Supplementum 163 - Swiss Medical Weekly

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27 S SWISS MED WKLY 2008;138(Suppl <strong>163</strong>) · www.smw.ch Poster Session 2 - SSP / SGP P130 Molecular classification of non-small-cell lung cancer and prediction of survival using gene expression signatures derived from clinical routine biopsies F. Baty1 , M. Facompré1 , S. Kaiser2 , M. Schumacher2 , M. Pless1 , L. Bubendorf1 , S. Savic1 , E. Marrer2 , W. Budach2 , M. Buess1 , J. Kehren2 , M. Tamm1 , M. Brutsche1 . 1 University Hospital Basel (Basel, CH); 2 Novartis AG (Basel, CH) Background: The usefulness of microarray-based technologies for the classification and prediction of outcome of non-small-cell lung cancer (NSCLC) has been shown previously. However, the need for large tumor samples limits its application to operated early stage tumors. The aim of this study was to evaluate the feasibility and utility of gene expression profiling using biopsies obtained during routine clinical work-up including minute bronchoscopic biopsies. Methods: Gene expression profiles (Novachip; 34207 transcripts) derived from biopsies of 41 consecutive chemotherapy-naïve NSCLC patients (mean follow-up: 22 months) and 15 controls with inflammatory lung diseases were analyzed. Gene signatures associated with different NSCLC phenotypes and survival were identified and confirmed using independent NSCLC data sets and tissue microarrays. Results: Classification based on functional genomics showed an overall sensitivity and specificity of 80% and 89% respectively, and was dependent on the proportion of tumor cells present in the biopsies. From an optimized metagene of 44 prognostic genes, 13 could be validated in 4 independent data sets on lung cancer. A metagene based on these 13 genes was further validated in an independent data set. The prognostic value of VEGFB expression was confirmed on a protein level by tissue microarray. Conclusion: The proposed strategy allows molecular tumor classification and prediction of survival in patients with NSCLC of all stages and is suitable for an integration in the daily clinical practice. P131 Comparing right lower lobe sleeve lobectomy with bilobectomy in the treatment of bronchial carcinoma P. Morand, C. Ludwig, J. Schnell, E. Stoelben. Kliniken der Stadt Köln gGmbH (Köln, D) Introduction: A tumour located in the right lower lobe, especially when arising in segment 6 has a close anatomical relationship to the middle lobe bronchus, which may make lower bilobectomy necessary. This procedure has an increased morbidity and mortality when compared to lobectomy. In this situation, sleeve lobectomy may be an alternative. These procedures are compared in terms of postoperative lung function, complication rate and oncological radicality. Patients and methods: Retrospective analysis of 52 patient records between 01.01.2005 and 31.12.2007 operated on an NSCLC (stage I-IIIb)of the right lower lobe. In 28 patients, a sleeve lobectomy with preservation of the middle lobe was performed, in 24 patients a bilobectomy. The average age was 63 years. Data recorded was: TNM classification, preoperative lung function and after at least 3 months, length of chest tube drainage in days, complications and rate of recurrence. Results: Preoperative FEV1 was comparable in both groups (sleeve lobectomy 74%, bilobectomy 76%). After sleeve lobectomy we observed one early anastomotic leakage that was due to a technical failure, requiring reintervention. No patient died. After bilobectomy no bronchial leakage was observed, one patient died of apoplexy during the hospital stay. Radical resection (R0) was achieved in 50/52 patients. The length of the operation was 121 min. for sleeve lobectomy and 144 for bilobectomy. Chest tube were removed on average in both groups after 5 days. After bilobectomy postoperative FEV1 was on average 69%, whereas after sleeve lobectomy it was 78%. Conclusions: Preservation of the middle lobe by means of a sleeve lobectomy is possible in almost half the patients. We had no evidence that this method was less radical. The complication rate was similar in both groups. The complete analysis of postoperative lung function and rate of recurrence will be presented. P132 Diagnostic value and risk assessment of surgical lung biopsy in patients with pulmonary complications after high-dose chemotherapy and stem cell transplantation F. Gambazzi, D. Stolz, L. Bubendorf, J. Halter, D. Heim, A. Buser, A. Gratwohl, D. Lardinois, M. Tamm. Universitätsspital Basel (Basel, CH) Pulmonary complications are frequent in patients with hematologic malignancies. Due to the variety of infectious and non-infectious pulmonary complications non-invasive and invasive diagnostic methods are used to initiate adequate treatment. Fears to perform an invasive surgical approach include bleeding, infection and respiratory failure. We therefore analysed the diagnostic value and postoperative complications of VATS or open lung biopsy in 53 patients with hematologic malignancies undergoing lung surgery between 2000 and 2007. 16 patients were treated with high dose chemotherapy and 37 patients with allogeneic or autologous stem cell transplantation. VATS biopsy was performed 37, OLB in 16 and diagnostic as well as therapeutic lung resection in 17 cases. 18.9% of patients were severely neutropenic (
Poster Session 2 – SSP / SGP P134 Hughes-Stovin syndrome presenting with life-threatening haemoptysis: a case report P. Dumont1 , T. Herren1 , Ch. von Garnier1 , M. Gugger1 , E. Perrin2 , P. Vock1 , L.P. Nicod1 . 1 Inselspital (Berne, CH); 2 HUG (Geneva, CH) Background: Hughes-Stovin syndrome is an extremely rare pathologic entity of unknown origin presenting with pulmonary artery mural thrombi and aneurysms and venous thrombosis (1). Some studies have suggested that Hughes-Stovin syndrome may represent an atypical manifestation of Behçet’s disease (2). Methods: We herein report the case of a 17-year old male who initially complained of recurrent hematemesis and hemoptysis in the past 6 months. In September 2006, he was admitted on ICU and intubated because of severe hemoptysis with acute respiratory failure and anemia (Hb 66g/L). Results: Initial diagnostic work-up revealed the presence of thrombosed pulmonary artery aneurysms of the left upper and lower lobes. Common causes of pulmonary artery aneurysms without arterio-venous communication (congenital vascular and cardiac abnormalities, pulmonary hypertension, mycotic and infectious disease including tuberculosis, vasculitis and other systemic diseases) were excluded. Major diagnostic criteria of the Behçet’s disease were not fulfilled. Though deep venous thrombosis at typical localization (lower extremities) was absent in this case, the presence of filling defects of the upper pulmonary vein at pulmonary CT angiogram as well as the absence of another likely differential supported the diagnosis of Hughes-Stovin syndrome. Our patient was initiated on immunosuppressive treatment associating prednisolone with monthly pulses of cyclophosphamide, subsequently substituted by oral azathioprine. Frequent clinical follow-ups and sequential CT angiogram studies revealed a complete regression of both pulmonary aneurysms. Moreover, the patient remained in excellent health and has not reported additional hemoptysis since. Conclusions: This case exemplifies that pulmonary aneurysms associated to Hughes-Stovin Syndrome respond to immunosuppression and should not receive anticoagulation despite presence of thrombosis. References (1) Hughes JP, Stovin PG. Segmental pulmonary artery aneurysms with peripheral venous thrombosis. Br J Dis Chest 1959;53:19–27. (2) Emad Y, et al. Hughes-Stovin syndrome: is it incomplete Behçet’s? Report of two cases and review of the literature. Clin Rheumatol. 2007;26(11):1993–6. P135 An unusual cause of haemoptysis: new diagnosis of an anomalous origin of the left pulmonary artery from the ascending aorta in a 20-year old man T. Herren, L.P. Nicod, M. Schwerzmann. Inselspital Bern (Bern, CH) A 20-year-old man with known 22q11 microdeletion and DiGeorge syndrome was admitted because of hemoptysis. DiGeorge Syndrome was diagnosed six years ago with detection of a right aortic arch, a PDA to the right pulmonary artery and an aberrant left subclavian artery. Subsequent analyses disclosed a microdeletion at chromosome 22q11.2. At the most recent admission, chest CT showed an until now not noticed anomalous origin of the left pulmonary artery (LPA) from the ascending aorta. At cardiac catherization, a non-stenosed LPA originating from the aorta and systemic pressure in the left lung were documented. The right ventricle was connected to the single right PA. Right mean PA pressure was mildly elevated at 30 mmHg. We interpreted the hemoptysis as a consequence of pulmonary hypertension in the left lung and suspected superinfection as cofactor. Hemoptysis stopped spontaneously. There is irreversible pulmonary vasculopathy in his left lung due the anomalous origin of the LPA. Fortunately, the decrease in left lung blood flow over time due to the progressive increase in pulmonary artery resistance reduced the volume load on the left ventricle. The PDA shunt flow is small and does not require intervention. Concerning the mild pulmonary hypertension in the RPA, we abstained from bosentan therapy because of mild symptoms and its potential to enhance LPA blood flow and thereby left ventricular volume load. SWISS MED WKLY 2008;138(Suppl <strong>163</strong>) · www.smw.ch 28 S P136 Infliximab therapy in patients with chronic progressive sarcoidosis – a retrospective follow-up study K. Hostettler, F. Baty, U. Studler, M. Tamm, M. Brutsche. Universitätsspital Basel (Basel, CH) Background: Infliximab is a monoclonal antibody against tumor necrosis factor-alpha, and its efficacy has been evaluated in patients with chronic sarcoidosis, demonstrating a significant improvement in percentage predicted forced vital capacity (FVC, %P) at week 24 (1). However, the clinical importance and the long-term benefit of infliximab treatment remain unclear. Methods: A retrospective chart review of all patients with histologically-confirmed pulmonary and/or extrapulmonary sarcoidosis who received infliximab (typically 3 mg/kg, 4-/6-/8-weekly intervals) for chronic steroid-resistant disease between January 2003 and November 2007 at the Clinic of Pneumology, University Hospital Basel. Lung function, 6-minute walk distance, cardio-pulmonary exercise tests, chest x-rays, index lesions (e.g. extent of skin involvement), and quality of life questionnaires, before and on/after infliximab therapy were assessed. Sarcoidosis is a heterogeneous disease, and responses to treatment are heterogeneous too; outcome measures were, therefore, defined as individualized treatment targets which were assessed for each subject individually. Results: In total 27 patients received infliximab, 11 (41%) patients with predominantly pulmonary involvement, and 16 (59%) patients with predominantly extrapulmonary disease (8 CNS, 5 lupus pernio, 1 eye, 1 hypercalciuria, and 1 heart). The mean duration of treatment was 14 (range 2 to 59) months. In 2/27 (7%) patients the treatment had to be stopped due to adverse effects (1 liver enzyme elevation, 1 allergic reaction). There was one drop-out after a single dose of infliximab due to missing cost coverage. Two of 11 patients (18%) with pulmonary sarcoidosis showed a >10%-improvement of FVC,%P, 7 (64%) patients showed a 0-10%-improvement, and in 2 (18%) patients FVC,%P declined during infliximab treatment. Of the 15 evaluable patients with mainly extrapulmonary sarcoidosis 6 (40%), 6 (40%) and 3 (20%) showed a complete remission, partial remission, and no response, respectively. Thus, overall 21/26 (81%) patients profited from infliximab treatment. Conclusions: Preliminary analysis of this retrospective follow-up study indicates that infliximab is very efficient in patients with steroidresistant sarcoidosis when assessed with individualized treatment targets. Patients with predominantly extrapulmonary sarcoidosis seem to profit more than patients with predominantly pulmonary disease. (1) Baughman AJRCCM 2006. P137 Chloroquine-induced acute eosinophilic pneumonia – a case report and review of the literature L. Knudsen, M. Gugger, P. Dumont, L.P. Nicod, C. von Garnier. Inselspital Bern (Bern, CH) Introduction: Chloroquine has a long-standing tradition in prophylaxis and treatment of malaria tropica, rheumatoid and autoimmune disorders including sarcoidosis. Common side-effects are frequently related to the gastrointestinal tract and centralnervous-system, but pulmonary unwanted secondary effects are rarely reported. Methods: We herein report the case of a previously healthy 41-year old woman, who presented with dry cough, cyanosis, and acute hypoxic respiratory failure, 13 days following chloroquine administration for rosacea. Results: Admission laboratory examinations showed increased inflammatory markers without blood eosinophilia. Initial Chest X-ray revealed Kerley-B-lines and the CT-thorax showed discrete subpleural ground-glass opacities. In pulmonary function test, a moderate obstruction was observed (FEV1 62%). The BALF examination demonstrated eosinophilia (17%) combined with mildly elevated neutrophils (11.5%), and histopathology of transbronchial biopsies showed eosinophilic granulocytes in the interstitial lung tissue. No evidence for an infection, including bacterial, viral, helminthic and fungal pathogens was found. Prick-test for Aspergillus fumigatus was not in favour of an allergic broncho-pulmonary aspergillosis. Other causes of elevated BALF eosinophilia, such as Churg-Strauss-syndrome, HIV-infection, and hypereosiniphilicsyndrom / chronic eosinophilic leukaemia were excluded. The timecourse of events, as well as the radiological and BALF finding were not characteristic for an idiopathic acute eosinophilic pneumonia. The symptoms subsided within 3 days following the cessation of chloroquine. In the literature, only 2 further well documented cases are reported with similar time-courses and findings. Typically, the reported latency was 1 to 2 weeks and the symptoms subsided within a few days after discontinuing chloroquine. In all cases BALF
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Page 5 and 6: Free Communications 1 - SSP / SGP 2
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Page 37 and 38: Poster Viewing P159 The chemokine r
Page 39 and 40: Poster Viewing P167 Dendritic cell
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Page 43 and 44: Poster Viewing T cell receptors (TC
Page 45 and 46: Poster Viewing P191 The chemokine C
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Page 55 and 56: Poster Viewing P233 Giant cell arte
Page 57 and 58: Poster Viewing P241 Examination of
Page 59 and 60: Poster Viewing P248 Assessment of i
Page 61 and 62: Poster Viewing Conclusion: Nausea e
Page 63 and 64: Poster Viewing P263 Postmortal dete
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Page 67: Index of authors SWISS MED WKLY 200

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