Prognostic significance of Lymphocyte-activation gene 3 (LAG3) in patients with solid tumors: a systematic review, meta-analysis and pan-cancer analysis.

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.

Construction and validation of a nomogram for predicting prolonged air leak after minimally invasive pulmonary resection.

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.

Feasibility research of enhanced recovery after surgery implemented in esophageal cancer patients who underwent neoadjuvant chemotherapy.

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.

Circular RNA circTRPS1-2 inhibits the proliferation and migration of esophageal squamous cell carcinoma by reducing the production of ribosomes.

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.

A nomogram combining thoracic CT and tumor markers to predict the malignant grade of pulmonary nodules ≤3 cm in diameter.

Background: With 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. Methods: A 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. Results: A 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. Conclusion: The 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.

Distinguishing EGFR mutant subtypes in stage IA non-small cell lung cancer using the presence status of ground glass opacity and final histologic classification: a systematic review and meta-analysis.

Background: The 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. Methods: A 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. Results: A 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). Conclusion: This meta-analysis showed that imaging parameters and histological classifications of pulmonary nodules may be able to predict stage IA NSCLC genetic changes.

Effects of Neoadjuvant Radiotherapy on Survival in Patients with Stage IIIA-N2 Non-Small-Cell Lung Cancer Following Pneumonectomy.

Background: Pneumonectomy is a drastic but sometimes inevitable treatment option for patients with non-small-cell lung cancer (NSCLC) to improve their chances for long-term survival. However, the optimal adjuvant radiotherapy used for patients with N2 NSCLC following pneumonectomy remains unclear in the literature. Methods: T1-4N0-2M0 NSCLC patients registered in the Surveillance, Epidemiology, and End Results database were retrospectively analyzed. Propensity score matching was applied to balance the assignment of patients. Cox proportional hazards models and Kaplan−Meier analyses were used to identify the factors related to overall survival rates. Restricted cubic splines were used to detect the possible nonlinear dependency of the relationship between the risk of survival and age. Results: A total of 4308 NSCLC patients were enrolled in this study. In N2 patients, the long-term outcome of the chemotherapy and postoperative radiotherapy groups was the worst (p = 0.014). Subgroup analyses showed that the influence of age on survival outcome was confined to patients who received chemotherapy and neoadjuvant radiotherapy (p = 0.004). Meanwhile, patients >65 years of age who received chemotherapy and neoadjuvant radiotherapy had significantly worse prognoses than those in the chemotherapy group (p = 0.005). Conclusions: Our results show that neoadjuvant radiotherapy may have potential benefits in patients aged ≤ 65 years who are scheduled for pneumonectomy, but not in elderly patients.

Comparison of perioperative outcomes between robotic-assisted and video-assisted thoracoscopic surgery for mediastinal masses in patients with different body mass index ranges: A population-based study.

Background: The 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. Methods: This 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. Results: A 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 < 0.001). There was no significant difference in operation duration, intraoperative estimated blood loss, postoperative chest tube drainage volume, NRS pain score, day of chest tube removal, complications of grade III or more, or in-hospital mortality rate (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 < 24 kg/m2 subgroup. Conclusion: RATS could reduce the incidence of postoperative complications, shorten the postoperative length of stay and might be a more cost-effective surgical treatment for overweight and obese patients with mediastinal masses.

Comparison of perioperative outcomes with or without routine chest tube drainage after video-assisted thoracoscopic pulmonary resection: A systematic review and meta-analysis.

Background: In 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. Methods: A 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. Results: A 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. Conclusions: This meta-analysis suggested that NT strategy is safe and feasible for selected patients scheduled for video-assisted thoracoscopic pulmonary resection. Systematic Review Registration: https://inplasy.com/inplasy-2022-4-0026, identifier INPLASY202240026.

Comparison of the perioperative outcomes between robotic-assisted thoracic surgery and video-assisted thoracic surgery in non-small cell lung cancer patients with different body mass index ranges.

Background: Non-small cell lung cancer (NSCLC) is the most common malignancy and one of the most common causes of cancer-related death worldwide. Robotic-assisted thoracic surgery (RATS) has gradually become a prevalent surgical method for patients with NSCLC. Previous studies have found that body mass index (BMI) is associated with postoperative outcomes. This study aimed to investigate the effectiveness of RATS compared to video-assisted thoracic surgery (VATS) in the treatment of NSCLC with different BMI, in terms of perioperative outcomes. Methods: The baseline and perioperative data, including BMI, of 849 NSCLC patients who underwent minimally invasive anatomic lung resections from August 2020 to April 2021 were retrospectively collected and analyzed. Propensity score matching analysis was applied to minimize potential bias between the two groups (VATS and RATS), and the perioperative outcomes were compared. Subgroup analysis was subsequently performed. Results: Compared to VATS, RATS had more lymph nodes dissected {9 [inter-quartile range (IQR), 6-12] vs. 7 (IQR, 6-10), P<0.001}, a lower estimated bleeding volume [40 (IQR, 30-50) vs. 50 (IQR, 40-60) mL, P<0.001], and other better postoperative outcomes, but a higher cost of hospitalization [¥83,626 (IQR, 77,211-92,686) vs. ¥75,804 (IQR, 66,184-83,693), P<0.001]. Multivariable logistic regression analysis indicated that RATS (P=0.027) and increasing BMI (P=0.030) were associated with a statistically significant reduction in the risk of postoperative complications. Subgroup analysis indicated that the advantages of RATS may be more obvious in patients with a BMI of 24-28 kg/m2, in which the RATS group had more lymph nodes dissected [9 (IQR, 6-12) vs. 7 (IQR, 5-10), P<0.001] and a decreased risk of total postoperative complications [odds ratio (OR), 0.443; 95% confidence interval (CI), 0.212-0.924; P=0.030] compared to the VATS group. Conclusions: Both, RATS and VATS can be safely applied for patients with NSCLC. Perioperative outcome parameters indicate advantages for RATS, however at a higher cost of hospitalization. The advantages of RATS might be more obvious in patients with a BMI of 24-28 kg/m2.

Genomics Analysis and Nomogram Risk Prediction of Occult Lymph Node Metastasis in Non-Predominant Micropapillary Component of Lung Adenocarcinoma Measuring ≤ 3 cm.

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. 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<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.

Robotic-assisted thoracoscopic surgery improves perioperative outcomes in overweight and obese patients with non-small-cell lung cancer undergoing lobectomy: A propensity score matching analysis.

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 < 0.001) and more LN stations examined (6 vs. 5, p < 0.001). The operative duration (95 minutes vs. 115 minutes, p < 0.001) and intraoperative estimated blood loss (65 mL vs. 80 mL, p < 0.001) were significantly reduced, and the drainage volume on postoperative day (POD) 1 (240 mL vs. 200 mL, p < 0.001) and hospitalization costs (¥81084.96 vs. ¥66142.55, p < 0.001) were significantly higher in the RAL group. Subgroup analysis indicated that the incidence of postoperative complications (17.9% vs. 26.7%, p = 0.042) was significantly reduced in the RAL group for overweight and obese patients (body mass index [BMI] ≥24 kg/m2 ), which became insignificant in the BMI < 24 kg/m2 subgroup (31.0% vs. 24.8%, p = 0.307). CONCLUSION: RAL might have potential advantages in terms of lymph node assessment, reducing intraoperative blood loss, and shortening operation duration. Overweight and obese patients could benefit more from RAL because of reduced risk of postoperative complications.

Enhanced Recovery After Surgery Improves Short-term Outcomes in Patients Undergoing Esophagectomy.

BACKGROUND: Enhanced recovery after surgery (ERAS) is a perioperative management protocol used to accelerate patient recovery. This study evaluated its benefits in patients with resectable esophageal cancer. METHODS: This retrospective study compared patients before (January 2013 to December 2016) and after (June 2018 to December 2020) ERAS protocol implementation in our hospital. A propensity score-matched analysis was used to compare short-term surgical outcomes between ERAS and non-ERAS groups. After propensity score matching each group included 243 patients. RESULTS: There were significant differences in hospital length of stay after surgery (7.40 vs 11.17 days, P < .001) and hospitalization cost (¥69380 vs ¥78075, P < .001) between the ERAS and non-ERAS groups. The time to chest tube removal (4.91 vs 7.16 days, P < .001) and first bowel movement (2.87 vs 3.97 days, P < .001) was significantly shorter in the ERAS group. However there was no significant difference in total postoperative complication morbidity (20.2% vs 25.1%, P = .193). The complication of postoperative atelectasis or pneumonia was significantly lower in the ERAS group (P = .003), but there was no significant difference in occurrence of at least grade III complications between the 2 groups (12.3% vs 11.5%, P = .889). CONCLUSIONS: We demonstrated that ERAS could reduce hospital stay, numerical pain scores, and hospitalization costs without increasing postoperative complication and readmission. Furthermore subgroup analyses revealed that ERAS was safe for older people (>70 years old).

The effect of the enhanced recovery after surgery program on lung cancer surgery: a systematic review and meta-analysis.

BACKGROUND: Lung cancer is one of the most common causes of cancer-related death worldwide. The enhanced recovery after surgery (ERAS) program is an effective evidence-based multidisciplinary protocol of perioperative care. However, the roles of ERAS in lung cancer surgery remain unclear. This systematic review and meta-analysis aimed to investigate the short-term impact of the ERAS program on lung resection surgery, especially in relation to postoperative complications. METHODS: A systematic literature search of PubMed, EMBASE, and the Cochrane Library databases until October 2020 was performed to identify the studies that implemented an ERAS program in lung cancer surgery. The studies were selected and subjected to data extraction by 2 reviewers independently, which was followed by quality assessment. A random effects model was used to calculate overall effect sizes. Risk ratio (RR), risk difference (RD), 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. RESULTS: A total of 21 studies with 6,480 patients were included. The meta-analysis indicated that patients in the ERAS group had a significantly reduced risk of postoperative complications (RR =0.64; 95% CI: 0.52 to 0.78) and shortened postoperative length of stay (SMD=-1.58; 95% CI: -2.38 to -0.79) with a significant heterogeneity. Subgroup analysis showed that the risks of pulmonary (RR =0.58; 95% CI: 0.45 to 0.75), cardiovascular (RR =0.73; 95% CI: 0.59 to 0.89), urinary (RR =0.53; 95% CI: 0.32 to 0.88), and surgical complications (RR =0.64; 95% CI: 0.42 to 0.97) were significantly lower in the ERAS group. No significant reduction was found in the in-hospital mortality (RD =0.00; 95% CI: -0.01 to 0.00) and readmission rate (RR =1.00; 95% CI: 0.76 to 1.32). In the qualitative review, most of the evidence reported significantly decreased hospitalization costs in the ERAS group. CONCLUSIONS: The implementation of an ERAS program for surgery of lung cancer can effectively reduce risks of postoperative complications, length of stay, and costs of patients who have undergone lung cancer surgery without compromising their safety.

Platelet Count is Associated with the Rate of Lymph Node Metastasis in Lung Adenocarcinoma.

PURPOSE: Emerging studies have revealed that platelets are involved in tumor metastasis in lung adenocarcinoma (ADC). The solid pathological subtype of lung ADC is associated with metastasis, recurrence, and poor prognosis. However, there is no study exploring the relationship between platelets and different lung pathological subtypes. PATIENTS AND METHODS: The association between platelet counts and lymph node metastasis was analyzed in 852 patients with lung ADC who underwent surgery and lymph node dissection. Multivariate logistic analysis was conducted to identify the risk factors of lymph node metastasis. Then, lymph node metastasis and other factors were analyzed to determine their correlation with platelet count and histological subtype. RESULTS: We found that the platelet count was associated with lymph node metastasis (P = 0.01) in multivariable analysis, independent of tumor size, predominant subtype, visceral pleural invasion, and microvessel invasion. In patients with a platelet count ≥300 × 109/L, the rate of lymph node metastasis was 38.5%, almost twice as high as that in patients with a platelet count <300 × 109/L (23.2%). Additionally, elevated platelet counts, even those within the normal range, were significantly associated with a higher rate of lymph node metastasis. The mean platelet count in patients with solid-predominant histology (269.70 ± 69.38 × 109/L) was significantly higher than that in patients with other histologies (P < 0.001). CONCLUSION: Elevated platelet counts are significantly associated with a higher rate of lymph node metastasis, even if the platelet counts are within the reference range. Platelet counts were significantly higher in patients with solid-predominant histology than in patients with other histologies. In addition, VEGF-C may play an important role in lymphatic metastasis in patients with lung ADC. We hypothesize that antiplatelet therapy may reduce lymph node metastasis in lung ADC patients.