Explore the vast range of titles available.

The four major histological types of lung cancer are adenocarcinoma, squamous cell carcinoma (SQ), large cell carcinoma and small cell carcinoma. Over the past few decades, the incidence of lung adenocarcinoma has increased gradually in most countries as the most frequently occurring histological type, displacing SQ. Adenocarcinoma is the predominant type of lung cancer among lifelong non-smokers and among females. Especially in East Asian countries, the cause(s) of the increase in adenocarcinomas are not clear. Several genetic mutations specific to lung adenocarcinomas have been found, representing attractive targets for molecular therapy. Recently, the pathological classification of lung adenocarcinoma was revised by integrating the newer clinical and biological knowledge concerning this prevailing type. Additional epidemiological, pathological and genetic studies are required to better understand this type of lung cancer.

The water submersion test (W-test) has the risk of overlooking air leaks during lung resection. We assessed the relationship between alveolar air leakage and intrathoracic gas concentrations as a novel intraoperative air leak detection method. We compared the W-test results with intrathoracic gas concentrations of desflurane, oxygen (O2), and carbon dioxide (CO2), prospectively measured using a gas analyser built-in into the anaesthesia machine before and after lung resection. Eighty-eight patients were included; 32 patients had a positive W-test, 31 of whom had elevated levels of all three gases. Eight of the 56 W-test negative patients had elevated levels of all three gases and were positive in a reconfirmation W-test. After repair, 27/31 patients demonstrated negative W-tests, but two patients with elevated levels of all three gases concentrations had postoperative air leaks. When intrathoracic O2 concentration increased, all patients showed an air leak. Conversely, no air leak was detected when intrathoracic concentrations without O2 were measured. We found a positive correlation (correlation coefficients: desflurane, r = 0.84; O2, r = 0.80; CO2. r = 0.77) between the number of bubbles observed in the W-test and gas concentrations. Intrathoracic gas concentration measurements could be a useful alternative or complementary method to the W-test for detecting intraoperative alveolar air leaks. Given that high concentration O2 is frequently use for reinflate the collapsed lungs, intrathoracic O2 measurement could be the most effective way to detect alveolar leakage.

The purpose of this study was to investigate the associated factors of insulation failure (IF) in reusable endoscopic instruments. The insulation coating of reusable endoscopic instruments underwent routine visual checks, hand washing to remove visible stains, and mechanized sterilization. We recorded the cleaning number and usage period of all instruments. The instruments were tested for IF using a detector. IF was found in eight of 69 devices (11.6%). Examining by clinical specialty, we found IF in 4 of 28 gastrointestinal (14.3%), 3 of 20 gynecological (15.0%), 1 of 12 urological (8.3%), and none of the nine thoracic devices. The median distance from the tip to the damaged part was 5 cm (3–5 cm). In the IF and the intact groups, the period of use [7 years (6–8) versus 7 years (4–8), P = 0.90] and the number of cleanings [281 (261–323) versus 261 (179–320), P = 0.27] were not significantly different. The IF group included products of three different companies; however, six of the eight (75.0%) were from the same company. Cleaning methods and usage period have a lower impact on IF. The use of reusable forceps as a monopolar device was found to pose a higher risk, requiring regular assessments.

Next‐generation sequencing (NGS) enables the diagnosis of large numbers of gene aberrations during one examination, and precision medicine has been developed for patients with advanced non–small cell lung cancer (NSCLC). However, peripheral lung lesions account for the majority of advanced lung cancers, especially lung adenocarcinoma. In these cases, it is difficult to obtain tissue samples which contain sufficient tumor cells by transbronchial biopsy (TBB) with forceps. Even when the target lesions are quite small, bronchial brushing can obtain enough tumor cells by endobronchial ultrasonography using guide sheath (EBUS‐GS). In this study, we investigate the suitability of bronchial brushing cytology specimens obtained by EBUS‐GS‐TBB to evaluate the correlation between the success rate of NGS and extracted DNA/RNA yields according to biopsy method. We prospectively collected 222 tumor samples obtained from patients with advanced lung cancer. All patients were enrolled in a prospective nationwide genomic screening project for lung cancer (LC‐SCRUM‐Japan/Asia). Genomic data were obtained from the clinico‐genomic database of LC‐SCRUM‐Japan/Asia. The extraction yields of DNA/RNA from samples obtained by EBUS‐GS‐TBB were relatively low compared with tissue samples. The success rate of DNA sequencing for EBUS‐GS‐TBB was 97.9%, with no significant differences between biopsy methods. The success rate of RNA sequencing for EBUS‐GS‐TBB was 80.4%, which was relatively low compared with surgical biopsy samples (P = 0.069). However, some rare oncogenic driver aberrations were detected from these specimens. This study demonstrated that cytology samples obtained by transbronchial brushing with EBUS‐GS‐TBB were suitable for NGS analysis. This study demonstrated that cytology samples obtained by transbronchial brushing with endobronchial ultrasonography using guide sheath (EBUS‐GS) were suitable for next‐generation sequencing (NGS) analysis. We believe the new knowledge of this study can contribute to the best practice and further research for patients with advanced non–small cell lung cancer (NSCLC).

There are few prospective reports of transbronchial lung cryobiopsy (TBLC) for malignant tumors in combination with forceps biopsy. We investigated the clinical parameters in which TBLC is superior to forceps biopsy. This is a prospective cohort study to analyse the efficacy of TBLC for suspected malignancy. TBLC was performed after brushing cytology and forceps biopsy, and the diagnostic yield for TBLC, brushing cytology, and forceps biopsy were examined. Adverse events were defined as those requiring additional procedures. Next-generation sequencing (NGS) analysis was performed in each case of non-small cell lung cancer. Of the 100 patients, malignancy was confirmed in 94 cases. The diagnostic yield for TBLC/forceps biopsy/brushing cytology was 86/81/82% respectively, while the diagnostic yield for all procedures combined was 94%. There was no significant difference in the diagnostic yield between TBLC and forceps biopsy. When comparing the biopsy site, the diagnostic yield for TBLC at the lower lobe was significantly higher than forceps biopsy (P < 0.01). Endobronchial ultrasonography imaging using a guide-sheath did not significantly differ in the diagnostic yield of TBLC. The success rate of NGS for TBLC specimens was 100% (26 cases). Adverse events included two cases of severe bleeding. TBLC of peripheral lesions may improve the diagnostic yield when combined with forceps biopsy and brushing cytology. The diagnostic yield of TBLC was higher at the lower lobes. Furthermore, TBLC provided sufficient specimen quality for NGS.

BackgroundAnatomic resection with lymph node dissection or sampling is the standard treatment for early non-small cell lung cancer (NSCLC), and wedge resection is an option for compromised patients. This study aimed to determine whether wedge resection can provide comparable prognoses for elderly patients with NSCLC. MethodsThe study analyzed the clinicopathologic findings and surgical outcomes during a median follow-up period of 39.6 months for 156 patients with solid dominant (consolidation-to-tumor ratio > 0.5) small (whole tumor size ≤ 2 cm) NSCLC among 892 patients 80 years of age or older with medically operable lung cancer between April 2015 and December 2016.ResultsThe 3-year overall survival (OS) rates after wedge resection and after segmentectomy plus lobectomy did not differ significantly (86.5 %; 95 % confidence interval [CI], 74.6–93.0 % vs 83.7 % 95 % CI, 74.0–90.0 %; P = 0.92). Multivariable Cox regression analysis of OS with propensity scores showed that the surgical procedure was not an independent prognostic predictor (hazard ratio [HR], 0.84; 95 % CI, 0.39–1.8; P = 0.64). The 3-year OS rates were slightly better after wedge resection for 97 patients who could tolerate lobectomy than after segmentectomy plus lobectomy (89.4 %; 95 % CI, 73.8–95.9 % vs 75.8 %; 95 % CI, 62.0–85.2 %; P = 0.14). The cumulative incidence of other causes for death was marginally higher after segmentectomy plus lobectomy than after wedge resection (P = 0.079).ConclusionsWedge resection might be equivalent to lobectomy or segmentectomy for selected patients 80 years of age or older with early-stage NSCLC who can tolerate lobectomy.

No therapeutic targets have been identified for lung squamous cell cancer (SqCC) which is the second most prevalent lung cancer because its molecular profiles remain unclear. This study aimed to unveil disease-related protein networks by proteomic and bioinformatic assessment of laser-microdissected cancerous cells from seven SqCCs compared with eight representative lung adenocarcinomas. We identified three network modules significant to lung SqCC using weighted gene co-expression network analysis. One module was intrinsically annotated to keratinization and cell proliferation of SqCC, accompanied by hypoxia-induced aerobic glycolysis, in which key regulators were activated ( HIF1A , ROCK2 , EFNA1-5 ) and highly suppressed ( KMT2D ). The other two modules were significant for translational initiation, nonsense-mediated mRNA decay, inhibited cell death, and interestingly, eIF2 signaling, in which key regulators, MYC and MLXIPL , were highly activated. Another key regulator LARP1 , the master regulator in cap-dependent translation, was highly suppressed although upregulations were observed for hub proteins including EIF3F and LARP1 targeted ribosomal proteins, among which PS25 is the key ribosomal protein in IRES-dependent translation. Our results suggest an underlying progression mechanism largely caused by switching to the cap-independent, IRES-dependent translation of mRNA subsets encoding oncogenic proteins. Our findings may help to develop therapeutic strategies to improve patient outcomes.

It is unclear how epidermal growth factor receptor EGFR major driver mutations (L858R or Ex19del) affect downstream molecular networks and pathways. This study aimed to provide information on the influences of these mutations. The study assessed 36 protein expression profiles of lung adenocarcinoma (Ex19del, nine; L858R, nine; no Ex19del/L858R, 18). Weighted gene co-expression network analysis together with analysis of variance-based screening identified 13 co-expressed modules and their eigen proteins. Pathway enrichment analysis for the Ex19del mutation demonstrated involvement of SUMOylation, epithelial and mesenchymal transition, ERK/mitogen-activated protein kinase signalling via phosphorylation and Hippo signalling. Additionally, analysis for the L858R mutation identified various pathways related to cancer cell survival and death. With regard to the Ex19del mutation, ROCK, RPS6KA1, ARF1, IL2RA and several ErbB pathways were upregulated, whereas AURK and GSKIP were downregulated. With regard to the L858R mutation, RB1, TSC22D3 and DOCK1 were downregulated, whereas various networks, including VEGFA, were moderately upregulated. In all mutation types, CD80/CD86 (B7), MHC, CIITA and IFGN were activated, whereas CD37 and SAFB were inhibited. Costimulatory immune-checkpoint pathways by B7/CD28 were mainly activated, whereas those by PD-1/PD-L1 were inhibited. Our findings may help identify potential therapeutic targets and develop therapeutic strategies to improve patient outcomes.

Introduction Lobectomy has been the standard surgery for even stage I lung cancer since the validity of limited resection for stage I lung cancer was denied by the randomized study reported in 1995. The aim of this non-randomized confirmatory going on since September 2013 is to confirm the efficacy of a segmentectomy for clinical T1N0 lung cancer with dominant ground glass opacity based on thin-slice computed tomography. Method A total of 390 patients from 42 Japanese institutions are recruited within 4 years. The primary endpoint of this study is a 5-year relapse-free survival in all of the patients who undergo a segmentectomy for a lung nodule. The secondary endpoints are overall survival, annual relapse-free survival, disease-free survival, proportion of local relapse, postoperative pulmonary function, proportion of segmentectomy completion, proportion of R0 resection completion by segmentectomy, adverse events, and serious adverse events. This trial has been registered at the UMIN Clinical Trials Registry as UMIN000011819 ( http://www.umin.ac.jp/ctr/ ). Results Patient’s accrual has been already finished in November, 2015 and the primary analysis will be performed in 2021. Conclusion This study is one of the pivotal trial of lung segmentectomy for early lung cancer. The result will provide a clear evidence for our daily clinics and will be possible contribution to preserving pulmonary function for lung cancer patients.