Abstract: Spontaneous pneumothorax represents a rare and potentially severe complication of Wegener's granulomatosis. A 31-year-old man with Wegener's granulomatosis on immunosuppressive therapy was admitted for a right massive spontaneous pneumothorax. After chest drainage he presented with a prolonged air leak that required a surgical treatment. Histologic findings did not reveal any necrotizing granulomatous vasculitis, but only subpleural fibrous tissue. We hypothesize that pneumothorax could be related to the subpleural fibrous retraction induced by immunosuppressive therapy.
Abstract: We report a rare case of malignant pleural mesothelioma presenting clinically with pneumothorax and histologically with an exclusive intrapulmonary lepidic growth. Neither intrathoracic nodules nor pleural thickening were found. The patient subsequently experienced acute abdominal pain with peritonitis and intestinal occlusion by peritoneal mesothelioma. The morphologic clues leading to the correct diagnosis of mesothelioma with prominent intrapulmonary growth are briefly discussed.
Abstract: PURPOSE: The current TNM staging system for non-small cell lung cancer subdivides stage IA and IB according to a tumor size threshold of 3 cm. Some authors have suggested that tumor size behaves as a continuous, but the optimal diameter thresholds to be adopted remain debated. METHODS: We conducted a retrospective study on 548 patients who underwent a complete surgical resection at our institute for stage IA and IB non-small cell lung cancer according to the current TNM staging system. Univariate and multiaviate analysis of overall and disease-specific survival were performed. RESULTS: Stage IA had an overall 5 years survival of 67% and a 5 years disease-specific survival of 85%. Stage IB had an overall 5 years of 49% and 5 years disease-specific survival of 53%. Tumors <2 cm had a significantly better survival than tumors > or =2 cm (overall survival: p=0.007; disease-specific survival: p=0.026), as well as tumors ranging from 2 to 5 cm in comparison with larger ones (overall survival: p=0.031; disease-specific survival: p=0.013). No significant difference was found between groups ranging from 2 to 5 cm. Tumors of 2-5 cm had 57% higher probability of death in comparison with tumors <2 cm and tumors >5 cm had a probability of death 60% higher than tumor of 2-5 cm. Age and tumor size (two thresholds diameter classification) resulted independent variables at multivariate analysis. CONCLUSION: the definition of T factor in the staging system of non-small cell lung cancer should consider two cutoffs according to tumor size. Two and 5 cm represent appropriate thresholds diameters that define subgroups with significant different prognosis.
Abstract: OBJECTIVE: Large cell neuroendocrine carcinoma of the lung are considered aggressive. However, reported prognoses are heterogeneous and the optimum treatment remains undefined. We retrospectively evaluated outcomes in a series of patients with a pathological diagnosis of large cell neuroendocrine lung carcinoma, who underwent lung resection. We also assessed the utility of chemotherapy in a small subgroup. PATIENTS AND METHODS: The clinical records of 144 consecutive patients were reviewed in a multicenter study. Survival times, assessed from the day of surgery until death or most recent follow-up, were estimated by the Kaplan-Meier method, and compared by the log rank test. RESULTS: There were 117 men and 27 women of median age 63 years. Twelve wedge resections, 3 segmentectomies, 95 lobectomies, 7 bilobectomies and 24 pneumonectomies were performed. Induction chemotherapy was given in 21 and postoperative chemotherapy in 24. Pathologically, 73 (50%) were stage I, 29 (20%) stage II, 40 (28%) stage III and 2 stage IV. Postoperative mortality was 2.8% and morbidity 26%. Overall 5-year survival was 42.5%: 52% for stage I, 59% for stage II and 20% for stage III (p=0.001 log-rank test on Kaplan-Meier curves). A trend to better outcome was associated with preoperative or postoperative chemotherapy in stage I disease (p=0.077) compared to no chemotherapy. The response rate to induction chemotherapy was 80% in the 15 patients with data available. CONCLUSION: large cell neuroendocrine carcinoma of the lung are confirmed as aggressive but are also chemosensitive. Our experience suggests that chemotherapy may improve prognosis in stage I disease.
Abstract: Lung metastasectomy is an accepted treatment for selected patients with pulmonary metastases. Resectability, disease-free interval and number of metastases are well characterised prognostic indicators after lung metastasectomy. Patients treated with lung metastasectomy for epithelial tumours were retrospectively reviewed. One hundred and forty-two patients were reviewed. The rate of mediastinal node metastases was 12%. Overall 5-year survival rate was 36% with a median survival time of 47 months. Recurrence rate after lung metastasectomy was 50%. Five-year disease-free survival was 26% with a median of 29 months. Mediastinal nodal status negatively affected survival at univariate analysis (5-years 32% for N+ and 40% for N-, P=0.013). Disease-free survival was significantly different according to nodal status: 5-year disease-free survival 17 and 28% for N+ and N-, respectively (P=0.053). Systemic recurrences were more frequent in patients with nodal involvement (P=0.058). Mediastinal nodal involvement resulted in a significant prognostic factor at multivariate analysis (N+: RRD=3.0; 95% CI 1.3-6.7). Patients with pulmonary metastases and nodal involvement had a poor prognosis and relapsed early after pulmonary metastasectomy. Nodal status should be considered in the selection of patients for lung metastasectomy.
Abstract: The current WHO classification of lung tumors recognizes bronchial typical carcinoid as low-grade neuroendocrine tumors. These tumors grow slowly but can metastasize to regional nodes (4 to 20%) and more rarely to extrathoracic sites. Symptoms are usually related to local compression and obstruction of the bronchial tree. Paraneoplastic syndrome can be present (carcinoid syndrome, Cushing's syndrome, acromegaly). Preoperative diagnosis is usually obtained with bronchoscopic biopsy. Computed tomography and somatostatin receptor scintigraphy are useful in the preoperative staging. Only selected cases can be treated endoscopically with laser resection. The complete surgical resection remains the only therapy with curative intent in the majority of patients. Parenchyma-sparing resections are indicated whenever possible. Overall survival after surgery is excellent (5-year rate, 87 to 100%) with low recurrence rate (2 to 11%). N-status and type of resection seem not to affect prognosis. Local relapse can be treated successfully with surgery, whereas distant metastases have a poor prognosis even after chemotherapy.
Abstract: OBJECTIVE: The aim of this study was to investigate the effectiveness, safety and appropriate mode of administration of intrapleural talc for pleurodesis, in the treatment of malignant pleural effusion (MPE). METHODS: Prospective not randomized trial was conducted to compare thoracoscopic talc poudrage (TP) with tube thoracostomy and talc slurry (TS) for the local control of malignant pleural effusion. Both procedures were previously standardized; 6g of talc was administered for each procedure. Only the patients with lung re-expansion after drainage entered the study. Patients at high risk for general anaesthesia, poor general conditions and short life-expectancy received talc slurry through a chest tube, at the bedside. All the other patients underwent videothoracoscopic talc poudrage, with a pneumatic atomizer, under general anaesthesia. Morbidity, 30-day freedom from recurrence and long-term results were assessed and the two groups were compared. RESULTS: One hundred and nine patients entered the study (72 TP, 37 TS). Sixty-three patients in the TP group (87.5%) and 27 in the TS group (73%) had an immediate successful pleurodesis (p = 0.049); 53 patients (88.3%) and 16 patients (69.6%) had a successful pleurodesis 90 days after the procedure; 59 patients (81.9%) and 23 patients (62.2%), respectively, had a life-long pleural symphysis (p = 0.023). Adverse effects were generally mild: chest pain (36.1% in TP patients, 48.6% in TS patients) and fever (38.8% and 35.1%, respectively) were the more common but the difference was not significant between the two groups. We observed neither acute respiratory failure nor mortality due to the procedure. CONCLUSIONS: Our study confirms that intrapleural talc carries good results in the treatment of malignant pleural effusion. TP was significantly more effective than TS; both methods were safe but TS had a higher incidence of thoracic pain during the procedure. Talc pleurodesis should be offered to every patient with MPE, apart from terminally ill ones, provided that a satisfying lung re-expansion has been achieved. TP should be performed whenever possible; otherwise, a slurry bedside procedure will be worthwhile, even in patients with low performance status (PS), though poorer results have to be expected. A careful selection is essential to define the proper technique.
Abstract: OBJECTIVE: Patients with non-small cell lung cancer (NSCLC) with metastases to ipsilateral mediastinal lymph nodes (N2) are an heterogeneous group of patients as regard to prognosis and treatment. Indication and timing of surgery remain controversial. The present study investigates the prognostic factors, in order to identify homogenous subgroups of patients. METHODS: Histologically proven N2-NSCLC patients, who underwent a complete surgical resection were retrospectively reviewed. Clinical and pathological features were reported and analyzed, and survival study was performed. RESULTS: One hundred eighty-three patients were analyzed. Overall 1.3 and 5 years survival rates were, respectively, 70, 35 and 20%, with a median survival time of 24 months. Univariate analysis showed a significant better prognosis for: incidental N2 respect to clinical N2 (5-years 35.4 vs 17.4%); single level lymph node involvement respect to multiple levels (5-years 23.8 vs 14.7%); metastases to superior mediastinal or aortic nodes respect to lower mediastinal nodes (5-years 32 and 24.3 vs 16.3%); right upper lobe tumors with superior mediastinal nodes and left upper lobe tumors with aortic nodes respect to lower lobes tumors with lower mediastinal nodes (5-years 31.8 and 26.9 vs 15.7%). Skip metastases had not a significant survival advantage respect to continuous lymphatic spread. N2 clinical status, the number of levels involved and the two specific patterns of lymphatic spread resulted significant prognostic factors at multivariate analysis. CONCLUSIONS: Clinical N2 status, number of lymph nodes levels involved and specific patterns of lymphatic spread identify homogenous subgroups of patients that can be proposed for different therapeutic strategies.
Abstract: PURPOSE: Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a relatively uncommon, high-grade neuroendocrine tumor sharing several features with small-cell lung carcinoma (SCLC) but currently considered as a variant of non-SCLC and accordingly treated with poor results. Little is known about the optimal therapy of LCNEC and the possible therapeutic molecular targets. PATIENTS AND METHODS: We reviewed 83 patients with pure pulmonary LCNEC to investigate their clinicopathologic features, therapeutic strategy, and immunohistochemical expression and the mutational status of the receptor tyrosine kinases (RTKs) KIT, PDGFRalpha, PDGFRbeta, and Met. RESULTS: LCNEC histology predicted a dismal outcome (overall median survival, 17 months) even in stage I patients (5-year survival rate, 33%). LCNEC strongly expressed RTKs (KIT in 62.7% of patients, PDGFRalpha in 60.2%, PDGFRbeta in 81.9%, and Met in 47%), but no mutations were detected in the exons encoding for the relevant juxtamembrane domains. Tumor stage and size (> or = 3 cm) and Met expression were significantly correlated with survival. At univariate and multivariate analysis, SCLC-based chemotherapy (platinum-etoposide) was the most important variable correlating with survival, both in the adjuvant and metastatic settings (P < .0001). CONCLUSION: Pulmonary LCNEC represents an aggressive tumor requiring multimodal treatment even for resectable stage I disease, and LCNEC seems to respond to adjuvant platinum-etoposide-based chemotherapy. Patients who received this therapy had the best survival rate. Despite our failure in finding mutational events in the tested RTKs, the strong expression of KIT, PDGFRalpha, PDGFRbeta, and Met in tumor cells suggests an important role of these RTKs in LCNEC, and these RTKs seem to be attractive therapeutic targets.
Abstract: BACKGROUND: Large cell neuroendocrine carcinoma (LCNEC) is a high-grade neuroendocrine tumor of the lung that shares some clinicopathologic and molecular features with small cell lung carcinoma (SCLC). Optimal treatment has not yet been standardized and significant prognostic factors are lacking. Because c-kit protein overexpression has been recently reported as a negative prognostic factor in SCLC we investigated its expression and prognostic value in a series of LCNEC. METHODS: Resected LCNEC fulfilling the morphologic criteria of the 1999 World Health Organization classification of lung tumors and showing neuroendocrine differentiation by appropriate immunohistochemical markers were retrospectively reviewed. Immunostaining for c-kit protein expression was performed using the polyclonal antibody CD117. Clinical and pathologic characteristic were reported and analyzed and a survival study was performed. RESULTS: Thirty-three patients underwent radical resection. Thirty-one were male (94%) and 32 were smokers (97%). Ten (30.3%), 11 (33.3%), 5 (15.2%), and 7 (21.2%) were at stage IA, IB, IIB, and IIIA respectively. Overall 1-, 3-, and 5-year survival rates were respectively 79%, 58%, and 51%. Survival analysis showed no differences for any of the clinicopathological features except for CD117 immunostaining: 1-year and 3-year survival rates were respectively 91% and 82% for CD117-negative LCNEC, and 72% and 44% for CD117-positive ones (p = 0.046). Positivity of CD117 was significantly related to recurrence rate: 60% versus 23% for CD117 positive and negative LCNEC respectively (p = 0.037). CONCLUSIONS: Radical resection of large cell neuroendocrine carcinoma achieves poor outcomes. The c-kit protein is frequently expressed in this neoplasia and its expression represents a negative prognostic factor. This immunohistochemical marker may represent the basic rationale to select LCNEC for novel targeted therapy.
Abstract: BACKGROUND: The management of a solitary pulmonary nodule is the subject of debate and minimally invasive diagnostic approaches have low sensitivity for small peripheral nodules. We discuss the role of video-assisted thoracoscopic surgery (VATS) in the management of solitary pulmonary nodules (SPNs) < or = 1 cm performed with a preoperative computed tomography-guided wire localization. METHODS: Thirty-five selected patients underwent VATS resection for SPN, with localization by guide wire before surgery. RESULTS: Seven patients, after VATS exploration, underwent thoracotomy because of pleuropulmonary adhesions, depth or dimensions. Histological diagnosis was obtained in all procedures; there was no postoperative morbidity or morbidity. CONCLUSION: Preoperative computed tomography hook-wire localization is a suitable strategy for peripheral nodules < or = 1 cm in diameter.
Abstract: The case of a 63-year-old woman with a solitary pulmonary nodule (SPN) is reported. Surgical wedge resection revealed an hamartoma. Digital examination of the lung parenchyma showed an unexpected (not previously visualized by thoracic imaging) second nodule that intraoperative frozen examination revealed an adenocarcinoma. The operation was completed with a right upper lobectomy and complete lymphoadenectomy. The authors recommend an early open surgical procedure for any SPNs with risk factors for developing lung cancer.
