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Background: With the popularity of lung cancer screening and advances in imaging technology, more and more synchronous multiple primary lung adenocarcinomas (SMPLA) are being diagnosed clinically, however, the clinical characteristics and prognosis of SMPLA with different EGFR mutations remains unclear. We aimed to explore clinical features and surgical outcomes of these patients to aid in the diagnosis and treatment of SMPLA. Methods: Medical records of patients with different EGFR mutations who have been diagnosed as SMPLA and underwent surgical resection from March 2015 to December 2019 were retrospectively analyzed. Clinical characteristics, surgical outcomes, recurrence-free survival (RFS) and overall survival (OS) were investigated. Results: A total of 70 patients (68.6% female and 77.1% non-somkers) were included. Total of 161 lesions in all patients, 84.4% were ground-glass opacity (GGO) lesions. EGFR mutations were detected in 108 lesions, most of which were L858R (35.4%) and 19Del (20.5%). The mutation rate of mixed GGO is significantly higher than that of pure GGO and solid nodules (SN); the mutation rate of invasive adenocarcinoma is significantly higher than that of other histology subtypes; the mutation rate of lesions >20 mm was significantly higher than that of ≤20 mm. However, there is no significant difference in the mutation rate of specific driver gene between different radiological features, pathological characteristics and sizes. After a median follow-up time of 29 months, the 3-year OS and RFS were 94.4% and 86.0%, respectively. Conclusions: A high discordance of EGFR mutations were identified between tumors in patients with SMPLA. Synchronous multiple lung adenocarcinomas with predominantly multiple GGO should be considered as SMPLA, and surgery may be aggressively performed for these patients due to a good prognosis. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to present the clinical and surgical results in patients who underwent segmental bronchial sleeve reconstruction. Methods: The clinical and pathological data of 16 patients with central non‐small cell lung cancer (NSCLC) who underwent segmental bronchial sleeve resection from April 2015 to May 2019 were retrospectively analyzed. Results: According to the type of segmental bronchial reconstruction, procedures were divided into four types: right upper S6 sleeve lobectomy in three cases (type A); left lower lingular sleeve lobectomy in 10 cases (type B); left upper S6 sleeve lobectomy in two cases (type C); and left lower propriolateral superior sleeve lobectomy in one case (type D). A total of three patients (18.75%) experienced anastomotic complications, including two with anastomotic stenosis and one with anastomotic fistula. All patients achieved R0 resection. Apart from one patient who died of acute lung infection after surgery, the rest were successfully discharged. The average follow‐up time was 28 months, and the overall survival rates of patients at one, two, and three years were 80.0%, 53.3%, and 40.0%, respectively. Conclusions: Segmental bronchial sleeve resection is complex in technique and may have an increased risk of complications compared to a standard sleeve resection, but it is an effective and safe procedure, especially for selected patients with central lung cancer. [ABSTRACT FROM AUTHOR]

Background: Since the development of the uniportal video-assisted thoracoscopic surgery (VATS) technique, the use of uniportal VATS has become increasingly popular for the surgical resection of non-small cell lung cancer (NSCLC). The objective of this study is to introduce a novel modularly designed surgical pattern for uniportal VATS for lung cancer resection and to investigate the safety, feasibility, and efficacy of this novel method.Materials and Methods: The clinical data of NSCLC patients who underwent a curative uniportal VATS lobectomy between March 2015 and April 2016, including via the modular pattern (MP) and the conventional pattern (CP), were retrospectively collected and analyzed. Perioperative and postoperative parameters, including the operation duration, estimated intraoperative blood loss, rate of conversion to thoracotomy, lymph node dissection number, and postoperative complications, were compared between the two groups.Results: A total of 321 patients were identified, among whom 221 underwent MP uniportal VATS lobectomy and 100 were treated via CP uniportal VATS lobectomy. Patients in the MP group experienced a shorter operation duration (135.58 ± 47.16 minutes versus 148.86 ± 42.53 minutes, P = .017) and less estimated intraoperative blood loss (75.20 ± 37.99 mL versus 89.50 ± 41.11 mL, P = .003) than patients in the CP group. No significant difference was observed in the intraoperative conversion rate (2.7% versus 5.0%, P = .477), total number of lymph nodes dissected (24.67 ± 7.73 versus 25.34 ± 7.62, P = .471), postoperative drainage duration (4.86 ± 1.96 days versus 4.78 ± 2.10 days, P = .755), length of stay (9.60 ± 2.93 days versus 9.97 ± 2.80 days, P = .286), or incidence of postoperative complications between the two groups. No postoperative deaths occurred.Conclusions: MP uniportal VATS lobectomy combined with mediastinal lymphadenectomy appears to be a safe and feasible technique for the treatment of NSCLC. The use of this technique can reduce the operation duration and intraoperative blood loss. [ABSTRACT FROM AUTHOR]

The αvβ6 integrin is a cell surface adhesion molecule that plays critical roles in the injury and inflammation processes. We hypothesized that polymorphisms in αvβ6 integrin genes (ITGAV and ITGB6) might be associated with the risk of radiation pneumonitis (RP) in lung cancer patients treated with thoracic radiation. We genotyped three potentially functional αvβ6 integrin single-nucleotide polymorphisms (rs1839123 and rs4129787 in ITGAV, and rs4665162 in ITGB6) and found that the genotypes of rs4665162 single-nucleotide polymorphisms were predictors of RP development (for grade ≥2 RP, HR = 1.505, 95 % CI 1.069-2.119, P = 0.019; for grade ≥3 RP, HR = 3.006, 95 % CI 1.431-6.313, P = 0.004). Our results showed that AG/GG genotypes of ITGB6 rs4665162 gene were associated with a higher risk of RP in patients with lung cancer receiving radiotherapy and thus may serve as a reliable predictor of RP. Further studies will be needed to confirm these findings. [ABSTRACT FROM AUTHOR]

• Membrane PD-L1 expression was rarely observed in the presence of ALK rearrangements. • Tumor bed infiltration CD8 + T cell more frequent in tumors with ALK mutations. • CD8+ T cells infiltrating ALK+ tumors were unable to express IFNG. Several lines of evidence have demonstrated that programmed cell death 1 (PD-1) inhibitors as monotherapies for anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer have little clinical activity. The underlying mechanisms remain not understood. In this study, using immunohistochemistry and in situ RT-PCR assays, we examined the expression of programmed cell death ligand 1 (PD-L1), PD-1, CD8, and interferon gamma (IFN-γ) in tumors. Both epidermal growth factor receptor (EGFR)-mutant and anaplastic lymphoma kinase (ALK)-positive tumors were associated with low or absent membrane PD-L1 expression. Interestingly, unlike EGFR-mutant tumors with few tumor-infiltrating CD8+ T cells, a significant number of PD-1-positive CD8+ T cells infiltrated the ALK-positive tumor bed; however, these cells did not express IFNG mRNA. These results demonstrate that the ALK-positive tumor microenvironment suppresses the immune function of tumor-infiltrating CD8+ T cells through a PD-1/PD-L1-independent mechanism, which might lead to the inability of ALK-positive tumors to respond to PD-1/PD-L1-based immunotherapy. [ABSTRACT FROM AUTHOR]

Abstract: Polymorphisms in 3′ untranslated region (UTR) of cancer-related genes might affect their regulation by microRNAs (miRNAs) and thereby contribute to carcinogenesis. In this study, we screened single nucleotide polymorphisms (SNPs) in 3′ UTR of cancer-related genes and investigated their effects on risk of lung cancer. First, we genotyped seven SNPs in a Chinese Han population with 600 lung cancer patients and 600 matched healthy controls and found that compared with the TT genotype of rs2239680 in 3′ UTR of baculoviral IAP repeat containing 5 (BIRC5), C allele was associated with a significantly increased risk of lung cancer and advanced pathologic stage, with the odds ratio for participants carrying the CT or CC genotype being 1.50 [95% confidence interval (CI) 1.20–1.89, P <0.01] and 2.29 (95% CI 1.64–3.18, P <0.01), respectively. These results were further replicated and confirmed in another independent population with 1000 lung cancer cases and 1000 matched healthy controls. In support of the postulation that the 3′ UTR SNP may directly affect miRNA-binding site, reporter gene assays indicated BIRC5 was a direct target of miR-335, and the rs2239680 T>C change resulted in altered regulation of BIRC5 expression. Moreover, BIRC5 was over expressed in lung cancer tissues compared with the normal lung tissues, and the protein levels of BIRC5 correlated with SNP genotypes in normal lung tissues. Our findings defined a 3′ UTR SNP in human BIRC5 oncogene that may increase individual susceptibility to lung cancer probably by attenuating the interaction between miR-335 and BIRC5. [Copyright &y& Elsevier]