Multicentric hepatocellular carcinomas tend to grow in more damaged segments of the liver

Ariizumi, Shun‐ichi; Takasaki, Ken; Yamamoto, Masakazu; Ohtsubo, Takehito; Saito, Akiko; Nakano, Masayuki

doi:10.1007/s005350070089

Cited by 12 publications

(16 citation statements)

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“…VEGF can substantially accelerate division and growth of vascular endothelial cells and angiogenesis. High VEGF levels can promote plasma protein exosmosis to induce fibrin deposition and new vessel generation, allowing invasion and metastasis; patients with HCC and higher VEFG expression in serum and HCC tissue have a poorer prognosis [9,26]. …”

Section: Discussionmentioning

confidence: 99%

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Connexin-43 can delay early recurrence and metastasis in patients with hepatitis B-related hepatocellular carcinoma and low serum alpha-fetoprotein after radical hepatectomy

Wang

et al. 2013

BMC Cancer

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BackgroundWe studied the relationships among Cx43, CD105, and VEGF in specimens of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) with different serum AFP levels with respect to recurrence and metastasis.MethodsExpressions of Cx43, CD105, and VEGF in 234 HCC tissue specimens were examined using tissue microarray and immunohistochemistry. Cx43 mRNA expression was examined in 38 frozen HCC specimens using RT-PCR. Correlations between these expressions and tumor recurrence, metastasis, and prognosis were analyzed using Kaplan–Meier and Cox regression analyses.ResultsCx43 expression correlated with early tumor recurrence (P = 0.001), disease-free survival (P = 0.026), and overall survival (P = 0.000) in patients with serum AFP < 400 ng/ml, but not in those with serum AFP ≥ 400 μg/L. Cx43 expression is an independent predictor of later recurrence and longer overall survival and is inversely correlated with expression of CD105 and VEGF (P = 0.018 and 0.023, respectively), histological differentiation (P = 0.002), vessel tumor embolism (P = 0.029), and focal number (P = 0.017). Immunohistochemistry showed that Cx43 expression in patients with low AFP was lower in patients with distant metastases than in those with no metastasis or those with liver metastasis. Patients with early recurrence expressed less Cx43 mRNA than did those with no recurrence (χ2 = 9.827, P = 0.002).ConclusionsCx43 expression can delay early HCC recurrence, metastasis, and poor prognosis after radical hepatectomy in patients with HBV-related HCC and low AFP.

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Section: Discussionmentioning

confidence: 99%

“…Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections induce approximately 75–80% of HCC in the world [9]. Chronic HBV infection accounts for about 60% of the total liver cancer in developing countries and about 23% of the cancer in developed countries.…”

Section: Introductionmentioning

confidence: 99%

Connexin-43 can delay early recurrence and metastasis in patients with hepatitis B-related hepatocellular carcinoma and low serum alpha-fetoprotein after radical hepatectomy

Wang

et al. 2013

BMC Cancer

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“…Multinodular HCCs in cirrhotic livers most commonly represent multicentric HCCs, whilst multinodular HCCs in non-cirrhotic liver are often related to intraheptic metastases [3]. Multicentric HCCs are particularly common in patients with chronic hepatitis C and tend to grow in more damaged segments of the liver [4,5]. The color of the cut surface may be green (due to bile production), yellow (due to fatty change), tan-brown, or grey-white ( fig.…”

Section: Pathologymentioning

confidence: 99%

Pathology and Pathogenesis of Hepatocellular Carcinoma

Röcken

Carl-McGrath²

2001

Dig Dis

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Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver and among the most common cancers worldwide. The distribution pattern of HCC shows geographical variation and its pathogenesis is multifactorial. Environmental, infectious, nutritional, metabolic, and endocrine factors contribute directly or indirectly to hepatocarcinogenesis. The synchronous occurrence of different risk factors, such as chronic viral hepatitis B and C, aflatoxin exposure, alcohol consumption or iron overload, in a single patient or patient population further increases the risk. HCC is commonly associated with chronic hepatitis and liver cirrhosis. Different genes have been implicated in the pathogenesis of HCC, and may be divided into four major groups: genes regulating DNA damage response; genes involved in cell cycle control; genes involved in growth inhibition and apoptosis, and genes responsible for cell–cell interaction and signal transduction. Hepatocarcinogenesis is mediated by loss of heterozygosity, somatic mutation, de novo methylation, and/or functional inactivation. As yet, there is no evidence for an ordered sequence of genomic events leading to hepatocarcinogenesis. The pattern of genomic alterations shows great variability, often between two different HCCs from a single patient. HCC evolves from precancerous lesions, and well-differentiated HCC further progresses to a less differentiated form. However, there is still great need for the definition of objective morphological, phenotypic and genetic markers for the progression of HCC.

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“…For resectable cases of HCC, the most patients have a good liver function in preoperation, whereas the late recurrence or death only associated with Child stage in this study, which suggest that liver function damage is the one of reasons which result in late death(no-tumor factors) beside early operative mortality or easy to recurrence. Ariizumi et al [52] showed that multicentric HCC tended to grow in more damaged segments of the liver. Thus, influence of tumor-related factors to patients who survived more than three years with no recurrence decreased gradually, meanwhile the influence of host-related factors, including liver functional status and multicentric in origin increased gradually [18,32] .…”

Section: Discussionmentioning

confidence: 99%

Prediction of recurrence and prognosis in patients with hepatocellular carcinoma after resection by use of CLIP score

Zhao¹,

Ma²,

Zhou³

et al. 2002

WJG

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The survival time of patients with hepatocellular carcinoma (HCC) after resection is hard to predict. Both residual liver function and tumor extension factors should be considered. A new scoring system has recently been proposed by the Cancer of the Liver Italian Program (CLIP). CLIP score was confirmed to be one of the best ways to stage patients with HCC. To our knowledge, however, the literature concerning the correlation between CLIP score and prognosis for patients with HCC after resection was not published. The aim of this study is to evaluate the recurrence and prognostic value of CLIP score for the patients with HCC after resection. METHODS:A retrospective survey was carried out in 174 patients undergoing resection of HCC from January 1986 to June 1998. Six patients who died in the hospital after operation and 11 patients with the recurrence of the disease were excluded at 1 month after hepatectomy. By the end of June 2001, 4 patients were lost and 153 patients with curative resection have been followed up for at least three years. Among 153 patients, 115 developed intrahepatic recurrence and 10 developed extrahepatic recurrence, whereas the other 28 remained free of recurrence. Recurrences were classified into early (3 year) recurrence. The CLIP score included the parameters involved in the Child-Pugh stage (0-2), plus macroscopic tumor morphology (0-2), AFP levels (0-1), and the presence or absence of portal thrombosis (0-1). By contrast, portal vein thrombosis was defined as the presence of tumor emboli within vascular channel analyzed by microscopic examination in this study. Risk factors for recurrence and prognostic factors for survival in each group were analyzed by the chi-square test, the Kaplan-Meier estimation and the COX proportional hazards model respectively. RESULTS:The 1-,3-,5-,7-,and10-year disease-free survival rates after curative resection of HCC were 57.2%,28.3%, 23.5%,18.8% and 17.8%,respectively. Median survival time was 28,16,10,4, and 5mo for CLIP score 0,1,2,3, and 4 to 5, respectively. Early and late recurrence developed in 109 patients and 16 patients respectively. By the chi-square test, tumor size, microsatellite, venous invasion, tumor type (uninodular, multinodular, massive), tumor extension (50% of liver parenchyma replaced by tumor), TNM stage, CLIP score, and resection margin were the risk factors for early recurrence, whereas CLIP score and ChildPugh stage were significant risk factors for late recurrence. In univariate survival analysis, Child-Pugh stages, resection margin, tumor size, microsatellite, venous invasion, tumor type, tumor extension, TNM stages, and CLIP score were associated with prognosis. The multivariate analysis by COX proportional hazards model showed that the independent predictive factors of survival were resection margins and TNM stages.CONCLUSION: CLIP score has displayed a unique superiority in predicting the tumor early and late recurrence and prognosis in the patients with HCC after resection.

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Multicentric hepatocellular carcinomas tend to grow in more damaged segments of the liver

Cited by 12 publications

References 18 publications

Connexin-43 can delay early recurrence and metastasis in patients with hepatitis B-related hepatocellular carcinoma and low serum alpha-fetoprotein after radical hepatectomy

Connexin-43 can delay early recurrence and metastasis in patients with hepatitis B-related hepatocellular carcinoma and low serum alpha-fetoprotein after radical hepatectomy

Pathology and Pathogenesis of Hepatocellular Carcinoma

Prediction of recurrence and prognosis in patients with hepatocellular carcinoma after resection by use of CLIP score

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