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Lung cancer is an extremely heterogeneous disease, with well over 50 different histological variants recognized under the fourth revision of the World Health Organization (WHO) typing system. Because these variants have differing genetic and biological properties correct classification of lung cancer is necessary to assure that lung cancer patients receive optimum management. Due to the recent understanding that histologic typing and EGFR mutation status are important for target the therapy in lung adenocarcinoma patients there was a great need for a new classification that addresses diagnostic issues and strategic management to allow for molecular testing in small biopsy and cytology specimens. For this reason and in order to address advances in lung cancer treatment an international multidisciplinary classification was proposed by the International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS), further increasing the histological heterogeneity and improving the existing WHO-classification. Is now the beginning of personalized therapy era that is ideally finalized to treat each individual case of lung cancer in different way.

Lung cancer is an extremely heterogeneous disease, with well over 50 different histological variants recognized under the fourth revision of the World Health Organization (WHO) typing system. Because these variants have differing genetic and biological properties correct classification of lung cancer is necessary to assure that lung cancer patients receive optimum management. Due to the recent understanding that histologic typing and EGFR mutation status are important for target the therapy in lung adenocarcinoma patients there was a great need for a new classification that addresses diagnostic issues and strategic management to allow for molecular testing in small biopsy and cytology specimens. For this reason and in order to address advances in lung cancer treatment an international multidisciplinary classification was proposed by the International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS), further increasing the histological heterogeneity and improving the existing WHO-classification. Is now the beginning of personalized therapy era that is ideally finalized to treat each individual case of lung cancer in different way.

BACKGROUND Intraoperative pulmonary artery (PA) bleeding is common during thoracic surgery. We investigated the efficacy of the gelatin matrix-thrombin solution FloSeal (Baxter International, Deerfield, IL, USA) for control of major PA bleeding. METHODS Retrospective data were collected on all intraoperative PA injuries during open or minimally invasive lobectomy or pneumonectomy between January 2000 and January 2014. Patients received either 4/0 prolene sutures (Standard) or the gelatin matrix-thrombin solution, plus sutures as needed (Matrix), with at least 6-month follow-up. Endpoints included time to hemostasis, total blood loss, transfusion and complications. RESULTS Of 2809 procedures, 39 (1.4%) had intraoperative PA injury, of which 21 received standard care and 18 the gelatin matrix-thrombin solution. Hemostasis was achieved in all Standard group patients after 2 minutes, and after 5 minutes in Matrix patients. Additional sutures were required in 4 (19.0%) Standard group patients. Three (16.7%) Matrix patients had a second solution application, while 17 (77.8%) received precautionary sutures. Mean blood loss on postoperative day 1 was 836.1±186.1 mL and 957.1±163.0 mL in the Matrix and Standard groups, respectively (P=0.003). Four (22.2%) Matrix patients received postoperative transfusions versus eight (38.0%) Standard patients (P=0.02). Two Standard and no Matrix patients underwent surgical revision. There were no complications and no mortalities. CONCLUSIONS Our analysis suggests that the gelatin matrix-thrombin solution is safe and effective for the control of major bleeding following intraoperative PA injury, and may improve outcomes. Further prospective studies are required to confirm our findings.

Aim To perform a systematic review and meta-analysis of published data on the role of fluorine-18-fluorodeoxyglucose positron emission tomography ( 18 F-FDG PET) in predicting the WHO grade of malignancy in thymic epithelial tumors (TETs). Methods A comprehensive literature search of studies published up to March 2014 was performed. Data on maximum standardized uptake value (SUV max ) in patients with low-risk thymomas (A, AB, B1), high-risk thymomas (B2, B3) and thymic carcinomas (C) according to the WHO classification were collected when reported by the retrieved articles. The comparison of mean SUV max between low-risk thymomas, high-risk thymomas and thymic carcinomas was expressed as weighted mean difference (WMD) and a pooled WMD was calculated including 95% confidence interval (95%CI). Results Eleven studies were selected for the meta-analysis. The pooled WMD of SUV max between high-risk and low-risk thymomas was 1.2 (95%CI: 0.4–2.0). The pooled WMD of SUV max between thymic carcinomas and low-risk thymomas was 4.8 (95%CI: 3.4–6.1). Finally, the pooled WMD of SUV max between thymic carcinomas and high-risk thymomas was 3.5 (95%CI: 2.7–4.3). Conclusions 18 F-FDG PET may predict the WHO grade of malignancy in TETs. In particular, we demonstrated a statistically significant difference of SUV max between the different TETs (low-grade thymomas, high-grade thymomas and thymic carcinomas).

Objective: Despite the intense debate concerning the prognostic impact of fissure involvement (FI) in patients with non–small-cell lung cancer, no specific surgical strategies have been yet recommended when this condition occurs. In this setting, we report our monocentric 10-years experience to investigate this issue. Methods: From January 2000 to January 2010, the clinical data of 40 non–small-cell lung cancer patients with FI undergoing curative resection were retrospectively reviewed. The sample was stratified according to the type of resection: group A (28 patients): anatomical resection (bilobectomy [21 patients], pneumonectomy [7 patients]); group B (12 patients): nonanatomical resection (lobectomy plus wedge resection [LWR]). The end-points were (1) impact of different surgical approach on the pulmonary function (measured before surgery and 1 month after discharge); (2) disease-specific survival; and (3) tumor recurrence.The t test, χ 2 , and log-rank tests, Kaplan–Meier method, and Cox and logistic regression analyses were used for the statistical analysis. Results: No differences between the two groups were found when comparing the clinical characteristics, histology, pN or pT status, p-stage, residual (R1) disease, tumor grading, or tumor size. Similarly, the baseline preoperative function (tested as forced expiratory volume in 1 second-%-predicted, FEV1%) was likewise comparable (92.5% ± 21.0% in group A versus 85.2% ± 20.0% in group B; p = not significant). The decline of FEV1% after surgery was slightly higher in group A (−24.9% ± 13.5%) when compared with that in group B (−19.5% ± 13.3%), but this difference was not statistically significant ( p = ns). Nevertheless, the 5-year disease-specific survival was 56% for group A and 47% for group B ( p = ns). The recurrence rate did not differ between the patients undergoing a LWR (3 of 12 patients) and those undergoing a bilobectomy or pneumonectomy (9 of 28 patients) ( p = ns). The presence of FI extended for more than 3 cm was found to be the most significant prognostic factor when analyzing survival ( p = 0.002) and recurrence rate ( p Conclusions: Our results suggest that nonanatomical resection (LWR) could be considered as a feasible surgical option (especially in "frail" patients with an extent of FI less than 3 cm) in the light of the similar oncological and functional outcome compared with anatomical resection. Further studies based on larger series are needed to confirm these preliminary data and also to investigate the impact on the postoperative quality of life.

Objective To systematically review and meta-analyze published data about the diagnostic performance of Fluorine-18-Fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET) and PET/computed tomography (PET/CT) in the assessment of pleural abnormalities in cancer patients. Methods A comprehensive literature search of studies published through June 2013 regarding the role of 18 F-FDG-PET and PET/CT in evaluating pleural abnormalities in cancer patients was performed. All retrieved studies were reviewed and qualitatively analyzed. Pooled sensitivity, specificity, positive and negative likelihood ratio (LR+ and LR−) and diagnostic odd ratio (DOR) of 18 F-FDG-PET or PET/CT on a per patient-based analysis were calculated. The area under the summary ROC curve (AUC) was calculated to measure the accuracy of these methods in the assessment of pleural abnormalities. Sub-analyses considering 18 F-FDG-PET/CT and patients with lung cancer only were carried out. Results Eight studies comprising 360 cancer patients (323 with lung cancer) were included. The meta-analysis of these selected studies provided the following results: sensitivity 86% [95% confidence interval (95%CI): 80–91%], specificity 80% [95%CI: 73–85%], LR+ 3.7 [95%CI: 2.8–4.9], LR− 0.18 [95%CI: 0.09–0.34], DOR 27 [95%CI: 13–56]. The AUC was 0.907. No significant improvement considering PET/CT studies only and patients with lung cancer was found. Conclusions 18 F-FDG-PET and PET/CT demonstrated to be useful diagnostic imaging methods in the assessment of pleural abnormalities in cancer patients, nevertheless possible sources of false-negative and false-positive results should be kept in mind. The literature focusing on the use of 18 F-FDG-PET and PET/CT in this setting remains still limited and prospective studies are needed.

To systematically review and meta-analyze published data about the diagnostic accuracy of fluorine-18-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) and PET/computed tomography (CT) in the differential diagnosis between malignant and benign pleural lesions.A comprehensive literature search of studies published through June 2013 regarding the diagnostic performance of (18)F-FDG-PET and PET/CT in the differential diagnosis of pleural lesions was carried out. All retrieved studies were reviewed and qualitatively analyzed. Pooled sensitivity, specificity, positive and negative likelihood ratio (LR+ and LR-) and diagnostic odds ratio (DOR) of (18)F-FDG-PET or PET/CT in the differential diagnosis of pleural lesions on a per-patient-based analysis were calculated. The area under the summary receiver operating characteristic curve (AUC) was calculated to measure the accuracy of these methods. Subanalyses considering device used (PET or PET/CT) were performed.Sixteen studies including 745 patients were included in the systematic review. The meta-analysis of 11 selected studies provided the following results: sensitivity 95% (95% confidence interval [95%CI]: 92-97%), specificity 82% (95%CI: 76-88%), LR+ 5.3 (95%CI: 2.4-11.8), LR- 0.09 (95%CI: 0.05-0.14), DOR 74 (95%CI: 34-161). The AUC was 0.95. No significant improvement of the diagnostic accuracy considering PET/CT studies only was found.(18)F-FDG-PET and PET/CT demonstrated to be accurate diagnostic imaging methods in the differential diagnosis between malignant and benign pleural lesions; nevertheless, possible sources of false-negative and false-positive results should be kept in mind.

Introduction Post-operative pulmonary rehabilitation in patients who have undergone surgery for lung cancer is a subject of open debate. Clinical practice in this setting is based on the results of observational trials, such as the one described here. Prospective randomized controlled trials have been registered and recruitment is ongoing. Methods From 2005 to 2008, 110 patients with surgical non-small cell lung cancer were entered into a post-operative inpatient pulmonary rehabilitation programme for 3 weeks. All patients were evaluated for pulmonary function after surgery (time 0; T0) and at the end of pulmonary rehabilitation programme (time 1; T1). Statistical analysis focused on improvement in pulmonary function parameters and physical performance in the 6-min walking test (6MWT). Mixed models multiple linear regression was used to identify parameters related to the primary end-points of this research. Results Patients' mean age was 70.1 years (standard deviation (SD) 8.5 years); male/female ratio 73/37. A total of 94 patients underwent lobectomy, 8 underwent pneumonectomy, and the remaining 8 underwent bilobectomy. Among the analysed parameters a significant improvement could be detected only with regards to the 6MWT (257.4 (SD 112.2) at T0 and 382.8 (SD 11.09) at T1). Conclusion Post-operative pulmonary rehabilitation in patients with surgical non-small cell lung cancer is effective in terms of exercise tolerance.

The two essential requirements for pathologic specimens in the era of personalized therapies for non-small cell lung carcinoma (NSCLC) are accurate subtyping as adenocarcinoma (ADC) versus squamous cell carcinoma (SqCC) and suitability for EGFR molecular testing, as well as for testing of other oncogenes such as EML4-ALK and KRAS. Actually, the value of EGFR expressed in patients with NSCLC in predicting a benefit in terms of survival from treatment with an epidermal growth factor receptor targeted therapy is still in debate, while there is a convincing evidence on the predictive role of the EGFR mutational status with regard to the response to tyrosine kinase inhibitors (TKIs). This is a literature overview on the state-of-the-art of EGFR oncogenic mutation in NSCLC. It is designed to highlight the preclinical rationale driving the molecular footprint assessment, the progressive development of a specific pharmacological treatment and the best method to identify those NSCLC who would most likely benefit from treatment with EGFR-targeted therapy. This is supported by the belief that a rationale for the prioritization of specific regimens based on patient-tailored therapy could be closer than commonly expected.

We aimed to assess whether high-dose preoperative chemoradiotherapy (CRT) improves outcome in esophageal cancer patients compared to surgery alone and to define possible prognostic factors for overall survival.Hundred-and-seven patients with disease stage IIA - III were treated with either surgery alone (n = 45) or high-dose preoperative CRT (n = 62). The data were collected retrospectively. Sixty-seven patients had adenocarcinomas, 39 squamous cell carcinomas and one undifferentiated carcinoma. CRT was given as three intensive chemotherapy courses by cisplatin 100 mg/m2 on day 1 and 5-fluorouracil 1000 mg/m2/day, from day 1 through day 5 as continuous infusion. One course was given every 21 days. The last two courses were given concurrent with high-dose radiotherapy, 2 Gy/fraction and a median dose of 66 Gy. Kaplan-Meier survival analysis with log rank test was used to obtain survival data and Cox Regression multivariate analysis was used to define prognostic factors for overall survival.Toxicity grade 3 of CRT occurred in 30 (48.4%) patients and grade 4 in 24 (38.7%) patients of 62 patients. One patient died of neutropenic infection (grade 5). Fifty percent (31 patients) in the CRT group did undergo the planned surgery. Postoperative mortality rate was 9% and 10% in the surgery alone and CRT+ surgery groups, respectively (p = 1.0). Median overall survival was 11.1 and 31.4 months in the surgery alone and CRT+ surgery groups, respectively (log rank test, p = 0.042). In the surgery alone group one, 3 and 5 year survival rates were 44%, 24% and 16%, respectively and in the CRT+ surgery group they were 68%, 44% and 29%, respectively. By multivariate analysis we found that age of patient, performance status, alcoholism andor= 4 pathological positive lymph nodes in resected specimen were significantly associated with overall survival, whereas high-dose preoperative CRT was not.We found no significant survival advantage in esophageal cancer stage IIA-III following preoperative high-dose CRT compared to surgery alone. Patient's age, performance status, alcohol abuse and number of positive lymph nodes were prognostic factors for overall survival.

Background The use of small-bore wire-guided chest drains for pleural effusions and pneumothorax has become popular; however, limited data are available on its efficacy and morbidity. The aim of this retrospective study is to measure, via the analysis of the so far largest reported cohort, the efficacy, safety, and tolerability of this approach in different clinical conditions. Methods In the period from January 2002 to December 2008, 1092 patients have undergone the positioning of a small-bore wire-guided chest drain (12F) for the evidence of pneumothorax or pleural effusion and have been monitored over time for morbidity, pain at the time of insertion (measured via the visual analogue scale), and drain failure for misplacement or blockage. Patients with trauma were excluded from this study. Results Male/female ratio and mean age were respectively 418:674 and 55.85 ± 18.6. Three-hundred ninety-nine (36.5%) drains were inserted for pneumothorax, 324 (29.7%) for malignant effusion, 97 (8.9%) for empyema, and 272 (24.9%) for nonmalignant effusion. The pain experience was on average "very mild" (mean visual analogue scale = 4.6 mm). The overall drain failure rate was 12.9%. The percentage of successful cases was 93.8% in malignant effusion, 93% in pneumothorax, and 92.3% in nonmalignant effusion; in the cases of pathologically diagnosed empyema, drains were more likely to get blocked (74.2%). We recorded 1 serious complication within the malignant effusion group. Conclusions Wire-guided 12F Seldinger-type drains are a well-tolerated and effective method of treating pneumothorax and uncomplicated pleural effusions (malignant and nonmalignant) with acceptable morbidity. The use of 12F small-bore chest drain is not indicated for the treatment of empyema.

ObjectiveWe have analyzed short- and long-term variations of pulmonary function in locally advanced non–small cell lung cancer after induction chemoradiotherapy.MethodsTwenty-seven patients with stage IIIA (N2) non–small cell lung cancer underwent resection with radical intent after induction chemoradiotherapy in the period 2003 to 2006. Pulmonary function has been evaluated by spirometry, diffusing capacity of the lung for carbon monoxide, and blood gas analysis before induction chemoradiotherapy (T0), 4 weeks after induction chemoradiotherapy and before surgery (T1), and 1 (T2), 3 (T3), 6 (T4), and 12 months (T5) after surgery.ResultsA 22.80% decrease of diffusing capacity of the lung for carbon monoxide (P < .001) was observed at T1. At T2 significant decreases in the following were present: vital capacity, −20.50% (P < .001); forced vital capacity, −22.50% (P < .001); forced expiratory volume in 1 second, −23.00% (P < .001); peak expiratory flow, −29.0 (P

Malignant pleural effusion is a frequent condition with important prognostic repercussions on duration and quality of life. The neoplasms that more frequently determine pleural effusion are lung and breast cancer and pleural mesothelioma. Lymphomas, tumours of the genitourinary tract and gastrointestinal tract as a group account for a further 25%. Surgical treatment has palliative purposes and finalized to reduction symptoms and to improve quality of life. More frequent clinical presentation is a massive pleural efusion associated to dyspnoea and cough. Pleural aspiration is the first choice treatment but the recurrence rate equals to 100% within 1 month. Repeated pleural aspirations are indicated in those patients that have lower expectation of life. The recurrence risk can be reduced with chemical pleurodesis that allows the adhesion between pleural surfaces. Pleurodesis can be realized by the instillation of several substances by the tube of drainage (slurry) or during thoracoscopy (poudrage). Video Assisted Thoracoscopy (VATS) is a safe and well tolerated technique, a complication rate is lower than 0.5%, VATS can be used to obtain diagnosis and to treat patients with malignant pleural effusion and better expectation of life.