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)

Using a proportional morbidity analysis method, the authors examined changes in the risk of malignancy among never-married men 20-49 years old (a surrogate population for homosexual men) in a high AIDS-risk area (City of San Francisco) and other lower AIDS-risk areas. This approach easily detected increases in Kaposi's sarcoma (odds ratio (OR) comparing 1973-1978 to 1984: 2,479-fold, proportional increase = 99.9%) and in non-Hodgkin's lymphomas (OR = 4.2-fold in 1984, p for trend less than 0.0001, proportional increase = 70%) in the City of San Francisco, with excesses especially in the Burkitt-like lymphomas and immunoblastic lymphomas. Extranodal lymphomas of the brain, but not other sites, were especially prominent (proportional increase = 96%). In addition, nonsignificant increases were seen for Hodgkin's disease (p for trend = 0.13) and for hepatoma (p for trend = 0.08). A posteriori, the authors noted increases in urinary tract tumors and acute lymphoblastic leukemia which warrant monitoring. Other tumors suggested to be AIDS-associated did not occur excessively in this population. Among single young men outside of San Francisco, Kaposi's sarcoma also increased significantly (OR = 182 in 1984), suggesting a lag of about three years behind the increases in the City of San Francisco. Some tumors may require a longer latent period before an association becomes manifest. In the meantime, however, these data indicate that the increases in AIDS-related cancers are limited to only a few malignancies.
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PMID:Cancer in a group at risk of acquired immunodeficiency syndrome (AIDS) through 1984. 363 Oct 49

At the University of California, San Francisco, 17 patients who met the following criteria-hepatic tumor unresectable because of location or inadequate liver reserve, no metastases, HBsAg negative, no tumor larger than 5 cm in diameter, and no more than three tumors--were enrolled prospectively in a protocol employing preoperative chemoembolization to assess whether orthotopic liver transplantation (OLT) could cure a majority of highly selected patients with hepatocellular carcinoma (HCC). Thirteen patients had biopsy-proven HCC, 2 had the fibrolamellar variant, and 2 had radiological findings of HCC but no biopsy confirmation. Fourteen had underlying liver disease. All arteriographically apparent lesions were chemoembolized using a mixture including Gelfoam powder, doxorubicin, mitomycin-c, and cisplatin. Eight patients with poor hepatic reserve were chemoembolized when a donor organ became available, whereas 9 patients were chemoembolized and then placed on the waiting list. The only complication of chemoembolization was a gangrenous gallbladder in 1 patient. Thirteen patients underwent liver transplantation (2 patients without prior histological confirmation of carcinoma had no identifiable tumor at OLT); 3 patients developed metastases between the time of enrollment and donor organ availability and subsequently died; and 1 patient underwent a trisegmentectomy. Ten of the 11 patients with biopsy-proven HCC who underwent transplantation remain free of recurrent cancer at a median of 40 months; 1 patient died at 6 months of lymphoproliferative disease with no cancer found at autopsy. Although the role of chemoembolization is uncertain, these data show that the majority of carefully selected patients with HCC may achieve long-term survival with OLT.
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PMID:Liver transplantation for hepatocellular carcinoma: results with preoperative chemoembolization. 934 74

We previously proposed modified staging criteria for predicting acceptable outcome after orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC). These were solitary tumor < or = 6.5 cm, or three or fewer nodules with the largest lesion < or = 4.5 cm and total tumor diameter < or = 8 cm, without gross vascular invasion (University of California, San Francisco [UCSF] criteria). In this study, we further evaluated the performance of the Milan criteria (solitary tumor < or = 5 cm, or three or fewer lesions none > 3 cm), the UCSF criteria, and the Pittsburgh modified tumor-node-metastasis (TNM) criteria. Pathologic HCC staging according to each set of criteria was performed in 70 patients. The difference in survival when comparing 24 patients with HCC exceeding Milan criteria versus 46 patients meeting Milan criteria did not reach statistical significance (HR, 2.0; P = .12). Using our definition for acceptable 2-year survival to be > or = 70%, the 14 patients (20%) meeting UCSF criteria but exceeding Milan criteria had a 2-year survival of 86% (95% CI, 54% to 96%). Survival for Pittsburgh stage I, II, and IIIA patients as a group was significantly better than for stages IIIB and IVA patients combined (HR, 4.2; P = .007), and similar to survival for patients meeting UCSF criteria. Advanced tumor exceeding UCSF criteria served reasonably well as a surrogate marker for poorly differentiated grade and microvascular invasion. In conclusion, our analyses suggest that UCSF criteria better predict acceptable posttransplant outcome than Milan criteria. UCSF criteria confer a different advantage over Pittsburgh criteria, which require information on microvascular invasion that is difficult to ascertain preoperatively without the attendant risk of biopsy.
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PMID:Liver transplantation for hepatocellular carcinoma: comparison of the proposed UCSF criteria with the Milan criteria and the Pittsburgh modified TNM criteria. 1220 Jul 75

The KK/San obese and diabetic mouse, a mutant strain from KK obese mice, exhibits significantly low plasma triglyceride levels. In KK/San mice, genetic analysis identified a mutation in the gene encoding angiopoietinlike protein 3 (Angptl3), a liver-specific secretory protein, which had suppressive effect on lipoprotein lipase activity. In the current study, LXR ligands augmented Angptl3 mRNA expression and protein production in hepatoma cells. LXR ligands and LXR.retinoid X receptor (RXR) complex increased the promoter activity of Angptl3 gene. Serial deletion and point mutation of Angptl3 promoter identified an LXR response element (LXRE). Gel mobility shift assay showed the direct binding of LXR.RXR complex to the LXRE of the Angptl3 promoter. Furthermore, treatment of mice with synthetic LXR ligand caused triglyceride accumulation in the liver and plasma, which was accompanied by induction of hepatic mRNAs of several LXR target genes, including sterol regulatory element binding protein-1c (SREBP-1c), fatty acid synthase (FAS), and Angptl3. In Angptl3-deficient C57BL/6J mice, LXR ligand did not cause hypertriglyceridemia but accumulation of triglyceride in the liver. Our results demonstrate that Angptl3 is a direct target of LXR and that induction of hepatic Angptl3 accounts for hypertriglyceridemia associated with the treatment of LXR ligand.
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PMID:Angiopoietin-like protein 3 mediates hypertriglyceridemia induced by the liver X receptor. 1267 13

Geographic variation in hepatocellular carcinoma (HCC) has not been previously studied in the United States. Using data collected by the Surveillance, Epidemiology, and End Results registries (SEER) and the 1990 Behavioral Risk Factor Surveillance System (BRFSS), we analyzed incidence and risk factors for HCC in nine geographic regions in the United States. We identified all individuals with HCC during 1975-1998 in five states (Connecticut, Iowa, Utah, New Mexico, and Hawaii) and four metropolitan areas (Detroit-Metropolitan, San Francisco-Oakland, Seattle-Puget Sound, and Atlanta-Metropolitan). Age-adjusted incidence rates were calculated for each geographic region. The association between HCC incidence and geographic regions were examined in Poisson multivariate regression model controlling for age, gender, race, and year of diagnosis. Hierarchical linear modeling was also used to examine these associations while adjusting for potential clustering of persons with similar characteristics within geographic regions, and to assess the effect of the prevalence of smoking, alcohol use, obesity, and diabetes in the underlying population in these geographical regions. A total of 11,547 persons with HCC were examined. Hawaii had the highest age-adjusted incidence rate (4.6), followed by San Francisco-Oakland (3.2), New Mexico (2.0), Detroit-Metropolitan (1.9), Seattle-Puget Sound (1.8), Atlanta-Metropolitan (1.7), Connecticut (1.6), Iowa (1.1), and Utah (1.0); all rates per 100,000. Whites had an age-adjusted incidence rate of 1.5, Blacks 3.2, and other races "Asian, American Indian, Pacific Islander" 7.0. However, Blacks and "other races" in Seattle-Puget Sound had higher age-adjusted incidence rates (4.4 and 8.2, respectively) than Blacks and other races in any other registry, while Whites in Hawaii had a higher rate (2.5) than Whites in any other registry. In general, men had a two to three times higher age-adjusted incidence rate than women. However, Hawaiian men had significantly higher age-adjusted rates (7.0) than men in other regions, while Utah had the lowest rates of HCC in men (1.5). Adjusting for variations in ethnicity, gender, age, and time of diagnosis, the Poisson regression analysis showed persistent geographic differences in HCC as well as a change in the order with New Mexico having the highest HCC incidence followed San Francisco-Oakland. Hierarchical linear modeling confirmed geographic variations in HCC but failed to show a significant effect for the prevalence of smoking, alcohol use, obesity, and diabetes in the underlying population. Significant geographic variation in HCC incidence exist in the United States. These variations are only partly explained by differences in age, gender, race, and year of diagnosis.
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PMID:Geographic variation within the United States in the incidence of hepatocellular carcinoma. 1281 24

The incidence of hepatocellular carcinoma (HCC), a frequent and incurable complication of cirrhosis, continues to rise. Orthotopic liver transplantation (OLT) has been proposed as a treatment for unresectable, intrahepatic HCC limited in extent to the Milan criteria adopted by the United Network of Organ Sharing (UNOS) in 1998. More recently, somewhat less restrictive University of California, San Francisco (UCSF)10, criteria were proposed. To examine the long-term outcomes of OLT for HCC patients and to assess the UNOS policy of assigning weighted allocation points to patients with HCC, we retrospectively analyzed 144 patients (113 after 1998) with HCC who underwent OLT over an 11-year period at 3 institutions from UNOS Region 1. We compared their outcomes with 525 patients (272 after 1998) who underwent OLT for nonmalignant liver disease. The 1- and 5-year survival rates were 80.3% and 46.7%, respectively, for patients with HCC and 81.5% and 70.6%, respectively, for patients without HCC (P = .020). However, there was no difference in survival between HCC and non-HCC patients after implementation of disease-specific allocation for HCC in 1998. A higher proportion of the HCC cohort was older and male and had chronic HCV infection and alcoholic liver disease. In univariate analysis, having alpha-fetoprotein (AFP) levels of 10 ng/mL or less and meeting clinical and pathologic UCSF criteria were each significant predictors of improved survival (P = .005, P = .02, and P = .03, respectively). AFP greater than 10 ng/mL and exceeding pathologic UCSF criteria were also significant predictors of recurrence (P = .003 and P = .02, respectively). In conclusion, taken together, our data suggest that OLT is an acceptable option for patients with early HCC and that UCSF criteria predict outcome better than Milan or UNOS criteria. Regardless of which criteria are adopted to define eligibility, strict adherence to the criteria is important to achieve acceptable outcomes.
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PMID:Liver transplantation outcomes for early-stage hepatocellular carcinoma: results of a multicenter study. 1549 58

In patients with cirrhosis and hepatocellular carcinoma (HCC), orthotopic liver transplantation (OLT) offers hope for cure of both the complicating HCC and the underlying chronic liver disease. Excellent 5 year survival has been reported when the restrictive Milan criteria are used to select transplant candidates. Alternative recommendations have recently been proposed by groups at University of California San Francisco, University of Pittsburgh and Mount Sinai. We review current and evolving concepts regarding selection criteria for OLT in patients with HCC, along with strategies to reduce waiting times, such as the impact of the implementation of the model for end-stage liver disease (MELD) scoring system on organ distribution and the role of living donor OLT for this indication. The possible efficacy of adjuvant anti-tumour therapies in limiting HCC growth while waiting for OLT, along with factors influencing the risk of HCC recurrence post-OLT, the major cause of death in this setting, are also discussed.
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PMID:Liver transplantation for hepatocellular carcinoma. 1575 10

Current selection criteria of liver transplantation (LT) for patients with hepatocellular carcinoma (HCC) were derived from the outcomes of cadaveric donor LT (CDLT). We tried to assess the applicability of such criteria to living donor LT (LDLT) through a comparative study between CDLT and LDLT. We analyzed the outcomes of 312 HCC patients who underwent LT at 4 Korean institutions during 1992 to 2002. There were no gross differences of tumor characteristics between CDLT group (n = 75) and LDLT group (n = 237). Overall 3-year survival rate (3-YSR) was 61.1% after CDLT and 73.2% after LDLT including 38 cases of perioperative mortality. Comparison of HCC recurrence curves did not reveal any statistical difference between these 2 groups. Patient survival period till 50% mortality after HCC recurrence was 11 months after CDLT and 7 months after LDLT. Significant risk factors for HCC recurrence were alpha-fetoprotein level, tumor size, microvascular invasion, gross major vessel invasion, bilateral tumor distribution, and histologic differentiation in the LDLT group on univariate analysis, and tumor size, gross major vessel invasion, and histologic differentiation on multivariate analysis. Milan criteria were met in 70.4%: Their 3-YSR was 89.9% after CDLT and 91.4% after LDLT with exclusion of perioperative mortality. University of California San Francisco criteria were met in 77.7%: Their 3-YSR was 88.1% after CDLT and 90.6% after LDLT. In conclusion, we think that currently available selection criteria for HCC patients can be applicable to LDLT without change of prognostic power.
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PMID:Liver transplantation for adult patients with hepatocellular carcinoma in Korea: comparison between cadaveric donor and living donor liver transplantations. 1618 45

In patients with hepatocellular carcinoma (HCC) exceeding conventional (T2) criteria for orthotopic liver transplantation (OLT), the feasibility and outcome following loco-regional therapy intended for tumor downstaging to meet T2 criteria for OLT are unknown. In this first prospective study on downstaging of HCC prior to OLT, the eligibility criteria for enrollment into a downstaging protocol included 1 lesion >5 cm and < or =8 cm, 2 or 3 lesions at least 1 >3 cm but < or =5 cm with total tumor diameter of < or =8 cm, or 4 or 5 nodules all < or =3 cm with total tumor diameter < or =8 cm. Patients were eligible for living-donor liver transplantation (LDLT) if tumors were downstaged to within proposed University of California, San Francisco (UCSF) criteria.13 A minimum follow-up period of 3 months after downstaging was required before cadaveric OLT or LDLT, with imaging studies meeting criteria for successful downstaging. Among the 30 patients enrolled, 21 (70%) met criteria for successful downstaging, including 16 (53%) who had subsequently received OLT (2 with LDLT), and 9 patients (30%) were classified as treatment failures. In the explant of 16 patients who underwent OLT, 7 had complete tumor necrosis, 7 met T2 criteria, but 2 exceeded T2 criteria. No HCC recurrence was observed after a median follow-up of 16 months after OLT. The Kaplan-Meier intention-to-treat survival was 89.3 and 81.8% at 1 and 2 yr, respectively. In conclusion, successful tumor downstaging can be achieved in the majority of carefully selected patients, but longer follow-up is needed to further access the risk of HCC recurrence after OLT.
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PMID:A prospective study on downstaging of hepatocellular carcinoma prior to liver transplantation. 1631 92

In patients with hepatocellular carcinoma (HCC) exceeding conventional Milan criteria (one lesion < or = 5 cm or two or three lesions < or = 3 cm) for orthotopic liver transplantation (OLT), down-staging of the tumor before OLT presents an unique and intriguing perspective on tumor biology and expanded criteria for OLT. According to the University of California, San Francisco protocol, the eligibility criteria for down-staging included one lesion < or = 8 cm, two or three lesions each < or = 5 cm with total tumor diameter < or = 8 cm, or four or five lesions each < or = 3 cm with total tumor diameter < or = 8 cm. In the majority of these patients, successful down-staging using well-defined endpoints could be achieved prior to OLT, without resulting in post-transplantation HCC recurrence. The promise of down-staging warrants consideration of a unified policy granting patients with HCC that has been successfully down-staged the same priority listing for OLT as those meeting conventional criteria.
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PMID:Expanded criteria for hepatocellular carcinoma: down-staging with a view to liver transplantation--yes. 1685 Mar 74


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