- Email: [email protected]
7. The Effect of Vocal Cord Injury on Pulmonary Allograft Function Following Bilateral Orthotopic Lung Transplant
ASSOCIATION FOR ACADEMIC SURGERY AND SOCIETY OF UNIVERSITY SURGEONS—ABSTRACTS 177 Introduction: Gender differences have been noted in acute ischemia and reperfusion injury (I/R). Estrogen and the estrogen receptors appear to play a critical role in cardiovascular gender differences, given that females have improved myocardial functional recovery associated with decreased inflammatory response and reduced apoptotic signaling compared with males. Indeed, our previous studies have shown that estrogen and estrogen receptor (ER) alpha exert protection against I/R on the female heart. However, it is unclear what role ER beta (ERb) plays on the gender differences associated with myocardial functional recovery following I/R. Therefore, we hypothesized that: 1) ERb enhances myocardial protection in female hearts, but not males; 2) ablation of ERb neutralizes gender differences in post-ischemic myocardial functional recovery. Methods: Adult male and female wildtype (WT) and ERb knockout (ERbKO) mouse hearts were isolated, perfused via Langendorff model, and subjected to 20 minutes ischemia, 60 minutes reperfusion. Myocardial contractile function (the positive/negative first derivative of pressure: ⫹/⫺ dP/dt) was continuously recorded. Data were analyzed with ANOVA, p⬍0.05⫽statistically significant. Results: Females had markedly improved functional recovery compared with males following I/R (p⬍0.01). After 20 min reperfusion, ERbKO females exhibited significantly less functional recovery than WT females and were similar to WT males (please see table). However, ablation of ERb did not significantly change post-ischemic functional recovery in males. Conclusion: Estrogen receptor beta plays a prominent role in estrogen induced myocardial protection.
Post-Ischemic Values of dP/dt (% of Equilibration) in WT and ERbKO Hearts From Male and Female
M WT F WT MERbKO FERbKO M WTdP/dt F WTdP/dt MERbKOdP/dt FERbKOdP/dt
10 min Reperfusion
20 min Reperfusion
30 min Reperfusion
40 min Reperfusion
50 min Reperfusion
60 min Reperfusion
23.17.4% 21.78.4% 7.43.0% 10.12.6% ⫺22.87.8%
35.88.7% 46.28.1% 20.66.0% 30.57.8% ⫺35.48.7%
36.06.3% 58.54.1%# 30.57.7% 38.07.6%* ⫺36.07.3%
42.74.9% 64.84.3%# 35.07.4% 42.07.2%** ⫺39.24.3%
47.02.7% 69.52.4%# 40.86.6% 44.77.0%** ⫺44.13.3%
48.11.9% 76.22.6%# 41.98.0% 50.08.1%*** ⫺45.92.9%
⫺60.77.6%#
⫺67.47.7%#
⫺69.75.5%#
⫺73.24.3%# ⫺43.68.6%
22.99.3%
50.510.4%
⫺7.22.1%
⫺21.76.5%
⫺31.28.7%
⫺37.08.8%
⫺41.89.0%
⫺11.23.4%
⫺31.07.9%
⫺37.27.6%* (*p ⬍ 0.05 vs. FWT)
⫺41.27.4%** (**p ⬍ 0.01 vs. FWT)
⫺43.97.5%** (***p ⬍ 0.001 vs. FWT)
⫺49.48.0%* (#p ⬍ 0.01 vs. MWT)
6. ROLE OF NONO IN TNF〈-INDUCED P4H〈1 SUPPRESSION. Cheng Zhang1, Ming-Xiang Zhang1, Ying H. Shen1, Yun Zhang2, Koichi Yoshimura5, Hiroki Aoki5, Masunori Matsuzaki5, Scott A. LeMaire1, Joseph S. Coselli1, Xing Li Wang1; 1Baylor College of Medicine, Houston, TX; 2Shandong University Qilu Hospital, Jinan, China; 5Yamaguchi University, Ube, Japan Previously, we have shown that TNF␣ inhibits P4H␣(I) expression via the ASK1-JNK pathway, resulting in reduced type I and III collagen synthesis in primary human aortic smooth muscle cells (HASMCs). This finding is significant because inflammation is an established causal factor in the pathogenesis of aortic aneurysm, in which arterial wall extracellular matrix (ECM) homeostasis plays a critical role. In the current study, we further investigated the molecular connections between inflammation and reduced collagen synthesis via the expression of P4H␣(I), the rate-limiting subunit for the P4H enzyme essential for procollagen hydroxylation, secretion, and deposition. Using 2-D electrophoresis and LC/MS-MS, we detected several nuclear proteins that may participate in TNF␣-induced P4H␣(I) suppression. One of these, human NonO protein, appeared to be responsible for the effect because NonO silence abolished the effect of TNF␣. Using JNK1 overexpression vector, we found that JNK1 directly suppressed the expression of P4H␣(I) comparing to the dominant negative expression vector. The JNK1 appeared to be
activated through the MKK4 upstream pathway, which was in turn activated by the ASK1. Furthermore, when NonO was silenced in HASMCs, the P4H␣(I)-suppressing effect of the overexpressed JNK1 disappeared. However, neither TNF␣ nor JNK1 altered the expression of NonO, which was expressed constitutively. A ChIP assay showed minimal binding between the NonO protein and P4H␣(I) DNA promoter under baseline conditions. However, exposure to TNF␣ or JNK1 caused a dramatic increase in binding between the NonO protein and P4H␣(I) promoter, which was associated with the suppressed P4H␣(I) expression. In an immunoprecipitation assay, several nuclear proteins were identified by the LC/MS-MS in complex with the DNA-bound NonO protein; of these proteins, DJ-1 was the only one associated with the P4H␣(I)-suppressing effect. DJ-1 bound to P4H␣(I) promoter via the NonO protein and DJ-1 knockdown incompletely reduced the TNF␣ effect on the binding between the P4H␣(I) promoter and the NonO protein. We conclude that the posttranslational modification of the nuclear DNA-binding protein NonO in complex with other nuclear transcriptional proteins is responsible for TNF␣-mediated P4H␣ suppression. 7. THE EFFECT OF VOCAL CORD INJURY ON PULMONARY ALLOGRAFT FUNCTION FOLLOWING BILATERAL ORTHOTOPIC LUNG TRANSPLANT. Keki R. Balsara, Broadus Zane Atkins, Errol L. Bush, Robert Duane Davis, Jr., Shu S. Lin; Duke University Medical Center, Durham, NC Introduction: Vocal cord injury following bilateral orthotopic lung transplantation (BOLT) is a known complication which places patients at increased risk of impaired phonation and tracheobronchial aspiration. Since chronic aspiration often results from gastroesophageal reflux disease (GERD) and since GERD has been found to be associated with chronic pulmonary allograft dysfunction, as evidenced by the development of bronchiolitis obliterans syndrome (BOS) in these lung transplant recipients, there is a prevailing hypothesis that GERD-related aspiration, facilitated by vocal cord injury, is a significant cause of BOS. Surgical intervention to treat GERD in lung transplant patients has resulted in recovery of graft function for those with early BOS. Traditional treatments for vocal cord injury include injection with medialization. In this study, the effect of vocal cord injury on pulmonary allograft function, notably in regards to aspiration and GERD, is examined. Methods: We completed a retrospective review of all adult, primary BOLTs performed between January of 2000 and July of 2005 at a single medical center (n ⫽ 227). All patients underwent formal pulmonary function tests and the peak one-year FEV1 (% predicted) was compared. All patients with clinical evidence of vocal cord injury following transplantation underwent direct laryngoscopy. GERD was determined by gastric emptying and pH probe studies. Wilcoxon rank sum tests were used to compare the data between vocal cord injury and noninjury groups. Results: Thirty-four patients were identified as having unilateral vocal cord paralysis and 193 did not. Average FEV1 for vocal cord injured patients was 71.7 ⫹/⫺17.7% and for non-vocal cord injured patients 79.3 ⫹/⫺19.67% (p ⫽ 0.035). Further analysis demonstrated that vocal cord medialization had no significant impact on FEV1 (p ⫽ 0.91). Moreover, in those with vocal cord injury, the presence or absence of documented reflux did not appear to make a difference in peak FEV1 (p ⫽ 0.15). Conclusions: We demonstrated a significant difference in peak FEV1 at one year between vocal cord injured and non-injured patients following BOLT. Vocal cord medialization appeared to have no impact on FEV1. This study suggests that vocal cord injury, by allowing reflux- or non-refluxrelated chronic aspiration to occur, may be one of the key elements in inducing pulmonary allograft dysfunction. This study is subject to non-randomized and selection biases, and prospective studies are required to better elucidate the interaction between GERD, vocal cord injury, and pulmonary allograft function. Because of this complex interaction, vocal cord medialization by itself, while adequate
178 ASSOCIATION FOR ACADEMIC SURGERY AND SOCIETY OF UNIVERSITY SURGEONS—ABSTRACTS for the treatment of dysphonia, may not be sufficient to significantly reduce pulmonary allograft dysfunction. 8. HIGH-VOLUME SURGICAL CENTERS PROVIDE IMPROVED OUTCOMES FOR LUNG CANCER PATIENTS: AN EXAMINATION OF 13,469 PATIENTS. Michael C. Cheung, Kara Hamilton, Juan C. Gutierrez, Recinda Sherman, Dido Franceschi, Leonidas G. Koniaris; University of Miami, Miami, FL Objective: To determine the impact of institutional surgical case volume on outcomes of patients with lung cancer. Methods: The Florida Cancer Data System (1998-2002) was queried for surgical patients undergoing resection for lung cancer. Facilities above the 67th percentile for volume were identified as high volume centers (HVCs). Results: A total of 13,469 patients undergoing surgery for lung cancer were identified. HVCs treated 4,598 cases (34.1%) while 8,871 cases (65.9%) were treated at low volume centers (LVCs). A disproportionate number of black (5.50% vs. 3.94%, p ⬍ 0.0001), Hispanic (6.18% vs. 3.65%, p ⬍0.0001) and patients olders than 75 years of age (28.98% vs. 26.19%, p ⫽ 0.0003) were treated at LVCs. Review of comorbidities revealed that hypertensive patients (84.45% vs. 78.81%, p ⬍ 0.0001) were more often seen at HVCs. Extensive resections such as extended lobectomies (5.01% vs. 3.87%, p ⬍ 0.0001) and pneumonectomies (15.64% vs. 9.59%, p ⬍ 0.0001) were performed more frequently at LVCs. Use of additional treatment modalities such as radiation and chemotherapy occurred at HVC more often (neoadjuvant radiation: 12.46% vs. 8.96%, adjuvant radiation: 2.46% vs. 1.74%, p ⬍ 0.0001; neoadjuvant chemotherapy: 9.03% vs. 7.05%, adjuvant chemotherapy: 4.72% vs. 2.54%, p ⬍ 0.001). Cohorts treated at HVCs experienced an improved median survival time (45.1 months vs. 39.8 months) as well as 1 month (98.4% vs. 97.3%, p ⬍0.00001) and 5 year (40.7% vs. 36.5%, p ⫽ 0.002) survival. By age-adjusted univariate analysis, significant benefit is observed for those treated at HVCs (HR ⫽ 0.861, p ⫽ 0.0001), having never smoked (HR ⫽ 0.638, p ⬍ 0.0001), or being a former smoker (HR ⫽ 0.822 p ⬍ 0.0001). No benefit was observed for radiation or chemotherapy, either before or after surgery. Multivariate analysis of the two cohorts revealed that surgical case volume (HR 0.871, p ⬍ 0.0001) and gender (HR 1.306, p ⬍ 0.0001) are independent predictors of improved outcomes. Being a former smoker (HR 0.851, p ⬍ 0.0001) or having never smoked (HR 0.779, p ⬍ 0.0001) also confers an improved outcome. No effect of race or ethnicity on outcome was observed. Conclusion: Surgical treatment for lung cancer at HVCs results in significantly better patient outcomes. Male gender and current smoking status confer significantly poorer outcomes. No benefit was observed for radiation or chemotherapy, before or after surgery.
CLINICAL TRIALS/OUTCOMES I: SURGICAL ONCOLOGY 9. OUTCOMES FOLLOWING PANCREATIC RESECTION: VARIABILITY AMONG HIGH-VOLUME PROVIDERS. Taylor S. Riall, William H. Nealon, James S. Goodwin, Courtney M. Townsend, Jr., Jean L. Freeman; University of Texas Medical Branch, Galveston, TX Background: A strong-volume outcome relationship has been demonstrated for pancreatic resection and regionalization of care to high-volume centers (⬎11 resections/year) has been recommended. However, it is unclear if volume alone should be the sole criteria for regionalization. Objective: To evaluate variability in outcomes among high-volume hospitals (⬎11 resections/year). Methods: We used the Texas Hospital Inpatient Discharge Database from 1999-2005 to evaluate variability in outcomes following
pancreatic resection among high-volume hospitals in Texas. The outcome variables of interest were mortality, length of stay (LOS), discharge to a skilled nursing facility (SNF), operation within 24 hours of hospital admission, and total hospital charges. Unadjusted and adjusted models were performed. Results: There were 12 high-volume hospitals in Texas. The number of resections at each hospital ranged from 78-608 cases for the seven year time period. In unadjusted models, there was significant variability in mortality (range: 0.7 - 7.7%, P⬍0.0001), LOS (median range: 9-21 days, P⬍0.0001), discharge to a SNF (range: 0.7% - 41.4%, P⬍0.0001), operation within 24 hours of admission (range: 41% 96%, P⬍0.0001), and total hospital charges (median range: $38,318-$110,860, P⬍0.0001). There were significant differences in the demographics, risks of mortality, and illness severity between the twelve high-volume hospitals. Therefore multivariate models were used to control for age group, gender, race/ethnicity, risk of mortality, illness severity, admission status, diagnosis, procedure, and insurance status. In the multivariate models, the particular hospital at which surgery was performed was a significant independent predictor of every outcome variable except mortality. Conclusions: For pancreatic resection there is significant variability in outcomes even among high-volume providers. Individual hospital likely accounts for much of the variability not explained by hospital volume. Although the structure measure of hospital volume is easy to measure, these data imply that is not a reliable single measure of quality or outcomes following pancreatic surgery. 10. ANGIOCIDIN: AN INDEPENDENT PROGNOSTIC FACTOR OF OUTCOME IN COLON CANCER. Catherine Liebig, Jonathan Wilks, Neeti Agarwal, Gordona Verstovsek, Daniel Albo; Baylor College of Medicine, Houston, TX Introduction: We have previously demonstrated that angiocidin promotes colon cancer tumor cell invasion in vitro and metastases in animal models. We now hypothesize that angiocidin is expressed in colon cancer and that its expression correlates with clinical outcomes in these patients. Methods: All consecutive cases of resected colorectal cancer at our institution during a 5-year period (n⫽347) were used to create a colon cancer tissue array. The array included tumor, normal, normal lymph node, and, when available, lymph node and/or liver metastasis specimens. Patient demographic, pathology, tumor stage, disease-free survival (DFS) and overall survival (OS) data (minimum 5 years follow up) were entered into a database. Tissue array slides were immunostained for angiocidin. Angiocidin immunostaining density was determined using a numerical scale from 1 to 4 by two observers blinded to the outcomes data. Survival curves were analyzed using a Kaplan-Meier method and compared by log rank test. Differences between means were analyzed using two-way ANOVA. Results: Overall, angiocidin was identified in 90% of colon cancer vs. only 10% of normal colon specimens. In lymph node metastases, angiocidin was identified in 85% of patients vs. only 10% of lymph nodes from node-negative patients. All patients with liver metastases expressed angiocidin in their metastatic deposits. For the entire cohort of patients, OS and DFS mirrored the intensity of angiocidin expression: Five year OS rates for low and high angiocidin expressing tumors were 67% and 36% respectively; five year DFS rates for low and high angiocidin expressing tumors were 57% and 34% respectively (p⫽0.03 and p⬍0.001, respectively; Figure 1 and 2). OS and DFS in node-negative patients also correlated with the intensity of angiocidin expression in primary tumors (p⫽0.004 and p⫽0.21, respectively; Figure 3). Conclusions: Angiocidin is present in primary and metastatic colon cancer. Furthermore, angiocidin immunostaining intensity in primary colon cancer tissues serves as an independent prognostic factor of outcome. Angiocidin should be considered for therapy stratification in patients with colon cancer.
Post-Ischemic Values of dP/dt (% of Equilibration) in WT and ERbKO Hearts From Male and Female
M WT F WT MERbKO FERbKO M WTdP/dt F WTdP/dt MERbKOdP/dt FERbKOdP/dt
10 min Reperfusion
20 min Reperfusion
30 min Reperfusion
40 min Reperfusion
50 min Reperfusion
60 min Reperfusion
23.17.4% 21.78.4% 7.43.0% 10.12.6% ⫺22.87.8%
35.88.7% 46.28.1% 20.66.0% 30.57.8% ⫺35.48.7%
36.06.3% 58.54.1%# 30.57.7% 38.07.6%* ⫺36.07.3%
42.74.9% 64.84.3%# 35.07.4% 42.07.2%** ⫺39.24.3%
47.02.7% 69.52.4%# 40.86.6% 44.77.0%** ⫺44.13.3%
48.11.9% 76.22.6%# 41.98.0% 50.08.1%*** ⫺45.92.9%
⫺60.77.6%#
⫺67.47.7%#
⫺69.75.5%#
⫺73.24.3%# ⫺43.68.6%
22.99.3%
50.510.4%
⫺7.22.1%
⫺21.76.5%
⫺31.28.7%
⫺37.08.8%
⫺41.89.0%
⫺11.23.4%
⫺31.07.9%
⫺37.27.6%* (*p ⬍ 0.05 vs. FWT)
⫺41.27.4%** (**p ⬍ 0.01 vs. FWT)
⫺43.97.5%** (***p ⬍ 0.001 vs. FWT)
⫺49.48.0%* (#p ⬍ 0.01 vs. MWT)
6. ROLE OF NONO IN TNF〈-INDUCED P4H〈1 SUPPRESSION. Cheng Zhang1, Ming-Xiang Zhang1, Ying H. Shen1, Yun Zhang2, Koichi Yoshimura5, Hiroki Aoki5, Masunori Matsuzaki5, Scott A. LeMaire1, Joseph S. Coselli1, Xing Li Wang1; 1Baylor College of Medicine, Houston, TX; 2Shandong University Qilu Hospital, Jinan, China; 5Yamaguchi University, Ube, Japan Previously, we have shown that TNF␣ inhibits P4H␣(I) expression via the ASK1-JNK pathway, resulting in reduced type I and III collagen synthesis in primary human aortic smooth muscle cells (HASMCs). This finding is significant because inflammation is an established causal factor in the pathogenesis of aortic aneurysm, in which arterial wall extracellular matrix (ECM) homeostasis plays a critical role. In the current study, we further investigated the molecular connections between inflammation and reduced collagen synthesis via the expression of P4H␣(I), the rate-limiting subunit for the P4H enzyme essential for procollagen hydroxylation, secretion, and deposition. Using 2-D electrophoresis and LC/MS-MS, we detected several nuclear proteins that may participate in TNF␣-induced P4H␣(I) suppression. One of these, human NonO protein, appeared to be responsible for the effect because NonO silence abolished the effect of TNF␣. Using JNK1 overexpression vector, we found that JNK1 directly suppressed the expression of P4H␣(I) comparing to the dominant negative expression vector. The JNK1 appeared to be
activated through the MKK4 upstream pathway, which was in turn activated by the ASK1. Furthermore, when NonO was silenced in HASMCs, the P4H␣(I)-suppressing effect of the overexpressed JNK1 disappeared. However, neither TNF␣ nor JNK1 altered the expression of NonO, which was expressed constitutively. A ChIP assay showed minimal binding between the NonO protein and P4H␣(I) DNA promoter under baseline conditions. However, exposure to TNF␣ or JNK1 caused a dramatic increase in binding between the NonO protein and P4H␣(I) promoter, which was associated with the suppressed P4H␣(I) expression. In an immunoprecipitation assay, several nuclear proteins were identified by the LC/MS-MS in complex with the DNA-bound NonO protein; of these proteins, DJ-1 was the only one associated with the P4H␣(I)-suppressing effect. DJ-1 bound to P4H␣(I) promoter via the NonO protein and DJ-1 knockdown incompletely reduced the TNF␣ effect on the binding between the P4H␣(I) promoter and the NonO protein. We conclude that the posttranslational modification of the nuclear DNA-binding protein NonO in complex with other nuclear transcriptional proteins is responsible for TNF␣-mediated P4H␣ suppression. 7. THE EFFECT OF VOCAL CORD INJURY ON PULMONARY ALLOGRAFT FUNCTION FOLLOWING BILATERAL ORTHOTOPIC LUNG TRANSPLANT. Keki R. Balsara, Broadus Zane Atkins, Errol L. Bush, Robert Duane Davis, Jr., Shu S. Lin; Duke University Medical Center, Durham, NC Introduction: Vocal cord injury following bilateral orthotopic lung transplantation (BOLT) is a known complication which places patients at increased risk of impaired phonation and tracheobronchial aspiration. Since chronic aspiration often results from gastroesophageal reflux disease (GERD) and since GERD has been found to be associated with chronic pulmonary allograft dysfunction, as evidenced by the development of bronchiolitis obliterans syndrome (BOS) in these lung transplant recipients, there is a prevailing hypothesis that GERD-related aspiration, facilitated by vocal cord injury, is a significant cause of BOS. Surgical intervention to treat GERD in lung transplant patients has resulted in recovery of graft function for those with early BOS. Traditional treatments for vocal cord injury include injection with medialization. In this study, the effect of vocal cord injury on pulmonary allograft function, notably in regards to aspiration and GERD, is examined. Methods: We completed a retrospective review of all adult, primary BOLTs performed between January of 2000 and July of 2005 at a single medical center (n ⫽ 227). All patients underwent formal pulmonary function tests and the peak one-year FEV1 (% predicted) was compared. All patients with clinical evidence of vocal cord injury following transplantation underwent direct laryngoscopy. GERD was determined by gastric emptying and pH probe studies. Wilcoxon rank sum tests were used to compare the data between vocal cord injury and noninjury groups. Results: Thirty-four patients were identified as having unilateral vocal cord paralysis and 193 did not. Average FEV1 for vocal cord injured patients was 71.7 ⫹/⫺17.7% and for non-vocal cord injured patients 79.3 ⫹/⫺19.67% (p ⫽ 0.035). Further analysis demonstrated that vocal cord medialization had no significant impact on FEV1 (p ⫽ 0.91). Moreover, in those with vocal cord injury, the presence or absence of documented reflux did not appear to make a difference in peak FEV1 (p ⫽ 0.15). Conclusions: We demonstrated a significant difference in peak FEV1 at one year between vocal cord injured and non-injured patients following BOLT. Vocal cord medialization appeared to have no impact on FEV1. This study suggests that vocal cord injury, by allowing reflux- or non-refluxrelated chronic aspiration to occur, may be one of the key elements in inducing pulmonary allograft dysfunction. This study is subject to non-randomized and selection biases, and prospective studies are required to better elucidate the interaction between GERD, vocal cord injury, and pulmonary allograft function. Because of this complex interaction, vocal cord medialization by itself, while adequate
178 ASSOCIATION FOR ACADEMIC SURGERY AND SOCIETY OF UNIVERSITY SURGEONS—ABSTRACTS for the treatment of dysphonia, may not be sufficient to significantly reduce pulmonary allograft dysfunction. 8. HIGH-VOLUME SURGICAL CENTERS PROVIDE IMPROVED OUTCOMES FOR LUNG CANCER PATIENTS: AN EXAMINATION OF 13,469 PATIENTS. Michael C. Cheung, Kara Hamilton, Juan C. Gutierrez, Recinda Sherman, Dido Franceschi, Leonidas G. Koniaris; University of Miami, Miami, FL Objective: To determine the impact of institutional surgical case volume on outcomes of patients with lung cancer. Methods: The Florida Cancer Data System (1998-2002) was queried for surgical patients undergoing resection for lung cancer. Facilities above the 67th percentile for volume were identified as high volume centers (HVCs). Results: A total of 13,469 patients undergoing surgery for lung cancer were identified. HVCs treated 4,598 cases (34.1%) while 8,871 cases (65.9%) were treated at low volume centers (LVCs). A disproportionate number of black (5.50% vs. 3.94%, p ⬍ 0.0001), Hispanic (6.18% vs. 3.65%, p ⬍0.0001) and patients olders than 75 years of age (28.98% vs. 26.19%, p ⫽ 0.0003) were treated at LVCs. Review of comorbidities revealed that hypertensive patients (84.45% vs. 78.81%, p ⬍ 0.0001) were more often seen at HVCs. Extensive resections such as extended lobectomies (5.01% vs. 3.87%, p ⬍ 0.0001) and pneumonectomies (15.64% vs. 9.59%, p ⬍ 0.0001) were performed more frequently at LVCs. Use of additional treatment modalities such as radiation and chemotherapy occurred at HVC more often (neoadjuvant radiation: 12.46% vs. 8.96%, adjuvant radiation: 2.46% vs. 1.74%, p ⬍ 0.0001; neoadjuvant chemotherapy: 9.03% vs. 7.05%, adjuvant chemotherapy: 4.72% vs. 2.54%, p ⬍ 0.001). Cohorts treated at HVCs experienced an improved median survival time (45.1 months vs. 39.8 months) as well as 1 month (98.4% vs. 97.3%, p ⬍0.00001) and 5 year (40.7% vs. 36.5%, p ⫽ 0.002) survival. By age-adjusted univariate analysis, significant benefit is observed for those treated at HVCs (HR ⫽ 0.861, p ⫽ 0.0001), having never smoked (HR ⫽ 0.638, p ⬍ 0.0001), or being a former smoker (HR ⫽ 0.822 p ⬍ 0.0001). No benefit was observed for radiation or chemotherapy, either before or after surgery. Multivariate analysis of the two cohorts revealed that surgical case volume (HR 0.871, p ⬍ 0.0001) and gender (HR 1.306, p ⬍ 0.0001) are independent predictors of improved outcomes. Being a former smoker (HR 0.851, p ⬍ 0.0001) or having never smoked (HR 0.779, p ⬍ 0.0001) also confers an improved outcome. No effect of race or ethnicity on outcome was observed. Conclusion: Surgical treatment for lung cancer at HVCs results in significantly better patient outcomes. Male gender and current smoking status confer significantly poorer outcomes. No benefit was observed for radiation or chemotherapy, before or after surgery.
CLINICAL TRIALS/OUTCOMES I: SURGICAL ONCOLOGY 9. OUTCOMES FOLLOWING PANCREATIC RESECTION: VARIABILITY AMONG HIGH-VOLUME PROVIDERS. Taylor S. Riall, William H. Nealon, James S. Goodwin, Courtney M. Townsend, Jr., Jean L. Freeman; University of Texas Medical Branch, Galveston, TX Background: A strong-volume outcome relationship has been demonstrated for pancreatic resection and regionalization of care to high-volume centers (⬎11 resections/year) has been recommended. However, it is unclear if volume alone should be the sole criteria for regionalization. Objective: To evaluate variability in outcomes among high-volume hospitals (⬎11 resections/year). Methods: We used the Texas Hospital Inpatient Discharge Database from 1999-2005 to evaluate variability in outcomes following
pancreatic resection among high-volume hospitals in Texas. The outcome variables of interest were mortality, length of stay (LOS), discharge to a skilled nursing facility (SNF), operation within 24 hours of hospital admission, and total hospital charges. Unadjusted and adjusted models were performed. Results: There were 12 high-volume hospitals in Texas. The number of resections at each hospital ranged from 78-608 cases for the seven year time period. In unadjusted models, there was significant variability in mortality (range: 0.7 - 7.7%, P⬍0.0001), LOS (median range: 9-21 days, P⬍0.0001), discharge to a SNF (range: 0.7% - 41.4%, P⬍0.0001), operation within 24 hours of admission (range: 41% 96%, P⬍0.0001), and total hospital charges (median range: $38,318-$110,860, P⬍0.0001). There were significant differences in the demographics, risks of mortality, and illness severity between the twelve high-volume hospitals. Therefore multivariate models were used to control for age group, gender, race/ethnicity, risk of mortality, illness severity, admission status, diagnosis, procedure, and insurance status. In the multivariate models, the particular hospital at which surgery was performed was a significant independent predictor of every outcome variable except mortality. Conclusions: For pancreatic resection there is significant variability in outcomes even among high-volume providers. Individual hospital likely accounts for much of the variability not explained by hospital volume. Although the structure measure of hospital volume is easy to measure, these data imply that is not a reliable single measure of quality or outcomes following pancreatic surgery. 10. ANGIOCIDIN: AN INDEPENDENT PROGNOSTIC FACTOR OF OUTCOME IN COLON CANCER. Catherine Liebig, Jonathan Wilks, Neeti Agarwal, Gordona Verstovsek, Daniel Albo; Baylor College of Medicine, Houston, TX Introduction: We have previously demonstrated that angiocidin promotes colon cancer tumor cell invasion in vitro and metastases in animal models. We now hypothesize that angiocidin is expressed in colon cancer and that its expression correlates with clinical outcomes in these patients. Methods: All consecutive cases of resected colorectal cancer at our institution during a 5-year period (n⫽347) were used to create a colon cancer tissue array. The array included tumor, normal, normal lymph node, and, when available, lymph node and/or liver metastasis specimens. Patient demographic, pathology, tumor stage, disease-free survival (DFS) and overall survival (OS) data (minimum 5 years follow up) were entered into a database. Tissue array slides were immunostained for angiocidin. Angiocidin immunostaining density was determined using a numerical scale from 1 to 4 by two observers blinded to the outcomes data. Survival curves were analyzed using a Kaplan-Meier method and compared by log rank test. Differences between means were analyzed using two-way ANOVA. Results: Overall, angiocidin was identified in 90% of colon cancer vs. only 10% of normal colon specimens. In lymph node metastases, angiocidin was identified in 85% of patients vs. only 10% of lymph nodes from node-negative patients. All patients with liver metastases expressed angiocidin in their metastatic deposits. For the entire cohort of patients, OS and DFS mirrored the intensity of angiocidin expression: Five year OS rates for low and high angiocidin expressing tumors were 67% and 36% respectively; five year DFS rates for low and high angiocidin expressing tumors were 57% and 34% respectively (p⫽0.03 and p⬍0.001, respectively; Figure 1 and 2). OS and DFS in node-negative patients also correlated with the intensity of angiocidin expression in primary tumors (p⫽0.004 and p⫽0.21, respectively; Figure 3). Conclusions: Angiocidin is present in primary and metastatic colon cancer. Furthermore, angiocidin immunostaining intensity in primary colon cancer tissues serves as an independent prognostic factor of outcome. Angiocidin should be considered for therapy stratification in patients with colon cancer.