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Query: UMLS:C0345904 (liver cancer)
 15,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To identify factors that might be useful as prognostic indexes for the risk of hepatocellular carcinoma in Italian patients with genetic hemochromatosis, 152 homozygotes were studied prospectively for 1 to 229 mo. Factors that were considered in estimating the risk of developing hepatocellular carcinoma were age, sex, cirrhosis (Child class), HBsAg, antibodies to HBsAg, antibodies to HBcAg, hepatitis C antibodies, alcohol abuse and the amount of iron removed during therapeutic phlebotomy to produce iron depletion. At diagnosis, cirrhosis was present in 97 patients and absent in 55. During follow-up, hepatocellular carcinoma developed in 28 of the 97 patients with cirrhosis but in none of those without. Among patients with cirrhosis, the cumulative probability of being free of hepatocellular carcinoma at 10 yr was 70%. For patients with and without HBsAg the probabilities of being free of liver cancer at 10 yr were, respectively, 54% and 75%; for those with and without history of alcoholism, 58% and 78%; and for those younger and older than 55 yr, 90% and 54%. In patients with cirrhosis, multivariate analysis using proportional-hazards (Cox) regression found that the only factors contributing significantly to the estimation of a prognostic index were age, presence of HBsAg and alcohol abuse. Age over 55 yr increased the relative risk of hepatocellular carcinoma 13.3-fold (p < 0.001), the presence of HBsAg increased it 4.9-fold (p < 0.02) and alcohol abuse increased it 2.3-fold (p < 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prognostic factors for hepatocellular carcinoma in genetic hemochromatosis. 798 40

Octachlorostyrene (OCS) is an environmental contaminant, present in fish of Northern European waters and the Great Lakes of America. It has many distribution and toxic similarities to hexachlorobenzene (HCB). Administration of OCS at 0.01% of the diet to C57BL/10ScSn mice within iron overload for 18 months gave only a low incidence of hepatic nodular hyperplasia (2/10 survivors) and no hepatocellular adenomas or carcinomas. In contrast, with a similar regime, HCB causes severe liver cancer or nodules in all exposed mice. Whole body autoradiography of mice given [14C]OCS or [14C]HCB showed no gross variations in distribution or covalent binding of the radiolabelled compound to account for the difference between the chemicals in the development of tumours. In 12-week studies, the CYP1A subfamily was induced to a greater degree by HCB than OCS and iron-enhanced uroporphyria was significantly greater with HCB. The findings are consistent with the proposal that uroporphyria and liver cancer induced in mice by HCB are associated through related mechanisms, but occur to a significantly lesser extent with OCS.
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PMID:Influence of iron on the induction of hepatic tumors and porphyria by octachlorostyrene in C57BL/10ScSn mice. 801 31

Superparamagnetic iron oxide particles (AMI-25) were evaluated as a liver contrast agent in high-field MR imaging (1.5 T). 16 patients with up to 5 presumed focal liver lesions (liver metastases n = 8, HCC n = 5, Klatskin tumours n = 2, FNH n = 1) received 15 mumol Fe/kg BW intravenously and were examined via standard T1- and T2-weighted spin-echo sequences. Quantitative image analysis showed a post-contrast increase of the contrast-to-noise ratio (C/N) from 1.6 to 7.4 on SE 2,500/15 images (p < .05). However, C/N was in the same range on plain SE 2,500/90 scans. Blind evaluation by two independent readers revealed that AMI-25-enhanced images did not provide a significantly increased number of lesions. Two patients reported minor, self-limited side-effects (flush, back pain). We conclude that in contrast to reports at mid-field MR imagers, the use of AMI-25 at 1.5 T does not significantly improve the detection of focal liver lesions on conventional SE images.
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PMID:[The MR tomography of focal liver lesions with the superparamagnetic contrast agent AMI-25 at 1.5 tesla]. 830 92

Eight patients with histologically or clinically diagnosed hepatocellular carcinoma and a total of 23 nodules were studied. SE 2000/20 (PDW-SE), SE-2000/80 (T2W-SE), SE 500/20 (T1W-SE), GRE 167/13/70 degrees (T1W-GE), and GRE 167/13/15 degrees (T2*W-GE) were used. Using each pulse sequence the pre-and post-contrast detection rates of the 23 nodules visualized by CT arterial portography (CTAP) were compared. With plain MRI, the detection rates were PDW-SE: 48%, T2W-SE: 74%, T1W-SE: 52%, T1W-GE 48% and T2*W-GE: 48%. After the administration of contrast medium all pulses sequences showed enhanced detection rates: 100%, 83%, 87%, 91%, and 96% respectively. Superparamagnetic iron oxide particle enhanced MRI showed a high detection rate comparable to CTAP, suggesting that this agent can make a major contribution to the diagnosis of HCC, particularly the detection of small HCC.
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PMID:[Usefulness of superparamagnetic iron oxide particles in the detection of hepatocellular carcinoma by MR imaging]. 838 92

Several clinical studies have suggested that excess hepatic iron accumulation is a progressive factor in some liver diseases including chronic viral hepatitis and hemochromatosis. However, it is not known whether iron-induced hepatotoxicity may be directly involved in hepatitis, cirrhosis, and liver cancer. The Long-Evans Cinnamon (LEC) rat, which accumulates excess copper in the liver as in patients with Wilson's disease, is of a mutant strain displaying spontaneous hemolysis, hepatitis, and liver cancer. We found previously that LEC rats harbored an additional abnormality: accumulation of as much iron as copper in the liver. In the present study, we compared the occurrence of hepatitis and liver cancer in LEC rats fed an iron-deficient diet (ID) with those in rats fed a regular diet (RD). The RD group showed rapid increments of hepatic iron concentrations as the result of hemolysis, characteristics of fulminant hepatitis showing apoptosis, and a 53% mortality rate. However, no rats in the ID group died of fulminant hepatitis. Hepatic iron, especially "free" iron concentration and the extent of hepatic fibrosis in the ID group were far less than those of the RD group. At week 65, all rats in the RD group developed liver cancer, whereas none did in the ID group. These results suggest that the accumulation of iron, possibly by virtue of synergistic radical formation with copper, plays an essential role in the development of fulminant hepatitis, hepatic fibrosis, and subsequent hepatocarcinogenesis in LEC rats.
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PMID:Hepatic iron deprivation prevents spontaneous development of fulminant hepatitis and liver cancer in Long-Evans Cinnamon rats. 877 Aug 63

HHC is the most common inherited metabolic disease among the white population worldwide, with a gene frequency of about 10% and a frequency of homozygosity of about 1 of 250. Many patients harbor a common haplotype of informative markers on chromosome 6p2l.23, suggesting a strong founder effect exerted by a common Celtic ancestor. With the advent of screening tests (serum Tf saturation, fe), many subjects with HHC are being identified before development of cirrhosis or diabetes mellitus, and early detection is important because prompt and vigorous iron reduction prevents development of such complications and assures normal life expectancy. The HIC can be estimated as accurately by specialized magnetic resonance imaging or susceptometric measurements as by chemical measurements on liver biopsy specimens. However, biopsy specimens retain value for showing fibrosis/cirrhosis and dysplastic hepatocytes, both of which increase risks of HCC development. There is growing evidence that iron in the liver plays an important role in non-HHC diseases, such as alcoholic liver disease, chronic viral hepatitis, and porphyria cutanea tarda. The complicated, manifold roles of iron in pathogenesis of the latter disorder include enhancement of production and irreversible oxidation of uroporphyrinogen, as well as formation of an inhibitor targeted specifically at hepatic uroporphyrinogen decarboxylase. The nature of the gene and gene product that are abnormal in HHC remain elusive, despite the intense efforts of several investigative groups. The search has been hampered by a dearth of informative markers in HHC patients in the relevant region of chromosome 6p. Note added in proof: The cloning of a candidate gene, the mutation of which may perhaps cause HLA-linked hemochromatosis, has just been reported (Feder et al: A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nature (Genetics) 1996;399-408). These workers identified a 250-kb region move than three megabases telomeric of the MHC that was identical in 85% of chromosomes of HHC patients. Within this region, they identified a gene related to the MHC class I family, termed HLA-H, containing two missense alterations one of which is predicted to inactivate this class of proteins. 83% of 178 patients were homozygous for this mutation (Cys 282Tyr). This variant was also found on 3.2% of control chromosomes, as would be expected for such a common disorder. Functional studies are awaited with great interest.
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PMID:An update on iron metabolism: summary of the Fifth International Conference on Disorders of Iron Metabolism. 878 49

Pathological changes arising in altered cell biology and diseases such as cancer are driven by changes in gene expression. In the inherited disease haemochromatotis (HC) progressive iron loading of the parenchymal cells (hepatocytes) of the liver leads to cellular toxicity. If left untreated, fibrosis, cirrhosis and ultimately liver cancer occur. By using differential display reverse transcriptase polymerase chain reaction (DDRT-PCR) techniques, we have identified and isolated several differentially displayed mRNAs that are excessively expressed or repressed in HC liver compared to normal human liver. One of these mRNAs was found to be strongly expressed in the liver of a patient with HC and in tumour tissue from a subject with hepatocellular carcinoma complicating HC (HC/HCC). The message of this gene was detected at a very low level in normal human liver. Northern analysis showed that this gene is also expressed in lymphocytes of HC patients and in MOLT-4 human T-lymphoid cells irrespective of iron status. The partial 1.0 kb cDNA sequence of the 9.5 kb transcript of this gene is unique and we propose that this gene may be related to cell proliferation and HC/HCC human liver.
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PMID:Molecular cloning of a novel mRNA highly expressed in haemochromatotic human liver and proliferating cells. 880 57

Hereditary hemochromatosis is an autosomal recessive disorder, the gene for which occurs in approximately 10% of Americans, most of whom are unaffected heterozygotes. Approximately 5/1000 white Americans are homozygous and at risk of developing severe and potentially lethal hemochromatosis. The disorder affects numerous organ systems, but the most common symptoms are fatigue, palpitations, joint pains, and impotence; the most common signs are those that relate to hypothalamic, cardiac, hepatic or pancreatic dysfunction, including poor cold tolerance, impotence in males, amenorrhea in females, cardiac arrhythmias, dyspnea, edema, hepatosplenomegaly, spider telangiectases, ascites, deformity, swelling or limitation of motion of joints, weight loss, hyperpigmentation. Characteristic abnormalities of laboratory tests include elevated serum iron concentration, high transferrin saturation, elevated serum ferritin concentration, elevated serum transaminases, hyperglycemia and low values for thyroid-stimulating hormone (TSH) and gonadotropins. Death may be the result of cardiac arrhythmia, congestive heart failure, liver failure or liver cancer. Since many of these complications cannot be reversed once they have developed, early diagnosis and treatment are essential. In view of the high prevalence in the American population (prevalence varies with ethnic background), the low cost of diagnosis and treatment, the efficacy of treatment if begun early, and, on the other hand, high costs and low success rate of late diagnosis and treatment, systematic screening for hemochromatosis is warranted for all persons over the age of 20 years. The initial screening should be by measurement of serum iron concentration and transferrin saturation. The practice guideline provides a diagnostic algorithm for cases in which the serum transferrin saturation is 60% or greater. It also provides guidelines for clinical management.
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PMID:Practice guideline development task force of the College of American Pathologists. Hereditary hemochromatosis. 886 84

Although the experience of orthotopic liver transplantation (OLT) for hereditary hemochromatosis (HHC) is limited, the existing data indicate that it carries a higher mortality when compared to transplantation for other causes of end-stage liver disease. Posttransplantation deaths are usually related to infectious or cardiac complications. HHC is often not diagnosed prior to OLT and one series has shown a high incidence of primary liver cancer diagnosed incidentally only at the time of transplantation. Factors that may account for the increase in postoperative mortality for HHC are the extent of iron deposition in extrahepatic sites in patients undiagnosed and thus untreated prior to transplantation. A high index of suspicion in subjects with end-stage liver disease should lead to improved diagnosis and allow for the prompt institution of either phlebotomy therapy or iron chelation therapy prior to transplantation. It is expected that these changes would reduce postoperative complications as well as improve long-term survival.
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PMID:Liver transplantation for hereditary hemochromatosis. 890 17

The performance of gadolinium-ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) and superparamagnetic iron oxide (SPIO) particles in detecting liver cancer was compared using alternative free-response receiver operating characteristic (AFROC) analysis, which allowed observers to indicate both the confidence level and the locations of all perceived abnormalities. Axial T1-weighted MR images (1.5 T) pre/post Gd-EOB-DTPA (25 mumol/kg) injection were obtained for 12 rats with chemically induced liver tumors (64 tumors). T2-weighted images (T2WI) were obtained pre/post SPIO (10 mumol/kg) injection for the same animal. Liver signal-to-noise ratio (SNR), tumor-liver contrast-to-noise ratio (CNR), and histopathologic sections corresponding to MR images were obtained. In AFROC, the location and the confidence level for each tumor were indicated independently on MR images by four radiologists. By plotting true-positive fraction and probability of false-positive per image, the area under the AFROC curve (A1) was estimated and statistically analyzed between each sequence. Either drug significantly improved tumor-liver CNR (P < .001) and tumor detection (diameter < or = 6 mm; P < .05). Gd-EOB-DTPA significantly (P < .05) improved the A1 in T1WI. There was no A1 difference between T2WI + SPIO and T1WI + Gd-EOB-DTPA. Gd-EOB-DTPA-enhanced T1WI showed the same performance as SPIO-enhanced T2WI in detecting liver tumors.
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PMID:Performance of Gd-EOB-DTPA and superparamagnetic iron oxide particles in the detection of primary liver cancer: a comparative study by alternative free-response receiver operating characteristic analysis. 903 1


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