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scope, the SEM processes included dehydration, critical point drying and platinum sputtering. Results: At day 1 post Tx, the allograft showed overall signs of destruction (Fig. A): alveoli were injured with thickening of the alveolar wall containing multiple perforations (single arrow). The capillary lumen between alveoli vanished. There was a widening of the perivascular space around vessels (double arrow) with invasion of inflammatory cells and erythrocytes. Furthermore, bronchioles and alveoli were covered with a thick layer of mucus. In contrast, the non-transplanted lung showed a normal architecture and alveoli and vessels remained in close contact to each other (Fig. B, Fig. E). At day 5 post Tx, the architecture of the alveoli was completely lost with invasion of multiple cells into the alveolar and perivascular space. Leukocytes and macrophages were found numerously in the perivascular tissue, with accumulation of mainly erythrocytes in the alveolar space (Fig. D). The architecture of the non transplanted lung on day 5 was normal. Interestingly, leukocytes percolated the basal membrane of the bronchioles (Fig. F) with concomitant macrophage invasion into terminal bronchioles (Fig. C). Conclusion: The SEM detects patho-morphological changes of acute rejection at an early state. The interstitial space, small vessels, alveoli and bronchioles of the allograft were severely altered by invasion of immune cells, with a significant involvement also of the non-transplanted lung. 50 swiss knife 2010; 7: special edition � �� 55.6 Survival of trimodal therapy of malignant pleural mesothelioma with extrapleural pneumonectomy R. Fahrner, G. L. Carboni, A. Ochsenbein, R. A. Schmid (Berne) Objective: Since multimodal therapy of malignant pleural mesothelioma (MPM) was introduced survival was improved particulary in subpopulations with epithelial histology, R0-resection and absence of broad chestwall invasion. This study aimed to evaluate the longterm outcomes after trimodal therapy including extrapleural pneumonectomy (EPP). Methods: Between October 1st 2000 to December 31st 2005 41 patients with histologically verified MPM were treated in our institution. After confirmation of the diagnosis with surgical biopsy (epithelial type n=17, mixed type n=4) and negative lymph node status in mediastinoscopy 21 patients (51%) underwent trimodal therapy with a median follow-up of 655 days (63-2567 days) and the other 20 patients underwent palliative treatment. Postoperative complications, 1-, 2- and 5-year survial rates and recurrence rates were analyzed retrospectively. Results: Patients with trimodal therapy had a median age of 64 years (40-75, 18 men). Neoadjuvant chemotherapy consisted mainly in a combination of platinum based agents (n=19), gemcitabine (n=15) or pemetrexed (n=4). EPP was done as standard surgical procedure, time from diagnosis and EPP was 117 days. Complications such as infections (n=11), arrhythmia (n=4), bleeding (n=2), patch avulsion (n=1) but no bronchus stump insufficiency occurred. 19 patients received adjuvant radiotherapy. 1-year-survival rate was 71% in the trimodal treatment group versus 21% in the palliative group (p=0.005). Survival rates in the trimodal treatment group were 28% after two years and 10% after five years. There were no statistical significant differences seen regarding sex, age, tumor stage or cell type. Tumor recurrence was detected after one and two years respectively 40% and 82%. Conclusion: At diagnosis the majority of patients has already a advanced stage disease and palliative approaches remain the only option. In the subpopulation of patients which underwent trimodal therapy survival was better than in the palliative treatment group but still long term survival is worse than in bronchogenic carcinoma, considering the high morbidity of EPP. � � � 55.7 Atypical expression and distribution of embryonic stem cell marker, OCT4, in human lung adenocarcinoma G. Karoubi 1 , L. Cortes-Dericks 1 , M. Gugger 1 , D. Galetta 2 , L. Spaggiari 2 , R. A. Schmid 1 ( 1 Berne, 2 Milan) Objective: Lung cancer is one of the leading causes of cancer-related deaths in the world. Although the origin still remains to be resolved, a prevailing hypothesis implies the involvement of cancer stem cells (CSCs) responsible for tumor initiation, maintenance and progression. OCT4, a major regulator of embryonic stem cell self-renewal, encodes two main spliced variants designated as OCT4A and OCT4B, and has recently been shown to have a dual role; as a potential adult stem cell marker, and as a cancer stem cell marker in germline and somatic tumors. Methods: In this study we sought to investigate the expression and intracellular distribution of OCT4A and OCT4B isoforms using flow cytometry, Western blot and quantitative RT-PCR analyses in normal and lung adenocarcinoma cell lines, primary cultures and tissue biopsies. Results: We demonstrate for the first time, the presence of rare OCT4A+ and OCT4B+ cells in normal lung. Notably, we observed higher levels of expression and atypical cytoplasmic distribution of OCT4A and not OCT4B, in the malignant setting, strongly indicating an oncogenic role in lung adenocarcinoma. Conclusion: We postulate that OCT4A+ cells represent a putative cancer stem cell population. Identification of these cells and the biological processes vital for their subsistence, will guide the development of diagnostic and therapeutic clinical approaches with the goal of eliminating lung adenocarcinoma. 55.8 Functional results of a new screwless fixation device for rib fractures in patients with flail chest T. Strauss, H. Hoffmann, J. Bremerich, M. Siegemund, M. Tamm, D. Lardinois (Basel) Objective: Selected patients with severe antero-lateral flail chest and impaired respiratory function who should recover quickly have an indication for operative stabilisation of the ribs. This is a prospective study of chest wall integrity and pulmonary function in these patients who underwent chest wall stabilisation with a new screwless fixation device (STRATOSTM, MedXpert, Germany). Methods: Between May 2008 and December 2009 14 patients (10m, 4w) with a mean age of 57 years (43-74) were operated for traumatic flail chest. The mean number of affected ribs was 8 (3-12), the sternum was fractured in 4 cases. Titanium rib clamps were placed and fixed to the stable parts of the most affected ribs and connected by titanium plates. Clinical outcome, pulmonary testing and dynamic assessment of the chest wall mobility by cine MRI were performed 6 months following surgery. Results: 9 patients (64%) had various combinations of injuries of the thorax, head, abdomen and extremities. 9 patients (64%) underwent unilateral, 5 patients (35%) bilateral stabilisation with a medium delay of 5,4 days (1-14) from admission. 30 day mortality was 0%. Immediate postoperative extubation was feasible in 5 patients (35%). No material dislocation was observed during follow up. Two patients were reoperated due to infection and hematoma. After operation patients remained in hospital for 24.3 days in the mean (8-71), patients with monotrauma only 11.5 days. At 6 months preliminary data show no restriction in the pulmonary function testing and cineMRI shows symmetric movement of the chest wall. Time to return to normal daily activity was 44 days after discharge. Shoulder function was impaired after 6 months in 4 patients. Conclusion: Our results suggest that antero-lateral flail chest injuries accompanied by respiratory insufficiency can be effectively stabilised by screwless titanium fixation device. 55.9 Primary pedunculated muscle flap coverage of bronchial and tracheal defects as an alternative to direct closure or bronchotracheal sleeve resection P. Dorn, M. Kuhn, M. Odermatt, M. Furrer (Chur) Objective: Bronchial airways after lung resections are usually closed either by manual or mechanical suture. To prevent bronchopleural fistula (BPF) additional reinforcement of the bronchial stump by a pedunculated muscle flap (PMF) is often recommended. In very central tumours sleeve resection with anastomosis is generally preferred to direct closure with the aim of minimizing airway stenosis or avoiding incomplete resection. As a further alternative we describe a technique where only a PMF is used to cover an open and unsutured central airway defect by means of three high-risk patients. Methods: CASE 1: A 40 year-old man underwent extended right pneumonectomy because of central non small cell lung cancer (NSCLC) with severe poststenotic pneumonia. The tracheal defect at the bifurcation was covered by a PMF without preceding bronchial suture closure. There was no evidence of air leakage in intraoperative testing and repetitive bronchoscopy. No complications were seen in the postoperative course. CASE 2: A 45 year-old woman underwent extended right pneumonectomy. After impressive tumour regression due to neoadjuvant chemotherapy the resection margin of the right bronchus was close to the carina. A PMF was used for coverage of the airway defect. Intraoperative testing including bronchoscopy showed no evidence of air leakage or contralateral prolapse of the muscle flap. The postoperative course was complicated by ARDS of the remaining left lung necessitating continuous positive airway pressure (CPAP). Delayed re-thoracotomy with muscle flap refixation had to be performed because of secondary air leakage. CASE 3: A 72 year-old man with NSCLC and neoadjuvant chemotherapy underwent right bilobectomy with extended resection of the right intermediate bronchus up to the main bronchus. The defect of the main bronchus was covered using a PMF. Intraoperative bronchoscopy and air leakage testing were normal. The postoperative course was uneventfull. Results: See above (Methods and Results). Conclusion: Primary coverage of a central bronchial or tracheal defect using only a PMF is feasible. Predominantly in high risk patients direct suture at risk or extensive sleeve resection may be avoided.
55.10 Optimized intrapleural cisplatin chemotherapy with a fibrin carrier after extrapleural pneumonectomya pre-clinical study I. Opitz, B. Erne, S. Demirbas, A. Jetter, B. Seifert, R. Stahel, W. Weder (Zürich) Objective: The aim of the study was to evaluate whether platinum concentration in the subpleural tissue and in the blood are optimized by local application of cisplatin loaded to a fibrin carrier compared to cisplatin-solution in a randomized setting of a pig model. Methods: After left-sided pneumonectomy plus parietal pleurectomy the pigs were randomly assigned to receive either 90 mg/m 2 cisplatin intrapleural solution (control, n=5) or to receive 5mg cisplatin combined to a fibrin sealant applied on a predefined area of the chest wall (study group, n=5). Platinum concentration in the plasma was determined at several early time points (1-24h) and at 2 and 5 days following treatment. Chest wall biopsies were assessed for platinum concentration after 2 and 4 hours and at day 2 and 5 after cisplatin application. The level of total platinum was measured by means of inductively coupled plasma sector field mass spectrometric detection with a matrix-matched calibration procedure. Results: The dose- and surface-corrected mean concentration of cisplatin in the chest wall tissue 2 h after the application was 504.1 g/L in animals treated with cisplatin-fibrin (geometric coefficients of variation, CV, 88%), compared to 249.1 g/L (CV 261%) in the control group. Five days after the application, mean concentrations in the tissue were 72.5 g/L (CV 216%) and 21.8 g/L (CV 427%) in fibrin- and solution treated animals, respectively. In plasma, the dose- and application surface-corrected exposure towards cisplatin (area under the concentration-time curve from 0-5 d after surgery) was clearly and significantly lower with cisplatin-fibrin than with cisplatin- solution: 68.5 g/L*h (CV 28%) versus 755.8 g/L*h (CV 110%). This is also reflected by significantly reduced serum-creatinine values in the study group in comparison to the control group (p=0.02) as well as significantly better well-being scores for the animals treated with cisplatin-fibrin at each day of the observation (all p
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Page 47 and 48: Conclusion: Pharmacological inhibit
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