Prospective study of early detection of hepatocellular carcinoma in patients with cirrhosis

Oka, Hiroko; Kurioka, Narito; Kim, Kosyun; Kanno, Toru; Kuroki, Tetsuo; Mizoguchi, Yasuhiro; Kobayashi, Kenzo

doi:10.1002/hep.1840120411

Cited by 376 publications

(226 citation statements)

References 34 publications

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“…24 One interpretation might be ''once developed, HCC easily recurs,'' although we must consider the possibility that the operative procedure and the proliferation pressure inherent with partial hepatectomy accelerate the recurrence. Furthermore, HCC recurs as IM or MO.…”

Section: Discussionmentioning

confidence: 48%

Determination of the Clonal Origin of Multiple Human Hepatocellular Carcinomas by Cloning and Polymerase Chain Reaction of the Integrated Hepatitis B Virus Dna

et al. 1999

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The poor prognosis of hepatocellular carcinoma (HCC) is partly the result of the high rate of recurrence that is caused either by intrahepatic metastasis (IM) or independent multicentric occurrence (MO). For convenience, discrimination of IM and MO is based on pathological findings, but reliable parameters are not sufficiently established. In the case of hepatitis B virus (HBV)-associated HCC, molecular discrimination of IM from MO can be achieved by comparison of integrated HBV DNAs. However, Southern blotting cannot be used for this purpose when one tumor is saved in frozen form and the other is in paraffin-embedded form. To solve this problem, we employed polymerase chain reaction (PCR) assays to confirm the clonality of primary and recurrent tumors. From the frozen tissue, we determined the junction between the integrated HBV and flanking genomic DNA by molecular cloning, and checked the existence of an identical junction in the DNA of paraffinembedded tissue by PCR. Using this method, as well as Southern blotting, we proved in 6 of 8 patients that two nodular HCC lesions resected metachronously or simultaneously were caused by MO, while the remaining 2 cases were caused by IM. In 1 IM case, band patterns between two HCCs detected by Southern blotting were not identical. (HEPATOLOGY 1999;29:1446-1452.) Hepatocellular carcinoma (HCC), one of the most common cancers in many parts of the world, is the third-leading cause of death from malignancy in Japan. In 1995, HCC was responsible for about 30,000 deaths, and the number of deaths continues to increase in Japan. 1 Improvement in imaging modalities and strict follow-up of patients with hepatitis B virus (HBV) or hepatitis C virus, including measurement of serum tumor markers, allows early detection of HCCs. In spite of technical advances in the treatment of HCC, such as surgical resection, percutaneous ethanol injection therapy, and microwave coagulation therapy, the longterm survival rate is still low. One of the major reasons for this poor prognosis is the high rate of recurrence, which is 20% to 40% within 1 year, and about 80% in 5 years after curative operation in Japan. 2-5 HCC recurrence may be the result of intrahepatic metastasis (IM) or independent multicentric occurrence (MO). Discrimination between the two is important not only for the study of hepatocarcinogenesis, but also for determination of therapeutic strategies. Some groups have reported that HCC with IM recurs earlier and has a poorer prognosis than its MO counterpart. 2,6 Aggressive therapy may not be warranted in cases with widespread metastatic dissemination, but in cases with MO, intervention should be taken within the limits of liver functional reserve. The diagnosis of IM or MO is mainly based on pathological findings as reported by the Liver Cancer Study Group of Japan 7 with modifications, 6,[8][9][10][11] or on the analysis of HBV-DNA integration by Southern blotting in cases of HBV-associated HCC. 8,[12][13][14][15][16][17][18] The pathological criteria for MO reflect the multiste...

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Section: Discussionmentioning

confidence: 48%

Determination of the Clonal Origin of Multiple Human Hepatocellular Carcinomas by Cloning and Polymerase Chain Reaction of the Integrated Hepatitis B Virus Dna

et al. 1999

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“…22 Between 3% and 18% of clinicbased cirrhotic patients were noncompliant. 14,16,26,27,28,34,39,45,61 These results compare with a 25% lack of compliance with fecal occult blood testing, in a colorectal cancer screening program of asymptomatic individuals. 62 Access is also an important factor in Third-World countries where screening with ultrasound is not feasible, and even AFP screening may be too expensive.…”

Section: The Screening Tests Must Be Acceptable To the Target Populationmentioning

confidence: 41%

Screening for hepatocellular carcinoma

1998

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“…Transcatheter intraarterial chemoembolization (TACE), with which complete necrosis of HCCs is thought to be difficult to achieve, is also impacted by the above factors [21]. To increase opportunities for meaningful intervention and to improve survival, early detection of HCC by measuring alpha-fetoprotein (AFP) and/or imaging screening is implemented in many countries [15,[22][23][24][25]. However, the poorer prognosis of patients with HCC-nonBC is reportedly attributable to its late detection in an advanced stage, owing to the lack of a surveillance system for early detection of HCC [26].…”

Section: Introductionsupporting

confidence: 46%

758 Frequency of Elevated Biomarkers in Patients With Cryptogenic Hepatocellular Carcinoma

Taura¹,

Ichikawa²,

Miyaaki³

et al. 2012

Journal of Hepatology

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Background:The incidence of hepatocellular carcinoma (HCC) continues to increase in Japan, but the clinical characteristics of Japanese patients with HCC have not been well described. The aim of this study was to determine the frequencies and utilities of elevated a-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) levels as biomarkers in cryptogenic HCC. Material/Methods:A total of 2638 patients with HCC diagnosed between 1999 and 2010 in the Nagasaki Association Study of Liver (NASLD) were recruited for this study. The cause of HCC was categorized into 4 groups; HCC-B, HCC-C, HCC-BC, and HCC-nonBC. The significance of factors was examined for HCC-nonBC using logistic regression analysis in all patients. Results:Multivariate analysis identified age, sex, BMI, alcohol consumption, platelet count, AST, ALT, AFP, DCP, and TNM stage as independent and significant risk factors for HCC-nonBC. According to TNM stage, the median AFP levels in HCC-nonBC with TNM stages I, II, and III were significantly lower than in either HCC-B or HCC-C. In TNM stage IV, the median AFP level in HCC-nonBC was significantly lower than in either HCC-B or HCC-BC. The median DCP levels in HCC-nonBC with TNM stages I and II were significantly higher than those in either HCC-B or HCC-C. In TNM stage III, the median DCP level in HCC-nonBC was significantly higher than that in HCC-C. Conclusions:DCP was more sensitive than AFP for the diagnosis of early stage cryptogenic HCC. DCP should be used as the main serum test for cryptogenic HCC detection.

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Prospective study of early detection of hepatocellular carcinoma in patients with cirrhosis

Cited by 376 publications

References 34 publications

Determination of the Clonal Origin of Multiple Human Hepatocellular Carcinomas by Cloning and Polymerase Chain Reaction of the Integrated Hepatitis B Virus Dna

Determination of the Clonal Origin of Multiple Human Hepatocellular Carcinomas by Cloning and Polymerase Chain Reaction of the Integrated Hepatitis B Virus Dna

Screening for hepatocellular carcinoma

758 Frequency of Elevated Biomarkers in Patients With Cryptogenic Hepatocellular Carcinoma

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