Medicine and Health Sciences Commons^™

Fak Is A Critical Regulator Of Neuroblastoma Liver Metastasis, Sora Lee, Jingbo Qiao, Pritha Paul, Kathleen L. O'Connor, B. Mark Evers, Dai H. Chung

Surgery Faculty Publications

Neuroblastomas express increased levels of gastrin-releasing peptide receptor (GRP-R). However, the exact molecular mechanisms involved in GRP-R-mediated cell signaling in neuroblastoma growth and metastasis are unknown. Here, we report that focal adhesion kinase (FAK), as a critical downstream target of GRP-R, is an important regulator of neuroblastoma tumorigenicity. We found that FAK expression correlates with GRP-R expression in human neuroblastoma sections and cell lines. GRP-R overexpression in SK-N-SH cells increased FAK, integrin α3 and β1 expressions and cell migration. These cells demonstrated flatter cell morphology with broad lamellae, in which intense FAK expression was localized to the leading edges of …

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 …

Compliance With Surgical Care Improvement Project Blood Glucose--A Marker For Euglycemia, But Does It Put Our Patients At Risk?, Isaac R Whitman, Maura Murphy, Marta M Gilson, Amy Campfield, Michel Haddad, Elizabeth Moxey, Glenn J R Whitman

Department of Surgery Faculty Papers

To improve outcomes in open heart surgery (OHS) patients, the Surgical Care Improvement Project (SCIP) requires 6 am postoperative day (POD) 1 and 2 blood glucose (BG) to be ≤200mg/dL. This study examined risk factors for SCIP noncompliance when using an insulin infusion protocol (IIP) and evaluated this SCIP metric as a surrogate for glycemic control. The authors divided 99 consecutive OHS patients, all subjected to 1 uniform IIP, into 2 groups: Group 1-SCIP compliant (n=79) and Group 2-SCIP noncompliant (n=20). They determined mean BG for the first 48 postoperative hours, percent of total time with hyperglycemia (% time BG …

A Clinical Prediction Model For Long-Term Functional Outcome After Traumatic Spinal Cord Injury Based On Acute Clinical And Imaging Factors., Jefferson R Wilson, Robert G Grossman, Ralph F Frankowski, Alexander Kiss, Aileen M Davis, Abhaya V Kulkarni, James S Harrop, Bizhan Aarabi, Alexander Vaccaro, Charles H Tator, Marcel Dvorak, Christopher I Shaffrey, Susan Harkema, James D Guest, Michael G Fehlings

Department of Neurosurgery Faculty Papers

To improve clinicians' ability to predict outcome after spinal cord injury (SCI) and to help classify patients within clinical trials, we have created a novel prediction model relating acute clinical and imaging information to functional outcome at 1 year. Data were obtained from two large prospective SCI datasets. Functional independence measure (FIM) motor score at 1 year follow-up was the primary outcome, and functional independence (score ≥ 6 for each FIM motor item) was the secondary outcome. A linear regression model was created with the primary outcome modeled relative to clinical and imaging predictors obtained within 3 days of injury. …

Baron Guillaume Dupuytren: When Brilliance Combats Professionalism., Sean M. Devitt, Md, Charles J. Yeo, Md, Pinckney J. Maxwell, Iv, Md

Department of Surgery Gibbon Society Historical Profiles

Baron Guilluame Dupuytren was a French anatomist and surgeon who practiced during the 1800s and is considered by some to be the most brilliant and gifted surgeons of his time. His contributions to the field of surgery are quite extensive, yet his eccentric personality and attitude toward his colleagues, students, and patients raises a very interesting question: could Dr. Dupuytren (Fig. 1) and his many contributions to the field of surgery have thrived in today’s era of professionalism? The concept of professionalism is emphasized to medical students starting from day one of their medical training. How would Dr. Dupuytren, an …

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 …

Adult Ecmo And Gastrointestinal Bleeding From Small Bowel Arteriovenous Malformations: A Novel Treatment Using Spiral Enteroscopy., Konrad Sarosiek, Hitoshi Hirose, Harrison T Pitcher, Nicholas C. Cavarocchi

Department of Surgery Faculty Papers

Hemorrhagic complications on extracorporeal membrane oxygenation (ECMO) are common because of the need for anticoagulation to maintain the oxygenator and circuitry. Gastrointestinal bleeding (GIB) is reported to occur in 3-6% of ECMO patients, ¹ requiring frequent transfusions as well as multiple diagnostic and therapeutic interventions. Multiple transfusions can result in volume overload, coagulopathies and infections leading to significant morbidity and mortality. We present the first published case of GIB from an arteriovenous malformation (AVM) treated with a novel therapy termed spiral enteroscopy while the patient remained on venoarterial (VA) ECMO.

Thickened Ascending Aortic Wall Mimicking Intramural Hematoma., Kentaro Yamane, Hitoshi Hirose, Benjamin A. Youdelman, James Diehl

Department of Surgery Faculty Papers

A 45-year-old Hispanic woman presented with a 3-day history of ‘‘burning’’ chest pain. A computed tomo- graphic angiogram of the chest revealed the ascending aorta had a maximum diameter of 40 mm with marked thickening of the aortic wall (Figure 1), which we con- cluded was an intramural hematoma. On entering the pericardium, a milky-white plaque-like area on the ascending aorta was encountered (Figure 2). The ascending aorta was firm to palpation. Intraoperative transesophageal echocardiography and epiaortic ultra- sound showed a hyperechoic aortic wall with no find- ings compatible with aortic dissection. The ascending aorta had an irregular surface contour, …

Profiling The Ethnic Characteristics Of Domestic Injuries In Children Younger Than Age 5 Years., Tolulope A. Oyetunji, Adrienne A. Stevenson, Aderonke O. Oyetunji, Sharon K. Onguti, Sarah A. Ames, Adil H. Haider, Benedict C. Nwomeh

Manuscripts, Articles, Book Chapters and Other Papers

The home remains a very common location for deadly injuries among children younger than 5 years. The aim of this study is to describe the demographic and injury characteristics of domestic injuries in children younger than 5 years. The National Trauma Data Bank's National Sample Program data set was queried for children younger than 5 years with the injury site classified as home. Bivariate analysis was performed to determine unadjusted differences by ethnicity. Appropriate weight was applied to the sample to determine accurate national estimates. A total of 7,364 children, representing 32,033 children, were analyzed. Overall mortality was 1.6 per …

Invited Commentary On: Orthotopic Heart Transplantation In Patients With Metabolic Risk Factors, Nicholas C. Cavarocchi, Paul Mather

Department of Surgery Faculty Papers

This is invited commentary to the following article:

Kilic, A., Conte, J. V., Shah, A. S., & Yuh, D. D. (2012). Orthotopic heart transplantation in patients with metabolic risk factors. Annals of Thoracic Surgery, 93(3), 718-724.

Early Versus Delayed Decompression For Traumatic Cervical Spinal Cord Injury: Results Of The Surgical Timing In Acute Spinal Cord Injury Study (Stascis), Michael G. Fehlings, Alexander Vaccaro, Jefferson R. Wilson, Anoushka Singh, David W. Cadotte, James S. Harrop, Bizhan Aarabi, Christopher Shaffrey, Marcel Dvorak, Charles Fisher, Paul Arnold, Eric M. Massicotte, Stephen Lewis, Raja Rampersaud

Department of Neurosurgery Faculty Papers

Background: There is convincing preclinical evidence that early decompression in the setting of spinal cord injury (SCI) improves neurologic outcomes. However, the effect of early surgical decompression in patients with acute SCI remains uncertain. Our objective was to evaluate the relative effectiveness of early (,24 hours after injury) versus late ($24 hours after injury) decompressive surgery after traumatic cervical SCI.

Methods: We performed a multicenter, international, prospective cohort study (Surgical Timing in Acute Spinal Cord Injury Study: STASCIS) in adults aged 16–80 with cervical SCI. Enrolment occurred between 2002 and 2009 at 6 North American centers. The primary outcome was …

A Placebo-Controlled, Double-Blind, Dose-Escalation Study To Assess The Safety, Tolerability And Pharmacokinetics/Pharmacodynamics Of Single And Multiple Intravenous Infusions Of Azd9773 In Patients With Severe Sepsis And Septic Shock, Peter E. Morris, Brian Zeno, Andrew C. Bernard, Xiangning Huang, Shampa Das, Timi Edeki, Steven G. Simonson, Gordon R. Bernard

Surgery Faculty Publications

INTRODUCTION: Tumor necrosis factor-alpha (TNF-α), an early mediator in the systemic inflammatory response to infection, is a potential therapeutic target in sepsis. The primary objective of this study was to determine the safety and tolerability of AZD9773, an ovine, polyclonal, anti-human TNF-α Fab preparation, in patients with severe sepsis. Secondary outcomes related to pharmacokinetic (PK) and pharmacodynamic (PD) parameters.

METHODS: In this double-blind, placebo-controlled, multicenter Phase IIa study, patients were sequentially enrolled into five escalating-dose cohorts (single doses of 50 or 250 units/kg; multiple doses of 250 units/kg loading and 50 units/kg maintenance, 500 units/kg loading and 100 units/kg maintenance, …

John Blair Deaver, M.D., And His Marvelous Retractor., Timothy E. Newhook, Md, Charles J. Yeo, Md, Pinckney J. Maxwell, Iv, Md

Department of Surgery Gibbon Society Historical Profiles

John Blair Deaver was born near Buck, Pennsylvania, in Lancaster County on July 25, 1855, to Dr. Joshua Montgomery Deaver and Elizabeth Clair Moore. The elder Deaver was a reputable country physician, educated at the University of Maryland, who fathered three physicians and a college president. John Blair Deaver (Fig. 1) went to boarding school at West Nottingham Academy in Maryland. After boarding school he taught in Lancaster County country schools to raise funds to attend the nation’s first medical school, the University of Pennsylvania. On receiving his M.D. degree in 1878, Dr. Deaver completed 1-year internships at both Germantown …

The Formal And Informal Surgical Ethics Curriculum: Views Of Resident And Staff Surgeons In Toronto., Frazer Howard, Martin F. Mckneally, Ross E.G. Upshur, Alex V. Levin

Wills Eye Hospital Papers

BACKGROUND: Understanding what staff surgeons think surgical trainees should learn and the ethical issues that trainees need to manage can strengthen surgical ethics education.

METHODS: Participants were recruited from the 15 surgical specialty and subspecialty programs at the University of Toronto. Semistructured interviews and focus groups were conducted with 13 ethics coordinators from the surgical staff and 64 resident trainees. Data were analyzed qualitatively using modified thematic analysis.

RESULTS: All coordinators and trainees felt that ethics education was an important component of surgical training. Real cases, varying teaching methods, and teachers with applicable clinical experience were valued. Trainees identified intraprofessional …

Surgical Outcome In Pet-Positive, Mri-Negative Patients With Temporal Lobe Epilepsy, Carla Lopinto-Khoury, Michael R. Sperling, Christopher Skidmore, Maromi Nei, James Evans, Ashwini Sharan, Scott Mintzer

Department of Neurology Faculty Papers

PURPOSE:

Fluorodeoxyglucose positron emission computed tomography (FDG-PET) hypometabolism is important for surgical planning in patients with temporal lobe epilepsy (TLE), but its significance remains unclear in patients who do not have evidence of mesial temporal sclerosis (MTS) on magnetic resonance imaging (MRI). We examined surgical outcomes in a group of PET-positive, MRI-negative patients and compared them with those of patients with MTS.

METHODS:

We queried the Thomas Jefferson University Surgical Epilepsy Database for patients who underwent anterior temporal lobectomy (ATL) from 1991 to 2009 and who had unilateral temporal PET hypometabolism without an epileptogenic lesion on MRI (PET+/MRI-). We compared …

Thoratec Heartmate Ii(®) Left Ventricular Assist Device Implantation In Patient With Patent Ventriculoperitoneal Shunt., Kentaro Yamane, Linda J Bogar, Shigeki Tabata, Hitoshi Hirose

Department of Surgery Faculty Papers

We report a case of HeartMate II® left ventricular assist device (LVAD) implantation as a destination therapy in a patient with a patent ventriculoperitoneal (VP) shunt after being suffered from subarachnoid hemorrhage. Because the patient's VP shunt was running through her right anterior chest and abdominal wall, a driveline exit site was selected in her left upper quadrant to avoid unnecessary perioperative complication in relation to the patent VP shunt tube. Tailored driveline placement was a key element of this LVAD implantation in this already sick patient with multiple comorbidities.

Macrophage Imbalance (M1 Vs. M2) And Upregulation Of Mast Cells In Wall Of Ruptured Human Cerebral Aneurysms: Preliminary Results., David Hasan, Nohra Chalouhi, Pascal Jabbour, Tomoki Hashimoto

Department of Neurosurgery Faculty Papers

BACKGROUND: M1 and M2 cells are two major subsets of human macrophages that exert opposite effects on the inflammatory response. This study aims to investigate the role of macrophage M1/M2 imbalance and mast cells in the progression of human cerebral aneurysms to rupture.

METHODS: Ten patients with cerebral aneurysms (five ruptured and five unruptured) underwent microsurgical clipping. During the procedure, a segment of the aneurysm dome was resected and immunostained with monoclonal antibodies for M1 cells (anti-HLA DR), M2 cells (anti-CD 163), and mast cells (anti-tryptase clone AA). A segment of the superficial temporal artery (STA) was also removed and …

James Marion Sims, M.D., Ll.D., Jonathan Tavares, B.S., Charles J. Yeo, Md, Pinckney J. Maxwell, Iv, Md

Department of Surgery Gibbon Society Historical Profiles

Few physicians have been as celebrated and loathed as James Marion Sims, M.D., LL.D. Dr. Sims’ modest early life and education never could have predicted that he would one day be called the ‘‘Father of American Gynecology.’’1, 2 Lauded by contemporaries and early historians as ‘‘one of the most original and gifted of American surgeons,’’ he performed the first successful operation to correct vesicovaginal fistulas (a condition that prior to 1852 was known as the ‘‘stumbling-block of gynecology’’).1 Today, the same work that earned Dr. Sims fame, fortune, and innumerable honors has been called into question, because of the unethical …

The Burden Of Breast Cancer In Italy: Mastectomies And Quadrantectomies Performed Between 2001 And 2008 Based On Nationwide Hospital Discharge Records., Prisco Piscitelli, Maddalena Barba, Massimo Crespi, Massimo Di Maio, Antonio Santoriello, Massiliamo D'Aiuto, Alfredo Fucito, Arturo Losco, Francesca Pentimalli, Pasquale Maranta, Giovanna Chitano, Alberto Argentiero, Cosimo Neglia, Alessandro Distante, Gian Luca Di Tanna, Maria Luisa Brandi, Alfredo Mazza, Ignazio R Marino, Antonio Giordano

Department of Surgery Faculty Papers

BACKGROUND: Where population coverage is limited, the exclusive use of Cancer Registries might limit ascertainment of incident cancer cases. We explored the potentials of Nationwide hospital discharge records (NHDRs) to capture incident breast cancer cases in Italy.

METHODS: We analyzed NHDRs for mastectomies and quadrantectomies performed between 2001 and 2008. The average annual percentage change (AAPC) and related 95% Confidence Interval (CI) in the actual number of mastectomies and quadrantectomies performed during the study period were computed for the full sample and for subgroups defined by age, surgical procedure, macro-area and singular Region. Re-admissions of the same patients were separately …

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 …