Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Between July 1986 and April 1989, 334 hospitalized adult Ethiopian patients with chronic liver disease were studied according to a protocol to define their clinical features and to identify risk factors with the aim of preventive intervention. Of these, 14 had chronic hepatitis, 208 cirrhosis and 112 hepatocellular carcinoma (HCC). Both clinical and histological diagnostic criteria were employed. A detailed questionnaire was used to document demographic and clinical data. A common clinical presentation among patients with chronic hepatitis was darkening of the face and hands with or without hypertrichosis of the face and blisters over the dorsi of the hands. This overt or latent form of porphyrea cutanea tarda (PCT) responds to chloroquine. Patients with cirrhosis of the liver commonly present for the first time with ascites, splenomegaly, haematemesis and/or melena from oesophageal varices, and mental changes due to hepatic encephalopathy. Overt or latent forms of PCT are also common features. Peculiar to these cirrhotics is the rarity of spider naevi, gynaecomastia, testicular atrophy, Dupuytren's contracture, parotid gland enlargement and clubbing of the fingers. Exhaustion, loss of appetite, rapid loss of weight, right upper quadrant and/or epigastric pain (all often of less than 6 months' duration, a big, hard, tender and grossly nodular liver with bruit, signs of portal hypertension, and/or hepatic encephalopathy, in a young male with a rapid down hill course characterize the Ethiopian patient with HCC. Serum anti-nuclear factor, anti-mitochondrial anti-bodies and anti-smooth muscle anti-bodies were absent in those with chronic hepatitis and were uncommon in the cirrhotics and HCC cases. One or more hepatitis B virus markers were found in 86% of chronic hepatitis, 88% cirrhosis and 78% HCC and the HBsAg carrier state was found in 36%, 29% and 23%, respectively. Among the HBsAg carriers, HBeAg positivity was less common than anti-HBe but anti-HDV was significantly higher than in the healthy general population. Alphafetoprotein (AFP) levels greater than 500 mg/ml were present in 16 (8%) cirrhotics and 58 (52%) patients with HCC. Histologically, 3 of the chronic hepatitis patients had progressed to cirrhosis, 8 of the cirrhotic patients had chronic active hepatitis and 85% of HCC cases occurred in a background of macronodular cirrhosis. Three cirrhotics developed HCC during follow-up.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Chronic liver disease in Ethiopia: a clinical study with emphasis on identifying common causes. 131

Hepatocellular carcinoma (HCC) may uncommonly present with distant metastasis in the absence of a documented neoplasm in the liver. The authors herein describe the case of a 60-year-old man with cirrhosis who developed unilateral enlargement of the breast and a subareolar mass. This problem was clinically thought to represent gynecomastia, but a mammary fine-needle aspiration biopsy demonstrated a malignant epithelial neoplasm composed of large granular amphophilic cells. Bile pigment was visualized in the tumor on aspirate smears and cell block preparations; immunostains showed reactivity for cytokeratin and alpha-fetoprotein, but there was no positivity for epithelial membrane antigen, gross cystic disease fluid protein-15, vimentin, estrogen receptors, progesterone receptors, or S100 protein. These results indicated a diagnosis of metastatic HCC, which was subsequently confirmed by computed tomography of the abdomen.
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PMID:Metastatic hepatocellular carcinoma of the breast, simulating gynecomastia: diagnosis by fine-needle aspiration biopsy. 133 27

The case of a 38 year-old man with hepatocellular carcinoma in a non-cirrhotic liver is reported. Hyperestrogenosis with gynecomastia, polycythemia and proteinuria were present. After complete removal of the tumor, estrogen levels, red blood-cell volume and urine analysis did not return to normal and these pathologic findings were probably not paraneoplastic syndromes. Outcome was good, the patient remaining completely well without evidence of recurrence during the ensuing 30 months. The likely explanation for the persistent hyperestrogenosis was an excessive conversion of sexual hormones. The authors suggest that this abnormal hyperestrogenic state could promote hepatic neoplasia as it has been established in animals.
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PMID:[Hepatocellular carcinoma and hyperestrogenia in a male]. 282 Aug 25

Thirty-three-year-old male patient, without recognized risk factors, presenting with recurrent thrombophlebitis and bilateral gynecomastia as the only sign of feminization. Twenty-seven months after onset hepatocarcinoma of the right lobe was diagnosed. The rest of the liver was normal. Gynecomastia resolved after surgical removal of the tumor. Thromboembolism did not recur.
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PMID:[Recurrent thrombophlebitis and bilateral gynecomastia. Primary manifestations of hepatocarcinoma]. 632 45

Seventy patients with primary liver cell carcinoma (PLC) were studied for the occurrence and relative incidence of paraneoplastic syndromes (PNS) between 1985 and 1990. Here we communicate results of the study involving hypercholesterolaemia, hypercalcemia, hypoglycaemia, gynaecomastia and polycythaemia. Hypercholesterolaemia occurred in 20% of our patients and is the most common PNS in our series; polycythaemia occurred in 15.6%, hypoglycaemia in 8.6% and hypercalcaemia in 7%. It is noteworthy that hypoglycaemia, which is one of the commonest and certainly the most dangerous PNS associated with PLC, occurred in few of our patients. The occurrence and incidence of PNS as obtained in the present study slightly differ from those in developed countries. The pathophysiological mechanisms underlying these systemic manifestations are discussed.
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PMID:Paraneoplastic syndromes in primary liver cell carcinoma in Nigeria. 816 31

We report a 15-year-old boy with hepatocellular carcinoma (HCC) of the fibrolamellar type. He presented with advanced disease and a non-resectable tumor. Clinical features included marked gynecomastia which had been present for 3 years, failure to enter puberty, and failure to thrive. These features might have been due to a high aromatase activity of the tumor. The course of the illness suggested that the tumor had been present for at least 3 years prior to diagnosis. At diagnosis the patient had multiple metastases which included infiltrated ascites. Cytogenetic analysis of the ascites revealed a near triploid karyotype with cell-to-cell variation and an abnormality of chromosome 1 q. This to our knowledge is the first karyotype report of fibrolamellar HCC in a child.
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PMID:A childhood fibrolamellar hepatocellular carcinoma with increased aromatase activity and a near triploid karyotype. 898 50

This report represents the first study in the literature linking development of severe gynecomastia, in a 17 1/2-yr-old boy, to high levels of aromatase expression in a large fibrolamellar hepatocellular carcinoma, which gave rise to extremely elevated serum levels of estrone (1200 pg/mL) and estradiol-17 beta (312 pg/mL) that suppressed FSH and LH (1.3 and 2.8 IU/L, respectively), and consequently testosterone (1.53 ng/mL). After removal of a 1.5-kg hepatocellular carcinoma, gynecomastia partially regressed, and essentially, normal hormone levels were restored (estradiol-17 beta, < 50 pg/mL; estrone, 74 pg/mL; testosterone, 6.85 ng/mL; and FSH/LH, 6.3/3.7 mIU/mL). Conversion of C19 steroids to estrogens occurs in a number of human tissues and is catalyzed by aromatase P450 (P450arom), the product of the CYP19 gene in a number of human tissues. Tissue-specific promoters are used to regulate P450arom gene transcription in adult human tissues, e.g. promoters I.4 and I.3 in adipose fibroblasts, and promoter II in the gonads. Human fetal liver uses promoter I.4 to express markedly high levels of P450arom, whereas hepatic P450arom expression normally becomes undetectable in postnatal life. Using immunohistochemistry, diffuse intracytoplasmic aromatase expression was detected in the liver cancer cells from this severely feminized boy. Northern analysis indicated the presence of P450arom transcripts in total RNA from the hepatocellular cancer but not in the adjacent liver nor in disease-free adult liver samples. Promoter use for aromatase expression was determined by a specific RT-PCR method. Promoters I.3 and II were used for P450arom gene expression in the hepatocellular cancer tissue. Because aromatase is not expressed in the disease-free adult liver, the presence of extremely high levels of aromatase expression in this fibrolamellar hepatocellular carcinoma tissue is intriguing, particularly because there is preferential use of the proximally located P450arom promoters I.3 and II by the tumor, instead of the much more distally located fetal liver-type promoter I.4.
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PMID:Molecular basis of severe gynecomastia associated with aromatase expression in a fibrolamellar hepatocellular carcinoma. 958 95

During the 10-year period from 1979 to 1988 we evaluated 60 boys who were more than 9 years old and who had significant breast development (greater than 4 cm in diameter) around the time of puberty. An endocrine abnormality was identified in seven subjects. The pathology included Klinefelter's syndrome; 46,XX maleness; primary testicular failure; partial androgen insensitivity; fibrolamellar hepatocarcinoma; and increased aromatase activity. Eight of the remaining 53 subjects had underlying medical problems, five of them having neurologic disorders. The 45 remaining subjects were considered to have significant idiopathic gynecomastia, a condition sometimes referred to as macromastia. These boys tended to be both taller and heavier than average, the mean Z score for height being 1.4 SDs above the mean and the mean weight score being 2.7 SDs above the mean. This study underscores the observation that pathologic causes of marked pubertal gynecomastia are unusual. However, the potential for significant health problems among boys with marked breast development supports the need for an endocrine evaluation of all affected subjects. Our data also indicate that boys with marked idiopathic breast development have greater body mass than other boys of similar age. This may contribute in part to the greater breast development in these subjects.
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PMID:Evaluation of boys with marked breast development at puberty. 963 1

The liver plays important roles in the clearance and metabolism of sex steroids. Its dysfunction is considered to influence the metabolic pathways of sex steroids, and to result in gynecomastia and other abnormalities of sex steroids. However, the details of its mechanism have not been well-characterized. We therefore examined the enzymes involved in the hepatic clearance and/or metabolism of sex steroids in human liver and its disorders using immunohistochemistry to determine whether there are any abnormalities of expression of these enzymes in human liver disorders. These enzymes are 17beta-hydroxysteroid dehydrogenase (17beta-HSD) type 2, an enzyme that catalyzes the biologically active estrogen, estradiol (E2), to inactive estrogen, estrone (El), and dehydroepiandrosterone sulfotransferase (DHEA-ST), which catalyzes sulfonation of dehydroepiandrosterone (DHEA) to form biologically inactive DHEA-S. A total of 162 cases including normal liver (n=31), chronic hepatitis (n=41), liver cirrhosis (n = 21), hepatocellular carcinoma (n = 47), cholangiocellular carcinoma (n = 22) and fetal liver (n = 4) were examined by immunohistochemistry. Both enzymes were expressed in the hepatocytes around portal area and central vein in normal liver. Immunopositive area for DHEA-ST was significantly larger in chronic hepatitis than in normal liver, but that of 17beta-HSD type 2 in chronic hepatitis was not different from normal liver. There were no significant differences in the immunopositive area for both enzymes between liver cirrhosis and normal liver. In hepatocellular carcinoma, immunoreactivity for both enzymes were categorized into Group A, or low positive group, and Group B, or high positive group. The latter tended to be poorly differentiated carcinoma. In cholangiocellular carcinoma, immunopositive areas of both enzymes were significantly smaller than those of normal liver. These findings indicate that the amount of expression of the enzymes involved in metabolism and/or clearance of sex steroids per hepatocyte did not decrease in liver cirrhosis. Therefore, sex steroids' abnormalities may be due to the decreased quantity of hepatocytes associated with liver cirrhosis. In hepatocellular carcinoma, some poorly differentiated cases were associated with increased expression of 17beta-HSD type 2 but its biological significance needs to be determined by further studies.
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PMID:17Beta-hydroxysteroid dehydrogenase type 2 and dehydroepiandrosterone sulfotransferase in the human liver. 1122 44

Hepatic fibrolamellar carcinoma (FLC) is an uncommon tumour that differs from hepatocellular carcinoma (HCC) in demographics, condition of the affected liver, tumour markers, and prognosis. FLC characteristically manifests as a large hepatic mass in adolescents or young adults with female predominance (mean age 23 years). Cirrhosis, elevated alpha-fetoprotein levels, and risk factors for HCC such as viral hepatitis are typically absent. FLC is usually associated with serum tumour markers such as vitamin B12 binding protein, and neurotensin. FLC is characterized pathologically by cords of tumour cells surrounded by abundant collagenous fibrous tissue arranged in a parallel or lamellar distribution. FLC usually appears on radiologic images as a lobulated heterogeneous mass with a central scar in an otherwise normal liver. The clinical presentation of patients with FLC is variable. These patients commonly have pain, and palpable right upper quadrant abdominal mass. An uncommon presenting sign is gynaecomastia in men. Use of percutaneous biopsy (FNAB) is beneficial if there is diagnostic uncertainty about the radiologic diagnosis (US, CT MRI). Although FLC is frequently recurrent, patients have a better prognosis than those with HCC, and aggressive surgical liver resection with extended lymphadenectomy or liver transplantation may be indicated. The presence of advanced-stage disease, direct invasion of adjacent organs, lymphadenopathy, or limited metastasis does not preclude attempts at curative resection. In inoperable cases, the patient may benefit from chemotherapy, permitting in up to 50% of these cases a curative resection. The case is reported of a 18-year-old man with bilateral gynecomastia secondary to an unknown hepatic fibrolamellar carcinoma producing oestrogens. Serum alpha-fetoprotein was negative; des-gamma-carboxy prothrombin (DCP) level was elevated. CT scan and MRI showed a solid hepatic tumour (theta 10 cm) without evidence of extrahepatic spreading. By a needle biopsy a fibrolamellar carcinoma was diagnosed. On March 1995 a right hemihepatectomy was performed. The postoperative course was uneventful and the patient recovered. Specimen's histologic examination confirmed the preoperative diagnosis. Intracellular (hepatocytes) oestrogens were found, but oestrogen and androgen receptors were negative. After surgery DCP and oestradiol levels rapidly decreased and gynaecomastia disappeared. A follow-up program was established. On April 2000 a probable recurrence within the caudate lobe was discovered by a liver CT scan without evidence of extrahepatic spreading. Tumour markers, FNAB, and bone scintigraphy were negative. On July 2000 the patient underwent second look laparotomy. Only a coeliac lymphadenopathy was found and a lymphadenectomy performed. Specimen's histologic examination showed a metastatic lymph nodal disease (FLC). The postoperative course was uneventful and the patient recovered. He is currently alive without evidence of recurrence 5 years after the second operation.
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PMID:[Surgical therapy of hepatic fibrolamellar carcinoma]. 1751 32


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