Prognostic value of neutrophil-to-lymphocyte ratio in colorectal cancer liver metastasis: A meta-analysis of results from multivariate analysis.

We aimed to evaluate the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in colorectal cancer liver metastasis (CRLM). A comprehensive search was conducted across PubMed, MedLine, and the Cochrane Library databases for articles published from January 1, 2000 to April 30, 2022 that investigated the long-term prognostic value of NLR in CRLM; only studies with multivariate analyses were enrolled. Hazard ratio (HR) with 95% confidence interval (CI) was used to determine the effect size. A total of 2,522 patients in 12 studies were selected; the meta-analysis demonstrated that elevated NLR correlated with poor overall survival (OS) and disease-free survival (DFS) (HR, 1.95, 95%CI, 1.698-2.223, P < 0.01; HR, 1.80, 95%CI, 1.363-2.363, P < 0.01; respectively). The 5-year OS and disease-free survival rates were higher in the patients with normal NLR than in patients with high NLR (47% vs. 27%, P < 0.01; 37% vs. 6%, P < 0.01, respectively). Further analysis of clinicopathological parameters indicated no significant difference between the patients with and without elevated NLR. Begg's and Egger's tests for publication bias revealed no significant publication bias (P = 0.891 and P = 0.926, respectively). Multivariate analysis revealed that NLR had an excellent prognostic ability in CRLM, which can be used in deciding the treatment and predicting the clinical outcomes. Further multicenter randomized controlled trials are required to verify this conclusion.

A simplified model for prophylactic transarterial chemoembolization after resection for patients with hepatocellular carcinoma.

BACKGROUND: Prophylactic transarterial chemoembolization (p-TACE) is frequently conducted for patients with hepatocellular carcinoma (HCC) in China, but the question of who could benefit from it remains controversial. Hence, we wanted to establish a nomogram model to identify patients eligible for p-TACE. METHODS: Data from HCC patients receiving R0 resection with or without p-TACE between January 2013 and December 2014 were identified, using primary liver cancer big data, to establish a nomogram model to predict overall survival (OS). Based on the model, Patients receiving R0 resection between January 2015 and December 2015 were divided into three subgroups, and survival curves were constructed using the Kaplan-Meier method and analyzed by the log-rank test among patients in each subgroup. RESULTS: A nomogram integrating the neutrophil to lymphocyte ratio, AFP, tumor diameter, and microvascular invasion was developed to predict the OS of patients with HCC receiving R0 resection, and significant differences were observed in the median OS of the subgroups of low-risk (≤20), intermediate-risk (20~120), and high-risk (>120) identified by the current model. This model showed good calibration and discriminatory power in the validation cohort and the external cohort (c-index of 0.669 and 0.676, respectively). In the external cohort, the Kaplan-Meier curves showed that p-TACE could only significantly prolong the median OS of high-risk patients (25.6 vs. 33.7 months, P<0.05), but no differences were observed in any subgroups stratified by the current staging systems (all P>0.05). CONCLUSION: This readily available nomogram model could help guide decisions about p-TACE, but it needs further validation.

The Clinical Value of Postoperative Transarterial Chemoembolization for Resectable Patients with Intermediate Hepatocellular Carcinoma After Radical Hepatectomy: a Propensity Score-Matching Study.

BACKGROUND AND AIMS: Surgical resection for patients with intermediate hepatocellular carcinoma (HCC) is preferred in China, but the prognosis remains far from satisfactory. Postoperative transarterial chemoembolization (p-TACE) has been conducted prevalently to prevent recurrence, but its efficacy remains controversial. Hence, we collected the data from primary liver cancer big data (PLCBD) to investigate the clinical value of p-TACE for patients with intermediate HCC and identify the potential beneficiaries. METHODS: Patients who were diagnosed with intermediate HCC between December 2012 and December 2015 were identified through the PLCBD. Disease-free survival (DFS) of patients who received p-TACE or not following radical resection was evaluated using Kaplan-Meier survival curves before and after 1:1 propensity scoring match (PSM). Subgroup analysis was conducted stratified by risk factors associated with recurrence. RESULTS: A total of 325 intermediate HCC patients receiving radical resection were eligible in this study, including 123 patients in the p-TACE group and 202 in the non-TACE group. Median DFS in the p-TACE group was significantly longer than in the non-TACE group (23.3 months vs. 18.0 months, P = 0.016) in the whole cohort with no severe complicates, which was confirmed in a well-matched cohort (17.4 months vs. 23.3 months, P = 0.012). In addition, p-TACE was identified as an independent risk factors of DFS by multivariate Cox regression analysis before and after PSM (both P < 0.05). After adjusting for other prognostic variables, patients were found to significantly benefit from p-TACE in DFS if they were male, or had hepatitis, diabetes, cirrhosis, AFP ≤ 400 ng/ml, anatomic hepatectomy, no severe surgical complication, no intraoperative transfusion, tumor number = 2, differentiation grading III, capsule, or had no transfusion (all P < 0.05). CONCLUSION: With the current data, we concluded that p-TACE was safe and efficient for the patients with intermediate HCC following radical resection, and male patients with hepatitis, diabetes, cirrhosis, AFP ≤ 400 ng/ml, anatomic hepatectomy, no severe surgical complication, no intraoperative transfusion, tumor number = 2, differentiation grading III, and capsule would benefit more from p-TACE.

Clinical Significance of C-Reactive Protein to Albumin Ratio in Patients with Hepatocellular Carcinoma: A Meta-Analysis.

AIM: To evaluate the prognostic significance of C-reactive protein to albumin ratio (CAR) for clinical outcomes in hepatocellular carcinoma (HCC) patients. Material and Methods. Eligible studies were searched by PubMed, MedLine, the Cochrane Library, from January 1, 2000, to June 30, 2019, investigating the prognostic value of CAR in patients with HCC. Primary endpoint was OS. Hazard ratio (HR) with 95% confidence interval (CI) was used to determine the effect size. RESULTS: 7 records including 2208 patients published since 2014 were enrolled into our meta-analysis. Clinicopathological characteristics were also correlated with the level of CAR. The pooled HR for the OS rate between low and high CAR groups was 2.13 (95% CI 1.70~2.68, P < 0.00001) using a random model, but sensitivity analysis showed that the pooled HR for the OS rates did not change substantially after removal of any included study. As for patients receiving surgery, the pooled HR for the OS rate between low and high CAR groups was 2.04 (95% CI 1.59~2.61, P < 0.00001). Subgroup analysis showed that CAR could be a prognostic biomarker for HCC patients regardless of regions (China, HR = 1.75, 95% CI 1.51~2.02; Japan, HR = 3.36, 95% CI 2.07~5.45; Korea, HR = 2.26, 95% CI 1.47~4.47; respectively), the cut-off value (<0.1, HR = 2.84, 95% CI 1.90~4.24; >0.1, HR = 1.99, 95% CI 1.52~2.61; respectively), and sample size (<200, HR = 2.85, 95% CI 2.01~4.03; >200, HR = 1.75, 95% CI 1.52~2.02; respectively). CONCLUSION: With the current data, we clearly concluded that CAR was closely correlated with prognosis of patients with HCC. Multicenter, prospective randomized trials are warranted to confirm the conclusion.

Does intermittent pringle maneuver loss its clinical value in reducing bleeding during hepatectomy? A systematic review and meta-analysis.

BACKGROUND: The intermittent Pringle's maneuver (IPM) is conducted mainly during the procedure of hepatectomy to control intraoperative blood loss (IBL), but it has been questioned since improvement of surgical technology and intraoperative management. Hence, we conducted a systematic review and meta-analysis to validate the clinical value of IPM. MATERIALS AND METHODS: Eligible studies that were designed to evaluate the IPM in the procedure of hepatectomy were searched for on PubMed, Medline, and other databases from establishment of the database to October 2019. The primary endpoints were IBL and intraoperative blood transfusion (IBT). The risk ratio (RR) with 95% confidence interval (CI) was used to determine the effect size. RESULTS: A total of 16 studies with six randomized controlled trials (RCTs) were enrolled in this meta-analysis, including 1,770 cases in the IPM group and 1,611 cases in the non-IPM group. Overall, there were no significant differences between the IPM and non-IPM groups in the amount of IBL and the incidence of IBT (RR = 0.96, 95% CI 0.67-1.37, P = 0.82), which was also confirmed in the subgroups of RCTs (P > 0.05). However, subgroup analyses showed that for patients with colorectal liver metastasis (CRLM), the amount of IBL was generally higher in the IPM group than in the non-IPM group, and the incidence of IBT was significantly higher in the IPM group (RR = 7.17, 95% CI 1.91-26.94, P = 0.004). In addition, no significant differences were observed in terms of postoperative complications between the two groups (all P > 0.05). CONCLUSION: With the current data, we concluded that IPM had lost its value in patients with CRLM, although it remained controversial in patients with hepatocellular carcinoma.

Does additional resection of a positive microscopic ductal margin benefit patients with perihilar cholangiocarcinoma: A systematic review and meta-analysis.

BACKGROUND: The incidence of a positive microscopic ductal margin (R1) after surgical resection for perihilar cholangiocarcinoma (pCCA) remains high, but the beneficial of additional resection has not been confirmed by any meta-analysis and randomized clinical trials (RCT), which also increased the risk of morbidity and mortality. Hence, a systematic review is warranted to evaluate the clinical value of additional resection of intraoperative R1 for pCCA. METHODS: Eligible studies were searched by PubMed, MedLine, Embase, the Cochrane Library, Web of Science, from Jan.1st 2000 to Nov.30th 2019, evaluating the 1-, 3-, and 5-year overall survival (OS) rates of additional resection of intraoperative pathologic R1 for pCCA. Odds ratio (OR) with 95% confidence interval (CI) was used to determine the effect size by a randomized-effect model. RESULTS: Eight studies were enrolled in this meta-analysis, including 179 patients in the secondary R0 group, 843 patients in the primary R0 group and 253 patients in the R1 group. The pooled OR for the 1-, 3-, and 5-year OS rate between secondary R0 group and primary R0 group were 1.03(95%CI 0.64~1.67, P = 0.90), 0.92(95%CI 0.52~1.64, P = 0.78), and 0.83(95%CI 0.37~1.84, P = 0.65), respectively. The pooled OR for the 1-, 3-, and 5-year OS rate between secondary R0 group and R1 group were 2.14(95%CI 1.31~3.50, P = 0.002), 2.58(95%CI 1.28~5.21, P = 0.008), and 3.54(95%CI 1.67~7.50, P = 0.001), respectively. However, subgroup analysis of the West showed that the pooled OR for the 1-, and 3-year OS rate between secondary R0 group and R1 group were 2.05(95%CI 0.95~4.41, P = 0.07), 1.91(95%CI 0.96~3.81, P = 0.07), respectively. CONCLUSION: With the current data, additional resection should be recommended in selected patients with intraoperative R1, but the conclusion is needed further validation.

Does the intermittent Pringle maneuver affect the recurrence following surgical resection for hepatocellular carcinoma? A systematic review.

BACKGROUND AND AIM: To evaluate the effect of intermittent pringle maneuver (IPM) on the long-term prognosis and recurrence of hepatocellular carcinoma (HCC). METHODS: Eligible studies were identified by PubMed and other databases from Jan 1st 1990 to Mar 31st 2019. Hazard ratios (HR) with 95% confidence interval (CI) were calculated to evaluate the effects of IPM on the long-term prognosis and recurrence of patients with HCC. RESULTS: Six studies were enrolled in this meta-analysis. Results showed that there were no differences between IPM group and non-IPM group in the pooled HRs for the overall survival (OS) and disease-free survival (DFS) (HR 1.04, 95%CI 0.84~1.28, P = 0.74; HR 0.93, 95%CI 0.81~1.07, P = 0.29; respectively). However, subgroup analysis showed that the pooled Odd ratios (OR) for the 1-year OS and DFS rates of the IPM group when compared with the non-IPM group were 0.65 (95% CI 0.45~0.94, P = 0.02), 0.38 (95% CI 0.20~0.72, P = 0.003), respectively. In addition, there were no significant differences in the proportions of liver cirrhosis, HBsAg (+), Child-Pugh A class, multiple tumor, vascular invasion, and major hepatectomy between groups of IPM and non-IPM. CONCLUSION: Since IPM would increase the risk of early-recurrence, it should be used cautiously in the procedure of hepatectomy for resectable HCC. However, the current conclusion needs further validation. TRIAL REGISTRY NUMBER: CRD 42019124923.

The effect of adjuvant therapy for patients with intrahepatic cholangiocarcinoma after surgical resection: A systematic review and meta-analysis.

BACKGROUD: Resection is still the only potentially curative treatment for patients with intrahepatic cholangiocarcinoma (ICC), but the prognosis remains far from satisfactory. However, the benefit of adjuvant therapy (AT) remains controversial, although it has been conducted prevalently. Hence, a meta-analysis was warranted to evaluate the effect of AT for patients with ICC after resection. PATIENTS AND METHODS: PubMed, MedLine, Embase, the Cochrane Library, Web of Science were used to identify potentially eligible studies from Jan.1st 1990 to Aug. 31st 2019, investigating the effect of AT for patients with ICC after resection. Primary endpoint was overall survival (OS), and secondary endpoints was recurrence-free survival (RFS). Hazard ratio (HR) with 95% confidence interval (CI) was used to determine the effect size. RESULTS: 22 studies with 10181 patients were enrolled in this meta-analysis, including 832 patients in the chemotherapy group, 309 patients in the transarterial chemoembolization (TACE) group, 1192 patients in the radiotherapy group, 235 patients in the chemoradiotherapy group, and 6424 patients in the non-AT group. The pooled HR for the OS rate and RFS rate in the AT group were 0.63 (95%CI 0.52~0.74), 0.74 (95%CI 0.58~0.90), compared with the non-AT group. Subgroup analysis showed that the pooled HR for the OS rate in the AT group compared with non-AT group were as follows: chemotherapy group was 0.57 (95%CI = 0.44~0.70), TACE group was 0.56 (95%CI = 0.31~0.82), radiotherapy group was 0.71 (95%CI = 0.39~1.03), chemoradiotherapy group was 0.73 (95%CI = 0.57~0.89), positive resection margin group was 0.60 (95%CI = 0.51~0.69), and lymph node metastasis (LNM) group was 0.67 (95%CI = 0.57~0.76). CONCLUSION: With the current data, we concluded that AT such as chemotherapy, TACE and chemoradiotherapy could benefit patients with ICC after resection, especially those with positive resection margin and LNM, but the conclusion needed to be furtherly confirmed.

The efficacy of transarterial chemoembolization combined with microwave ablation for unresectable hepatocellular carcinoma: a systematic review and meta-analysis.

Purpose: To evaluate the clinical value of transarterial chemoembolization (TACE) combined with microwave ablation (MWA) for unresectable hepatocellular carcinoma (HCC).Patients and methods: Eligible studies were identified using PubMed, MedLine, Embase, the Cochrane Library, and Web of Science, investigating the synergistic effect of TACE + MWA in the treatment of advanced HCC. Endpoints were the 1-, 2- and 3-year survival rates, local control rate (LCR), objective remission rate (ORR), and adverse event (AE). Odds ratio (OR) with 95% confidence interval (CI) was used to determine the effect size.Results: Nine studies including 351 patients in the TACE + MWA group and 653 patients in the TACE group were enrolled in this meta-analysis. The pooled OR for the 1-, 2-, and 3-year survival rates were in favor of TACE + MWA (OR = 3.29, 95% CI 2.26-4.79; OR = 2.82, 95% CI 2.01-3.95; OR = 4.50, 95% CI 2.96-6.86; respectively). The pooled OR for the ORR and LCR were also in favor of TACE + MWA (OR = 4.64, 95%CI 3.11-6.91; OR = 3.93, 95% CI 2.64-5.87; respectively). No significant difference in the incidence of severe AE was observed between TACE + MWA group and TACE group (p > .05). However, subgroup analysis showed that patients with tumor size >5 cm were more likely to be benefited from TACE + MWA, rather than patients with tumor size ≤5 cm.Conclusion: With the current data, we concluded that combination TACE and MWA was safe, and should be strongly recommended to unresectable patients with tumor size >5 cm, but TACE alone was enough for unresectable patients with tumor size ≤5 cm. However, the conclusion needs further validation.

Does high-grade dysplasia/carcinoma in situ of the biliary duct margin affect the prognosis of extrahepatic cholangiocarcinoma? A meta-analysis.

BACKGROUND: High-grade dysplasia/carcinoma in situ (HGD/CIS) of the biliary duct margin was found to not affect the prognosis of patients with extrahepatic cholangiocarcinoma by recent studies, but it has not yet reached a conclusion. METHODS: Eligible studies were searched by PubMed, PMC, MedLine, Embase, the Cochrane Library, and Web of Science, from Jan. 1, 2000 to Jun. 30, 2019, investigating the influences of surgical margin status of biliary duct on the prognosis of patients with resectable extrahepatic cholangiocarcinoma. Overall survival (OS) and local recurrence were evaluated by odds ratio (OR) with 95% confidence interval (CI). RESULTS: A total of 11 studies were enrolled in this meta-analysis, including 1734 patients in the R0 group, 194 patients in the HGD/CIS group, and 229 patients in the invasive carcinoma (INV) group. The pooled OR for the 1-, 2-, and 3-year OS rate between HGD/CIS group and R0 group was 0.98 (95% CI 0.65~1.50), 1.01 (95% CI 0.73~1.41), and 0.98 (95% CI 0.72~1.34), respectively. The pooled OR for the 1-, 2-, and 3-year OS rate between HGD/CIS group and INV group was 1.83 (95% CI 1.09~3.06), 4.52 (95% CI 2.20~9.26), and 3.74 (95% CI 2.34~5.96), respectively. Subgroup analysis of extrahepatic cholangiocarcinoma at early stage showed that the pooled OR for the 1-, 2-, and 3-year OS rate between HGD/CIS group and R0 group was 0.54 (95% CI 0.21~1.36), 0.75 (95% CI 0.35~1.58), and 0.74 (95% CI 0.40~1.37), respectively, and the pooled OR for the 1-, 2-, and 3-year OS rate between HGD/CIS group and INV group was 3.47 (95% CI 1.09~11.02), 9.12 (95% CI 2.98~27.93), and 9.17 (95% CI 2.95~28.55), respectively. However, the pooled OR for the incidence of local recurrence between HGD/CIS group and R0 group was 3.54 (95% CI 1.66~7.53), and the pooled OR for the incidence of local recurrence between HGD/CIS group and INV group was 0.93 (95% CI 0.50~1.74). CONCLUSION: With the current data, we concluded that HGD/CIS would increase the risk of local recurrence compared with R0, although it did not affect the prognosis of patients with extrahepatic cholangiocarcinoma regardless of TNM stage. However, the conclusion needs to be furtherly confirmed.

A systematic review of the comparison of the incidence of seeding metastasis between endoscopic biliary drainage and percutaneous transhepatic biliary drainage for resectable malignant biliary obstruction.

BACKGROUND AND AIM: Endoscopic biliary drainage (EBD) and percutaneous biliary drainage (PTBD) are the two main strategies of preoperative biliary drainage (PBD) for resectable malignant biliary obstruction (MBO) worldwide, but which is better remains unclear. Seeding metastasis (SM) has been reported repeatedly in the recent decade, although it is rarely taken into consideration in the choice of PBD. Hence, a systematic review was badly warranted to evaluate the incidence of SM between PTBD and EBD in the preoperative treatment of MBO. METHODS: PubMed, MEDLINE, the Cochrane Library, and Web of Science were used to identify any potentially eligible studies comparing the incidence of SM between EBD and PTBD from Nov 1990 to Mar 2018. The effect size was determined by odds ratio (OR) with 95% confidence interval (CI). RESULTS: Ten studies were enrolled in this study, including 1379 cases in the EBD group and 1085 cases in the PTBD group. Results showed that the incidence of SM in the EBD group was significantly lower than that in the PTBD group (10.5% vs. 22.0%, OR = 0.35, 95% CI 0.23~0.53). Subgroup analysis stratified by the definition of SM showed that the pooled ORs for peritoneal metastasis and tube-related SM between EBD and PTBD were 0.42 (95% CI 0.31~0.57) and 0.17 (95% CI 0.10~0.29), respectively. Subgroup analysis stratified by the location of MBO showed that the pooled ORs for the incidence of SM between EBD and PTBD for perihilar cholangiocarcinoma, distal cholangiocarcinoma, and pancreatic cancer were 0.27 (95% CI 0.13~0.56), 0.32 (95% CI 0.17~0.60), and 0.27 (95% CI 0.19~0.40), respectively. CONCLUSION: EBD should be the optimal PBD for MBO considering the SM, but it deserved further validation.

Does postoperative adjuvant transarterial chemoembolization benefit for all patients with hepatocellular carcinoma combined with microvascular invasion: a meta-analysis.

Purpose: To evaluate the clinical efficacy of postoperative adjuvant transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) patients combined with microvascular invasion (MVI). Patients and methods: Eligible studies were searched by PubMed, MedLine, Embase, the Cochrane Library, Web of Science, from 1st January 2000 to 31st December 2018, comparing the overall survival (OS) rates and disease-free survival (DFS) rates between postoperative adjuvant TACE and operation only for HCC patients with MVI. Hazard ratio (HR) with 95% confidence interval (CI) was used to determine the effect size. Results: Eight studies were enrolled in this meta-analysis, including 774 patients in the postoperative adjuvant TACE group and 856 patients in the operation only group. The pooled HR for the OS and DFS rates were significantly different between the postoperative adjuvant TACE group and the operation only group (HR 0.57, 95%CI 0.48 ∼ 0.68, p < .00001; HR 0.66, 95%CI 0.58 ∼ 0.74, p < .00001; respectively). However, in the subgroup analysis stratified by proportion of multiple-nodules, no significant differences were observed in the pooled HR for the OS/DFS rates between the postoperative adjuvant TACE group and the operation only group (HR 0.83, 95%CI 0.60 ∼ 1.13, p = .23; HR 0.76, 95%CI 0.41 ∼ 1.40, p = .37; respectively). Conclusions: Postoperative adjuvant TACE will benefit patients with HCC and MVI, but not for multiple-HCC with MVI. However, more high-quality studies are warranted to validate the conclusion.

Comparison of long-term efficacy between endoscopic and percutaneous biliary drainage for resectable extrahepatic cholangiocarcinoma with biliary obstruction: A systematic review and meta-analysis.

BACKGROUND/AIM: For resectable extrahepatic cholangiocarcinoma with biliary obstruction, it remains a controversy whether to choose percutaneous transhepatic biliary drainage (PTBD) or endoscopic biliary drainage (EBD). A systematic review was conducted to compare the long-term efficacy between the two techniques. MATERIALS AND METHODS: Eligible studies were searched from January 1990 to May 2018, comparing the long-term efficacy between EBD and PTBD for extrahepatic cholangiocarcinoma. Primary end point was overall survival (OS) rate, and secondary end points included postoperative severe complications and seeding metastasis. Effect size on outcomes was calculated using a fixed- or random-effect model, accompanied with hazard ratio (HR) and 95% confidence interval (CI). RESULT: Six studies were included in this meta-analysis. Meta-analysis showed that EBD was superior to PTBD in OS (HR = 0.70, 95% CI 0.59-0.84,P= 0.0002). But subgroup results showed that the superiority disappeared in distal cholangiocarcinoma (HR = 0.76, 95% CI 0.56-1.01,P= 0.06). Other prognostic factors such as intraoperative blood transfusion, lymphatic metastasis and seeding metastasis, were inconsistent between groups. In addition, regional disparity was obviously apparent between Japanese and non-Japanese studies. CONCLUSION: The conclusion that EBD was superior to PTBD in OS for resectable extrahepatic cholangiocarcinoma with biliary obstruction is less convincing, and more trials need to be conducted in future.

Metallothioneins may be a potential prognostic biomarker for tumors: A Prisma-compliant meta-analysis.

BACKGROUND: Metallothioneins (MTs) were reported to be associated with many kinds of tumors' prognosis, although MTs expression varied greatly among tumors. To assess the prognostic value of Metallothioneins (MTs) in different kinds of tumors, comprehensive literature search was conducted to perform a meta-analysis. METHODS: Eligible studies were identified by PubMed, MEDLINE, Web of Science (WOS), the Cochrane Library of Systematic Reviews, EMBASE, China National Knowledge Infrastructure (CNKI), WANFANG database and SinoMed database up to December 2017, which was designed to assess the prognostic value of MTs in different kinds of tumors. The main endpoint events were overall survival (OS) and disease-free survival (DFS). Hazard ratios (HRs) and its variance were retrieved from the original studies directly or calculated using Engauge Digitizer version 4.1. Random or fixed effects model meta-analysis was employed depending on the heterogeneity. Publication bias was evaluated by funnel plots, Begg and Egger tests. RESULTS: A total of 22 studies were enrolled in this meta-analysis, including 2843 tumor tissues (1517 were MTs negative/low, and 1326 were MTs high). Results showed that there was significant association between MTs expression and tumors' OS (HR = 1.60; 95%CI 1.34∼1.92, P < .00001). Subgroup analysis showed that high level of MTs expression was associated with prolonged OS in liver cancer (HR = 0.65, 95%CI 0.48∼0.89, P = .007), but it was on the contrary in the tumor of ovary (HR = 1.47, 95%CI 1.01∼2.14, P = .04), bladder (HR = 1.71, 95%CI 1.21∼2.42, P = .002), intestine (HR = 3.13, 95%CI 1.97∼4.97, P < .00001), kidney (HR = 3.31, 95%CI 1.61∼6.79, P = .001). However, there was no significant association between MTs expression and OS in breast (HR = 1.02, 95%CI 0.69∼1.51, P = .93). CONCLUSIONS: MTs could be taken as a potential prognostic biomarker for tumors, and uniqueness of MTs prognostic value in liver cancer deserved further study.