In a consecutive series of 393 patients with excised and pathologically proven primary liver cancer (PLC)—including 374 hepatocellular carcinomas (CCC), nine cholangiocellular carcinomas (CCC), and ten mixed type of HCC and CCC—33 patients (8.4%) had one or two other malignancies in the extrahepatic organ(s). Of these, 29 had double cancers and four, triple cancers. This was synchronous in 11 patients, metachronous in 20 (including 18 with double cancers and two with triple cancers) and synchronous and metachronous in two with triple cancers. Metachronous cancer was found in 21 patients 1 year before hepatectomy for PLC and in three patients, 1 year after hepatectomy. The median age of PLC patients with multiple primary cancer (MPC) was 63.6 ± 6.9 years; this was significantly greater than that of PLC patients without MPC (P < 0.01). The associated cancer was gastric cancer in 11 patients (29.7%), colorectal cancer in six, pharyngeal cancer in four, and other cancers in ten different organs in 16. Thirteen of 22 patients had a history of blood transfusion. The incidence of liver cirrhosis in PLC associated with MPC (57.6%) was significantly lower than that without MPC (82.8%, P < 0.01). The differential diagnosis of PLC from liver metastasis was possible retrospectively in 78.6% using sonograms, 79.3% using computed tomograms, and 91.3% using angiograms. The survival rates of patients with PLC with (n = 33) and without (n = 299) MPC who had undergone hepatectomy were 97.0% and 85.4% at 1 year, 55.5% and 59.5% at 3 years, and 40.5% and 40.1% at 5 years, respectively. There was no significant difference between the survival rates of those who underwent operations for PLC and extrahepatic primary cancer(s) synchronously and metachronously.
A 65-year-old woman (C1I) and a 65-year-old man (C2I) contracted acute hepatitis C 40 or 42 years after marriage, respectively, in Japan. They had no discernible risk factors for acquiring hepatitis C virus (HCV) infection, except that they had monogamous sexual relationships with their spouses (C1S [66-year-old] with hepatocellular carcinoma and C2S [64-year-old] with liver cirrhosis, respectively) who were infected with HCV of the same genotype (1b) and had a high-titer HCV RNA in the serum (bDNA probe assay, 17 Meq/ml [C1S] and 15 Meq/ml [C2S]). The HCV isolates from Patients C1I and C1S and those from Patients C2I and C2S shared identity of 99.9% and 99.1%, respectively, in the 1,087-nucleotide (nt) sequence of the NS5B region, although these four isolates were only 91.7%-96.2% identical to the 94 reported genotype 1b isolates including those from Japanese patients. To confirm the high degree of genetic relatedness among ten HCV clones from each spouse within each pair of spouses, the E1 and E2 junctional region sequence (268 or 271 nt) including hypervariable region 1 (HVR-1) was analyzed. There was a close relationship between clones obtained from each spouse within each couple. Regarding the HVR-1 amino acid sequence, nine of the ten C1I clones were 100% identical with six of the ten C1S clones, and one each of the C2I and C2S clones differed by only one amino acid residue. This study indicates that two Japanese patients with acute hepatitis C had acquired HCV infection most probably by interspousal sexual transmission during a long-lasting marriage.
Objective: IgG4-related sclerosing cholangitis (IgG4-SC) is recognized as a benign steroid-responsive disease; however, little is known about the risk of development of cancer in patients with IgG4-SC and about how to counter this risk. Design: We conducted a retrospective review of the data of 924 patients with IgG4-SC selected from a Japanese nationwide survey. The incidence, type of malignancy, and risk of malignancy in these patients were examined. Then, the standardized incidence ratio (SIR) of cancer in patients with IgG4-SC was calculated. Results: Relapse was recognized in 19.7% (182/924) of patients, and cancer development was noted in 15% (139/924) of patients. Multivariate analysis identified only relapse as an independent risk factor for the development of cancer. In most of these patients with pancreato-biliary cancer, the cancer developed within 8 years after the diagnosis of IgG4-SC. The SIR for cancer after the diagnosis of IgG4-SC was 12.68 (95% confidence interval [CI] 6.89-8.79). The SIRs of cancers involving the biliary system and pancreas were 27.35 and 18.43, respectively. The cumulative survival rate was significantly better in the group that received maintenance steroid treatment (MST) than in the group that did not; thus, MST influenced the prognosis of these patients. Conclusion: Among the cancers, the risk of pancreatic and biliary cancers is the highest in these patients. Because of the elevated cancer risk, surveillance after the diagnosis and management to prevent relapse are important in patients with IgG4-SC to reduce the risk of development of cancer.K Kubota et al.IgG4-related sclerosing cholangitis and cancer 557
A 71-year-old (C1I) and 69-year-old (C2I) Japanese female contracted fulminant hepatitis B after 50 and 49 years of marriage, respectively. Both index cases exhibited high levels of anti-HBc IgM antibodies (24.2 and 31.5 S/CO, respectively), suggestive of acute hepatitis B virus (HBV) infection, although they had no discernible risk factors for HBV infection, except for chronically HBV-infected spouses with detectable HBV DNA (3.3 log copies/ml [C1S: 72-year-old] and 7.2 log copies/ml [C2S: 71-year-old]). The HBV genotype/subgenotype was identical in each couple (B/B1 or C/C2). The HBV isolates from the index cases and spouses shared a nucleotide sequence identity of 99.5% and 99.7%, respectively, over the entire genome, and these four isolates had the highest nucleotide sequence identity of only 97% to HBV isolates deposited in DNA databases. Phylogenetic trees confirmed a close relationship of the HBV isolates between C1I and C1S and between C2I and C2S, supported by a high bootstrap value of 100% within each couple, indicating the transfer of HBV infection between spouses. These four isolates shared a precore mutation of G1896A known to be associated with fulminant hepatitis B. Although the history of sexual contact within a reasonable incubation period was obscure for one stable, monogamous couple (C1I and C1S), the other couple had a monogamous sexual relationship within six months prior to disease onset. This study indicates that two elderly Japanese patients with fulminant hepatitis B acquired HBV infection via interspousal (most likely sexual) transmission during long-lasting marriages.
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