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Transcriptional Regulation of Post-Pneumonectomy Angiogenesis in Peripheral Lung Regeneration
Vol. 221, No. 4S1, October 2015
Scientific Forum Abstracts
readmissions after pulmonary resections. We examined the NSQIP database to provide baseline data for quality improvement efforts. METHODS: The ACS-NSQIP dataset for years 2012-2013 was investigated. Patients who underwent lung resections were identified by CPT code, stratified into video-assisted thoracic surgery (VATS) and THOR groups, and further stratified by ICD9 into cancer vs non-cancer. Outcomes included 30-day morbidity and mortality in addition to rates and reason for readmission. RESULTS: We identified 8,930 lung resection patients; 59.5% of resections were performed for lung cancer and of these, 73% were lobectomy. Overall, 56% of cases were performed using VATS. Morbidity and mortality rates were 9% and 1.2% for VATS vs 15.3% and 2% for THOR (p<0.001). Median length of stay was 4 days for VATS (interquartile range [IQR] 2-6 days), and 5 days (IQR 4-8 days) for THOR (p<0.001). Unplanned readmission occurred within 30 days in 7.4% of patients and was not dependent on surgical approach or preoperative diagnosis. The reason for readmission was more likely related to air leak in the VATS group vs infections in the THOR group. Multivariate predictors of readmission included American Society of Anesthesiologists (ASA) 3, pneumonectomy, and the occurrence of postoperative complications as shown in the table. Table. Multivariate Analysis of Factors Associated with Readmission in Pulmonary Resection American Society of Anesthesiologists 3 Pneumonectomy Superficial wound infection Deep wound infection Organ space infection Occurrence of pneumonia Venous thromboembolism Sepsis Return to operating room
Odds ratio
95% CI
p Value
1.75 1.52 3.59 14.9 11.11 3.1 4.59 3.62 4.25
1.383-2.227 1.004-2.308 2.083-6.217 2.854-77.874 5.44-22.72 2.337-4.114 2.941-7.176 2.256 -5.812 3.161-5.736
<0.0001 0.048 <0.0001 0.0014 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001
CONCLUSIONS: Short-term outcomes in both cancer and noncancer patients are improved with VATS. Readmission rates are similar; however, the increased incidence of air-leak complications in VATS points toward a need to continue to refine surgical technique. The Comparative-Effectiveness of Neoadjuvant Therapy vs Upfront Surgery in Patients with Early-Stage Esophageal Cancer Zaid Abdelsattar, MD, Rishindra M Reddy, MD, FACS, Basil S Nasir, MB, BCH, Jules Lin, MD, FACS, KR Shen, MD, FACS, Samantha Hendren, MD, MPH, FACS, Sandra L Wong, MD, FACS University of Michigan, Ann Arbor, MI, University of British Columbia, Vancouver, BC, Mayo Clinic, Rochester, MN
S153
INTRODUCTION: Although esophagectomy remains the cornerstone of therapy for early-stage esophageal cancer, the use of neoadjuvant chemoradiation therapy (NCRT) is controversial. In this context, we compared the effectiveness of NCRT vs upfront surgery in a nationally representative sample. METHODS: We identified all patients with cT2N0 or cT3N0 esophageal cancer between January 2003 and December 2011 from the National Cancer Database (NCDB). Using an instrumental variable (IV) approach, which attempts to mimic conditions of randomized trials and account for measured and unmeasured confounding, we fit 2-stage residual inclusion models to estimate the effect of NCRT vs upfront-surgery on 90-day postoperative mortality and long-term survival. RESULTS: Of 5,142 patients with cT2N0 (n¼2,177) or cT3N0 (n¼2,965), 2,983 patients (58%) received NCRT. In the unadjusted analysis, patients receiving NCRT were younger (61+9.2 vs 66+10.7 years; p<0.001) and had lower Charlson-Deyo comorbidity scores (p<0.001). NCRT was associated with higher rates of R0 resection (89.8% vs 81.4%; p<0.001) and lower rates of pathologic upstaging (18.7% vs 26.9%; p<0.001). In the IV adjusted analysis, NCRT was associated with improved survival for cT3N0 (median survival of 46 vs 35 months; adjusted hazard ratio 0.77; p¼0.001) but not for cT2N0 (median survival 50 vs 49 months; p¼0.903). In addition, NCRT was associated with higher postoperative mortality at 90 days (adjusted rate 8.1% vs 6.4%; p¼0.023) in all patients. CONCLUSIONS: Compared with upfront surgery, NCRT did not improve long-term survival in patients with cT2N0 esophageal cancer, and was associated with increased 90-day postoperative mortality. On the other hand, NCRT was associated with an 11-month survival benefit in patients with cT3N0 cancers. Transcriptional Regulation of Post-Pneumonectomy Angiogenesis in Peripheral Lung Regeneration Robert D Bennett, MD, Alexandra B Ysasi, Cristian D Valenzuela, MD, Willi L Wagner, Janeil Belle, MD, Andreas Pabst, MD, Akira Tsuda, PhD, Maximilian Ackermann, MD, Steven J Mentzer, MD, FACS Brigham and Women’s Hospital, Boston, MA, University Medical Center of Johannes Gutenberg-University, Mainz, Germany, Harvard University School of Public Health, Boston, MA INTRODUCTION: In most mammals, including humans, pneumonectomy results in growth of the remaining lung; in mice, more than 3 km of capillaries develop within 3 weeks of pneumonectomy. To identify anatomic regions of active regeneration and the genes regulating parenchymal angiogenesis, we used laser microdissection and quantitative polymerase chain reaction (qPCR) analysis. METHODS: Eight- to 11-week, C57BL/6 mice underwent left pneumonectomy. Lungs were harvested as controls, and on days 1,
S154
Scientific Forum Abstracts
3, and 7 after pneumonectomy. Peripheral alveolar ductal regions from lung sections (300 m) were laser microdissected and enzymatically dissociated. Cells derived from alveolar ducts within the peripheral regenerating lung were compared with cell populations from sham thoracotomy and phrenic nerve transection controls. Custom PCR arrays were used to investigate expression of 96 genes implicated in lung regeneration and capillary angiogenesis. RESULTS: Targeted sampling of peripheral alveolar ducts revealed significant endothelial cell population dynamics over the time period of lung regeneration (21 days). In peripheral alveolar ducts, we observed the dynamic regulation of several angiogenesis-related genes including
J Am Coll Surg
Pecam1, Vegfa, Erbb2, Pdgfra, Fgf1, Kdr, Flt1, and Fn1 (p<0.001). The angiogenic gene profile of regenerating capillaries contrasted sharply with whole lung digests and surgical controls (p<0.001). In addition to new capillary growth, active remodeling was suggested by, apoptotic (Casp3) and anti-apoptotic (Bcl2) genes (p<0.01). CONCLUSIONS: Spatially sampled peripheral, subpleural endothelial cells show distinct population changes post-pneumonectomy, with transcriptional patterns distinct from those observed in bulk organ analysis. These data provide insights into clinical observations in lung disease and suggest new targets for antiangiogenesis therapy.
Scientific Forum Abstracts
readmissions after pulmonary resections. We examined the NSQIP database to provide baseline data for quality improvement efforts. METHODS: The ACS-NSQIP dataset for years 2012-2013 was investigated. Patients who underwent lung resections were identified by CPT code, stratified into video-assisted thoracic surgery (VATS) and THOR groups, and further stratified by ICD9 into cancer vs non-cancer. Outcomes included 30-day morbidity and mortality in addition to rates and reason for readmission. RESULTS: We identified 8,930 lung resection patients; 59.5% of resections were performed for lung cancer and of these, 73% were lobectomy. Overall, 56% of cases were performed using VATS. Morbidity and mortality rates were 9% and 1.2% for VATS vs 15.3% and 2% for THOR (p<0.001). Median length of stay was 4 days for VATS (interquartile range [IQR] 2-6 days), and 5 days (IQR 4-8 days) for THOR (p<0.001). Unplanned readmission occurred within 30 days in 7.4% of patients and was not dependent on surgical approach or preoperative diagnosis. The reason for readmission was more likely related to air leak in the VATS group vs infections in the THOR group. Multivariate predictors of readmission included American Society of Anesthesiologists (ASA) 3, pneumonectomy, and the occurrence of postoperative complications as shown in the table. Table. Multivariate Analysis of Factors Associated with Readmission in Pulmonary Resection American Society of Anesthesiologists 3 Pneumonectomy Superficial wound infection Deep wound infection Organ space infection Occurrence of pneumonia Venous thromboembolism Sepsis Return to operating room
Odds ratio
95% CI
p Value
1.75 1.52 3.59 14.9 11.11 3.1 4.59 3.62 4.25
1.383-2.227 1.004-2.308 2.083-6.217 2.854-77.874 5.44-22.72 2.337-4.114 2.941-7.176 2.256 -5.812 3.161-5.736
<0.0001 0.048 <0.0001 0.0014 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001
CONCLUSIONS: Short-term outcomes in both cancer and noncancer patients are improved with VATS. Readmission rates are similar; however, the increased incidence of air-leak complications in VATS points toward a need to continue to refine surgical technique. The Comparative-Effectiveness of Neoadjuvant Therapy vs Upfront Surgery in Patients with Early-Stage Esophageal Cancer Zaid Abdelsattar, MD, Rishindra M Reddy, MD, FACS, Basil S Nasir, MB, BCH, Jules Lin, MD, FACS, KR Shen, MD, FACS, Samantha Hendren, MD, MPH, FACS, Sandra L Wong, MD, FACS University of Michigan, Ann Arbor, MI, University of British Columbia, Vancouver, BC, Mayo Clinic, Rochester, MN
S153
INTRODUCTION: Although esophagectomy remains the cornerstone of therapy for early-stage esophageal cancer, the use of neoadjuvant chemoradiation therapy (NCRT) is controversial. In this context, we compared the effectiveness of NCRT vs upfront surgery in a nationally representative sample. METHODS: We identified all patients with cT2N0 or cT3N0 esophageal cancer between January 2003 and December 2011 from the National Cancer Database (NCDB). Using an instrumental variable (IV) approach, which attempts to mimic conditions of randomized trials and account for measured and unmeasured confounding, we fit 2-stage residual inclusion models to estimate the effect of NCRT vs upfront-surgery on 90-day postoperative mortality and long-term survival. RESULTS: Of 5,142 patients with cT2N0 (n¼2,177) or cT3N0 (n¼2,965), 2,983 patients (58%) received NCRT. In the unadjusted analysis, patients receiving NCRT were younger (61+9.2 vs 66+10.7 years; p<0.001) and had lower Charlson-Deyo comorbidity scores (p<0.001). NCRT was associated with higher rates of R0 resection (89.8% vs 81.4%; p<0.001) and lower rates of pathologic upstaging (18.7% vs 26.9%; p<0.001). In the IV adjusted analysis, NCRT was associated with improved survival for cT3N0 (median survival of 46 vs 35 months; adjusted hazard ratio 0.77; p¼0.001) but not for cT2N0 (median survival 50 vs 49 months; p¼0.903). In addition, NCRT was associated with higher postoperative mortality at 90 days (adjusted rate 8.1% vs 6.4%; p¼0.023) in all patients. CONCLUSIONS: Compared with upfront surgery, NCRT did not improve long-term survival in patients with cT2N0 esophageal cancer, and was associated with increased 90-day postoperative mortality. On the other hand, NCRT was associated with an 11-month survival benefit in patients with cT3N0 cancers. Transcriptional Regulation of Post-Pneumonectomy Angiogenesis in Peripheral Lung Regeneration Robert D Bennett, MD, Alexandra B Ysasi, Cristian D Valenzuela, MD, Willi L Wagner, Janeil Belle, MD, Andreas Pabst, MD, Akira Tsuda, PhD, Maximilian Ackermann, MD, Steven J Mentzer, MD, FACS Brigham and Women’s Hospital, Boston, MA, University Medical Center of Johannes Gutenberg-University, Mainz, Germany, Harvard University School of Public Health, Boston, MA INTRODUCTION: In most mammals, including humans, pneumonectomy results in growth of the remaining lung; in mice, more than 3 km of capillaries develop within 3 weeks of pneumonectomy. To identify anatomic regions of active regeneration and the genes regulating parenchymal angiogenesis, we used laser microdissection and quantitative polymerase chain reaction (qPCR) analysis. METHODS: Eight- to 11-week, C57BL/6 mice underwent left pneumonectomy. Lungs were harvested as controls, and on days 1,
S154
Scientific Forum Abstracts
3, and 7 after pneumonectomy. Peripheral alveolar ductal regions from lung sections (300 m) were laser microdissected and enzymatically dissociated. Cells derived from alveolar ducts within the peripheral regenerating lung were compared with cell populations from sham thoracotomy and phrenic nerve transection controls. Custom PCR arrays were used to investigate expression of 96 genes implicated in lung regeneration and capillary angiogenesis. RESULTS: Targeted sampling of peripheral alveolar ducts revealed significant endothelial cell population dynamics over the time period of lung regeneration (21 days). In peripheral alveolar ducts, we observed the dynamic regulation of several angiogenesis-related genes including
J Am Coll Surg
Pecam1, Vegfa, Erbb2, Pdgfra, Fgf1, Kdr, Flt1, and Fn1 (p<0.001). The angiogenic gene profile of regenerating capillaries contrasted sharply with whole lung digests and surgical controls (p<0.001). In addition to new capillary growth, active remodeling was suggested by, apoptotic (Casp3) and anti-apoptotic (Bcl2) genes (p<0.01). CONCLUSIONS: Spatially sampled peripheral, subpleural endothelial cells show distinct population changes post-pneumonectomy, with transcriptional patterns distinct from those observed in bulk organ analysis. These data provide insights into clinical observations in lung disease and suggest new targets for antiangiogenesis therapy.