Purpose: Activation of MET oncogene as the result of amplification or activation mutation represents an emerging molecular target for cancer treatment. We comprehensively studied MET alterations and the clinicopathologic correlations in a large cohort of treatment-na€ ve non-small cell lung carcinoma (NSCLC).Experimental Design: Six hundred eighty-seven NSCLCs were tested for MET exon 14 splicing site mutation (METD14), DNA copy number alterations, and protein expression by Sanger sequencing, FISH, and IHC, respectively.Results: METD14 mutation was detected in 2.62% (18/687) of NSCLC. The mutation rates were 2.6% in adenocarcinoma, 4.8% in adenosquamous carcinoma, and 31.8% in sarcomatoid carcinoma. METD14 mutation was not detected in squamous cell carcinoma, large cell carcinoma, and lymphoepithelioma-like carcinoma but significantly enriched in sarcomatoid carcinoma (P < 0.001). METD14 occurred mutually exclusively with known driver mutations but tended to coexist with MET amplification or copy number gain (P < 0.001). Low-level MET amplification and polysomy might occur in the background of EGFR or KRAS mutation whereas high-level amplification (MET/CEP7 ratio !5) was mutually exclusive to the major driver genes except METD14. Oncogenic METD14 mutation and/or high-level amplification occurred in a total of 3.3% (23/687) of NSCLC and associated with higher MET protein expression. METD14 occurred more frequently in older patients whereas amplification was more common in ever-smokers. Both METD14 and high-level amplification were independent prognostic factors that predicted poorer survival by multivariable analysis.Conclusions: The high incidence of METD14 mutation in sarcomatoid carcinoma suggested that MET inhibition might benefit this specific subgroup of patients.

Lobectomy showed better survival than sublobar resection for patients with NSCLC ≤ 1 cm and > 1 to 2 cm. For patients in whom lobectomy is unsuitable, segmentectomy should be recommended for NSCLC > 1 to 2 cm, whereas surgeons could rely on surgical skills and the patient profile to decide between segmentectomy and wedge resection for NSCLC ≤ 1 cm.

The central role of lung ischaemia-reperfusion injury in pulmonary dysfunction after cardiac surgery, particularly thoracic organ transplantation, has been well recognised.Lung tissue necrosis after prolonged ischaemia is known to worsen lung function, which was believed to be due largely to adjacent tissue inflammation. Recent studies suggest that lung apoptosis following ischaemia-reperfusion could be equally important in the development of post-operative lung dysfunction.The current literature on the mechanism and pathways involved in pulmonary dysfunction and, in particular, its relationship with apoptosis after lung ischaemia-reperfusion is briefly reviewed here.A better understanding of lung apoptosis, as well as the upstream pathways, may help in the development of therapeutic strategies that could benefit patients undergoing cardiac and lung transplantation.

OBJECTIVES Our goal was to report the results of the first consensus paper among international experts in uniportal video-assisted thoracoscopic surgery (UniVATS) lobectomy obtained through a Delphi process, the objective of which was to define and standardize the main procedural steps, optimize its indications and perioperative management and identify elements to assist in future training. METHODS The 40 members of the working group were convened and organized on a voluntary basis by the Uniportal VATS Interest Group (UVIG) of the European Society of Thoracic Surgeons (ESTS). An e-consensus finding exercise using the Delphi method was applied to require 75% agreement for reaching consensus on each question. Repeated iterations of anonymous voting continued for 3 rounds. RESULTS Overall, 31 international experts from 18 countries completed all 3 rounds of questionnaires. Although a technical quorum was not achieved, most of the responders agreed that the maximum size of a UniVATS incision should be ≤4 cm. Agreement was reached on many points outlining the currently accepted definition of a UniVATS lobectomy, its indications and contraindications, perioperative clinical management and recommendations for training and future research directions. CONCLUSIONS The UVIG Consensus Report stated that UniVATS offers a valid alternative to standard VATS techniques. Only longer follow-up and randomized controlled studies will predict whether UniVATS represents a valid alternative approach to multiport VATS for major lung resections or whether it should be performed only in selected cases and by selected centres. The next step for the ESTS UVIG is the establishment of a UniVATS section inside the ESTS databases.