Surgery Commons^™

Pediatric Ovarian Growing Teratoma Syndrome., Rebecca M. Rentea, Aaron Varghese, Atif Ahmed, Alexander Kats, Michelle Manalang, Tazim Dowlut-Mcelroy, Richard J. Hendrickson

Manuscripts, Articles, Book Chapters and Other Papers

Ovarian immature teratoma is a germ cell tumor that comprises less than 1% of ovarian cancers and is treated with surgical debulking and chemotherapy depending on stage. Growing teratoma syndrome (GTS) is the phenomenon of the growth of mature teratoma elements with normal tumor markers during or following chemotherapy for treatment of a malignant germ cell tumor. These tumors are associated with significant morbidity and mortality due to invasive and compressive growth as well as potential for malignant transformation. Current treatment modality is surgical resection. We discuss a 12-year-old female who presented following resection of a pure ovarian immature teratoma …

Impact Of Hur Inhibition By The Small Molecule Ms-444 On Colorectal Cancer Cell Tumorigenesis., Fernando F. Blanco, Ranjan Preet, Andrea Aguado, Vikalp Vishwakarma, Laura E. Stevens, Alok Vyas, Subhash Padhye, Liang Xu, Scott J. Weir, Shrikant Anant, Nicole Meisner-Kober, Jonathan R. Brody, Dan A. Dixon

Department of Surgery Faculty Papers

Colorectal cancer (CRC) is the third most common cancer and a leading cause of cancer-related mortality. Observed during CRC tumorigenesis is loss of post-transcriptional regulation of tumor-promoting genes such as COX-2, TNFα and VEGF. Overexpression of the RNA-binding protein HuR (ELAVL1) occurs during colon tumorigenesis and is abnormally present within the cytoplasm, where it post-transcriptionally regulates genes through its interaction with 3'UTR AU-rich elements (AREs). Here, we examine the therapeutic potential of targeting HuR using MS-444, a small molecule HuR inhibitor. Treatment of CRC cells with MS-444 resulted in growth inhibition and increased apoptotic gene expression, while similar treatment doses …

Four-Dimensional (4d) Subharmonic Aided Pressure Estimation For Monitoring Neoadjuvant Chemotherapy Response Of Breast Cancer, Kibo Nam, Maria Stanczak, Anush Sridharan, Adam C. Berger, Tiffany Avery, John R. Eisenbrey, Flemming Forsberg

Department of Radiology Posters

Introduction

Neoadjuvant chemotherapy is a well-established treatment option for patients with non-metastatic breast cancer. The patient response is correlated with survival. However, the optimal method for monitoring neoadjuvant therapy response has not been established. One factor that may affect the response of neoadjuvant therapy is the interstitial fluid pressure (IFP). Increased IFP prevents an effective delivery of therapeutic agents and reduces the efficacy of the therapy. Recently, subharmonic-aided pressure estimation (SHAPE) using contrast-enhanced ultrasound (CEUS) has been developed and its potential was demonstrated in animals as a non-invasive technique for IFP measurements. The SHAPE method estimates IFP based on the …

Asymptomatic Left Ventricular Myxoma In A 12-Year-Old Male., Meghan Chlebowski, James O'Brien, Casey Hertzenberg, Jonathan B. Wagner

Manuscripts, Articles, Book Chapters and Other Papers

Cardiac myxoma is the most common cardiac tumor in patients of all ages; the majority are encountered as single left atrial tumors. Left ventricular myxomas are exceedingly rare, having been recorded in a small number of case reports involving children worldwide. We report a case of a left ventricular myxoma with left ventricular outflow tract obstruction in a previously healthy, asymptomatic adolescent black male. Transthoracic echocardiograms revealed a single, large (2.5 × 5-cm), lobulated, mobile mass within the left ventricular cavity that oscillated into the outflow tract, thereby causing moderate obstruction during systole. Advanced images delineated the location and tissue …

Targeting Wnt/Β-Catenin Pathway In Hepatocellular Carcinoma Treatment, Valery Vilchez, Lilia M. Turcios, Francesc Marti, Roberto Gedaly

Surgery Faculty Publications

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide. Liver cancer is generally related to hepatitis B or C infection and cirrhosis. Usually, patients with HCC are asymptomatic and are diagnosed at late stages when surgical treatment is no longer suitable. Limited treatment options for patients with advanced HCC are a major concern. Therefore, there is an urge for finding novel therapies to treat HCC. Liver cancer is highly heterogeneous and involved deregulation of several signaling pathways. Wnt/β-catenin pathway is frequently upregulated in HCC and it is implicated in maintenance of tumor initiating cells, drug …

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 …

Does The Expression Of Ki-67, P16 And Cox-2 At Initial Diagnosis Of Breast Atypia Or Usual Ductal Hyperplasia Predict A Second Clinically Significant Event?, Judy A. Tjoe, Philippe Gascard, Jianxin Zhao, Gary F. Neitzel, Maharaj Singh, Brittany Last, James Marx, Thea Tlsty, Sanjay Kansra

Journal of Patient-Centered Research and Reviews

Background: Women diagnosed with atypical ductal hyperplasia (ADH) or atypical lobular hyperplasia (ALH) have a fivefold increased risk of developing breast cancer. Because ADH/ALH can be precursors or predictive markers of a subsequent clinically significant event (SCSE), i.e. atypia, in situ or invasive carcinoma, the clinical outcome for these patients ranges anywhere from remission to invasive malignancy. Currently we cannot predict which atypical breast lesion is likely to be associated with future cancer, resulting in aggressive management and, possibly, overtreatment. Kerlikowske et al. reported that a combination of three biomarkers (cell cycle regulator p16INK4a, proliferation antigen Ki-67 and stress response …

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Trends In Initial Management Of Prostate Cancer In New Hampshire, Johann Ingimarsson, Maria Celaya, Michael Laviolette, Judy R. Rees, Elias Hyams

Dartmouth Scholarship

Purpose Prostate cancer management strategies are evolving with increased understanding of the disease. Specifically, there is emerging evidence that ‘‘low-risk’’ cancer is best treated with observation, while localized ‘‘high-risk’’ cancer requires aggressive curative therapy. In this study, we evaluated trends in management of prostate cancer in New Hampshire to determine adherence to evidence- based practice. Methods From the New Hampshire State Cancer Registry, cases of clinically localized prostate cancer diagnosed in 2004–2011 were identified and classified according to D’Amico criteria. Initial treatment modality was recorded as surgery, radiation therapy, expectant management, or hormone therapy. Temporal trends were assessed by Chi-square …

Breast Cancer Screening: Early Detection Is Not Enough, Judy A. Tjoe

Journal of Patient-Centered Research and Reviews

N/A

Physicians' Attitudes About Recommending Surgery For Early Stage Lung Cancer And Possible Reasons For Racial Disparities, Franklin R. Mcguire

Journal of Health Disparities Research and Practice

PHYSICIANS’ ATTITUDES ABOUT RECOMMENDING SURGERY FOR EARLY STAGE LUNG CANCER AND POSSIBLE REASONS FOR RACIAL DISPARITIES

ABSTRACT

Purpose: Patient refusal for lung cancer surgery is significant, but other factors, such as negative framing of the treatment discussion, may be involved. Physician attitudes could influence the nuances of and therefore the conclusions of these discussions. We determined physicians’ attitudes and the influence it has on possible decisions against lung cancer surgery, particularly surgical rates for blacks, using a companion survey.

Methods: The study is a prospective, multicenter observational trial conducted at five sites in North and South Carolina from December …

The Influence Of Race/Ethnicity And Place Of Service On Breast Reconstruction For Medicare Beneficiaries With Mastectomy, Tracy Onega, Julie Weiss, Karla Kerlikowske, Karen Wernli

Dartmouth Scholarship

Racial disparities in breast reconstruction for breast cancer are documented. Place of service has contributed to disparities in cancer care; but the interaction of race/ethnicity and place of service has not been explicitly examined. We examined whether place of service modified the effect of race/ethnicity on receipt of reconstruction. We included women with a mastectomy for incident breast cancer in SEER-Medicare from 2005-2009. Using Medicare claims, we determined breast reconstruction within 6 months. Facility characteristics included: rural/urban location, teaching status, NCI Cancer Center designation, cooperative oncology group membership, Disproportionate Share Hospital (DSH) status, and breast surgery volume. Using multivariable logistic …

Outcomes Of Recurrent Rectal Cancer After Transanal Excision, Sachin Vaid, Christopher Buzas, John S. Park Md, Robert J. Sinnott Md

Department of Surgery

No abstract provided.

Novel Anticancer Agents In Clinical And Preclinical Trials, Adnan Salim

Section of Neurosurgery

No abstract provided.

Cryo Surgery Of The Prostate: An Effective, Minimally Invasive Cancer Therapy With Superior Health-Related Quality-Of-Life Outcomes, Martyn A. Vickers Jr

Oncology

What is the best treatment for localized, aggressive prostate cancer? One option is Cryo Surgery, a primary option that utilizes localized freezing to destroy diseased tissue. If you or your patients wish to consider Cryo Surgery, be sure to discuss this option with an urologist who performs Cryo Surgery of the prostate. Many urologists have not observed or been trained in the performance of this procedure. Prostate cancer allows you time to carefully consider all treatment options. Make an educated decision!

Metabotropic Glutamate Receptor-1 As A Novel Target For The Antiangiogenic Treatment Of Breast Cancer, Cecilia L. Speyer, Ali H. Hachem, Ali A. Assi, Jennifer S. Johnson, John Austin Devries, David H. Gorski

Department of Surgery

Metabotropic glutamate receptors (mGluRs) are normally expressed in the central nervous system, where they mediate neuronal excitability and neurotransmitter release. Certain cancers, including melanoma and gliomas, express various mGluR subtypes that have been implicated as playing a role in disease progression. Recently, we detected metabotropic glutamate receptor-1 (gene: GRM1; protein: mGluR1) in breast cancer and found that it plays a role in the regulation of cell proliferation and tumor growth. In addition to cancer cells, brain endothelial cells express mGluR1. In light of these studies, and because angiogenesis is both a prognostic indicator in cancer correlating with a poorer …

Metabotropic Glutamate Receptor-1 Contributes To Progression In Triple Negative Breast Cancer, Malathi Banda, Cecilia L. Speyer, Sara N. Semma, Kingsley O. Osuala, Nicole Kounalakis, Keila E. Torres Torres, Nicola J. Barnard, Hyunjin J. Kim, Bonnie F. Sloane, Fred R. Miller, James S. Goydos, David H. Gorski

Department of Surgery

TNBC is an aggressive breast cancer subtype that does not express hormone receptors (estrogen and progesterone receptors, ER and PR) or amplified human epidermal growth factor receptor type 2 (HER2), and there currently exist no targeted therapies effective against it. Consequently, finding new molecular targets in triple negative breast cancer (TNBC) is critical to improving patient outcomes. Previously, we have detected the expression of metabotropic glutamate receptor-1 (gene: GRM1; protein: mGluR1) in TNBC and observed that targeting glutamatergic signaling inhibits TNBC growth both in vitro and in vivo. In this study, we explored how mGluR1 contributes to TNBC …

Thoracic Multidisciplinary Clinic (Tmdc) And The Treatment Of Stage Iii Non-Small Cell Lung Cancer, Eliot L. Friedman Md, Michael F. Szwerc Md, Robert Kruklitis Md, Michael J. Weiss

Department of Medicine

No abstract provided.

Failure Patterns In Resected Pancreas Adenocarcinoma: Lack Of Predicted Benefit To Smad4 Expression., Jordan M. Winter, Laura H. Tang, David S. Klimstra, Weiguo Liu, Irena Linkov, Murray F. Brennan, Michael I. DʼAngelica, Ronald P. Dematteo, Yuman Fong, William R. Jarnagin, Eileen M. OʼReilly, Peter J. Allen

Department of Surgery Faculty Papers

OBJECTIVE: To determine whether SMAD4 expression is associated with recurrence pattern after resection for pancreatic ductal adenocarcinoma (PDA).

BACKGROUND: SMAD4 expression status has been reported to be associated with patterns of failure in PDA, but studies have not examined recurrence patterns after resection.

METHODS: A tissue microarray was constructed including 127 patients with resected PDA and either short-term (<12 >months) or long-term (>30 months) survival. SMAD4 expression was evaluated by immunohistochemistry and categorized as present or lost in tumor cells. Conventional pathologic features (lymph node metastases, positive resection margin, poor grade, and tumor size) were recorded, and disease-specific outcomes …

Giant Cell Tumour Of The Sacrum: Function-Preserving Surgery With Extended Curettage And Ilio-Lumbar Fusion, Riaz Hussain Lakhdawala, Tashfeen Ahmad, Ather Enam

Section of Orthopaedic Surgery

Giant cell tumours of the sacrum pose a unique therapeutic challenge due to the inaccessibility of the tumour, significant intra-operative blood loss from extensive vascularity, high rate of local recurrence with conservative surgery, and loss of neurological function and mechanical instability with en-bloc excision. We present a case where successful outcome was achieved by tailoring treatment in consideration of the above issues. A 28 year old male diagnosed on biopsy to have giant cell tumour of the sacrum presented to us with low-back pain, left-sided S1 radiculopathy, ankle weakness and urinary incontinence. MRI showed a tumour involving the S1 and …

Comparison Of Vaginal Cuff Closure Outcomes In Patients Having Robotic-Assisted Total Laparoscopic Hysterectomy: V-Loc Vs. Vicryl (Poster), Martin A. Martino Md, R Melody Reynolds Md, A Ei Haraki Md, Rachel Morcrette Pa-C, Kyle M. Langston Pa-C, Gregory F. Kainz Md, Richard Boulay Md, M Bijoy Thomas Md

Department of Obstetrics & Gynecology

No abstract provided.

Autoclaved Tumor Bone For Skeletal Reconstruction In Paediatric Patients: A Low Cost Alternative In Developing Countries, Masood Umer, Hafiz Muhammad Umer, Irfan Qadir, Haroon Rashid, Rabia Awan, Raza Askari, Shamvil Ashraf

Section of Orthopaedic Surgery

We reviewed in this series forty patients of pediatric age who underwent resection for malignant tumors of musculoskeletal system followed by biological reconstruction. Our surgical procedure for reconstruction included (1) wide en bloc resection of the tumor; (2) curettage of tumor from the resected bone; (3) autoclaving for 8 minutes (4) bone grafting from the fibula (both vascularized and nonvascularized fibular grafts used); (5) reimplantation of the autoclaved bone into the host bone defect and fixation with plates. Functional evaluation was done using MSTS scoring system. At final followup of at least 18 months (mean 29.2 months), 31 patients had …

Targeting And Killing Of Glioblastoma With Activated T Cells Armed With Bispecific Antibodies, Ian M. Zitron, Archana Thakur, Oxana Norkina, Geoffrey R. Barger, Lawrence G. Lum, Sandeep Mittal

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Since most glioblastomas express both wild-type EGFR and EGFRvIII as well as HER2/neu, they are excellent targets for activated T cells (ATC) armed with bispecific antibodies (BiAbs) that target EGFR and HER2.

Methods

ATC were generated from PBMC activated for 14 days with anti-CD3 monoclonal antibody in the presence of interleukin-2 and armed with chemically heteroconjugated anti-CD3×anti-HER2/neu (HER2Bi) and/or anti-CD3×anti-EGFR (EGFRBi). HER2Bi- and/or EGFRBi-armed ATC were examined for in vitro cytotoxicity using MTT and ⁵¹Cr-release assays against malignant glioma lines (U87MG, U118MG, and U251MG) and primary glioblastoma lines.

Results

EGFRBi-armed ATC killed up to 85% of U87, …

Quantitative, Spectrally-Resolved Intraoperative Fluorescence Imaging, Pablo A. Valdés, Frederic Leblond, Valerie L. Jacobs, Brian C. Wilson, Keith D. Paulsen, David W. Roberts

Dartmouth Scholarship

Intraoperative visual fluorescence imaging (vFI) has emerged as a promising aid to surgical guidance, but does not fully exploit the potential of the fluorescent agents that are currently available. Here, we introduce a quantitative fluorescence imaging (qFI) approach that converts spectrally-resolved data into images of absolute fluorophore concentration pixel-by-pixel across the surgical field of view (FOV). The resulting estimates are linear, accurate, and precise relative to true values, and spectral decomposition of multiple fluorophores is also achieved. Experiments with protoporphyrin IX in a glioma rodent model demonstrate in vivo quantitative and spectrally-resolved fluorescence imaging of infiltrating tumor margins for the …

Analytic Lymph Node Number Establishes Staging Accuracy By Occult Tumor Burden In Colorectal Cancer., Terry Hyslop, David S. Weinberg, Stephanie Schulz, Alan Barkun, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND AND OBJECTIVES: Recurrence in lymph node-negative (pN0) colorectal cancer suggests the presence of undetected occult metastases. Occult tumor burden in nodes estimated by GUCY2C RT-qPCR predicts risk of disease recurrence. This study explored the impact of the number of nodes analyzed by RT-qPCR (analytic) on the prognostic utility of occult tumor burden.

METHODS: Lymph nodes (range: 2-159) from 282 prospectively enrolled pN0 colorectal cancer patients, followed for a median of 24 months (range: 2-63), were analyzed by GUCY2C RT-qPCR. Prognostic risk categorization defined using occult tumor burden was the primary outcome measure. Association of prognostic variables and risk category …

Malignant Peripheral Nerve Sheath Tumor (Mpnst): An Overview With Emphasis On Pathology, Imaging And Management Strategies., Timothy C. Beer

Jefferson Hospital Staff Papers and Presentations

MPNSTs are rare malignancies that are classically associated with pre-existing plexiform neurofibromas in neurofibromatosis type 1 (NF-1) patients, but also occur in association with radiation as well as sporadically in patients with no known risk factors. The typical presentation of sporadic MPNST is a new painless enlarging mass. The typical presentation of MPNST in an NF-1 patient is rapid enlargement or new onset of pain associated with a pre-existing plexiform neurofibroma. Although both MPNST and benign neurofibromas share in common the absence of neurofibromin function due to loss of both NF-1 alleles, malignant transformation to MPNST requires several additional aberrations, …

A Comparative Analysis Of Toluidine Blue With Frozen Section In Oral Squamous Cell Carcinoma, Montasir Junaid, Moaz M. Choudhary, Zain A. Sobani, Ghulam Murtaza, Sadaf Qadeer, Naeem S. Ali, Mumtaz J. Khan, Anwar Suhail

Department of Surgery Docs

Background:Surgical excision of the primary tumor with safe margins remains the mainstay of treatment for oral cavity squamous cell carcinoma (OSCC). The standard of care for assessment of intraoperative margins is frozen section histopathology. Unfortunately the facility is not available at most centers in limited resource countries. Toluidine blue, a metachromatic dye, has been well described in clinical identification of malignant and premalignant lesion in the oral cavity. Considering this we decided to explore intraoperative use of toluidine blue staining, in comparison with frozen sections, for the assessment of tumor-free margins.

Methods:

After obtaining clearance from the in-house ethical …

Lymph Node Ratio Is An Important And Independent Prognostic Factor For Patients With Stage Iii Melanoma, Adam C. Berger, Michael Fierro, John C. Kairys, David Berd, Takami Sato, Jocelyn Andrel, Terry Hyslop, Michael J. Mastrangelo

Kimmel Cancer Center Faculty Papers

INTRODUCTION:

The incidence of melanoma is dramatically increasing worldwide. We hypothesized that the ratio of metastatic to examined lymph node ratio (LNR) would be the most important prognostic factor for stage III patients.

METHODS:

We retrospectively reviewed our institutional database of melanoma patients and identified 168 patients who underwent lymph node dissection (LND) for stage III disease between 1993 and 2007. Patients were divided into three groups based on LNR (≤10%, n = 93; 10-≤25%, n = 45; and >25%, n = 30). Univariate and multivariate analysis was performed using Cox proportional hazards model.

RESULTS:

The median survival time of …

Benchmarking Quality Metrics For Endometrial Cancer Patients: Robotics Vs. Laparoscopy, Martin A. Martino Md, Jocelyn Shubella, Shamol Williams Msii, Rachel Morcrette Pa-C, Jeremy Patriarco, Hai-Yen Nguyen Md, Amy Hordendorf, M Bijoy Thomas Md, Richard Boulay Md

Department of Obstetrics & Gynecology

No abstract provided.