Imaging Evaluation of Peritoneal Metastasis: Current and Promising Techniques.

Early diagnosis, accurate assessment, and localization of peritoneal metastasis (PM) are essential for the selection of appropriate treatments and surgical guidance. However, available imaging modalities (computed tomography [CT], conventional magnetic resonance imaging [MRI], and 18fluorodeoxyglucose positron emission tomography [PET]/CT) have limitations. The advent of new imaging techniques and novel molecular imaging agents have revealed molecular processes in the tumor microenvironment as an application for the early diagnosis and assessment of PM as well as real-time guided surgical resection, which has changed clinical management. In contrast to clinical imaging, which is purely qualitative and subjective for interpreting macroscopic structures, radiomics and artificial intelligence (AI) capitalize on high-dimensional numerical data from images that may reflect tumor pathophysiology. A predictive model can be used to predict the occurrence, recurrence, and prognosis of PM, thereby avoiding unnecessary exploratory surgeries. This review summarizes the role and status of different imaging techniques, especially new imaging strategies such as spectral photon-counting CT, fibroblast activation protein inhibitor (FAPI) PET/CT, near-infrared fluorescence imaging, and PET/MRI, for early diagnosis, assessment of surgical indications, and recurrence monitoring in patients with PM. The clinical applications, limitations, and solutions for fluorescence imaging, radiomics, and AI are also discussed.

Characterization of the biological and transcriptomic signatures of natural killer cells derived from cord blood and peripheral blood.

Longitudinal studies have indicated the pivotal role of natural killer cells (NKs) in the elimination of certain infections and malignancies. Currently, perinatal blood (PB) and cord blood (CB) have been considered with promising prospective for autogenous and allogeneic NKs transplantation, yet the similarities and differences at the biological and molecular levels are largely obscure. We isolated mononuclear cells (MNCs) from PB and CB, and compared the biological phenotypes of resident NKs by flow cytometry and cell counting. Then, we turned to our well-established "3ILs" strategy and co-culture for NK cell activation and cytotoxicity analyses, respectively. Finally, with the aid of transcriptomic analyses, we further dissected the signatures of PB-NKs and CB-NKs. CB-NKs revealed superiority in cellular vitality over PB-NKs, together with variations in subpopulations. CB-NKs showed higher cytotoxicity over PB-NKs against K562 cells. Furthermore, we found both NKs revealed multifaceted conservations and differences in gene expression profiling and genetic variations, together with gene subsets and signaling pathway. Collectively, both NKs revealed multifaceted similarities and diverse variations at the cellular and transcriptomic levels. Our findings would benefit the further exploration of the biological and transcriptomic properties of CB-NKs and PB-NKs, together with the development of NK cell-based cytotherapy.

Decoding the biological properties and transcriptomic landscapes of human natural killer cells derived from bone marrow and umbilical cord blood.

Longitudinal studies have highlighted allogeneic natural killer (NK) cell-based cytotherapy for cancer immunosurveillance and immunotherapy, yet the deficiency of systematic and detailed comparison of NK cells from candidate sources including umbilical cord blood (UC) and bone marrow (BM) largely hinders the large-scale application. Herein, we isolated resident NK cells (rUC-NK, rBM-NK) from mononuclear cells (MNC), and analyzed the corresponding expanded NK cell counterparts (eUC-NK, eBM-NK). Then, the eUC-NK and eBM-NK were turned to multifaceted bioinformatics from the aspects of gene expression profiling and genetic variations. The percentages of total or activated NK cells in rBM-NK group were approximate 2-fold higher over those in the rUC-NK group, respectively. Instead, the proportion of total NK cells in eUC-NK was higher than that in the eBM-NK group, and in particular, the CD25+ memory-like NK cell subset. Furthermore, eUC-NK and eBM-NK manifested multidimensional similarities and diversities in gene expression pattern and genetic spectrum, whereas both eUC-NK and eBM-NK exhibited effective tumor killing capacity. Collectively, we dissected the cellular and transcriptomic signatures of NK cells generated from UC-MNC and BM-MNC, which supplied new literature for further exploring the characteristics of the indicated NK cells and would benefit the clinical application for cancer immunotherapy in future.

Therapeutic challenge for immunotherapy targeting cold colorectal cancer: A narrative review.

Cold colorectal tumors are not likely to trigger a robust immune response and tend to suppress the immune response. There may be three reasons. First, the complex tumor microenvironment of cold colorectal cancer (CRC) leads to tolerance and clearance of immunotherapy. Second, the modification and concealment of tumor-specific targets in cold CRC cause immune escape and immune response interruption. Finally, the difference in number and function of immune cell subsets in patients with cold CRC makes them respond poorly to immunotherapy. Therefore, we can only overcome the challenges in immunotherapy of cold CRC through in-depth research and understanding the changes and mechanisms in the above three aspects of cold CRC.

Research progress of Astragalus membranaceus in treating peritoneal metastatic cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Peritoneal metastasis is a manifestation of advanced cancer often associated with a poor prognosis and poor response to treatment. Astragalus membranaceus (Fisch.) Bunge is a commonly used medicinal material in traditional Chinese medicine with various biological activities. In patients with cancer, Astragalus membranaceus has demonstrated anti-tumor effects, immune regulation, postoperative recurrence and metastasis prevention, and survival prolongation. AIM OF THE STUDY: Peritoneal metastasis results from tumor cell and peritoneal microenvironment co-evolution. We aimed to introduce and discuss the specific mechanism of action of Astragalus membranaceus in peritoneal metastasis treatment to provide a new perspective for treatment and further research. MATERIALS AND METHODS: We consulted reports on the anti-peritoneal metastases effects of Astragalus membranaceus from PubMed, Web of Science, China National Knowledge Infrastructure, and Wanfang databases, as well as Google Scholar. Meanwhile, we also obtained data from published medical works and doctoral and master's theses. Then, we focused on the research progress of Astragalus membranaceus in peritoneal metastatic cancer treatment. Plant names are provided in accordance with "The Plant List" (www.theplantlist.org). RESULTS: To date, more than 200 compounds have been isolated from Astragalus membranaceus. Among them, Astragalus polysaccharides, saponins, and flavonoids are the main bioactive components, and their effects on cancer have been extensively studied. In this review, we systematically summarize the effects of Astragalus membranaceus on the peritoneal metastasis microenvironment and related mechanisms, including maintaining the integrity of peritoneal mesothelial cells, restoring the peritoneal immune microenvironment, and inhibiting the formation of tumor blood vessels, matrix metalloproteinase, and dense tumor spheroids. CONCLUSIONS: Our analysis demonstrates that Astragalus membranaceus could be a potential therapeutic for preventing the occurrence of peritoneal metastasis. However, it might be too early to recommend its use owing to the paucity of reliable in vivo experiment, clinical data, and evidence of clinical efficacy. In addition, previous studies of Astragalus membranaceus report inconsistent and contradictory findings. Therefore, detailed in vitro, in vivo, and clinical studies on the mechanism of Astragalus membranaceus in peritoneal metastatic cancer treatment are warranted.

Feasibility of Enhanced Recovery After Surgery Protocols Implemented Perioperatively in Endoscopic Submucosal Dissection for Early Gastric Cancer: A Single-Center Retrospective Study.

Background: Endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) has advantages over traditional radical gastrectomy. We investigated whether enhanced recovery after surgery (ERAS) protocols are appropriate in the ESD perioperative period. Materials and Methods: We screened 129 consecutive patients, and 12 were excluded. All study patients underwent ESD for EGC. Of the 117 included patients, 57 received traditional perioperative care between January 2017 and December 2018, and 60 patients received perioperative care according to ERAS protocols between January 2019 and September 2020. The primary study endpoint was ESD-related complications. Secondary endpoints included the following postoperative parameters: anal exhaust time, incidence of nausea or vomiting, length of hospitalization, fever rate, abdominal pain on the visual analog scale (VAS), and reported perioperative satisfaction. Results: Complications were comparable between the 2 groups. In the ERAS group, no patients experienced delayed bleeding or perforation. One traditional group patient bled, and one perforated. Postoperative anal exhaust time, nausea or vomiting incidence, hospitalization, fever rate, and VAS pain scores were significantly lower, and perioperative satisfaction rate was significantly higher in the ERAS group. Conclusions: ERAS protocols are both feasible and safe for patients undergoing ESD. ERAS protocols enhance the advantages of ESD for EGC without increasing complications.

Research progress on the antitumor effects of astragaloside IV.

One of the most important and effective components of Astragalus membranaceus is astragaloside IV (AS-IV), which can exert anti-tumor effects through various pathways. For instance, AS-IV exerts an anti-tumor effect by acting at the cellular level, regulating the phenotype switch of tumor-associated macrophages, or inhibiting the development of tumor cells. Furthermore, AS-IV inhibits tumor cell progression by enhancing its sensitivity to antitumor drugs or reversing the drug resistance of tumor cells. This article reviews the different mechanisms of AS-IV inhibition of epithelial-mesenchymal transition (EMT), migration, proliferation, and invasion of tumor cells, inducing apoptosis and improving the sensitivity of anti-tumor drugs. This review summarizes recent progress in the current research into AS-IV anti-tumor effect and provides insight on the next anti-tumor research of AS-IV.

The efficacy and safety of glucocorticoid for perioperative patients with hepatectomy: a systematic review and meta-analysis.

OBJECTIVE: Glucocorticoids have been used in patients undergoing perioperative hepatectomy, however their safety and efficacy remain controversial. This meta-analysis was conducted to investigate this issue and further provide reference for clinical practice. METHODS: PubMed/MEDLINE, Embase, and Cochrane Library were searched for randomized controlled trials (RCTs) from database inception to December 2022. Literature screening and data extraction were performed independently by two reviewers. The methodological quality of the RCTs was assessed using the Jadad scale. RevMan 5.4 was used for the meta-analysis. RESULTS: A total of 11 RCTs involving 905 patients were included. Compared with the control group, we found perioperative glucocorticoid administration significantly lowered overall complication rate [RR = 0.67; 95% CI (0.55, 0.83); P = 0.0003], infectious complication rate [RR = 0.41; 95% CI (0.21, 0.82); P = 0.01] and postoperative liver failure [RR = 0.63; 95% CI (0.41, 0.97); P = 0.03]. In addition, glucocorticoids appear to improve liver function (TBil) [MD = -0.36, 95% CI (-0.59, -0.14), P = 0.001] and reduce the release of certain inflammatory cytokines (IL-6) [MD = -48.52, 95% CI (-56.88, -40.16), P < 0.00001]. CONCLUSION: Based on the available evidence, glucocorticoids appear to be safe and effective in patients undergoing hepatectomy, but further research is needed.

Advances in the application of robotic surgical systems to gastric cancer: A narrative review.

Gastric cancer is one of the common malignant tumors in the gastrointestinal tract, and surgery is currently an important treatment for progressive gastric cancer. With the development of technology, the simultaneous maturation of artificial intelligence (AI), fifth-generation (5G) telecommunication networks and the internet of things (IOT) has brought significant efficacy and new opportunities for the surgical treatment of gastric malignancies. The combination of 5G network and remote surgical robotic system is the future trend of radical gastric cancer surgery, and the "unmanned" treatment mode of fully automated robotic gastric cancer radical surgery will be realized soon.

High FN1 expression correlates with gastric cancer progression.

OBJECTIVE: High stromal ratio of gastric cancer is associated with a poor prognosis. Fibronectin 1(FN1) is the main component of gastric cancer stroma. The focus of this research was to investigate the FN1 express pattern, the connection between FN1 expression, clinicopathological parameters, survival, and mismatch repair genes (MMR) or immune checkpoints in gastric cancer patients. METHODS: Eighty-six paired stomach cancer tissues, neighboring normal tissues, and eight independent gastric cancer tissues were used to create 180 points tissue microarrays. The association between epithelial fibronectin (E-FN1), stromal fibronectin (S-FN1) expression, and clinical characteristics was analyzed using the chi-square test or Fisher's exact test, and the survival analysis curve was analyzed using the log-rank test, followed by univariate and multivariate Cox regression. The correlation between FN1 and MMR or immune checkpoints was analyzed by Spearman correlation. RESULTS: FN1 is mainly expressed in gastric cancer tissues, with low or no expression in adjacent normal tissues. In tumor tissues, FN1 is mostly distributed in the stroma. High E-FN1 expression was associated with a decreased overall survival (OS), while S-FN1 expression did not. High S-FN1 expression correlated with older age (P<0.001), higher pathological grade (P<0.001), pathological type (P<0.001), vessel/lymphatic invasion (P<0.001), advanced T stage (P=0.001), N stage (P=0.01), and worse TNM stage(P = 0.033). FN1 expression was not associated with MMR or immune checkpoints (MLH1, MSH2, MSH6, PDL1, PD1, PMS2, and CD8). CONCLUSIONS: High E-FN1 expression predicted poor OS, while S-FN1 is associated with gastric cancer progression.

Mechanisms of Peritoneal Mesothelial Cells in Peritoneal Adhesion.

A peritoneal adhesion (PA) is a fibrotic tissue connecting the abdominal or visceral organs to the peritoneum. The formation of PAs can induce a variety of clinical diseases. However, there is currently no effective strategy for the prevention and treatment of PAs. Damage to peritoneal mesothelial cells (PMCs) is believed to cause PAs by promoting inflammation, fibrin deposition, and fibrosis formation. In the early stages of PA formation, PMCs undergo mesothelial-mesenchymal transition and have the ability to produce an extracellular matrix. The PMCs may transdifferentiate into myofibroblasts and accelerate the formation of PAs. Therefore, the aim of this review was to understand the mechanism of action of PMCs in PAs, and to offer a theoretical foundation for the treatment and prevention of PAs.

Clinical efficacy and safety of robot assisted surgery for choledochal cysts excisions: a systematic review and meta-analysis.

BACKGROUND: This study aimed to evaluate the safety and therapeutic effect of Robot-assisted surgery (RAS) for choledochal cysts (CCs) excisions. RESEARCH DESIGN AND METHODS: PubMed, EMBASE, Cochrane Library, Web of Science, CNKI, WanFang, VIP, and CBM were searched from database inception to 1 May 2022. The Newcastle-Ottawa scale (NOS) was used to conduct quality assessments, and RevMan (Version 5.4) was used to perform the meta-analysis. RESULTS: In all, 9 studies, involving 623 patients, were analyzed. RAS compared with LAS was associated with less intraoperative blood loss, shorter time to start solid diets, shorter postoperative hospital stay, and lower complications. There was no significant difference in operative time between the two groups, but the total costs were higher in RAS. Our subgroup analysis showed that RAS had significant advantages over LAS in the child group: minor bleeding, shorter length of hospital stay, and fewer postoperative complications. CONCLUSIONS: The available evidence indicates that the RAS system has the advantages of less intraoperative blood loss, minor tissue damage, quick recovery, and sound healing in treating choledochal cyst, which proves that the RAS is safely feasible. Especially in children, RAS tends to be a better choice.

Decoding the multidimensional signatures of resident and expanded natural killer cells generated from perinatal blood.

Natural killer (NK) cells are lymphocytes and play a pivotal role in innate and adaptive immune responses against infections and malignancies. Longitudinal studies have indicated the feasibility of perinatal blood for large-scale NK cell generation, yet the systematic and detailed comparations of the signatures of resident and expanded NK cells (rNKs, eNKs) are largely obscure. Herein, we harvested rNKs from umbilical cord blood (rUC-NKs) and placental blood (rP-NKs) as well as the corresponding eNKs (eUC-NKs, eP-NKs). Furthermore, the biological properties and transcriptomic signatures including cellular subpopulations, cytotoxicity, gene expression profiling, genetic characteristics, signaling pathways and gene set-related biological process were investigated. The enriched rNKs and eNKs exhibited diversity in biomarker expression pattern, and eNKs with higher percentages of NKG2D+, NKG2A+, NKp44+ and NKp46+ subsets. rNKs or eNKs with different origins showed more similarities in transcriptomic signatures than those with the same origin. Our data revealed multifaceted similarities and differences of the indicated rNKs and pNKs both at the cellular and molecular levels. Our findings provide new references for further dissecting the efficacy and molecular mechanisms of rNKs and eNKs, which will collectively benefit the fundamental and translational studies of NK cell-based immunotherapy.

Role of Peritoneal Mesothelial Cells in the Progression of Peritoneal Metastases.

Peritoneal metastatic cancer comprises a heterogeneous group of primary tumors that originate in the peritoneal cavity or metastasize into the peritoneal cavity from a different origin. Metastasis is a characteristic of end-stage disease, often indicative of a poor prognosis with limited treatment options. Peritoneal mesothelial cells (PMCs) are a thin layer of cells present on the surface of the peritoneum. They display differentiated characteristics in embryonic development and adults, representing the first cell layer encountering peritoneal tumors to affect their progression. PMCs have been traditionally considered a barrier to the intraperitoneal implantation and metastasis of tumors; however, recent studies indicate that PMCs can either inhibit or actively promote tumor progression through distinct mechanisms. This article presents a review of the role of PMCs in the progression of peritoneum implanted tumors, offering new ideas for therapeutic targets and related research.

Centromeric protein K (CENPK) promotes gastric cancer proliferation and migration via interacting with XRCC5.

BACKGROUND: CENPK is a novel oncogene which is aberrantly expression in some malignant tumors. However, the role and mechanisms of CENPK in gastric cancer have not been explored. METHODS: In this study, we use RT-PCR and IHC to study CENPK expression in gastric cancer cells and tissues. In addition, we constructed the two kinds of CENPK siRNA lentivirus to knock down CENPK. Then, we use High content living cell imaging System, Cell Counting Kit-8, colony formation, wound healing and Transwell assays to demonstrate the function of CENPK on gastric cancer cells AGS and MKN45. Meanwhile, we use flow cytometry assay to study CENPK function on gastric cancer cell apoptosis and cell cycle arrest. Subcutaneous tumorigenesis in nude mice was also performed to confirm CENPK function on gastric cancer. Finally, we use Co-IP, LC-MS and function rescue assay to study the downstream interaction molecular of CENPK. RESULTS: We demonstrated that CENPK expression were up-regulated in GC cell lines. Poor differentiation and III-IV stage had more percentages of high CENPK expression. Knocking down CENPK could significantly suppress GC cells proliferation, migration and invasion, and induce GC cells apoptosis and G1/S phase transition arrest. Subcutaneous tumorigenesis confirmed the tumor-promoting effects of CENPK in vivo. Remarkably, we found for the first time that XRCC5 might be interacted with CENPK through Co-IP, LC-MS and rescue study. CONCLUSION: CENPK promotes GC cell proliferation and migration via interacting with XRCC5 and may be a novel prognostic factor or therapeutic target for CENPK.

Comparative efficacy and safety of local palliative therapeutics for unresectable malignant biliary obstruction: a Bayesian network meta-analysis.

BACKGROUND: Both radiofrequency ablation (RFA), photodynamic therapy (PDT), and biliary stent alone are common local palliative therapies for unresectable malignant biliary obstruction (MBO), but the best modality is uncertain. RESEARCH DESIGN AND METHODS: Embase, Cochrane Library, PubMed, and Web of Science were systematically searched up to 30 January 2022, for eligible studies that compared either two or all modalities in unresectable MBO. RESULTS: Thirty-three studies with 2974 patients were included in this study. The PDT+Stent and RFA+Stent groups had better overall survival and longer mean survival time than Stent alone (all P < 0.05). Moreover, patients with RFA+Stent demonstrated better mean duration of stent patency (MD: 2.0, 95%CI,1.1 to 2.8, P < 0.05) than Stent alone. The three modalities had similar postoperative mild bleeding, cholangitis, and pancreatitis (all P ≥ 0.05). According to network ranking, PDT+Stent was most likely to provide better survival, RFA+Stent was most likely to maintain stent patency. CONCLUSIONS: RFA or PDT plus biliary stent is effective and safe local palliative therapy for unresectable MBO, but the current studies cannot absolutely determine which modality is the best. We should offer patients the most appropriate treatment according to the advantage of each therapy and the patient's performance status.

Early predictive value of circulating biomarkers for sorafenib in advanced hepatocellular carcinoma.

INTRODUCTION: Sorafenib is currently the first-line therapeutic regimen for patients with advanced hepatocellular carcinoma (HCC). However, many patients did not experience any benefit and suffered extreme adverse events and heavy economic burden. Thus, the early identification of patients who are most likely to benefit from sorafenib is needed. AREAS COVERED: This review focused on the clinical application of circulating biomarkers (including conventional biomarkers, immune biomarkers, genetic biomarkers, and some novel biomarkers) in advanced HCC patients treated with sorafenib. An online search on PubMed, Web of Science, Embase, and Cochrane Library was conducted from the inception to 15 August 2021. Studies investigating the predictive or prognostic value of these biomarkers were included. EXPERT OPINION: The distinction of patients who may benefit from sorafenib treatment is of utmost importance. The predictive roles of circulating biomarkers could solve this problem. Many biomarkers can be obtained by liquid biopsy, which is a less or noninvasive approach. The short half-life of sorafenib could reflect the dynamic changes of tumor progression and monitor the treatment response. Circulating biomarkers obtained from liquid biopsy resulted as a promising assessment method in HCC, allowing for better treatment decisions in the near future. ABBREVIATIONS: Alpha-fetoprotein (AFP); American Association for the Study of Liver Diseases (AASLD); Angiopoietin (Ang); Barcelona Clinic Liver Cancer stage (BCLC); Circulating endothelial progenitor (CEP); Circulating free DNA (cfDNA); Complete response (CR); Des-γ-carboxy prothrombin (DCP); Endothelium-derived nitric oxide synthase (eNOS); Hepatocellular carcinoma (HCC); Hepatocyte growth factor (HGF); Hepatoma arterial-embolization prognosis score (HAP); High mobility group box 1 (HMgb1); Interferon-gamma (IFN-γ); Long non-coding RNA (lncRNAs); Micro RNAs (miRNAs); Monocyte-to-lymphocyte ratio (MLR); National Comprehensive Cancer Network (NCCN); Neutrophil-lymphocyte ratio (NLR); Newcastle-Ottawa Scale (NOS); Nitric oxide (NO); Overall survival (OS); Partial response (PR); Platelet-lymphocyte ratio (PLR); Prediction of survival in advanced sorafenib-treated HCC (PROSASH); Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA); Prognostic nutritional index (PNI); Progression-free survival (PFS); Progressive disease (PD); Randomized controlled trials (RCTs); Response Evaluation Criteria in Solid Tumors (RECIST); Single nucleotide polymorphisms (SNPs); Sorafenib advanced HCC prognosis score (SAP); Stable disease (SD); Time to progression (TTP); Transcatheter arterial chemoembolization (TACE); Vascular endothelial growth factor (VEGF).

Proximal Gastrectomy Versus Total Gastrectomy for Siewert II/III Adenocarcinoma of the Gastroesophageal Junction: a Systematic Review and Meta-analysis.

BACKGROUND: The incidence of adenocarcinoma of the esophagogastric junction (AEG) has rapidly increased in recent years. Popular surgical approaches for AEG are proximal gastrectomy (PG) and total gastrectomy (TG), but it is controversial as to which approach is superior. Therefore, we conducted a systematic review and meta-analysis to evaluate the short- and long-term clinical outcomes of PG and TG for AEG. METHODS: PubMed, Embase, Web of Science, and Cochrane Library were searched from inception to 1 June 2021. The Newcastle-Ottawa scale was used to conduct quality assessments, and RevMan (Version 5.4) was used to perform the meta-analysis. RESULTS: In all, 1,734 patients with Siewert II/III AEG in 12 studies were included in the meta-analysis. PG was associated with less number of harvested lymph nodes (WMD = - 9.00, 95% CI - 12.61 to - 5.39, P < 0.00001), smaller tumor size (WMD = - 1.02, 95% CI - 1.71 to - 0.33, P = 0.004), shorter hospital length of stay (WMD = - 3.99, 95% CI - 7.27 to - 0.71, P = 0.02), and better long-term nutritional status compared with TG. Overall complications, other complications, and overall survival were not significantly different between the two groups. Moreover, subgroup analysis revealed that the occurrence of anastomotic strictures and reflux esophagitis was associated with the use of novel gastrointestinal tract (GI) anastomoses (double-tract reconstruction, jejunal interposition, and semi-embedded valve anastomosis) after PG. CONCLUSIONS: Based on the available evidence, we recommend that surgeons accept PG combined with multiple novel anastomoses as an optimal surgical approach in patients diagnosed with resectable Siewert type II/III AEG.

Local palliative therapies for unresectable malignant biliary obstruction: radiofrequency ablation combined with stent or biliary stent alone? An updated meta-analysis of nineteen trials.

BACKGROUND: Recently, there has been a burgeoning interest in radiofrequency ablation combined with stent (RFA + Stent) for unresectable malignant biliary obstruction (MBO). This study aimed to perform a meta-analysis to evaluate the efficacy and safety of RFA + Stent compared with biliary stent alone. METHODS: We searched PubMed, Cochrane Library, Embase, and Web of Science databases from their inception dates to June 20, 2021, for studies that compared RFA + Stent and stent alone for unresectable MBO. The main outcomes were survival, patency, and adverse effects. All meta-analyses were calculated using the random-effects model. RESULTS: A total of 19 studies involving 1946 patients were included in this study. Compared with stent alone, RFA + Stent was significantly associated with better overall survival (HR 0.55; 95% CI 0.48, 0.63; P < 0.00001), longer mean survival time (SMD 2.20; 95% CI 1.17, 3.22; P < 0.0001), longer mean stent patency time (SMD 1.37; 95% CI 0.47, 2.26; P = 0.003), higher stent patency at 6 months (OR 2.82; 95% CI 1.54, 5.18; P = 0.0008). The two interventions had similar incidence of postoperative abdominal pain (OR 1.29; 95% CI 0.94, 1.78; P = 0.11), mild bleeding (OR 1.28; 95% CI 0.65, 2.54; P = 0.48), cholangitis (OR 1.09; 95% CI 0.76, 1.55; P = 0.65), pancreatitis (OR 1.39; 95% CI 0.82, 2.38; P = 0.22). Furthermore, the serum bilirubin levels and stricture diameter after operations were significantly alleviated than before operations, but the degree of alleviation between the two groups were not significantly different (all P > 0.05). CONCLUSION: Although the alleviation of serum bilirubin and stricture diameter did not differ between the two interventions, RFA + Stent can significantly improve the survival and stent patency with comparable procedure-related adverse events than stent alone. Thus, RFA + Stent should be recommended as an attractive alternative to biliary stent alone for patients with unresectable MBO.