Surgery Commons^™

False Lumen Embolization As A Rescue Technique In The Setting Of Acute And Chronic Dissecting Aneurysms As Adjunct To Thoracic Endovascular Aortic Repair., Stephanie Rakestraw, Anthony Feghali, Tuong Nguyen, Dawn Salvatore, Paul Dimuzio, Babak Abai

Department of Surgery Faculty Papers

Complicated type B aortic dissection (TBAD) is a life-threatening condition requiring surgical intervention. One such complication in the acute or chronic setting is aneurysmal degeneration. The dissected aortic wall is weakened, and the pressures in the false lumen are often high. In the past decade, thoracic endovascular aortic repair (TEVAR) has become the treatment of choice for TBAD. TEVAR can be complicated by lack of false lumen thrombosis, increasing the risk of death. We present three cases of TBAD with patent false lumens after TEVAR that were treated by false lumen coil embolization.

A Step Towards Personalizing Next Line Therapy For Resected Pancreatic And Related Cancer Patients: A Single Institution's Experience, Cinthya Y. Lowder, Teena Dhir, Austin B. Goetz, Henry L. Thomsett, Joseph Bender, Talar Tatarian, Subha Madhavan, Emanuel F. Petricoin, Edik Blais, Harish Lavu, Jordan M. Winter, James Posey Iii, Jonathan Brody, Michael J. Pishvaian, Charles J. Yeo

Department of Surgery Faculty Papers

Background: There is a lack of precision medicine in pancreatic ductal adenocarcinoma (PDA) and related cancers, and outcomes for patients with this diagnosis remain poor despite decades of research investigating this disease. Therefore, it is necessary to explore novel therapeutic options for these patients who may benefit from personalized therapies.

Objective: Molecular profiling of hepatopancreaticobiliary malignancies at our institution, including but not limited to PDA, was initiated to assess the feasibility of incorporating molecular profiling results into patient oncological therapy planning.

Methods: All eligible patients from Thomas Jefferson University (TJU) with hepatopancreaticobiliary tumors including PDA, who agreed to molecular testing …

Ultra-Fast Conductive Media For Rna Electrophoretic Mobility Shift Assays., Samantha Z Brown, Lebaron C Agostini, Henry L Thomsett, Jonathan R Brody

Department of Surgery Faculty Papers

The use of RNA electrophoretic mobility shift assays (REMSAs) for analysis of RNA-protein interactions have been limited to lengthy assay time and qualitative assessment. To vastly improve assay efficiency, feasibility and quality of data procured from REMSAs, we combine here some of the best-known labeling and electrophoretic techniques. Nucleic acid fragments are end-labeled with fluorescent tags, as opposed to the radioactive or biotin tags. The fluorescent probes may be detected directly from the electrophoresis gel, eliminating the need for cumbersome membrane transfer and immunoblotting. Modifying the REMSA protocol to include low-molarity, lithium borate conductive media and near-infrared-labeled probes allows for …

Extended Prophylactic Antibiotics For Mastectomy With Immediate Breast Reconstruction: A Meta-Analysis, Yang Hai, Weelic Chong, Melissa Lazar

Department of Surgery Faculty Papers

Background: The risk of surgical site infection (SSI) for breast surgery in patients without additional risk factors is low, below 5%. Evidence shows the risk of SSI is significantly elevated in patients undergoing immediate breast reconstruction (IBR). However, there is no consensus regarding the use of extended antibiotic prophylaxis. We aim to determine the effect of extended antibiotic prophylaxis on the incidence of SSI after IBR.

Methods: PubMed and Scopus were searched by 2 independent reviewers. Data abstracted included types of study, basic characteristics, detailed antibiotic prophylaxis information, SSI event, and other secondary outcomes. We calculated the risk ratio (RR) …

Optimizing Cancer Cure Dialog: An Analysis Of Pancreatic Cancer Patients' Views Regarding Survival And Cure., Avinoam Nevler, Scott W. Keith, Harish Lavu, Theresa P. Yeo, Shawnna Cannaday, Charles J. Yeo, Jordan M. Winter

Department of Surgery Faculty Papers

BACKGROUND: Pancreatic ductal adenocarcinoma (PDA) is a highly lethal cancer. Clinicians commonly refer to surgical therapy as resection with curative intent. However, PDA cure rates after resection remain unknown and the definition of cure remains vague. We investigated how patients (the majority undergoing resection), family members, and clinicians understand the concept of cure, to better inform discussions with patients regarding PDA prognosis.

METHODS: In a prospective survey, cohorts were asked to indicate the best definition of cure from three choices: 5-year survival endpoint (typically used in the literature), a biological endpoint without biochemical or radiographic signs of disease (similar to …

False In Name Only-Gastroduodenal Artery Pseudoaneurysm In A Recurrently Bleeding Patient: Case Report And Literature Review., M. Binetti, A. Lauro, R. Golfieri, S Vaccari, V D'Andrea, I. R. Marino, M. Cervellera, M. Renzulli, V. Tonini

Department of Surgery Faculty Papers

INTRODUCTION: Although the diagnosis of visceral pseudoaneurysm is unusual, it requires emergent attention due to the risk of rupture. We describe a 70-year old man with a gastroduodenal artery (GDA) pseudoaneurysm manifest as recurrent hæmorrhage.

AREAS COVERED: We highlight the possible ætiologies, clinical presentations, diagnostic tools and treatment options for this condition. In this instance, the patient was successfully treated by selective angio-embolization.

EXPERT COMMENTARY: A visceral pseudoaneurysm should be considered in patients with abdominal pain and GI hæmorrhage. At present, angio-embolization is first-line therapy.

Ethical Standards For Cardiothoracic Surgeons' Participation In Social Media., Thomas K. Varghese, John W. Entwistle, John E. Mayer, Susan D. Moffatt-Bruce, Robert M. Sade

Department of Surgery Faculty Papers

No abstract provided.

Optimal Timing And Route Of Nutritional Support After Esophagectomy: A Review Of The Literature., Richard Zheng, Courtney L. Devin, Michael J. Pucci, Adam C. Berger, Ernest L. Rosato, Francesco Palazzo

Department of Surgery Faculty Papers

Some controversy surrounds the postoperative feeding regimen utilized in patients who undergo esophagectomy. Variation in practices during the perioperative period exists including the type of nutrition started, the delivery route, and its timing. Adequate nutrition is essential for this patient population as these patients often present with weight loss and have altered eating patterns after surgery, which can affect their ability to regain or maintain weight. Methods of feeding after an esophagectomy include total parenteral nutrition, nasoduodenal/nasojejunal tube feeding, jejunostomy tube feeding, and oral feeding. Recent evidence suggests that early oral feeding is associated with shorter LOS, faster return of …

Guidance Of Sentinel Lymph Node Biopsy Decisions In Patients With T1-T2 Melanoma Using Gene Expression Profiling., John T. Vetto, Eddy C. Hsueh, Brian R. Gastman, Larry D. Dillon, Federico A. Monzon, Robert W. Cook, Jennifer Keller, Xin Huang, Andrew Fleming, Preston Hewgley, Pedram Gerami, Sancy Leachman, Jeffrey D. Wayne, Adam C. Berger, Martin D. Fleming

Department of Surgery Faculty Papers

AIM: Can gene expression profiling be used to identify patients with T1-T2 melanoma at low risk for sentinel lymph node (SLN) positivity?

PATIENTS & METHODS: Bioinformatics modeling determined a population in which a 31-gene expression profile test predicted <5% SLN positivity. Multicenter, prospectively-tested (n = 1421) and retrospective (n = 690) cohorts were used for validation and outcomes, respectively.

RESULTS: Patients 55-64 years and ≥65 years with a class 1A (low-risk) profile had SLN positivity rates of 4.9% and 1.6%. Class 2B (high-risk) patients had SLN positivity rates of 30.8% and 11.9%. Melanoma-specific survival was 99.3% for patients ≥55 years with class 1A, T1-T2 tumors and 55.0% for class 2B, SLN-positive, T1-T2 tumors.

CONCLUSION: The 31-gene expression profile test identifies patients …

Nelfe-Dependent Myc Signature Identifies A Unique Cancer Subtype In Hepatocellular Carcinoma., Hien Dang, Yotsawat Pomyen, Sean P. Martin, Dana A. Dominguez, Sun Young Yim, Ju-Seog Lee, Anuradha Budhu, Ashesh P. Shah, Adam S. Bodzin, Xin Wei Wang

Department of Surgery Faculty Papers

The MYC oncogene is dysregulated in approximately 30% of liver cancer. In an effort to exploit MYC as a therapeutic target, including in hepatocellular carcinoma (HCC), strategies have been developed on the basis of MYC amplification or gene translocation. Due to the failure of these strategies to provide accurate diagnostics and prognostic value, we have developed a Negative Elongation Factor E (NELFE)-Dependent MYC Target (NDMT) gene signature. This signature, which consists of genes regulated by MYC and NELFE, an RNA binding protein that enhances MYC-induced hepatocarcinogenesis, is predictive of NELFE/MYC-driven tumors that would otherwise not be identified by gene amplification …

Who Is Pirating Medical Literature? A Bibliometric Review Of 28 Million Sci-Hub Downloads., Brian M. Till, Niclas Rudolfson, Saurabh Saluja, Jesudian Gnanaraj, Lubna Samad, David Ljungman, Mark Shrime

Department of Surgery Faculty Papers

We aimed to define the proportion of downloads on Sci-Hub that are medical in nature and to consider these data at the national level, evaluating the relation between density of medical literature downloads and scientific output, national income classifications, and indicators of internet penetrance.

Interpersonal Violence In Peacetime Malawi., Rebecca G. Maine, Brittney Williams, Jennifer A. Kincaid, Gift Mulima, Carlos Varela, Jared R. Gallaher, Trista D. Reid, Anthony G. Charles

Department of Surgery Faculty Papers

Background: The contribution of interpersonal violence (IPV) to trauma burden varies greatly by region. The high rates of IPV in sub-Saharan Africa are thought to relate in part to the high rates of collective violence. Malawi, a country with no history of internal collective violence, provides an excellent setting to evaluate whether collective violence drives the high rates of IPV in this region.

Methods: This is a retrospective review of a prospective trauma registry from 2009 through 2016 at Kamuzu Central Hospital in Lilongwe, Malawi. Adult (>16 years) victims of IPV were compared with non-intentional trauma victims. Log binomial …

Metabolic Dependencies In Pancreatic Cancer., Ali Vaziri-Gohar, Mahsa Zarei, Jonathan R. Brody, Jordan M. Winter

Department of Surgery Faculty Papers

Pancreatic ductal adenocarcinoma (PDA) is a highly lethal cancer with a long-term survival rate under 10%. Available cytotoxic chemotherapies have significant side effects, and only marginal therapeutic efficacy. FDA approved drugs currently used against PDA target DNA metabolism and DNA integrity. However, alternative metabolic targets beyond DNA may prove to be much more effective. PDA cells are forced to live within a particularly severe microenvironment characterized by relative hypovascularity, hypoxia, and nutrient deprivation. Thus, PDA cells must possess biochemical flexibility in order to adapt to austere conditions. A better understanding of the metabolic dependencies required by PDA to survive and …

Surgeon's Perspective On Short Bowel Syndrome: Where Are We?, Ignazio R. Marino, Augusto Lauro

Department of Surgery Faculty Papers

Short bowel syndrome (SBS) is due to a massive loss of small bowel: the reduction of gut function is below the minimum necessary to maintain health (in adults) and growth (in children) so intravenous supplementation is required. Parenteral nutrition represents the milestone of treatment and surgical attempts should be limited only when the residual bowel is sufficient to increase absorption, reducing diarrhea and slowing the transit time of nutrients, water and electrolytes. The surgical techniques lengthen the bowel (tapering it) or reverse a segment of it: developed in children, nowadays are popular also among adults. The issue is mainly represented …

3,3'-Diindolylmethane Enhances Apoptosis In Docetaxel-Treated Breast Cancer Cells By Generation Of Reactive Oxygen Species., Susan Lanza-Jacoby, Guanjun Cheng

Department of Surgery Faculty Papers

CONTEXT: A major problem in the treatment of cancer is the development of toxic side effects and resistance to chemotherapy. The use of plant compounds to overcome resistance and prevent toxicity is a potential strategy for treatment.

OBJECTIVE: We evaluated whether 3,3'-diindolylmethane (DIM) enhanced the sensitivity of breast cancer cells to docetaxel (DOC).

MATERIALS AND METHODS: MDA-MB231 and Sk-BR-3 cells were treated with and without 25 or 50 µM of DIM and 1 nM of DOC for 48 and 72 h, respectively. MTT assay was used to measure cell survival. Apoptosis and intracellular reactive oxygen species (ROS) were determined by …

Early And Late Complications Of Bariatric Operation., Robert Lim, Alec Beekley, Dirk C. Johnson, Kimberly A. Davis

Department of Surgery Faculty Papers

Weight loss surgery is one of the fastest growing segments of the surgical discipline. As with all medical procedures, postoperative complications will occur. Acute care surgeons need to be familiar with the common problems and their management. Although general surgical principles generally apply, diagnoses specific to the various bariatric operations must be considered. There are anatomic considerations which alter management priorities and options for these patients in many instances. These problems present both early or late in the postoperative course. Bariatric operations, in many instances, result in permanent alteration of a patient's anatomy, which can lead to complications at any …

Consecutive Case Series Of Melanoma Sentinel Node Biopsy For Lymphoseek Compared To Sulfur Colloids, Caitlin Silvestri, Adrienne Christopher, Md, Charles Intenzo, Md, John C. Kairys, Md, Sung Kim, Md, Alliric Willis, Md, Adam C. Berger, Md

Department of Surgery Faculty Papers

Introduction: Sentinel lymph node biopsy (SLNB) is an important adjunct in the staging of patients with melanoma. Preoperative lymphoscintigraphy (LS) with radiolabeled isotopes is essential to localize sentinel nodes for removal. Our study compared the effectiveness of Lymphoseek to standard sulfur colloids (SC) in patients with melanoma undergoing SLNB.

Methods: We queried our IRB-approved melanoma database to identify 370 consecutive patients who underwent SLNB from 2012-2016 with at least one year of follow up. There were 185 patients in each group. Data points included characteristics of the primary melanoma lymphoscintigraphy, and SLNB. Student’s t-test and Chi-Square were used to analyze …

Prevalence Of And Factors Associated With Negative Microscopic Diagnosis Of Cutaneous Leishmaniasis In Rural Peru., Ryan Lamm, Clark Alves, Grace Perrotta, Meagan Murphy, Catherine Messina, Juan F. Sanchez, Erika Perez, Luis Angel Rosales, Andres G. Lescano, Edward Smith, Hugo Valdivia, Jack Fuhrer, Sarah-Blythe Ballard

Department of Surgery Faculty Papers

Cutaneous leishmaniasis is endemic to South America where diagnosis is most commonly conducted via microscopy. Patients with suspected leishmaniasis were referred for enrollment by the Ministry of Health (MoH) in Lima, Iquitos, Puerto Maldonado, and several rural areas of Peru. A 43-question survey requesting age, gender, occupation, characterization of the lesion(s), history of leishmaniasis, and insect-deterrent behaviors was administered. Polymerase chain reaction (PCR) was conducted on lesion materials at the Naval Medical Research Unit No. 6 in Lima, and the results were compared with those obtained by the MoH using microscopy. Factors associated with negative microscopy and positive PCR results …

A Rare Case Of Clostridium Septicum Aortitis With Colon Adenocarcinoma, Niti Shahi, Mariano Arosemena, Jeontaik Kwon, Paul J. Dimuzio, Babak Abai, Dawn M. Salvatore

Department of Surgery Faculty Papers

Clostridium septicum aortitis is a rare, highly morbid condition typically accompanied by malignant disease, such as hematologic cancer or colon adenocarcinoma. Presenting symptoms commonly described include acute onset of abdominal pain, nausea, and fevers. Prompt diagnosis of infectious aortitis is critical to prevent deadly complications, such as sepsis and vascular catastrophe. The described management largely involves surgical resection of the infected aorta, débridement, and arterial revascularization through extra-anatomic bypass or aortic graft placement.

A Sub-Type Of Familial Pancreatic Cancer: Evidence And Implications Of Loss-Of-Function Polymorphisms In Indoleamine-2,3-Dioxygenase-2., Avinoam Nevler, Alexander J. Muller, Joseph A. Cozzitorto, Austin Goetz, Jordan M. Winter, Theresa P. Yeo, Harish Lavu, Charles Yeo, George C. Prendergast, Jonathan Brody

Department of Surgery Faculty Papers

BACKGROUND: Variation in an individual's genetic status can impact the development of pancreatic ductal adenocarcinoma; however, the majority of familial pancreatic cancers (FPC) cannot yet be attributed to a specific inherited mutation. We present data suggesting a correlation between loss-of-function single nucleotide polymorphisms (SNPs) in an immune regulator gene, indoleamine-2,3-dioxygenase-2 (IDO2), and an increased risk of FPC.

STUDY DESIGN: Germline DNA from patients who underwent resection for pancreatic ductal adenocarcinoma (n = 79) was sequenced for the IDO2 SNPs R248W and Y359Stop. Genotypes resulting in inactivation of IDO2 (Y325X homozygous, R248W homozygous) were labeled as homozygous, and the other genotypes …

Out Of The Straitjacket., Michael Weinstein

Department of Surgery Faculty Papers

No abstract provided.

Tracheal Injury Detected Immediately After Median Sternotomy By Inexperienced Surgeons: Two Case Reports., Jun Takeshita, Kei Nishiyama, Atsushi Fukumoto, Suguru Ohira, Satoru Beppu, Nozomu Sasahashi, Nobuaki Shime

Department of Surgery Faculty Papers

BACKGROUND: Although median sternotomy is standard during cardiac surgery, the procedure is associated with a risk of injury to mediastinal organs. Here, we discuss two cases of tracheal injury following median sternotomy during cardiac surgery.

CASE PRESENTATION: Ventilation failure occurred in a 78-year-old Japanese man and a 71-year-old Japanese man after median sternotomy, and tracheal injury was identified. The sites of injury were directly repaired and covered with mediastinal fat tissue, following which ventilation was successful. The burn-like deposits observed at the site of tracheal injury and on the removed endotracheal tube support the notion that the injuries in our …

Development Of An Objective Assessment Tool For Total Laparoscopic Hysterectomy: A Delphi Method Among Experts And Evaluation On A Virtual Reality Simulator., Sophie Knight, Rajesh Aggarwal, Md, Phd, Frcs, Facs, Aubert Agostini, Anderson Loundou, Stéphane Berdah, Patrice Crochet

Department of Surgery Faculty Papers

INTRODUCTION: Total Laparoscopic hysterectomy (LH) requires an advanced level of operative skills and training. The aim of this study was to develop an objective scale specific for the assessment of technical skills for LH (H-OSATS) and to demonstrate feasibility of use and validity in a virtual reality setting.

MATERIAL AND METHODS: The scale was developed using a hierarchical task analysis and a panel of international experts. A Delphi method obtained consensus among experts on relevant steps that should be included into the H-OSATS scale for assessment of operative performances. Feasibility of use and validity of the scale were evaluated by …

A Standardized Comparison Of Peri-Operative Complications After Minimally Invasive Esophagectomy: Ivor Lewis Versus Mckeown., Andrew M. Brown, Michael J. Pucci, Adam C. Berger, Talar Tatarian, Nathaniel R. Evans Iii, Ernest L. Rosato, Francesco Palazzo

Department of Surgery Faculty Papers

BACKGROUND: While our institutional approach to esophageal resection for cancer has traditionally favored a minimally invasive (MI) 3-hole, McKeown esophagectomy (MIE 3-hole) during the last five years several factors has determined a shift in our practice with an increasing number of minimally invasive Ivor Lewis (MIE IL) resections being performed. We compared peri-operative outcomes of the two procedures, hypothesizing that MIE IL would be less morbid in the peri-operative setting compared to MIE 3-hole.

METHODS: Our institution's IRB-approved esophageal database was queried to identify all patients who underwent totally MI esophagectomy (MIE IL vs. MIE 3-hole) from June 2011 to …

Surgical Approaches To Adenocarcinoma Of The Gastroesophageal Junction: The Siewert Ii Conundrum., Andrew M. Brown, Danica N. Giugliano, Adam C. Berger, Michael J. Pucci, Francesco Palazzo

Department of Surgery Faculty Papers

BACKGROUND: The Siewert classification system for gastroesophageal junction adenocarcinoma has provided morphological and topographical information to help guide surgical decision-making. Evidence has shown that Siewert I and III tumors are distinct entities with differing epidemiologic and histologic characteristics and distinct patterns of disease progression, requiring different treatment. Siewert II tumors share some of the characteristics of type I and III lesions, and the surgical approach is not universally agreed upon. Appropriate surgical options include transthoracic esophagogastrectomy, transhiatal esophagectomy, and transabdominal extended total gastrectomy.

PURPOSE: A review of the available evidence of the surgical management of Siewert II tumors is presented. …

#Ilooklikeasurgeon: Embracing Diversity To Improve Patient Outcomes., Heather Logghe, Christian Jones, Alison Mccoubrey, Edward Fitzgerald

Department of Surgery Faculty Papers

No abstract provided.

Posttranscriptional Regulation Of Parg Mrna By Hur Facilitates Dna Repair And Resistance To Parp Inhibitors, Saswati N. Chand, Mahsa Zarei, M. J. Schiewer, Akshay R. Sanan, Carmella Romeo, Shruti Lal, Joseph A. Cozzitorto, Avinoam Nevler, Laura Scolaro, Eric R. Londin, Wei Jiang, Nicole Meisner-Kober, Michael J. Pishvaian, Karen E. Knudsen, Charles Yeo, John M Pascal, Jordan M. Winter, Jonathan R. Brody

Department of Surgery Faculty Papers

The majority of pancreatic ductal adenocarcinomas (PDAC) rely on the mRNA stability factor HuR (ELAV-L1) to drive cancer growth and progression. Here, we show that CRISPR-Cas9–mediated silencing of the HuR locus increases the relative sensitivity of PDAC cells to PARP inhibitors (PARPi). PDAC cells treated with PARPi stimulated translocation of HuR from the nucleus to the cytoplasm, specifically promoting stabilization of a new target, poly (ADP-ribose) glycohydrolase (PARG) mRNA, by binding a unique sequence embedded in its 3⁰ untranslated region. HuR-dependent upregulation of PARG expression facilitated DNA repair via hydrolysis of polyADP-ribose on related repair proteins. Accordingly, strategies to …

Completion Dissection Or Observation For Sentinel-Node Metastasis In Melanoma., Mark B. Faries, John F. Thompson, Alistair J. Cochran, Robert H. Andtbacka, Nicola Mozzillo, Jonathan S. Zager, Tiina Jahkola, Tawnya L. Bowles, Alessandro Testori, Peter D. Beitsch, Harald J. Hoekstra, Marc Moncrieff, Christian Ingvar, Michel W.J.M. Wouters, Michael S. Sabel, Edward A. Levine, Doreen Agnese, Michael Henderson, Reinhard Dummer, Carlo R. Rossi, Rogerio I. Neves, Steven D. Trocha, Frances Wright, David R. Byrd, Maurice Matter, Eddy Hsueh, Alastair Mackenzie-Ross, Douglas B. Johnson, Patrick Terheyden, Adam C. Berger, Tara L. Huston, Jeffrey D. Wayne, B. Mark Smithers, Heather B. Neuman, Schlomo Schneebaum, Jeffrey E. Gershenwald, Charlotte E. Ariyan, Darius C. Desai, Lisa Jacobs, Kelly M. Mcmasters, Anja Gesierich, Peter Hersey, Steven D. Bines, John M. Kane, Richard J. Barth, Gregory Mckinnon, Jeffrey M. Farma, Erwin Schultz, Sergi Vidal-Sicart, Richard A. Hoefer, James M Lewis, Randall Scheri, Mark C. Kelley, Omgo E. Nieweg, R. Dirk Noyes, Dave S.B. Hoon, He-Jing Wang, David A. Elashoff, Robert M. Elashoff

Department of Surgery Faculty Papers

BACKGROUND: Sentinel-lymph-node biopsy is associated with increased melanoma-specific survival (i.e., survival until death from melanoma) among patients with node-positive intermediate-thickness melanomas (1.2 to 3.5 mm). The value of completion lymph-node dissection for patients with sentinel-node metastases is not clear.

METHODS: In an international trial, we randomly assigned patients with sentinel-node metastases detected by means of standard pathological assessment or a multimarker molecular assay to immediate completion lymph-node dissection (dissection group) or nodal observation with ultrasonography (observation group). The primary end point was melanoma-specific survival. Secondary end points included disease-free survival and the cumulative rate of nonsentinel-node metastasis.

RESULTS: Immediate completion …

Quantification And Expert Evaluation Of Evidence For Chemopredictive Biomarkers To Personalize Cancer Treatment., Shruti Rao, Robert A. Beckman, Shahla Riazi, Cinthya S. Yabar, Simina M. Boca, John L. Marshall, Michael J. Pishvaian, Jonathan R. Brody, Subha Madhavan

Department of Surgery Faculty Papers

Predictive biomarkers have the potential to facilitate cancer precision medicine by guiding the optimal choice of therapies for patients. However, clinicians are faced with an enormous volume of often-contradictory evidence regarding the therapeutic context of chemopredictive biomarkers.We extensively surveyed public literature to systematically review the predictive effect of 7 biomarkers claimed to predict response to various chemotherapy drugs: ERCC1-platinums, RRM1-gemcitabine, TYMS-5-fluorouracil/Capecitabine, TUBB3-taxanes, MGMT-temozolomide, TOP1-irinotecan/topotecan, and TOP2A-anthracyclines. We focused on studies that investigated changes in gene or protein expression as predictors of drug sensitivity or resistance. We considered an evidence framework that ranked studies from high level I evidence for randomized …

Crispr Knockout Of The Hur Gene Causes A Xenograft Lethal Phenotype., Shruti Lal, Edwin C, Cheung, Mahsa Zarei, Ranjan Preet, Saswati N. Chand, Nicole C. Mambelli-Lisboa, Carmella Romeo, Matthew C. Stout, Eric Londin, Austin Goetz, Cinthya Y. Lowder, Avinoam Nevler, Charles Yeo, Paul M. Campbell, Jordan M. Winter, Dan A. Dixon, Jonathan Brody

Department of Surgery Faculty Papers

Pancreatic ductal adenocarcinoma (PDA) is the third leading cause of cancer-related deaths in the United States, whereas colorectal cancer is the third most common cancer. The RNA-binding protein HuR (ELAVL1) supports a pro-oncogenic network in gastrointestinal (GI) cancer cells through enhanced HuR expression. Using a publically available database, HuR expression levels were determined to be increased in primary PDA and colorectal cancer tumor cohorts as compared with normal pancreas and colon tissues, respectively. CRISPR/Cas9 technology was successfully used to delete the HuR gene in both PDA (MIA PaCa-2 and Hs 766T) and colorectal cancer (HCT116) cell lines. HuR deficiency has …