Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The incidence of hepatocellular carcinoma (HCC) is increasing in the United States. Although liver transplantation is an effective means of treating selected patients, pretransplantation tumor progression may preclude some patients from undergoing transplantation. The aim of this study is to determine the safety and efficacy of percutaneous radiofrequency thermal ablation (RFA) in 33 consecutive patients with nonresectable HCC and advanced cirrhosis. Mean subject age was 57.2 +/- 10.6 years, mean Child-Turcotte-Pugh score was 7.0 +/- 1.4, and mean maximal tumor diameter was 3.6 +/- 1.1 cm. Using contrast-enhanced computed tomography and magnetic resonance imaging, 22 patients (66%) had a complete radiological response at 3 months post-RFA, whereas 11 patients (33%) had an incomplete radiological response. During follow-up, 18 patients (54%) experienced tumor progression and 9 subjects underwent repeated ablation for either residual disease or tumor progression. The overall actuarial patient survival rate of the 33 patients was 58% at 2 years, whereas the transplantation-free patient survival rate was 34% at 2 years. Fifteen of 23 transplant candidates were successfully bridged to liver transplantation after a mean post-RFA follow-up of 7.9 +/- 6.7 months. The extent of tumor necrosis in the explant varied, but no subjects had evidence of tumor seeding on post-RFA imaging, at liver transplantation, or in the explant. The 3-year actuarial posttransplantation patient survival rate was 85%. Two patients have developed posttransplantation recurrence, and both had microscopic vascular invasion in their explants. In summary, our data show that RFA is a safe and effective treatment modality for patients with advanced cirrhosis and nonresectable HCC. Although the ability of RFA to prevent or delay tumor progression requires further prospective study, its favorable safety profile and promising efficacy make it an attractive treatment option for liver transplant candidates with nonresectable HCC.
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PMID:Percutaneous radiofrequency thermal ablation of hepatocellular carcinoma: a safe and effective bridge to liver transplantation. 1247 57

The prognosis of patients with liver cirrhosis (LC) has been improved by the advanced diagnostic modalities and medical treatment of the disease. During the follow-up period, the opportunity for discovery of carcinomas of the liver and the other digestive organs is increased in LC patients, who are recognized as a compromised hosts with impaired hepatic functional reserve, portal hypertension, and depressed reticuloendothelial function. Thus LC patients are susceptible to infection as a major form of morbidity after surgical treatment, which can result in sepsis and subsequent hepatic failure. Based on the adequate evaluation of cancer progression and hepatic functional reserve, a procedure yielding the necessary results with the minimum surgical treatment and careful perioperative management should be performed for LC patients to avoid critical complications such as sepsis and hepatic failure.
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PMID:[Infection as a major morbidity in surgical treatment for patients with liver cirrhosis]. 1259 26

We prospectively studied the global applicability of liver transplantation in Catalonia, a region with a high rate of organ donation. We followed 232 adult patients assessed as possible candidates for liver transplantation over 12 months in the three hospitals that perform the procedure in this region. The liver disease leading to patient assessment was cirrhosis in most cases, alone (159 patients) or associated with hepatocellular carcinoma (57 patients). After being assessed, 150 patients (65%) were accepted for transplantation and included on the waiting list, and 82 (32%) were excluded. Death during the period of assessment, advanced tumoral disease, early stage of liver disease, and extrahepatic co-morbidities were the most important reasons for exclusion. The median time of assessment of patients accepted for transplantation was 40 days. Of the 150 patients included on the waiting list, 131 (87%) received transplants, 17 (11%) were removed from the list, and two were still waiting for transplantation at the end of the follow-up period. Death and tumor progression were the most important reasons for patients' removal from the waiting list. The median time on the waiting list was 59 days. In conclusion, among liver-transplant candidates the overall applicability of this therapy in Catalonia was relatively low (131 out of 232 transplant candidates finally underwent transplantation, 56%), and inadequate liver-transplant indications and death or tumor progression during the period of assessment or while the patient was on the waiting list were the most frequent reasons why liver transplantations did not proceed.
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PMID:Applicability of liver transplantation in Catalonia at the end of the millennium. A prospective study of adult patient selection for liver transplantation. 1273 Aug 8

A novel gene, p73, encoding a protein with significant homology to p53 and showing functional similarities to p53, was identified at chromosome 1p36, at which tumor suppressor gene of hepatocellular carcinoma (HCC) is supposed to be. Involvement of p73 in hepatocarcinogenesis is controversial and clinical value of p73 alterations remains obscure. We investigated allelic status of p73 in 63 patients with HCC. Loss of heterozygosity (LOH) in p73 was analyzed by PCR-RFLP analysis. The results were compared with LOH on chromosome 1p surrounding p73 locus, mutations of p53 and p73, and clinicopathologic characteristics. LOH on p73 was observed in 33% of informative tumors. LOH in p73 was not always observed between the regions with LOH on chromosome 1p examined despite the significant association of LOH in p73 with LOH on chromosome 1p. No mutations were detected in p73. Tumors with LOH in p73 were more frequently detected in liver without cirrhosis than that with cirrhosis. There was no significant statistic association between the presence of LOH in p73 and six different clinicopathologic characteristics such as age, sex, histological type, T stage, tumor diameter, and virus status. Disease-free survival rates of the patients with LOH in p73 were significantly poorer than those without LOH in p73. Multivariate analysis indicated that presence of LOH in p73 was independent prognostic factor in patients with HCC. These findings suggested that p73 might play some role in tumor progression of HCC even though p73 should not be considered a candidate gene on chromosome 1p of HCC and does not function as a tumor suppressor gene like p53. Identifying the patients with LOH of p73 in tumors could be useful to predict early recurrence and to stratify the patients who need adjuvant therapy after operation.
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PMID:Clinical value of alterations in p73 gene, related to p53 at 1p36, in human hepatocellular carcinoma. 1471 22

Transforming growth factor-beta1 (TGF-beta1) has been implicated in tumor progression. The relationship of this cytokine as measured in plasma to anti-tumor immunity and prognosis was investigated. This study consisted of 70 consecutive patients with unresectable hepatocellular carcinoma (HCC) (median age, 65 years). Forty-four healthy age-matched subjects and 32 patients with cirrhosis but no carcinoma served as controls. Patients with HCC were divided into those with plasma TGF-beta1 concentrations above (group A, n=21) or below (group B, n=49) 10 ng/ml (the mean concentration+2SD in the concentrations of the controls with cirrhosis was 8.7 ng/ml). Age, gender, Child-Pugh grade, and tumor stage distributions were similar in groups A and B. Considering all tumor stages together and individually, group A had a significantly shorter survival (median for all stages, 2 months) than group B (median for all stages, 10 months; P<0.01, generalized Wilcoxon's test). Groups A and B had significantly shorter survival than controls with cirrhosis (P<0.001 for each). Lymphokine-activated killer (LAK) activity in group A was significantly lower than that in group B (P<0.001). Natural killer (NK) activity in group A was also significantly lower than that in group B (P<0.05). Plasma TGF-beta1 concentration was a significant predictor of survival by Cox's proportional-hazards regression analysis (multivariate analysis, P<0.01). LAK and NK activities were also weak but significant predictors (P<0.05 and <0.05, respectively). These data suggest that plasma TGF-beta1 concentration is a predictor of outcome of patients with unresectable HCC. Circulating TGF-beta1 supposedly contributes to the suppression of anti-tumor immunity in the advanced disease.
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PMID:Possible contribution of circulating transforming growth factor-beta1 to immunity and prognosis in unresectable hepatocellular carcinoma. 1510 97

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancer death in the world. The present study aimed to investigate the genes involved in viral carcinogenesis and tumor progression in liver transplant recipients with hepatitis C virus (HCV) and HCC. To accomplish this, we performed the analysis of hepatic gene expression in HCV-infected liver recipient patients with stages of disease ranging from early cirrhosis with preserved volume and function to late cirrhosis with diminished volume and function with and without HCC. We found consistent differences between the gene expression patterns in HCV-HCC and those of early HCV-cirrhosis, late HCV cirrhosis, and normal control livers. The expression patterns in HCC were also readily distinguished between early and advanced HCC tumor stages. Moreover, we found different gene expression patterns between early cirrhosis and late cirrhosis. In conclusion, these findings confirm the presence of multiple molecular alterations during HCV-HCC hepatocarcinogenesis and, clinically, indicate the possibility for identifying prognostic factors associated with HCC progression in liver transplant patients waiting for a donor and/or posttransplantation recurrence.
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PMID:Hepatocellular carcinoma in HCV-infected patients awaiting liver transplantation: genes involved in tumor progression. 1510 52

Nerve growth factor (NGF) is suggested to have a role in tumor progression in addition to its role in differentiation and survival of neuronal cells. We investigated expression of NGF and its receptors, TrkA and p75NTR, in hepatocellular carcinomas (HCCs). Although hepatocytes and hepatic stellate cells (HSCs) showed respectively weak and intense NGF immunostaining in the background livers of patients suffering from liver cirrhosis (LC) or chronic hepatitis (CH), intense staining was demonstrated in HCC cells of 33 of 54 (61.1%) tumors. RT-PCR detected NGF mRNA in 7 freshly-isolated HCC samples, and in 2 of 4 cases, in which both background livers and tumors could be analyzed, NGF mRNA was more abundant in the tumors than the background livers. TrkA was detected in the smooth muscle cells of hepatic arteries, but it was negative in tumor cells as well as non-neoplastic hepatocytes. p75NTR and alpha-smooth muscle actin (alphaSMA) was expressed in HSCs in the background liver and fibroblast-like cells in stromal septa, whereas HSCs within the HCC tissues were mostly negative for p75NTR but positive for alphaSMA. This suggests that HSCs in HCC have a different property from those in background livers. Furthermore, the stromal septa contained abundant nerve fibers, which may be related to the increased NGF expression in HCC cells. NGF and its receptors are then thought to have a role in cellular interactions involving HCC cells, HSCs, arterial cells and nerve cells in HCC tissues.
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PMID:Expression of NGF in hepatocellular carcinoma cells with its receptors in non-tumor cell components. 1552 89

The model for end-stage liver disease (MELD) has been a prevailing system to prioritize cirrhotic patients awaiting liver transplantation. An "exceptional" MELD score of 20 and 24 points is assigned for stage T1 and T2 patients with small hepatocellular carcinoma (HCC), respectively. However, this strategy is based on scarce data and the optimal score for these patients remains uncertain. We investigated 238 patients with small HCC who were candidates for liver transplantation and underwent arterial chemoembolization or percutaneous injection therapy using acetic acid or ethanol. Tumor stage (P = .001) and Child-Turcotte-Pugh (CTP) class (P < .001) were independent risk factors predicting tumor progression or death in survival analysis. The risk of disease progression in HCC patients stratified by tumor stage was mapped and equated with the risk of mortality of 456 cirrhotic patients without HCC. The 6- and 12-month rates of disease progression were 4% and 6%, respectively, for stage T1 HCC patients (n = 50; mean MELD: 9.5). These rates were close to and no higher than the mortality rate in MELD category 8-12 at the corresponding time period (7.1% and 11.3%, respectively; n = 141). For stage T2 patients (n = 188; mean MELD: 9.3), the corresponding rates were 5.3% and 13.8%, respectively, which were close to and no higher than the mortality rate in MELD category 10-14 (9.0% and 13.9%, respectively, n = 166). In conclusion, the risk of disease progression is quite low for selected HCC patients undergoing loco-regional therapy. A lower MELD score may be suggested to be equivalent to the risk of short- and mid-term mortality in the cirrhosis group.
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PMID:Determination of the optimal model for end-stage liver disease score in patients with small hepatocellular carcinoma undergoing loco-regional therapy. 1555 87

In the present study, the expression of P53 and MDM2 proteins were examined in specimens from a group of 20 patients (9 with primary hepatocellular carcinoma HCC and 11 with liver cirrhosis LC, linked to HBV infections as a major aetiologic factor) by immunohistochemistry. The immunostaining findings were correlated with P53 mutation analysis using PCR-SSCP, PCR-HDF and direct sequencing, and MDM2 amplification studies by differential PCR. P53 immunopositivity was found in 9 out of the 20 (45.0%) cases. Mutations of the P53 gene were detected in 5 (55%) tumors and 3 (27%) LC samples; 7 of these cases revealed P53 immunoreactivity. The mutations were base transitions at codons 175, 245 and 273; no changes were observed at codon 249, characteristic for aflatoxins action. MDM2 immunopositivity was revealed in 9 out of 20 (45.0%) specimens. MDM2 amplification occurred in 4 (44.4%) and 1 (9.1%) cases, HCC and LC specimens respectively; only in 2 tumors (10.0%), which exhibited MDM2 immunoreactivity. Overall, MDM2 positivity was not associated with MDM2 amplification in 7 out of the 20 studied samples (35.0%). Two HCC patients were found to have both gene abnormalities. Either the mutation rate of the P53 gene as well as the amplification level of the MDM2 gene was higher in HCC than in precancerous liver tissue stages. These results support the notion that besides P53 alterations, MDM2 gene deregulation seems to be an important event in hepatocarcinogenesis. Additionally, the mechanism of MDM2-mediated degradation of P53 protein, without involving stabilization and inactivation of P53 gene, should be considered for the understanding of all features of tumor progression processes.
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PMID:A comparative study of P53/MDM2 genes alterations and P53/MDM2 proteins immunoreactivity in liver cirrhosis and hepatocellular carcinoma. 1594 41

T-cadherin is a unique receptor of adiponectin, which plays a critical role in various angiogenesis. In the present study, T-cadherin expression in tumor vessels of hepatocellular carcinoma (HCC) and, subsequently, the molecular mechanism, which induced T-cadherin expression in sinusoidal endothelial cells were investigated. Sinusoidal endothelium in nontumorous liver, chronic hepatitis, or liver cirrhosis expressed little or no T-cadherin. By contrast, T-cadherin was found in intratumoral capillary endothelial cells of 34 out of 63 HCC specimens. In positive cases, focal T-cadherin expression was found in well-differentiated HCC, whereas diffuse and intense T-cadherin expression was observed in poorly differentiated HCC specimens. T-cadherin was much expressed in intratumoral capillary endothelial cells in a less differentiated HCC region than that in a well-differentiated region in five specimens, in which various differentiated HCC components were coexistent. In a double-cell chamber assay, fibroblast growth factor-2 appeared to have a critical role to induce T-cadherin in cultured liver sinusoidal endothelial cells. The present finding indicated that T-cadherin was selectively expressed in intratumoral capillary endothelial cells of many HCCs, increasingly expressed as tumor progression, and T-cadherin may have a positive role in angiogenesis of HCC. In addition, cross talk between the signal pathways mediated by fibroblast growth factor-2 and adiponectin was suggested.
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PMID:An adiponectin receptor, T-cadherin, was selectively expressed in intratumoral capillary endothelial cells in hepatocellular carcinoma: possible cross talk between T-cadherin and FGF-2 pathways. 1627 86


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