2012 Surgical Summer Research Students

Ben BiesterveldStudent: Ben Biesterveld
Ranked among top ten of 128 posters - received $500 prize
Preceptor: Dr. David Gourlay
Title: Inhibition of Alkaline Phosphatase and Progression of Necrotizing Enterocolitis

Necrotizing enterocolitis (NEC) is a complex disease of the neonatal GI tract. It is characterized as a hyper-inflammatory state with severe intestinal damage and gut barrier breakdown. Bacterial endotoxin, lipopolysaccharide (LPS), is implicated as mediator of NEC by signaling its receptor, TLR4 and causing a robust inflammatory response. Intestinal alkaline phosphatase (IAP) is an endogenous enzyme produced on the brush border of enterocytes that has been shown to dephosphorylate LPS, preventing interaction with TLR4. Our lab has shown that AP activity is significantly decreased in a neonatal rat model of NEC. Additionally, we have shown that enteral IAP supplementation is successful at attenuating NEC-associated symptoms. It is unclear whether the decrease in AP activity in NEC pups is a factor contributing to the disease progression, or a consequence of the loss of intestinal tissue that express IAP during NEC. My project is aimed at using inhibitors specific to IAP and tissue nonspecific alkaline phosphates (TNAP) to answer that question. I hypothesize that inhibition of IAP and not TNAP heightens sensitivity to LPS, leading to more severe NEC. I will be analyzing AP activity, intestinal injury, and expression of IAP, TNAP, TLR4 and inflammatory factors downstream of TLR4 to test my hypothesis.

Michael CainStudent: Michael Cain
Preceptor: Dr. Ronald Woods
Title: Major Neonatal Biventricular Cardiac Repair and Assessment of Optimal Timing of Surgery

Dextro-transposition of the Great Arteries (d-TGA) is the most common cyanotic cardiac anomaly, affecting 20-30 per 100,000 children and comprising nearly 10 percent of all congenital malformations. Anatomically, d-TGA is characterized by discordance of the ventriculoarterial connections of the heart, such that the aorta arises from the morphological right ventricle and the pulmonary artery arises from the morphological left ventricle, and therefore causes a separation of the systemic and pulmonary circulation. Due to development of severe cyanosis, short term catheter and/or pharmacological palliation followed by neonatal repair with an arterial switch operation prior to hospital discharge has become the standard of care. The current study aims to evaluate the impact of timing of the arterial switch operation in a cohort of patients presenting to Children’s Hospital of Wisconsin between January of 2000 and May of 2011 so as to better elucidate the optimal postnatal time of intervention. Previous studies on timing of repair have focused only on the risk of left ventricular de-conditioning associated with surgical correction after 1-2 months of age. Despite a general perception that slightly older neonates respond more favorably to surgical stress, there is a paucity of data evaluating outcomes and timing of repair within 2-3 weeks of life. The purpose of the study is to provide further insight into the optimal timing of surgical correction of d-TGA by investigating the relationship of morbidity and mortality with the timing of surgical intervention during the first month of life.

Brock CardonStudent: Brock Cardon
Preceptors: Dr. Terri deRoon-Cassini, Dr. Karen Brasel
Title: Efficacy of a Four-Item PTSD Screen in Trauma Patients with Long-Term Psychological Distress

Development of psychiatric disorders after traumatic injury, such as post-traumatic stress disorder (PTSD), often causes major complications in patients' future recovery. Since 2007, the MCW trauma team has instituted the use of the Post Traumatic Stress Disorder Checklist—Civilian version (PCLC), a 17-item questionnaire, to screen patients immediately following and six months after traumatic injury. Use of this screening procedure has greatly enhanced our ability to help patients with acute and chronic PTSD symptoms. Recently, a shorter, four-item questionnaire consisting of items currently on the PCLC has been shown to identify patients with acute PTSD symptoms with similar effectiveness. Our project seeks to examine the specificity and sensitivity of this shorter questionnaire in identifying patients with chronic PTSD symptoms at six months. To do so, we will retrospectively analyze the PCLC data compiled since 2007 from patients who completed surveys, both immediately following their injury as well as six months after. Our overall aim is to further improve and simplify our ability to identify patients with acute and chronic PTSD symptoms in order to target treatment to those most at risk for long-term psychological distress.

Michael ConnollyStudent: Michael Connolly
Preceptor: Dr. Jon Gould
Title: Validation of a Virtual Reality Based Robotic Surgical Skills Curriculum

The clinical application of robotic assisted surgery (RAS) is rapidly increasing. The skills necessary to perform robotic surgery are unique from those required for both open and laparoscopic surgery. A validated laparoscopic surgical skills curriculum has transformed the way surgeons acquire laparoscopic skills, but no such curriculum exists for robotic skills. Based on previously published data and expert opinion, we developed a robotic skills curriculum. We sought to evaluate this curriculum for evidence of construct validity (ability to discriminate between users of different skill levels). Four expert surgeons (defined as having performed >20 RAS) and twelve novice surgeons (second-year medical students with no surgical or RAS experience) were evaluated. The curriculum comprised five tasks utilizing the daVinci™ Skills Simulator (Pick & Place, Camera Targeting 2, Peg Board 2, Matchboard 2, and Suture Sponge 3). All subjects completed three consecutive repetitions of each task. Computer-derived performance metrics included time, economy of motion, master work space, instrument collisions, excessive force, distance of instruments out of view, drops, missed targets (in the case of the suture sponge), and overall score (a composite of all metrics). Performance of the two groups was compared using the Wilcoxon Rank Sum test with p <0.05 considered significant.

Brett FlanaganStudent: Brett Flanagan
Preceptors: Dr. Karen Brasel, Dr. Terri deRoon-Cassini
Title: Development of a Trauma Specific Quality of Life Measure

Patient quality of life can be used as an overarching assessment of how a patient is physically and mentally coping after traumatic injury. Many quality of life measures have been developed, including a generalized version called the SF-36. The goal of our study is to analyze a newly developed, trauma-specific, quality of life measure three months post-injury. Common types of trauma include falls, motor vehicle/motorcycle crashes, hand injuries, and gunshot wounds, all of which can be considered injurious disease. The survey questions, generated from qualitative analysis in trauma patient interviews, should assess their quality of life and correlate with the generalized SF-36 assessment. Trained research assistants administer the surveys via telephone to improve the completion rate. An exploratory factor analysis will help eliminate irrelevant or repeated questions and aid in question grouping. Additionally, concurrent validity will be explored with SF-36 and the post-traumatic stress disorder (PTSD) measure. Trauma summaries and additional narrative information is also being collected to aid future studies. Hopefully the trauma specific quality of life assessment will be a more successful tool in assessing quality of life in traumatically injured samples.

Michael HwangStudent: Michael Hwang
Preceptor: Dr. Kiran Turaga
Title: Systematic Review of Patients Undergoing Hepatic Resection in the Setting of Extra-Hepatic Disease

Survival for patients with metastatic colorectal cancer has improved significantly over the years due to improvements in systemic chemotherapy in conjunction with aggressive surgical resection and multi-modality therapies. Patients with liver-only metastases have a very favorable five-year survival and a possibility of cure when they undergo a complete resection. However, patients with metastases outside of the liver historically have been considered poor candidates for surgery, given the concern for systemic spread of the disease past the liver. With the advancement of chemotherapy agents and longer survival in recent years, there are now several reports of improved survival for patients undergoing resection of their extra-hepatic disease along with a hepatic resection. This strategy promises patients the ability to become disease free after careful selection. We will conduct a systematic review of the literature to collect and analyze the survival data of patients undergoing hepatic resection in the setting of resectable extrahepatic disease.

Bill KrauseStudent: Bill Krause
Preceptor: Dr. Travis Webb
Title: Retrospective Review of Geriatric Small Bowel Obstruction Treatment and Outcomes Compared to a Younger Cohort

As the segment of Americans 65 years of age and older rapidly increases, the number of emergency surgeries for that population also is increasing. To help prevent medical injury and reduce societal costs, research must be implemented to study specific emergency surgeries and their outcomes in the geriatric population. One such surgery is emergency abdominal surgery to treat a small bowel obstruction (SBO). We will be conducting a retrospective chart review of patients admitting from the emergency department with an SBO, and will compare a geriatric population to a younger cohort. We will be measuring different treatment factors and outcome results. Given the great impact of SBO treatment on the elderly and the increasing burden of elderly trauma on the healthcare system, it is imperative that more research is performed to provide guidance to clinicians attempting to achieve excellence in the emergency surgical care of the geriatric patient. By comparing the variances in treatment and outcomes of SBO management, we may be able detect certain differences in the geriatric population that will lead to better results and avoid unnecessary harm.

Jonathan LinStudent: Jonathan Lin
Preceptor: Dr. Amanda Kong
Title: Risk of Associated Tubular Carcinoma after Surgical Excision of a Complex Sclerosing Lesion or Radial Scar Diagnosed on Core Needle Biopsy of the Breast

Radial scars (RS) and complex sclerosing lesions (CSL) are benign breast lesions of unknown etiology that usually are found incidentally or upon screening mammography. There is currently no consensus among studies on whether the these lesions represent an independent risk factor for breast malignancy, are susceptible to malignant transformation themselves, or are simply a benign finding. Despite this lack of agreement, the current treatment for these lesions is excision upon diagnosis due to their possible association with breast cancer. In this study, we will analyze the medical records of women who have had a RS/CSL diagnosed on core needle biopsy to determine the incidence of carcinoma upon excision, the development of cancer in these patients following lesion excision, the characteristics of RS/CSL associated with malignancy, and the outcome of those RS/CSL that are not excised. We will also investigate other clinical variables associated with the presence of a RS/CSL such as body mass index, past hormonal use, family history of breast cancer, and clinical presentation of the lesion. The study aims to provide more information regarding the management of patients with a RS/CSL.

Tami MooreStudent: Tami Moore
Preceptor: Dr. Parvaneh Rafiee
Title: Wnt 5a as a Tumor Suppressor in OE 33 Esophageal Cancer Cells

Barrett’s Esophagus (BE), a change in the epithelial lining of the esophagus, is a complication often associated with the exposure to acidic environments due to gastroesophageal reflux disease. BE is often asymptomatic and benign, but in a small percentage of people with this disorder, BE progresses to Esophageal Adenocarcinoma (EAC), a highly malignant form of esophageal cancer. The family of Wnt proteins is important during development and embryogenesis, and they have been found to be involved in Wnt canonical pathways leading to cell survival and proliferation, as well as non-canonical Wnt pathways, which can lead to inhibition of canonical pathways possibly through Wnt 5a proteins. In support of this, it has been shown that there is a downregulation of Wnt 5a expression in both BE and EAC.  
My goal is to determine the role of Wnt 5a in cell proliferation and migration in OE33 esophageal cancer cell lines as well as its exact effect on the Wnt canonical pathways. I expect that Wnt 5a expression will lead to decreased proliferation and migration via inhibition of the Wnt canonical pathway in OE33 cell lines. Using various assays, I will determine cell proliferation and cell migration in cancer cells treated with recombinant Wnt 5a protein.

Ryan ScottStudent: Ryan Scott
Preceptor: Dr. Susan Tsai
Title: Evaluation of hENT-1 and RRM1 as prognostic markers in pancreatic cancer

Pancreatic cancer is the fourth leading cause of cancer death in the United States. Given the aggressive tumor biology of pancreatic cancer, early administration of effective agents is important and aids in the selection of individuals for surgical resection. Two biomarkers have been identified from retrospective series to have predictive value for pancreatic cancer chemosensitivity to gemcitabine, ribonucleoside-diphosphate reductase 1 (RRM1) and human equilibrative nucleoside transporter 1 (hENT-1). However, the expression levels of these biomarkers and their correlative effects can be mixed (e.g., hENT-1 expression suggests gemcitabine sensitivity, while RRM1 expression suggests gemcitabine resistance). The overall objective of this project is to assess the relative impact of hENT-1 versus RRM1 expression in pancreatic cancer sensitivity to gemcitabine. The aims of this project are twofold. The first is to compare the hENT-1 and RRM1 immunohistochemical profiling of resected pancreatic specimens as it relates to disease-free and overall survival in pancreatic ductal adenocarcinoma patients. The second is to correlate hENT-1 and RRM1 expression with gemcitabine-induced apoptosis using established and primary pancreatic cancer cell lines. The results of this study could potentially be used in the future for a more personalized treatment plan for PDAC based on the expression levels of these different biomarkers.

Jonathan SeligmanStudent: Jonathan Seligman
Preceptor: Dr. Jon Gould
Title: Retrospective, Population-Based Analysis of Emergent versus Non-Emergent Paraesophageal Hernia Repair Using the Nationwide Inpatient Sample

A large hiatal (paraesophageal) hernia that is mostly asymptomatic is often managed expectantly (no surgery). This is based largely on data from more than a decade ago, which suggest that the risks associated with elective repair exceed the risks of hernia progression and the potential need for emergent surgery related to the hernia. As the population ages and surgeons become more adept at treating these massive stomach hernias laparoscopically, it may be time to reconsider this approach. The aim of this project is to characterize and compare the clinical outcomes of patients admitted to the hospital who undergo repair of intrathoracic stomach either emergently or non-emergently. Our hypothesis is that increases in age and comorbidities, along with an emergent presentation are associated with increases in hospital morbidity and mortality rates following surgical repair of paraesophageal hernias. We also believe that a laparoscopic approach is independently associated with decreased morbidity and mortality rates compared to alternative approaches (open abdominal or thoracic). To investigate these questions, we will use data from the Nationwide Inpatient Sample (years 2005–2009).

Holly YongStudent: Holly Yong
Preceptor: Dr. Tracy Wang
Title: Thyroid Follicular Neoplasms in the Elderly: Does the Risk of Malignancy Justify Thyroidectomy?

Fine-needle aspiration (FNA) is a sensitive and specific diagnostic tool for preoperative determination of thyroid malignancy. However, approximately 20–30% of thyroid nodules will be classified as “atypical”, and require thyroidectomy to definitively rule out carcinoma. Although thyroidectomy is associated with low rates of morbidity and mortality, recent studies have shown the elderly to have higher postoperative complication and readmission rates. The purpose of this study is to investigate the malignancy rates of elderly patients undergoing thyroidectomy for atypical follicular lesions. A retrospective chart review will be performed of all patients who underwent thyroidectomy by MCW endocrine surgeons since July 2009; for patients with atypical follicular cytology, preoperative cytology and postoperative histology results will be compared by age groups to determine rates of malignancy and postoperative morbidity, including emergency room visits, hospital readmissions, and endocrine-specific complications, including hypoparathyroidism and recurrent laryngeal nerve injury. This work is supported by the National Institute on Aging T35 Training Grant.