Paolo Olivo Lausi

Malignant pleural mesothelioma: clinicopathologic and survival characteristics in a consecutive series of 394 patients

OBJECTIVE Treatment of malignant pleural mesothelioma (MPM) remains disappointing, although recent reports suggest that multimodality therapy including surgery may provide a significant survival benefit. The aims of this single institution study were: to investigate clinicopathologic characteristics and potential prognostic factors in MPM patients, and to ascertain whether surgery followed by adjuvant therapy had an independent prognostic role. METHODS Retrospective review of a prospectively compiled computerized database of all patients with MPM evaluated between 1989 and 2003. Kaplan-Meier method, log-rank test, and Cox model were used in the statistical analysis. RESULTS There were 394 patients: 270 men (68.5%), 124 women, median age 64 (range 28-93). Twenty-seven patients (6.8%) underwent surgical resection (extrapleural pneumonectomy 15, pleurectomy/decortication 12), followed by adjuvant therapy. As of March 2006, 381 patients (96.7%) had died (median survival, 11.7 months; range 0.03-117.9). Median follow-up of 13 surviving patients (3.3%) was 45.2 months (range 28.7-126.5). Overall survival at 2 years was 18.8%. Multimodality therapy including surgery yielded a median survival of 14.5 months and a 2-year survival rate of 29.6%. Using univariate analysis, age (p=0.009), chest pain (p=0.01), weight loss (p=0.001), performance status (p=0.0001), platelet count (p=0.008), histology (p=0.0001), macroscopic appearance of pleural surface (non-specific inflammation, tumor-like thickening, or nodules; p=0.0001), visceral pleura involvement (p=0.0001), degree of involvement of pleural cavity (less than or more than one third of the cavity; p=0.0001), and multimodality therapy (p<0.01) were found to be significant prognostic factors. At multivariate analysis, performance status, platelet count, histology, and degree of involvement of pleural cavity remained independently associated with survival, whereas multimodality therapy failed to enter the model. CONCLUSIONS Significant predictors of survival include performance status, platelet count, histology, and degree of involvement of pleural cavity. Within the confines of this retrospective study and the small number of patients undergoing multimodality therapy, the role of surgery in the treatment of MPM remains unclear. Further investigation is warranted to determine the optimal treatment strategy in this disease.

Bone Sialoprotein Is Predictive of Bone Metastases in Resectable Non–Small-Cell Lung Cancer: A Retrospective Case-Control Study

PURPOSE Bone metastases (BM) in non-small-cell lung cancer (NSCLC) may be detected at diagnosis or during the course of the disease, and are associated with a worse prognosis. Currently, there are no predictive or diagnostic markers to identify high-risk patients for metastatic bone dissemination. PATIENTS AND METHODS Thirty patients with resected NSCLC who subsequently developed BM were matched for clinicopathologic parameters to 30 control patients with resected NSCLC without any metastases and 26 patients with resected NSCLC and non-BM lesions. Primary tumors were investigated by immunohistochemistry for 10 markers involved in bone resorption or development of metastases. Differences among groups were estimated by chi2 test, whereas the prognostic impact of clinicopathologic parameters and marker expression was evaluated by univariate (Wilcoxon and Mantel-Cox tests) and multivariate (Cox proportional hazards regression model) analyses. RESULTS The presence of bone sialoprotein (BSP) was strongly associated with bone dissemination (P < .001) and, independently, with worse outcome (P = .02, Mantel-Cox test), as defined by overall survival. To evaluate BSP protein expression in nonselected NSCLC, a series of 120 consecutive resected lung carcinomas was added to the study, and BSP prevalence reached 40%. No other markers showed a statistically significant difference among the three groups or demonstrated a prognostic impact, in terms of both overall survival and time interval to metastases. CONCLUSION BSP protein expression in the primary resected NSCLC is strongly associated with BM progression and could be useful in identifying high-risk patients who could benefit from novel modalities of surveillance and preventive treatment.

Efficacy and safety of human fibrinogen-thrombin patch (TachoSil®) in the treatment of postoperative air leakage in patients submitted to redo surgery for lung malignancies: a randomized trial

OBJECTIVES Previous studies of the human fibrinogen-thrombin patch TachoSil® for air leak management in thoracic surgery have excluded patients undergoing redo surgery, a group at high risk of persistent air leaks. This is the first study to assess TachoSil® in patients undergoing redo surgery. METHODS Patients who had undergone pulmonary resection for primary lung cancer or lung metastasis and were scheduled for completion lobectomy plus lymphadenectomy due to tumour recurrence were eligible. After complete lobectomy, patients with intraoperative Macchiarini grade 3 air leaks (or >30% of the tidal volume at plethysmographic assessment) were randomized to receive either TachoSil® or further lung parenchymal stapling/suturing procedures according to standard surgical practice. RESULTS A total of 24 patients were randomized to TachoSil® (n = 13) or standard treatment (n = 11). Mean duration of surgery was significantly shorter in the TachoSil® group than in the standard group (3.6 vs 4.0 h; P = 0.023). The mean duration of air leaks was also significantly reduced in the TachoSil® group (4.7 vs 10.0 days; P < 0.001), and the removal of both the first and the second chest tubes occurred earlier (mean 3.8 vs 5.5 days; P = 0.005; and 6.1 vs 10.8 days; P < 0.001, respectively). TachoSil® was also effective in reducing persistent (≥ 9 days) air leaks (1 vs 7 patients; P = 0.008). There were no significant differences between groups in other postoperative complications. Mean length of hospital stay was significantly shorter in TachoSil®-treated patients (6.9 vs 9.5 days; P < 0.001). CONCLUSIONS TachoSil® was superior to standard stapling and suturing aerostatic techniques in reducing postoperative air leaks in patients undergoing redo thoracic surgery.

Historical perspectives: The evolution of the thymic epithelial tumors staging system

Thymic epithelial tumors (thymomas, thymic carcinomas and neuroendocrine tumors - NETs) are rare primary mediastinal neoplasms, recently classified as orphan diseases. Their rarity might explain the fact that currently, no official staging system has been defined by the Union Internationale Contre le Cancer (UICC) and the American Joint Commission on Cancer (AJCC). However, the appropriate staging of these tumors has been matter of debate and several proposals have been published over the years, but very few have received a clinical validation. Recently an international database for thymic malignancies has been provided by the International Thymic Malignancy Interest Group (ITMIG); one of its aims is to accomplish a new and evidence based staging system, to allow progress in clinical management in thymic tumors. This paper will review the history of proposed staging systems, comparing resemblances and differences, being a sort of starting point for the development of a new widely accepted clinical staging system.

Air leaks following pulmonary resection for malignancy: risk factors, qualitative and quantitative analysis

Air leaks are a common complication of pulmonary resection. The aims of this study were to analyze risk factors for postoperative air leak and to evaluate the role of air leak measurement in identifying patients at increased risk for cardiorespiratory morbidity and prolonged air leak. From March to December 2009, 142 consecutive patients underwent pulmonary resection for malignancy and were prospectively followed up. Preoperative and intraoperative risk factors for air leak were evaluated. Air leaks were qualitatively and quantitatively labeled twice daily. There were 52 (36.6%) patients who had an air leak on day 1, and 32 (22.5%) who had an air leak on day 2. Air leak was ≥180 ml/min in 12 (37.5%) of these patients. Independent predictors of air leak on day 2 included type of pulmonary resection, presence of adhesions, and incomplete fissures. Cardiorespiratory morbidity was significantly higher (34.4%) in patients who experienced air leak on day 2 than in those who did not (10.9%) (P=0.002). Nine (75%) out of 12 patients with air leak ≥180 ml/min on day 2 had prolonged air leak (greater than five days) (P=0.0001).

Exploring Stage I non-small-cell lung cancer: development of a prognostic model predicting 5-year survival after surgical resection †

OBJECTIVES Despite impressive results in diagnosis and treatment of non-small-cell lung cancer (NSCLC), more than 30% of patients with Stage I NSCLC die within 5 years after surgical treatment. Identification of prognostic factors to select patients with a poor prognosis and development of tailored treatment strategies are then advisable. The aim of our study was to design a model able to define prognosis in patients with Stage I NSCLC, submitted to surgery with curative intent. METHODS A retrospective analysis of two surgical registries was performed. Predictors of survival were investigated using the Cox model with shared frailty (accounting for the within-centre correlation). Candidate predictors were: age, gender, smoking habit, morbidity, previous malignancy, Eastern Cooperative Oncology Group performance status, clinical N stage, maximum standardized uptake value (SUV(max)), forced expiratory volume in 1 s, carbon monoxide lung diffusion capacity (DLCO), extent of surgical resection, systematic lymphadenectomy, vascular invasion, pathological T stage, histology and histological grading. The final model included predictors with P < 0.20, after a backward selection. Missing data in evaluated predictors were multiple-imputed and combined estimates were obtained from 10 imputed data sets. RESULTS Analysis was performed on 848 consecutive patients. The median follow-up was 48 months. Two hundred and nine patients died (25%), with a 5-year overall survival (OS) rate of 74%. The final Cox model demonstrated that mortality was significantly associated with age, male sex, presence of cardiac comorbidities, DLCO (%), SUV(max), systematic nodal dissection, presence of microscopic vascular invasion, pTNM stage and histological grading. The final model showed a fair discrimination ability (C-statistic = 0.69): the calibration of the model indicated a good agreement between observed and predicted survival. CONCLUSIONS We designed an effective prognostic model based on clinical, pathological and surgical covariates. Our preliminary results need to be refined and validated in a larger patient population, in order to provide an easy-to-use prognostic tool for Stage I NSCLC patients.

Surgery of colorectal cancer lung metastases: analysis of survival, recurrence and re-surgery

BACKGROUND Surgery is considered an effective therapeutic option for patients with lung metastasis (MTS) of colorectal cancer (CRC). The purpose of the study was to evaluate efficacy and feasibility of lung metastasectomy in CRC patients and to explore factors of prognostic relevance. METHODS This is a retrospective study of patients operated for lung MTS of CRC from 2004 to 2012 in a single Institution. Overall survival (OS) was the primary endpoint. Secondary endpoints were progression free survival (PFS) in resection status R0 and OS in in patients submitted to re-resections. In order to evaluate prognostic factors, a multivariable Cox proportional hazard model was performed. RESULTS One-hundred eighty-eight consecutive patients were included in the final analysis. The median follow-up (FU) was 45 months. The 5-year OS and PFS were 53% (95% CI: 44-60%) and 33% (95% CI: 25-42%), respectively. Two- and 5-year survival after re-resection were 79% (95% CI: 63-89%) and 49% (95% CI: 31-65%), respectively. Multivariate adjusted analysis showed that primary CRC pathological TNM stages (P=0.019), number of resected MTS ≥5 (P=0.009) and lymph nodal involvement (P<0.0001) are independent predictors of poor prognosis. CONCLUSIONS Patients operated and re-operated for lung MTS from CRC cancers showed encouraging survival rates. Our results indicated that primary CRC stage, number of MTS and lymph nodal involvement are strong predictive factors. Prognosis after surgery remained comforting up to four resected MTS. Adjuvant chemotherapy seems to have a benefit on survival in patients affected by multiple metastases. Finally, according to the high rate of unidentified lymph node involvement in pre-operative setting, lymph node sampling should be advisable for a correct staging.

Does myasthenia gravis influence overall survival and cumulative incidence of recurrence in thymoma patients? A Retrospective clinicopathological multicentre analysis on 797 patients

OBJECTIVE Aim of this study is to evaluate whether Myasthenia Gravis (MG) might influence Overall Survival (OS) and Cumulative Incidence of Recurrence (CIR) in thymoma patients. METHODS this is a multicenter retrospective study of patients operated in 6 high-volume Italian Institutions between 1990 and 2012. OS was estimated by the Kaplan-Meier method and CIR by considering death from any cause as a competing event. Crude and adjusted comparisons by MG for OS and CIR were performed using Cox and Fine&Gray models. Adjusted models included MG, age, gender, stage, histology, induction therapy, completeness of resection, adjuvant therapy. RESULTS Seven hundred ninety-seven patients were included: 375 (47%) had MG. MG patients were younger and more frequently female, with a B2-B3 thymoma. At the end of the study, 129 patients (54 with MG) developed a recurrence and 165 (66 with MG) died. At univariate analysis, MG showed a slight protective effect on OS, not confirmed by the multivariate model. Age, incomplete resection, advanced stages and thymic carcinoma were negative prognostic variables. Univariate analyses showed no evidence of MG protective effect on CIR. Advanced stages and induction therapy were significant negative predictors. CONCLUSION our study showed that MG was significantly associated with female, lower age and B2-B3 thymoma; it demonstrated a slight protective effect on OS at the univariate analysis which was not confirmed in multivariate as well as no impact on CIR. Advanced tumor stages and thymic carcinoma histology for OS and induction therapy and advanced stages for CIR were negative prognostic variables.

Thymic neuroendocrine tumors.

Thymic neuroendocrine tumors are rare and account for approximately 2% to 5% of all thymic tumors. Despite the suggestion of benign behavior implied by their name, thymic carcinoids have been noted to present a more aggressive biologic behavior than their counterparts in other sites. Because of the lack of data, adequate-sized prospective trials are required for validation, and the enrollment of patients with advanced disease into available clinical trials is encouraged.

VATS lobectomy program: the trainee perspective.

Due to its intrinsic characteristics, video assisted thoracic surgery (VATS) lobectomy is currently the recommended surgical approach for early stage lung cancer treatment. The importance of increasing the number of surgeons capable of performing VATS lobectomies is implicit and of utmost importance. In fact, the need of performing independently and routinely VATS lobectomies for early stage lung cancer will soon be a prerequisite to the new generation of thoracic surgeons. The feeling that VATS lobectomy teaching should be part of their training is strongly felt among trainees but, at the moment, a formal, uniform and certified process of learning VATS lobectomy is not available in all training centres. Perhaps, through the supervision, support and aid from national and European Thoracic Surgery Societies, programs of integration of recognized, standardized and certified teaching of VATS lobectomy could be planned and undertaken by the training centres, both at national as well as European level.