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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
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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.
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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.