ASSOCIATION FOR ACADEMIC SURGERY AND SOCIETY OF UNIVERSITY SURGEONS—ABSTRACTS280

31.13. The Change from Scarless Regeneration to ScarFormation with Increased Fetal Tendon Wound Size IsAssociated with Significant Upregulation of Inflamma-tory Genes. D. M. Bermudez,1 B. J. Herdrich,1 M. Allukian,III,1 B. Chin,1 Z. Zhang,2 L. J. Soslowsky,3 K. W. Liechty4;1University of Pennsylvania School of Medicine and theCenter for Fetal Diagnosis and Therapy at the Children’sHospital of Philadelphia, Philadelphia, PA; 2Center forBiomedical Informatics at the Children’s Hospital ofPhiladelphia, Philadelphia, PA; 3Penn Center forMusculoskeletal Disorders, University of Pennsylvania Schoolof Medicine, Philadelphia, PA; 4Department of Surgery,University of Mississippi Medical Center, Jackson, MS

Purpose: The adult healing response to tendon injury results insignificant morbidity including contracture, scarring and de-creased mobility. The majority of these complications of the heal-ing process are due to scar formation or fibrosis. In contrast, thefetal response to tendon injury is regenerative or scarless, andlacks fibrosis. However, we have shown that if the fetal tendonwound increases in size, there is a change from regenerative to re-parative healing and scar formation. We hypothesized that thischange is associated with upregulation of inflammatory gene ex-pression. Methods: To test our hypothesis, we used our fetalsheep tendon model of regenerative and reparative healing, whichremoves gestational age as a potentially confounding variable. Inthis model, small wounds (50% tenotomy) heal regenerativelywhereas large wounds (50% tenotomy with a 2 mm excision) healreparatively. Small and large wounds were created in the lateralforelimb extensor tendon in 70-75 day gestation fetal sheep(n¼ 4). The tendons were harvested 3 days after wounding andprocessed for RNA isolation. An ovine specific, microarray genechip was then used to analyze gene expression. Two gene groupsof interest, ‘‘wound response’’ and ‘‘inflammatory response,’’ wereselected from the Gene Ontology database. These two gene groupswere analyzed for a significant difference in gene expression be-tween the large and small tendon wound groups. Results: A totalof 15,010 genes were analyzed for differential gene expression. Theraw microarray signals were processed by loess normalization andlog2-transformation. A gene was considered to be differentiallyexpressed between small and large wounds if it had at leasta two-fold change and a p-value less than 0.05 (t-test). 56 geneswere upregulated in small tendon injuries and 213 genes were up-regulated in large tendon injuries. We evaluated whether therewas differential gene expression between the ‘‘wound response’’and ‘‘inflammatory response’’ groups of genes. Using all otherprobes as background reference, both gene sets as a whole weresignificantly over-expressed in large wounds compared to smallwounds (p¼ 4.8e-3 and 4.3e-8 respectively). Conclusion: In re-sponse to injury, there is a differential gene expression responsebetween small regenerative and large reparative wounds. Under-standing the mechanisms of this regulation may help to identifypotential therapeutic targets to promote regenerative healing inthe adult and prevent the complications of fibrosis in adult tendonhealing.

31.14. Incidence and Outcomes of Extremity Sarcomas inChildren. R. Yang, M. C. Cheung, M. P. Ogilvie, Y. Zhuge,L. G. Koniaris, J. E. Sola; University of Miami Miller Schoolof Medicine, Miami, FL

Objective: To examine incidence, risk, and outcomes for extremitysarcomas in pediatric patients. Methods: The Surveillance, Epidemi-ology, and End Results database (1973_2005) was queried for all pa-tients under 20 years of age. Results: A total of 1,107 pediatricpatients with extremity sarcomas were identified for an overall age-adjusted incidence of 0.46 cases per 100,000 children. The medianage at diagnosis was 12 years. Most patients were older than 10 yearsof age (72%, n¼ 798), male (55%, n¼ 606), Caucasian (77%, n¼ 855),and non-Hispanic (82%, n¼ 908). The most common tissue of originwas muscle (21%, n¼ 235), overwhelmingly rhabdomyosarcomas(RMS) and mostly alveolar type. Of the tumors with known differen-tiation, most were anaplastic (12.9%, n¼ 145). Most patients pre-sented with local disease (59%, n¼ 657), and underwent surgicalintervention (88%, n¼ 973) regardless of histological type, but didnot have radiotherapy (62%, n¼ 685). Tumors derived from musclewere more likely to present in younger children (p< 0.001) and withdistant disease (p< 0.001). Older patients were more likely to receiveradiotherapy than patients less than 5 years of age (40.4% versus5.8%, p< 0.001). Median survival time (MST) for the entire cohortwas 120 months, and five- and ten-year survival times were 77%and 72%, respectively. By univariate analysis, there was no differencein survival related to gender, race, ethnicity, or age. Tumors derivedfrom muscle had significantly worse survival (MST 116 months, five-and ten-year survivals 55% and 50%, respectively, p< 0.001). Pa-tients with regional disease had significantly improved survivalwhen compared to those with distant disease (87% and 82% five-and ten-year survivals versus 30% and 26%, p< 0.001). Surgical in-tervention significantly prolonged survival (MST 120 months versus57 months and five- and ten-year survival of 81% and 76% versus47% and 44%, respectively, p< 0.001). Radiotherapy was associatedwith worse survival (70% and 64% versus 81% and 77% five- andten-year survivals, p< 0.001). Multivariate analysis identified mus-cle tissue of origin (HR 2.126, CI 1.070 - 4.226, p¼ 0.031), regionalor distant disease (HR 1.827, CI 1.284 - 2.628, p¼ 0.001, and HR5.916, CI 4.217 - 8.300, p< 0.001, respectively), and lack of surgical in-tervention (HR 2.134, CI 1.505 - 3.025, p< 0.001) as independent pre-dictors of poor outcome. Conclusions: Extremity sarcomas are mostcommon in older children. The mainstay of therapy remains surgicalintervention. Factors that predict improved survival include earlydetection and prompt resection of these tumors.

31.15. Incidence and Outcome of Pediatric Malignant Neuro-endocrine Tumors. J. C. Gutierrez, M. C. Cheung, Y.Zhuge, L. G. Koniaris, J. E. Sola; University of Miami MillerSchool of Medicine, Miami, FL

Purpose: Malignant neuroendocrine tumors (NET) are rare solidtumors infrequently seen in children. We sought to examine currentincidence trends and outcomes for children with NET. Methods:The SEER registry was examined for patients between birth and 19years of age between 1973 and 2004. Results: Overall, 481 patientswere identified with malignant NET. Females outnumbered males53 vs 47% for an age-population adjusted incidence of 0.995 and0.504 per 100,000, respectively. Adolescents (15-19 years) comprised55% (n¼ 266) of the cohort, while 9.6% (n¼ 61) were less than 10years old. The majority of patients were white (81%), non-Hispanic(83%), who had the highest and increasing incidence (0.751/100,000population and APC¼ 0.842, p< 0.05). Tumors were classified as ma-lignant carcinoid (n¼ 189, 39.3%), neural (n¼ 127, 26.4%), medullary

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thyroid carcinoma (n¼ 88, 18.3%), neuroendocrine carcinoma (n¼ 50,10.4%), pheochromocytoma (n¼ 17, 3.5%), and paraganglioma (n¼ 7,1.5%). Only 15.6% of tumors were in the appendix. Over 60% (n¼ 232)of patients had localized disease, while 13.5% (n¼ 52) presented withdistant metastasis. Children less than 5 years of age had worse 5-yearsurvival (< 50% vs> 76% if older, p¼ 0.009). Blacks had lower 5-yearsurvival compared to whites (61% vs 81%, p¼ 0.001). Favorable tu-mor locations included appendix, lung, and thyroid (> 95% 5 year sur-vival), whereas soft tissue, and ovary location were associated withpoor survival (p< 0.001). Distant metastasis, radiation therapy, andno surgery were all associated with less than 55% 5-year survival(vs> 80% 5-year survival for localized disease, no radiation, andsurgery, p< 0.001). Conclusions: Pediatric NET are seen rarely inchildren but whites have the highest incidence which significantly in-creased for this group throughout the study period. Black childrenand those less than 5 years of age had lower survival.

31.16. Review of Survival by Extent of Resection in High RiskNeuroblastoma. K. Day,1 M. Zimmerman,2 J. Shilyansky3;1Carver College of Medicine, Iowa City, IA; 2University ofIowa College of Public Health, Iowa City, IA; 3University ofIowa Hospitals and Clinics, Iowa City, IA

Introduction: Neuroblastoma is a childhood malignancy of neuralcrest origin. Patients are stratified based on n-myc amplification,Shimada classification, stage and age. Children in the high riskgroup have approximately 15% long-term survival. The role of com-plete surgical resection in the treatment of stage IV (InternationalNeuroblastoma Staging System) Neuroblastoma is controversial.Methods: We conducted a review of published peer-reviewed litera-ture reporting outcomes following the surgical resection of stage IVand high risk stage III (N-myc amplified) neuroblastoma availableon PubMed by keyword search of the terms: ‘‘neuroblastoma’’,‘‘high risk’’, ‘‘metastasis’’, ‘‘resection’’, ‘‘complete’’, ‘‘gross total’’ and‘‘incomplete’’. All articles and their cross-references that reportedthe overall survival, complication rate, and/or three and/or five-year event-free survival following resection of stage IV neuroblas-toma in patients greater than one year of age were included. Articlesthat did not include any of the above data, included resection ofalternate tumor subtypes, or described non-surgical treatmentwere excluded. Our primary endpoint was comparison of survival af-ter complete versus incomplete resection, with secondary endpointsof the effect of localized radiation and neoadjuvant chemotherapy,and complication rates associated with extent of resection. Results:41 articles making reference to either the primary or secondaryendpoints were identified with long-term survival data comparingextent of resection in a small minority of these reports. Complete re-section improved survival compared to incomplete resection almostinvariably in these publications, though follow-up intervals andmethod of reporting were inconsistent. This increased survival cor-relates with increased local tumor control. Survival may be en-hanced by localized radiation therapy, which was reported ina limited number of publications. Comparisons of complication ratesby the extent of resection varied widely and did not exhibit consis-tent association with extent of resection. Conclusions: Completeresection of residual tumor in stage IV neuroblastoma following neo-adjuvant chemotherapy, possibly in combination with radiationtherapy, provides the best long-term chance for survival ascompared to incomplete resection. Differences in post-surgical com-plications were equivocal. Further research is necessary to deter-mine the optimal multimodality treatment regimen for advancedstage neuroblastoma.

31.17. Non-Wilms Tumors of the Kidney in the PediatricPopulation: A Review of Outcomes and Predictors ofSurvival. Y. Zhuge, M. C. Cheung, R. Yang, J. C. Gutierrez,

L. G. Koniaris, J. E. Sola; University of Miami Miller Schoolof Medicine, Miami, FL

Objective: To determine the outcomes and predictors of survivalfor pediatric non-Wilms renal tumors. Methods: The Surveillance,Epidemiology, and End Results database (1973-2005) was queriedfor all patients under 20 years of age. Results: A total of 349 casesof pediatric non-Wilms renal tumors were identified. The major his-tologic groups include renal cell carcinomas (RCC) (44.1%), clearcell sarcoma (CCS) (17.2%), and malignant rhabdoid tumors(MRT) (11.5%). Overall, a bimodal age distribution was observed,with tumors commonly presenting in patients 2 year old or youngerand in patients 16 years old or greater. However, greater than 50%of patients with RCC were diagnosed after the age of 15 years,whereas in patients with CCS or MRT, greater than 50% of thesepatients were younger than the age of 5 years. Of patients withCCS, a 3:1 predominance of male patients was observed. At thetime of diagnosis, RCC (56.8%) and CCS (52.5%) tumors weremore likely locally staged while MRT were more likely in advancedstages (51.3%, p< 0.001). Overall 10-year survival for the entire co-hort was 63% with improved survival observed in patients withCCS (79%) and RCC (70%) versus MRT (29%, p< 0.001). Byunivariate analysis, surgical resection improves overall survival(10-year survival: 68% vs. 30%, p< 0.001), while no differencewas observed for patients undergoing radiotherapy (10-year overallsurvival: 60% vs. 63%, p¼ 0.814). By multivariate analysis, worseoverall survival was observed for patients >10 years old (HR4.01, p¼ 0.013) and those diagnosed with advanced disease(HR¼ 12.78, p< 0.001). In addition, patients diagnosed withMRT (HR¼ 11.61, p< 0.001) had significantly worse prognosiswhen compared to those diagnosed with RCC. Surgical resectionwas observed to improve overall survival (HR¼ 0.36, p¼ 0.001)while no difference in survival was observed with radiotherapy(p¼ 0.837). Conclusion: Pediatric non-Wilms renal tumors arecomposed mainly of RCC, CCS, and MRT. Younger patients andthose diagnosed with RCC have improved survival while a diagno-sis of MRT portends a worse prognosis. Surgical extirpation is theonly identifiable treatment modality that significantly improvessurvival.

31.18. Long Term Outcomes of Surgically Treated BiliaryAtresia - Four Decades of Experience. L. E. Fischer,L. M. Flanigan, R. P. Altman, R. A. Cowles; ColumbiaUniversity College of Physicians and Surgeons, New York, NY

Background: Biliary atresia (BA) is an inflammatory sclerosingcholangiopathy of uncertain etiology which is fatal without surgicalintervention. Kasai portoenterostomy (KP) and, if needed, livertransplantation (LTx) have offered prolonged survival to this co-hort of patients. We sought to describe the long term outcomes ofall patients with BA treated at two centers by two surgeons overthirty six years. In addition, we attempted to evaluate the trendsin care over time as the treatment team has gained experiencewith KP, LTx, and overall management of children with BA.Patients and Methods: All patients who underwent KP for BAwere evaluated. Initial KP and treatment were provided by oneof the two senior authors. Data were kept both prospectively andgathered retrospectively when needed. Information was obtainedregarding age, sex, race, presenting laboratory values and associ-ated conditions. Outcomes such as bile drainage, survival withKP only, need for LTx, and overall survival were evaluated. Deathwas presumed in all cases of patients lost to follow-up with evi-dence of poor health or liver failure at last follow-up. Results:238 children with BA underwent KP between June 1972 and March2009. Gender and ethnicity were distributed as follows: 128 (53.6%)female, 154 (64.4%) Caucasian, 32 (13.4%) African American, 27