Recent advances in the role of exosomes in liver fibrosis.

BACKGROUND AND AIM: We aim to summarize the current status of research on the role of exosomes in liver fibrosis. METHODS: A review of the relevant literature was performed and the key findings were presented. RESULTS: Most studies focused on the role of exosomes derived from mesenchymal stem cells, other types of stem cells, and liver resident cells including hepatocytes, cholangiocytes, and hepatic stellate cells in liver fibrosis. Exosomes have been reported to play an essential role in the inactivation or activation of hepatic stellate cells through the delivery of non-coding RNAs and proteins. In recent years, this exosome cargo has become a research hotspot. CONCLUSIONS: Recent studies have indicated the potential therapeutic benefit of exosomes in liver fibrosis.

Identification of invasion-metastasis associated MiRNAs in gallbladder cancer by bioinformatics and experimental validation.

BACKGROUND: Recent studies exploring the roles of invasion-metastasis associated miRNAs in gallbladder cancer (GBC) are limited. In the study, we aimed to identify the invasion-metastasis associated miRNAs in GBC by bioinformatics and experimental validation. METHODS: MiRNAs of different expression were identified by comparing GBC tumor samples with different survival from Gene Expression Omnibus database. MiRTarBase was used for identifying the potential target genes of miRNAs. Then, we performed Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. And miRNA-gene and protein-protein interaction (PPI) network were constructed for hub genes evaluation. We further explored and compared miR-642a-3p and miR-145-5p expression in both The Cancer Genome Atlas database and our hospital data. Finally, quantitative real-time PCR, wound healing assay, and Transwell assay were conducted to validate the invasion-metastasis associated miRNAs in GBC. RESULTS: In GSE104165 database, 25 up-regulated and 97 down-regulated miRNAs were detected with significantly different expression in GBC tumor samples. Then, 477 potential target genes were identified from the 2 most up-regulated miRNAs (miR-4430 and miR-642a-3p) and 268 genes from the 2 most down-regulated miRNAs (miR-451a and miR-145-5p). After GO and KEGG analysis, mTOR and PI3K-Akt signaling pathways were found associated with the potential target genes. Based on PPI network, the top 10 highest degree hub nodes were selected for hub genes. Furthermore, the miRNA-hub gene network showed significant miR-642a-3p up-regulation and miR-145-5p down-regulation in both GBC tissues and cell lines. In the experimental validation, miR-145-5p up-regulation and miR-642a-3p down-regulation were confirmed to suppress GBC invasion and metastasis. CONCLUSIONS: MiR-642a-3p and miR-145-5p were identified as invasion-metastasis associated miRNAs via bioinformatics and experimental validation, and both up-regulation of miR-642a-3p and down-regulation of miR-145-5p would be served as novel treatment options for GBC in the future.

Inhibition of AMPK/PFKFB3 mediated glycolysis synergizes with penfluridol to suppress gallbladder cancer growth.

BACKGROUND: Penfluridol (PF) is an FDA-approved antipsychotic drug that has recently been shown to have anticancer activity. However, the anticancer effects and underlying mechanisms of PF are not well-established in gallbladder cancer (GBC). METHODS: The anticancer efficacy of PF on GBC was investigated via a series of cell functions experiments, including cell viability, colony formation, apoptosis assays, and so on. The corresponding signaling changes after PF treatment were explored by western blotting. Then, nude mice were utilized to study and test the anticancer activity of PF in vivo. Besides, glucose consumption and lactic production assays were used to detect the glycolysis alteration. RESULTS: In this study, we discovered that PF greatly inhibited the proliferation and invasion ability of GBC cells (GBCs). The glucose consumption and lactic generation ability of GBCs were dramatically elevated following PF treatment. Additionally, we discovered that inhibiting glycolysis could improve PF's anticancer efficacy. Further studies established that the activation of the AMPK/PFKFB3 signaling pathway medicated glycolysis after PF treatment. We proved mechanistically that inhibition of AMPK/PFKFB3 singling pathway mediated glycolysis was a potential synergetic strategy to improve the anticancer efficacy of PF on GBC. CONCLUSIONS: By inhibiting AMPK, the anticancer effects of PF on GBCs were amplified. As a result, our investigations shed new light on the possibility of repurposing PF as an anticancer drug for GBC, and AMPK inhibition in combination with PF may represent a novel therapeutic strategy for GBC. Video abstract.

Adjuvant transarterial chemoembolization to sorafenib in unresectable hepatocellular carcinoma: A meta-analysis.

BACKGROUND AND AIM: An increasing number of transarterial chemoembolization (TACE) plus sorafenib combination therapy has been applied for unresectable hepatocellular carcinoma (HCC). However, it remains controversial whether combination therapy is superior to sorafenib monotherapy. Therefore, we aimed to perform a meta-analysis to evaluate the efficacy and safety of the combination therapy of TACE plus sorafenib for unresectable HCC. METHODS: This meta-analysis was based on the relative outcomes from a specific search of online databases between January 2008 and November 2019, and subgroup analyses were conducted to identify potential predictive factors. RESULTS: A total of 3868 patients (TACE plus sorafenib vs sorafenib, 1181 vs 2687) were identified from nine studies, including one randomized controlled trial and eight retrospective cohort studies. The pooled results revealed that TACE plus sorafenib combination therapy significantly improves overall survival with the combined hazard ratio 0.74 (95% confidence interval [CI] = 0.66-0.84, P < 0.001), time to progression (hazard ratio = 0.73, 95%CI = 0.65-0.82, P < 0.001), and objective response rate (odds ratio = 2.19, 95% CI = 1.31-3.66, P = 0.003). Subgroup analysis indicated that patients who developed macrovascular invasion achieve significantly great overall survival (P for interaction = 0.001) with combination therapy, in contrast to nonmacrovascular invasion patients. In addition, no significant differences in adverse events were observed. CONCLUSION: This meta-analysis demonstrated that TACE plus sorafenib combination therapy is superior to sorafenib monotherapy and should be recommended as an optimal treatment choice for unresectable HCC.

Role of cellular, molecular and tumor microenvironment in hepatocellular carcinoma: Possible targets and future directions in the regorafenib era.

Hepatocellular carcinoma (HCC) remains as one of the major causes of cancer-related mortality, despite the recent development of new therapeutic options. Regorafenib, an oral multikinase inhibitor, is the first systemic therapy that has a survival benefit for patients with advanced HCC that have a poor response to sorafenib. Even though regorafenib has been approved by the FDA, the clinical trial for regorafenib treatment does not show significant improvement in overall survival. The impaired efficacy of regorafenib caused by various resistance mechanisms, including epithelial-mesenchymal transitions, inflammation, angiogenesis, hypoxia, oxidative stress, fibrosis and autophagy, still needs to be resolved. In this review, we provide insight on regorafenib microenvironmental, molecular and cellular mechanisms and interactions in HCC treatment. The aim of this review is to help physicians select patients that would obtain the maximal benefits from regorafenib in HCC therapy.

End-to-end intestinal anastomosis using a novel biodegradable stent for laparoscopic colonic surgery: a multicenter study.

PURPOSE: Our animal studies have demonstrated the safety and feasibility of end-to-end intestinal anastomosis using a stent for laparoscopic colonic surgery. Therefore, we designed a non-inferiority trial to investigate the outcomes of stent anastomosis (SA) vs. those of conventional hand-sewn anastomosis (CA). METHODS: A multicenter randomized controlled trial was conducted between December, 2016 and April, 2018. The primary outcome was the healing condition of the anastomoses, evaluated by endoscopy 6 months postoperatively. The secondary outcomes were the anastomotic completion time, anastomotic leak, intestinal obstruction, peritoneal effusion, and bleeding. Quality of life (QOL) was evaluated by questionnaires. RESULTS: The subjects of this study were 60 patients, randomly divided into a SA group (n = 30) and a CA group (n = 30). There were no differences in anastomotic healing conditions (P = 1.00). The stent procedure was associated with a significantly shorter anastomosis time than the hand-sewn anastomosis (13.517 ± 4.281 vs. 20.333 ± 2.998 min, respectively; P < 0.001). There were no significant differences in anastomotic leakage, intestinal obstruction, peritoneal effusion, or bleeding between the groups. Questionnaires revealed almost no discrepancy between baseline QOL scores and those assessed 2, 4, 8, 12, and 24 weeks postoperatively in either group. CONCLUSIONS: Intestinal anastomosis with a stent is a non-inferior strategy for laparoscopic colonic surgery, which requires less time for the anastomosis.

Simulation training of laparoscopic biliary-enteric anastomosis with a three-dimensional-printed model leads to better skill transfer: a randomized controlled trial.

AIM: A new simulation model and training curriculum for laparoscopic bilioenteric anastomosis has been developed. Currently, this concept lacks evidence for the transfer of skills from simulation to clinical settings. This study was conducted to determine whether training with a three-dimensional (3D) bilioenteric anastomosis model result in greater transfer of skills than traditional training methods involving video observation and a general suture model. METHODS: Fifteen general surgeons with no prior experience in laparoscopic biliary-enteric anastomosis were included in this study and randomised into three training groups: video observation only, practice using a general suture model, and practice using a 3D-printed biliary-enteric anastomosis model. Following five training sessions, each surgeon was asked to perform a laparoscopic biliary-enteric anastomosis procedure on an isolated swine organ model. The operative time and performance scores of the procedure were recorded and compared among the three training groups. RESULTS: The operation time in the 3D-printed model group was significantly shorter than the suture and video observation groups ( P =0.040). Furthermore, the performance score of the 3D-printed model group was significantly higher than those of the suture and video observation groups ( P =0.001). Finally, the goal score for laparoscopic biliary-enteric anastomosis in the isolated swine organ model was significantly higher in the 3D model group than in the suture and video observation groups ( P =0.004). CONCLUSIONS: The utilisation of a novel 3D-printed model for simulation training in laparoscopic biliary-enteric anastomosis facilitates improved skill acquisition and transferability to an animal setting compared with traditional training techniques.

Landslide susceptibility assessment based on frequency ratio and semi-supervised heterogeneous ensemble learning model.

Epistemic uncertainty in data-driven landslide susceptibility assessment often tends to be increased by the limited accuracy of an individual model, as well as uncertainties associated with the selection of non-landslide samples. To address these issues, this paper centers on the landslide disaster in Ji'an City, China, and proposes a heterogeneous ensemble learning method incorporating frequency ratio (FR) and semi-supervised sample expansion. Based on the superimposed results of 12 environmental factor frequency ratios (FFR), non-landslide samples were selected and input into light gradient boosting machine (LightGBM), random forest (RF), and convolutional neural network (CNN) models for prediction along with historical landslide samples. The predicted probability values are integrated by four heterogeneous ensemble strategies to expand samples from high-confidence results. The model's performance is evaluated using the area under the receiver operating characteristic curve (AUC), partition frequency ratio (PFR), and other verification methods. The results demonstrate that the negative sample based on FFR sampling is more accurate than the random sampling method, and the FR-SSELR model based on frequency ratio sampling and semi-supervised ensemble strategy exhibits the highest performance (AUC = 0.971, ACC = 0.941). A more reasonable landslide susceptibility map was drawn based on this model, with the lowest percentage of landslides in the low and very low susceptibility zones (sum of PFR = 0.194), as well as the highest percentage of landslides in the high and very high susceptibility zones (sum of PFR = 6.800). Furthermore, the FR-SSELR model improved economic benefits by 3.82-14.2%, offering valuable guidance for decision-making regarding landslide management and the sustainability of Ji'an City.

What eliminates the chance for cure: a multi-center evaluation on 10-year follow-up of gallbladder cancer after surgical resection.

Curative resection stands as the sole potential cure for gallbladder cancer (GBC); nevertheless, a dearth of knowledge persists regarding long-term follow-up data and prognostic factors that hinder achieving a cure post-surgery. A retrospective cohort study was conducted by analyzing pathologically confirmed initial resections for GBC between 2000 and 2013 across three Chinese medical centers. The concept of observed cure refers to a 10-year survival period devoid of any disease recurrence. Employing a semiparametric proportional hazards mixture cure model enabled the identification of clinicopathological factors impeding a cure for GBC post-surgery. In our current study, a total of 331 patients were included, with a follow-up period exceeding a decade. The median overall survival (OS) was recorded at 31.6 months, with 39 patients (11.78%) achieving a 10-year OS, classified as 10-year survivors. Within this subset, 36 patients reached a 10-year relapse-free survival, denoting cure, and yielding an observed cure rate of 10.88%. Notably, factors such as combined surgical resection involving invaded organs, positive lymph node metastasis, and R1 resection (below 1%) were identified as virtually precluding a cure. Additionally, patients with T3-4 stage, hepatic invasion, advanced AJCC stage or poor tumor differentiation exhibited a low likelihood of achieving cure (below 5%). The discovery of these prognostic factors holds significant value in tailoring individualized treatment strategies and enhancing clinical decision-making processes.

Association between type 2 diabetes, alcohol intake frequency, age at menarche, and gallbladder cancer: a two-sample Mendelian randomization study.

Background: Gallbladder cancer (GBC) is a rare malignancy of the digestive tract, characterized by a remarkably poor prognosis. Currently, there is a controversy on the relationship between type 2 diabetes (T2D) and GBC. Additionally, no definitive conclusions were established regarding the causal relationships between alcohol intake frequency (AIF), age at menarche (AAM) and GBC. The objective of this study was to elucidate the causal association between T2D, AIF, AAM, and GBC. Methods: Single-nucleotide polymorphisms (SNPs) associated with exposures and outcomes were sourced from the Integrative Epidemiology Unit (IEU) Open Genome-Wide Association Study (GWAS) database. Specifically, the data of GBC comprised 907 East Asians (pathological results of all cases were registered into Biobank Japan) and 425,707 SNPs; T2D comprised 655,666 Europeans with 5,030,727 SNPs; AIF comprised 462,346 Europeans and 9,851,867 SNPs; AAM comprised 243,944 Europeans and 9,851,867 SNPs. The measurement of exposure traits is collected uniformly from the UK Biobank (UKB) database and presented in the form of standard deviation (SD) or the logarithmic form of the odds ratio (logOR). We employed a two-sample Mendelian randomization (MR) analysis to discern the causalities between T2D, AIF, AAM, and GBC. Sensitivity analyses were conducted to identify and address potential heterogeneity, horizontal pleiotropy, and outliers. Results: Our findings indicated that T2D reduced GBC risk [odds ratio (OR) =0.044; 95% confidence interval (CI): 0.004-0.55; P=0.015, inverse variance-weighted (IVW)]. However, no causal relationship was observed between AIF (OR =0.158; 95% CI: 5.33E-05 to 466.84; P=0.65, IVW), AAM (OR =0.19; 95% CI: 0.0003-140.34; P=0.62, IVW), and GBC. Sensitivity analysis revealed no evidence of horizontal pleiotropy, heterogeneity, or outliers, suggesting the robustness and reliability of our conclusions. Conclusions: T2D emerged as a potentially protective factor against GBC, whereas neither AIF nor AAM demonstrated a causal relationship with GBC risk. Regulation of glucose metabolism may be one of the methods for preventing GBC.

Lipid metabolism in tumor-infiltrating regulatory T cells: perspective to precision immunotherapy.

Regulatory T cells (Tregs) are essential to the negative regulation of the immune system, as they avoid excessive inflammation and mediate tumor development. The abundance of Tregs in tumor tissues suggests that Tregs may be eliminated or functionally inhibited to stimulate antitumor immunity. However, immunotherapy targeting Tregs has been severely hampered by autoimmune diseases due to the systemic elimination of Tregs. Recently, emerging studies have shown that metabolic regulation can specifically target tumor-infiltrating immune cells, and lipid accumulation in TME is associated with immunosuppression. Nevertheless, how Tregs actively regulate metabolic reprogramming to outcompete effector T cells (Teffs), and how lipid metabolic reprogramming contributes to the immunomodulatory capacity of Tregs have not been fully discussed. This review will discuss the physiological processes by which lipid accumulation confers a metabolic advantage to tumor-infiltrating Tregs (TI-Tregs) and amplifies their immunosuppressive functions. Furthermore, we will provide a summary of the driving effects of various metabolic regulators on the metabolic reprogramming of Tregs. Finally, we propose that targeting the lipid metabolism of TI-Tregs could be efficacious either alone or in conjunction with immune checkpoint therapy.

Adavosertib-encapsulated metal-organic frameworks for p53-mutated gallbladder cancer treatment via synthetic lethality.

Adavosertib (ADA) is a WEE1 inhibitor that exhibits a synthetic lethal effect on p53-mutated gallbladder cancer (GBC). However, drug resistance due to DNA damage response compensation pathways and high toxicity limits further applications. Herein, estrone-targeted ADA-encapsulated metal-organic frameworks (ADA@MOF-EPL) for GBC synthetic lethal treatment by inducing conditional factors are developed. The high expression of estrogen receptors in GBC enables ADA@MOF-EPL to quickly enter and accumulate near the cell nucleus through estrone-mediated endocytosis and release ADA to inhibit WEE1 upon entering the acidic tumor microenvironment. Ultrasound irradiation induces ADA@MOF-EPL to generate reactive oxygen species (ROS), which leads to a further increase in DNA damage, resulting in a higher sensitivity of p53-mutated cancer cells to WEE1 inhibitor and promoting cell death via conditional synthetic lethality. The conditional factor induced by ADA@MOF-EPL further enhances the antitumor efficacy while significantly reducing systemic toxicity. Moreover, ADA@MOF-EPL demonstrates similar antitumor abilities in other p53-mutated solid tumors, revealing its potential as a broad-spectrum antitumor drug.

Clinical utility of resected pancreatic volume ratio calculation for predicting postoperative new-onset diabetes mellitus after distal pancreatectomy-a propensity-matched analysis.

Background: Limited literature is available on new-onset diabetes mellitus (NODM) after distal pancreatectomy. This study aimed to investigate the correlation between surgery-related factors and the incidence of NODM after distal pancreatectomy. Methods: Patients were divided into the NODM-positive or NODM-negative group according to the diagnosis of NODM. After propensity score matching, the correlation between operation-related factors and the incidence of NODM was analyzed. The diagnostic threshold for predicting NODM was determined using the receiver operating characteristic (ROC) curve and the Youden index. Results: No significant correlation was observed between the NODM incidence after distal pancreatectomy and operative blood loss, spleen preservation, surgical method (open or laparoscopy), postoperative ALB and HB (first day after surgery), and postoperative pathology. However, a significant correlation was found between the NODM incidence and the postoperative pancreatic volume or the resected pancreatic volume ratio. Resected pancreatic volume ratio was identified as a predictive risk factor for NODM. Youden index of the ROC curve was 0.548, with a cut off value of 32.05% for resected pancreatic volume ratio. The sensitivity and specificity of the cut off values were 0.952 and 0.595, respectively. Conclusions: This study demonstrated that the volume ratio of pancreatic resection is a risk factor for the incidence of NODM after distal pancreatectomy. This can be used to predict the incidence of NODM and may have further clinical applications.

Erratum to "Research trends in cholangiocarcinoma treatments during the last 3 decades" [Heliyon 9(7) (July 2023) e17100].

[This corrects the article DOI: 10.1016/j.heliyon.2023.e17100.].

Debris flow susceptibility assessment based on information value and machine learning coupling method: from the perspective of sustainable development.

Accurately assessing the susceptibility of debris flow disasters is of great significance for reducing the cost of disaster prevention and mitigation, as well as disaster losses. Machine learning (ML) models have been widely used in the susceptibility assessment of debris flow disasters. However, these models often have randomness in the selection of non-disaster data, which can lead to redundant information and poor applicability and accuracy of susceptibility evaluation results. To address this issue, this paper focuses on debris flow disasters in Yongji County, Jilin Province, China; optimizes the sampling method of non-disaster datasets in machine learning susceptibility assessment; and proposes a susceptibility prediction model that couples information value (IV) with artificial neural network (ANN) and logistic regression (LR) models. A debris flow disaster susceptibility distribution map with higher accuracy was drawn based on this model. The model's performance is evaluated using the area under the receiver operating characteristic curve (AUC), information gain ratio (IGR), and typical disaster point verification methods. The results show that the rainfall and topography were found to be decisive factors in the occurrence of debris flow disasters, and the IV-ANN model established in this study had the highest accuracy (AUC = 0.968). Compared to traditional machine learning models, the coupling model produced an increase in economic benefit of about 25% while reducing the average disaster prevention and control investment cost by about 8%. Based on model's susceptibility map, this paper proposes practical disaster prevention and control suggestions that promote sustainable development in the region, such as establishing monitoring systems and information platforms to aid disaster management.

Research trends in cholangiocarcinoma treatments during the last 3 decades.

Background: Over the past 30 years, numerous studies have focused on the treatment of cholangiocarcinoma (CCA), and these treatments have greatly evolved. Objectives: To better understand the research trends, we evaluated the most influential publications and attempted to identify their characteristics using bibliometric methods. Methods: The most influential publications were identified from the Clarivate Analytics Web of Science Core Collection database. The general characteristics of included papers were identified, and the research trends were explored via the bibliometric method. Results: The average total number of citations for of the listed publications were 312 (range from 165 to 1922). The highest number of papers were published during period II (2001-2010, n = 50), followed by period III (2011-2020, n = 28), and period I (1991-2000, n = 22). The United States and Germany have made remarkable achievements in this field. Institutionally, Mayo Clinic and Memorial Sloan-Kettering Cancer Center were the leading institutions, with Blumgart and Zhu from the United States being the most influential authors. Close collaboration was established between the leading countries, institutions, and authors. The Annals of Surgery contributed the most to the papers with the highest total number of citations. Surgery predominated during period I (n = 14, 63.6%), with a gradual decline occurring during periods II (n = 19, 41.3%, P = 0.085) and period III (n = 3, 9.4%, P = 0.002). Contrastingly, the number of publications related to systemic therapy has increased significantly since period II and peaked in period III. Conclusions: Surgery remains the most important treatment for CCA. However systemic therapy has become a research and clinical application hotspot. These findings will contribute to the translation of treatments for CCA and provide researchers with relevant research directions.

Wedge resection versus segment IVb and V resection of the liver for T2 gallbladder cancer: a systematic review and meta-analysis.

Objectives: Although guidelines recommend extended cholecystectomy for T2 gallbladder cancer (GBC), the optimal hepatectomy strategy remains controversial. The study aims to compare the prognosis of T2 GBC patients who underwent wedge resection (WR) versus segment IVb and V resection (SR) of the liver. Methods: A specific search of online databases was performed from May 2001 to February 2023. The postoperative efficacy outcomes were synthesized and meta-analyses were conducted. Results: A total of 9 studies involving 2,086 (SR = 627, WR = 1,459) patients were included in the study. The primary outcomes included disease-free survival (DFS) and overall survival (OS). For DFS, the 1-year DFS was statistically higher in patients undergoing SR than WR [risk ratio (RR) = 1.07, 95% confidence interval (CI) = 1.02-1.13, P = 0.007]. The 3-year DFS (P = 0.95), 5-year DFS (P = 0.77), and hazard ratio (HR) of DFS (P = 0.72) were similar between the two groups. However, the 3-year OS was significantly lower in patients who underwent SR than WR [RR = 0.90, 95% CI = 0.82-0.99, P = 0.03]. Moreover, SR had a higher hazard HR of OS [HR = 1.33, 95% CI = 1.01-1.75, P = 0.04]. No significant difference was found in 1-year (P = 0.32) and 5-year (P = 0.9) OS. For secondary outcomes, patients who received SR tended to develop postoperative complications (POC) [RR = 1.90, 95% CI = 1.00-3.60, P = 0.05]. In addition, no significant differences in intrahepatic recurrence (P = 0.12) were observed. Conclusions: In conclusion, SR can improve the prognosis of T2 GBC patients in DFS. In contrast to WR, the high HR and complications associated with SR cannot be neglected. Therefore, surgeons should evaluate the condition of the patients and take their surgical skills into account when selecting SR. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier, CRD42022362974.

Laparoscopic vs open radical resection in management of gallbladder carcinoma: A systematic review and meta-analysis.

BACKGROUND: Radical resection offers the only hope for the long-term survival of patients with gallbladder carcinoma (GBC) above the T1b stage. However, whether it should be performed under laparoscopy for GBC is still controversial. AIM: To compare laparoscopic radical resection (LRR) with traditional open radical resection (ORR) in managing GBC. METHODS: A comprehensive search of online databases, including Medline (PubMed), Cochrane Library, and Web of Science, was conducted to identify comparative studies involving LRR and ORR in GBCs till March 2023. A meta-analysis was subsequently performed. RESULTS: A total of 18 retrospective studies were identified. In the long-term prognosis, the LRR group was comparable with the ORR group in terms of overall survival and tumor-free survival (TFS). LRR showed superiority in terms of TFS in the T2/tumor-node-metastasis (TNM) Ⅱ stage subgroup vs the ORR group (P = 0.04). In the short-term prognosis, the LRR group had superiority over the ORR group in the postoperative length of stay (POLS) (P < 0.001). The sensitivity analysis showed that all pooled results were robust. CONCLUSION: The meta-analysis results show that LRR is not inferior to ORR in all measured outcomes and is even superior in the TFS of patients with stage T2/TNM Ⅱ disease and POLS. Surgeons with sufficient laparoscopic experience can perform LRR as an alternative surgical strategy to ORR.