Successful Introduction of Video-Assisted Thoracic Surgery (VATS) Lobectomy to General Surgery Residents: Analysis of 235 Consecutive Cases

Successful Introduction of Video-Assisted Thoracic Surgery (VATS) Lobectomy to General Surgery Residents: Analysis of 235 Consecutive Cases

172 ASSOCIATION FOR ACADEMIC SURGERY AND SOCIETY OF UNIVERSITY SURGEONS ABSTRACTS signaling and TAAD formation, we examined insulin’s direct effect...

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ASSOCIATION FOR ACADEMIC SURGERY AND SOCIETY OF UNIVERSITY SURGEONS

ABSTRACTS

signaling and TAAD formation, we examined insulin’s direct effects on MMP and TIMP expression in cultured human thoracic aortic smooth muscle cells. We observed that low doses of insulin (0.05 1.0 nM) in hibited the expression of MMP 3, 9, and 13 but had minimal effects on MMP 12 and slightly increased MMP 2 levels. Additionally, at this dose range, insulin stimulated the expression of all 3 TIMPs ( 1, 2, and 3). We also found that insulin regulated MMP and TIMP expres sion through Akt and ERK pathways; silencing Akt with specific siRNA significantly reversed insulin’s inhibition of MMP expression and pre vented insulin from stimulating TIMP expression. Conclusions: The insulin pathway can directly inhibit MMP expression while stimulating TIMP expression. Impaired insulin signaling may be one mechanism for the increased susceptibility to ECM destruction in TAAD.

showed similar MMP 9 activity response to the pressure induced stress (Figure 1). Conclusion: We propose a novel approach to examine the response of human thoracic aorta to hypertension using an in line pul satile pressure perfusion model. Our preliminary findings correlate with clinical observations that patients with bicuspid aortic valve asso ciated ascending aortic aneurysms present a unique physiologic re sponse to hypertension when compared to tricuspid aortic valve associated ascending aortic aneurysms.

9.3. A Novel Ex Vivo Pressure-Induced Model for the Examination of Human Thoracic Aortic Aneurysms. A. Kiankhooy, J. Schmoker, L. Trombley, M. Sager, J. Campbell, K. Mann; University of Vermont, Burlington, VT

Introduction: Only 20% of pulmonary lobectomies performed in the United States utilize a minimally invasive approach. Analysis of operative data from finishing cardiothoracic surgery residents suggests that exposure to video assisted thoracic surgery (VATS) lo bectomy during their two to three years of cardiothoracic training is still limited. It is unclear what the impact of proposals to trun cate the general surgery prerequisite for cardiothoracic residency would be. Our hypothesis is that early and graded introduction of VATS lobectomy to surgical trainees might be accomplished safely and efficiently, with initial exposure during their general surgical training. Methods: We retrospectively reviewed 235 consecutive VATS lobectomies performed from January 2005 through July 2009. Preoperative patient characteristics (age, sex, FEV1, DLCO) and comorbidities (coronary disease, COPD, heart failure, hyper tension) were examined. In addition, postoperative outcomes (oper ative time, blood loss, time to chest tube removal, length of stay) and complications (arrhythmia, prolonged airleak, pneumonia, rein tubation, pulmonary embolus, wound infection, empyema, reopera tion for hemothorax, renal failure, and re admissions) were examined. The data were analyzed with regard to the experience of the assisting resident as represented by post graduate year (PGY). PGY 2, 3, and 4 represented general surgery residents; PGY 6 and 7 were cardiothoracic trainees. Results: VATS lobec tomy was performed with an assisting PGY 2 resident in 24 cases (10.2%), PGY 3 in 25 (10.6%), PGY 4 in 86 (36.6%), PGY 6 in 69 (29.4%), and PGY 7 in 31 (13.2%). When comparing patients oper ated on by the various PGY levels, there were no statistically sig nificant differences noted in preoperative patient characteristics or comorbidities. Similarly, analysis of postoperative outcomes re vealed no significant differences in operative time, blood loss, or time to chest tube removal. Median length of stay was 4 days for all groups. Postoperative complication rates also were not signifi cantly different between PGY levels, with the exception of a higher

Purpose: Studies examining extracellular matrix phenotype in hu man thoracic aortic aneurysms are limited by the static assessment of freshly harvested tissue. Our goal was to design a model which pro vides a physiologically relevant pulsatile pressure stimulus as occurs in the setting of hypertension in vivo. We describe the physiologic response of bicuspid aortic valve associated aortic aneurysm (BAV AAA) tissue and tricuspid aortic valve associated aortic aneurysm tis sue (TAV AAA) to pathological pressure (180mmHg at 70 80 bpm) uti lizing a novel pressure induced stress model. Methods: BAV AAA (n 2) and TAV AAA (n 2) were obtained from individuals undergo ing ascending aortic aneurysm resection. To ensure equal stress stimuli among specimens, equally sized neo aortic tubes (8 mm circumference) were constructed from resected segments of each proximal anterior aor tic aneurysm wall. Tubes were incorporated into an in line pulsatile pressure induced continuous perfusion system for 3 hours. Extracellu lar matrix reactive oxygen species (ROS), ERK 1/2, Pro MMP2, MMP2 and MMP9 were examined using immunofloresence confocal micros copy, immunoblotting, and zymography. Results: Goal pressure induced stress was achieved in all experiments with minimal variabil ity over the 3 hour time course (Table 1). At 3 hours ROS activity was similar in TAV AAA (7567 6 4363) and BAV AAA (7102 6 1629). ERK 1/2 was greater in TAV AAA (0.04 6 0.01) versus BAV AAA (0.0150 6 0.005). BAV AAA demonstrated greater pressure induced Pro MMP2 (6.195 6 0.975) and MMP2 (3.050 6 0.916) activity when compared to TAV AAA (Pro MMP2 2.560 6 1.620; MMP2 .0.885 6 0.105). TAV AAA (2.030 6 0.020) and BAV AAA (2.005 6 1.785)

9.4. Successful Introduction of Video-Assisted Thoracic Surgery (VATS) Lobectomy to General Surgery Residents: Analysis of 235 Consecutive Cases. S. P. Gangadharan, D. D. Odell, M. S. Kent, I. A. Makey, M. Miles, M. M. DeCamp; Beth Israel Deaconess Medical Center, Boston, MA

ASSOCIATION FOR ACADEMIC SURGERY AND SOCIETY OF UNIVERSITY SURGEONS pulmonary embolus rate (6.5%) noted in the PGY 7 group (p 0.0246). (Table 1) One in hospital mortality (0.4%) was observed. Conclusions: Our results show that VATS lobectomy can be introduced to trainees at varying levels of experience with out compromising outcomes. While these data are supportive of early introduction of VATS lobectomy during surgical training, the level of autonomy and responsibility in the operating room must be individualized for each resident 9.5. Autophagy Protects Mesothelioma from HDAC Inhibitor Induced Apoptosis by Targeting Mitochondria. P. Rascoe,1 X. Cao,1 C. S. Peddaboina,1 J. E. Littlejohn,2 L. Zhang,1 W. R. Smythe1; 1Scott & White Memorial Hospital, Temple, TX; 2 Texas A&M Health Science Center College of Medicine, Temple, TX Introduction: The diverse anticancer effects of histone deacetylase (HDAC) inhibitors have been linked to induction of both apoptosis and autophagy in malignant pleural mesothelioma (MPM); however, the precise mechanisms underlying these processes have yet to be fully elucidated. Methods: Human MPM cell lines I 45 and REN were exposed to the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA). Apoptosis was assessed via cell cycle analysis, cas pase 3 activity, and Annexin V labeling. Autophagy induction was as sessed by cleavage of LC3 to LC3 b on western blot and aggregation of EGFP LC3 b in a stably transfected I 45 cell line via fluorescence mi croscopy. Mitochondrial membrane potential was measured by JC 1 staining. Mitophagy was demonstrated by transiently expressing Mito RedÒ protein in the EGFP LC3B I 45 cells and measuring over lay on fluorescence microscopy. siRNA knockdown was performed via transient transfection of Beclin 1, BAK, BAX, and NIX sequences which are known to reduce protein levels by >50% after 24hrs. Results: The HDAC inhibitor (SAHA) decreases mitochondrial mem brane potential and induces both apoptosis and autophagy in the me sothelioma cell line I 45. We demonstrate that these SAHA induced processes are mutually exclusive events; first by reducing Beclin 1 (blocking autophagy) which results in increased apoptotic cell death, and second by reducing BAK and BAX (blocking apoptosis) which results in an increased autophagic population of cells. We further investigated this finding by demonstrating that SAHA induced sequestration of mitochondria into autophagosomes (mitophagy), and does so in conjunction with an increase in expression of NIX (a mi tochondrial BH3 only protein involved in mitophagy). We find that this process is dependant on NIX, as no mitophagy is observed in REN cells (Nix null) and we can abrogate mitophagy in I 45 (Nix wild type) by siRNA knockdown of NIX. Conclusion: We show that au tophagy has an antiapoptotic effect in mesothelioma cells during HDAC inhibitor therapy and propose Nix associated clearance of damaged mitochondria from the cytoplasm (mitophagy) as a potential mechanism whereby apoptosis is avoided.

9.6. Synchronous Non Small Cell Lung Cancers Should Not Be Classified as Stage IV - A Seer Database Analysis. A. Bhaskarla,1 P. Tang,1 T. Mashtare,1 T. Demmy,1 C. Nwogu,2 A. Adjei,2 M. Reid,2 S. Yendamuri1; 1State University of New York Buffalo, Buffalo, NY; 2Roswell Park Cancer Institute, Buffalo, NY Introduction: The seventh edition of the TNM staging system for non small cell lung cancer (NSCLC) proposes the inclusion of syn chronous primary tumors as stage IV (M1a), thereby discouraging their resection. We sought to examine the validity of this proposal using the population based Survey Epidemiology End Results (SEER) database. Methods: Data of all patients in the SEER data base with at least two NSCLC lung primaries and adequate staging information (N 5210) was obtained. A time point of 6 months was chosen to separate synchronous from metachronous second primary lung cancers. The overall survival of these patients was compared to

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that of patients with metachronous second lung cancers and those with stage IV lung cancers in all patients with NSCLC in the SEER database. Results: The median overall survival of patients with synchronous NSCLCs (N 1858) was worse than those with metachronous NSCLCs (N 3352)(median survival 30 months vs 106 months respectively; p < 0.01). Multivariate Cox regression analysis demonstrated that synchronous tumors have a worse out come compared to metachronous lesions independent of age, race, gender and stage and histology of both primaries (p < 0.01; Figure 1A). However, this outcome is much better than those of all stage

IV NSCLC patients in the SEER database (N 127,654; median sur vival 4 months; Figure 1B). Conclusions: Synchronous NSCLCs have an outcome worse than metachronous NSCLCs but much better than that suggested by a stage IV (M1a) designation. These patients should receive appropriate stage specific therapy suitable for the independent stage of each cancer without considering them unresectable.

9.7. Are Drowning Victims Good Donors for Lung Transplantation? Analysis of Over 18,000 Lung Transplants. F. Zafar,1 J. S. Heinle,1 G. B. Mallory, Jr,2 M. G. Schecter,2 O. Elidemir,2 D. L. Morales1; 1Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Division of Congenital Heart Surgery, Texas Children’s Hospital, Houston, TX; 2 Department of Pediatrics Pulmonology, Baylor College of Medicine, Houston, TX Background: Drowning accounts for 8,000 deaths annually in the US. Many of these victims may be suitable donors because they are ‘‘dry drownings’’ and/or drowning in cold water. Therefore there are approximately 1,200 potential donors annually. However, many still question the efficacy of these potential lung donors. To evaluate the suitability of donor lungs from drowning victims, we analyzed outcomes from the United Network of Organ Sharing (UNOS) data base. Methods: The UNOS database was queried for all lung trans plants (LTx) performed from 10/1987 5/2008. 37 LTx donors with drowning as the mechanism of death were identified out of a total of 18,181 LTx (0.2%). Since the first LTx from a drowned donor (DD) was performed in 1991, an average of 2 transplants per year are done using DD. 27%(10) of LTx recipients using a DD were chil dren (18 years.) Results: Mean age and weight of DD was 23 6 15 years and 58 6 26 kgs, younger and smaller than the cohort of do nors (nonDD) compared with other causes of death (30 6 14years and 71 6 18 kgs) (p 0.001). A third of the DD were from two states [Texas (7) and Minnesota (5)]. 24%(9) were on inotropic medication at the time of procurement, similar to the nonDD [24%(4397)]. Kaplan Meier graft survival of recipients of DD and nonDD was not different (p 0.9). Grafts from DD and nonDD had similar 1 year survival [82%, 76% (p 0.3)] and half lives [6 years, 4.5 years (p 0.3)]. Incidence of post transplant morbidities such as airway dehiscence, dialysis, drug treated infections, stroke, acute rejection and necessity of other surgical procedures were not different be tween LTx recipients with DD & nonDD. Hospital mean length of