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Abstract Background Lymphocyte-activation gene 3 (LAG3) is a recently discovered immune checkpoint molecule that has been linked to immunosuppression and the advancement of cancer in different types of solid tumors. This study aimed to evaluate the prognostic importance of LAG3 and its role in the immune system within solid tumors. Methods Extensive literature searches were conducted using the Pubmed, EMBASE, and Cochrane Library databases to identify relevant studies exploring the effect of LAG3 on survival outcomes. Pooled hazard ratios (HRs) with its 95% confidence intervals (CIs) were calculated to evaluate the prognostic values of LAG3. Afterwards, subgroup analysis and sensitivity analysis were conducted. Pan-cancer analysis investigated the possible relationships between LAG3 expression and genetic alterations, RNA methylation modification-related genes, genomic instability, immune checkpoint genes, and infiltration of immune cells. Results A total of 43 studies with 7,118 patients were included in this analysis. Higher expression of LAG3 was associated with worse overall survival (HR = 1.10, 95% CI 1.01–1.19, P = 0.023), but not disease-free survival (HR = 1.41, 95% CI 0.96–2.07, P = 0.078), progression-free survival (HR = 1.12, 95% CI 0.90–1.39, P = 0.317) or recurrence-free survival (HR = 0.98, 95% CI 0.81–1.19, P = 0.871). Subgroup analysis showed that LAG3 might play different prognostic roles in different solid tumors. LAG3 expression was positively associated with immune cell infiltration and immune checkpoint genes in all of the cancers included. LAG3 expression was also found to be associated with microsatellite instability (MSI), copy number variation (CNV), simple nucleoside variation (SNV), tumor mutation burden (TMB), and neoantigen in various types of cancers. Conclusions Elevated expression of LAG3 is linked to poorer prognosis among patients diagnosed with solid cancers. LAG3 might play varying prognostic roles in different types of solid tumors. Given its substantial involvement in cancer immunity and tumorigenesis, LAG3 has garnered attention as a promising prognostic biomarker and a potential target for immunotherapy.

BackgroundThe progression of early stage non-small cell lung cancer (NSCLC) is closely related to epidermal growth factor receptor (EGFR) mutation status. The purpose of this study was to systematically investigate the relationship between EGFR mutation status and demographic, imaging, and ultimately pathologic features in patients with NSCLC.MethodsA complete literature search was conducted using the PubMed, Web of Science, EMBASE, and Cochrane Library databases to discover articles published by May 15, 2023 that were eligible. The relationship between EGFR mutation status and specific demographic, imaging, and ultimately pathologic features in patients with NSCLC was evaluated using pooled odds ratios (ORs) and their 95% confidence intervals (CIs). The standardized mean difference (SMD) with 95% CIs was the appropriate statistic to summarize standard deviations (SDs) means for continuous variables.ResultsA total of 9 studies with 1789 patients were included in this analysis. The final findings suggested that patients with a greater age, female gender, and non-smoking status would have a relatively higher incidence of EGFR mutations. Additionally, the risk of EGFR mutations increased with larger tumor diameter, tumor imaging presentation of mixed ground glass opacity (mGGO), and tumor pathological findings of minimally invasive adenocarcinoma (MIA) or invasive adenocarcinoma (IAC). Significantly, malignancies presenting as MIA are more likely to contain L858R point mutations (OR = 1.80; 95% CI: 1.04–3.13; p = 0.04) rather than exon 19 deletions (OR = 1.81; 95% CI: 0.95–3.44; p = 0.07).ConclusionThis meta-analysis showed that imaging parameters and histological classifications of pulmonary nodules may be able to predict stage IA NSCLC genetic changes.

Abstract Circular RNAs play important roles in many cancers, including esophageal squamous cell carcinoma (ESCC), but the precise functions of most circular RNAs are poorly understood. Here we detected significant downregulation of circTRPS1-2 in ESCC based on high-throughput sequencing of three pairs of ESCC tissue and adjacent normal tissue, followed by PCR validation with another 30 tissue pairs. Patients with ESCC whose circTRPS1-2 expression was below the median level for the sample showed significantly shorter median overall survival (13 months) than patients whose circTRPS1-2 expression was above the median (36 months). Overexpressing circTRPS1-2 in the human ESCC cell lines K150 and E109, which express low endogenous levels of circTRPS1-2, inhibited cell proliferation and migration. Conversely, knocking down circTRPS1-2 using short interfering RNA promoted cell proliferation and migration. Similar results were observed in mice bearing K150 xenografts in which circTRPS1-2 was overexpressed or knocked down. Several ribosomal proteins co-immunoprecipitated with circTRPS1-2 from K150 cells in culture, and K150 cells overexpressing circTRPS1-2 showed reduced numbers of ribosomes by A260 absorbance measure and electron microscopy. Our results suggest that circTRPS1-2 can inhibit ESCC proliferation and migration by reducing the production of ribosomes, establishing its potential usefulness in ESCC treatment and prediction of prognosis.

Abstract Background The effectiveness of robotic‐assisted lobectomy (RAL) for patients with non–small‐cell lung cancer (NSCLC) has not been fully evaluated. Methods This retrospective study compared the perioperative outcomes of NSCLC patients who underwent RAL and video‐assisted lobectomy (VAL) using propensity score matching (PSM) analysis. Subgroup analyses were then performed. Results A total of 822 NSCLC patients (359 RAL cases and 463 VAL cases) were included, and there were 292 patients in each group after PSM. Compared with the VAL group, the RAL group had a significantly higher number of lymph nodes (LNs) harvested (10 vs. 8, p

BackgroundWith the popularity of computed tomography (CT) of the thorax, the rate of diagnosis for patients with early-stage lung cancer has increased. However, distinguishing high-risk pulmonary nodules (HRPNs) from low-risk pulmonary nodules (LRPNs) before surgery remains challenging.MethodsA retrospective analysis was performed on 1064 patients with pulmonary nodules (PNs) admitted to the Qilu Hospital of Shandong University from April to December 2021. Randomization of all eligible patients to either the training or validation cohort was performed in a 3:1 ratio. Eighty-three PNs patients who visited Qianfoshan Hospital in the Shandong Province from January through April of 2022 were included as an external validation. Univariable and multivariable logistic regression (forward stepwise regression) were used to identify independent risk factors, and a predictive model and dynamic web nomogram were constructed by integrating these risk factors.ResultsA total of 895 patients were included, with an incidence of HRPNs of 47.3% (423/895). Logistic regression analysis identified four independent risk factors: the size, consolidation tumor ratio, CT value of PNs, and carcinoembryonic antigen levels in blood. The area under the ROC curves was 0.895, 0.936, and 0.812 for the training, internal validation, and external validation cohorts, respectively. The Hosmer-Lemeshow test demonstrated excellent calibration capability, and the fit of the calibration curve was good. DCA has shown the nomogram to be clinically useful.ConclusionThe nomogram performed well in predicting the likelihood of HRPNs. In addition, it identified HRPNs in patients with PNs, achieved accurate treatment with HRPNs, and is expected to promote their rapid recovery.

Abstract Background Prolonged air leak (PAL) remains one of the most frequent postoperative complications after pulmonary resection. This study aimed to develop a predictive nomogram to estimate the risk of PAL for individual patients after minimally invasive pulmonary resection. Methods Patients who underwent minimally invasive pulmonary resection for either benign or malignant lung tumors between January 2020 and December 2021 were included. All eligible patients were randomly assigned to the training cohort or validation cohort at a 3:1 ratio. Univariate and multivariate logistic regression were performed to identify independent risk factors. All independent risk factors were incorporated to establish a predictive model and nomogram, and a web-based dynamic nomogram was then built based on the logistic regression model. Nomogram discrimination was assessed using the receiver operating characteristic (ROC) curve. The calibration power was evaluated using the Hosmer-Lemeshow test and calibration curves. The nomogram was also evaluated for clinical utility by the decision curve analysis (DCA). Results A total of 2213 patients were finally enrolled in this study, among whom, 341 cases (15.4%) were confirmed to have PAL. The following eight independent risk factors were identified through logistic regression: age, body mass index (BMI), smoking history, percentage of the predicted value for forced expiratory volume in 1 second (FEV1% predicted), surgical procedure, surgical range, operation side, operation duration. The area under the ROC curve (AUC) was 0.7315 [95% confidence interval (CI): 0.6979–0.7651] for the training cohort and 0.7325 (95% CI: 0.6743–0.7906) for the validation cohort. The P values of the Hosmer-Lemeshow test were 0.388 and 0.577 for the training and validation cohorts, respectively, with well-fitted calibration curves. The DCA demonstrated that the nomogram was clinically useful. An operation interface on a web page ( https://lirongyangql.shinyapps.io/PAL_DynNom/ ) was built to improve the clinical utility of the nomogram. Conclusion The nomogram achieved good predictive performance for PAL after minimally invasive pulmonary resection. Patients at high risk of PAL could be identified using this nomogram, and thus some preventive measures could be adopted in advance.

Abstract Background Enhanced recovery after surgery (ERAS) is a perioperative management protocol to accelerate patient recovery. This study aimed to evaluate the feasibility of ERAS protocols implemented in patients who underwent neoadjuvant chemotherapy (NACT) before minimally invasive McKeown esophagectomy. Methods This retrospective study compared the short-term clinical outcomes in esophagectomy patients from June 2018 to June 2021. Subjects were divided into two categories: those who underwent NACT (NACT group) and the non-NACT group. Results There was no significant difference in total postoperative complication morbidity between the NACT and non-NACT groups (21.2% vs. 20.7%, P=0.936). In addition, the hospital length of stay post-surgery (7.90 vs. 7.71 days, P=0.424) was not significantly longer when compared to the non-NACT group. The time to chest tube removal (5.37 vs. 5.13 days, P=0.238) and first bowel movement (2.92 vs. 3.01 days, P=0.560) was also similar between the two groups. Conclusions There was no significant difference in postoperative complications rate, postoperative hospital length of stay, and readmission rate between the two group. This study proved that ERAS protocols seemed to be safe and feasible for patients who received NACT before esophagectomy.

BackgroundIn recent years, an increasing number of thoracic surgeons have attempted to apply no routine chest tube drainage (NT) strategy after thoracoscopic lung resection. However, the safety and feasibility of not routinely placing a chest tube after lung resection remain controversial. This study aimed to investigate the effect of NT strategy after thoracoscopic pulmonary resection on perioperative outcomes.MethodsA comprehensive literature search of PubMed, Embase, and the Cochrane Library databases until 3 January 2022 was performed to identify the studies that implemented NT strategy after thoracoscopic pulmonary resection. Perioperative outcomes were extracted by 2 reviewers independently and then synthesized using a random-effects model. Risk ratio (RR) and standardized mean difference (SMD) with 95% confidence interval (CI) served as the summary statistics for meta-analysis. Subgroup analysis and sensitivity analysis were subsequently performed.ResultsA total of 12 studies with 1,381 patients were included. The meta-analysis indicated that patients in the NT group had a significantly reduced postoperative length of stay (LOS) (SMD = -0.91; 95% CI: -1.20 to -0.61; P < 0.001) and pain score on postoperative day (POD) 1 (SMD = -0.95; 95% CI: -1.54 to -0.36; P = 0.002), POD 2 (SMD = -0.37; 95% CI: -0.63 to -0.11; P = 0.005), and POD 3 (SMD = -0.39; 95% CI: -0.71 to -0.06; P = 0.02). Further subgroup analysis showed that the difference of postoperative LOS became statistically insignificant in the lobectomy or segmentectomy subgroup (SMD = -0.30; 95% CI: -0.91 to 0.32; P = 0.34). Although the risk of pneumothorax was significantly higher in the NT group (RR = 1.75; 95% CI: 1.14–2.68; P = 0.01), the reintervention rates were comparable between groups (RR = 1.04; 95% CI: 0.48–2.25; P = 0.92). No significant difference was found in pleural effusion, subcutaneous emphysema, operation time, pain score on POD 7, and wound healing satisfactory (all P > 0.05). The sensitivity analysis suggested that the results of the meta-analysis were stabilized.ConclusionsThis meta-analysis suggested that NT strategy is safe and feasible for selected patients scheduled for video-assisted thoracoscopic pulmonary resection.Systematic Review Registrationhttps://inplasy.com/inplasy-2022-4-0026, identifier INPLASY202240026.

BackgroundThe effectiveness of robotic-assisted thoracoscopic surgery (RATS) for mediastinal masses has not been fully evaluated. This study aimed to compare the perioperative outcomes between RATS and video-assisted thoracoscopic surgery (VATS) for mediastinal masses, and then explore which group of people would benefit more from RATS.MethodsThis retrospective study compared the perioperative outcomes of patients with mediastinal masses who underwent RATS and VATS from September 2018 to December 2021. Subgroup analysis were performed according to body mass index (BMI) ranges.ResultsA total of 212 patients with mediastinal masses (106 RATS cases and 106 VATS cases) were included. Compared with the VATS group, the RATS group had a significantly reduced incidence of overall postoperative complications (5.7% vs. 14.2%, p = 0.039), complications of grade II or less (3.8% vs. 12.3%, p = 0.023), and pneumonia (2.8% vs. 9.4%, p = 0.045). Hospitalization costs were significantly higher in the RATS group (¥ 49350.0 vs. ¥ 32551.9, p 0.05). Subgroup analysis indicated that the incidence of overall postoperative complications (3.1% vs. 15.2%, p = 0.017), complications of grade II or less (1.5% vs. 12.1%, p = 0.033) and postoperative length of stay (4 days vs. 4.5 days, p = 0.046) were significantly reduced in the RATS group for overweight and obese patients (BMI ≥ 24 kg/m2), while these differences became insignificant in the BMI

BackgroundThe efficacy of sublobar resection and selective lymph node dissection is gradually being accepted by thoracic surgeons for patients within early-stage non-small cell lung cancer (NSCLC). Nevertheless, there are still some NSCLC patients develop lymphatic metastasis at clinical T1 stage. Lung adenocarcinoma with a micropapillary (MP) component poses a higher risk of lymph node metastasis and recurrence even when the MP component is not predominant. Our study aimed to explore the genetic features and occult lymph node metastasis (OLNM) risk factors in patients with a non-predominant micropapillary component (NP-MPC) in a large of patient’s cohort with surgically resected lung adenocarcinoma.MethodsBetween January 2019 and December 2021, 6418 patients who underwent complete resection for primary lung adenocarcinoma at the Qilu Hospital of Shandong University. In our study, 442 patients diagnosed with lung adenocarcinoma with NP-MPC with a tumor size ≤3 cm were included. Genetic alterations were analyzed using amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Abnormal protein expression of gene mutations was validated using immunohistochemistry. A nomogram risk model based on clinicopathological parameters was developed to predict OLNM. This model was invalidated using the calibration plot and concordance index.ResultsIn our retrospective cohort, the incidence rate of the micropapillary component was 11.17%, and OLNM was observed in 20.13% of the patients in our study. ARMS-PCR suggested that EGFR exon 19 del was the most frequent alteration in NP-MCP patients compared with other gene mutations (frequency: 21.2%, P

Background: The efficacy of sublobar resection and selective lymph node dissection is gradually being accepted by thoracic surgeons for patients within early-stage non-small cell lung cancer (NSCLC). Nevertheless, there are still some NSCLC patients develop lymphatic metastasis at clinical T1 stage. Lung adenocarcinoma with a micropapillary (MP) component poses a higher risk of lymph node metastasis and recurrence even when the MP component is not predominant. Our study aimed to explore the genetic features and occult lymph node metastasis (OLNM) risk factors in patients with a non-predominant micropapillary component (NP-MPC) in a large of patient's cohort with surgically resected lung adenocarcinoma. Methods: Between January 2019 and December 2021, 6418 patients who underwent complete resection for primary lung adenocarcinoma at the Qilu Hospital of Shandong University. In our study, 442 patients diagnosed with lung adenocarcinoma with NP-MPC with a tumor size =3 cm were included. Genetic alterations were analyzed using amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Abnormal protein expression of gene mutations was validated using immunohistochemistry. A nomogram risk model based on clinicopathological parameters was developed to predict OLNM. This model was invalidated using the calibration plot and concordance index. Results: In our retrospective cohort, the incidence rate of the micropapillary component was 11.17%, and OLNM was observed in 20.13% of the patients in our study. ARMSPCR suggested that EGFR exon 19 del was the most frequent alteration in NP-MCP patients compared with other gene mutations (frequency: 21.2%, P<0.001). Patients harboring exon 19 del showed significantly higher risk of OLNM (P< 0.001). A nomogram was developed based on five risk parameters, which showed good calibration and reliable discrimination ability (C-index = 0.84) for evaluating OLNM risk. Conclusions.: Intense expression of EGFR exon 19 del characterizes lung adenocarcinoma in patients with NP-MCP and it's a potential risk factor for OLNM. We firstly established a nomogram based on age, CYFRA21-1 level, tumor size, micropapillary and solid composition, that was effective in predicting OLNM among NP-MCP of lung adenocarcinoma measuring = 3 cm. [ABSTRACT FROM AUTHOR]