Prognostic factors of hepatocellular carcinoma in patients undergoing hepatic resection

Izumi, Ryohei; Shimizu, Koïchi; Yagi, Minoru; Matsui, Osamu; Nonomura, Akitaka; Miyazaki, Itsuo

doi:10.1016/0016-5085(94)90707-2

Cited by 366 publications

(234 citation statements)

References 29 publications

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“…On the other hand, the Apo D expression values in tumor tissue specimens were significantly associated with the histological grade of the tumor, which is one of the most important prognostic factors for patients with HCC. [28][29][30] An immunohistochemical analysis also revealed a stepwise decrease in the expression at the protein level of well to moderately and poorly differentiated HCC. The prognosis of HCC patients with a low expression of Apo D was significantly worse than that in patients with a high expression.…”

Section: Discussionmentioning

confidence: 92%

Clinicopathologic and prognostic values of apolipoprotein D alterations in hepatocellular carcinoma

Utsunomiya

Ogawa

Yoshinaga

et al. 2005

Intl Journal of Cancer

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We previously identified apolipoprotein D (Apo D) as a novel tumor suppressor gene based on the pharmacological unmasking of epigenetic silencing. We analyzed Apo D expression using realtime reverse transcription-PCR and evaluated its expression status based on the clinicopathological parameters of 70 patients with hepatocellular carcinoma (HCC). Immunohistochemical staining was also performed. We determined the methylation status of Apo D gene promoter by methylation-specific PCR (MSP). The Apo D gene-expression in tumor tissue was significantly lower than that in nontumor tissue (p = 0.011). A low Apo D expression significantly correlated with less-differentiated HCC ( p = 0.019). Immunohistochemical studies confirmed a decreased Apo D expression in poorly differentiated tumors. The prognosis of patients with a lower Apo D gene-expression was significantly worse than that in those with a higher expression (p = 0.028). The Apo D gene-expression was an independent prognostic factor (relative risk: 2.36, p = 0.018). An MSP assay showed a low-level of methylation in well differentiated HCC and a high-level of methylation in less differentiated tumors. Apo D may be a novel tumor suppressor gene of HCC, and its expression status may be a useful biomarker for predicting the patient outcome. ' 2005 Wiley-Liss, Inc.Key words: apolipoprotein D; hepatocellular carcinoma; histological grade; prognostic factor; methylationWe recently performed a comprehensive survey of commonly inactivated tumor suppressor genes in esophageal cancer cell lines based on functional reactivation by a demethylating agent. 1 A total of 58 silenced genes were thus identified using this approach, and one of those genes was Apolipoprotein D (Apo D). In our report, we detected the promoter hypermethylation of Apo D gene using bisulfite DNA sequencing. The methylation status of Apo D correlated closely with the Apo D expression status. Moreover, the growth suppressive activity of Apo D was also demonstrated by a colony focus assay. 1 These findings thus prompted us to analyze the clinical significance of the Apo D expression status in human cancers.Apo D, belonging to the lipocalin superfamily, is a glycoprotein of about 30 kDa found in the high-density lipoprotein fraction of human plasma. 2 The functional role of Apo D remains unclear, but the observation that this protein forms complexes with lecithin-cholesterol acyltransferase suggests that Apo D may be involved in cholesterol esterification. 3 More recently, the Apo D gene-expression was reported to be induced by retinoic acid in breast cancer cell lines. The induction of the Apo D expression was accompanied by an inhibition of cell proliferation and a progression through a more differentiated phenotype. These finding suggest that the mechanisms controlling retinoic acid-induced growth arrest, cell differentiation and Apo D synthesis may be directly coordinated in human breast cancer cells. 4 Furthermore, a low expression of Apo D determined by an immunohistochemical study was significantly as...

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Section: Discussionmentioning

confidence: 92%

Clinicopathologic and prognostic values of apolipoprotein D alterations in hepatocellular carcinoma

Utsunomiya

Ogawa

Yoshinaga

et al. 2005

Intl Journal of Cancer

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“…28,29 The most powerful prognostic factor of poor survival was vascular invasion in this study, and similar results were reported in patients who underwent liver resection or transplantation. 1,[30][31][32] Although the BCLC system was validated as the most suitable prognostic system for patients with HCC in Italy and the United States, it was not considered a suitable prognostic system in the Eastern countries until now. 33,34 Furthermore, in the current study, surgical patients were excluded from the analysis, which may be an important reason that the BCLC system was inferior to the JIS system or the CLIP system in predicting the survival of patients with HCC.…”

Section: Discussionmentioning

confidence: 99%

Comparison of 7 staging systems for patients with hepatocellular carcinoma undergoing transarterial chemoembolization

Cho

Chung

Kim

et al. 2007

Cancer

110

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BACKGROUND.Many liver staging systems have been proposed for patients with hepatocellular carcinoma after locoregional therapy; however, controversies persist regarding which system is the best. In this study, the authors compared the performance of 7 staging systems in a cohort of patients with hepatocellular carcinoma who underwent transarterial chemoembolization.METHODS.In total, 131 patients with hepatocellular carcinoma who underwent transarterial chemoembolization between August 1998 and February 2005 were included in the study. Demographic, laboratory, and tumor characteristics were determined at diagnosis and before therapy. At the time of censorship, 109 patients had died (83.2%). Predictors of survival were identified by using the Cox proportional hazards model. The likelihood‐ratio chi‐square statistic and the Akaike Information Criterion were calculated for 7 prognostic systems to evaluate their discriminatory ability. Comparisons of the survival rate between each stage were performed to evaluate the monotonicity of the gradients using Kaplan‐Meier estimation and the log‐rank test.RESULTS.The 5‐year survival rate for the entire cohort was 13.6%. The independent predictors of survival were serum albumin level (≤3.4 g/dL), the presence of ascites, serum α‐fetoprotein level (>60 ng/mL), and portal or hepatic vein tumor thrombosis (P = .001, P = .001, P = .004, and P = .000, respectively). The Cancer of the Liver Italian Program classification system was superior to the other 6 prognostic systems regarding discriminatory ability and the monotonicity of the gradients.CONCLUSIONS.In this comparison of many staging systems, the Cancer of Liver Italian Program system provided the best prognostic stratification for a cohort the patients with hepatocellular carcinoma who underwent transarterial chemoembolization. Cancer 2008. © 2007 American Cancer Society.

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“…Six patients required a second OLT after a median follow up of 14 months (range, [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. The reasons for retransplantation were severe rejection in 3 cases (one had also multiple biliary strictures), hepatic arterial thrombosis in 1, primary graft nonfunction in 1, and HCV related cirrhosis in 1.…”

Section: Retransplantationmentioning

confidence: 99%

“…3,7 Finally, two recent studies have shown that if OLT is restricted only to patients with early HCC (some years ago these tumors would have been identified only in the explanted livers), the risk of recurrence is minimal and the survival is identical to that of patients without HCC. 11,12 These encouraging data would favor OLT as the first therapeutic option to be considered in patients with HCC 13 as surgical resection is hampered by a higher recurrence rate during follow up [14][15][16][17] ; however, OLT is a highly invasive procedure with potentially severe complications in the early, medium, and long-term follow up. In addition, it must be stressed that HCC in most of the patients arises on liver cirrhosis caused by infection with HBV or HCV, 2,18 which frequently infects the graft, 19,20 and that the progression of the liver disease may be faster than in immunologically competent individuals.…”

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confidence: 99%

Liver transplantation for small hepatocellular carcinoma: The tumor-node-metastasis classification does not have prognostic power

et al. 1998

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From a theoretical point of view, orthotopic liver transplantation (OLT) should be considered the ideal therapeutic option for patients with hepatocellular carcinoma (HCC).This neoplasm usually appears in the setting of liver cirrhosis, 1,2 and thus, OLT would eliminate the tumor and the oncogenic underlying liver. However, the first series of OLT for HCC showed disappointing results. [3][4][5][6] The inclusion of patients with advanced HCC prompted a high recurrence rate (higher than 50% at 3 years) whereas the survival rate (20%-50% at 5 years) was clearly less than that of non-HCC patients. Subsequent reports showed that HCC stage is a key point in determining the success of OLT in these patients and suggested that patients with early HCC could benefit from OLT both in terms of recurrence and survival. 5,7-10 Thereby, the recurrence rate of patients with incidental tumors which were discovered at the time of the pathological examination of the explanted liver is negligible. 3,7 Finally, two recent studies have shown that if OLT is restricted only to patients with early HCC (some years ago these tumors would have been identified only in the explanted livers), the risk of recurrence is minimal and the survival is identical to that of patients without HCC. 11,12 These encouraging data would favor OLT as the first therapeutic option to be considered in patients with HCC 13 as surgical resection is hampered by a higher recurrence rate during follow up [14][15][16][17] ; however, OLT is a highly invasive procedure with potentially severe complications in the early, medium, and long-term follow up. In addition, it must be stressed that HCC in most of the patients arises on liver cirrhosis caused by infection with HBV or HCV, 2,18 which frequently infects the graft, 19,20 and that the progression of the liver disease may be faster than in immunologically competent individuals. 21 As previously reported, 22-25 the treatment schedule applied in our Liver Unit in patients with HCC considered OLT only for those patients with solitary tumors smaller than 5 cm in whom resection was contraindicated, whereas the stage according to the TNM staging system was not taken into account. The present study analyzes the outcome of the cohort of the first 58 HCC patients submitted to OLT following this pre-established treatment algorithm, describing the accuracy of the preoperative staging, the recurrence and survival data, and also the rate of viral infection of the new liver. PATIENTS AND METHODS PatientsBetween January 1989 and December 1995, 877 patients with HCC were diagnosed, staged, and treated in our Liver Unit according to a previously published schedule. [22][23][24][25] Patients with HCC were Abbreviations: HCC, hepatocellular carcinoma; OLT, orthotopic liver transplantation; TNM, tumor-node-metastasis classification system; pTNM, pathological tumor-nodemetastasis classification.From the

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Prognostic factors of hepatocellular carcinoma in patients undergoing hepatic resection

Cited by 366 publications

References 29 publications

Clinicopathologic and prognostic values of apolipoprotein D alterations in hepatocellular carcinoma

Clinicopathologic and prognostic values of apolipoprotein D alterations in hepatocellular carcinoma

Comparison of 7 staging systems for patients with hepatocellular carcinoma undergoing transarterial chemoembolization

Liver transplantation for small hepatocellular carcinoma: The tumor-node-metastasis classification does not have prognostic power

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