Accuracy of 18F-FDG in Detecting Stage I Lung Adenocarcinomas According to IASLC/ATS/ERS Classification.

BACKGROUND: Only a small number of studies have explored the clinicopathological features of pulmonary adenocarcinoma (PA) associated with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) false-negative (FN) results. Herein, we investigated the FDG-PET diagnostic performance by stratifying PAs according to International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification. METHODS: From January 2002 to December 2016, all consecutive patients who underwent pulmonary resection for stage I PA at six thoracic surgery institutions were retrospectively reviewed. The diagnostic performance of FDG-PET was analysed according to IASLC/ATS/ERS classification and two validated subclassifications. Univariable and multivariable logistic analysis were used to identify predictors of FDG-PET FN results. RESULTS: Five hundred and fifty (550) patients with stage I PA were included in the analyses. Most of the patients were male (n=354 [64.4%]) and smokers (n=369 [67.1%]). Ninety-seven (n=97 [17.6%]) FN cases were observed at FDG-PET imaging. On multivariable analysis, a lepidic pattern was found to be independently associated with FDG-PET FN results (odds ratio [OR], 3.20; p<0.001), while a solid pattern more commonly presented with a positive finding (OR, 0.40; p=0.066). According to Nakamura's classification, we observed an independent association between lepidic pattern and FDG-PET FN results (OR, 3.17; p<0.001), while solid/micropapillary patterns were independently related with increased FDG uptake (OR, 0.35; p=0.021). According to Yoshizawa's classification, Intermediate-grade tumours were independently correlated with FN FDG-PET results (OR, 2.78; p=0.005). CONCLUSIONS: In our cohort, histopathological features were significantly associated with FDG uptake. In particular, some adenocarcinoma subtypes (mostly Lepidic pattern) have a tendency towards FN FDG-PET findings. The correlation between computed tomography findings, clinical characteristics, and FDG uptake is mandatory, in order to tailor the precise diagnostic and therapeutic pathway for each patient.

Electromagnetic Navigation Bronchoscopy: Where Are We Now? Five Years of a Single-Center Experience.

INTRODUCTION: Electromagnetic navigation (ENB) is a guidance tool used in the diagnosis of solitary pulmonary nodules (SPNs) and masses. Its diagnostic yield is highly variable (38-71%) and a recent study has put in doubt the role of ENB in sampling SPNs in a real-life setting. The aim of this study is to describe the 5-year experience of our center with ENB, analyzing the population, possible confounding factors, and the diagnostic yield and accuracy of this technique. METHODS: We conducted a retrospective observational study including all consecutive patients who underwent ENB for SPNs and masses from January 2011 to December 2015. RESULTS: We included 113 patients; 79% had SPNs, 21% masses. The majority were localized in the upper and middle lobes (80%) and 61% presented a bronchus sign. 54% of the patients had a previous negative fluoroscopy-guided bronchoscopy. ENB achieved the diagnosis in 78 patients (69%) with 64 malignant and 14 were benign lesions. The diagnostic yield and accuracy of ENB were respectively 0.69 and 0.76. The only factor influencing the ability to reach a diagnosis was the presence of bronchus sign (p = 0.002). No procedural complications were reported. CONCLUSION: ENB is a safe procedure with a similar diagnostic yield in the real-life and research setting. Bronchus sign is an important factor in determining the diagnostic yield. ENB efficacy can be maximized by expertise and by a careful selection of each case.

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.

Inference on germline BAP1 mutations and asbestos exposure from the analysis of familial and sporadic mesothelioma in a high-risk area.

Inherited loss-of-function mutations in the BAP1 oncosuppressor gene are responsible for an inherited syndrome with predisposition to malignant mesothelioma (MM), uveal and keratinocytic melanoma, and other malignancies. Germline mutations that were inherited in an autosomal dominant fashion were identified in nine families with multiplex MM cases and 25 families with multiple melanoma, renal cell carcinoma, and other tumors. Germline mutations were also identified in sporadic MM cases, suggesting that germline mutations in BAP1 occur frequently. In this article, we report the analysis of BAP1 in five multiplex MM families and in 103 sporadic cases of MM. One family carried a new truncating germline mutation. Using immunohistochemistry, we show that BAP1 is not expressed in tumor tissue, which is in accordance with Knudson's two hits hypothesis. Interestingly, whereas the three individuals who were possibly exposed to asbestos developed MM, the individual who was not exposed developed a different tumor type, that is, mucoepidermoid carcinoma. This finding suggests that the type of carcinogen exposure may be important for the cancer type that is developed by mutation carriers. On the contrary, the other families or the 103 sporadic patients did not show germline mutations in BAP1. Our data show that BAP1 mutations are very rare in patients with sporadic MM, and we report a new BAP1 mutation, extend the cancer types associated with these mutations, and suggest the existence of other yet unknown genes in the pathogenesis of familial MM.

Giant Cervico-mediastinal Well-differentiated Liposarcoma.

Liposarcomas are rare entities and those located in the neck and mediastinum are exceptional. We report the case of a 58 year-old Caucasian male who presented with dysphonia, mild dysphagia to solids, dyspnoea at exertion and cough due to a giant mass of the neck originating from the deep cervical space at C6 vertebral level spreading into the posterior mediastinum. The lesion, that was associated with a right vocal cord palsy, caused severe lateral displacement of the trachea and oesophagus. The case has been managed by complete surgical resection through a combined cervical and thoracic approach associated with a tracheostomy due to the risk of bilateral recurrent nerve dysfunction at the end of the intervention. The tumour was diagnosed as a encapsulated low-grade liposarcoma. Six months after surgery the tracheostomy was closed. At 24 months clinical and radiological follow-up the patient is doing well and disease free.

Surgery for non-small cell lung cancer in younger patients: what are the differences?

BACKGROUND: Non-small cell lung cancer (NSCLC) in young adults is uncommon. The objective of this study was to evaluate the clinicopathological characteristics, outcomes and prognosis of people younger than 50 years old treated surgically for NSCLC. METHODS: A retrospective study was conducted using the institutional database of four thoracic surgery units to collect patients with NSCLC younger than 50 years who had undergone surgery. These patients were compared with older patients (>75-years) operated in the same institutions and in the same period. RESULTS: We identified 113 young patients and 347 older patients. Younger patients were more likely to be female, non-smokers, with fewer comorbidities. Younger patients were more likely to be symptomatic at the time of diagnosis. Risk factors for poor prognosis in younger patients were T-stage, and disease-free-interval less than 548 days. Kaplan-Meier analysis showed a lower five-year survival in older patients compared with the younger ones (66% vs 38%, p=0.001). CONCLUSIONS: In conclusion NSCLC in younger patients has some distinct clinicopathological characteristics. The overall-survival of young patients is better than in older patients. Young patients receive more complete and aggressive treatment that could explain better survival. Further prospective studies with larger patient populations are required, to clarify the biological and genetic variance of NSCLC in younger patients.

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.

Epidermal growth factor receptor overexpression in malignant pleural mesothelioma: prognostic correlations.

BACKGROUND: To evaluate epidermal growth factor receptor (EGFR) phenotypic expression and related gene status in malignant pleural mesothelioma (MPM) and to correlate the results with patients' prognosis. METHOD: Eighty-three cases of MPM specimens were submitted to immunohistochemical (IHC) staining to evaluate the expression of EGFR protein; positive cases were submitted to fluorescence in situ hybridization (FISH) to investigate the gene status. Results were correlated with clinico-pathological characteristics and long-term survival. RESULTS: Thirty-eight cases (46%) demonstrated a positive IHC reaction [30/57 (52%) epithelial and 8/20 (40%) biphasic whereas sarcomatous MPM were negative]. No association was recorded between EGFR IHC positive staining and age, gender, or asbestos exposure. Three out of 38 (8%) cases submitted to FISH were positive revealing gene amplification or polysomy. Mean follow-up was 15.4 months (range 2-44). Epithelial subtype only was confirmed to affect prognosis (2-years survival rate 40 vs. 18% for non-epithelial subtype, P = 0.042). When epithelial MPM patients were considered, IHC EGFR positive staining was demonstrated to be a negative prognostic factor (2-years survival rate 26 vs. 60% for IHC EGFR negative staining; P = 0.026). CONCLUSIONS: EGFR overexpression is identified by IHC in 52% of epithelial MPM and is demonstrated to be a factor negatively affecting prognosis. Phenotypic overexpression seems not to be related to gene status alteration.

Survival results in biphasic malignant pleural mesothelioma patients: A multicentric analysis.

OBJECTIVE: The best strategy of care for biphasic malignant pleural mesothelioma (Biph-MPM) is controversial. In this study, a large dataset of Biph-MPM cases was reviewed to identify prognostic factors and to evaluate the role of a multimodal approach, including cancer-directed surgery. METHODS: A total of 213 patients with Biph-MPM treated at 4 tertiary centers who experienced MPM from January 2009 to December 2016 were selected, and clinical, pathologic, and surgical information was retrieved. A Cox regression model was used to identify predictors of survival, and the Kaplan-Meier method was used to summarize overall survival. RESULTS: The mean age and the male/female ratio were 68.4 ± 9.5 years and 5:1, respectively. Tumors were assigned to stages I (127, 59.6%), II (3, 1.4%), III (76, 35.4%), and IV (7, 3.3%) according to the Eighth Tumor, Node, Metastasis (TNM) edition. A multimodal treatment including pleurectomy/decortication was performed in 58 patients (27.2%), chemotherapy alone in 99 patients (46.5%), and best supportive care in 56 (26.3%). The median overall survival was 11 months. A univariate analysis revealed that survival was significantly associated with the percentage forced expiratory volume in 1 second (P < .0001), performance status (P = .0002), multimodal treatment including surgery (P < .0001), and TNM stage (P = .011). A multivariable analysis confirmed performance status, percentage forced expiratory volume in 1 second, TNM, and a multimodal approach as independent variables affecting long-term survival. CONCLUSIONS: Despite the overall poor prognosis of biphasic histology, a multimodal approach, including cancer-directed surgery, is associated with improved long-term results in very selected patients with Biph-MPM.

Risk of recurrence in stage I adenocarcinoma of the lung: a multi-institutional study on synergism between type of surgery and type of nodal staging.

BACKGROUND: In last years, an increasing interest emerges on the role of sub-lobar resection and lobe-specific lymph nodal dissection in the treatment of early-stage lung cancer. The aim of our study was to define the impact on cumulative incidence of recurrence (CIR) of type of surgical resection and type of nodal staging in this subset of patients. Furthermore, we evaluated the possible synergism between the different kinds of procedure. METHODS: An analysis of 969 consecutive stage I pulmonary adenocarcinoma patients, operated in six Thoracic Surgery Institutions between 2001 and 2013, was conducted. Type of surgical resection included lobectomy and sub-lobar resection; while pneumonectomy and bilobectomy were excluded from the analysis. Nodal staging procedures were classified in nodal sampling (NS), lobe-specific lymph node dissection (LS-ND) and systematic lymph node dissection (SND). Multivariable-adjusted comparisons for CIR was performed using Fine and Grey model, taking into account of death by any cause as competing event. In order to evaluate synergism between the different procedures, the test of interaction between type of surgical resection and type of nodal staging was carried out and results presented in a stratified way. RESULTS: Eight-hundred forty-six (87%) patients were submitted to lobectomy, while 123 (13%) to sub-lobar resection. Four-hundred fifty-five (47%) patients received SND, 98 (10%) LS-ND and 416 (43%) NS. Two-hundred forty-seven (26%) patients developed a local/distant recurrence with a 5-year CIR of 24.2%. Multivariable-adjusted comparisons showed an independent negative effect of sub-lobar resection (HR =1.52; 95% CI: 1.07-2.17), LS-ND (HR =1.74; 95% CI: 1.16-2.6) and NS (HR =1.49; 95% CI: 1.12-1.98) on CIR. Test of interaction showed a homogeneity of results among subgroups. CONCLUSIONS: Patients affected by stage I pulmonary adenocarcinoma and submitted to lobectomy presented a significant lower recurrence rate than those submitted to sub-lobar resection. Moreover, SND presented an independent positive effect on recurrence development than other lymph node assessment strategy. Finally, lobectomy in combination with systematic lymph nodal resection showed the best results in term of CIR.

Peripheral Blood DNA Methylation as Potential Biomarker of Malignant Pleural Mesothelioma in Asbestos-Exposed Subjects.

INTRODUCTION: Malignant pleural mesothelioma (MPM) is an aggressive tumor strongly associated with asbestos exposure. Patients are usually diagnosed when current treatments have limited benefits, highlighting the need for noninvasive early diagnostic tests to monitor asbestos-exposed people. METHODS: We used a genome-wide methylation array to identify, in asbestos-exposed subjects, novel blood DNA methylation markers of MPM in 163 MPM cases and 137 cancer-free controls (82 MPM cases and 68 controls, training set; replication in 81 MPM cases and 69 controls, test set) sampled from the same areas. RESULTS: Evidence of differential methylation between MPM cases and controls was found (more than 800 cytosine-guanine dinucleotide sites, false discovery rate p value (pfdr) < 0.05), mainly in immune system-related genes. Considering the top differentially methylated signals, seven single- cytosine-guanine dinucleotides and five genomic regions of coordinated methylation replicated with similar effect size in the test set (pfdr < 0.05). The top hypomethylated single-CpG (cases versus controls effect size less than -0.15, pfdr < 0.05 in both the training and test sets) was detected in FOXK1 (Forkhead-box K1) gene, an interactor of BAP1 which was found mutated in MPM tissue and as germline mutation in familial MPM. In the test set, comparison of receiver operating characteristic curves and the area under the curve (AUC) of two models, including or excluding methylation, showed a significant increase in case/control discrimination when considering DNA methylation together with asbestos exposure (AUC = 0.81 versus AUC = 0.89, DeLong's test p = 0.0013). CONCLUSIONS: We identified signatures of differential methylation in DNA from whole blood between asbestos exposed MPM cases and controls. Our results provide the rationale to further investigate, in prospective studies, the potential use of blood DNA methylation profiles for the identification of early changes related to the MPM carcinogenic process.

Prevention of malignant seeding at drain sites after invasive procedures (surgery and/or thoracoscopy) by hypofractionated radiotherapy in patients with pleural mesothelioma.

INTRODUCTION: Literature data show that mesothelioma cells can implant along the surgical pathway of invasive procedures such as thoracotomy and thoracoscopy. We investigated the use of hypofractionated radiotherapy for preventing such malignant seeding. MATERIAL AND METHODS: Thirty-two consecutive patients diagnosed with pleural mesothelioma were included in the present retrospective study. All patients underwent surgery and/or thoracoscopy for diagnosis, staging or talc pleurodesis. They were treated with electron external beam radiation therapy (21 Gy in 3 fractions over 1 week), directed to the surgical pathway after the invasive procedure. After completion of radiation treatment, 20 of 32 patients (63%) underwent chemotherapy. RESULTS: After a mean follow-up of 13.6 months (range 3-41) from the end of radiation therapy, no patient had tumour progression in the treated area. The treatment was well tolerated, as only erythema grade I (Radiation Therapy Oncology Group, RTOG, scale) was noted in 11 patients. Seventeen patients died of disease with local progression after a mean survival time of 12.6 months (range 3-27); thirteen patients are alive with disease after a mean follow-up of 13.9 months (range 4-41); two patients are alive without evidence of disease after a mean follow-up of 16.50 months (range 6-27). DISCUSSION: The present study shows the efficacy and safety of local radiotherapy in preventing malignant seeding after thoracoscopy in patients with pleural mesothelioma although larger prospective trials are probably still needed to validate this treatment approach.

Simultaneous diagnosis of CD3+ T-cell large granular lymphocyte leukaemia and true thymic hyperplasia.

CD3+ T-cell large granular lymphocyte (LGL) leukaemia is a mature T-cell neoplasm of cytotoxic T-lymphocytes. Neutropenia represents the most frequent peripheral blood cytopenia associated with CD3+ T-cell LGL leukaemia. A wide variety of diseases associated with LGL leukaemia have been reported, both autoimmune and neoplastic. We describe for the first time the association of true thymic hyperplasia with CD3+ T-cell line LGL leukaemia. The patient presented with severe symptomatic neutropenia. Complete and persistent haematological and molecular remission was induced with an association of low-dose methotrexate and cyclosporin A, followed by thymectomy.

Detection of oncogenic viruses SV40, BKV, JCV, HCMV, HPV and p53 codon 72 polymorphism in lung carcinoma.

As a part of our continuous search for oncogenic viruses in bronchial cancer, we extended our HPV studies to analyse also SV40, BKV, JCV and HCMV sequences in bronchial cancer and related these data with p53 codon 72 polymorphism. Fresh tumor samples from 78 patients with lung cancer were analysed for SV40, BKV, JCV, HCMV and HPV sequences by PCR. HPV genotypes were determined using reverse blot hybridization and sequencing, and all HPV-positive tumors were tested for the presence of E6/E7 transcripts by RT-PCR. All samples were analysed for p53 codon 72 polymorphism, using PCR-based RFLP method. Of the 78 cases studied, 11 (14.1%) were positive for T-Ag gene of SV40, while BKV and JCV sequences were both amplified in 1 tumor only. Altogether, 10/78 lesions were HPV-positive; six HPV16, one HPV31, two HPV6/53 and one HPV16/18. All HPV DNA-positive samples except one also expressed E6 and E7 transcripts. HCMV was amplified in 18 (23%) cases. RFLP analysis of p53 codon 72 revealed 32 homozygotes for arg/arg allele (50.8%), 26 heterozygotes for arg/pro allele (41.3%), and 5 homozygotes for pro/pro allele (7.9%). P53 codon 72 polymorphism was not significantly different between cases (n=63) and controls (n=50) (p=0.455), among virus positive and negative patients, nor was it related to HPV genotypes (p=0.384), expression of E6 (p=0.384) and E7 oncogenes (p=0.293). Of all possible combinations of virus co-detection, only SV40-HCMV association was statistically significant (OR=5.500, 95%CI 1.43-21.02; p=0.015). Taken the known mechanisms of these individual viruses, there is a chance that these viruses could affect cell cycle control and inhibit apoptosis, thus potentially causing genetic instability and promote oncogenesis.

Does adjuvant radiation therapy improve disease-free survival in completely resected Masaoka stage II thymoma?

OBJECTIVE: To determine whether or not patients with completely resected Masaoka stage II thymoma benefit from postoperative radiotherapy (RT). METHODS: We retrospectively review the case records and compared the long-term outcomes of patients affected by Masaoka stage II thymoma treated by resection alone with same stage thymoma patients submitted to resection and RT. Surgical specimens were reviewed to confirm pathological stage, negative resection margins and histological subtype. RESULTS: Between 1988 and 2000, we performed 197 resections for thymoma; 58 patients resulted to be affected by completely resected tumours with microscopic transcapsular invasion (stage IIA, n=25) or macroscopic invasion into the surrounding fatty tissue with or without adhesion to the mediastinal pleura (stage IIB, n=33). Thirty-two patients underwent only complete surgical resection (14 stage IIA and 18 stage IIB); 26 patients underwent complete resection and subsequent mediastinal RT (11 stage IIA and 15 stage IIB). RT dosages were 45-54grays (Gy), in 25-30 fractions. Histological subtypes were similarly represented in both groups. Median follow-up was 91 months (range 9-170). Five intrathoracic recurrences occurred: three radiated patients (2 stage IIB - 1 AB and 1 B2 thymoma; 1 stage IIA B1 thymoma) and two not-radiated patients (1 stage IIA AB thymoma and 1 stage IIB B1 thymoma). Disease-free survival rate at 5- and 10-year were 94% and 87%, respectively. Log-rank test showed no difference in Kaplan-Meier survival curves (p=0.432) between radiated and not-radiated patients. CONCLUSIONS: These data support the concept that radical surgical resection alone should be considered a sufficient treatment for stage II thymoma.

Lymph node isolated tumor cells and micrometastases in pathological stage I non-small cell lung cancer: prognostic significance.

OBJECTIVE: To determine the prevalence and prognostic significance of lymph node micrometastases and isolated tumor cells (ITC) in patients submitted for radical resection for pathological stage I non-small cell lung cancer (NSCLC). METHODS: From January 1998 through December 2005, 87 consecutive pT1-2, pN0 NSCLC patients were enrolled. Surgical specimens were submitted to pathological routine examinations to define histotype, grade, stage, vascular invasion, necrosis and tumor proliferative index. A total of 694 regional lymph nodes were examined by means of serial sections stained with hematoxylin and eosin and labelled by immunohistochemistry (antibody AE1/AE3, DAKO). Relationships between these parameters and patients' prognosis were investigated. RESULTS: By histological examination, there were 36 squamous-cell carcinoma, 38 adenocarcinoma and 13 large-cell carcinoma. Micrometastases and ITC were detected in 19 lymph nodes (2.7%) of 14 patients (16%). Significant correlation was observed between micrometastases or ITC and adenocarcinoma (p=0.03) and the absence of necrosis (p=0.05). No relationship was demonstrated between micrometastases or ITC and T-status, vascular invasion or proliferative index (p>0.05). Median follow-up was 3.2 (range 0.25-8.6) years. Two- and 5-year disease-free survival was similar for patients with and without micrometastases or ITC (79% and 64% vs 81% and 64%, respectively). Recurrence occurred in three patients with (two local, 66%) and in 21 patients without micrometastases or ITC (three local, 14%) (p=0.186). By multivariate analysis only T-status was demonstrated to be a significant prognostic factor. DISCUSSION: Micrometastases or ITC to regional lymph nodes are demonstrated to be not a rare aspect of pathological stage I resected lung cancer. In our series, the presence of lymph nodes micrometastases does not affect long-term disease-free survival.

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.

Germline mutations in DNA repair genes predispose asbestos-exposed patients to malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer caused by asbestos exposure. An inherited predisposition has been suggested to explain multiple cases in the same family and the observation that not all individuals highly exposed to asbestos develop the tumor. Germline mutations in BAP1 are responsible for a rare cancer predisposition syndrome that includes predisposition to mesothelioma. We hypothesized that other genes involved in hereditary cancer syndromes could be responsible for the inherited mesothelioma predisposition. We investigated the prevalence of germline variants in 94 cancer-predisposing genes in 93 MPM patients with a quantified asbestos exposure. Ten pathogenic truncating variants (PTVs) were identified in PALB2, BRCA1, FANCI, ATM, SLX4, BRCA2, FANCC, FANCF, PMS1 and XPC. All these genes are involved in DNA repair pathways, mostly in homologous recombination repair. Patients carrying PTVs represented 9.7% of the panel and showed lower asbestos exposure than did all the other patients (p = 0.0015). This suggests that they did not efficiently repair the DNA damage induced by asbestos and leading to carcinogenesis. This study shows that germline variants in several genes may increase MPM susceptibility in the presence of asbestos exposure and may be important for specific treatment.

Pulmonary metastases from epithelial tumours: late results of surgical treatment.

OBJECTIVE: Development of distant metastases is one of the primary characteristics of malignant tumours. During the last decades, lung metastasectomy has been progressively accepted as a therapeutic option in oncology patients. The present paper aims to evaluate the long-term results and factors influencing prognosis in patients submitted to lung resection for metastases from extrapulmonary epithelial tumours. METHODS: We retrospectively analysed data of 202 patients undergoing 207 procedures of lung metastasectomy between January 1980 and December 2003. Factors that may influence long-term prognosis such as completeness of resection, histology of the tumour, disease-free interval, number of resected lesions, involvement of hilar or mediastinal lymph nodes, systemic treatments were investigated. RESULTS: Complete resection was carried out in 169 patients (83.7%). The more frequent lung resection was sublobar in 67.6% of cases, but rarely in selected patients bilobectomy or pneumonectomy has been carried out too. Perioperative morbidity and mortality were 7.7% and 0.9%. Mean disease-free interval was 49+/-48 months. Mean follow-up was 33+/-31 months, 5-year and 10-year survival rates for completely resected patients were 43% and 17%, respectively. By univariate and multivariate analyses, completeness of resection, disease-free interval of 36 months or more, and single resected metastasis were found to be significant prognostic factors. CONCLUSIONS: Resection of epithelial lung metastases allows an acceptable prognostic result in appropriately selected patients with very low perioperative morbidity and mortality. Factors such as high disease-free interval, single metastasis and completeness of resection are demonstrated and confirmed to be significantly associated with long-term survival.

Large-cell neuroendocrine carcinoma of the lung: a clinicopathologic study of eighteen cases and the efficacy of adjuvant treatment with octreotide.

OBJECTIVE: This study was undertaken to evaluate the efficacy of a new adjuvant protocol with octreotide, alone or in combination with radiotherapy, in radically resected large cell neuroendocrine carcinomas of the lung. METHODS: Between 1990 and 2001, a total of 18 consecutive patients affected by large cell neuroendocrine carcinomas of the lung were operated on. Lobectomy and systemic lymphadenectomy were performed in all cases. Postoperative radiotherapy was performed when stage was higher than Ib. Ten patients with positive results of preoperative indium In-111 pentetreotide scintigraphy received octreotide after the operation. RESULTS: Nine patients (50%) had local recurrences or distant metastases (mean recurrence time 14 months); palliative chemotherapy was given, but all patients died. In 10 cases (55.5%) octreotide alone or in combination with radiotherapy was administered as adjuvant treatment; 9 of these patients (90%) are alive and free of disease ( P = .0007), and the other had liver and brain metastases 21 months after surgery. CONCLUSIONS: Our preliminary results seem to demonstrate the efficacy of octreotide as adjuvant therapy in large cell neuroendocrine carcinomas of the lung when results of preoperative indium In-111 pentetreotide scintigraphy were positive. Further study are required to assess the utility of octreotide in patients with negative results of indium In-111 pentetreotide scintigraphy.