P. Camplese

Frequent mutations in the neurotrophic tyrosine receptor kinase gene family in large cell neuroendocrine carcinoma of the lung.

The neurotrophic tyrosine receptor kinase (NTRK) family is potentially implicated in tumorigenesis and progression of several neoplastic diseases, including lung cancer. We investigated a large number of pulmonary neuroendocrine tumors (PNETs) and non‐small cell lung carcinomas (NSCLCs) without morphological evidence of neuroendocrine differentiation for mutations in the NTRK gene family. A total of 538 primary lung carcinomas, including 17 typical carcinoids (TCs), 10 atypical carcinoids (ACs), 39 small cell lung carcinomas (SCLCs), 29 large cell neuroendocrine carcinomas (LCNECs), and 443 NSCLCs were evaluated by single‐strand conformation polymorphism (SSCP) and sequencing of the tyrosine kinase domain (TKD) of NTRK1, NTRK2, and NTRK3. The NTRK1 gene was never found to be mutated. A total of 10 somatic mutations were detected in NTRK2 and NTRK3, mostly located in the activating and catalytic loops. NTRK mutations were seen in 9 (10%) out of 95 PNETs but in 0 out of 443 NSCLCs investigated. No mutations were observed in TCs, ACs, and SCLCs. Interestingly, all the mutations were restricted to the LCNEC histotype, in which they accounted for 31% of cases. A mutational analysis, performed after microdissection of LCNECs combined with adenocarcinoma (ADC), showed that only neuroendocrine areas were positive, suggesting that NTRK mutations are involved in the genesis of the neuroendocrine component of combined LCNECs. Our data indicate that somatic mutations in the TKD of NTRK genes are frequent in LCNECs. Such mutational events could represent an important step in the cancerogenesis of these tumors and may have potential implications for the selection of patients for targeted therapy. Hum Mutat 29(5), 609–616, 2008.

Composite chest wall reconstruction using titanium plates and mesh preserves chest wall function

FIGURE 1. A, Left clavicle and first rib reconstruction; B, rib reconstruction with titanium plates and a dual-mesh patch. TECHNIQUE Surgical reconstruction was performed in 13 patients using a Titanium Fixation System (Synthes, West Chester, Pa); Figure 1, A, consisting of titanium plates and self-tapping unlock screws. All plates can be joined by U-shaped release pins, which allows quick and easy surgical access in case of reoperations. There were 3 patients groups (Table 1). In groups A and B, rib reconstruction was performed with titanium plates and a dual-mesh patch was placed and fixed to the plates to avoid direct contact between prosthesis and lung parenchyma (Figure 1, B). In group C, the first patient, in particular, received an en bloc sternectomy for sternum infection after cardiac surgery, and then 4 titanium plates were fixed to the clavicle and to both sides of the second, fourth, and fifth rib, respectively, successively covered with a titanium patch. In all cases of sternum resection, a bilateral pectoralis major muscle flap was carried out to cover the prosthesis. There was no postoperative mortality. A subcutaneous seroma occurred in 2 patients and atrial fibrillation and prolonged air leakage in 1 patient. A 3-day stay in the intensive care unit was required for hemodynamic instability in a patient with malignant mesothelioma having extrapleural pneumonectomy and chest resection. All the other patients were extubated immediately at the end of the surgical procedures. Preand postoperative data showed a good preservation of respiratory function even after lung resection if compared with predictive values (Table 1).

Pleurectomy-decortication in malignant pleural mesothelioma: are different surgical techniques associated with different outcomes? Results from a multicentre study†

OBJECTIVES The potential benefit of surgery for malignant pleural mesothelioma (MPM), especially concerning pleurectomy/decortication (P/D), is unclear from the literature. The aim of this study was to evaluate the outcome after multimodality treatment of MPM involving different types of P/D and to analyse the prognostic factors. METHODS We reviewed 314 patients affected by MPM who were operated on in 11 Italian centres from 1 January 2007 to 11 October 2014. RESULTS The characteristics of the population were male/female ratio: 3.7/1, and median age at operation was 67.8 years. The epithelioid histotype was observed in 79.9% of patients; neoadjuvant chemotherapy was given to 57% of patients and Stage III disease was found following a pathological analysis in 62.3% of cases. A total of 162 (51.6%) patients underwent extended P/D (EP/D); 115 (36.6%) patients had P/D and 37 (11.8%) received only a partial pleurectomy. Adjuvant radiotherapy was delivered in 39.2% of patients. Median overall survival time after surgery was 23.0 [95% confidence interval (CI): 19.6-29.1] months. On multivariable (Cox) analysis, pathological Stage III-IV [ P  = 0.004, hazard ratio (HR):1.34; 95% CI: 1.09-1.64], EP/D and P/D ( P  = 0.006, HR for EP/D: 0.46; 95% CI: 0.29-0.74; HR for P/D: 0.52; 95% CI: 0.31-0.87), left-sided disease ( P  = 0.01, HR: 1.52; 95% CI: 1.09-2.12) and pathological status T4 ( P  = 0.0003, HR: 1.38; 95% CI: 1.14-1.66) were found to be independent significant predictors of overall survival. CONCLUSIONS Whether the P/D is extended or not, it shows similarly good outcomes in terms of early results and survival rate. In contrast, a partial pleurectomy, which leaves gross tumour behind, has no impact on survival.

Standardized uptake value and radiological density attenuation as predictive and prognostic factors in patients with solitary pulmonary nodules: our experience on 1,592 patients

BACKGROUND Multislice computed tomography (MSCT) increased detection of solitary pulmonary nodules (SPNs), changing the management based on radiological and clinical factors. When 18-fluorine fluorodeoxyglucose positron emission tomography combined with computed tomography (18F-FDG-PET/CT) was considered for the evaluation of nodules, the maximum standardized uptake value (SUVmax) more than 2.5 is used frequently as a cut off for malignancy. The purpose of this study is to evaluate SUVmax PET/CT and pulmonary attenuation patterns at MSCT in patients with SPN according to morphological and pathological characteristics of the lesion. METHODS A retrospective study on 1,592 SPN patients was carried out following approval by the Italian Registry of VATS Lobectomies. RESULTS All patients underwent VATS lobectomy. On histologic examination, 98.1% had primary or second metachronous primary lung cancers. In addition, 10.7% presented occult lymph node metastases (pN1 or pN2) on histological examination. Nodule attenuation on CT was associated with the histology of the lesion (p= 0.030); in particular, pure ground glass opacities (pGGOs) and partially solid nodules were related to adenocarcinomatous histotypes. Conversely, a significant relationship between SUVmax and age, nodule size, pathological node status (pN) was found (P=0.007, P=0.000 and P=0.002 respectively). CONCLUSIONS Nodule attenuation can predict the histology of the lesion whereas SUVmax may relate to the propensity to lymph node metastases.

Safety of lymphadenectomy during video-assisted thoracic surgery lobectomy: analysis from a national database

OBJECTIVES The Italian VATS Group database was accessed to evaluate whether preoperative and intraoperative factors may affect the safety of lymphadenectomy (LA) during video-assisted thoracic surgery lobectomy. METHODS All video-assisted thoracic surgery lobectomy procedures performed between 1 January 2014 and 30 March 2017 for non-small-cell lung cancer with cN0 or cN1 disease were identified in the database. LA safety was evaluated based on intraoperative (operative time, bleeding and conversion rate) and postoperative (30-day morbidity and mortality, chest drain duration and length of stay) outcomes and was correlated with the number of resected lymph nodes and the rates of nodal upstaging. Continuous variables were presented as mean ± standard deviation and compared using the unpaired t-test; the χ2 test was used for categorical variables. Univariable analysis was performed on selected variables. Significant variables (P < 0.30) were entered into a Cox multivariable logistic regression model, using the overall and specific occurrence of complications as dependent variables. The Spearmans rank correlation coefficient was applied as needed. RESULTS A total of 3181 cases (2077 men, 65.3%; mean age of 69 years) met the enrolment criteria. Final pathology was consistent with adenocarcinoma (n = 2262, 67.5%), squamous cell (n = 520, 15.5%), typical (n = 184, 5.5%) and atypical carcinoid (n = 48, 1.4%) and other (n = 335, 10%). The mean number of resected lymph nodes was 13.42 ± 8.24; nodal upstaging occurred in 308 of 3181 (9.68%) cases. Six hundred and fifty-five complications were recorded in 404 (12.7%) patients; in this series, no mortality was observed. Univariable and multivariable analyses did not show any association between the extension of LA and intraoperative or postoperative outcomes. The number of resected lymph nodes and nodal upstagings showed a minimal correlation with intraoperative outcomes and a moderate correlation with postoperative air leak (ρ = 0.35 and ρ = 0.48, respectively), arrhythmia (ρ = 0.29 and ρ = 0.35, respectively), chest drain duration (ρ = 0.35 and ρ = 0.51, respectively) and length of stay (ρ = 0.35). CONCLUSIONS Based on the VATS Group data, video-assisted thoracic surgery LA proved to be safe and displayed good outcomes even when performed with an extended approach.

About idiopathic chylopericardium: a case report

Idiopathic chylopericardium is a rare clinical entity, whose precise etiology is still unclear and few cases are reported till this date. This case report describes the history, physical examination, evaluation, diagnosis and treatment of a 45-years-old male patient with primary idiopathic chylopericardium. Radiological findings and biochemical analysis of the pericardial fluid following pericardiocentesis sustained this diagnosis. Correspondence to: Mirko Barone, Department of General and Thoracic Surgery, University Hospital “SS Annunziata”. University “G.d’Annunzio”. Via dei Vestini n.1, 66100 Chieti , Italy, Tel: +39 0871/358289; Fax: +39 0871/358220; E-mail: mir87mb@libero.it

Surgical management of cardiac tamponade: Is left anterior minithoracotomy really safe and effective?

Objective: Cardiac tamponade is a life-threatening clinical entity that requires an emergency treatment. Cardiac tamponade can be caused both by benign and malignant diseases. A variety of methods have been described for the treatment of these cases from needle-guided pericardiocentesis, balloon-based techniques to surgical pericardiotomy. The Authors report their experience in surgical management of cardiac tamponade and an exhaustive review of literature. Methods: This study involved 61 patients (37 males and 24 females) with an average age of 61.80 ± 16.32 years. All patients underwent emergency surgery due to the presence of cardiac tamponade. Results: Cardiac tamponade was caused by a benign disease in 57.40% of patients. In cancer patients group, lung cancer, breast cancer and malignant pleural mesothelioma were the most common neoplasms (17-27, 87%). The average preoperative size of pericardial effusion at M-2D echocardiography was 30.15 ± 5.87 mm. Postoperative complications were observed in 11 patients (18%). The reoperation rate was 3.3% (2 patients) due to relapsed cardiac tamponade. 30-day mortality rate was 3.3%. Overall cumulative survival was 29.9 ± 20.1 months. Twenty-nine patients (47.5%) died during the follow up period. By dividing the population into two groups, group B (benign) and group M (malignant), there was a statistically significant difference (P < 0.001) in terms of survival. Conclusion: In conclusions, anterior minithoracotomy for surgical treatment of cardiac tamponade has to be held into account in patients both with benign diseases and malignancies.

Systemic inflammation in malignant pleural mesothelioma: Is neutrophyl-to-lymphocyte ratio a prognostic index?

Malignant Pleural Mesothelioma (MPM) is an aggressive, asbestos-related tumor that arises from the mesothelium. It is a neoplasm with an increasing incidence with a poor and a dismal prognosis. Inflammation plays a crucial role in the initiation and tumor progression. In addition, the history of MPM is characterized by symptoms referred to increased inflammatory responses such as fever, sweating and loss of weight. Recent studies have identified the neutrophil-to-lymphocyte ratio (NLR) as a feaseble and simple marker of systemic inflammation. The Authors report a retrospective study in 54 patients with malignant pleural mesothelioma (MPM). MPM patients were more likely to be male (75.9% versus 24.1%) with a median age of 67 years. The epithelial histotype was predominant (77.8%) compared to the biphasic (11.1%), sarcomatous (9.5%) and desmoplastic (1.9%) ones. Neutrophil-to-Lymphocite ratio (NLR) was assessed at diagnosis with a mean value of 4.31. The aim of the study was to test bivariate correlations between independent factors (age, sex, histology, NLR, lymphocyte count, lymph node involvement) and the overall survival of the population under investigation. The median overall survival (OS) in the general population included in the study was 13 months. Median Disease Free Interval (DFI) was 3 months. Patients with the epithelial histotype survived significantly longer than those presenting with sarcomatoid, biphasic or desmoplastic subtypes (15 months versus 2, 8 and 10 months respectively; p<0.001). Patients with NLR<3 showed a median overall survival of 22 months, while 3<NLR<5 and NLR>5 ones had a poorer survival rate (12 and 8 months respectively). There was evidenced of a strong correlation between patients with inflammation index less than three and overall survival (p<0.001). The Neutrophil-to-Lymphocyte Ratio (NLR) can be an independent, easily reproducibile and comparable prognostic index in patients with malignant pleural mesothelioma. Abbreviations: MPM: Malignant Pleural Mesothelioma, NLR: Neutrophil to Lymphocyte Ratio, OS: Overall Survival, DFI: Disease Free Interval

Pulmonary resection for NSCLC in octogenarians: a single center experience

Background Lung cancer is the second leading cancer death among octogenarians [] and in particular NSCLC accounts for more than 90% of all lung cancers. Since life expectancy is improving, lung cancers are observed among octogenarians people more often. Surgical resection remains the treatment of choice for early stage lung cancer. The authors report the outcomes of pulmonary resection for NSCLC in octogenarians.