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).

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.

The efficacy and safety of 5-fluorouracil based adjuvant therapy in resected biliary tract cancer: A systematic review and meta-analysis.

OBJECTIVES: The adjuvant therapy (AT) for biliary tract cancer (BTC) patients after surgery has always been controversial. More therapeutic regimens and high-quality evidence were needed to evaluate AT's survival benefit further. Thus, this study was performed to investigate the efficacy and safety of the 5-fluorouracil (5-FU) regimen in resected BTC patients. METHODS: PubMed, Cochrane Library, Web of Science, and the Embase were systematically searched from inception to Feb.3, 2021, for eligible studies. The pooled analyses were performed using Review Manager, Stata, and SPSS software. RESULTS: A total of 9 trials involving 1339 participants were included in the meta-analysis. Resected BTC patients could significantly benefit from a 5-FU regimen (HR:0.51, 95%CI, 0.38-0.69, P<0.0001), regardless of gallbladder carcinoma (GBC) or cholangiocarcinoma (CCA). Moreover, both adjuvant chemotherapy (HR:0.61, 95%CI, 0.47-0.79, P=0.0003) and chemoradiotherapy (HR:0.35, 95%CI, 0.14-0.83, P=0.02) could significantly improve clinical survival of resected BTC patients than the surgery alone group. In the subgroup analyses, patients with node-positive (P=0.02) or vascular invasion disease (P=0.002) could better benefit from postoperative AT. CONCLUSION: This study provides the latest evidence to support the 5-FU regimen in resected BTC patients regardless of GBC or CCA. Furthermore, high-risk patients are more likely to benefit from it, such as node-positive or vascular invasion disease.

Efficacy and safety of preoperative biliary drainage in patients undergoing pancreaticoduodenectomy: an updated systematic review and meta-analysis.

OBJECTIVES: This study aimed to evaluate the effect of preoperative biliary drainage (PBD) on outcomes of pancreaticoduodenectomy (PD) in patients with biliary obstruction. METHODS: We searched PubMed, EMBASE, Cochrane library, and Web of Science from database inception to 11 March 2021. We used the ROBINS-I tool and Cochrane risk of bias tool 2.0 to assess the risk of bias. The data were statistically analyzed using the RevMan software (Version 5.4). RESULTS: In all, 43 studies, including 23,076 patients, were analyzed, of which 13,922 patients were treated with PBD and 9154 were treated with no preoperative biliary drainage (NPBD). The morbidity     , infection morbidity      , and postoperative pancreatic fistulae (POPF)       in patients undergoing PBD, were significantly higher than those in patients undergoing NPBD. Further, PBD may lead to a significantly worse 2- and 3-year overall survival (OS) rates           . In subgroup meta-analysis, the differences in morbidity, POPF, and OS outcomes lost significance between the PBD and NPBD groups when the mean total serum bilirubin (TSB) concentration was below 15 mg/dl. CONCLUSIONS: Routine PBD still cannot be recommended because it showed no beneficial effect on postoperative outcomes. However, in patients with < 15 mg/dl TSB concentration, PBD tends to be a better choice.

Immune checkpoint blockade in the treatment of malignant tumor: current statue and future strategies.

After being stagnant for decades, there has finally been a paradigm shift in the treatment of cancer with the emergence and application of immune checkpoint inhibitors (ICIs). The most extensively utilized ICIs are targeting the pathways involving programmed death-1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4). PD-1, as an crucial immune inhibitory molecule, by and large reasons the immune checkpoint response of T cells, making tumor cells get away from immune surveillance. Programmed cell death ligand-1 (PD-L1) is exceptionally expressed in most cancers cells and approves non-stop activation of the PD-1 pathway in the tumor microenvironment. PD-1/PD-L1 inhibitors can block the combination of PD-1 and PD-L1, inhibit hostile to regulatory signals, and restore the activity of T cells, thereby bettering immune response. The current researchers assume that the efficacy of these drugs is related to PD-L1 expression in tumor tissue, tumor mutation burden (TMB), and other emerging biomarkers. Although malignant tumors can benefit from the immunotherapy of PD-1/PD-L1 inhibitors, formulating a customized medication model and discovering biomarkers that can predict efficacy are the new trend in the new era of malignant tumor immunotherapy. This review summarizes the mechanism of action of PD-1/PD-L1 inhibitors, their clinical outcomes on various malignant tumors, their efficacy biomarkers, as well as predictive markers of irAEs.

Incisional negative pressure wound therapy for clean-contaminated wounds in abdominal surgery: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: The role of incisional negative-pressure wound therapy (iNPWT) in preventing surgical site infections (SSIs) in clean-contaminated abdominal wounds is still controversial. This meta-analysis was performed to evaluate whether the use of iNPWT could reduce SSIs and other complications in clean-contaminated abdominal surgery. METHODS: The authors searched PubMed, EMBASE, Cochrane library, and Web of Science from database inception to 23 January 2021 for randomized controlled trials (RCTs). They assessed the risk of bias using the Cochrane Collaboration risk of bias tool and conducted a meta-analysis using RevMan 5.4. RESULTS: Eleven RCTs, including 4112 patients, were analyzed, of which 2057 were treated with iNPWT and 2055 with standard dressings. The SSI rates (OR = 0.76, 95% CI = 0.61-0.94, P = 0.01), in patients undergoing an iNPWT intervention were significantly lower than those in patients receiving standard dressings. There was no statistically significant difference between the rates of incision dehiscence, seroma, and readmission between groups. CONCLUSIONS: Application of iNPWT for clean-contaminated wounds in abdominal surgery reduced SSI rates but showed similar rates of wound dehiscence, seroma, and readmission compared with standard dressings.

Comparison of intraoperative endoscopic retrograde cholangiopancreatography and laparoscopic common bile duct exploration combined with laparoscopic cholecystectomy for treating gallstones and common bile duct stones: a systematic review and meta-analysis.

BACKGROUND: This study aimed to compare the efficacy and safety of laparoscopic cholecystectomy combined with intraoperative endoscopic retrograde cholangiopancreatography (LC-IntraERCP) and laparoscopic cholecystectomy combined with laparoscopic common bile duct exploration (LC-LCBDE) to determine which one-stage therapeutic strategy provides better outcomes for patients with gallstones and common bile duct stones. METHODS: Cochrane Library, EMBASE, PubMed, and Web of Science databases were searched to identify eligible articles from the database inception to September 2020. The revised Cochrane risk of bias tools for randomized trials (RoB-2) and non-randomized interventions (ROBINS-I) was used to assess the quality of the included studies. The overall quality of evidence was assessed through the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool. The primary outcomes consisted of surgical success, retained stones, and overall postoperative complications, while secondary outcomes included postoperative bleeding, postoperative pancreatitis, postoperative bile leakage, conversion to laparotomy, and operative time. RESULTS: Eight studies (four RCTs and four Non-RCTs with high quality) with 2948 patients were included. No significant difference was seen between the two groups regarding surgical success, overall postoperative complications, conversion to laparotomy, and operative time. The meta-analysis demonstrated that in the LC-IntraERCP group, the rate of retained stones (OR 0.51, 95% CI 0.28-0.91) and postoperative bile leakage were lower (OR 0.25, 95% CI 0.09-0.69), while in the LC-LCBDE group, postoperative bleeding (OR 5.24, 95% CI 1.65-16.65) and postoperative pancreatitis (OR 4.80, 95% CI 2.35-9.78) decreased. CONCLUSIONS: LC-IntraERCP and LC-LCBDE exhibited similar efficacies when surgical success rate, overall postoperative complications, conversion to laparotomy, and operative time were compared. However, LC-IntraERCP is probably to be more effective in terms of lowering the rate of retained stones.

T-tube or no T-tube for biliary tract reconstruction in orthotopic liver transplantation: an updated systematic review and meta-analysis.

Objectives: Biliary tract reconstruction with or without T-tube is commonly used in orthotopic liver transplantation (OLT). However, the efficacy and safety of T-tube usage remain controversial. This meta-analysis was conducted to assess the latest evidence of clinical outcomes.Methods: Embase, Cochrane Library, PubMed, and Web of Science were systematically searched from inception to 20 January 2021 for eligible studies. The analyses were performed using Review Manager and Stata.Results: A total of 24 trials involving 3320 participants were included in the meta-analysis. Compared with the no T-tube group, there was a higher incidence of overall biliary complications (OR:1.54; 95%CI, 1.06-2.24; P = 0.02), bile leaks (OR:2.34; 95%CI,1.57-3.48; P < 0.0001), cholangitis (OR:2.78; 95%CI,1.19-6.51; P = 0.002), and longer cold ischemia time (MD:22.27; 95%CI,0.80-43.74; P = 0.04) in the T-tube group. Furthermore, the no T-tube group had significantly higher odds of biliary strictures than the T-tube group (OR:0.60; 95%CI, 0.47-0.78; P = 0.0001).Conclusion: T-tube is still not routinely recommended, but is a good choice for OLT patients at high risk of biliary strictures. Notably, the higher rate of biliary complications in the T-tube group did not translate into an increase in endoscopic or re-operative interventions.