Notwithstanding mediastinal lymphadenectomy is a cornerstone of surgical management of primary lung tumors, results and evidences are still debated for clinical stage I disease. In this aspect, current guidelines appear conflicting, as being both radical lymph node dissection and systematic node sampling equally advocated by several Authors. However, though lymphadenectomies are not risk-free procedures, N-status is an undoubted and significant prognostic factor in NSCLC patients. For these reasons, the adoption of a preoperative predictive non-invasive model should be clinically useful to stratify patients according to risk of lymphatic metastases. A multicentre retrospective study from January 2014 to June 2017 enrolling 2502 early stage NSCLC patients (up to cIB disease) with a mean age of 67.35 ± 8.89 years was conducted by analysing demographic, radiological and pathological features and correlating themselves to pN+ disease through a bivariate analysis, relative risk estimation and Receiver Operative Curves estimation. Diagnostic performance of a derived risk coefficient (RC = Σ factors) was finally evaluated. With a mean Charlson's Comorbidity Score of 4.34 ± 1.80 and an excellent ECOG Status (ECOG 0-1) in 98.1%, 66.2% presented a very early stage disease (cT1a/b N0 M0) with predominant solid nodule density at chest CT (n. 1992 – 79.6%) and a mean SUVmax of 4.37± 4.95. Each patient underwent a R0 video-assisted thoracoscopic lobectomy with a radical node dissection in 69.9% and a systematic lymph node sampling in remaining cases. Concerning with histology, primary pulmonary invasive adenocarcinoma was the predominant pattern (n. 1417 56.6%) and a cumulative incidence of occult hilar-mediastinal lymph node metastases of 8.8% was reported. At bivariate analysis and relative risk estimation, male gender (p=0.033), clinical T-stage (p=0.000), nodule diameter (p=0.000), nodule density (p=0.005), the presence of visceral pleura or bronchial invasion (p=0.000) and a SUV max >3.5 (p=0.001) significantly correlated with pN+ disease. By deriving a risk coefficient function and adopting it to general population through a ROC curve, a RC > 58 presented a not negligible predictive value (sensibility: 82.73%, specificity 74.36%, PPV 23.73%, NPV 97.81%). Although a prospective study is needed, a preoperative clinically easily reproducible predictive model for early stage NSCLC patients should represent a useful tool for a proper stratification of pN+ high risk patients. In particular, by considering its high negative predictive value, the aforementioned risk coefficient could allow to discriminate low risk cohort patients amenable to limited lymph node assessment rather than radical dissections with their fearsome related risks.

AIMAir leakage represents a major problem in lung surgery. Absorbable fibrin sealant patch (AFSP), a collagen sponge coated with human fibrinogen and thrombin, can be used as an adjunct to primary stapling or suturing. This study compared the efficacy of AFSP with manual suturing after primary stapling.METHODSThis was a prospective, multicenter, randomized study. Patients undergoing lobectomy, bilobectomy, anatomical segmentectomy for lung cancer or wedge resection for pulmonary metastasis with air leakage grade 1 or 2 according to Macchiarini scale after stapler suture were randomized to receive AFSP or standard surgical treatment (ST). The primary endpoint was the reduction of intraoperative air leakage intensity. Duration of postoperative air leakage and number of days until removal of last chest drain were secondary endpoints. Safety was recorded for all patients.RESULTSA total of 346 patients were enrolled in 14 centres, 179 of whom received AFSP and 167 ST. Intraoperative air leak intensity was reduced in 90.5% of AFSP patients and 82% of ST patients (P=0.03). A significant reduction in postoperative air leakage duration was observed in the AFSP group (P=0.0437). The median number of days until removal of last drainage was 6 (3-37) in the AFSP group and 7 (2-27) in the ST (P=0.38). Occurrence of adverse events was comparable in both groups.CONCLUSIONAFSP was more efficacious than standard ST as an adjunct to primary stapling in reducing intraoperative air leakage intensity and duration of postoperative air leakage in patients undergoing pulmonary surgery. AFSP was well tolerated.

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.

PURPOSE:It has been reported that EGFR mutations in lung carcinomas make the disease more responsive to treatment with tyrosine kinase inhibitors. We decided to evaluate the prevalence of EGFR mutations in a large series of non-small-cell lung carcinomas (NSCLCs) and to develop a rapid and sensitive screening method. PATIENTS AND METHODS We examined 860 consecutive NSCLC patients for EGFR mutations in exons 18, 19, and 21 using a dual technical approach--direct sequencing of polymerase chain reaction (PCR) products and PCR single-strand conformation polymorphism (SSCP) analysis. Moreover, all lung adenocarcinomas were analyzed for K-ras mutations at codon 12 by allele-specific oligoprobe hybriditations.RESULTS:There were no EGFR mutations in 454 squamous carcinomas and 31 large cell carcinomas investigated. Thirty-nine mutations were found in the series of 375 adenocarcinomas (10%). Mutations were present in 26% of 86 bronchioloalveolar carcinomas (BACs) and in 6% of 289 conventional lung adenocarcinomas; P = .000002. EGFR mutations and K-ras mutations were mutually exclusive. A multivariable analysis revealed that BAC histotype, being a never smoker, and female sex were independently associated with EGFR mutations (odds ratios: 4.542, 3.632, and 2.895, respectively). The SSCP analysis was accurate and sensitive, allowing identification of mutations that were undetectable (21% of cases) by direct sequencing.CONCLUSION:Mutations in the EGFR tyrosine kinase domain define a new molecular type of lung carcinoma, more frequent in particular subsets of patients. The SSCP assay is a rapid and reliable method for the detection of EGFR kinase domain mutations in lung cancer.

Purpose: The Int6 gene was originally identified as a common insertion site for the mouse mammary tumor virus in virally induced mouse mammary tumors. Recent studies indicate that Int6 is a multifaceted protein involved in the regulation of protein translation and degradation through binding with three complexes: the eukaryotic translation initiation factor 3, the proteasome regulatory lid, and the constitutive photomorphogenesis 9 signalosome. This study aimed to investigate the prognostic role of Int6 in a large series of stage I non-small cell lung cancers (NSCLC) patients with long-term follow-up.Experimental Design: We determined the methylation status of Int6 DNA by methylation-specific PCR and the steady-state levels of Int6 RNA by quantitative real-time reverse transcription-PCR in 101 NSCLCs and matched normal lung tissues.Results: In 27% of the tumors, Int6 RNA levels were reduced relative to normal tissue. In 85% of the tumors with reduced Int6 expression, the transcription promoter and first exon were hypermethylated, whereas only 4% of the tumors with elevated Int6 RNA levels were hypermethylated (P < 0.000001). Low levels of Int6 RNA were found a significant predictor of overall and disease-free survival (P = 0.0004 and P = 0.0020, respectively). A multivariate analysis confirmed that low Int6 expression was the only independent factor to predict poor prognosis, for both overall (P = 0.0006) and disease-free (P = 0.024) survival.Conclusions: Our results suggest that Int6 expression, evaluated by quantitative real-time PCR, may represent a new prognostic factor in patients with stage I NSCLC.

Purpose: The aim of this study was to evaluate the prevalence and the clinical significance of HIN-1 mRNA expression in early stage non-small cell lung carcinomas (NSCLCs). Experimental Design: A series of 91 NSCLC patients with stage I neoplastic disease was studied. HIN-1 expression was investigated by quantitative real-time reverse transcription-PCR on tumor specimens and matching normal lung tissues. Variables were analyzed by χ2 test and Fisher’s exact tests. Survival was evaluated with the method of Kaplan-Meier. Multivariate analysis was performed with Cox’s proportional hazards model. Results: Seventy one (78%) tumors showed a reduction of HIN-1 mRNA compared with the normal counterpart. The range of reduction varied greatly, from −2-fold to −3350-fold. Setting a cutoff at −46-fold (median value of HIN-1 mRNA reduction), 46 cases (51%) had a markedly reduced expression, and 45 cases (49%) showed a normal or slightly reduced expression. A statistically significant association between low HIN-1 mRNA levels and T status was observed (P = 0.036). Univariate survival curves, estimated using the method of Kaplan-Meier, defined a significant association between HIN-1 expression and both overall survival (P = 0.0095) and disease-free survival (P = 0.0122). A multivariate analysis, performed by Cox’s proportional hazards regression model, confirmed that a low HIN-1 expression was the only significant factor to predict poor prognosis. Conclusions: Our data indicate that HIN-1 expression, measured by real-time reverse transcription-PCR, is a possible prognostic factor in patients with stage I NSCLC. Additional studies are required to further validate this potential prognostic marker.

Pancreaticoduodenal artery (PD A) aneurysms are rare, with a reported incidence of 2% among all splanchnic artery aneurysms. Most of these lesions are undetectable until symptoms of rupture occur. In similar cases (65%), PDA rupture is usually associated with a high mortality rate, with fatal bleeding into the retroperitoneal space, intraperitoneal cavity or gastrointestinal tract. Clinical picture without rupture also has been reported (35%) and is often associated with atypic abdominal signs and symptoms or diagnosed incidentally on radiology studies. The Authors report a case of octogenarian patient with ruptured PDA aneurysm and bleeding into the retroperitoneal space presenting with stable clinical condition. Surgical treatment was performed successfully after radiological diagnosis of retroperitoneal haematoma with good outcome. Patients presenting catastrophic clinical condition need rapid resuscitation and emergency laparotomy: control of the bleeding site may be successful and aetiologycal diagnosis delayed after perioperative angiography. Further laparotomy is mandatory for a definitive treatment such as PDA obliteration or resection. An alternative therapy is the transcatheter embolization. In patients with relatively stable condition, radiological study is stressed. Anyway, the aneurysm should be obliterated whenever possible to avoid rebleeding or local complications such as erosion of the neighboring structure. In conclusion, an appropriate and early treatment lead to a good outcomes.

90K, also known as Mac-2 binding protein, is a secreted glycoprotein that binds galectins, beta1-integrins, collagens, and fibronectin, and has some relevance in cell-cell and cell-extracellular matrix adhesion. Previous studies have shown that serum levels of 90K have prognostic value in several neoplasms. In the present study, the role of the expression of 90K as an adverse prognostic indicator in 72 pathological stage I non-small cell lung cancer patients was investigated immunohistochemically. All of the patients underwent complete surgical removal of the tumor. The median length of follow-up care was 54 months. High level of 90K expression (90K staining of > or =50% of the neoplastic cells) was observed in 20 of the 72 (28%) tumors. Expression of 90K was confirmed by ELISA. The results showed that a high expression of 90K correlates with adverse prognosis. Among patients with high 90K expression, the disease-free and overall survival rates were significantly lower than the same rates of those with low expression (P = 0. 0001 and P = 0. 0003, respectively). The incidence of distant metastases in the patients with high 90K expression (60%; 12 of 20 patients) was significantly higher than that of in the patients with low expression (21%; 11 of 53 patients; P = 0.0038). The results of multivariate analysis confirmed that a high 90K expression was a significant factor to predict poor prognosis. We suggest that 90K expression could be a useful prognostic factor in patients with stage I non-small cell lung cancer, likely as an indicator of the metastatic propensity of the tumor.

A surgical treatment of patients with lung cancer non-microcitoma and isolated adrenal metastasis has been reported in literature although limited in number and follow up. The Authors report 12 cases of patients operated for lung cancers non-microcitoma and isolated adrenal metastasis. One patients was lost in the follow up, two patients died 3 and 6 months after the adrenalectomy. The other patients are alive after 88, 39, 36, 17, 13 months after the adrenalectomy. Four of these patients are also disease free. Other 4 patients, more recently operated, are alive and disease free after 3, 3, 9 and 9 months after the adrenalectomy. The Authors believe that a surgical treatment is justified in these patients, considering the results of the series reported in literature and also their own results.