International Tailored Chemotherapy Adjuvant (ITACA) trial, a phase III multicenter randomized trial comparing adjuvant pharmacogenomic-driven chemotherapy versus standard adjuvant chemotherapy in completely resected stage II-IIIA non-small-cell lung cancer.

BACKGROUND: Several strategies have been investigated to improve the 4% survival advantage of adjuvant chemotherapy in early-stage non-small-cell lung cancer (NSCLC). In this investigator-initiated study we aimed to evaluate the predictive utility of the messenger RNA (mRNA) expression levels of excision repair cross complementation group 1 (ERCC1) and thymidylate synthase (TS) as assessed in resected tumor. PATIENTS AND METHODS: Seven hundred and seventy-three completely resected stage II-III NSCLC patients were enrolled and randomly assigned in each of the four genomic subgroups to investigator's choice of platinum-based chemotherapy (C, n = 389) or tailored chemotherapy (T, n = 384). All anticancer drugs were administered according to standard doses and schedules. Stratification factors included stage and smoking status. The primary endpoint of the study was overall survival (OS). RESULTS: Six hundred and ninety patients were included in the primary analysis. At a median follow-up of 45.9 months, 85 (24.6%) and 70 (20.3%) patients died in arms C and T, respectively. Five-year survival for patients in arms C and T was of 65.4% (95% CI (confidence interval): 58.5% to 71.4%) and 72.9% (95% CI: 66.5% to 78.3%), respectively. The estimated hazard ratio (HR) was 0.77 (95% CI: 0.56-1.06, P value: 0.109) for arm T versus arm C. HR for recurrence-free survival was 0.89 (95% CI: 0.69-1.14, P value: 0.341) for arm T versus arm C. Grade 3-5 toxicities were more frequently reported in arm C than in arm T. CONCLUSION: In completely resected stage II-III NSCLC tailoring adjuvant chemotherapy conferred a non-statistically significant trend for OS favoring the T arm. In terms of safety, the T arm was associated with better efficacy/toxicity ratio related to the different therapeutic choices in the experimental arm.

Simultaneous cardiac and lung surgery for incidental solitary pulmonary nodule: learning from the past.

BACKGROUND: Incidental solitary pulmonary nodules (ISPN) detected prior to scheduled cardiac surgery are rare but challenging. We evaluated the long-term outcome of patients with ISPN undergoing simultaneous cardiac and lung surgery. METHODS: The clinical records of 33 consecutive patients with ISPN undergoing cardiac and lung surgery, either simultaneously (n = 30) or sequentially (n = 3), were retrospectively evaluated and completed by detailed follow-up. RESULTS: On histological examination, 14 cases (42.4%) of primary NSCLC were identified. Benign findings consisted mostly of hamartoma and inflammation. Malignant ISPN were larger in size (22.5 ± 12.4 vs. 13.6 ± 8.6 mm) and ISPN with a diameter >10 mm had a higher incidence of malignancy compared to those ≤10 mm (56.0% vs. 0%). Patients undergoing concomittant heart and lung surgery received either a wedge resection (n = 26) or a lobectomy (n = 4). The 5-year survival of patients with malignant ISPN was lower than that of patients with benign ISPN (43.6% vs. 85.6%). CONCLUSIONS: Our results corroborate a high incidence of malignancy in ISPN detected prior to scheduled cardiac surgery. Simultaneous cardiac and lung surgery for NSCLC appears to be associated with a poor long-term outcome.

[Protective pneumothorax in CT-guided mediastinal puncture]. / Protektiver Pneumothorax bei CT-gesteuerter Mediastinalpunktion.

PURPOSE: To achieve an extrapulmonary pathway for biopsy of mediastinal masses. METHODS: In 6 patients a protective, temporary pneumothorax was established before performing large-bore needle biopsies of mediastinal masses using a Verres-needle. RESULTS: Transpleural, extrapulmonary access was easy to achieve. One patient developed a tension pneumothorax after biopsy which was drained by percutaneous small chest tube. Another patient showed mediastinal tumor bleeding through the biopsy needle. As a prophylactic measure the bleeding was stopped by injection of tissue glue through the biopsy needle. CONCLUSION: The use of protective pneumothorax allows cutting needle biopsies of mediastinal masses where aspiration cytology yields no secure specific diagnosis.

[Diagnosis of multiple myeloma by demonstrating plasma cells in bronchoalveolar lavage]. / Diagnose eines Multiplen Myeloms durch den Nachweis von Plasmazellen in der bronchoalveolären Lavage.

HISTORY AND CLINICAL FINDINGS: A 61-year-old man was transferred from a peripheral hospital with the diagnosis of interstitial lung disease and an unclear mediastinal tumour. At the time of admission the patient had congestive heart disease NYHA class IV. INVESTIGATIONS: The echocardiogram showed a small left ventricle with concentric hypertrophy and a left ventricular ejection fraction of 35 %. The myocardium was relatively echo-rich with solid structures inside. Chest X-ray showed a massive rightsided pleural effusion. The abdominal ultrasound demonstrated ascites and hepatomegaly. The bronchoalveolar lavage showed an increased part of CD3 negative and CD16/CD56 positive cells, which were identified as plasma cells by light and electron microscopy. Aspiration and investigation of the bone marrow verified the diagnosis of a IgG multiple myeloma, highly differentiated characterised by monoclonal expression of light-lambda chains. Additionally Bence-Jones-proteins were found in the urine and osteolysis in the x-ray of the skull and the humerus. DIAGNOSIS: Multiple myeloma, IgG-lambda, stage IIA. THERAPY AND CLINICAL COURSE: Chemotherapy with prednisolone and melphalan was initiated. His general condition increased after administration of the first cycle of chemotherapy. CONCLUSION: Cardiopulmonary involvement is seldom seen in multiple myeloma but should be excluded when clinical symptoms are present.

[Automated quantitative image cytometry of bronchial washings in suspected lung cancer: comparison with cytology, histology and clinical diagnosis]. / Automatisierte quantitative Image-Zytometrie bronchialer Spülflüssigkeiten bei Verdacht auf broncho-pulmonale Tumoren: Vergleich mit Zytologie, Histologie und Klinischer Diagnose.

INTRODUCTION: Automated image cytometry represents a new method for the quantitative analysis of nuclear structure and DNA-content of exfoliative airway epithelial cells. In the present investigation, we examined the correlation between automated cytometry, conventional cytology and histopathology with the final diagnosis as the "gold standard". METHODS: In 142 patients (100 males and 42 females) with suspected lung cancer and 50 controls (COPD, asthma), bronchial washings (5-10 ml) were obtained during bronchoscopy before taking biopsies for cytological and/or histological examinations. The washings were collected in 20 ml Saccomanno's fixative and centrifuged (500 g, 15 min). The cell pellet was resuspended in Saccomanno's solution. Two specimens were stained according to Papanicolaou and another two using the Feulgen reaction with thionine. Image cytometry was performed by means of a special, trainable classifier for exfoliative cells of the respiratory tract, using the Cyto-Sacant (Oncometrics, Vancouver). RESULTS: In the patients with suspected lung cancer we found numerous abnormal nuclei in 97 samples, 36 samples contained normal cells only, and 9 samples were insufficient. In our control group there was no sample with abnormal nuclei, and all washings were evaluable. Compared to the final diagnosis of lung cancer, we found a sensitivity of 90% (92/102) and a specificity of 84% (26/31). For histology sensitivity was 91% (73/80) and specificity 100%, while we found a sensitivity of 92% (92/100) and specificity of 100% for cytology. For automated cytometry the positive predicted value was 95%, the negative predicted value 71%. CONCLUSIONS: In the investigation of patients with suspected lung cancer, automated image cytometry of bronchial washings is a sensitive and reliable method for the detection of malignant changes in the tracheobronchial mucosa. The automated procedure seems well suited not only for analysing bronchial washings, but also for a screening procedure.