Article

Liver cancer in atomic-bomb survivors: histological characteristics and relationships to radiation and hepatitis B and C viruses.

Department of Pathology, Hiroshima Prefectural Hospital, Japan.
Journal of Radiation Research (Impact Factor: 1.45). 07/2001; 42(2):117-30. DOI: 10.1269/jrr.42.117
Source: PubMed

ABSTRACT Histological features of primary liver cancer among atomic-bomb survivors and their relationship to hepatitis B (HBV) and C viral (HCV) infections are of special interest because of the increased risk of liver cancer in persons exposed to ionizing radiation and the high and increasing liver cancer rates in Japan and elsewhere. We conducted a pathology review of liver cancers occurring from 1958 to 1987 among subjects in the 120,321 member cohort of 1945 Hiroshima and Nagasaki residents. A panel of pathologists classified tumor histological types and defined accompanying cirrhotic changes of the liver. Archival tissue samples were assessed for HBV using pathology stains and PCR. Reverse transcriptase (RT) PCR was used to determine HCV status. We used unconditional logistic regression to compare 302 hepatocellular carcinoma (HCC) cases to 53 cholangiocarcinoma (CC) cases, adjusting for age, year of diagnosis, sex and viral status. Cirrhotic changes occurred significantly more often among HCC than CC cases (76% in HCC and 6% in CC). Compared to CC cases, HCC cases were 10.9 times more likely to be HBV-positive (95% confidence interval: 2.1-83.2) and 4.3 times more likely to be HCV-positive (95% confidence interval: 1.1-20.5). No significant differences were found between HCC and CC cases in radiation exposures. The predominance of HCC in the atomic-bomb survivors follows the background liver cancer pattern in Japan. Our findings suggest that HBV and HCV are involved in the pathogenesis of HCC with or without cirrhosis and are significantly less important in that of CC.

0 Bookmarks
 · 
82 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We investigated the dosimetric differences among volumetric-modulated arc radiotherapy (RapidArc, RA) plans designed for various target volumes in hepatocellular carcinoma (HCC). Ten HCC patients underwent 3D-CT scanning at free breathing (FB), 3D-CT at end inspiration hold (EIH) assisted by an Active Breathing Coordinator (ABC), and 4D-CT scanning. Gross tumor volumes (GTVs) were manually contoured on CT images. The individualized internal gross target volume (IGTV(1)) was obtained from 10 GTVs from 4D-CT images. Tumor individual margins were measured from GTV(FB) to IGTV(1). The IGTV(2) was obtained from GTV(FB) by applying individual margins. Four planning target volumes (PTV(1-4)) were obtained from IGTV(1), IGTV(2), GTV(FB), and GTV(EIH), respectively. An RA plan was designed for each of the PTVs (RA(1)(-)(4)). One 358° arc was used for PTVs(1)(-)(3,) while three 135° arcs were used for PTV(4). It was found that PTV(2) and PTV(3) were larger than PTV(1) and PTV(4). The mean values of PTV(3)/PTV(1) and PTV(3)/PTV(4) were 2.5 and 1.9, respectively. The individual margins in the X, Y and Z axial directions varied greatly among these patients. There were no significant differences in the conformal index or homogeneity index among the four RA plans. RA(1) and RA(4) significantly reduced the radiation dose of normal liver tissue compared with RA(2) and RA(3) (P < 0.01). There were no significant differences between the radiation doses of the stomach and duodenum. RapidArc combined with 4D-CT or ABC technology is a promising method in radiotherapy of HCC, and accurately targeted the tumor volume while sparing more normal liver tissue.
    Journal of Radiation Research 08/2012; · 1.45 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Recent studies of atomic bomb survivors have shown that risks of liver cancer are significantly increased by radiation exposure. This contrasts with mortality studies of other radiation-exposed populations, which generally have not shown a significant radiation effect for this cancer. Because the liver is a frequent site to which other tumors metastasize, liver cancer is one of the most difficult cancers to correctly diagnose. Studies of liver cancer in A-bomb survivors and other populations have documented high percentages of tumors metastasized to the liver being incorrectly diagnosed as liver tumors. In addition, many deaths due to liver cancer have been incorrectly attributed to cirrhosis or chronic hepatitis. Studies of incident or pathology-confirmed liver cancer cases in A-bomb survivors have found higher radiation risk estimates for liver cancer than mortality studies in this cohort. Most studies of radiation and liver cancer in other radiation-exposed cohorts have been mortality studies, and thus, would include many misclassified liver cancers.Liver cancer was consistently associated with radiation exposure in studies of four cohorts exposed to Thorotrast, a previously used radiology contrast agent. However, the histologic subtypes of liver cancer and type of radiation exposure (external rather than internal) differ from those experienced by the A-bomb survivors. Liver cancer in atomic bomb survivors is primarily hepatocellular carcinoma (HCC), rather than the cholangiocarcinoma and hemangiosarcoma subtypes more associated with Thorotrast exposure.A recent case control study of the joint effects of radiation and viral hepatitis in the etiology of HCC, showed that A-bomb radiation had a significantly stronger effect among subjects who were infected with the hepatitis C virus (HCV). No significant interaction between hepatitis B viral infections and radiation in the etiology of this disease was found. We compared incidence and mortality studies of liver cancer conducted in a wide variety of radiation-exposed populations, in terms of their radiation risk estimates for liver cancer, the background level of liver cancer in the cohort, HCV prevalence in the population from which the cohort was drawn, and other factors. The differences between the radiation risk estimates for atomic bomb survivors and other cohorts may reflect liver cancer diagnosis errors. Varying risk estimates may also reflect differences in the prevalence of HCV in radiation-exposed cohorts.
    International Congress Series 01/2002; 1236:59-66.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Inflammatory markers have been associated with increased risk of several cancers, including colon, lung, breast, and liver, but the evidence is inconsistent. We conducted a nested case-control study in the longitudinal cohort of atomic-bomb survivors. The study included 224 HCC cases and 644 controls individually matched to cases on gender, age, city, and time and method of serum storage, and counter-matched on radiation dose. We measured C-reactive protein (CRP) and interleukin (IL)-6 using stored sera obtained within six years before hepatocellular carcinoma (HCC) diagnosis from 188 HCC cases and 605 controls with adequate volumes of donated blood. Analyses with adjustment for hepatitis virus infection, alcohol consumption, smoking habit, body mass index (BMI), and radiation dose showed that relative risk (RR) of HCC (95% confidence interval [CI]) in the highest tertile of CRP levels was 1.94 (0.72-5.51) compared with the lowest tertile (P = 0.20). RR of HCC (95%CI) in the highest tertile of IL-6 levels was 5.12 (1.54-20.1) compared with the lowest tertile (P = 0.007). Among subjects with BMI >25.0 kg/m(2) , a stronger association was found between a 1-SD increase in log IL-6 and HCC risk compared with subjects in the middle quintile of BMI (21.3-22.9 kg/m(2) ), resulting in adjusted RR (95%CI) of 3.09 (1.78-5.81) (P = 0.015). The results indicate that higher serum levels of IL-6 are associated with increased HCC risk, independently of hepatitis virus infection, lifestyle-related factors, and radiation exposure. The association is especially pronounced among subjects with obesity. © 2013 Wiley Periodicals, Inc.
    International Journal of Cancer 06/2013; · 6.20 Impact Factor

Full-text

Download
1 Download
Available from