Pleural Mesothelioma: Treatable Traits of a Heterogeneous Disease.

Pleural mesothelioma is an aggressive disease with diffuse nature, low median survival, and prolonged latency presenting difficulty in prognosis, diagnosis, and treatment. Here, we review all these aspects to underline the progress being made in its investigation and to emphasize how much work remains to be carried out to improve prognosis and treatment.

Liquid Biopsy Detecting Circulating Tumor Cells in Patients with Non-Small Cell Lung Cancer: Preliminary Results of a Pilot Study.

Lung cancer is still the leading cause of cancer-related death worldwide. Interest is growing towards early detection and advances in liquid biopsy to isolate circulating tumor cells (CTCs). This pilot study aimed to detect epithelial CTCs in the peripheral blood of early-stage non-small cell lung cancer (NSCLC) patients. We used Smart BioSurface® (SBS) slide, a nanoparticle-coated slide able to immobilize viable nucleated cellular fraction without pre-selection and preserve cell integrity. Forty patients undergoing lung resection for NSCLC were included; they were divided into two groups according to CTC value, with a cut-off of three CTCs/mL. All patients were positive for CTCs. The mean CTC value was 4.7(± 5.8 S.D.) per ml/blood. In one patient, next generation sequencing (NGS) analysis of CTCs revealed v-raf murine sarcoma viral oncogene homolog B(BRAF) V600E mutation, which has also been identified in tissue biopsy. CTCs count affected neither overall survival (OS, p = 0.74) nor progression-free survival (p = 0.829). Multivariable analysis confirmed age (p = 0.020) and pNodal-stage (p = 0.028) as negative predictors of OS. Preliminary results of this pilot study suggest the capability of this method in detecting CTCs in all early-stage NSCLC patients. NGS on single cell, identified as CTC by immunofluorescence staining, is a powerful tool for investigating the molecular landscape of cancer, with the aim of personalized therapies.

The Overweight Paradox: Impact of Body Mass Index on Patients Undergoing VATS Lobectomy or Segmentectomy.

The aim of this study was to assess the impact of BMI on perioperative outcomes in patients undergoing VATS lobectomy or segmentectomy. Data from 5088 patients undergoing VATS lobectomy or segmentectomy, included in the VATS Group Italian Registry, were collected. BMI (kg/m2) was categorized according to the WHO classes: underweight, normal, overweight, obese. The effects of BMI on outcomes (complications, 30-days mortality, DFS and OS) were evaluated with a linear regression model, and with a logistic regression model for binary endpoints. In overweight and obese patients, operative time increased with BMI value. Operating room time increased by 5.54 minutes (S.E. = 1.57) in overweight patients, and 33.12 minutes (S.E. = 10.26) in obese patients (P < 0.001). Compared to the other BMI classes, overweight patients were at the lowest risk of pulmonary, acute cardiac, surgical, major, and overall postoperative complications. In the overweight range, a BMI increase from 25 to 29.9 did not significantly affect the length of stay, nor the risk of any complications, except for renal complications (OR: 1.55; 95% CI: 1.07-2.24; P = 0.03), and it reduced the risk of prolonged air leak (OR: 0.8; 95% CI: 0.71-0.90; P < 0.001). 30-days mortality is higher in the underweight group compared to the others. We did not find any significant difference in DFS and OS. According to our results, obesity increases operating room time for VATS major lung resection. Overweight patients are at the lowest risk of pulmonary, acute cardiac, surgical, major, and overall postoperative complications following VATS resections. The risk of most postoperative complications progressively increases as the BMI deviates from the point at the lowest risk, towards both extremes of BMI values. Thirty days mortality is higher in the underweight group, with no differences in DFS and OS.

Port Placement Strategies for Robotic Pulmonary Lobectomy: A Narrative Review.

BACKGROUND: Despite the use of robotics becoming increasingly popular among thoracic surgeons worldwide, there remains debate over the best robotic approach for lung resections. In this paper, we delineated the main port placement strategies and discussed their advantages and disadvantages. METHODS: A PubMed literature review was performed using key phrases such as "robotic lobectomy technique", "RATS lobectomy", and "port placement robotic lobectomy". After the final review, 22 articles were included as references, of which 10 described common robotic port mapping techniques. RESULTS: Several port strategies for robot-assisted pulmonary lobectomies have been proposed and described in the literature, each showing its own limitations and advantages. CONCLUSIONS: New robotic surgeons may choose their port strategy according to personal preference and previous surgical experience, especially regarding open or VATS resections. Robust data comparing different port placements in robotic surgery are lacking. Further research should be directed toward comparisons of clinical outcomes with different robotic approaches.

Malignant pleural mesothelioma: Germline variants in DNA repair genes may steer tailored treatment.

INTRODUCTION: Malignant pleural mesothelioma (MPM) is a tumour associated with asbestos exposure. Approximately, 10% of patients with MPM carry a germline pathogenic variant (PV), mostly in DNA repair genes, suggesting the occurrence of inherited predispositions. AIM: This article aimed to 1) search for new predisposing genes and assess the prevalence of PVs in DNA repair genes, by next-generation sequencing (NGS) analysis of germline DNA from 113 unselected patients with MPM and 2) evaluate whether these patients could be sensitive to tailored treatments. METHODS: NGS was performed using a custom panel of 107 cancer-predisposing genes. To investigate the response to selected drugs in conditions of DNA repair insufficiency, we created a three-dimensional-MPM cell model that had a defect in ataxia telangiectasia mutated (ATM), the master regulator of DNA repair. RESULTS: We identified PVs in approximately 7% of patients with MPM (8/113) and a new PV in BAP1 in a further patient with familial MPM. Most of these PVs were in genes involved or supposedly involved in DNA repair (BRCA1, BRIP1, CHEK2, SLX4, FLCN and BAP1). In vitro studies showed apoptosis induction in ATM-silenced/inhibited MPM spheroids treated with an enhancer of zeste homologue 2 inhibitor (tazemetostat). CONCLUSIONS: Overall these data suggest that patients with MPM and DNA repair insufficiency may benefit from this treatment, which induces synthetic lethality.

The Redax® Coaxial Drain in pulmonary lobectomy: a study of efficacy.

BACKGROUND: Pleural drainage is required after pulmonary lobectomy to evacuate air-leak and fluid. We compared the performance of the new Redax® Coaxial Drain (CD) (Redax, Mirandola, Italy) with a standard chest tube (CT) in terms of fluid and air-leak evacuation. METHODS: Fifty-two patients receiving a 24-F CD under water-seal after pulmonary lobectomy through open surgery or video-assisted thoracic surgery (VATS) were matched according to demographic, clinical and pathological variables with 104 patients receiving a 24-F CT. Fluid evacuation and post-operative day 0 (POD0) fluid evacuation rate, air-leak rate, tension pneumothorax or increasing subcutaneous emphysema, tube occlusion at removal, visual analog scale (VAS) score at rest and during cough, chest drain duration, pleural fluid accumulation or residual pleural cavity after tube removal, post-operative morbidity and mortality rate were recorded and compared between the two groups. RESULTS: No differences were recorded in post-operative morbidity and mortality rates. Fluid drainage rates on POD0 were significantly higher in CD group (73% vs. 48%; P=0.004); air-leak occurrence was similar in both groups and no differences were recorded in terms of tension pneumothorax or increasing subcutaneous emphysema rates; VAS score was lower for CD when compared with CT and it reached significant difference in the subgroups of patients operated on by VATS; no cases of occlusion at removal were recorded in CD patient. CONCLUSIONS: Redax® CD is safe and efficient in air-leak and fluid evacuation; due to its design and constituting material it is superior to standard CTs in terms of fluid evacuation rate and patient post-operative comfort.

Extralobar Pulmonary Sequestration Presenting with Recurring Massive Pleural Effusion in a Young Woman: A Challenging Case.

We report a case of extralobar pulmonary sequestration (ELS) in a young woman, presenting with right recurring massive pleural effusion. The patient initially underwent a diagnostic Video Assisted Thoracic Surgery (VATS) for a suspected diffuse malignancy. After the aspiration of the pleural effusion we observed a highly vascularised cystic mass, with its origin from the right lower lobe. As we tried to retract the right lower lobe, the mass broke with massive bleeding requiring emergency right lateral thoracotomy. The mass was succesfully excised, resembling an extra-lobar pulmonary sequestration. The patient was discharged on post-operative day 5.

Fibrosis pulmonar tardía (neumonía intersticial usual) en un paciente con antecedentes de neumonía asociada a H1N1 no complicada / No disponible

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Persistent lung expansion after pleural talc poudrage in non-surgically resected malignant pleural mesothelioma.

BACKGROUND: To investigate the prognostic effect of persistent lung expansion after pleural talcage and other variables in non-surgically resected malignant pleural mesothelioma (MPM) patients. METHODS: All consecutive patients submitted to video-assisted thoracoscopic (VAT) pleurodesis by talc poudrage for MPM between 2006 and 2011 were studied. The following parameters were prospectively recorded: age; sex; smoking history; asbestos exposure; C-reactive protein (CRP) levels; platelet (PLT) count; Eastern Cooperative Oncology Group performance status (ECOG PS); histologic subtype; clinical stage (cStage); chemotherapy; pleural fluid volume; and persistence of lung expansion at 3 months follow-up. Survival was assessed in June 2013. RESULTS: A total of 172 patients were considered; 146 of 172 patients demonstrated a complete lung expansion at discharge, whereas only 85 of 172 patients had persistent expanded lung on the affected side at the 3-month follow-up chest x-ray. Median survival was 11.5 months (95% confidence interval [CI], 10% to 14%) and 2-year disease-specific survival was 13% (95% CI, 7% to 24%) for the entire cohort. Multivariate analysis showed that non-epithelioid histology (hazard ratio [HR], 2.81; 95% CI, 1.82% to 5.09%), pleural fluid recurrence (HR 2.54; 95% CI, 1.73% to 4.40%), cStage greater than II (HR 2.36; 95% CI, 1.50% to 4.32%), ECOG PS greater than 1 (HR 2.19; 95% CI, 1.26% to 4.23%), CRP greater than 5 mg/L (HR 2.01; 95% CI, 1.18% to 4.12%), and PLT count greater than 400,000 (HR 1.76; 95% CI 1.14% to 3.92%) were independent predictors of poor prognosis. CONCLUSIONS: Persistent lung expansion after pleural talc poudrage and absence of fluid recurrence is demonstrated to be a stronger factor in predicting survival rather than clinical stage and other clinical variables in not surgically resected MPM patients.

Schwannoma del nervio vago mediastínico tratado exitosamente con toracoscopia biportal videoasistida / Mediastinal Vagus Nerve Scwhannoma Succesfully Treated by a Biportal VATS Approach

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Metastasis to subsegmental and segmental lymph nodes in patients resected for non-small cell lung cancer: prognostic impact.

BACKGROUND: We investigated the prognostic significance of segmental and subsegmental (level 13 and 14) lymph nodes metastasis in patients with resected non-small cell lung cancer (NSCLC). METHODS: The pattern of lymph nodal metastasis was analyzed in 124 patients with pN1 NSCLC. Long-term outcomes were compared for 390 pN0, 124 pN1, and 82 pN2 consecutive patients submitted to planned pulmonary resection for NSCLC between 2000 and 2006. The pN1 status was stratified into 3 groups according to the highest level of lymph node involvement: level 10 (hilar); level 11+12 (lobar + interlobar); and level 13+14 (segmental + subsegmental). RESULTS: The 5-year overall survival (OS) rates for pN0, pN1, and pN2 patients were 93%, 66%, and 25%, respectively. The highest level of lymph node involvement was a significant prognostic indicator; the 5-year OS rate for level 13+14, level 11+12, level 10 pN1, and pN2 was 81%, 58%, 48%, and 25%, respectively. Significant differences were recorded in long-term outcome when pN0 and pN1 level 13+14, pN1 level 13+14, and pN1 level 11+12, pN1 level 11+12 and pN1 level 10 were compared (p < 0.05). The median number of examined level 13+14 lymph nodes was 2 (range 0 to 6) and 57% pN1 patients had metastasis at level 13+14 lymph nodes. CONCLUSIONS: The highest level of lymph node metastases may be used to stratify outcome of patients with pN1 disease. Routine examination of level 13+14 lymph nodes is to be recommended to correctly identify patients at risk of relapse and predict long-term prognosis.

Non-small cell lung cancer in surgically treated women.

AIM AND BACKGROUND: To determine whether female patients operated on for non-small cell lung cancer (NSCLC) have a survival advantage compared to male patients. METHODS AND STUDY DESIGN: We analyzed data from 1,426 prospectively collected patients submitted to lung resection for NSCLC between 1999 and 2008. RESULTS: Two groups, including 1,014 male and 412 female patients, were compared. Female patients were significantly younger, were more frequently asymptomatic, were less likely to be smokers, had better preoperative respiratory function, had a lower frequency of COPD, and were less commonly affected by cardiovascular comorbidity than men. Adenocarcinoma was more frequently present and early pathological stage (stage IA) more frequently detected in women at diagnosis. The operative mortality was significantly lower among women (1.6% vs 4.6%) (P = 0.012), and women underwent significantly more segmentectomies and fewer pneumonectomies (P = 0.001). The disease-related 5-year survival rate was significantly higher in women (66% vs 51%) (P = 0.0008). At univariate analysis the absence of symptoms at presentation, lower pathological stage, squamous cell type, and female gender were positive factors influencing long-term survival. At multivariate analysis low pathological stage, squamous cell type and female gender were confirmed as independent positive prognostic predictors. Women had a significant survival advantage irrespective of the histological subtype at pathological stage IA, IB, IIB and IIIA disease (P <0.05). CONCLUSIONS: Female gender was confirmed to be a particular subset amongst patients affected by NSCLC and exerted a positive effect on disease-related survival of patients submitted to surgical resection. This important effect of gender should be cautiously kept in mind in analyzing the results of current and future trials for lung cancer therapy.

Metástasis exclusivas en el timo de un cáncer de pulmón no microcítico resecado / Single Thymic Gland Metastasis From Resected Non-Small-Cell Lung Cancer

Los tumores primarios del timo son excepcionales, pero se han descrito unos pocos casos de tumores secundarios. Describimos el caso de una paciente con metástasis exclusivas en el timo a partir de un adenocarcinoma de pulmón resecado por completo 3 años antes. La duda diagnóstica aumentó porque la lesión tímica no se asociaba a la recidiva del síndrome paraneoplásico y a un aumento de los valores de antígeno carcinoembrionario (ACE) documentados en el momento del tratamiento del tumor primario. La lesión se diagnosticó y trató al mismo tiempo mediante timectomía transcervical. Al año de seguimiento, la paciente sigue viva y libre de la enfermedad(AU)

Primary thymic tumors are rare, but secondary ones are exceptionally uncommon. We report the case of a single metastasis within the thymic gland from a lung adenocarcinoma that had been completely resected 3 years before. There was high diagnostic doubt because the thymic lesion was not associated with the recurrence of the paraneoplastic syndrome or the increased CEA levels described at the moment of the treatment of the primary tumor. The lesion was diagnosed and treated at the same time by transcervical thymectomy. At the one-year follow-up, the patient is alive and disease-free(AU)

Single thymic gland metastasis from resected non-small-cell lung cancer.

Primary thymic tumors are rare, but secondary ones are exceptionally uncommon. We report the case of a single metastasis within the thymic gland from a lung adenocarcinoma that had been completely resected 3 years before. There was high diagnostic doubt because the thymic lesion was not associated with the recurrence of the paraneoplastic syndrome or the increased CEA levels described at the moment of the treatment of the primary tumor. The lesion was diagnosed and treated at the same time by transcervical thymectomy. At the one-year follow-up, the patient is alive and disease-free.