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Yong-Ping Yang,
Jian-Hui Qu,
Xiu-Juan Chang,
Yin-Ying Lu, Wen-Lin Bai,
Zheng Dong,
Hong Wang,
Lin-Jing An,
Zhong-Xian Xu,
Chun-Ping Wang,
Zhen Zeng,
Ke-Qin Hu
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ABSTRACT: BACKGROUND: Cryoablation is one of the local therapies for hepatocellular carcinoma (HCC), but its safety and effect has not been studied in patients with Child class A or B and Barcelona Clinic Liver Cancer (BCLC) stage C HCC. Metastasis-associated in colon cancer-1 (MACC1) overexpression has been associated with poor prognosis of HCC, but its predictive value to post-cryoablation outcomes remains unknown in patients with BCLC stage C HCC. METHODS: This study assessed the safety and outcomes of cryoablation measured by time to progression (TTP) and overall survival (OS), and predictive value of MACC1 mRNA and protein overexpression in tumorous tissue to post-cryoablation outcomes in 120 advanced HCC patients with child-pugh class A or B by quantitative polymerase chain reaction and immunohistochemical staining. The potenial correlation of MACC1 and c-Met expression to tumor cell proliferation and apoptosis was also analyzed. RESULTS: The cryoablation in patients with advanced unresectable HCC resulted in a median TTP and OS of 5.5 (4.2- 6.7) months and 10.5 (9.0-12.0) months, respectively and no significant complications, comparable to the historical report for RFA therapy. The MACC1 mRNA and nuclear protein expression was significantly increased in tumorous tissues in these patients than that in normal liver tissue controls. Higher expression of MACC1 mRNA and nuclear protein in tumorous tissues in these patients was associated with shorter post cryoablation median TTP and OS than that with lower MACC1 expression. CONCLUSIONS: Cryoablation is a safe and effective therapeutic option for patients with advanced HCC and Child-pugh class A or B cirrhosis; and a higher intratumoral expression of MACC1 or nuclear translocation predicts poor outcomes of cryotherapy in these patients.
Journal of Translational Medicine 02/2013; 11(1):41. · 3.41 Impact Factor
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ABSTRACT: To assess the rate and risk factors for tumour seeding in a large cohort of patients.
Over an 8-year period, 1436 hepatocellular carcinoma (HCC) patients with 2423 tumour nodules underwent 3015 image-guided percutaneous cryoablation sessions [1215 guided by ultrasonography and 221 by spiral computed tomography (CT)]. Follow-up CT or magnetic resonance imaging was performed every 3 mo. The detailed clinical data were recorded to analyse the risk factors for seeding.
The median follow-up time was 18 (range 1-90) mo. Seeding was detected in 11 patients (0.76%) at 1-24 (median 6.0) mo after cryoablation. Seeding occurred along the needle tract in 10 patients and at a distant location in 1 patient. Seeded tumours usually showed similar imaging and histopathological features to the primary HCCs. Univariate analyses identified subcapsular tumour location and direct subcapsular needle insertion as risk factors for seeding. Multivariate analysis showed that only direct subcapsular needle insertion was an independent risk factor for seeding (P = 0.017; odds ratio 2.57; 95%CI: 1.47-3.65). Seeding after cryoablation occurred earlier in patients with poorly differentiated HCC than those with well or moderately differentiated HCC [1.33 ± 0.577 mo vs 11.12 ± 6.896 mo; P = 0.042; 95%CI: (-19.115)-(-0.468)].
The risk of seeding after cryoablation for HCC is small. Direct puncture of subcapsular tumours should be avoided to minimise seeding.
World Journal of Gastroenterology 12/2012; 18(45):6587-96. · 2.47 Impact Factor
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Xiu-Juan Chang,
Chun-Ping Wang,
Jian-Hui Qu,
Yin-Ying Lu,
Yan Chen, Wen-Lin Bai,
Xu-Dong Gao,
Li-Yan Hao,
Gui-Lin Xu,
Hong Wang,
Yong-Ping Yang
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ABSTRACT: To clarify the expression and clinical significance of metastasis-associated in colon cancer 1 (MACC1) mRNA in hepatocellular carcinoma (HCC).
The expression and distribution of MACC1 were assessed by quantitative real-time polymerase chain reaction (RT-PCR) and immunohistochemical staining (IHC) in a cohort of hepatitis B virus-related HCC, including 138 in early (A), 96 in intermediate (B) and 120 in advanced stages (C). The association of MACC1 mRNA with disease progression and outcomes was analyzed by univariate and multivariate Cox analysis.
The intratumoral expressions of MACC1 mRNA in HCC stage I (0.001 76, range: 0.000 54 - 0.002 47), stage II (0.002 49, range: 0.000 55 - 0.006 78) and stage III (0.008 35, range: 0.006 86 - 0.009 88) were about 3-, 4- and 14-fold higher than that in the normal liver tissue (0.000 59, range: 0.000 57 - 0.000 60), respectively. Intratumoral expression of MACC1 mRNA increased with disease progression from stage I to stage III. HCC clinical staging classification, age, portal vein invasion and tumor differentiation were significantly associated with intratumoral high expression of MACC1 mRNA (All P < 0.05). Immunohistochemical staining showed that there was an increased MACC1 expression in cytoplasm of HCC cells and positive nuclear staining in some cases. Increased MACC1 mRNA expression could predict poor outcome and recurrence in stage A and B HCC postoperatively. The median tumor-free survival and total survival of patients with high MACC1 mRNA expression were 34.0 and 40 months, respectively, significantly lower than that in those with low expression (48.0 and 48.0 months) (all P < 0.01). Cox analysis showed that Child-Pugh grading and high expression of MACC1 mRNA were independent predictive factors, and high expression of MACC1 was an independent predictive factor affecting the tumor-free survival.
MACC1 mRNA up-regulation is a feature of disease progression in HCC. MACC1 mRNA expression in the HCC may become an independent predictive factor for recurrence and survival in postoperative HCC patients.
Zhonghua zhong liu za zhi [Chinese journal of oncology] 10/2012; 34(10):748-52.
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Jian-Hui Qu,
Xiu-Juan Chang,
Yin-Ying Lu, Wen-Lin Bai,
Yan Chen,
Lin Zhou,
Zhen Zeng,
Chun-Ping Wang,
Lin-Jing An,
Li-Yan Hao,
Gui-Lin Xu,
Xu-Dong Gao,
Min Lou,
Ji-Yun Lv,
Yong-Ping Yang
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ABSTRACT: To investigate the intratumoral expression of metastasis-associated in colon cancer 1 (MACC1) and c-Met and determine their clinical values associated with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).
A retrospective study admitted three hundred fifty-four patients with HBV-related HCC. The expression and distribution of MACC1 and c-Met were assessed by quantitative real-time polymerase chain reaction and immunohistochemistry staining. Prognostic factors influencing survival, metastasis and recurrence were assessed.
Intratumoral MACC1 level was found to be associated with HCC disease progression. Both median tumor-free survival (TFS) and overall survival (OS) were significantly shorter in the postoperative HCC patients with high intratumoral MACC1 expression, as compared to those with low intratumoral MACC1 levels (TFS: 34 mo vs 48.0 mo, P < 0.001; OS: 40 mo vs 48 mo, P < 0.01). Multivariable analysis indicated that high MACC1 expression or co-expression with c-Met were independent predictors for HCC clinic outcome (P < 0.001).
High intratumoral MACC1 expression can be associated with enhanced tumor progression and poor outcome of HBV-related HCC. MACC1 may serve as a prognostic biomarker for postoperative HCC.
World Journal of Gastroenterology 06/2012; 18(23):2995-3003. · 2.47 Impact Factor
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Xiu-juan Chang,
Yin-ying Lu, Wen-lin Bai,
Yan Chen,
Lin-jing An,
Lin Zhou,
Hong Wang,
Yu Wu,
Ze Liu,
Min Lou,
Zhen Zeng,
Shu-hui Su,
Yong-ping Yang
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ABSTRACT: Investigate the clinical efficacy of cryotherapy ablation treatment for advanced hepatocellular carcinoma. analyse the predictive factors of cryotherapy ablation treatment.
There were 190 cases of hepatitis B-related HCC patients with advanced HCC from 2005 to 2008 in our hospital. By using clinical cohort method, they included cryoablation group (147 cases) and control group (43 cases), The median survival time and time to disease progression were compared. Evaluate clinical significance of age, gender, location of portal vein tumor thrombus, HBeAg, tumor histological grade, Child-Pugh classification, end-stage liver disease (MELD) score, advanced liver cancer prediction system (ALCPS) score and the Eastern Cooperative Oncology Group performance status (ECOG PS) score for predicting the efficacy of cryoablation. Group rates were compared with the x2 test, survival analysis by using Kaplan-Meier method, survival rates were compared by Log-rank analysis; multiple factor survival analysis by using Cox regression model.
Median survival time of cryoablation group and Control group was 7.5 (4.2 to 14.6) months and 3.2 (1.2 to 8.6) months, median TTP was 3.5 (2.5 to 4.5) months and 1.5 (1.0 to 3.5 months), the differences were statistically significant ( P less than 0.05 ). Median OS and TTP of advanced HCC patients who had Well-differentiated tumor, Child-pugh A-class and low score of MELD score, ALCPS score, ECOG PS score were significantly longer than the poorly differentiate, Child-Pugh B-class and the high those scores ( P less than 0.05). ECOG PS ( P less than 0.05, 95% CI 1.074 to 2.143) and ALCPS (P less than 0.05, 95% CI 1.005 to 2.121) were independent predictors for OS of advanced HCC.
Cryoablation treatment can prolong median OS and TTP of advanced HCC; ECOG PS and ALCPS are important predictors for survival time of advanced HCC.
Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 10/2011; 19(10):759-63.
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Zhen Zeng,
Feng Shi,
Lin Zhou,
Min-Na Zhang,
Yan Chen,
Xiu-Juan Chang,
Yin-Ying Lu, Wen-Lin Bai,
Jian-Hui Qu,
Chun-Ping Wang,
Hong Wang,
Min Lou,
Fu-Sheng Wang,
Ji-Yun Lv,
Yong-Ping Yang
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ABSTRACT: The programmed cell death-1 receptor/programmed cell death-1 ligand (PD-1/PD-L1) pathway plays a crucial role in tumor evasion from host immunity. This study was designed to evaluate the association between circulating PD-L1/PD-1 and prognosis after cryoablation in patients with HBV-related hepatocellular carcinoma (HCC).
In the present study, 141 HBV-related HCC patients were enrolled and of those 109 patients received cryoablation. Circulating PD-L1/PD-1 expression was tested by flow cytometry, and 23 patients were simultaneously evaluated for intratumoral PD-L1 expression by immunohistochemical staining. Circulating PD-1/PD-L1 expression was associated with severity of diseases in patients with HCC, and the circulating PD-L1 expression was closely correlated with intratumoral PD-L1 expression. Of the clinical parameters, PD-1/PD-L1 expression was associated with tumor size, blood vessel invasion and BCLC staging. Moreover, PD-1/PD-L1 expression dropped after cryoablation while being elevated at the time of tumor recurrence. Patients with higher expression of circulating PD-L1, as well as circulating PD-1, had a significantly shorter overall survival and tumor-free survival than those with lower expression. Multivariate analysis confirmed that circulating PD-L1 could serve as an independent predictor of overall survival and tumor-recurrence survival in HCC patients after cryoablation.
Upregulation of circulating PD-L1/PD-1 is associated with poor post-cryoablation prognosis in patients with HBV-related hepatocellular carcinoma.
PLoS ONE 01/2011; 6(9):e23621. · 4.09 Impact Factor
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Lin Zhou,
Chun-Ping Wang,
Yin-Ying Lu, Wen-Lin Bai,
Jian-Hui Qu,
Min Lou,
Zhen Zeng,
Yu Wu,
Yan Chen,
Hong Wang,
Xiu-Juan Chang,
Yong-Ping Yang
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ABSTRACT: We present the case of one 58-year-old man with advancd hepatocellular carcinoma and hepatitis-B virus-related liver cirrhosis who received hepatic cryoablation. Magnetic resonance imaging (MRI) showed multiple liver tumors and the diameter of the largest tumor was more than 10cm. The patient received 2 percutaneous cryoablations in December 2009 and January 2010. Ten months later, MRI showed that not only the treated areas underwent necrosis but also the non-treated area decreased. The a-fetoprotein (AFP) level and the frequency of circulated regulatory T cell (Treg) before treatment were 13,800ng/mL and 15.6%, respectively. Following the cryoablations they dropped to 436ng/mL and 7.6%, respectively, 10 months later. The patient remains in good condition until now.
Hepato-gastroenterology 59(113):252-4. · 0.66 Impact Factor
