aqueous intracellular metabolites, SNPs, and mRNA transcripts in a double-blinded study of patients with different stages of NAFLD that involves profiling liver biopsies, plasma, and urine samples. Using linear discriminant analysis, a panel of 20 plasma metabolites that includes glycerophospholipids, sphingolipids, sterols, and various aqueous small molecular weight components involved in cellular metabolic pathways, can be used to differentiate between NASH and steatosis. This identification of differential biomolecular signatures has the potential to improve clinical diagnosis and facilitate therapeutic intervention of NAFLD.
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http://dx.doi.org/10.1194/jlr.P056002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4340319PMC
March 2015

2014 SSAT State-of-the-Art Conference: advances in diagnosis and management of gastroesophageal reflux disease.

J Gastrointest Surg 2015 Mar 18;19(3):458-66. Epub 2014 Dec 18.

Division of General and Gastrointestinal Surgery, The Ohio State University Medical Center, N729 Doan Hall, 410 W. 10th Avenue, Columbus, OH, 43210, USA,

Gastroesophageal reflux disease affects at least 10 % of people in Western societies and produces troublesome symptoms and impairs patients' quality of life. The effective management of GERD is imperative as the diagnosis places a significant cost burden on the United States healthcare system with annual direct cost estimates exceeding 9 billion dollars annually. While effective for many patients, 30-40 % of patients receiving medical therapy with proton pump inhibitors experience troublesome breakthrough symptoms, and recent evidence suggests that this therapy subjects patients to increased risk of complications. Given the high cost of PPI therapy, patients are showing a decrease in willingness to continue with a therapy that provides incomplete relief; however, due to inconsistent outcomes and concern for procedure-related side effects following surgery, only 1 % of the GERD population undergoes anti-reflux surgery annually. The discrepancy between the number of patients who experience suboptimal medical treatment and the number considered for anti-reflux surgery indicates a large therapeutic gap in the management of GERD. The objective of the SSAT State-of-the-Art Conference was to examine technologic advances in the diagnosis and treatment of GERD and to evaluate the ways in which we assess the outcomes of these therapies to provide optimal patient care.
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http://dx.doi.org/10.1007/s11605-014-2724-9DOI Listing
March 2015

Endoscopic mucosal resection for staging and treatment of early esophageal carcinoma: a single institution experience.

Surg Endosc 2015 Aug 4;29(8):2121-5. Epub 2014 Dec 4.

Division of General and Gastrointestinal Surgery, The Ohio State University, Columbus, OH, 43210, USA,

Background: Endoscopic mucosal resection (EMR) has emerged for evaluation and treatment of esophageal nodules. We report our initial experience with EMR for T staging and management of early esophageal cancer.

Methods: We reviewed patients undergoing EMR for esophageal adenocarcinoma between 2008 and 2013. The primary outcome measure was needed for esophagectomy. Secondary outcomes included complete eradication of adenocarcinoma, recurrence or persistence of cancer, nodal status for those undergoing esophagectomy, and complications of endoscopic treatment.

Results: During the study period, 24 patients underwent EMR demonstrating carcinoma, and a grossly margin negative endoscopic resection was achieved in all cases. Ten patients (42 %) had evidence of submucosal invasion and were referred for esophagectomy. Patients with margin negative EMR (n = 10, 42 %) or positive radial margins (n = 4, 16 %) underwent endoscopic surveillance and treatment with radiofrequency ablation or repeat EMR as needed. Thirteen patients (93 %) with intramucosal cancer (IMC) have been successfully managed with ongoing endoscopic surveillance and treatment with a median follow-up of 15.5 months. One patient underwent esophagectomy due to recurrent IMC in the setting of long-segment multifocal high-grade dysplasia. There were no esophageal perforations, one patient developed a self-limited gastrointestinal hemorrhage following EMR, and one had an esophageal stricture following endoscopic management.

Conclusions: IMC can be successfully managed endoscopically and thus esophagectomy is avoided in a significant proportion of patients. Endoscopic management may be utilized in the setting of complete resection or radial margin involvement without evidence of submucosal invasion. Close endoscopic follow-up is of paramount importance even in those with negative margins, because recurrent disease may occur following EMR in these patients.
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http://dx.doi.org/10.1007/s00464-014-3962-3DOI Listing
August 2015

Efficacy of transoral fundoplication vs omeprazole for treatment of regurgitation in a randomized controlled trial.

Gastroenterology 2015 Feb 13;148(2):324-333.e5. Epub 2014 Oct 13.

Department of Surgery, Oregon Health & Science University, Portland, Oregon.

Background & Aims: Transoral esophagogastric fundoplication (TF) can decrease or eliminate features of gastroesophageal reflux disease (GERD) in some patients whose symptoms persist despite proton pump inhibitor (PPI) therapy. We performed a prospective, sham-controlled trial to determine if TF reduced troublesome regurgitation to a greater extent than PPIs in patients with GERD.

Methods: We screened 696 patients with troublesome regurgitation despite daily PPI use with 3 validated GERD-specific symptom scales, on and off PPIs. Those with at least troublesome regurgitation (based on the Montreal definition) on PPIs underwent barium swallow, esophagogastroduodenoscopy, 48-hour esophageal pH monitoring (off PPIs), and high-resolution esophageal manometry analyses. Patients with GERD and hiatal hernias ≤2 cm were randomly assigned to groups that underwent TF and then received 6 months of placebo (n = 87), or sham surgery and 6 months of once- or twice-daily omeprazole (controls, n = 42). Patients were blinded to therapy during follow-up period and reassessed at 2, 12, and 26 weeks. At 6 months, patients underwent 48-hour esophageal pH monitoring and esophagogastroduodenoscopy.

Results: By intention-to-treat analysis, TF eliminated troublesome regurgitation in a larger proportion of patients (67%) than PPIs (45%) (P = .023). A larger proportion of controls had no response at 3 months (36%) than subjects that received TF (11%; P = .004). Control of esophageal pH improved after TF (mean 9.3% before and 6.3% after; P < .001), but not after sham surgery (mean 8.6% before and 8.9% after). Subjects from both groups who completed the protocol had similar reductions in GERD symptom scores. Severe complications were rare (3 subjects receiving TF and 1 receiving the sham surgery).

Conclusions: TF was an effective treatment for patients with GERD symptoms, particularly in those with persistent regurgitation despite PPI therapy, based on evaluation 6 months after the procedure. Clinicaltrials.gov no: NCT01136980.
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http://dx.doi.org/10.1053/j.gastro.2014.10.009DOI Listing
February 2015

Long-term cost-effectiveness of medical, endoscopic and surgical management of gastroesophageal reflux disease.

Surgery 2015 Jan 26;157(1):126-36. Epub 2014 Sep 26.

Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH.

Background: The long-term cost effectiveness of medical, endoscopic, and operative treatments for adults with gastroesophageal reflux disease (GERD) remains unclear. We sought to estimate the cost effectiveness of medical, endoscopic, and operative treatments for adults with GERD who require daily proton pump inhibitor (PPI) therapy.

Methods: A Markov model was generated from the payer's perspective using a 6-month cycle and 30-year time horizon. The base-case patient was a 45-year-old man with symptomatic GERD taking 20 mg of omeprazole twice daily. Four treatment strategies were analyzed: PPI therapy, transoral incisionless fundoplication (EsophyX), radiofrequency energy application to the lower esophageal sphincter (Stretta) and laparoscopic Nissen fundoplication. The model parameters were selected using the published literature and institutional billing data. The main outcome measure was the incremental cost-effectiveness ratio (cost per quality-adjusted life-year gained) for each therapy.

Results: In the base case analysis, which assumed a PPI cost of $234 over 6 months ($39 per month), Stretta and laparoscopic Nissen fundoplication were the most cost-effective options over a 30-year time period ($2,470.66 and $5,579.28 per QALY gained, respectively). If the cost of PPI therapy exceeded $90.63 per month over 30 years, laparoscopic Nissen fundoplication became the dominant treatment option. EsophyX was dominated by laparoscopic Nissen fundoplication at all points in time.

Conclusion: Low-cost PPIs, Stretta, and laparoscopic Nissen fundoplication all represent cost-effective treatment strategies. In this model, when PPIs exceed $90 per month, medical therapy is no longer cost effective. Procedural GERD therapy should be considered for patients who require high-dose or expensive PPIs.
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http://dx.doi.org/10.1016/j.surg.2014.05.027DOI Listing
January 2015

Near-infrared fluorescent cholangiography facilitates identification of biliary anatomy during laparoscopic cholecystectomy.

Surg Endosc 2015 Feb 2;29(2):368-75. Epub 2014 Jul 2.

Division of General and Gastrointestinal Surgery, Center for Minimally Invasive Surgery, The Ohio State University Wexner Medical Center, 558 Doan Hall, 410 West 10th Avenue, Columbus, OH, 43210, USA.

Background: Intraoperative cholangiography (IOC) is the current gold standard for biliary imaging during laparoscopic cholecystectomy (LC). However, utilization of IOC remains low. Near-infrared fluorescence cholangiography (NIRF-C) is a novel, noninvasive method for real-time, intraoperative biliary mapping. Our aims were to assess the safety and efficacy of NIRF-C for identification of biliary anatomy during LC.

Methods: Patients were administered indocyanine green (ICG) prior to surgery. NIRF-C was used to identify extrahepatic biliary structures before and after partial and complete dissection of Calot's triangle. Routine IOC was performed in each case. Identification of biliary structures using NIRF-C and IOC, and time required to complete each procedure were collected.

Results: Eighty-two patients underwent elective LC with NIRF-C and IOC. Mean age and body mass index (BMI) were 42.6 ± 13.7 years and 31.5 ± 8.2 kg/m(2), respectively. ICG was administered 73.8 ± 26.4 min prior to incision. NIRF-C was significantly faster than IOC (1.9 ± 1.7 vs. 11.8 ± 5.3 min, p < 0.001). IOC was unobtainable in 20 (24.4 %) patients while NIRF-C did not visualize biliary structures in 4 (4.9 %) patients. After complete dissection, the rates of visualization of the cystic duct, common bile duct, and common hepatic duct using NIRF-C were 95.1, 76.8, and 69.5 %, respectively, compared to 72.0, 75.6, and 74.3 % for IOC. In 20 patients where IOC could not be obtained, NIRF-C successfully identified biliary structures in 80 % of the cases. Higher BMI was not a deterrent to visualization of anatomy with NIRF-C. No adverse events were observed with NIRF-C.

Conclusions: NIRF-C is a safe and effective alternative to IOC for imaging extrahepatic biliary structures during LC. This technique should be evaluated further under a variety of acute and chronic gallbladder inflammatory conditions to determine its usefulness in biliary ductal identification.
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http://dx.doi.org/10.1007/s00464-014-3677-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4415528PMC
February 2015

Efficacy and durability of robotic Heller myotomy for achalasia: patient symptoms and satisfaction at long-term follow-up.

Surg Endosc 2014 Nov 31;28(11):3162-7. Epub 2014 May 31.

Center for Minimally Invasive Surgery, The Ohio State University Wexner Medical Center, 410 W. 10th Avenue, N729 Doan Hall, Columbus, OH, 43210, USA,

Background: Laparoscopic Heller myotomy (LHM) has become the standard treatment for achalasia in the USA. Robot-assisted Heller myotomy (RHM) has emerged as an alternative approach due to improved visualization and fine motor control, but long-term follow-up studies have not been reported. We sought to report the long-term outcomes of RHM and compare them to those of LHM.

Methods: A retrospective cohort study was performed for patients who underwent laparoscopic or RHM between 1995 and 2006. Long-term follow-up was performed via mail or telephone questionnaire. The primary outcome measure was durable relief of dysphagia without need for further intervention. Secondary outcomes included gastroesophageal reflux symptoms, disease-specific quality of life, and patient satisfaction with their operation.

Results: Seventy-five patients underwent laparoscopic (n = 19) or robotic (n = 56) myotomy during the study period. Long-term follow-up was obtained in 53 (71 %) patients with a median interval of 9 years. RHM was associated with a decreased mucosal injury rate (0 vs. 16 %, p = 0.01) and median hospital stay (1 vs. 2 days, p < 0.01) compared to conventional laparoscopy. All patients reported initial dysphagia relief, and 80 % required no further intervention. This did not differ between groups. Sixty-two percent required medications to control reflux symptoms at long-term follow-up, including 56 % following robotic myotomy and 80 % after laparoscopic myotomy (p = 0.27). Overall, 95 % of patients were satisfied with their operation, and 91 % would choose surgery again given the benefit of hindsight.

Conclusion: There is a dearth of long-term follow-up data to support the effectiveness of RHM. This study demonstrates durable dysphagia relief in the vast majority of patients with a high degree of patient satisfaction and a low rate of esophageal mucosal injury. While a significant proportion of patients report reflux symptoms, these symptoms are well controlled with medical acid suppression.
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http://dx.doi.org/10.1007/s00464-014-3576-9DOI Listing
November 2014

Robotic-assisted Roux-en-Y gastric bypass in a patient with situs inversus.

J Robot Surg 2014 Jun 18;8(2):169-71. Epub 2013 Apr 18.

Department of General Surgery, Vanderbilt University, 1161 21st Ave S, CCC-4312 MCN, Nashville, TN, 37232-2730, USA.

We report the case of a morbidly obese patient with situs inversus who presented for robotic-assisted Roux-en-Y gastric bypass. To do the procedure, the ports were reversed and the first assistant stood on the opposite side of the table. With these minor modifications to technique, the surgery was successfully performed without confusion over the patient's anatomy. There were no intraoperative complications. The patient's postoperative course was uneventful and he was discharged on postoperative day 3. We believe this is the first reported robotic-assisted Roux-en-Y gastric bypass in a patient with situs inversus.
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http://dx.doi.org/10.1007/s11701-013-0402-7DOI Listing
June 2014

Laparoscopic Roux-en-Y gastric bypass for treatment of symptomatic paraesophageal hernia in the morbidly obese: medium-term results.

Surg Obes Relat Dis 2014 Nov-Dec;10(6):1063-7. Epub 2014 Feb 10.

Center for Minimally Invasive Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio. Electronic address:

Background: The ideal surgical approach for treatment of symptomatic paraesophageal hernias (PEH) in obese patients remains elusive. The objective of this study was to assess the safety, feasibility, and effectiveness of combined laparoscopic PEH repair and Roux-en-Y gastric bypass (RYGB) for the management of symptomatic PEH in morbidly obese patients.

Methods: Fourteen patients with symptomatic PEH and morbid obesity (body mass index [BMI]>35 kg/m(2)) underwent laparoscopic PEH repair with RYGB between 2008 and 2011. Demographic characteristics and preoperative and perioperative details were analyzed. Patients were contacted in October 2013 for follow-up. BMI, reflux symptoms, and disease-specific quality of life (QoL) data were obtained.

Results: There were 11 females (79%). Median age and preoperative BMI were 48 years and 42 kg/m(2), respectively. Mean operative time was 180 minutes, with median length-of-stay of 4 days. There were no perioperative deaths, and 5 patients experienced postoperative complications including 1 gastrojejunostomy leak. Complete follow-up with a median follow-up interval of 35 months was available in 9 (64%) patients. The median % excess weight loss was 67.9%. Thirty-three percent required antisecretory medications for reflux control, compared to 89% preoperatively. Seventy-eight percent of patients reported good to excellent QoL outcomes assessed by the Gastroesophageal Reflux Disease Health-Related Quality of Life questionnaire. Overall, 89% of patients were satisfied with their operation and would undergo the procedure again.

Conclusion: Combined laparoscopic PEH repair and RYGB is a safe, feasible, and effective treatment option for morbidly obese patients with symptomatic PEH, and offers good to excellent disease-specific quality-of-life outcomes at medium-term follow-up. To date, this is the largest series with the longest follow-up in this unique patient population.
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http://dx.doi.org/10.1016/j.soard.2014.02.004DOI Listing
September 2015

Early weight regain after gastric bypass does not affect insulin sensitivity but is associated with elevated ghrelin.

Obesity (Silver Spring) 2014 Jul 29;22(7):1617-22. Epub 2014 Apr 29.

Department of Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee.

Objectives: We sought to determine: (1) if early weight regain between 1 and 2 years after Roux-en-Y gastric bypass (RYGB) is associated with worsened hepatic and peripheral insulin sensitivity, and (2) if preoperative levels of ghrelin and leptin are associated with early weight regain after RYGB.

Methods: Hepatic and peripheral insulin sensitivity and ghrelin and leptin plasma levels were assessed longitudinally in 45 subjects before RYGB and at 1 month, 6 months, 1 year, and 2 years postoperatively. Weight regain was defined as ≥5% increase in body weight between 1 and 2 years after RYGB.

Results: Weight regain occurred in 33% of subjects, with an average increase in body weight of 10 ± 5% (8.5 ± 3.3 kg). Weight regain was not associated with worsening of peripheral or hepatic insulin sensitivity. Subjects with weight regain after RYGB had higher preoperative and postoperative levels of ghrelin compared to those who maintained or lost weight during this time. Conversely, the trajectories of leptin levels corresponded with the trajectories of fat mass in both groups.

Conclusions: Early weight regain after RYGB is not associated with a reversal of improvements in insulin sensitivity. Higher preoperative ghrelin levels might identify patients that are more susceptible to weight regain after RYGB.
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http://dx.doi.org/10.1002/oby.20776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4077938PMC
July 2014

Why fundamentals of endoscopic surgery (FES)?

Surg Endosc 2014 Mar 7;28(3):701-3. Epub 2013 Dec 7.

Section of Minimally Invasive Surgery, Department of Surgery, The Wexner Medical Center, The Ohio State University, N708 Doan Hall, 410 West Tenth Avenue, Columbus, OH, 43210, USA,

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http://dx.doi.org/10.1007/s00464-013-3299-3DOI Listing
March 2014

Gastrectomy in advanced gastric cancer effectively palliates symptoms and may improve survival in select patients.

J Gastrointest Surg 2014 Mar;18(3):491-6

Background: The role of gastrectomy in the face of incurable gastric cancer is evolving. We sought to evaluate our experience with incomplete (i.e., R2) gastrectomy in advanced gastric cancer.

Methods: We reviewed 210 locally advanced or metastatic gastric cancers (1992-2008). Patient characteristics and outcomes were compared between three groups: gastrectomy (N = 99), exploration without resection (N = 66), and no surgery (N = 45).

Results: Clinicopathologic characteristics were similar between groups. Symptoms successfully resolved after gastrectomy in 48 % with a complication rate of 32 % and mortality of 6 %. Overall median survival for all patients was 6.2 months: 10.0 months after gastrectomy, 4.1 months after exploration without resection, and 5.3 months for no surgery (p < 0.001). Perioperative complications were the only predictor of symptom resolution following resection (OR = 0.175). Resolution of symptoms (p < 0.001, Hazards Ratio (HR) = 0.09) and preoperative nausea/vomiting (p = 0.017, HR = 0.55) improved survival, while linitis plastica (p = 0.035, HR = 4.05) and spindle cell morphology (p = 0.011, HR = 1.98) were predictors of poor survival in patients undergoing resection.

Conclusions: Gastrectomy in the setting of advanced gastric cancer may be useful in up to half of patients with an acceptable perioperative mortality rate. Symptom resolution offers a potential survival advantage but is dependent upon a complication-free course, so should only be considered selectively.
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http://dx.doi.org/10.1007/s11605-013-2415-yDOI Listing
March 2014

Endoscopic management of high-grade dysplasia and intramucosal carcinoma: experience in a large academic medical center.

Surg Endosc 2014 Mar;28(3):777-82

Background: Esophagectomy has been the standard treatment for Barrett's esophagus (BE) with high-grade dysplasia (HGD) and intramucosal cancer (IMC). Recently, endoscopic mucosal resection (EMR) and radiofrequency ablation (RFA) have become the preferred treatment for these patients in some centers. We report a single institution series of patients undergoing endoscopic management of HGD and IMC.

Methods: Nineteen patients underwent endoscopic treatment for HGD or IMC between 2009 and 2012. The primary outcome measure was progression of BE necessitating esophagectomy. Secondary outcomes included complete eradication of intestinal metaplasia (CE-IM), complete eradication of dysplasia (CE-D), recurrence or progression of BE or dysplasia, and complications. Patients were followed for a median follow-up interval of 19 months following completion of RFA treatment.

Results: Three patients (16 %) had a presenting diagnosis of IMC, and 16 (84 %) were treated for HGD. Twelve (63 %) had long-segment BE; the median length of BE was 5 cm. Ten (53 %) patients underwent EMR prior to RFA. CE-D was achieved in 88 % of patients, and CE-IM was achieved in 65 % of patients. A median of 2 (1-7) treatments were required, and there were no immediate post-procedure complications. Two patients developed recurrent dysplasia following complete eradication of BE, and each case was successfully managed with repeat RFA. Three patients (16 %) required esophagectomy within 6 months following RFA. A complete surgical resection was achieved in each case, and none of the patients developed lymph node metastases.

Conclusions: Complete eradication of HGD and IMC can be achieved via endoscopic therapy, thus avoiding esophagectomy in the majority of patients. However, a subset of patients will fail this treatment approach and will require surgical resection. With aggressive endoscopic treatment and surveillance, these patients can be identified at an early stage while curative resection is still possible.
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http://dx.doi.org/10.1007/s00464-013-3240-9DOI Listing
March 2014