Neoadjuvant chemoradiotherapy, chemotherapy, and radiotherapy do not significantly increase the incidence of anastomotic leakage after esophageal cancer surgery: a meta-analysis.

This study investigated whether neoadjuvant therapies, such as neoadjuvant chemoradiotherapy (NCRT), neoadjuvant chemotherapy (NCT), and neoadjuvant radiotherapy (NRT), would affect the incidence of anastomotic leakage (AL) after esophageal cancer surgery. Published randomized controlled trials were reviewed, and the incidence of AL after esophageal cancer was statistically analyzed in each study. Meta-analysis was performed using Revman and Stata software. A total of 17 randomized controlled trials with 2874 patients were reviewed showing that, in general, preoperative neoadjuvant therapies were not significant risk factors for AL after esophageal cancer surgery (relative risk [RR] = 0.82, 95% CI = 0.64-1.04). NCRT and NRT did not significantly increase the risk of postoperative AL in patients with esophageal cancer (RR = 0.81, 95% CI = 0.63-1.05; RR = 0.64, 95% CI = 0.14-2.97, respectively). Moreover, NCT has no significant correlation with the occurrence of AL (RR = 1.01, 95% CI = 0.57-1.80). NCRT, NCT, and NRT do not significantly increase the incidence of gastroesophageal AL after esophageal cancer surgery.

Minimally invasive versus open esophagectomy after neoadjuvant therapy for esophageal cancer: a meta-analysis.

OBJECTIVES: Neoadjuvant therapy and minimally invasive esophagectomy (MIE) are widely used in the comprehensive treatment of esophageal cancer. This study aimed to investigate the advantages of MIE for esophageal cancer after neoadjuvant therapy. METHODS: Published clinical studies were reviewed and survival data and safety data were extracted. We compared the long-term survival and safety of MIE versus open esophagectomy after neoadjuvant surgery in a series of meta-analyses. RESULTS: 6 retrospective studies were included. Overall, MIE could significantly improve the overall survival of patients with esophageal cancer after neoadjuvant therapy compared with open esophagectomy [hazard ratio (HR) = 0.86, 95% confidence interval (CI) (0.75, 0.98)]. Compared with open esophagectomy, MIE could significantly reduce intraoperative blood loss and operative time [mean difference (MD) = -40.28.78, 95% CI (- 62.98, - 17.58); MD = -28.78, 95% CI (- 42.48, - 15.07), respectively]. There was no significant difference in 30-day and 90-day mortality between MIE and open esophagectomy [odds ratio (OR) = 0.42, 95% CI (0.09, 2.01); OR 0.80, 95% CI (0.25, 2.60), respectively]. MIE could not significantly reduce the incidence of anastomotic leakage, recurrent laryngeal nerve palsy and chylothorax [OR 0.70, 95% CI (0.37, 1.32); OR 1.43, 95% CI (0.33, 6.25); HR = 1.79, 95% CI (0.67, 4.75), respectively], but the incidence of pneumonia was significantly reduced [HR = 0.43, 95% CI (0.22, 0.82)]. In addition, the length of hospital stay and the incidence of total complications were significantly reduced after MIE [MD = -2.61, 95% CI (- 3.10, - 2.12); HR = 0.66, 95% CI (0.45, 0.98), respectively]. CONCLUSION: MIE after neoadjuvant therapy is effective and safe. Compared with open esophagectomy, MIE can improve the long-term survival and reduce the incidence of postoperative complications of esophageal cancer patients.

Efficacy and safety of immune checkpoint inhibitors versus chemotherapy in the second-line treatment of advanced esophageal squamous cell carcinoma: a meta-analysis and systematic review.

Background: Esophageal cancer (EC) is the seventh most common cancer in the world, with 604,000 new cases diagnosed each year. Immune checkpoint inhibitors (ICIs) including programmed death ligand-1 (PD-L1) inhibitors have demonstrated a considerable survival advantage over chemotherapy in numerous randomized controlled trials (RCTs), particularly in patients with advanced esophageal squamous cell carcinoma (ESCC). In this analysis, we aimed to demonstrate that ICIs are more safe and effective than chemotherapy when used as a second-line treatment for advanced ESCC. Methods: Publications on the safety and efficiency of ICIs in advanced ESCC that were available prior to February 2022 were searched in the Cochrane Library, Embase, and PubMed databases. Studies with missing data were eliminated, and studies that compared the treatments between the immunotherapy group and chemotherapy group were included. Statistical analysis was carried out using RevMan 5.3, and risk and quality were evaluated with relevant evaluation tools. Results: Five studies met the inclusion criteria were selected, involving 1,970 patients with advanced ESCC. We compared chemotherapy and immunotherapy in the second-line treatment of advanced ESCC. ICIs considerably enhanced both the objective response rate (P=0.007) and overall survival (OS; P=0.001). However, the effect of ICIs on progression-free survival (PFS) was not significant (P=0.43). ICIs presented fewer grade 3-5 treatment-related adverse events (TRAEs), and there was also a suggested linkage between both PD-L1 expression and the effectiveness of the therapeutic intervention. Conclusions: For patients with advanced ESCC, ICIs are more effective and safer than chemotherapy, and thus have a higher treatment value.

Prognosis and surgical outcomes of the total thymectomy versus thymomectomy in non-myasthenic patients with early-stage thymoma: A systematic review and meta-analysis.

Whether thymectomy (TM) or thymomectomy (TMM) is better for non-myasthenic patients with early-stage thymoma. We conducted a meta-analysis to compare the clinical outcomes and prognoses of non-myasthenic patients with early-stage thymoma treated using thymectomy versus thymomectomy. PubMed, Embase, Cochrane Library and CNKI databases were systematically searched for relevant studies on the surgical treatment (TM and TMM) of non-myasthenic patients with early-stage thymoma published before March 2022. The Newcastle-Ottawa scale was used to evaluate the quality of the studies, and the data were analyzed using RevMan version 5.30. Fixed or random effect models were used for the meta-analysis depending on heterogeneity. Subgroup analyses were performed to compare short-term perioperative and long-term tumor outcomes. A total of 15 eligible studies, including 3023 patients, were identified in the electronic databases. Our analysis indicated that TMM patients might benefit from a shorter duration of surgery (p = 0.006), lower blood loss volume (p < 0.001), less postoperative drainage (p = 0.03), and a shorter hospital stay (p = 0.009). There were no significant differences in the overall survival rate (p = 0.47) or disease-free survival rate (p = 0.66) between the two surgery treatment groups. Likewise, TM and TMM were similar in the administration of adjuvant therapy (p = 0.29), resection completeness (p = 0.38), and postoperative thymoma recurrence (p = 0.99). Our study revealed that TMM might be a more appropriate option in treating non-myasthenic patients with early-stage thymoma.

Factors influencing surgical choice and anxiety in patients with pulmonary nodules smaller than 8 mm.

Background: The detection of pulmonary nodules significantly impacts the lives and mental health of patients. Although the 2020 National Comprehensive Cancer Network (NCCN) guidelines recommend scheduled surveillance for nodules ≤8 mm, patients often opt to have their nodules surgically removed. Methods: A cross-sectional questionnaire was administered to patients with small pulmonary nodules who presented to a local grade 3 hospital with small pulmonary nodules and decided to receive surgery versus prescribed monitoring. The questionnaire included four aspects: (I) patient characteristics; (II) nodule-specific knowledge; (III) doctor-patient communication; and (IV) nodular-specific distress. Nodular-specific distress was measured by the Impact of Event Scale-Revised (IES-R). Results: A total of 234 (69%) patients responded to the survey and were included in the final analysis. Poor performance in activities of daily living (ADLs), the presence of solid nodules, multifocal disease, and a family history of lung cancer were significantly associated with reported anxiety. Most notably, facilitating patient choice for surgery was the computed tomography (CT) scan results, with reference to lung nodule size and number of nodules, where concerns related to lung nodule, cancer risk, and fear of surgery or death had a significant psychological impact on patients. Conclusions: In this cohort of patients who elected to have their small pulmonary nodules surgically removed, we identified key factors underlying their anxiety toward guideline recommended surveillance. Our findings will be useful for clinicians when discussing treatment options with their patients.

The role of miR-145-5p in esophageal squamous cell carcinoma tumor-associated macrophages and selection of immunochemotherapy.

Background: The impact of miR-145-5p in immune infiltration and the potential application in esophageal squamous cell carcinoma (ESCC) immunochemotherapy remains unknown. Methods: Transcriptomic data for ESCC tissues and normal tissues and clinical materials of patients with ESCC were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. The differences in mRNA levels in cancer tissues and noncancerous tissues were analyzed, and we subsequently investigated the association between miR-145-5p expression and the key parameters of ESCC progression and prognosis. Additionally, cytological experiments were performed to evaluate the biological functions of miR-145-5p. Pathways potentially affected by miR-145-5p were analyzed by Gene Set Enrichment Analysis (GSEA) and REACTOME. We also analyzed the function of miR-145-5p in immune infiltration through the TIMER2 (Tumor Immune Estimation Resource) database. Results: The analysis of gene chip data from the TCGA database and GEO database (including GSE13937 and GSE43732) showed that the expression of miR-145-5p is downregulated in ESCC (P<0.05) and that patients with high miR-145-5p levels had lower survival rates (P<0.05). The expression of miR-145-5p was significantly correlated with the disease-free survival (DFS) rate (P<0.05) and M stage (P<0.05) in the TCGA database and was significantly correlated with the T stage (P<0.05) and TNM stage (P<0.05) in the GSE13937 database. Functional experiments showed that miR-145-5p attenuated proliferation (P<0.05), migration (P<0.01) and invasion (P<0.01) in the Eca109 cell line. Both GSEA gene enrichment and REACTOME gene enrichment revealed that miR-145-5p was associated with tumor signaling pathways and immune signaling pathways. Immune infiltration analysis revealed that the expression level of miR-145-5p was significantly correlated with the infiltration level of macrophages (P<0.05) and was positively correlated with the level of gene markers of M2 macrophages and tumor-associated macrophages (P<0.05). Conclusions: MiR-145-5p acts as a tumor suppressor microRNA in ESCC and is an important noncoding RNA in the high M2-like tumor-associated macrophage infiltration of ESCC. Assessing the miR-145-5p level in ESCC samples has translational meaning, which help illustrate the immune infiltration status, predict the prognostic outcome, and select the type of immunochemotherapy.

A single-arm, multicenter, phase II clinical study of tislelizumab plus albumin-bound paclitaxel/cisplatin as neoadjuvant therapy for borderline resectable esophageal squamous cell carcinoma.

Background: Esophageal cancer responds poorly to conventional radiotherapy, chemotherapy, and/or surgery. Immunotherapy works by boosting the body's immune system, and preoperative immunotherapy combined with chemotherapy may increase the survival rate of patients with esophageal cancer. Here we further explore immunotherapy's role in treating borderline resectable (BR) esophageal squamous cell carcinoma (ESCC) by combining immunotherapy with chemotherapy. Methods: In this multicenter, randomized controlled study of preoperative immunotherapy plus chemotherapy for BR ESCC, immunotherapy plus chemotherapy [i.e., tislelizumab plus albumin-bound paclitaxel (ABP)/cisplatin] will be given according to the inclusion and exclusion criteria. Patients are to be observed and recorded for various indicators, the follow-up visits are standardized, and a database is to be established for the statistical analysis, with an attempt to clarify the value of preoperative immunotherapy plus chemotherapy in improving the survival of patients with BR ESCC. The primary endpoints are disease-free survival (DFS), major pathologic response (MPR), and pathologic complete response (pCR). The secondary endpoints include the objective response rate (ORR) and overall survival (OS) in subjects with PD-L1 expression levels of <1%, ≥1%, ≥20%, and ≥50%. Discussion: The role of preoperative concurrent immunotherapy plus chemotherapy in improving the survival rates of patients with BR ESCC will be explored in this study. Given that the 5-year survival rate of BR ESCC is 10%, we hope that a reasonable immunotherapy plus chemotherapy regimen with higher efficacy and lower toxicity will further increase the pCR. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2100051514.

Prognosis of patients with esophageal squamous cell carcinoma undergoing surgery versus no surgery after neoadjuvant chemoradiotherapy: a retrospective cohort study.

Background: Esophageal surgery is an invasive surgical method with high surgical risk, and seriously affects postoperative quality of life. This study compared the prognosis of patients with locally advanced esophageal squamous cell carcinoma (ESCC) treated with neoadjuvant chemoradiotherapy (Neo-CRT) plus surgery and Neo-CRT alone, in order to explore the necessity of continuing operation after Neo-CRT. Methods: We retrospectively analyzed 223 patients who received Neo-CRT in Taizhou Hospital Affiliated to Wenzhou Medical University from June 2007 to December 2014. According to the treatment, the patients were divided into Neo-CRT plus surgery group (operation group, n=185) and single Neo-CRT group (non-operation group, n=38). Patients in both groups were followed up for a long time until death or deadline. The overall survival (OS), adverse reactions, recurrence and death results of the two groups were evaluated. The risk factors of poor prognosis were analyzed. Results: The two groups were comparable. The median follow-up time was 23.5 months in non-operation group and 112.9 months in operation group. The 1-year survival rate, 2-year survival rate and 5-year survival rate in non-operation group were 69.9%, 47.7% and 31.8%, respectively. The rates in operation group were 94.0%, 79.3% and 65.0%, respectively. The incidence of low hemoglobin was 73.7% (non-operation group) and 53.0% (operation group). The infection rates were 15.8% and 2.7%, respectively. There was no significant difference in the incidence of leukopenia, neutropenia and thrombocytopenia between the two groups. Multivariate analysis showed that recurrence and treatment were independent risk factors affecting the prognosis of patients. Conclusions: To sum up, no matter in terms of recurrence rate or OS rate, the prognosis of patients in the operation group was better than that in the non-operation group. Therefore, Neo-CRT combined with esophagectomy is recommended for locally advanced ESCC with acceptable surgical risk.

Efficacy and Benefit of Postoperative Chemotherapy in Micropapillray or Solid Predominant Pattern in Stage IB Lung Adenocarcinoma: A Systematic Review and Meta-Analysis.

Background: The benefit of postoperative chemotherapy remains controversial for patients with either a micropapillary or solid pattern in stage IB non-small cell lung cancer. This study is designed to explore the significance of postoperative chemotherapy in patients with either a micropapillary or solid pattern in stage IB lung adenocarcinoma. Method: To conduct the meta-analysis, PubMed, Cochrane Library, Embase and Medline were used to collect literature on long-term follow-up studies published before March, 2021, involving postoperative chemotherapy for patients with both a micropapillary or solid pattern in stage IB lung adenocarcinoma as compared to non-postoperative chemotherapy. Survival data was extracted from the literature, including the overall survival and disease-free survival. Based on overall survival and disease-free survival, hazard ratios and their 95% of confidence intervals were applied to assess the prognostic effect of postoperative chemotherapy. Review Manager software was used to merge the effect size for the meta-analysis. Result: In total, 6 papers with 956 patients were included. In terms of the prognosis of patients suffering from lung cancer when receiving postoperative chemotherapy, this study comprehensively reviews and evaluates the available evidence of micropapillary or solid patterns. After excluding the heterogeneity between the studies, we found that the pooled results from 6 studies report that postoperative chemotherapy was associated with a better overall survival rate when compared with non-postoperative chemotherapy (hazard ratio = 0.58, 95% confidence interval, 0.44-0.77; P = 0.0002). Postoperative chemotherapy also significantly improved the disease-free survival in patients with either a micropapillary or a solid pattern in stage IB lung adenocarcinoma (postoperative chemotherapy vs. non-postoperative chemotherapy, hazard ratio = 0.51, 95% confidence interval, 0.40-0.64; P < 0.001). However, a subgroup analysis showed that compared with non-postoperative chemotherapy, tumor size was unrelated to the prognosis of patients in stage IB undergoing postoperative chemotherapy (hazard ratio = 0.98, 95% confidence interval, 0.94-1.02; P = 0.27). Conclusion: Postoperative chemotherapy results in a better long-term survival rate for patients with either a solid or a micropapillary pattern in stage IB lung adenocarcinoma. Multi-center, prospective, clinical trials are needed to validate our findings.

Efficacy and Safety of Neoadjuvant Targeted Therapy vs. Neoadjuvant Chemotherapy for Stage IIIA EGFR-Mutant Non-small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

Purpose: The role of targeted therapy in the neoadjuvant field of stage IIIA epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) is still controversial. We sought to evaluate the efficacy and safety of neoadjuvant targeted therapy (NTT) with neoadjuvant chemotherapy (NCT) used as a benchmark comparator. Methods: A systematic search was conducted in four databases (Pubmed, Cochrane Library, Embase, CNKI) for eligible studies on NTT published before October 2020. The primary endpoints were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and grade 3/4 adverse events (AEs). Statistical analysis and bias assessment were performed by RevMan 5.3. Results: A total of 319 patients, including 3 randomized controlled trials and 2 non-randomized controlled trials, were included in the meta-analysis. Perform the second subgroup analysis after excluding 2 non-randomized controlled trials. The meta-analysis reveals that, for EGFR mutation-positive stage IIIA NSCLC patients, compared with NCT, NTT can significantly increase ORR (relative risk [RR]:1.70, 95% confidence interval [CI]:1.35-2.15; subgroup-RR:1.56, 95% CI 1.23-2.0) and significantly reduce grade 3/4 AEs (RR:0.5, 95% CI 0.34-0.75; subgroup-RR: 0.53, 95% CI 0.26-1.08). The OS of the NTT arm is slightly higher, but the difference is not significant (hazards ratio [HR]: 0.74, 95% CI: 0.43-1.27; subgroup-HR: 0.64 95% CI 0.40-1.03). No difference in PFS was found (HR: 0.81, 95% CI 0.27-2.44). Conclusion: In neoadjuvant setting, targeted therapy has a definitive effect on patients with EGFR mutation-positive stage IIIA NSCLC and is even better than chemotherapy in terms of toxicity and tumor response rate. Systematic Review Registration: PROSPERO, identifier CRD42021221136.