Texture analysis of advanced non-small cell lung cancer (NSCLC) on contrast-enhanced computed tomography: prediction of the response to the first-line chemotherapy.

OBJECTIVES: To assess whether tumour heterogeneity, quantified by texture analysis (TA) on contrast-enhanced computed tomography (CECT), can predict response to chemotherapy in advanced non-small cell lung cancer (NSCLC). METHODS: Fifty-three CECT studies of patients with advanced NSCLC who had undergone first-line chemotherapy were retrospectively reviewed. Response to chemotherapy was evaluated according to RECIST1.1. Tumour uniformity was assessed by a TA method based on Laplacian of Gaussian filtering. The resulting parameters were correlated with treatment response and overall survival by multivariate analysis. RESULTS: Thirty-one out of 53 patients were non-responders and 22 were responders. Average overall survival was 13 months (4-35), minimum follow-up was 12 months. In the adenocarcinoma group (n = 31), the product of tumour uniformity and grey level (GL*U) was the unique independent variable correlating with treatment response. Dividing the GL*U (range 8.5-46.6) into tertiles, lesions belonging to the second and the third tertiles had an 8.3-fold higher probability of treatment response compared with those in the first tertile. No association between texture features and response to treatment was observed in the non-adenocarcinoma group (n = 22). GL*U did not correlate with overall survival. CONCLUSIONS: TA on CECT images in advanced lung adenocarcinoma provides an independent predictive indicator of response to first-line chemotherapy.

Second Italian consensus conference on malignant pleural mesothelioma: state of the art and recommendations.

Malignant pleural mesothelioma (MPM) is a relevant public health issue. A large amount of data indicate a relationship between mesothelioma and asbestos exposure. MPM incidence has considerably and constantly increased over the past two decades in industrialized countries and is expected to peak in 2010-2020. In Italy, the standardized incidence rate in 2008 was 3.6 and 1.3 per 100,000 in men and women respectively, with wide differences from one region to another. The approach to this disease remains difficult and complex in terms of pathogenic mechanism, diagnosis, staging and treatment thus an optimal strategy has not yet been clearly defined. The Second Italian Multidisciplinary Consensus Conference on Malignant Pleural Mesothelioma was held in Turin (Italy) on November 24-25, 2011: recommendations on MPM management for public health institutions, clinicians and patients are presented in this report.

High prevalence of serum antibodies reacting with simian virus 40 capsid protein mimotopes in patients affected by malignant pleural mesothelioma.

Human malignant pleural mesothelioma (MPM) is considered a rare tumor, but recent estimations indicate that one-quarter million people will die of this neoplasm in Europe in the next three decades. The mineral asbestos is considered the main causative agent of this neoplasm. MPM is largely unresponsive to conventional chemotherapy/radiotherapy. In addition to asbestos exposure, genetic predisposition to asbestos carcinogenesis and to simian virus (SV)40 infection has also been suggested. SV40 is a DNA tumor virus found in some studies to be associated at high prevalence with MPM. SV40 sequences have also been detected, although at a lower prevalence than in MPM, in blood specimens from healthy donors. However, some studies have failed to reveal SV40 footprints in MPM and its association with this neoplasm. These conflicting results indicate the need for further investigations with new approaches. We report on the presence of antibodies in serum samples from patients affected by MPM that specifically react with two different SV40 mimotopes. The two SV40 peptides used in indirect ELISAs correspond to viral capsid proteins. ELISA with the two SV40 mimotopes gave overlapping results. Our data indicate that in serum samples from MPM-affected patients (n = 97), the prevalence of antibodies against SV40 viral capsid protein antigens is significantly higher (26%, P = 0.043) than in the control group (15%) represented by healthy subjects (n = 168) with the same median age (66 y) and sex. Our results suggest that SV40 is associated with a subset of MPM and circulates in humans.

Effects of combined therapies on the survival of pleural mesothelioma patients treated in Brescia, 1982-2006.

AIMS AND BACKGROUND: During the 1990's, the traditional unimodal treatments (surgery, radiotherapy, chemotherapy, immunotherapy) for malignant pleural mesothelioma started to be combined in bimodal or multimodal strategies. However, recent population-based analyses of the survival of patients with malignant pleural mesothelioma indicate that even these treatments have not led to significant improvements in prognosis, which remains very poor. The present study assessed the survival of patients given combined treatments and multimodal therapies in a specialized hospital department. METHODS: The study population comprised 530 patients diagnosed with malignant pleural mesothelioma from 1982 to 2006: 343 of them were residents in the province of Brescia (Lombardy, Northern Italy) and 187 were residents outside the province, with a follow-up to 31 December 2009. Kaplan-Meier survival analyses and Cox proportional risks model were used to test sex, age at diagnosis, histological type and treatments, as prognostic factors. RESULTS: The estimated median survival for the whole group of patients was 317 days (257 for residents and 398 for non-residents), and respectively 310 and 340 days in the groups diagnosed in the periods 1982-2000 and 2001-2006. Multivariate analysis confirmed that the prognosis was better for younger patients and cases of epithelioid type malignant pleural mesothelioma, whereas for patients receiving any single treatment the prognosis was not significantly better than for those given palliative care alone. However, patients receiving combined treatments or the multimodality approach had significantly longer median survival and the relative risk of death was respectively 0.57 and 0.61 compared to untreated patients (or those only given symptomatic therapy). CONCLUSIONS: This is the first study in Italy to assess the effectiveness of different treatment approaches in a significant number of patients treated in one hospital. Further studies are needed to confirm the improvement in prognosis - even if modest--on larger numbers of patients and taking into account the different stages of the disease.

Expert opinions of the first italian consensus conference on the management of malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a very important public health issue. A large amount of data indicates a relationship between mesothelioma and asbestos exposure. The incidence has both considerably and constantly increased over the past 2 decades in the industrialized countries and is expected to peak in 2010-2020. In Italy, a standardized-rate incidence in 2002 among men was 2.98 per 100,000 and 0.98 per 100,000 among women, with wide differences from one region to another. Stage diagnosis and definition may be difficult. Management of patients with MPM remains complex, so an optimal treatment strategy has not yet been clearly defined. The First Italian Consensus Conference on Malignant Pleural Mesothelioma was held Bologna (Italy) in May 20, 2008. The Consensus Conference was given the patronage of the Italian scientific societies AIOM, AIRO, AIPO, SIC, SICO, SICT, SIAPEC-IAP, AIOT, GOAM, and GIME. This Consensus did not answer all of the unresolved questions in MPM management, but the Expert Opinions have nonetheless provided recommendations, presented in this report, on MPM management for clinicians and patients.

Translational therapies for malignant pleural mesothelioma.

Malignant pleural mesothelioma is a highly invasive tumor arising from the mesothelial cells of serosal surfaces. Several chemotherapeutic agents have been tested for the treatment of this disease and doublet cisplatin with antifolates has been demonstrated to have significant efficacy in Phase III studies. However, the benefit of these treatments remains poor and the median survival time of patients is low, ranging between 9 and 17 months. Targeted therapies are being developed in oncology and emerging evidence suggests that they offer disease control in several tumors. This article reviews the knowledge on the malignant pleural mesothelioma molecular pathway and focuses on results of clinical trials conducted on this devastating disease.

Accuracy of pleural biopsy using thoracoscopy for the diagnosis of histologic subtype in patients with malignant pleural mesothelioma.

BACKGROUND: Promising results with trimodality therapy combining surgery, chemotherapy, and radiotherapy have been obtained in the management of patients with malignant pleural mesothelioma (MPM). However, the histologic subtype has to be taken into account because of its influence on prognosis. The aim of the current study was to analyze retrospectively the accuracy, sensitivity, and specificity of preoperative thoracoscopy for diagnosis of the histologic subtype of MPM. METHODS: The histologic reports from all consecutive patients undergoing 'intent-to-treat' surgery from 3 institutions as well as the initial pathologic diagnosis obtained using thoracoscopy were reviewed and compared after institutional review board approval. All cases of MPM were confirmed by a panel of pathologists. RESULTS: Ninety-five patients were included in the current study. Of these 95 patients, 75 underwent extrapleural pneumonectomy, 9 patients underwent pleurectomy/decortication, and 11 patients underwent pleurectomy. Of the 95 patients with a final diagnosis of MPM, 80 (84.2%) were classified as having epithelial and 15 (15.8%) as having biphasic subtype. Among the 87 patients classified as having MPM of epithelial subtype after the initial thoracoscopy, 75 cases (86.2%) were confirmed to be a true histologic diagnosis and 12 cases (13.8%) were found to be of biphasic subtype at final diagnosis. One patient with a biphasic subtype at initial thoracoscopy was found to have MPM of epithelial subtype after surgery. The sensitivity and specificity values of an epithelial subtype diagnosis after thoracoscopy were 94% and 20%, respectively, with a positive predictive value of 86% and a negative predictive value of 37%. Conversely, the sensitivity and specificity values of a biphasic subtype diagnosis after thoracoscopy were 20% and 98%, respectively, with a positive predictive value of 75% and a negative predictive value of 87%. CONCLUSIONS: Pleural biopsy performed using thoracoscopy is considered to be the cornerstone of the diagnosis and pleural staging of MPM. However, this procedure appears to be less efficient in diagnosing the histologic subtype as either epithelial or biphasic.

Treatment of sonographically stratified multiloculated thoracic empyema by medical thoracoscopy.

INTRODUCTION: In cases of empyema, some form of intervention, either chest tube drainage, thoracoscopy, video-assisted thoracic surgery (VATS), or thoracotomy, with or without pleural fibrinolysis, is required. What the best approach is and when and how to intervene is a matter of debate. STUDY OBJECTIVE: To analyze the safety and outcome of medical thoracoscopy in the treatment of multiloculated empyema. METHODS: We report a retrospective series of 127 patients with thoracic empyema treated with medical thoracoscopy from 1989 to 2003 in three hospitals in Switzerland and Italy. All patients had multiloculated empyema as identified by chest ultrasonography. In the absence of multiloculation, or in case of fibrothorax, simple chest tube drainage or surgical VATS/thoracotomy were performed, respectively. RESULTS: Mean age +/- SD was 58 +/- 18 years (range, 9 to 93 years). In 47%, a microbiological diagnosis was made. Complications occurred in 9% of patients (subcutaneous emphysema, n = 3; air leak of 3 to 7 days, n = 9). No mortality was observed. Forty-nine percent of patients received postinterventional intrapleural fibrinolysis. Medical thoracoscopy was primarily successful in 91% of cases. In four patients, the insertion of an additional chest tube or a second medical thoracoscopy was required. Finally, 94% of patients were cured by nonsurgical means. Six percent of patients required surgical pleurectomy, mostly through thoracotomy. CONCLUSION: Multiloculated empyema as stratified by ultrasonography can safely and successfully be treated by medical thoracoscopy.

[Survival analysis of malignant mesothelioma treated in Brescia, northern Italy, 1982-2000]. / Analisi della sopravvivenza dei mesoteliomi maligni trattati a Brescia dal 1982 al 2000.

OBJECTIVE: To study the survival for malignant mesothelioma on general population cases over the 1982-2000 period and to evaluate the effectiveness of the new therapeutic protocols (intrapleural immunotherapy and mulitmodality therapy) to improve the prognosis on the group of selected hospital patients treated from 1996 to 2000. DESIGN: Survival analysis of malignant mesothelioma on the general population cases and survival analysis for the 1996-2000 period on the selected group of hospital patients. SETTING: The Malignant Mesothelioma Register of the Brescia Province (northern Italy) and Pulmonology Dept. of the General hospital of Brescia. PARTICIPANTS: 353 mesothelioma cases observed in the province of Brescia from 1982 to 2000, 215 of which are residents in the province and 138 from other provinces, 324 are pleural and 29 peritoneal mesothelioma, 141 of all diagnosed between 1982 and 1995 and 212 between 1996 and 2000. MAIN OUTCOME MEASURES: Observed survival (%) at one, three, five-year and median survival by gender, site and residence on the general population cases treated with conventional therapy and on selected hospital patients group treated with intrapleural immunotherapy and mulimodality therapy. RESULTS: Median survival for pleural mesothelioma is of 233 days for the men and 291 days for the women in the group of incident cases; median survival is higher for cases from other provinces (388 and 496 days respectively). From 1996 the number of cases treated with new therapic protocols is steadily increasing, patients without therapy (or only talcaggio) passed from 87% in the period between 1982-1995 to 43% in the period 1996-2000. Nevertheless, multivariate analysis by the Cox model based on incident cases proved that histological subtype and age are the only most important prognostic factors (cases with fibrous morphology and older age are associated with lower survival). CONCLUSION: In the incident case group the increase of survival for pleural mesothelioma of cases treated with recent therapeutic protocols doesn't reach statistical significance. These results are similar to those of previous studies conducted to identify prognostic factors for mesothelioma survival; they don't permit confirmation of the efficacy of the recent therapy on the population base cases and only allow one to suppose them in the cases of the non resident population. The efficacy of the recent therapy has to be further investigated with regard to the stage of the disease.

Minithoracoscopy: a less invasive approach to thoracoscopy.

STUDY OBJECTIVES: To evaluate minithoracoscopy using 3-mm instrumentation for diagnosis of pleural effusions. In the initial phase of the study, minithoracoscopy was used only for small loculated effusions not accessible with standard-sized endoscopes. Indication was later extended to larger nonloculated effusions that could have been examined using conventional thoracoscopy. PATIENTS: A total of 30 patients were studied, including 12 patients with nonloculated effusions of undetermined etiology, 17 patients with loculated effusions, and 1 patient with bilateral effusion. TECHNIQUE: The double-entry site technique was used with placement of two trocars, ie, one for the telescope and one for the biopsy forceps or accessory instruments. All procedures were performed under local anesthesia with mild sedation (midazolam). RESULTS: Minithorascopy provided high diagnostic yield (93.4%). Visualization using minithoracoscopy instrumentation was equal to that obtained using conventional thoracoscopy instrumentation. Tolerance and cosmetic results were good. CONCLUSIONS: Minithoracoscopy is safe and effective for routine diagnostic applications.

Indicators predictive of success of embolisation: analysis of 88 patients with haemoptysis.

PURPOSE: To identify the risk factors related to relapse of haemoptysis in patients treated with arterial embolisation. MATERIAL AND METHODS: Eighty-eight patients with haemoptysis (60 M, 28 F; average age 58.9) were examined by bronchial arteriography: 64/88 were subsequently embolised. The clinical and angiographic parameters, immediate and long-term results were analysed. Follow-up ranged from 8 days to 104 months. No major complications were observed. RESULTS: Patients treated with embolisation (64/88= 72.7%) were divided into two groups. Group 1 (23/64= 35.9%) included patients with relapse of haemoptysis and Group 2 (41/64=64.1%) patients without recurrence during follow-up. In all 64 patients with haemoptysis, embolisation succeeded in stopping the haemorrhage, long-term efficacy was observed in 64.1%; when the treatment was repeated, secondary success was 68.75%. Recurrence after embolisation was correlated to chronic lung disease (p=0.04) especially to pulmonary tuberculosis or mycetoma (p=0.007) and to systemic-pulmonary shunts (p=0.02). The absence of a history of massive haemoptysis was related to a greater likelihood of non-recurrence (p=0.0035). Moreover, complicated tuberculous lesions (Log-rank test p=0.0027), chronic lung disease (p=0.0272) and systemic-pulmonary shunts (p=0.0406) were predictive of an earlier relapse (Kaplan Meier curves and Log-rank test). Comparison of tuberculosis and/or mycetoma with systemic-pulmonary shunting showed the greater impact of infectious lesions on early recurrence. CONCLUSIONS: Embolisation of abnormal vascularisation, which can be repeated in cases of failure, proved successful in patients with haemoptysis showing definitive or long-term resolution of the clinical picture in about 70% of cases. Patients with tuberculosis or mycetoma with systemic-pulmonary shunting and haemodynamic alterations have a higher risk of early recurrence.