Boston - American Association for Thoracic Surgery

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89 TH ANNUAL MEETING MAY 9–MAY 13, 2009BOSTON, MASSACHUSETTSF13. Replacement of the Trachea with Fully Bioengineered Graft in PigsTetsuhiko Go, 1 Philipp Jungebluth, 1 Adelaide Asnaghi, 2 Sara Mantero, 2 Maria-Teresa Conconi, 3 Antony Hollander, 4 Martin Birchall, 4 Paolo Macchiarini 1*1. General Thoracic Surgical Experimental Laboratory, Universitat de Barcelona,Barcelona, Spain; 2. Department of Bioengineering, Politecnico di Milano, Milano,Italy; 3. Pharmaceutical Science, University of Padua, Padua, Italy; 4. Departmentof Cellular and Molecular Medicine, School of Medical Sciences, Bristol, UnitedKingdomInvited Discussant: Yolonda L. ColsonOBJECTIVE: Evaluate the outcome of a fully bioengineered tracheal graft in pigs.METHODS: Non-immunogenic tracheal matrices were obtained via detergentenzymaticmethod (DEM) from pig donors. MHC-unmatched animals (weighing65 ± 4 Kg) were divided into four groups (each, n = 5) and 6 cm of their tracheasreplaced with a DEM matrix alone (group I) or seeded with recipients autologouschondrocytes (group II) or epithelial cells (group III), or both (groupIV). Epithelialcells (via bronchial-epithelial biopsies) and stem cells (bone marrow aspiration)were harvested from recipients and in-vitro cultured. Stem cells were differentiatedinto chondrocytes using specific growth factors. Both cell types were seeded simultaneouslyusing a novel bioreactor allowing dynamic and physiological cell culture.Pigs were observed during study period of 60 days via bronchoscopy, blood samplesand biopsies. Grafts were evaluated mechanically and immunohistologicallypre-implantation and post-mortem.RESULTS: Matrices were completely covered with both chondrocytes and epithelialcells within 72 hours using the new device. Extent of seeding affected animalslife time and outcome significantly (p < 0.05) (group I: 11 ± 2days; II: 29 ± 4 days;III: 34 ± 4 days; IV: 60 ± 1 days). Animals died due to severe respiratory disorders(group I), grafts bacteria contamination (group II) or stenosis and anastomoticfailure (group III). Group IV animals showed bronchoscopically healthy and blandcovered graft surface without any collapse of the graft. No rejection signs occurredin this immunosuppression-free model. Grafts strain abilities were equal to nativetracheas (tissue deformation: 211 ± 13 vs 206 ± 12%).CONCLUSION: The obtained bioengineered tracheal graft demonstrated itshigh potential as airway replacement.* AATS Member142
AMERICAN ASSOCIATION FOR THORACIC SURGERYF14. DYRK2, a Dual-Specificity Tyrosine-(Y)-Phosphorylation-Regulated Kinase Gene, Expression can be a Predictive Markerfor Chemotherapy in Non-small Cell Lung CancerShin-ichi Yamashita, Katsunobu KawaharaSurgery II, Oita University Faculty of Medicine, Yufu, JapanInvited Discussant: David JablonsOBJECTIVE: Several predictive markers of treatment and survival benefit werereported such as ERCC1 in NSCLC (non-small cell lung cancer). We report herethe correlation between clinicopathological factors in non-small cell lung cancer(NSCLC) and expression of DYRK2, a dual-specificity tyrosine-(Y)-phosphorylationregulated kinase gene, furthermore, the possibility to predict benefit from chemotherapyfor patients in recurrent NSCLC.METHODS: DYRK2 expression in 157 patients with NSCLC were evaluated byimmunohistochemistry (IHC) and quantitative RT-PCR. The correlation betweenthe expression levels of this gene and clinicopathological factors were investigated.In the other series, forty patients with recurrent disease after surgery received severalcombinations of platinum-based chemotherapy. Chemotherapy effectiveness wasevaluated according to RECIST criterion and the relationship between clinicaleffectiveness and the expression levels of this gene by IHC were evaluated.TUESDAYMorningRESULTS: We could not find any correlation between age, sex, pathological stage,tumor size, histological type and DYRK2 expression. However, this gene expressionwas significantly related to nodal metastases (P < 0.05). Overall response rate is22.2% (4 out of 18) in DYRK2 positive group compared with 4.5% (1 out of 22) innegative group. On the other hand, 17 PD (progressive disease) is consisted of 3DYRK2 positive patients and 14 DYRK2 negative patients.(p = 0.0086) The mediantime to the progression of disease was 120 days in the DYRK2 negative group, ascompared with 310 days in the DYRK2 positive group(HR = 1.984, 95% CI =[1.039–3.788], p = 0.034).CONCLUSION: Our study showed that DYRK2 has the critical role of nodalmetastases in NSCLC. Furher, patients with recurrent NSCLC and DYRK2-positive tumors derived a substantial benefit from chemotherapy, as comparedwith patients with DYRK2-negative tumors.143
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AATS FUTURE MEETINGSMay 1-5, 2010Me
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