Prognostic Impact of Surgical Margin in Hepatectomy On Patients with Hepatocellular Carcinoma: A Meta-Analysis of Observational Studies

Abstract Objective This study aims to comprehensively evaluate the prognostic impact of the surgical margin in hepatectomy on patients diagnosed with hepatocellular carcinoma (HCC). Methods A comprehensive and systematic search for eligible articles published in English before July 2021 was conducted in PubMed, Cochrane Library, Web of Science, and Embase electronic databases. Notably, overall survival (OS) and disease-free survival (DFS) were the primary endpoints. Results In total, 37 observational studies with 12,295 cases were included in this meta-analysis. The results revealed that a wide surgical margin (≥1 cm) was associated with better OS (hazard ration (HR), 0.70; 95% confidence interval (CI), 0.63-0.77) and DFS (HR, 0.66; 95% CI, 0.61-0.71) compared to a narrow surgical margin (<1 cm). Subgroup analyses were conducted based on median follow-up time, gender, country, hepatitis B surface antigen (HBsAg) status, tumor number, and liver cirrhosis. The prognostic benefit of a wide surgical margin was consistent in most subgroups, however, analysis of studies from Western countries showed that margin width was not associated with prognosis. Conclusion In summary, a wide surgical margin prolongs the long-term prognosis of HCC patients compared to a narrow surgical margin.

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Evaluation of Antiviral Therapy Performed after Curative Therapy in Patients with HBV-Related Hepatocellular Carcinoma: An Updated Meta-Analysis

Canadian Journal of Gastroenterology and Hepatology ◽

10.1155/2016/5234969 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 3

Author(s):

Peng Yuan ◽

Peng Chen ◽

Yeben Qian

Keyword(s):

Hepatocellular Carcinoma ◽

Meta Analysis ◽

Disease Free Survival ◽

Curative Therapy ◽

B Virus ◽

Effect Of Treatment ◽

Long Term Prognosis ◽

One Year ◽

The One ◽

The Impact

Background.The long-term prognosis after curative therapy for hepatitis B virus- (HBV-) related hepatocellular carcinoma (HCC) remains unsatisfactory due to the high incidence of recurrence. The effect of treatment with nucleotide analogues (NAs) in patients with HBV-related HCC after curative therapy remains unclear.Objective.To assess the impact of using NAs after curative therapy.Method.A computerized literature search was performed; eligible studies were identified from databases. The pooled risk ratios (RRs) and 95% CIs were calculated using Review Manager 5.3.Result.The meta-analysis included a total of 15 studies with 8060 patients. The one-year and three-year recurrence (one-year recurrence: RR 0.41 [95% CI 0.28 to 0.61];P<0.00001; three-year recurrence: RR 0.63 [95% CI 0.43 to 0.94];P=0.001) and the one-, three-, and five-year overall survival (OS) and disease-free survival (DFS) were significantly better in the treatment group.Conclusion.NAs can reduce the recurrence and improve the prognosis of HBV-related HCC after curative therapy.

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Prognostic Significance of High Survivin Expression in Patients with Gastrointestinal Cancer: A Meta-Analysis

10.20944/preprints201704.0062.v1 ◽

2017 ◽

Author(s):

Pingping Xu ◽

Jiajia Lin ◽

Qi Lin ◽

Dexiang Zhu ◽

Wentao Tang ◽

...

Keyword(s):

Cancer Patients ◽

Meta Analysis ◽

Prognostic Significance ◽

Survivin Expression ◽

Disease Free Survival ◽

Cochrane Library ◽

Prognostic Impact ◽

Gi Cancer ◽

Literature Searches ◽

The Cochrane Library

Previous studies on the prognostic impact of survivin expression in gastrointestinal (GI) cancer have yielded inconsistent results. This study was initiated to assess the relationship between survivin expression and overall survival (OS) or disease free survival (DFS) in GI cancer patients. We applied system literature searches on EMBASE, PubMed, Web of science, and the Cochrane library to conduct this up-to-date meta-analysis. Thirty studies with totally 3622 GI cancer patients were collected. The prevalence of high survivin expression in GI cancer was 0.57 (95% CI: 0.51-0.63). High survivin expression was significantly associated with shorter OS (HR 1.57, 95% CI: 1.42-1.74) and DFS (HR 1.38, 95% CI: 1.21-1.58). Subgroup analysis also showed significant association between high survivin expression and poorer OS or DFS in gastric cancer or colorectal cancer. In summary, our study indicated that high survivin expression was related to poor prognosis in GI cancer. Well-designed studies with large sample and more convincing data are needed to confirm our conclusion.

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Prognostic significance of platelet-to-lymphocyte ratio in urothelial carcinoma patients: a meta-analysis

Cancer Cell International ◽

10.1186/s12935-019-1032-6 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 2

Author(s):

Yuhai Bao ◽

Yin Wang ◽

Xiaodong Li ◽

Mingjun Pan ◽

Hongze Zhang ◽

...

Keyword(s):

Urothelial Carcinoma ◽

Meta Analysis ◽

Prognostic Significance ◽

Disease Free Survival ◽

Cochrane Library ◽

Prognostic Impact ◽

Platelet To Lymphocyte Ratio ◽

Cancer Specific Survival ◽

Free Survival ◽

Lymphocyte Ratio

Abstract Background The prognostic value of pre-treatment platelet-to-lymphocyte ratio (PLR) in patients with urothelial carcinoma (UC) remains controversial. Therefore, this meta-analysis aimed to identify the prognostic impact of PLR on UC. Methods The PubMed, Embase, Web of Science, and Cochrane Library databases were systematically searched. Hazard ratios (HRs) with 95% confidence intervals (CIs) were used to summarize the correlations between PLR and overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), and cancer-specific survival (CSS). Odds ratios (ORs) with 95% CIs were used to measure the association between PLR and tumor clinicopathological factors. Results The meta-analysis included 15 studies published from 2015 to 2019 with a total of 5354 patients. Overall, a high PLR was correlated to poorer PFS (HR = 1.81, 95% CI 1.28–2.56, p = 0.001) and DFS (HR = 1.09, 95% CI 1.31–2.16, p < 0.001) but not poor OS (HR = 1.23, 95% CI 0.95–1.59, p = 0.124) or CSS (HR = 1.000, 95% CI 0.998–1.002, p = 0.919) in UC. In addition, an elevated PLR was correlated with patient age > 65 years (OR = 1.72, 95% CI 1.25–2.38, p = 0.001) and hypertension (OR = 1.48, 95% CI 1.01–2.18, p = 0.046). However, no significant association was observed between PLR and sex (OR = 0.79, 95% CI 0.56–1.14, p = 0.206) or diabetes (OR = 1.29, 95% CI 0.77–2.15, p = 0.333). Conclusions Our results demonstrated a significant correlation between elevated PLR and poor prognosis in UC. The prognostic role of PLR may help guide the management and prognostication of UC patients.

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Prognostic Influence of Spontaneous Tumor Rupture in Patients with Hepatocellular Carcinoma After Hepatectomy: A Meta-Analysis of Observational Studies

10.21203/rs.3.rs-665806/v1 ◽

2021 ◽

Author(s):

Jiaxuan Xu ◽

Lihu Gu ◽

Binbin Xu ◽

Yuexiu Si ◽

Yujing He ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Risk Factor ◽

Hepatic Resection ◽

Meta Analysis ◽

Disease Free Survival ◽

Cochrane Library ◽

Tumor Rupture ◽

Free Survival ◽

Spontaneous Tumor ◽

Ruptured Hepatocellular Carcinoma

Abstract Background: This study aims to comprehensively analyze the influence of spontaneous tumor rupture on the prognosis of hepatocellular carcinoma patients following hepatic resection.Methods: We systematically searched four online electronic databases, including PubMed, Embase, Web of Science, and Cochrane Library, for eligible studies published from inception to March 2021. The main endpoints were overall survival (OS) and disease-free survival (DFS).Results: This meta-analysis included 21 observational articles with 57241 cases. The results revealed that spontaneous tumor rupture was associated with worse OS (hazard ratio (HR), 1.65; 95% confidence interval (CI), 1.33-2.05) and DFS (HR, 1.42; 95% CI, 1.12-1.80) in resectable hepatocellular carcinoma patients. This phenomenon was observed in most subgroups, which were classified by recorded survival time, age, country, alpha-fetoprotein (AFP) concentration, liver cirrhosis, and microvascular invasion. However, in subgroups of macrovascular invasion positive, spontaneous tumor rupture was not a risk factor for OS (HR, 1.55; 95% CI, 0.99-2.42) and DFS (HR, 1.23; 95% CI, 0.91-1.65) in hepatocellular carcinoma patients after hepatectomy. For macrovascular invasion negative, compared with non-ruptured hepatocellular carcinoma patients, ruptured hepatocellular carcinoma patients exhibited worse prognosis for OS (HR, 1.55; 95% CI, 0.99-2.42) and DFS (HR, 1.23; 95% CI, 0.91-1.65) following hepatectomy.Conclusions: Spontaneous tumor rupture was a prognostic risk factor for hepatocellular carcinoma patients after hepatic resection. However, in macrovascular invasion patients, spontaneous tumor rupture was not a prognostic risk factor.

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Laparoscopic versus open major liver resection for hepatocellular carcinoma: systematic review and meta-analysis of comparative cohort studies

BMC Cancer ◽

10.1186/s12885-019-6240-x ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 7

Author(s):

Zi-Yu Wang ◽

Qing-Lian Chen ◽

Ling-Ling Sun ◽

Shu-Ping He ◽

Xiao-Fen Luo ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Resection ◽

Blood Loss ◽

Hospital Stay ◽

Weighted Mean Difference ◽

Meta Analysis ◽

Disease Free Survival ◽

Operation Time ◽

Cochrane Library ◽

Random Effects Models

Abstract Background The application of laparoscopic liver resection (LLR) has expanded rapidly in recent decades. Although multiple authors have reported LLR shows improved safety and efficacy in treating hepatocellular carcinoma (HCC) compared with open liver resection (OLR), laparoscopic (LMLR) and open (OMLR) major liver resections for HCC treatment remain inadequately evaluated. This work aimed to test the hypothesis that LMLR is safer and more effective than OMLR for HCC. Methods Comparative cohort and registry studies on LMLR and OMLR, searched in PubMed, the Science Citation Index, EMBASE, and the Cochrane Library, and published before March 31, 2018, were collected systematically and meta-analyzed. Fixed- and random-effects models were employed for generating pooled estimates. Heterogeneity was assessed by the Q-statistic. Results Nine studies (1173 patients) were included. Although the pooled data showed operation time was markedly increased for LMLR in comparison with OMLR (weighted mean difference [WMD] 74.1, 95% CI 35.1 to 113.1, P = 0.0002), blood loss was reduced (WMD = − 107.4, 95% CI − 179.0 to − 35.7, P = 0.003), postoperative morbidity was lower (odds ratio [OR] 0.47, 95% CI 0.35 to 0.63, P < 0.0001), and hospital stay was shorter (WMD = − 3.27, 95% CI − 4.72 to − 1.81, P < 0.0001) in the LMLR group. Although 1-year disease-free survival (DFS) was increased in patients administered LMLR (OR = 1.55, 95% CI 1.04 to 2.31, P = 0.03), other 1-, 3-, and 5-year survival outcomes (overall survival [OS] and/or DFS) were comparable in both groups. Conclusions Compared with OMLR, LMLR has short-term clinical advantages, including reduced blood loss, lower postsurgical morbidity, and shorter hospital stay in HCC, despite its longer operative time. Long-term oncological outcomes were comparable in both groups.

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The Clinicopathologic and Prognostic Significance of c-Myc Expression in Hepatocellular Carcinoma: A Meta-Analysis

Frontiers in Bioinformatics ◽

10.3389/fbinf.2021.706835 ◽

2021 ◽

Vol 1 ◽

Author(s):

Zhao Min ◽

Zhang Xunlei ◽

Chen Haizhen ◽

Zhao Wenjing ◽

Yu Haiyan ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Publication Bias ◽

Meta Analysis ◽

Prognostic Significance ◽

Disease Free Survival ◽

Cochrane Library ◽

Poor Overall Survival ◽

Hazard Ratios ◽

Incidence And Mortality

Background: The incidence and mortality rates of hepatocellular carcinoma (HCC) are increasing worldwide. Therefore, there is an urgent need to elucidate the molecular drivers of HCC for potential early diagnosis and individualized treatment. Whether c-Myc expression plays a role in the clinicopathology and prognosis of patients with HCC remains controversial. This meta-analysis aimed to survey the prognostic role of c-Myc in HCC.Methods: We searched PubMed, Cochrane Library, Embase, Web of Science, and Google Scholar databases for studies published through March 2020 that examined the association between c-Myc expression and clinicopathology or prognosis in HCC patients. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were used to investigate the prognostic significance of c-Myc expression. Odds ratios were calculated to evaluate the association between c-Myc expression and clinicopathologic features. We also tested for publication bias.Results: Our meta-analysis included nine studies with 981 patients with HCC published between 1999 and 2016. A meta-analysis of these studies demonstrated that high c-Myc expression indicated a poor overall survival (OS) (HR = 2.260, 95% CI: 1.660–3.080, and p < 0.001) and disease-free survival (DFS) (HR = 1.770, 95% CI: 1.430–2.450, and p < 0.001) in patients with HCC. However, high c-Myc expression was not associated with HBsAg, pathological type, TNM stage, or cirrhosis. We did not find any significant publication bias among the included studies, indicating that our estimates were robust and reliable.Conclusion: c-Myc overexpression could predict poor OS and DFS in HCC patients. c-Myc could be a useful prognostic biomarker and therapeutic target for HCC.

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Prognostic Influence of Spontaneous Tumor Rupture in Patients With Hepatocellular Carcinoma After Hepatectomy: A Meta-Analysis of Observational Studies

Frontiers in Surgery ◽

10.3389/fsurg.2021.769233 ◽

2021 ◽

Vol 8 ◽

Author(s):

Jiaxuan Xu ◽

Jiaze Hong ◽

Yiran Wang ◽

Lingling Zhou ◽

Binbin Xu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Risk Factor ◽

Hepatic Resection ◽

Meta Analysis ◽

Disease Free Survival ◽

Cochrane Library ◽

Tumor Rupture ◽

Free Survival ◽

Spontaneous Tumor ◽

Ruptured Hepatocellular Carcinoma

Objective: This study aims to comprehensively analyze the influence of spontaneous tumor rupture on the prognosis of hepatocellular carcinoma patients following hepatic resection.Methods: We systematically searched four online electronic databases, including PubMed, Embase, Web of Science, and Cochrane Library, for eligible studies published from inception to March 2021. The main endpoints were overall survival (OS) and disease-free survival (DFS).Results: This meta-analysis included 21 observational articles with 57,241 cases. The results revealed that spontaneous tumor rupture was associated with worse OS (hazard ratio (HR), 1.65; 95% confidence interval (CI), 1.33–2.05) and DFS (HR, 1.42; 95% CI, 1.12–1.80) in resectable hepatocellular carcinoma patients. This phenomenon was observed in most subgroups, which were classified by recorded survival time, age, country, alpha-fetoprotein (AFP) concentration, liver cirrhosis, and microvascular invasion. However, in subgroups of macrovascular invasion positive, spontaneous tumor rupture was not a risk factor for OS (HR, 1.55; 95% CI, 0.99–2.42) and DFS (HR, 1.23; 95% CI, 0.91–1.65) in hepatocellular carcinoma patients after hepatectomy. For macrovascular invasion negative, compared with non-ruptured hepatocellular carcinoma patients, ruptured hepatocellular carcinoma patients exhibited worse prognosis for OS (HR, 1.55; 95% CI, 0.99–2.42) and DFS (HR, 1.23; 95% CI, 0.91–1.65) following hepatectomy.Conclusions: Spontaneous tumor rupture was a prognostic risk factor for hepatocellular carcinoma patients after hepatic resection. However, in macrovascular invasion patients, spontaneous tumor rupture was not a prognostic risk factor.

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Meta-Analysis of Postoperative Adjuvant Hepatic Artery Infusion Chemotherapy Versus Surgical Resection Alone for Hepatocellular Carcinoma

Frontiers in Oncology ◽

10.3389/fonc.2021.720079 ◽

2021 ◽

Vol 11 ◽

Author(s):

Qiao Ke ◽

Lei Wang ◽

Weimin Wu ◽

Xinhui Huang ◽

Ling Li ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatic Artery ◽

Surgical Resection ◽

Meta Analysis ◽

Disease Free Survival ◽

Cochrane Library ◽

Hepatic Artery Infusion ◽

Infusion Chemotherapy ◽

Hepatic Artery Infusion Chemotherapy

BackgroundTo systematically identify the long-term efficacy of postoperative adjuvant hepatic artery infusion chemotherapy (HAIC) for patients with hepatocellular carcinoma (HCC).MethodsPubMed, MedLine, Embase, the Cochrane Library, and Web of Science were searched to collect the eligible studies up to March 31, 2021, that compared the surgical resection (SR) versus SR+HAIC for HCC patients. The endpoints were overall survival (OS) rates and disease-free survival (DFS) rates, and the effect size was determined by hazard ratio (HR) with 95% CI.ResultsA total of 12 studies (two randomized controlled trials (RCTs) and 10 non-RCTs) including 1,333 patients were eligible for this meta-analysis. The pooled results showed that OS and DFS rates in the SR+HAIC group were both better than those in the SR alone group (HR = 0.56, 95% CI = 0.41–0.77, p < 0.001; HR = 0.66, 95% CI = 0.55–0.78, p < 0.001, respectively). Furthermore, the subgroup analysis showed that patients would benefit from SR+HAIC regardless of chemotherapy regimens and courses (all p < 0.05), and patients with microvascular or macrovascular invasion would also benefit more from SR+HAIC in terms of OS and DFS (all p < 0.05).ConclusionPostoperative adjuvant HAIC could improve the long-term prognosis of HCC patients, especially for those with microvascular or macrovascular invasion, regardless of chemotherapy regimens and courses, but it deserves further validation.

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Prognostic value of programmed cell death ligand 1 (PD-L1) for hepatocellular carcinoma: a meta-analysis

Bioscience Reports ◽

10.1042/bsr20200459 ◽

2020 ◽

Vol 40 (4) ◽

Author(s):

Xiao-Song Li ◽

Jun-Wei Li ◽

Hui Li ◽

Tao Jiang

Keyword(s):

Hepatocellular Carcinoma ◽

Meta Analysis ◽

Disease Free Survival ◽

Tumor Infiltrating Lymphocytes ◽

Cochrane Library ◽

Tumor Differentiation ◽

Clinical Value ◽

Free Survival ◽

Poor Tumor Differentiation ◽

Infiltrating Lymphocytes

Abstract The prognostic role of programmed death ligand-1 (PD-L1) expression in hepatocellular carcinoma (HCC) has been widely studied but the results are controversial. In this comprehensive meta-analysis, we elucidated the clinical value of PD-L1 in HCC. Relevant studies were systematically searched in the Cochrane Library, EMBASE, and PubMed until June 27, 2019. Eligible studies were validated for the prognostic effect of PD-L1 on the overall survival (OS), disease-free survival (DFS), and relapse-free survival (RFS) in HCC using a hazard ratio (HR) and its 95% confidence interval (95% CI). Twenty-three studies with 3529 patients were involved in this meta-analysis. The pooled results revealed that high membrane-bound PD-L1 (mPD-L1) expression was associated with poor OS (HR: 1.42; 95% CI: 1.12–1.80; P = 0.004) and had no significant correlation with RFS (HR: 1.14; 95% CI: 0.85–1.54; P = 0.39), and DFS (HR: 1.36; 95% CI: 0.81–2.28; P = 0.25). The results also indicated that high soluble PD-L1 (sPD-L1) levels were associated with worse OS (HR: 2.93; 95% CI: 2.20–3.91; P < 0.00001). In addition, high mPD-L1 expression was associated with high alpha-fetoprotein levels (AFP; OR = 1.46; 95% CI: 1.16–1.84; P = 0.001), hepatitis (OR = 0.72; 95% CI: 0.54–0.98; P = 0.03), poor tumor differentiation (OR = 0.68; 95% CI: 0.55–0.84; P = 0.03), and tumor-infiltrating lymphocytes (OR = 3.39; 95% CI: 1.06–10.91; P = 0.04). The mPD-L1 expression had no significant correlation with age, number of tumors, gender, tumor size, liver cirrhosis, vascular invasion, tumor encapsulation, or TNM stage. The study revealed that high mPD-L1 expression in the tumor tissue and high sPD-L1 levels were associated with shorter OS in HCC. Moreover, overexpression of mPD-L1 was significantly associated with poor tumor differentiation, hepatitis, AFP elevation, and tumor-infiltrating lymphocytes.

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Meta-analysis of Percutaneous vs. Surgical Approaches Radiofrequency Ablation in Hepatocellular Carcinoma

Frontiers in Surgery ◽

10.3389/fsurg.2021.788771 ◽

2022 ◽

Vol 8 ◽

Author(s):

Xiaozhun Huang ◽

Yibin Liu ◽

Lin Xu ◽

Teng Ma ◽

Xin Yin ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Radiofrequency Ablation ◽

Perioperative Complications ◽

Meta Analysis ◽

Survival Rates ◽

Disease Free Survival ◽

Analysis Data ◽

Cochrane Library ◽

Surgical Approaches ◽

Significant Difference

Background: Radiofrequency ablation (RFA) is a curative modality for hepatocellular carcinoma (HCC) patients who are not suitable for resection. It remains controversial whether a surgical or percutaneous approach is more appropriate for HCC.Method: A search was performed on the PubMed, Web of Science, Embase, and Cochrane Library databases from the date of database inception until April 17, 2021. Studies reporting outcomes of comparisons between surgical RFA (SRFA) and percutaneous RFA (PRFA) were included in this study. The meta-analysis was performed using the Review Manager 5.3 and Stata 12.0 software.Result: A total of 10 retrospective studies containing 12 cohorts, involving 740 patients in the PRFA group and 512 patients in the SRFA group, were selected. Although the tumor size in PRFA group was smaller than the SRFA group (p = 0.007), there was no significant difference in complete ablation rate between the SRFA and PRFA groups (95.63% and 97.33%, respectively; Odds ratio [OR], 0.56; 95% confidence intervals [CI], 0.26–1.24; p = 0.15). However, the SRFA group showed a significantly lower local tumor recurrence than the PRFA group in the sensitivity analysis (28.7% in the PRFA group and 21.79% in the SRFA group, respectively; OR, 1.84; 95% CI, 1.14–2.95; p = 0.01). Pooled analysis data showed that the rate of severe perioperative complications did not differ significantly between the PRFA and SRFA groups (14.28% and 12.11%, respectively; OR, 1.30; 95% CI, 0.67-2.53; p = 0.44). There was no significant difference in the 1-, 3-, and 5-year overall survival rates, as well as the 1- and 3-year disease-free survival (DFS) between the PRFA and SRFA groups. The 5-year DFS of the PRFA group was significantly lower than the SRFA group (hazard ratio 0.73; 95% CI 0.54–0.99).Conclusion: Based on our meta-analysis, the surgical route was superior to PRFA in terms of local control rate. Furthermore, the surgical approach did not increase the risk of major complications.

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