Elevated Pretherapy Serum IL17 in Primary Hepatocellular Carcinoma Patients Correlate to Increased Risk of Early Recurrence after Curative Hepatectomy

Abstract Background The inflammation indexes in blood routine play an essential role in evaluating the prognosis of patients with hepatocellular carcinoma, but the effect on early recurrence has not been clarified. The study aimed to investigate the risk factors of early recurrence (within 2 years) and recurrence-free survival after curative hepatectomy and explore the role of inflammatory indexes in predicting early recurrence. Methods The baseline data of 161 patients with hepatocellular carcinoma were analyzed retrospectively. The optimal cut-off value of the inflammatory index was determined according to the Youden index. Its predictive performance was compared by the area under the receiver operating characteristic curve. Logistic and Cox regression analyses were used to determine the risk factors of early recurrence and recurrence-free survival. Results The area under the curve of monocyte to lymphocyte ratio (MLR) for predicting early recurrence was 0.700, which was better than systemic inflammatory response index (SIRI), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and systemic immune-inflammatory index (SII). MLR, tumour size, tumour differentiation and BCLC stage are all risk factors for early recurrence and recurrence-free survival of HCC. Combining the above four risk factors to construct a joint index, the area under the curve for predicting early recurrence was 0.829, which was better than single MLR, tumour size, tumour differentiation and BCLC stage. Furthermore, with the increase of risk factors, the recurrence-free survival of patients is worse. Conclusion The combination of MLR and clinical risk factors is helpful for clinicians to identify high-risk patients with early recurrence and carry out active postoperative adjuvant therapy to improve the prognosis of patients.

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Contrast-enhanced ultrasound–based ultrasomics score: a potential biomarker for predicting early recurrence of hepatocellular carcinoma after resection or ablation

British Journal of Radiology ◽

10.1259/bjr.20210748 ◽

2021 ◽

Author(s):

Hui Huang ◽

Si-min Ruan ◽

Meng-fei Xian ◽

Ming-de Li ◽

Mei-qing Cheng ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

High Risk ◽

Risk Group ◽

Early Recurrence ◽

High Risk Group ◽

Low Risk ◽

Primary Hepatocellular Carcinoma ◽

Contrast Enhanced Ultrasound ◽

Combined Model ◽

Contrast Enhanced

Objectives: This study aimed to construct a prediction model based on contrast-enhanced ultrasound (CEUS) ultrasomics features and investigate its efficacy in predicting early recurrence (ER) of primary hepatocellular carcinoma (HCC) after resection or ablation. Methods: This study retrospectively included 215 patients with primary HCC, who were divided into a developmental cohort (n = 139) and a test cohort (n = 76). Four representative images—grayscale ultrasound, arterial phase, portal venous phase and delayed phase —were extracted from each CEUS video. Ultrasomics features were extracted from tumoral and peritumoral area inside the region of interest. Logistic-regression was used to establish models, including a tumoral model, a peritumoral model and a combined model with additional clinical risk factors. The performance of the three models in predicting recurrence within 2 years was verified. Results: The combined model performed best in predicting recurrence within 2 years, with an area under the curve (AUC) of 0.845, while the tumoral model had an AUC of 0.810 and the peritumoral model one of 0.808. For prediction of recurrence-free survival, the 2 year cumulative recurrence rate was significant higher in the high-risk group (76.5%) than in the low-risk group (9.5%; p < 0.0001). Conclusion: These CEUS ultrasomics models, especially the combined model, had good efficacy in predicting early recurrence of HCC. The combined model has potential for individual survival assessment for HCC patients undergoing resection or ablation. Advances in knowledge: CEUS ultrasomics had high sensitivity, specificity and PPV in diagnosing early recurrence of HCC, and high efficacy in predicting early recurrence of HCC (AUC > 0.8). The combined model performed better than the tumoral ultrasomics model and peritumoral ultrasomics model in predicting recurrence within 2 years. Recurrence was more likely to occur in the high-risk group than in the low-risk group, with 2-year cumulative recurrence rates respectively 76.5% and 9.5% (p < 0.0001).

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Factors predicting long-term outcome of early stage hepatocellular carcinoma after primary curative treatment - the role of surgical or nonsurgical methods

10.21203/rs.3.rs-117992/v1 ◽

2020 ◽

Author(s):

Ming-Jeng Kuo ◽

Chi-Ling Chen ◽

Lein-ray Mo

Keyword(s):

Hepatocellular Carcinoma ◽

Late Recurrence ◽

Early Recurrence ◽

Curative Treatment ◽

Treatment Modalities ◽

Long Term Outcome ◽

Increased Risk ◽

Significant Difference ◽

Early Hcc ◽

Time Varying Covariates

Abstract Background The effect of putative factors on the clinical course of early hepatocellular carcinoma (HCC) after primary surgical or nonsurgical curative treatment, which remains elusive, was quantified. Methods Patients with newly diagnosed early HCC who received surgical resection (SR) or percutaneous radiofrequency ablation (RFA) with or without transcatheter arterial chemoembolization (TACE) from January 2003 to December 2016 were enrolled. The cumulative overall survival (OS) and disease-free survival (DFS) were compared. A polytomous logistic regression was used to estimate factors regarding early and late recurrence. Independent predictors of OS were identified using Cox proportional hazard regression. Results One hundred twenty-five patients underwent SR, and 176 patients underwent RFA, of whom 72 were treated with TACE followed by RFA. Either match analysis based on propensity score or multiple adjustment regression showed no significant difference in DFS and OS between the two groups. Multivariate analysis showed high AFP (>= 20 ng/mL), and multinodularity significantly increased risk of early recurrence (<=1year). In contrast, hepatitis B virus, hepatitis C virus and multinodularity were significantly associated with late recurrence (>1year). Multivariate Cox regression with recurrent events as time-varying covariates identified older age (HR=1.55, 95% CI:1.01-2.36), clinically significant portal hypertension (CSPH) (HR=1.97, 95% CI:1.26-3.08), early recurrence (HR=6.62, 95% CI:3.79-11.6) and late recurrence (HR=3.75, 95% CI:1.99-7.08) as independent risk factors of mortality. A simple risk score showed fair calibration and discrimination in early HCC patients after primary curative treatment. In the Barcelona Clinic Liver Cancer (BCLC) stage A subgroup, SR significantly improved DFS comparing to those received RFA with or without TACE. Conclusion Host and tumor factors rather than the initial treatment modalities determine the outcomes of early HCC after primary curative treatment. Statistical models based on recurrence types can predict early HCC prognosis but further external validation is necessary.

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Serum α-fetoprotein level as a biomarker for early recurrence after R0 resection in primary hepatocellular carcinoma

Family Medicine and Community Health ◽

10.15212/fmch.2013.0202 ◽

2013 ◽

Vol 1 (2) ◽

pp. 9-14

Author(s):

Songpeng Li ◽

Liqun Wu

Keyword(s):

Hepatocellular Carcinoma ◽

Early Recurrence ◽

Primary Hepatocellular Carcinoma ◽

R0 Resection

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Risk factors and patterns of early recurrence after curative hepatectomy for hepatocellular carcinoma

Surgical Oncology ◽

10.1016/j.suronc.2015.12.002 ◽

2016 ◽

Vol 25 (1) ◽

pp. 24-29 ◽

Cited By ~ 42

Author(s):

Fumitoshi Hirokawa ◽

Michihiro Hayashi ◽

Mitsuhiro Asakuma ◽

Tetsunosuke Shimizu ◽

Yoshihiro Inoue ◽

...

Keyword(s):

Risk Factors ◽

Hepatocellular Carcinoma ◽

Early Recurrence ◽

Curative Hepatectomy

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TERT Mutations Correlated With the Prognosis of Patients With Hepatitis B-Related Hepatocellular Carcinoma Underwent Curative Hepatectomy

10.21203/rs.3.rs-283746/v1 ◽

2021 ◽

Author(s):

Kangjian Song ◽

Junyu Huo ◽

Fu He ◽

Qingwei Zhu ◽

Liqun Wu

Keyword(s):

Risk Factors ◽

Hepatocellular Carcinoma ◽

Overall Survival ◽

Hepatitis B ◽

Poor Prognosis ◽

Early Recurrence ◽

Single Factor ◽

Risk Factors For Recurrence ◽

Independent Risk Factors ◽

Curative Hepatectomy

Abstract Background To explore the value of TERT mutations in predicting the early recurrence and prognosis of hepatitis B-related hepatocellular carcinoma (HCC) patients underwent curative hepatectomy.Methods A total of 81 patients with hepatitis B-related HCC were enrolled and all patients underwent curative hepatectomy. Associations were sought between TERT mutations and recurrence rate within 2 years after hepatectomy, time to progress (TTP) and overall survival (OS).Results TERT mutations (HR: 2.985, 95%CI: 1.158-7.692, p=0.024) and Barcelona clinic liver (BCLC) stage B (HR: 3.326, 95%CI: 1.019-10.856, p=0.046) were independent risk factors for recurrence within 2 years after hepatectomy. Patients with a TERT mutation had poor TTP (p=0.003) and OS (p=0.013) than others. TERT mutations (HR: 2.245, 95%CI: 1.185-4.252, p=0.013) and BCLC stage B (HR: 2.132, 95%CI: 1.082-4.198, p=0.029) were independent risk factors for poor TTP after curative hepatectomy. A predictive model based on TERT mutations and BCLC stage had better ability to predict early recurrence after hepatectomy of HCC patients than any single factor (AUC: 0.688 vs. 0.639, 0.688 vs. 0.607, respectively). Patients with both TERT mutations and BCLC stage B had poorer TTP and OS than others (p=0.001, p<0.001, respectively).Conclusion TERT mutations had ability to predict early recurrence and poor prognosis for hepatitis B-related HCC patients underwent curative hepatectomy.

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Transglutaminase 2 is upregulated in primary hepatocellular carcinoma with early recurrence as determined by proteomic profiles

International Journal of Oncology ◽

10.3892/ijo.2017.3917 ◽

2017 ◽

Vol 50 (5) ◽

pp. 1749-1759 ◽

Cited By ~ 5

Author(s):

Hiromi Yamaguchi ◽

Kazumichi Kuroda ◽

Masahiko Sugitani ◽

Tadatoshi Takayama ◽

Kiyoshi Hasegawa ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Transglutaminase 2 ◽

Early Recurrence ◽

Primary Hepatocellular Carcinoma

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Factors predicting long-term outcomes of early-stage hepatocellular carcinoma after primary curative treatment: the role of surgical or nonsurgical methods

BMC Cancer ◽

10.1186/s12885-021-07948-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ming-Jeng Kuo ◽

Lein-Ray Mo ◽

Chi-Ling Chen

Keyword(s):

Hepatocellular Carcinoma ◽

External Validation ◽

Late Recurrence ◽

Early Recurrence ◽

Curative Treatment ◽

Treatment Modalities ◽

Increased Risk ◽

Significant Difference ◽

Early Hcc ◽

Time Varying Covariates

Abstract Background We quantified the elusive effects of putative factors on the clinical course of early hepatocellular carcinoma (HCC) after primary surgical or nonsurgical curative treatment. Methods Patients with newly diagnosed early HCC who received surgical resection (SR) or percutaneous radiofrequency ablation (RFA) with or without transcatheter arterial chemoembolization (TACE) from January 2003 to December 2016 were enrolled. The cumulative overall survival (OS) and disease-free survival (DFS) rates were compared. A polytomous logistic regression was used to estimate factors for early and late recurrence. Independent predictors of OS were identified using Cox proportional hazard regression. Results One hundred twenty-five patients underwent SR, and 176 patients underwent RFA, of whom 72 were treated with TACE followed by RFA. Neither match analysis based on propensity score nor multiple adjustment regression yielded a significant difference in DFS and OS between the two groups. Multivariate analysis showed high AFP (> 20 ng/mL), and multinodularity significantly increased risk of early recurrence (< 1 year). In contrast, hepatitis B virus, hepatitis C virus and multinodularity were significantly associated with late recurrence (> 1 year). Multivariate Cox regression with recurrent events as time-varying covariates identified older age (HR = 1.55, 95% CI:1.01–2.36), clinically significant portal hypertension (CSPH) (HR = 1.97, 95% CI:1.26–3.08), early recurrence (HR = 6.62, 95% CI:3.79–11.6) and late recurrence (HR = 3.75, 95% CI:1.99–7.08) as independent risk factors of mortality. A simple risk score showed fair calibration and discrimination in early HCC patients after primary curative treatment. In the Barcelona Clinic Liver Cancer (BCLC) stage A subgroup, SR significantly improved DFS compared to RFA with or without TACE. Conclusion Host and tumor factors rather than the initial treatment modalities determine the outcomes of early HCC after primary curative treatment. Statistical models based on recurrence types can predict early HCC prognosis but further external validation is necessary.

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Risk factors of early recurrence after curative hepatectomy in hepatocellular carcinoma

Tumor Biology ◽

10.1177/1010428317720863 ◽

2017 ◽

Vol 39 (10) ◽

pp. 101042831772086 ◽

Cited By ~ 8

Author(s):

Young Mi Hong ◽

Mong Cho ◽

Ki Tae Yoon ◽

Chong Woo Chu ◽

Kwang Ho Yang ◽

...

Keyword(s):

Risk Factors ◽

Hepatocellular Carcinoma ◽

Early Recurrence ◽

Curative Hepatectomy

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Expression and prognostic value of ING3 in human primary hepatocellular carcinoma

Experimental Biology and Medicine ◽

10.1258/ebm.2011.011346 ◽

2012 ◽

Vol 237 (4) ◽

pp. 352-361 ◽

Cited By ~ 16

Author(s):

Hai-Yan Yang ◽

Hao-Ling Liu ◽

Lan-Tian Tian ◽

Rui-Peng Song ◽

Xuan Song ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Human Hepatocellular Carcinoma ◽

Primary Hepatocellular Carcinoma ◽

Pathological Characteristics ◽

Kaplan Meier ◽

Increased Risk ◽

And Function ◽

The Relationship ◽

Low Expression ◽

Liver Tissues

The tumor-suppressor ING3 has been shown to be involved in tumor transcriptional regulation, apoptosis and the cell cycle. Some studies have demonstrated that ING3 is dysregulated in several types of cancers. However, the expression and function of ING3 in human hepatocellular carcinoma (HCC) remains unclear. The aim of this study is to investigate ING3 expression in hepatic tumors and its clinical relevance in hepatic cancer. The expression of ING3 protein was examined in 120 dissected HCC tissues and 47 liver tissues adjacent to the tumor by immunohistochemical assays and confirmed by Western blot analysis in 20 paired frozen tumor and non-tumor liver tissues. The relationship between ING3 staining and clinico-pathological characteristics of HCC was further analyzed. The mRNA expression of ING3 in the dissected tissues was also analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) and realtime PCR. Both mRNA and protein concentrations of ING3 were found to be downregulated in the majority of HCC tumors in comparison with matched non-tumor hepatic tissues. Analysis of the relationship between ING3 staining and clinico-pathological characteristics of HCC showed that the low expression of ING3 protein is correlated with more aggressive behavior of the tumor. Kaplan–Meier curves demonstrated that patients with a low expression of ING3 have a significantly increased risk of shortened survival time. In addition, multivariate analysis suggested that the level of ING3 expression may be an independent prognostic factor. Our findings indicate that ING3 may be an important marker for human hepatocellular carcinoma progression and prognosis, as well as a potential therapeutic target.

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