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Open in new tab Download slide OBJECTIVES Anastomotic leak (AL) is one of the most serious complications after oesophageal cancer surgery. A high cervical anastomosis using a narrow gastric tube based on optimized procedures has the potential to reduce the AL after a McKeown oesophagectomy. METHODS A narrow gastric tube was defined as 2–2.5 cm in diameter. Meanwhile, we defined a high anastomosis (HA) and a normal anastomosis (NA) based on the position of the intraoperative cervical anastomosis above or below the level of the inferior thyroid artery, respectively. A total of 533 patients who had a McKeown oesophagectomy from March 2018 to March 2023 were included in this study, including 281 patients in the NA group and 252 patients in the HA group. Potential confounding factors in baseline characteristics were balanced by propensity score matching. RESULTS After matching, 190 patients remained in both groups. When comparing the pathological and surgical results, we found that more lymph nodes, both in total number (21.1 ± 10.0 vs 15.8 ± 7.7, P  = 0.001) and thoracic part (13.5 ± 7.8 vs10.8 ± 6.1, P  = 0.005), were harvested from the HA group. The pathological T and TNM stages of patients in the HA group were earlier than those in the NA group (P  = 0.001). Overall postoperative complications (P  = 0.001), including pulmonary infection (P  = 0.001), AL (P  < 0.001), leakage-related pyothorax (P  < 0.001), recurrent laryngeal nerve palsy (P  = 0.031) and pleural effusion (P  < 0.001), were all significantly lower in the HA group. Finally, multivariable logistic regression analysis indicated that HA was an independent protective factor for AL (odds ratio = 0.331, 95% confidence interval: 0.166–0.658; P  = 0.002). CONCLUSIONS For patients undergoing a McKeown oesophagectomy, a high cervical anastomosis using a narrow gastric tube can effectively reduce leakage-related complications. [ABSTRACT FROM AUTHOR]

Simple Summary: The superior vena cava (SVC)'s involvement in non-small-cell lung cancer (NSCLC) has been considered a technical and oncological contraindication for surgery. In recent decades, different studies have demonstrated that surgery should not be contraindicated per se, but in highly selected cases and specialized centers, it could be curative with acceptable risks. Nevertheless, the tangential resection of the SVC or patch reconstruction have different surgical risks from prosthetic replacement. Moreover, the percentage of SVC involvement may influence the prognoses of these selected patients. Our intention was to investigate the relation between the rate of SVC involvement and surgical and oncological outcomes. The conclusions of our retrospective study may improve the management of patients with T4 NSCLC and SVC invasion. Background: Surgery for non-small-cell lung cancers (NSCLCs) invading the superior vena cava (SVC) is rarely performed due to surgical complexities and reported poor prognoses. Different methods have been described to reconstruct the SVC, such as direct suture, patch use or prosthesis, according to its circumferential involvement. The aim of our study was to analyze the short- and long-term results of different types of SVC resection and reconstruction for T4 NSCLCs. Methods: Between January 2000 and December 2019, 80 patients received an anatomical lung resection with SVC surgery in this multicenter retrospective study. The partial resection and direct suture or patch reconstruction group included 64 patients, while the complete resection and prosthesis reconstruction group included 16 patients. The primary endpoints were as follows: long-term survival and disease-free survival. The secondary endpoints were as follows: perioperative complications and 30- and 90-day mortality. Unpaired t-tests or Mann–Whitney U tests for non-parametric variables were applied to discrete or continuous data, and the chi-square test was applied to dichotomous or categorical data. Survival rates were calculated using the Kaplan–Meier method and compared using the log-rank test. Results: No differences were found between the two groups in terms of general characteristics and surgical, oncological and survival outcomes. In particular, there were no differences in terms of early (50.0% vs. 68.8%, p = 0.178) and late complication frequency (12.5% vs. 12.5%, p = 1.000), 30- and 90-day mortality, R status, recurrence, overall survival (33.89 ± 40.35 vs. 35.70 ± 51.43 months, p = 0.432) and disease-free survival (27.56 ± 40.36 vs. 31.28 ± 53.08 months, p = 0.668). The multivariate analysis demonstrated that age was the only independent predictive factor for overall survival. Conclusions: According to our results, SVC resection has good oncological and survival outcomes, regardless of the proportion of circumferential involvement and the type of reconstruction. [ABSTRACT FROM AUTHOR]

Background. Increasing evidence supports that immune cell infiltration (ICI) patterns play a key role in the tumor progression of lung squamous cell carcinoma (LUSC). However, to date, the immune infiltration picture of LUSC has not been elucidated. Method. TCGA was used to download multiomics data from LUSC samples. At the same time, we included two datasets on lung squamous cell carcinoma, GSE17710 and GSE157010. To reveal the landscape of tumor immune microenvironment (TIME), the ESTIMATE algorithm, ssGSEA approach, and CIBERSORT analysis are used. To quantify the ICI pattern in a single tumor, consistent clustering is used to determine the LUSC subtype based on the ICI pattern, and principal component analysis (PCA) is used to obtain the ICI score. The prognostic value of the Kaplan-Meier curves is confirmed. GSEA (Gene Set Enrichment Analysis) was used to perform functional annotation. To investigate the immunotherapeutic effects of the ICI score, the immunophenotyping score (IPS) is used. Finally, analyze the mutation data with the "maftools" R package. Results. We identified four different immune infiltration patterns with different prognosis and biological characteristics in 792 LUSC samples. The identification of ICI patterns in individual tumors developed under ICI-related characteristic genes based on the ICI score helps to analyze the biological process, clinical results, immune cell infiltration, immunotherapy effects, and genetic variation. Immune failure is indicated by a high ICI score subtype marked by immunosuppression. Patients with low ICI scores have an abundance of efficient immune cells, which corresponds to the immunological activation phenotype and may have therapeutic benefits. The immunophenotypic score was used as a surrogate indicator of immunotherapy results, and samples with low ICI scores obtained significantly higher immunophenotypic scores. Finally, the relationship between the ICI score and tumor mutation burden (TMB) was proven. Conclusion. This study fully clarified the indispensable role of the ICI model in the complexity and diversity of TIME. The quantitative identification of ICI patterns in a single tumor will help draw the picture of TIME and further optimize precision immunotherapy. [ABSTRACT FROM AUTHOR]

The surgical treatment of advanced non-small-cell-lung-cancer (NSCLC) invading mediastinal organs and great vessels is still controversial. The aim of this multicentre study is to analyse oncological outcomes, surgical outcomes and prognostic factors of patients with NSCLC involving heart and great vessels. 362 patients treated surgically for locally advanced T4-NCSLC between 1990 and 2020 were retrospectively reviewed. Patients were divided into five subgroups: pulmonary artery(n = 129), left atrium(n = 82), superior vena cava(n = 80), aorta(n = 43), and multiple vascular structures(n = 28). Resection was complete in 327(90%) patients. Overall 90-day mortality was 8.8%, influenced by poly-transfusions, pneumonectomy, bronchopleural fistula and previous cardiovascular disease (4.5HR.p = 0.03, 3.7HR p = 0.01, 14.0HR.p < 0.001 and 3.0HR p < 0.01). One-, 3- and 5-year survival rates were 75%, 43%, 33%, respectively and there were significant differences among the five groups(p < 0.001). Survival was significantly affected by induction radiotherapy, nodal status, pTNM-stage and radicality (3.8HR p = 0.03, 2.6HR p = 0.001, 1.6HR p < 0.05 and 1.6HR p < 0.05). Surgery provided acceptable results in selected patients with T4-NSCLC with major vascular infiltration in expert centres. Nodal-status and radicality influenced the overall-survival and disease-free survival. Neoadjuvant chemotherapy appears to have a positive effect on long-term results, particularly in N2-patients. [ABSTRACT FROM AUTHOR]

Background: We investigated the prognostic effects and their patterns of immune infiltration of hippo pathway core genes in lung squamous cell carcinoma, in order to find some clues for underlying mechanisms of LUSC tumorigenesis and help developing new therapeutic methods. Methods: The mutational data, transcriptome data and corresponding clinical medical information of LUSC patients were extracted from The Cancer Genome Atlas (TCGA) database. Differential expression genes (DEGs) and Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were explored. Survival analysis for the hippo core genes and the prognostic model were performed. Immune infiltration was estimated by CIBERSORT algorithm and some immune checkpoints-related genes were further investigated. Results: Overall, 551 LUSC samples were included in our study, consisting of 502 LUSC tumor samples and 49 adjacent normal samples, respectively. There were 1910 up-regulated DEGs and 2253 down-regulated DEGs were finally identified. The top five mutational hippo pathway core genes were LATS1 (4%), WWC1 (2%), TAOK1 (2%), TAOK3 (2%), and TAOK2 (2%), respectively. the mutation of LATS2 was highly associated with co-mutational NF2 (P <0.05) and TAOK1 (P <0.05). In survival analyses, we found only WWC1 (log-rank p = 0.046, HR = 1.32, 95% CI = 1–1.73) and LATS2 (log-rank p = 0.013, HR = 1.41, 95%CI = 1.08–1.86) had significant prognostic roles. After getting the three subgroups according to the subtyping results, we demonstrated that T cell gamma delta (p = 5.78e-6), B cell memory (p = 4.61e-4) and T cell CD4+ memory resting (p = 2.65e-5) had significant differences among the three groups. SIGLEC15 (P <0.01) and CD274 (P <0.05) also had statistical differences among the three subgroups. Conclusions: Our study verified the prognostic roles of WWC1 and LATS2 in LUSC patients. Immune checkpoints-related genes SIGLEC15 and CD274 had statistical differences among the three subgroups, which may provide new perceptions on the molecular mechanisms in LUSC and maybe helpful for precisely selecting specific LUSC patients with potential immunotherapy benefits. [ABSTRACT FROM AUTHOR]

Acute and chronic inflammation often leads to fibrosis, which is also the common and final pathological outcome of chronic inflammatory diseases. To explore the common genes and pathogenic pathways among different fibrotic diseases, we collected all the reported genes of the eight fibrotic diseases: eye fibrosis, heart fibrosis, hepatic fibrosis, intestinal fibrosis, lung fibrosis, pancreas fibrosis, renal fibrosis, and skin fibrosis. We calculated the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment scores of all fibrotic disease genes. Each gene was encoded using KEGG and GO enrichment scores, which reflected how much a gene can affect this function. For each fibrotic disease, by comparing the KEGG and GO enrichment scores between reported disease genes and other genes using the Monte Carlo feature selection (MCFS) method, the key KEGG and GO features were identified. We compared the gene overlaps among eight fibrotic diseases and connective tissue growth factor (CTGF) was finally identified as the common key molecule. The key KEGG and GO features of the eight fibrotic diseases were all screened by MCFS method. Moreover, we interestingly found overlaps of pathways between renal fibrosis and skin fibrosis, such as GO:1901890-positive regulation of cell junction assembly, as well as common regulatory genes, such as CTGF, which is the key molecule regulating fibrogenesis. We hope to offer a new insight into the cellular and molecular mechanisms underlying fibrosis and therefore help leading to the development of new drugs, which specifically delay or even improve the symptoms of fibrosis. [ABSTRACT FROM AUTHOR]

Aberrant activation of ERK signaling is a hallmark of lung cancer. Although constitutively activating mutations of EGFR and KRAS contribute to the hyperactivation of ERK1/2, other mechanisms remain elusive. In this study, the zinc finger protein ZNF251 was found to be upregulated in clinical lung cancer samples, and it promoted the growth of lung cancer cells and the growth of primary lung KPC cells from mouse models (Ad‐Cre, KrasG12D, and P53f/f). In studying the molecular mechanism, ZNF251 was found to inhibit the expression of dual‐specificity phosphatase 6, a negative regulator of ERK activation, by directly binding to its promoter region. Taken together, our data indicate the tumor‐promoting effects of ZNF251 in lung cancer and suggest that ZNF251 is a therapeutic target. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide Open in new tab Download slide OBJECTIVES Our goal was to assess the influence of working hours and working at night on intraoperative complications on surgeons conducting video-assisted pulmonary resections. METHODS We identified all patients who underwent video-assisted thoracoscopic surgery (VATS) in Shanghai Chest Hospital from January 2015 to April 2017. Univariable and multivariable logistic analyses were used to analyse independent risk factors for intraoperative complications. A 1:4 propensity score matching analysis was conducted to verify those results. RESULTS A total of 15 767 patients who underwent VATS pulmonary resection were included in this study. Among them, 15 280 patients (96.1%) were operated on during daytime working hours and 487 (3.1%) at night. A total of 203 (1.3%) intraoperative complications occurred. Vascular injury was the main cause of intraoperative complications, accounting for 92.1% (187/203). Multivariable logistic regression indicated that age [odds ratio (OR) = 1.68, 95% confidence interval (CI) 1.43–1.98; P  < 0.001], gender (OR = 1.71, 95% CI 1.26–2.32; P  = 0.001), surgical experience (OR = 2.07, 95% CI 1.56–2.75; P  < 0.001), type of surgery (OR = 0.31, 95% CI 0.20–0.49; P  < 0.001) and operative periods (OR = 2.69, 95% CI 1.61–4.86; P  < 0.001) were independent predictors for intraoperative complications. The incidence of intraoperative complications during night-time surgery was significantly higher than that during daytime working hours. A 1:4 propensity score matching-based results verification showed that night-time surgery was still an independent risk factor after propensity score matching (OR = 2.76, 95% CI 1.47–5.15; P  = 0.002). CONCLUSIONS The incidence of intraoperative complications from VATS pulmonary resection performed during night hours was significantly higher than that performed during working hours. In the present labour environment, thoracic surgeons should avoid night-time surgery whenever possible. [ABSTRACT FROM AUTHOR]