Medicine and Health Sciences Commons^™

Mutational Profiles Reveal An Aberrant Tgf-Β-Cea Regulated Pathway In Colon Adenomas., Jian Chen, Gottumukkala S Raju, Wilma Jogunoori, Shoujun Gu, Lopa Mishra, + 27 More

Surgery Faculty Publications

Mutational processes and signatures that drive early tumorigenesis are centrally important for early cancer prevention. Yet, to date, biomarkers and risk factors for polyps (adenomas) that inordinately and rapidly develop into colon cancer remain poorly defined. Here, we describe surprisingly high mutational profiles through whole-genome sequence (WGS) analysis in 2 of 4 pairs of benign colorectal adenoma tissue samples. Unsupervised hierarchical clustered transcriptomic analysis of a further 7 pairs of adenomas reveals distinct mutational signatures regardless of adenoma size. Transitional single nucleotide substitutions of C:G>T:A predominate in the adenoma mutational spectrum. Strikingly, we observe mutations in the TGF-β pathway …

Vitamin D Deficiency Promotes Liver Tumor Growth In Transforming Growth Factor-Β/Smad3-Deficient Mice Through Wnt And Toll-Like Receptor 7 Pathway Modulation., Jian Chen, Lior H Katz, Nina M Muñoz, Shoujun Gu, Ji-Hyun Shin, Lopa Mishra, +13 Additional Authors

Surgery Faculty Publications

Disruption of the TGF-β pathway is associated with liver fibrosis and suppression of liver tumorigenesis, conditions associated with low Vitamin D (VD) levels. However, potential contributions of VD to liver tumor progression in the context of TGF-β signaling remain unexplored. Our analyses of VD deprivation (VDD) in in vivo models of liver tumor formation revealed striking three-fold increases in tumor burden in Smad3(+/-) mice, with a three-fold increase in TLR7 expression compared to controls. ChIP and transcriptional assays confirm Smad3 binding at two TLR7 promoter SBE sites. Molecular interactions between TGF-β pathway and VDD were validated clinically, where an absence …

Transoral Fundoplication Offers Durable Symptom Control For Chronic Gerd: 3-Year Report From The Tempo Randomized Trial With A Crossover Arm, Karim S. Trad, Mark Fox, Gilbert Simoni, Ahmad Shughoury, Peter Mavrelis, Mamoon Raza, Jeffrey Heise, William Barnes

Surgery Faculty Publications

Background

Four randomized controlled trials have demonstrated the short-term efficacy and safety of transoral esophagogastric fundoplication (TF) performed with the EsophyX® device in eliminating troublesome gastroesophageal reflux disease (GERD) symptoms in well-selected patient populations. The aim of this study was to assess the durability of these outcomes at 3 years post-procedure.

Methods

The TF EsophyX versus Medical PPI Open Label trial was conducted in seven US sites. Between June and August 2012, we enrolled patients with small (<2 cm) or absent hiatal hernias who suffered from troublesome GERD symptoms while on PPI therapy for at least 6 months and had abnormal esophageal acid exposure (EAE). Randomization was to TF group (n = 40) or to PPI group (n = 23). Following evaluation at 6 months, all remaining PPI patients (n …

Adult Gli2+/-;Gli3Δ699/+ Male And Female Mice Display A Spectrum Of Genital Malformation., Fei He, Pedram Akbari, Rong Mo, Jennifer J Zhang, Chi-Chung Hui, Peter C. Kim, Walid A Farhat

Surgery Faculty Publications

Disorders of sexual development (DSD) encompass a broad spectrum of urogenital malformations and are amongst the most common congenital birth defects. Although key genetic factors such as the hedgehog (Hh) family have been identified, a unifying postnatally viable model displaying the spectrum of male and female urogenital malformations has not yet been reported. Since human cases are diagnosed and treated at various stages postnatally, equivalent mouse models enabling analysis at similar stages are of significant interest. Additionally, all non-Hh based genetic models investigating DSD display normal females, leaving female urogenital development largely unknown. Here, we generated compound mutant mice, Gli2+/-;Gli3Δ699/+, …

Two Cases Of Monoclonal Nodular Pulmonary Amyloidosis And Review Of The Literature, Kendal Endicott, Conor Hynes, Cindy M. Hsieh, Edina Paal, Gregory D. Trachiotis

Surgery Faculty Publications

Nodular pulmonary amyloidosis (NPA) is an uncommon pathology of insoluble protein depositing in pulmonary parenchyma. This localized pulmonary form of amyloidosis is most often found to contain combinations of kappa and lambda immunoglobulin light chain and immunoglobulin heavy chain proteins with a polyclonal lymphoplasmacystic infiltrate. Herein we present two cases of NPA of the rarely reported monoclonal (light-chain restricted) form with review of the literature and discussion of the clinical, radiographic, and histologic features of NPA.

Surgeon's Guide To Anticoagulant And Antiplatelet Medications Part Two: Antiplatelet Agents And Perioperative Management Of Long-Term Anticoagulation., Louise Y Y Yeung, Babak Sarani, Jordan A Weinberg, Paul B Mcbeth, Addison K May

Surgery Faculty Publications

An increasing number of potent antiplatelet and anticoagulant medications are being used for the long-term management of cardiac, cerebrovascular, and peripheral vascular conditions. Management of these medications in the perioperative and peri-injury settings can be challenging for surgeons, mandating an understanding of these agents and the risks and benefits of various management strategies. In this two part review, agents commonly encountered by surgeons in the perioperative and peri-injury settings are discussed and management strategies for patients on long-term antiplatelet and anticoagulant therapy reviewed. In part one, we review warfarin and the new direct oral anticoagulants. In part two, we review …

High Incidence Of Fracture Events In Patients With Long-Gap Esophageal Atresia (Lgea): A Retrospective Review Prompting Implementation Of Standardized Protocol., Sigrid Bairdain, Brenda Dodson, David Zurakowski, Lawrence Rhein, Brian D Snyder, Melissa Putman, Russell W Jennings

Surgery Faculty Publications

PURPOSE: To identify factors associated with an increased risk of fractures in Long-Gap Esophageal Atresia (LGEA) patients. Following implementation of a risk-stratified program, we hypothesized a reduction in fracture incidence within this potentially high-risk population.

METHODS: A retrospective review of LGEA-patients admitted between 2005 and 2014 was conducted. Symptomatic fractures with radiographic confirmation were defined as events. Univariate and multivariable analysis evaluated factors including admission weight-for-age z-score, primary versus secondary Foker process (FP), weight at Foker Stage I, days and episodes of paralysis, number of parenteral nutrition (PN) days, cumulative dose of loop diuretics adjusted for body weight and days …

Combination Of Id2 Knockdown Whole Tumor Cells And Checkpoint Blockade: A Potent Vaccine Strategy In A Mouse Neuroblastoma Model., Lina Chakrabarti, Clifford Morgan, Anthony D. Sandler

Surgery Faculty Publications

Tumor vaccines have held much promise, but to date have demonstrated little clinical success. This lack of success is conceivably due to poor tumor antigen presentation combined with immuno-suppressive mechanisms exploited by the tumor itself. Knock down of Inhibitor of differentiation protein 2 (Id2-kd) in mouse neuroblastoma whole tumor cells rendered these cells immunogenic. Id2-kd neuroblastoma (Neuro2a) cells (Id2-kd N2a) failed to grow in most immune competent mice and these mice subsequently developed immunity against further wild-type Neuro2a tumor cell challenge. Id2-kd N2a cells grew aggressively in immune-compromised hosts, thereby establishing the immunogenicity of these cells. Therapeutic vaccination with Id2-kd …

A Case Of Pediatric Melanoma: Treatment Considerations In Advanced Disease., Frank P Albino, Benjamin C. Wood, Albert Oh, Gary F Rogers, Tina Sauerhammer

Surgery Faculty Publications

We document a 3-year-old healthy African American girl who developed malignant melanoma on her lower extremity. The clinical appearance offered little indication of the lesion’s severity (T4), and only the history of de novo presentation and disproportionate growth raised clinical suspicion. This case report highlights the subtle clinical findings of this condition and presents controversies related to surgical management of pediatric melanoma.

Maternal Analgosedation And Breastfeeding: Guidance For The Pediatrician, Karel Allegaert, Johannes N. Van Den Anker

Surgery Faculty Publications

As part of analgosedative treatment modalities after delivery (e.g. caesarean related pain, birth related trauma, pre-existing pain syndromes), mothers are treated with different analgosedatives that may also affect the nursing infant. This review aims to summarize the available knowledge on commonly prescribed analgosedatives (opioids, intravenous and inhalational anesthetics, benzodiazepines, non-opioid analgesics, and local anesthetics) during breastfeeding.

We propose that the use of systemic non-opioid analgesics, local anesthetics, inhalational or intravenous anesthetics is safe when mothers are nursing. When systemic opioids are used, we recommend pediatricians to consider clinical monitoring of the infant for sedation. The duration of maternal exposure ( …

Needle Loss In Subclavian Vein During Central Venous Catheter Placement: Case Report Of A Rare Complication, Daniela Botolin, Annie Mooser, Duane Stillions, Keith Mortman, Shawn N. Sarin, Joseph C. Babrowicz

Surgery Faculty Publications

We present a case of needle separation during central venous catheter (CVC) placement in a super morbidly obese patient with subsequent surgical intervention in its retrieval. This complication, potentially lethal due to the relevant anatomy of such a procedure, alerts critical care physicians and surgeons to the possibility of equipment failure and stresses proper technique in what has become a routine procedure. It also emphasizes the routine use of ultrasound-guidance for cannulation in patients of any body habitus. While infection and arrhythmia are the generally known complications of CVC placement, clinicians must be alert to unanticipated events such as needle …

Efficacy Of Transoral Fundoplication Vs Omeprazole For Treatment Of Regurgitation In A Randomized Controlled Trial., John G. Hunter, Peter J. Kahrilas, Reginald C.W. Bell, Erik B. Wilson, Karim S. Trad, James P. Dolan, Kyle A. Perry, Brant K. Oelschlager, Nathaniel J. Soper, Brad E. Snyder, Miguel A. Burch, William Scott Melvin, Kevin M. Reavis, Daniel G. Turgeon, Eric S. Hungness, Brian S. Diggs

Surgery Faculty Publications

Background

The aim of this randomized, crossover study was to determine if transoral fundoplication (TF) could further improve clinical outcomes in partial responders to high-dose (HD) proton-pump inhibitor (PPI) therapy and to evaluate durability of TF.

Methods

In seven United States centers, patients with hiatal hernia ≤2 cm and abnormal esophageal acid exposure (EAE) were randomized to TF (n = 40) or HD PPIs (n = 23) group. At 6-month follow-up, PPI patients underwent crossover. We assessed clinical outcomes 6-month post TF in crossover patients (COP), as compared to 6-month of HD PPI therapy, and 12-month outcomes in patients initially …

Single Center Experience On Dosing And Adverse Events Of Recombinant Factor Seven Use For Bleeding After Congenital Heart Surgery, Mustafa Kurkluoglu, Alyson M. Engle, John P. Costello, Narutoshi Hibino, David Zurakowski, Richard A. Jonas, John T. Berger, Dilip S. Nath

Surgery Faculty Publications

There are limited data on the relationship between the administered dose of recombinant factor seven (rFVIIa) and the development of adverse clinical outcomes after congenital heart surgery. This single institution case series reports on dosing, adverse events, and blood product usage after the administration of rFVIIa in the congenital heart surgery patient population. A retrospective review identified 16 consecutive pediatric patients at an academic, free-standing, children’s hospital who received rFVIIa to curtail bleeding following congenital heart surgery between April 2004 and June 2012. Patients were assessed for survival to hospital discharge versus in-hospital mortality and the presence or absence of …

Pneumonectomy In A Patient With Swyer-James-Macleod Syndrome, Mariana Vignola Cruz, Gregory D. Trachiotis

Surgery Faculty Publications

Swyer-James-MacLeod syndrome is a rare disease that results in parenchymal damage believed to be caused by recurrent lung infections in childhood. We report a case of a previously healthy young woman that presented with insidious progression of exertional dyspnea with restrictive lung physiology. Axial imaging demonstrated a hyperinflated emphysematous right lung with lower lobe fibrosis, nodules and air-fluid filled cysts, with a small right pulmonary artery and contralateral shifting of the mediastinum. She underwent right pneumonectomy ultimately resulting in improvement of her symptoms, with surgical pathology indicating extensive emphysema, bronchiectasis, fibrosis with osseous metaplasia, and placental transmogrification of alveolar septa, …

A Single Center Experience With Coronary Endarterectomy And Vein Patch Reconstruction, C. F. Hynes, Gregory D. Trachiotis

Surgery Faculty Publications

Background: To evaluate the medium and late term outcomes of coronary artery bypass grafting with pull-through coronary endarterectomy using a saphenous vein patch for bypass distal anastomosis site.

Methods: Retrospective review of all coronary artery bypass graft (CABG) procedures performed from January 1, 2000 through June 30, 2013 with and without concomitant coronary endarterectomy (CE), was carried out at the Veterans Affairs Medical Center in Washington DC. Patients who underwent concomitant valve operations were excluded. Primary outcome was overall survival, with analyses performed examining CE as well as the use of cardiopulmonary bypass. Secondary outcomes included 30-day mortality and post-operative …

A Retrospective Study Of The Impact Of 21-Gene Recurrence Score Assay On Treatment Choice In Node Positive Micrometastatic Breast Cancer., Thomas G Frazier, Kevin R Fox, J Stanley Smith, Christine Laronga, Anita Mcswain, Devchand Paul, +10 More

Surgery Faculty Publications

To assess clinical utility of the 21-gene assay (Oncotype DX® Recurrence Score®), we determined whether women with HER2(−)/ER+ pN1mi breast cancer with low ( vs. 57.9% in the intermediate-risk group and 100% in the high-risk group (p < 0.001). A total of 80.2% of the low-risk group were recommended endocrine therapy alone, while 77.8% of the high-risk group were recommended both endocrine and chemotherapy (p < 0.001). The Oncotype DX Recurrence Score result provides actionable information that can be incorporated into treatment planning for women with HER2(−)/ER+ pN1mi breast cancer. The Recurrence Score result has clinical utility in treatment planning for HER2(−)/ER+ pN1mi breast cancer patients.

Efficacy Of Transoral Fundoplication For Treatment Of Chronic Gastroesophageal Reflux Disease Incompletely Controlled With High-Dose Proton-Pump Inhibitors Therapy: A Randomized, Multicenter, Open Label, Crossover Study., Karim S. Trad, Gilbert Simoni, William Edris Barnes, Ahmad Bassel Shughoury, Mamoon Raza, Jeffrey Alan Heise, Daniel Gilles Turgeon, Mark Alan Fox, Peter George Mavrelis

Surgery Faculty Publications

Background

The aim of this randomized, crossover study was to determine if transoral fundoplication (TF) could further improve clinical outcomes in partial responders to high-dose (HD) proton-pump inhibitor (PPI) therapy and to evaluate durability of TF.

Methods

In seven United States centers, patients with hiatal hernia ≤2 cm and abnormal esophageal acid exposure (EAE) were randomized to TF (n = 40) or HD PPIs (n = 23) group. At 6-month follow-up, PPI patients underwent crossover. We assessed clinical outcomes 6-month post TF in crossover patients (COP), as compared to 6-month of HD PPI therapy, and 12-month outcomes in patients initially …

Culture-Independent Evaluation Of The Appendix And Rectum Microbiomes In Children With And Without Appendicitis, Hope T. Jackson, Emmanuel F. Mongodin, Katherine P. Davenport, Claire M. Fraser, Anthony D. Sandler, Steven L. Zeichner

Surgery Faculty Publications

Purpose

The function of the appendix is largely unknown, but its microbiota likely contributes to function. Alterations in microbiota may contribute to appendicitis, but conventional culture studies have not yielded conclusive information. We conducted a pilot, culture-independent 16S rRNA-based microbiota study of paired appendix and rectal samples.

Methods

We collected appendix and rectal swabs from 21 children undergoing appendectomy, six with normal appendices and fifteen with appendicitis (nine perforated). After DNA extraction, we amplified and sequenced 16S rRNA genes and analyzed sequences using CLoVR. We identified organisms differing in relative abundance using ANOVA (p

Results

We identified 290 taxa in …

Bilateral Laparoscopic Partial Adrenalectomy: A Case Presentation And Review Of The Literature, Sean Satey, Nathan Richards, Frederick J. Brody

Surgery Faculty Publications

Laparoscopic adrenalectomy is the standard of care for benign adrenal diseases. Partial adrenalectomy has been performed for various tumors to preserve adrenal function while avoiding steroid supplements postoperatively. This article discusses a patient that underwent bilateral laparoscopic partial adrenalectomies for bilateral pheochromocytomas and reviews the literature on partial adrenalectomy. A 40-year-old woman with a recent diagnosis of hypertension and an emergent Caesarian section for pre-eclampsia presented to an outside clinic with labile blood pressure, diaphoresis, palpitations, and headache. Physical examination was unremarkable with no bruits appreciated in the neck or abdomen. Medical management of her hypertension was initiated with minimal …

Childhood Achalasia: A Comprehensive Review Of Disease, Diagnosis And Therapeutic Management, Ashanti L. Franklin, Mikael Petrosyan, Timothy D. Kane

Surgery Faculty Publications

Achalasia is an esophageal motility disorder characterized by failure of lower esophageal sphincter (LES) relaxation and is rare in children. The most common symptoms are vomiting, dysphagia, regurgitation, and weight loss. Definitive diagnosis is made with barium swallow study and esophageal manometry. In adults, endoscopic biopsy is recommended to exclude malignancy however; it is not as often indicated in children. Medical management often fails resulting in recurrent symptoms and the ultimate definitive treatment is surgical. Laparoscopic Heller myotomy with or without an anti-reflux procedure is the treatment of choice and has become standard of care for children with achalasia. Peroral …

Transoral Incisionless Fundoplication Effective In Eliminating Gerd Symptoms In Partial Responders To Proton Pump Inhibitor Therapy At 6 Months: The Tempo Randomized Clinical Trial, Karim S. Trad, William E. Barnes, Gilbert Simoni, Ahmad B. Shughoury, Peter G. Mavrelis, Mamoon Raza, Jeffrey Heise, Daniel G. Turgeon, Mark A. Fox

Surgery Faculty Publications

Background. Incomplete control of troublesome regurgitation and extraesophageal manifestations of chronic gastroesophageal reflux disease (GERD) is a known limitation of proton pump inhibitor (PPI) therapy. This multicenter randomized study compared the efficacy of transoral incisionless fundoplication (TIF) against PPIs in controlling these symptoms in patients with small hiatal hernias.

Methods. Between June and August 2012, 63 patients were randomized at 7 US community hospitals. Patients in the PPI group were placed on maximum standard dose (MSD). Patients in the TIF group underwent esophagogastric fundoplication using the EsophyX₂ device. Primary outcome was elimination of daily troublesome regurgitation or …

Ruptured Splenic Artery Aneurysms And The Use Of An Adapted Fast Protocol In Reproductive Age Women With Hemodynamic Collapse: Case Series, Hope T. Jackson, Silviu C. Diaconu, Patrick J. Maluso, Bruce Abell, Juliet Lee

Surgery Faculty Publications

Nontraumatic symptomatic hypotension in all patients requires prompt diagnosis and appropriate treatment for optimum outcome. The female population specifically has an expanded differential diagnosis that should be considered when these patients present with hemodynamic collapse. While the most common causes of hypotension in pregnant patients are dehydration, ruptured ectopic pregnancy, and placental and uterine abnormalities, less common nonobstetrical etiologies such as hepatic rupture and ruptured abdominal and visceral artery aneurysms should also be considered. Splenic artery aneurysms are associated with high rates of mortality and in cases of pregnancy, maternal and fetal mortality. These high rates can be attributed to …

Loss Of Nuclear Pten In Hcv-Infected Human Hepatocytes, Wenjie Bao, Liliana Florea, Ningbin Wu, Zhao Wang, Krishna K. Banaudha, Jason Qian, Laurent Houzet, Rakesh Kumar, Ajit Kumar

Surgery Faculty Publications

Background

Hepatitis C virus (HCV) infection is a major risk factor for chronic hepatitis and hepatocellular carcinoma (HCC); however, the mechanism of HCV-mediated hepatocarcinogenesis is not well understood. Insufficiency of PTEN tumor suppressor is associated with more aggressive cancers, including HCC. We asked whether viral non-coding RNA could initiate oncogenesis in HCV infected human hepatocytes. The results presented herein suggest that loss of nuclear PTEN in HCV-infected human hepatocytes results from depletion of Transportin-2, which is a direct target of viral non-coding RNA, vmr11.

Methods

The intracellular distribution of PTEN in HCV-infected cells was monitored by immunostaining and Western blots …

Hereditary Angioedema: What The Gastroenterologist Needs To Know, M. Aamir Ali, Marie L. Borum

Surgery Faculty Publications

Up to 93% of patients with hereditary angioedema (HAE) experience recurrent abdominal pain. Many of these patients, who often present to emergency departments, primary care physicians, general surgeons, or gastroenterologists, are misdiagnosed for years and undergo unnecessary testing and surgical procedures. Making the diagnosis of HAE can be challenging because symptoms and attack locations are often inconsistent from one episode to the next. Abdominal attacks are common and can occur without other attack locations. An early, accurate diagnosis is central to managing HAE. Unexplained abdominal pain, particularly when accompanied by swelling of the face and extremities, suggests the diagnosis of …

Experience With Miniaturized Cardiopulmonary Bypass In Cardiac Surgery: A Prospective Comparison Of The Novosci Ready System To Off-Pump And Conventional Coronary Artery Bypass Grafting, Dominic Emerson, Debbie Baldwin, Miguel Pinales, Michael Greenberg, Melissa Mattes, Gregory D. Trachiotis

Surgery Faculty Publications

The major source of morbidity following cardiopulmonary bypass (CPB) is the systemic inflammatory response (SIRS response) which leads to multiple derangements in different organ systems. To combat this, miniaturized cardiopulmonary bypass circuits (MCPBC) have been created to lessen the inflammatory response to CPB. Here we examine early outcomes following coronary artery bypass grafting (CABG) using a MCPBC system compared to conventional bypass techniques at a single institution. Methods: 60 consecutive patients undergoing elective CABG were prospectively enrolled. Nine patients underwent coronary artery bypass grafting (CABG) with conventional CPB (cCABG), 33 underwent off-pump CABG (OPCAB), and the remaining 18 patients underwent …

Rhinoscleroma Presenting As A Nasal-Palatal Mass With Airway Obstruction, Mark C. Domanski, Alexander Rivero, David E. Kardon

Surgery Faculty Publications

We report a case of a 45-year-old male with severe rhinoscleroma. The patient presented to the emergency room with dyspnea from a long-standing nasal-palatal mass. A tracheostomy was required for airway control. While dyspnea in the presence of an upper airway mass is typical of malignancy, consideration of non-oncological etiologies is important. We review the epidemiology, pathology, diagnosis, and treatment of rhinoscleroma.

Surgical Management Of Pediatric Gastroesophageal Reflux Disease, Hope T. Jackson, Timothy D. Kane

Surgery Faculty Publications

No abstract provided.

T-Cell Activation Is Enhanced By Targeting Il-10 Cytokine Production In Toll-Like Receptor-Stimulated Macrophages, Ryan Walk, Steven Elliott, Felix C. Blanco, Jason A. Snyder, Ashley M. Jacobi, Scott Rose, Mark Behlke, Aliasger Salem, Stanislav Vukmanovic, Anthony D. Sandler

Surgery Faculty Publications

Toll-like receptor (TLR) agonists represent potentially useful cancer vaccine adjuvants in their ability to stimulate antigen-presenting cells (APCs) and subsequently amplify the cytotoxic T-cell response. The purpose of this study was to characterize APC responses to TLR activation and to determine the subsequent effect on lymphocyte activation. We exposed murine primary bone marrow-derived macrophages to increasing concentrations of agonists to TLRs 2, 3, 4, and 9. This resulted in a dose-dependent increase in production of not only tumor necrosis factor–alpha (TNF-α), a surrogate marker of the proinflammatory response, but also interleukin 10 (IL-10), a well-described inhibitory cytokine. Importantly, IL-10 secretion …

Single-Port Laparoscopic Surgery In Children: Concept And Controversies Of The New Technique, Felix C. Blanco, Timothy D. Kane

Surgery Faculty Publications

Single-incision laparoscopic surgery (SILS) is emerging as an alternative technique to conventional laparoscopy for the treatment of common surgical diseases. Despite its wide use, the adoption of SILS in children has been slower since the broad application of minimally invasive techniques in children, in general, has historically lagged behind those in adults. This paper reviews the evolution of SILS from its original conception and its application in the field of pediatric surgery.