2013 UTGSM Resident & Fellow Research Day by Univ. of TN Graduate School of Medicine

RESIDENT & FELLOW RESEARCH DAY 2013 Abstracts

The University of Tennessee Graduate School of Medicine and

Academy of Scholars Committee

Healing

Education

Discovery

The Academy of Scholars Committee

Department Anesthesiology

Pages 2-3

Cytopathology

Family Medicine

General Surgery

9 - 11

Internal Medicine

13 - 15

Obstetrics / Gynecology

17 - 20

Oral & Maxillofacial Surgery

Oral Head & Neck Surgery

Pathology Pulmonary Disease Radiology

26 - 29 31 33 - 34

Urology

Vascular Surgery

Anesthesiology

2013 Annual Research Day University of Tennessee Graduate School of Medicine

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INCIDENCE OF HYPOTENSION BETWEEN EPIDURAL ADMINISTERED LIDOCAINE AND CHLOROPROCAINE FOR CESAREAN SECTION Anesthesiology Brian Adams, MD Patrick McConville 3264 Original Research

Compare the hemodynamic effects of chloroprocaine versus lidocaine by analyzing the frequency of hypotension episodes. A retrospective database search identified 118 parturients who underwent epidural anesthesia for cesarean section with lidocaine or chloroprocaine. The number of hypotension episodes were recorded with an episode defined as a systolic blood pressure <90 mmHg or a =20% decrease from pre-operative baseline. Variables including age, pre-operative blood pressure, hypertensive disease, estimated blood loss, ephedrine use (mg), phenylephrine use (mg), and total intravenous fluid administration (mL) were collected. Patients receiving chloroprocaine were 4.66 times (95% CI 1.31-16.6) more likely to experience an episode of hypotension compared to those receiving lidocaine. No difference existed between groups using the =20% decrease from baseline criteria (p=0.16) but a difference existed for systolic <90 mmHg (p= 0.049). The mean number of hypotension episodes in chloroprocaine versus lidocaine patients was 12.57 to 7.82. 10% of chloroprocaine patients experienced no episodes of hypotension compared to 34.1% of lidocaine patients. No significant differences existed between age, estimated blood loss, phenylephrine use, pre-operative blood pressure, or total intravenous fluids. Those receiving chloroprocaine did receive significantly more ephedrine. Chloroprocaine patients experienced more hypotension episodes more frequently. Despite this finding, no significant difference existed for phenylephrine use, total intravenous fluids, or blood loss as one might expect. Attempting to isolate the hemodynamic effects of the two drugs is not easy and further studies may clarify any variation. Our study was limited by chloroprocaine patient size and the need for accurate variable charting.

2013 Annual Research Day University of Tennessee Graduate School of Medicine

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PREOPERATIVE PREDICTORS FOR INTRAOPERATIVE DOUBLE LOW AND TRIPLE LOW Anesthesiology Ron Benton Pitkanen, MD Robert M. Craft, MD; Roger C. Carroll, PhD; Justin Barnes, MS 3611 Original Research

The combination of low mean alveolar concentration (MAC) requirements, low mean arterial pressure (MAP), and/or low bispectral index (BIS) are phenomena known as “triple low” and “double low” respectively. Triple low is associated with 30-day mortality. Using this as a surrogate for mortality, we investigated whether preoperative comorbidities predicted an increased incidence of double/triple low intraoperatively. Mean intraoperative MAC, MAP, and BIS were defined for 18,256 patients from 18--99 years old undergoing non-emergent, non-cardiac surgery via general inhalational anesthetic, who had a preoperative evaluation within 30 days. Means and standard deviations were established for MAC, MAP and BIS intraoperatively. Categories for double/triple low as assessed by both case-based and time-based methods were correlated with the preoperative evaluation. Multiple regression analysis with stepwise elimination was utilized to determine independent predictors of double/triple low. Values that exceeded one standard deviation below the mean for MAC (<0.8), MAP (<75) , and BIS (<40) correlated well with those of Sessler, et al. Age, ASA classification, tobacco use, low BMI, renal failure, CHF, and CVA were all independent predictors of intraoperative double low. Advanced age, low BMI, and renal failure were independent predictors of triple low. Advanced age, low BMI, and renal failure were predictors of triple low. Anesthesiologists usually correlate higher BMI with worsened outcomes, but our data suggests otherwise for this specific occurrence. Renal failure has been associated with negative outcomes, thus the association with triple low may be more expected. Further investigations into these relationships with respect to causality are still needed.

Cytopathology

2013 Annual Research Day University of Tennessee Graduate School of Medicine

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CELL BLOCK PREPARATION FOR TRANSBRONCHIAL FINE NEEDLE ASPIRATION CASES GENERATES ADEQUATE TISSUE FOR ANCILLARY TESTING Cytopathology George M. Sneed, D.O. Lisa D. Duncan, M.D.; Matthew J. Curzon, M.D.; Paul Branca, M.D. 3571 Original Research

Transbronchial fine needle aspiration (TBNA) is routinely performed to diagnose lung and mediastinal lesions and establish carcinoma nodal stage. TBNA is less invasive than radiographic-guided core biopsy and mediastinoscopy. No tissue for immunohistochemistry (IHC) and molecular testing is a procedure limitation. This study describes the utility of an optimized cell block (CB) preparation technique. 47 patients had TBNA of mediastinal or lung lesions, resulting in 80 cell blocks. Needle rinse from TBNA material was collected in Saccomanno's then subjected to centrifugation. CB adequacy and diagnoses were compared with aspirate smears. Ancillary testing performed from CB was documented. 67 (84%) CB were from lymph nodes and 13 (16%) from lung lesions. 41 CB (51%) had companion aspirate smears. Aspirate smears from 2 patients (4.3%) were malignant with a non-diagnostic companion CB. 18 CB (38% of patients) were malignant (4 squamous cell carcinoma, 5 small cell carcinoma, 5 adenocarcinoma, 2 non-small cell carcinoma, 1 carcinoid, 1 favor Hodgkins lymphoma). 2 CB (2 patients) had sarcoid and 1 had Histoplasmosis. 14 malignant CB had successful IHC. Epithelial growth factor receptor mutation was negative in 2 cases (2 patients). Anaplastic lymphoma kinase mutation was successfully performed on 2 of 3 CB (3 patients). Our CB preparation method for TBNA is effective in accurately diagnosing lung and mediastinal lesions, providing material for IHC and molecular testing. Patient care is improved by providing a less invasive procedure which can successfully procure diagnostic tissue suitable for molecular testing needed to guide patient therapy.

Family Medicine

2013 Annual Research Day University of Tennessee Graduate School of Medicine

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THE PSYCHOLOGICAL IMPACT OF CARDIOVASCULAR SCREENING: THE ATHLETE’S PERSPECTIVE Family Medicine Jonathan B. Laymance, MD, Irfan M. Asif, MD

Serena Johnson, Jason Schmeig, Brett Toresdahl, MD, Hank Pelto, MD, Tiffany Smith, Jeffrey Fairbrother PhD, Rebecca Zakrajsek, PhD, Leslee Fisher, PhD, Kimberly G. Harmon, MD, and Jonathan A. Drezner, MD 3316 Original Research

To determine the psychological implications of cardiovascular screening in athletes. Prospective, non-randomized controlled trial. High school athletes received a standardized history and physical exam (control group) or a history and physical + ECG (ECG group). Pre- and post-screen validated assessments for health attitudes, anxiety, and impact of screening on sport were conducted using a 5-point Likert scale (-2 to 2). T-tests and ANOVA measured differences between groups. 955 student-athletes participated in the study (control=153; ECG= 802); 49.7% female, mean age 15.5 years. In the ECG group, 576 had negative screens, 220 had an abnormal screen (by history 19.7%, physical 6.7%, or ECG 1.8%) but normal work-up (false-positive), and 6 were identified with a serious cardiac condition (true-positive, 0.75%). Those who received an ECG were more likely to: 1) be satisfied (p<0.001), 2) feel safer during competition (p<0.003), 3) support that all athletes should receive cardiac screening (p<0.001), and 4) state the ECG positively impacted their training (p<0.001). Individuals requiring additional testing did not report anxiety (mean score= 0.25). Compared to control subjects, individuals with false-positive results had similar positive psychological benefits as above. ECG screening does not cause undue anxiety in athletes and there are a number of positive psychological benefits. Significance: The American Heart Association supposition that ECG screening causes excessive anxiety in athletes is unproven. Psychological distress should not be used as a rationale against ECG screening.

General

Surgery

2013 Annual Research Day University of Tennessee Graduate School of Medicine

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IN VIVO TESTOSTERONE SUPPLEMENTATION DECREASES CIRCULATING INTERLEUKIN FAMILY ISOFORMS AND DIFFERENTIALLY REGULATES MMPS

General Surgery Brian Freeman, MD

Mountain D.J.H., Brock T.C., Chapman J., Kirkpatrick S.S., Stevens S.L., Goldman M.H., Klein F.A., Freeman M.B., Grandas O.H. 3622 Original Research

Androgen deficiency (AD) is associated with increased risk of vascular disease, yet the molecular mechanisms remain unclear. Our group has previously demonstrated female sex hormones influence hyperplasia development via inflammatory-modulated matrix metalloproteinase (MMP) regulation. Here we investigated the effect of testosterone on circulating MMPs and inflammatory cytokines. We hypothesize that AD is acting as a pro-inflammatory modulator contributing to dysfunctional vascular remodeling. Aged orchiectomized rats were implanted with testosterone pellets (TST; 0.5-150mg). Serum was collected 0-28d. TST levels in young, aged intact (AI), and placebo controls were 2.72±0.35, 2.31±0.66, and 0.15±0.07ng/ml per ELISA. Sub-physiological, physiological, and supraphysiological levels were achieved at 14d with 0.5, 2.5, and 35mg pellets (0.37±0.09, 2.89±0.44, 13.45±0.65ng/ml). Inflammatory cytokine arrays indicated interleukin family isoforms IL-1a, IL-2, IL-6, IL-10, and IL-1R6 were elevated in the absence of TST, while TST supplementation decreased interleukins in a dose-dependent manner, approaching basal young and AI levels. MMP inhibitor TIMP-1 was decreased in AI and placebo vs. young, while TST increased TIMP-1 in a dose-dependent manner. ELISA indicated MMP-9 was significantly decreased in AI vs. young (25.2±2.4, 53.1±8.6ng/ml). Placebo, sub-physiological, and physiological TST had no significant effect, while supra-physiological levels significantly elevated MMP-9 (72.0±17.9ng/ml) compared to all aged groups. Testosterone downregulates interleukins and differentially affects circulating MMP isoforms in vivo. Future studies will examine the role of AD in inflammatory cytokine and MMP-modulated hyperplasia development in animal models of vascular disease. AD could be playing a role in vascular disease via the regulation of inflammatory signaling cascades. 9

2013 Annual Research Day University of Tennessee Graduate School of Medicine

Academy of Scholars

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IMPROVED OUTCOMES FOR PERMANENT HEMODIALYSIS ACCESS

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General Surgery Sagar S. Gandhi, MD

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Juan Gallegos MD, Rebecca Jarvis RN, Patrick B. Barlow, R. Eric Heidel PhD, Mitchell H. Goldman MD, Oscar Grandas MD 3416 Original Research

To examine our patency rates, compare them to national averages and draw conclusions to improve outcomes. The secondary goal of our study was to examine patient factors that may contribute to failure of HD accesses. A retrospective review of the UTMCK Vascular Access Database was performed which consisted of approximately 1200 patients from 2008-2012. Five hundred sixteen first permanent accesses were performed. Our Fistula First rate was 89.5%. Our primary patency rate, assisted primary rate, secondary patency rate for AVF was 77%, 76% and 63% respectively (n = 340) and for AVG was 84%, 85 %, and 73% respectively (n = 41). Cumulative patency rates were 86%, 82%, 77%, 69% at 3, 6, 12, and 24 months respectively. Mean follow up was 17 months. When reviewing patient comorbidities, only CHF was found to be statistically significant for patency(p = 0.03). A Fistula First rate above the national average can be obtained. Furthermore, our patency rates are higher than rates quoted in the literature. Increased patency rates can be achieved with a protocol in which all patients have preoperative venous mapping, vascular surgeons who are committed to the Fistula First initiative and who are aggressive in early interventions. Furthermore, a vascular access center can assist in improving primary patency rates by providing a single channel for feedback, close surveillance, and education of HD centers. It can also reduce costs by triaging patients so that same day interventions can be performed, which can decrease the number of admissions and reduce ED visits.

2013 Annual Research Day University of Tennessee Graduate School of Medicine

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REMOTE CUTANEOUS PHOTOGRAPHY FOR PUBLIC DERMAL SCREENINGS

General Surgery Valerie Sams, MD Georgette Samaras, BS, David Shupp, MD, Matthew Hanngi, MD, Lindsey Fish, MD, Matthew Jones, MD, John Bell, MD, Keith Gray MD, James Lewis, MD 3048 Original Research

There are no randomized studies that demonstrate an overall survival benefit from public cutaneous screenings; however, there may be a substantial benefit to screening targeted individuals. We hypothesized that a cutaneous screening program using photography would direct individuals with photographically suspicious lesions toward intervention. Institutional IRB for the study was obtained. Participants were offered the opportunity to participate in photographic dermal screening and attended community screening venues between September 2010 and May 2011. After obtaining informed consent and personal history, targeted lesions were digitally photographed, stored on a secure database, and graded by a physician. A grading system was created to describe the degree of suspicion that a lesion was malignant and the quality of the photograph itself. Lesions were given a score designated “skin-rads” (SR) score of 0-3. SR0 meant the photo could not be evaluated, SR1 was visually benign, SR2 needed clinical evaluation and SR3 recommended biopsy. Participants with SR2/3 lesions were referred to clinicians and contacted for results of the biopsy. Of the 297 lesions photographed, 165 (55.6%) were SR1, 88 (29.6%) SR2, 27 (9.1%) SR3, and 18 (5.6%) SR0. Seventy-seven participants had SR2 or SR3 lesions of which we were able to contact 41(53%). Eighteen (44%) sought medical attention and 11 (26.8%) underwent biopsy. Biopsy results included 4 non-melanoma carcinomas, 2 melanomas, 3 benign lesions and 4 with unknown results. Public Photographic Dermal Screening (PPDS) can identify patients with suspicious lesions who need further evaluation. This process continues to be refined and studied at our institution.

Internal Medicine

2013 Annual Research Day University of Tennessee Graduate School of Medicine

Academy of Scholars

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FUNCTIONAL NEUROIMAGING IN ATHLETES WITH CONCUSSION

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Internal Medicine Maxwell Rajan, MD

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Wen Ching Liu, PhD; Dzung Dinh, MD MBA, University of Illinois 177732 Original Research

Concussion is a common, yet complex entity. Incidence is estimated at 6/1000 within the general population, more within participants of contact sports. However, little is known about the actual patterns of damage or their evolution. Diffusion tensor imaging (DTI) is a novel imaging modality for identifying changes in neural tract function; using water as the MR contrast, DTI can identify change in axon diffusion pattern and axon water flux. A prospective, controlled study to identify neural tracts damaged by concussion during subacute and resolving injury was done. Subjects were gathered from a university soccer and high school football team. Soccer subjects were pre-scanned using DTI and fMRI (0- and 2-back protocols) and observed over the season for evidence of headtrauma. High school football players were directly admitted to the study via emergency department without baseline scans. Scans were administered at 24-48 hours and two weeks post-injury. Scans were pooled and processed using exhaustive, two-sample ttest with family-wise error rate correction and threshold-free cluster enhancement. Significant disruption in diffusion patterns were found in major anterior-posterior running tracts and in the limbic system (p<0.05), while significant increases in flux were found upstream of damage (p<0.05). Superimposed fMRI data identified gray matter regions with high probability of housing the cell bodies of high flux axons. . Given that increased flux is occurring upstream of white matter with altered diffusion properties, neural up-regulation is likely within the setting of concussion.

2013 Annual Research Day University of Tennessee Graduate School of Medicine

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AN ASSESSMENT OF COLIFORM BACTERIA IN WATER SOURCES NEAR APPALACHIAN TRAIL SHELTERS WITHIN THE GREAT SMOKY MOUNTAINS NATIONAL PARK Internal Medicine Brian C. Reed, MD Mark Rasnake, MD 3610 Original Research

It has long been held that water obtained from wilderness sources should be treated prior to drinking. Compliance with this practice among hikers is variable. This project focuses on coliform bacteria in water samples taken near popular Appalachian Trail shelters during two seasons. Water was collected from designated water access points near 10 high elevation trail shelters within the Great Smoky Mountains National Park (GSMNP) during summer and fall months. These samples were inoculated on a commercial coliform detection kit for quantitative determination of total coliform counts and Escherichia coli counts. During summer, 7 out of 10 samples were positive for coliform bacteria and 6 for E. coli. The MPN of CFU for coliform bacteria ranged from 0 to 489 CFU/100mL, with the MPN for E. coli varying from 0 to 123 CFU/100mL. A total of three sites were negative for coliform bacteria. These data differed from the fall collection, revealing 4 out of 7 samples positive for coliform bacteria and 1 for E. coli. The MPN of CFU for coliform bacteria varied from 0 to 119 CFU/100mL and 0 to 5 to CFU/100mL for E. coli. EPA drinking water standards require 0 CFU/ 100mL to be considered safe. After a preliminary analysis of 10 water sources along Appalachian Trail, the majority of water access points require treatment during the summer season. Coliform burden was not as worrisome through the fall months, though was still a concern for some sites. This data will illuminate infectious disease risks for wilderness travelers.

2013 Annual Research Day University of Tennessee Graduate School of Medicine

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A NOVEL APPROACH WITH A NOVEL PRODUCT: AEROSOLIZING PHYTOBACTERIA FOR DISINFECTION

Internal Medicine Matthew D Stone, MD David Bemis, PhD; Mark Rasnake, MD FACP 3331 Original Research

Evaluate an aerosolized formula of bactalave as a possible solution to cleaning a hospital room. A study was performed with metal discs inoculated with a known concentration of methicillin-resistant Staphlycoccus aureus (MRSA), vancomycin-resistant enterococci (VRE), Acinetobacter baumanii, and Klebsiella pneumoniae. Discs with organism burdems of 103, 104, 105, and 106 colony forming units were prepared then placed in a simulated patient room with groups of discs in covered and open areas. A prototype machine was used to aerosolize a solution of phytobacteria based disinfectant. The room was fogged for a variable amount of time and then allowed to settle for 15 minutes. Discs were collected and cultured in broth to evaluate for any growth after exposure to the disinfectant. A control set of discs were not exposed to disinfectants. Uncovered bacteria with direct exposure showed no growth of any pathogens at inoculations of 104 or less. Higher organism burdens of MRSA and VRE were more resistant to inactivation. Uncovered disc with indirect exposure had no growth up to10x3 colony units for MRSA, 10x-4 colony units for VRE, 10x-5 colony units for K. pneumoniae, and all concentrations for A. baumanii. The covered bacteria had postexposure growth at all concentrations except in the K. pneumoniae and A. baumanii groups which both had no growth up to 10x-5 colony units. All control discs had growth at all concentrations. This study demonstrates the effectiveness of a phytobacteria based disinfectant in decontaminating hospital equipment. Initial results indicate the importance direct contact with the disinfectant.

Obstetrics Gynecology

2013 Annual Research Day University of Tennessee Graduate School of Medicine

Academy of Scholars

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COSTS OF CONTRACEPTIVES VARY BY INCOME

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Obstetrics and Gynecology Audrey Barry, MD

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Nikki B Zite, MD; Lorraine S Wallace, PhD 3634 Original Research

For many patients, cost is a leading barrier to obtaining contraceptives. As a result, cost-associated lack of access has been hypothesized as one of the major factors associated with high unintended pregnancy rates. A previous study showed wide discrepancies in the cost of prescription medication as a function of geographic location; the goal of this study was to determine whether this disparity exists for prescription contraceptives (PCs). Prices for seven commonly used PCs (oral and transvaginal) were obtained from the MyFloridarx.com website for pharmacies throughout the state. Median household income data were obtained for all Florida zip codes from the 2010 census. Median household incomes were then divided into quintiles with prices of the 7 PCs compared across zip code income groups across the state. Nearly every PC was more expensive to obtain for those residing in low-income zip codes. A combination of ANOVA and Kruskal-Wallis tests were used to determine statistical significance of the price variations, which showed a significant main effect for income group in two PC prices. Post hoc analyses demonstrated that the highest income group reported significantly lower prices than other income zip codes for two PCs ( p=.003, .001, .007, & .000). Prescription contraceptives remain an important option for contraceptive use. This study shows several contraceptive options are more expensive in lower income areas. Ensuring that costs of contraceptives are equivalent among socioeconomic groups could foster improved access for all women.

2013 Annual Research Day University of Tennessee Graduate School of Medicine

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HIGH GRADE PRIMITIVE NEUROECTODERMAL TUMOR OF THE UTERUS: A CASE REPORT

Obstetrics and Gynecology A. Mitch Dizon, MD Larry C. Kilgore, MD, Kristopher J. Kimball, MD 3501 Case Presentation

Primitive neuroectodermal tumors (PNETs) are small round cell tumors from cells similar to embryonic ectoderm. PNETs are usually in the central axis, soft tissues, or bones. PNETs of the uterus are extremely rare. Early diagnosis is essential as localized disease responds relatively well to intense multi-modality treatment. A 50yo female with history of treatment for breast cancer presented with abdominopelvic pain. CT scan revealed an enlarged uterus with ill-defined mass contiguous with the uterine fundus suggestive of sarcoma. CA-125 was 407. The patient was referred to Gynecologic Oncology, undergoing diagnostic laparoscopy, exploratory laparotomy, radical hysterectomy, bilateral salpingo-oophorectomy, omentectomy, optimal debulking, and extensive lysis of adhesions. A 15 cm, necrotic mass arose from the uterine fundus. Immunohistochemical stains were positive for CD 99, FLI-1, and Vimentin. Pathology revealed high-grade PNET. The patient received adjuvant Carboplatin and Etoposide. Recent CT scan identified no evidence of disease. PNETs are usually in the central nervous system, soft tissues, or bones. The ovary is the most common site in the female genital tract; the uterus is rare, reported in less than 50 cases. Risk factors include adolescent or postmenopausal age, and Caucasian or Hispanic race. The most common symptom is abnormal vaginal bleeding. The differential diagnosis includes tumors exhibiting neuroectodermal elements. Diagnosis is based on microscopic evaluation and immunohistochemical stains. The standard chemotherapy regimen of Vincristine, Doxorubicin, Cyclophosphamide, and Etoposide has yielded good results; Carboplatin with Etoposide shows similar survival with less toxicity. Due to PNET’s rarity and aggressiveness, mortality is high despite combination therapy.

2013 Annual Research Day University of Tennessee Graduate School of Medicine

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CHRONIC OPIATE USE IN PREGNANCY AND NEWBORN HEAD CIRCUMFERENCE

Obstetrics and Gynecology Kevin Visconti, MD Kerry Hennessy, Craig Towers, Bobby Howard 3548 Original Research

To evaluate whether opiate abuse/usage in pregnancy affects newborn head circumference. Maternal opiate use has significantly increased in our location and large dosages of prescription oral agents are the primary drugs ingested. All newborns admitted to the NICU for treatment of neonatal abstinence syndrome were prospectively collected. The birth and perinatal ultrasound information were retrospectively obtained and analyzed. Data included the gestational age (GA) at delivery, gender, birth weight, head circumference (HC) at birth, opiate type, and the perinatal ultrasound assessment of growth parameters prior to delivery. From January 1, 2010 to May 30, 2012, 332 neonates were admitted for the treatment of NAS. A total of 96 (29.5%) had a HC <10th percentile for GA (p<0.01). Of these 96, 25 (7.7%) were <3rd percentile and 71 (21.8%) were >3rd<10th percentile; however, 62.5% were AGA in birth weight at delivery. Of the 332 total cases, 196 had at least one ultrasound evaluation prior to delivery and of these, 141 were within 10 days of birth. Based on the ultrasound parameters, a HC<5th percentile was found in 38.3% of cases of which 74% were consistent with the post-delivery findings. Of interest, the femur length measurements were <5th percentile in 36.2% of fetuses in these 141 ultrasound evaluations; however, 70.5% of those with a small femur length were AGA in weight at delivery. Opiate abuse/usage in pregnancy in the form of oxycodone, oxymorphone, and buprenorphine appears to increase the risk for a head circumference <10th and <3rd percentile when compared to controls.

2013 Annual Research Day University of Tennessee Graduate School of Medicine

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BLOOD CONTAMINATED AMNIOTIC FLUID AND THE LAMELLAR BODY COUNT FETAL LUNG MATURITY TEST

Obstetrics and Gynecology Kevin Visconti, MD Craig Towers, Mark Hennessy, Bobby Howard, Stephanie Porter, Beth Weitz 3369 Original Research

To determine if blood contamination falsely elevates the Lamellar Body Count (LBC) fetal lung maturity test. Because the TDx-FLM test is no longer available, many laboratories are converting to LBC. Lamellar bodies are the size of platelets and are counted by hematology cell counters. Previous studies are limited by small numbers; used stored pooled amniotic fluid specimens; and added non-pregnant heparinized or EDTA blood, none of which occur in clinical practice. The concern with blood contaminated amniotic fluid obtained by amniocentesis is the platelets in the blood could falsely elevate the LBC. Mothers undergoing amniocentesis for fetal lung maturity were prospectively consented to participate. Approximately 8cc’s of clear amniotic fluid were obtained with 6cc’s for patient evaluation and 2cc’s for study assessment. 1-2 drops of the patient’s blood was added to the 2cc sample creating a specimen that was grossly blood contaminated at a level previously determined to be consistent with those found in clinical practice. Tests were run in tandem using the non-contaminated sample for clinical purposes. Of the 50 study patients, the LBC decreased by > 3000 in 33 samples (66%) and remained unchanged in 16 specimens (32%). In only 1 case (2%) did the value increase – the actual result of 37,000 increased to 44,000 (both of which exceeded the mature level in our institution). Maternal blood contamination of amniotic fluid obtained for fetal lung maturity testing does not falsely increase the LBC in 98% of cases. Therefore, a mature blood contaminated LBC test result is reliable.

Oral and Maxillofacial Surgery

2013 Annual Research Day University of Tennessee Graduate School of Medicine

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A FIVE YEAR RETROSPECTIVE REVIEW OF PRIMARY PALATOPLASTY CASES UTILIZING AN ACELLULAR COLLAGEN INTERPOSITIONAL GRAFT

Oral and Maxillofacial Surgery David O Pickett DMD, MS JW Hudson DDS 3376 Case Presentation

Herein we report a series of primary palatoplasties reconstructed with acellular collagen membrane that aided in maintaining closure between the oral and nasal cavity without the development of an oronasal fistula, and did not interfere during speech habilitation. Six patients were identified and followed for one year. Patient #1: 10 month old male, patient #2: 12 month old female, patient #3: 12 month old female, patient #4: 6 year old male, patient #5: 12 month old female and patient #6: 18 month old female; all with primary cleft palatoplasty. An acellular collagen membrane was placed between the muscular layer and the oral mucosa during primary palatoplasty procedure. Tisseel was utilized to stabilize the acellular collagen graft and to provide a further seal between the nasal and oral cavities. Pictures, and post follow up speech evaluations were utilized to follow progress. At the one year follow up, no oronasal fistulae had developed where the acellular collagen membrane augmentation was used. Speech form and function were preserved. Patients are continuing near (normal) growth development, as would be anticipated. 1. The use of an acellular collagen graft to aid in the 3 layer of closure of primary palatoplasty surgery is a very effective strategy both in primary and secondary healing and in preventing oronasal fistulation. 2. To perform a second surgery for oronasal fistula closure increases the risk of an unfavorable outcome. 3. The risk associated with utilization of acellular collagen membranes appears nonexistent.

Oral Head & Neck surgery

2013 Annual Research Day University of Tennessee Graduate School of Medicine

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SECONDARY FINDINGS OF POSITRON EMISSION TOMOGRAPHY/COMPUTED TOMOGRAPHY (PET/CT) SCANS IN HEAD AND NECK CANCER PATIENTS

Oral/Head and Neck Surgery Andrew WC Lee, MSc, DDS, MD Robert E Heidel, PhD; Eric R Carlson, DMD, MD, FACS 3613 Original Research

Positron emission tomography/computed tomography (PET/CT) scanning has become a useful imaging modality in staging of many human malignancies. Studies of various human cancers have demonstrated the ability of PET/CT to identify serendipitous findings. The objective of this study was to evaluate the incidence of secondary findings in head and neck cancer patients subjected to staging PET/CT studies. Four hundred one 18F-FDG PET/CT scans were retrospectively analyzed in 310 head and neck cancer patients from 2002 to 2012. There were 149 females and 161 males between the ages of 18 to 95 years (mean = 63). Secondary, serendipitous diagnoses were divided into organ systems, which were then subcategorized into specific clinical findings. Patients with incidental findings were followed longitudinally and those requiring subsequent surgical procedures were recorded. A total of 929 secondary findings were noted in 275 of 310 patients (88.7%). Pulmonary nodules accounted for 27.2% of the findings; followed by 12.2% perihilar lymphadenopathy; 9.9% hepatobiliary disease; 6.5% renal lesions; 5.3% thyroid diseases; and 4.7% colon lesions. Fourteen patients (5.0%) underwent surgical procedures to address their secondary diagnoses. Nine secondary malignancies were noted amongst these serendipitous findings (2.9%). This study identified that the number needed to treat was 20 to preserve or improve the quality of life of patients in this study cohort. PET/CT is valuable in staging patients with head and neck cancer. It can provide structural and functional imaging of many serendipitous secondary findings. Although most incidental findings were benign, secondary malignancies were identified, thereby permitting expedient treatment.

Pathology

2013 Annual Research Day University of Tennessee Graduate School of Medicine

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INTRATHYROIDAL BRANCHIAL CLEFT-LIKE EPIDERMOID CYST ASSOCIATED WITH NODULAR HASHIMOTO’S THYROIDITIS: A RARE PATHOLOGIC FINDING IN A COMMON PATHOLOGIC ENTITY Pathology Matthew J. Curzon, M.D. Sarah Carroll, M.D.; Laurentia Nodit, M.D.; Amila Orucevic, M.D., PhD 3630 Case Presentation

Intrathyroidal lymphoepithelial/epidermoid cysts are identified rarely, with only a handful of cases described in the literature. We report a case of intrathyroidal branchial cleft-like epidermoid cyst arising in the background of Hashimoto’s thyroiditis. A 71 year old female with history of hypothyroidism treated with levothyroxyn had a “gurgling type” of feeling and neck symptoms for some time. On ultrasound of the thyroid, a 1.3 cm cystic and solid nodule was identified in the right upper pole. Fine needle aspiration of the lesion showed numerous benign squamous cells with no associated follicular cells. Differential diagnosis included epidermal inclusion cyst, thyroglossal duct cyst, and squamous metaplasia. The patient underwent a right thyroid lobectomy. On gross examination, a 1.0 cm cyst filled with brown creamy fluid was seen in the background of brown slightly nodular thyroid parenchyma. On microscopic examination, the cyst was lined with squamous epithelium and showed keratinous material within the lumen. Thin fibrotic cyst wall was only very focally associated with lymphoid tissue, and surrounding thyroid gland showed lymphocytic thyroiditis. A diagnosis of intrathyroidal branchial cleft-like epidermoid cyst arising in the background of nodular Hashimoto’s thyroiditis was issued. in rare published case reports of intrathyroidal Proposed etiologies lymphoepithelial/epidermoid cysts included development from embryological remnants of branchial pouches, a metaplastic process of follicular epithelium, teratomatous origin, and an immunological mechanism secondary to inflammation-induced squamous metaplasia with subsequent cystic degeneration and enlargement. Intrathyroidal branchial cleft-like epidermoid cyst in our patient is most likely caused by immunologic mechanisms induced by Hashimoto’s thyroiditis.

2013 Annual Research Day University of Tennessee Graduate School of Medicine

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INCIDENCE AND DESCRIPTION OF NEVUS CELL RESTS AND THEIR DISTINCTION FROM ISOLATED TUMOR CELLS IN SENTINEL LYMPH NODES REMOVED FOR MELANOMA STAGING Pathology Karyn L. DeSouza, MD Lisa D. Duncan MD, James Lewis MD 3252 Original Research

Sentinel lymph node excision is integral to melanoma surgical staging. Individual immunohistochemical (IHC) positive cells are challenging, requiring distinction between isolated tumor cells and benign nevus cell rests (NCR), as even isolated tumor cells represent N1 disease. In this study, the incidence and growth pattern of nevus cell rests are described to form a basis of comparison for isolated IHC positive cells in sentinel lymph nodes removed for melanoma. Melanoma triple stain was performed on nodes from the axilla, inguinal area, cervical area, and intraparotid area removed for non-melanoma related conditions, simulating regions typically sampled during melanoma sentinel node procedures. Location, size, and histomorphology of nevus cell rests were recorded. Triple stain positive NCR were identified in 4.5% inguinal nodes, 0.5% cervical nodes, (0.9%) axillary nodes, and 0% intraparotid nodes. NCR in these cases were intracapsular, demonstrate spindle cell morphology, and were not perceptible on routine stains. NCR in 13 additional cases had 16 total NCR with a combined epithelioid and spindle morphology, the majority of which were intracapsular. Incidence of NCR is higher in the inguinal location relative to other anatomic locations studied. NCR identified only by immunohistochemistry are predominantly intracapsular and have a spindled fibroblastic morphology. This finding in sentinel nodes can create diagnostic confusion with metastasis, emphasizing recognition of this pattern in NCR. Isolated cell pattern was not observed in any of our study cases. Our results suggest that an isolated cell pattern identified in melanoma-specific IHC stains should be interpreted as metastatic melanoma.

2013 Annual Research Day University of Tennessee Graduate School of Medicine

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LOWER UTERINE SEGMENT CELLS IN A THINPREP PAP SMEAR: A DETAILED CYTOLOGIC DESCRIPTION OF A DIAGNOSTICALLY CHALLENGING BENIGN FINDING Pathology N. Lynn Ferguson, MD Lucy E. DeFanti, DO; Angela Yates, MD; Lisa D. Duncan, MD 3580 Original Research

Lower uterine segment (LUS) cells are occasionally identified in ThinPrep Pap smears and can cause diagnostic confusion, mimicking endometrial, endocerivcal, and ectocervical neoplasms. Cytology literature is deplete of comprehensive descriptions of LUS cells, complicating appropriate classification. Our objective was to selectively collect and describe LUS cells then compile a photomicrograph database to facilitate education of cytotechnologists and pathologists in this diagnostically challenging finding. This study includes 21 consecutive benign hysterectomy specimens. The lower uterine segment of the bisected uterus was identified by standard accepted criteria. This area was selectively swabbed with a ThinPrep pap collection spatula and endocervical brush. The specimen was suspended in PreservCyt solution and processed by the standardized ThinPrep method. LUS cells were described and a photomicrograph database was created. 16 specimens yielded lower uterine segment cells for microscopic examination. 5 cases were excluded due to low cellularity, and 2 were excluded due to a post-surgical diagnosis of at least low grade squamous intraepithelial lesion. The remaining 14 cases were reviewed and a photomicrograph database was created. LUS cells had large hyperchromatic nuclei, prominent nucleoli, nuclear overlap, and large finger like cellular arrangements. LUS cells are poorly characterized in ThinPrep Pap smears and are difficult to classify due to similarities with dysplastic/malignant entities. Our study describes LUS cells and provides a photomicrograph database to be utilized as an educational tool for cytotechnologists and pathologists who must be able to recognize this cell type to prevent misdiagnosis.

2013 Annual Research Day University of Tennessee Graduate School of Medicine

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PROGNOSTIC VALUE OF YOUNG AGE, BREAST CARCINOMA RECEPTOR SUBTYPES AND PATHOLOGIC TUMOR CHARACTERISTICS ON OVERALL SURVIVAL OF CAUCASIAN WOMEN WITH BREAST CANCER

Pathology Solomon Lee, DO N. Lynn Ferguson, E. Robert Heidel, John Bell and Amila Orucevic 3156 Original Research

Triple negative breast carcinoma (TNBC) subtype (ER-/PR-/HER2-) has been associated with worse overall prognosis in comparison to other carcinoma subtypes in studies involving young and ethnic minorities. Our published institutional study of 593 Caucasian women with breast cancer diagnosed from 2000-2004 questioned whether TNBC subtype may carry the same prognostic value in Caucasians. We have now evaluated the same cohort for the prognostic value of young age on breast cancer overall survival (OS), when controlled for ER/PR/HER2 subtype and pathologic tumor characteristics. Study of 593 invasive breast cancer cases identified 42 young women age<40. After grouping patients into <40 or >40 y/o, ER/PR/HER2 status and its effect on OS were analyzed using a Kaplan-Meier curve, along with effect of tumor grade and tumor-node status using a multivariate Cox regression. Same analyses were performed on groups divided by age: <40, 41-50, 51-60, 61-70 and >70. TNBC patients showed shorter OS than ER+/PR+/HER2-, regardless of age (p=.003- .03). TNBC subtype divided into five age groups showed statistically significant effect of age on OS. This significance disappeared when the >40 age groups were combined. Overall, patients >70 showed 2.6x higher mortality rates, and patients 41-50 and 51-60 showed 0.4x and 0.5x relative mortality rates compared to <40, respectively. Patients <40 and 61-70 had similar OS. Our data suggest that TNBC subtype, young age and old age may carry worse overall prognosis in Caucasian females compared to other carcinoma subtypes and middle age. However, additional studies are required for validation.

Pulmonary Disease

2013 Annual Research Day University of Tennessee Graduate School of Medicine

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ROLE OF DIASTOLIC HEART DYSFUNCTION ON CLINICAL COURSE OF PATIENTS WITH ACUTE COPD EXACERBATION WITH POSITIVE PRESSURE VENTILATION REQUIREMENTS.

Pulmonary Disease Arseniy V. Tsapenko, MD, DO Patrick B. Barlow, Michael T. McCormack, MD, FCCP 3539 Original Research

Positive pressure ventilation (PPV) is being used as a standard rescue modality of lung ventilation in patients with respiratory failure secondary to COPD with acute exacerbation (COPDAE).We suspected that those patients with diastolic heart failure (DHF) in the settings of COPDAE with requirements to be on PPV have more complicated respiratory failure recovery course rather than those patients with no DHF. The purpose of this study was to evaluate if patients with DHF have longer hospitalization course compare to similar patient with no DHF . Patients, who were participated in this study, were selected as per study design criteria. All of these patients were admitted with COPDAE and required PPV were distributed in two groups with and without evidence of DHF on transthoracic ECHO. Descriptive statistic of study sample between DHF and no-DHF patient groups was performed, analyzed and compared. 43 patients admitted with COPDAE who were on PPV were included in this study. 15 patients were in no-DHF group and 28 patients were in DHF group. Descriptive statistics of no-DHF and DHF groups were following: Female n(%)/Male n(%) : 8(58%)/ 7(42%) and 16(57%)/13(43%) respectively, age mean(SD) : 59.00( 7.98) and 63.39(8.05) respectively, days on PPV mean( SD) : 3.60 (2.20) and 4.65 (3.92) respectively. Patients admitted for COPDAE with DHF with PPV requirement will spend longer time on PPV before their respiratory status improves compare to patients admitted for COPDAE with no-DHF.

Radiology

2013 Annual Research Day University of Tennessee Graduate School of Medicine

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18F-FDG PET/CT PROVIDES ACCURATE GROSS TUMOR VOLUME DEFINITION FOR 90Y RADIOEMBOLIZATION Radiology Ted T. Chang, MD Yong C. Bradley MD, Alexander S. Pasciak PhD* 3502 Original Research

Yttrium-90 (90Y) radioembolization is an innovative treatment for primary and metastatic liver cancer. 90Y treatment dosage calculations commonly use the SIRTex Body Surface Area (BSA) method which requires measurement of tumor and normal liver volumes from a pre-treatment hepatic protocol CT. These patients, however, often receive concomitant 18F-FDG PET/CT studies to evaluate disease burden. This study compares the biologic tumor volume (BTV) obtained by fused PET/CT and gross tumor volume (GTV) obtained with contrast enhanced CT and the subsequent differences in the prescribed treatment dosage. A retrospective review of patients undergoing off-label radioembolization with 90Y microspheres from 1/1/2011 – 1/1/2013 was conducted. Per our institutional protocol, these patients received pretreatment hepatic protocol CT and 18F FDG PET/CT within 2 weeks prior to treatment. Both the GTV and BTV were measured by two radiologists on an Siemens XD3 workstation. These volumes were then used in the SIRTex BSA model to determine differences in Y90 treatment activity. Tumor volume determination by both PET/CT and CT showed only minimal differences, averaging 2.9% between GTV and BTV. The subsequent BSA dosage calculations for the administered 90Y activity were similar between both groups with an average percent difference of less than 1%. Differences in tumor volume determined from contrast enhanced CT and those determined from FDG PET/CT do not affect 90Y radioembolization treatment dosage when the manufacturer recommended calculation model is used. These findings may allow for additional flexibility in pretreatment imaging with no resultant affect on treatment outcome.

2013 Annual Research Day University of Tennessee Graduate School of Medicine

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RESULTS OF THE FIRST INTRA-PROCEDURAL Y90 PET/CT PERFORMED TO OPTIMIZE TREATMENT EFFICACY OF RADIOEMBOLIZATION FOR HEPATIC MALIGNANCY

Radiology Ted T. Chang, MD Austin C. Bourgeois MD, John J. Snidow MD, Alexander S. Pasciak PhD* 3502 Case Presentation

Radioembolization using yttrium-90 (90Y) microspheres is a popular treatment for hepatic malignancies. However, the efficacy of this treatment can depend significantly on patient-specific anatomical variations which can affect the uptake of microspheres in the tumor. Using standard imaging methods, anatomical variations cannot be assessed prior to treatment, leaving no opportunity for modification of the treatment dosage to improve efficacy. We present the results from the first published intra-procedural quantitative 90Y PET/CT performed with the goal of ensuring maximum treatment efficacy. A patient with biopsy-proven hepatocellular carcinoma was referred for 90Y radioembolization. The manufacturer-recommended dosage of 90Y microspheres, which is not patient-specific, was infused in the first part of a two-step treatment. Immediately after the infusion, a 90Y PET/CT was performed which indicated that a sub-tumoricidal dose was delivered. An additional infusion of 90Y microspheres was delivered on the same day to ensure a tomoricidal therapy, based on the information obtained from the 90Y PET/CT. Following the two-part therapy, the average absorbed dose to the tumor was 115.2 Gy. This level of dose is comparable to published tumoricidal thresholds and is significantly higher than it would have been if the manufacturer recommended treatment protocol was used. Follow-up contrast-enhanced CT has shown a significant reduction in tumor burden with expected positive long-term outcome. 90Y PET/CT has the capability to determine the patient-specific absorbed dose following 90Y microsphere radioembolization. A two-step treatment utilizing this novel imaging method can be effectively used to ensure tumoricidal dose delivery and treatment efficacy.

Urology

2013 Annual Research Day University of Tennessee Graduate School of Medicine

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PREDICTIVE VALUE OF CURRENT IMAGING MODALITIES FOR THE DETECTION OF UROLITHIASIS DURING PREGNANCY: A MULTICENTER, LONGITUDINAL STUDY Urology John Beddies MD

Elizabeth Johnson MD, Nikki Zite MD, Amy Krambeck MD, Elias Hyams MD, Tracy Marien MD, Ojas Shah MD, Brian Matlaga MD, Vernon Pais, Jr. MD and Wesley White MD 3386 Original Research

To determine the optimal imaging study by which to diagnose and subsequently treat pregnant patients with suspected urolithiasis. A retrospective, multi-center study was performed to determine the comparative accuracy of imaging modalities employed prior to surgical management of suspected urolithiasis in pregnant patients. Patients with clinical suspicion of urolithiasis were evaluated with directed imaging, including renal ultrasound (RUS) alone, RUS and lowdose computed tomography (LDCT), or RUS and magnetic resonance urography (MRU). The rate of negative ureteroscopy was determined and the positive predictive values (PPV) of the aforementioned imaging modalities were calculated. A total of 51 pregnant patients underwent ureteroscopy. Twenty-four women (47%) underwent RUS and LDCT, 22 women (43%) underwent ultrasound alone, and 5 women (10%) underwent RUS and MRU. Negative ureteroscopy, occurred in 7 of the 51 patients (14%). Patients who had a CT scan had the lowest rate of negative ureteroscopy at 4.2% (1/24 patients). Patients with ultrasound alone had the highest incidence of negative ureteroscopy at 23% (5/22 patients), and patients with MRU had a 20% incidence of negative ureteroscopy (1/5 patients). Positive predictive values of CT, MR, and ultrasound were 95.8%, 80%, and 77% respectively. Among pregnant women undergoing intervention in our series, the rate of negative ureteroscopy was 14%. In the group taken to surgery after imaging with ultrasound alone, 23% had no ureteral stone, giving it the lowest PPV of the utilized modalities. Alternative advanced imaging techniques, particularly LDCT, offer improved diagnostic information that can optimize subsequent management and largely obviate unnecessary intervention.

Vascular Surgery

2013 Annual Research Day University of Tennessee Graduate School of Medicine

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HORMONAL REGULATION OF LYSYL OXIDASE IN VASCULAR REMODELING

Vascular Surgery Jason R Chapman, MD

Deidra JH Mountain PhD; Stacy S Kirkpatrick BS; Scott L Stevens MD; Josh D Arnold MD; Mitchell H Goldman MD; Michael B Freeman MD; Oscar H Grandas MD 3621 Original Research

Lysyl oxidase (LOX) initiates the covalent cross-linking of elastin and collagen in wound healing and has been shown to increase in vascular lesions post-intervention. We have previously demonstrated dysfunctional matrix metalloproteinase regulation in hormone replacement therapy (HRT)-modulated intimal hyperplasia (IH). Likewise, we hypothesize that HRT plays a role in LOX-mediated IH. Here we investigated the effect of estrogen and progesterone on LOX expression in vitro and in vivo. Human vascular smooth muscle cells (VSMCs) were treated with estrogen (Est; 0- 500nM) for 24h. LOX expression was measured by qPCR normalized to 18S. Aged ovariectomized (OVX) female rats were implanted with slow-release Est (0.72mg), progesterone (Prog; 200mg), combination (EP), or placebo (Plac) pellets and 6 weeks later underwent carotid artery balloon angioplasty. Vessels were stained 14 days postinjury with Trichrome-elastin and LOX-specific antibodies. Intima:Media (I:M) ratios are used to quantify degree of hyperplasia. Data is reported as mean±SEM, n=4-7. I:M decreased in OVX rats receiving Plac (0.925±0.046, P<0.05) vs. non-OVX controls (1.345±0.074). I:M slightly increased in OVX animals receiving Est (1.022±0.077) and EP (1.066±0.104) vs. Plac. While neither Est or Prog alone had an effect on LOX expression in vitro or in vivo, EP combination therapy significantly increased LOX expression in vivo (% intima area stained: non-OVX control, 42.25±6.83; OVX – EP, 78.20±6.05; P<0.05) HRT increased I:M ratios, though significance was not reached with the doses given. While LOX expression may be playing a role in EP-mediated IH, other mechanisms should be investigated to delineate the role of HRT in IH development.