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)

Hepatocellular carcinoma (HCC) is primarily observed in the older children and in most cases it develops in association with liver cirrhosis. Liver transplantation offers a good chance for long-term cure. To evaluate the outcome of children with HCC and the impact of living-donor orthotopic liver transplantation (OLT) on survival a retrospective review of radiographic, laboratory, pathologic, and therapeutic data in 13 children (six female and seven male) with chronic liver disease accompanied with HCC were studied. The patients were divided into two groups according to therapeutic modality: transplanted and non-transplanted patients. Kaplan-Meier survival curves in various therapeutic groups were plotted. The mean age of patients was 6.4 +/- 4.8 yr. Pediatric end-stage liver disease score was adapted to model for end-stage liver disease score for HCC and ranged between 1-44 and 18-44, respectively. The underlying liver diseases were tyrosinemia type 1 (n = 6), chronic hepatitis B infection (n = 6), glycogen storage disease type 1 (n = 1). Alfa-feto protein levels were elevated in all patients except one. Median number of tumor nodules was three (1-10), median maximal diameter of tumor nodules was 3.4 cm (0.5-8). Eleven patients were eligible for OLT whereas two patients were not eligible. Seven of the 11 patients considered for transplantation underwent living-donor OLT. Remaining four patients died while waiting on cadaveric transplant list. Overall 1 and 4-yr survival rates for all patients were 53.3 and 26.6%, respectively, and were found significantly higher in transplanted children than non-transplanted children (72%, 72% vs. 33% and 16.6%). No patient had tumor recurrence at median of 36-month follow-up after OLT. OLT is a life-saving procedure for children with chronic liver disease accompanying with HCC. Living-donor OLT avoids the risk of tumor progression and transplant ineligibility in these children.
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PMID:Hepatocellular carcinoma in children and effect of living-donor liver transplantation on outcome. 1649 86

Increased expression of epidermal growth factor receptor (EGFR), a transmembrane tyrosine kinase, is associated with tumor progression in many carcinomas. Epidermal growth factor receptor inhibitors have shown promise in treating some of these tumors. Fibrolamellar hepatocellular carcinoma (FL-HCC) is an aggressive neoplasm that occurs in young patients with no history of cirrhosis. This study examines the expression and gene copy number of EGFR in FL-HCC. Formalin-fixed, paraffin-embedded FL-HCC (n = 13) sections were stained with a monoclonal antibody against EGFR. Fluorescence in situ hybridization analysis was performed using probes against EGFR gene and centromeric region of chromosome 7 (CEP 7). Epidermal growth factor receptor and CEP 7 signals were counted in 50 tumor nuclei per case as well as 300 normal hepatocyte nuclei. The EGFR to CEP 7 signal ratio was calculated for each case. Most (92%, 12/13) of FL-HCC showed strong and diffuse staining with anti-EGFR antibody. Fluorescence in situ hybridization was informative in 11 cases, 10 of which showed extra EGFR gene copy numbers (mean, 3.69; range, 3.13-5.0). Epidermal growth factor receptor was overexpressed in all these cases. The mean number of EGFR signals per cell in FL-HCC was double that of normal hepatocytes (3.69 versus 1.80); the mean EGFR/CEP 7 ratio in tumor cells was 1.05. In conclusion, EGFR is strongly overexpressed on the cell membrane in nearly all cases of FL-HCC. Similar gains of chromosome 7 are observed, indicating that the extra EGFR gene copies are due to polysomy rather than gene amplification. The strong expression of EGFR in FL-HCC tumors suggests that they may respond to treatment with EGFR antagonists.
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PMID:Epidermal growth factor receptor expression and gene copy number in fibrolamellar hepatocellular carcinoma. 1656 14

Hepatocellular carcinoma is one of the major cancer killers. It affects patients with chronic liver disease who have established cirrhosis, and currently is the most frequent cause of death in these patients. The main risk factors for its development are hepatitis B and C virus infection, alcoholism and aflatoxin intake. If acquistion of risk factors is not prevented and cirrhosis is established, the sole option to improve survival is to detect the tumor at an early stage when effective therapy may be indicated. Early detection plans should be based on hepatic ultrasonography every 6 months, whereas determination of tumor markers is not efficient. Upon detection of a hepatic nodule, there is a need to establish unequivocal diagnosis, either through biopsy or through the application of non-invasive criteria based on the specific radiology appearance of the tumor: fast arterial uptake of contrast followed by venous washout. Effective treatment for liver cancer includes surgical resection, liver transplantation and percutaneous ablation. These options provide a high rate of complete responses and are assumed to improve survival that should exceed 50% at 5 years. If the tumor is diagnosed at an advanced stage, the sole option that improves survival is transarterial chemoembolization. Ongoing research should further advance the time at diagnosis and identify new and effective options targeting molecular pathways governing tumor progression.
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PMID:New aspects of diagnosis and therapy of hepatocellular carcinoma. 1679 26

The present study investigated the significance of the serum brain-derived neurotrophic factor (BDNF) and platelets in relation to the clinicopathological features of hepatocellular carcinoma (HCC) patients. Localization of the BDNF expression in human HCC tissues was performed by immunohistochemistry. The measurement of soluble BDNF in the serum was performed by enzyme-linked immunosorbent assay. BDNF was expressed in the cytoplasm of the tumor cells. A positive correlation between the tissue and serum levels of BDNF was identified in the HCC patients. The serum levels of BDNF were positively correlated with the platelet counts in the HCC patients. A higher level of serum BDNF was significantly correlated with a tumor size >5 cm, poorly differentiated HCC, the presence of microsatellite tumor nodules, and the absence of cirrhosis in the non-tumorous tissues. A higher level of the serum BDNF/platelet ratio was associated with a poorer disease-free survival after hepatic resection. This study suggested that the tumor cell was a source of serum BDNF in HCC. A higher serum BDNF level was associated with a more advanced tumor status in the HCC patients. The interaction between serum BDNF and platelets might play an important role in HCC tumor progression.
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PMID:Significance of the serum brain-derived neurotrophic factor and platelets in hepatocellular carcinoma. 1708 44

The purpose of this study was to evaluate the long-term survival results and complications of percutaneous radiofrequency ablation (RFA) in patients with early-stage hepatocellular carcinoma (HCC). Between April 1999 and May 2005, 570 patients with 674 early-stage HCCs underwent percutaneous RFA as a first-line treatment option in a single institution. We evaluated the effectiveness rates, local tumor progression rates, survival rates, and complications. We also assessed the prognostic values of survival rates by using Cox proportional hazard models. The primary technique effectiveness rate was 96.7% (652 of 674). The cumulative rates of local tumor progression at 1, 2, and 3 years were 8.1%, 10.9%, and 11.8%, respectively. The cumulative survival rates at 1, 2, 3, 4, and 5 years were 95.2%, 82.9%, 69.5%, 60.8%, and 58.0%, respectively. Patients with Child-Pugh class A cirrhosis, of younger age (<or=58 years), or having lower AFP level (<or=100 microg/L) demonstrated better survival results (P < 0.05). A total of 11 major complications (1.9% per treatment) were found during the follow-up period. There was no procedure-related death. Percutaneous RFA can be used successfully as a first-line treatment modality for early-stage HCCs. Child-Pugh class, age, and AFP level before RFA were significant prognostic predictors of long-term survival.
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PMID:Percutaneous radiofrequency ablation for early-stage hepatocellular carcinoma as a first-line treatment: long-term results and prognostic factors in a large single-institution series. 1709 64

Partial hepatic resection has been the mainstay of curative treatment for hepatocellular carcinoma (HCC) in cirrhotic patients with preserved liver function. Liver transplantation for HCC was initially developed as a treatment option for patients with unresectable tumors associated with Child B or C cirrhosis. However, in recent years, some authors have advocated liver transplantation even for resectable early HCC associated with Child A cirrhosis. Whether transplantation or liver resection is the optimal initial treatment for early HCC in compensated cirrhosis depends on the survival results and also the availability of liver grafts. Recent studies comparing liver resection and transplantation for early HCC in Child A cirrhotic patients demonstrated similar long-term survival. While liver transplantation is associated with a lower tumor recurrence rate, this benefit is counteracted by long-term complications such as immunosuppression related infections and neoplasms. Patients put on transplantation waiting list run a significant risk of tumor progression and dropout, while liver resection is immediately applicable to all. A premature liver transplantation may expose patients to the side effects of immunosuppression earlier than necessary. With the current shortage of liver grafts, advocating primary liver transplantation for patients with early HCC associated with compensated cirrhosis will increase waiting time of transplantation and further increases the chance of dropout. Resection first and salvage transplantation for recurrent tumors or liver failure has been shown to be a feasible strategy in the majority of patients, and this appears to be the optimal strategy with the best use of organs.
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PMID:Optimal initial treatment for early hepatocellular carcinoma in patients with preserved liver function: transplantation or resection? 1710 69

Most patients with hepatocellular carcinoma (HCC) also have cirrhosis, an independent cause of death. We considered an alternative definition of tumor-related death in patients with HCC and attempted to validate our definition. Two hundred thirty-seven HCC patients were diagnosed, followed, and died over a 12-year period and were evaluated every 2 months, including their last 6 months of life. We defined death by cancer if there was, in the last 6 months of life, a CT scan increase of >25% in the sum of tumor index lesions' cross-sectional areas or new onset of, or increase in, either vascular invasion or metastatic disease (Group 1). Patients with stable cancer were considered to have died from any other cause (Group 2). We found that 135 (57%) patients died from cancer progression (Group 1), whereas 102 (43%) patients did not (Group 2). There was a statistically significant difference between Group 1 and Group 2 patients in percentage with bilobar disease (P = 0.03), more than one tumor (P = 0.01), an increase in AFP (P = 0.04), vascular invasion (P = 0.001), and the presence of metastases (P = 0.01). We conclude that 57% of patients with unresectable HCC died as a direct result of cancer progression, but 43% did not. The latter died from complications of their cirrhosis, including sepsis, GI bleeds, and renal failure.
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PMID:Causes of death in patients with unresectable hepatocellular carcinoma. 1743 87

The emergence of hepatocellular carcinoma (HCC) is thought to be a stepwise process, with high-grade dysplastic nodules (HGDN) representing premalignant lesions arising in a background of cirrhosis. Earlier studies have revealed altered expression of transforming growth factor-alpha (TGF-alpha) (a mitogen capable of inducing hepatocarcinogenesis in mice) in HCC and its surrounding parenchyma. DNA topoisomerase II-alpha (Topo II-alpha) is a nuclear protein targeted by several chemotherapeutic agents and is overexpressed in HCC. The expression of both TGF-alpha and Topo II-alpha in putative preneoplastic hepatocytic lesions, however, has not been extensively studied. We examined the patterns of TGF-alpha and Topo II-alpha expression in noncirrhotic liver, liver cirrhosis, low-grade dysplastic nodules (LGDN), HGDN, and HCC to define the possible relationships of these markers to tumor progression. Paraffin sections from formalin-fixed material were immunostained with antibodies against TGF-alpha, Topo II-alpha, and Ki-67. Forty-six HCC, 17 HGDN, and 12 low-grade dysplastic nodules were identified in 52 cirrhotic livers from explanted or resected specimens. Nuclear staining for Ki-67 and Topo II-alpha was significantly increased in the progression from cirrhosis, through HGDN, to HCC, whereas the scores for TGF-alpha in these lesions showed an inverse relationship. In comparison with 18 HCC arising in noncirrhotic livers, the expression of TGF-alpha is significantly stronger in cirrhotic liver than in noncirrhotic parenchyma and its expression is also stronger in HCC arising in cirrhosis than in HCC arising in noncirrhotic parenchyma. The increased expression of Topo II-alpha and Ki-67 from HGDN to HCC, when compared with cirrhosis, suggests that HGDN is a precursor lesion in hepatocarcinogenesis. The inverse relationship between these proliferative markers and TGF-alpha expression in these lesions and stronger expression of TGF-alpha in HCC arising in cirrhosis suggest that TGF-alpha may play an important role in the early events of liver carcinogenesis.
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PMID:The expression of transforming growth factor-alpha in cirrhosis, dysplastic nodules, and hepatocellular carcinoma: an immunohistochemical study of 70 cases. 1746 Apr 50

It is important to clarify the histologic progression of intrahepatic cholangiocarcinoma (ICC) in consideration of its origin from the intrahepatic large or small biliary ducts. On the basis of the gross and histologic assessment, we classified 87 cases of ICC smaller than 5 cm in diameter into hilar type (H-ICC, n=38) or peripheral type (P-ICC, n=49) to compare their clinical and histologic features. Biliary dysplasia was observed in 65.8% (25/38) of H-ICC cases, whereas hepatitis virus infection and liver cirrhosis were associated with 46.7% (21/45) and 28.6% (14/49) of P-ICC, respectively. The frequency of perineural invasion, lymph node metastasis, and extrahepatic recurrence of H-ICC was significantly higher than that of P-ICC (P<0.0001, 0.0106, and 0.0279, respectively). H-ICC cases showed frequent vascular invasion and intrahepatic metastasis even with small tumor size, compared with P-ICC cases. H-ICC showed large duct involvement within the tumor, and in the cases of large tumor size, intraductal spread was detected in the tumor periphery. P-ICC of small size contained preserved architecture of the portal tracts. The survival of patients with H-ICC was worse than that of patients with P-ICC (P=0.0121). The independent and best prognostic factor by multivariate analysis was intrahepatic metastasis for H-ICC and lymph node metastasis for P-ICC. Our results suggest that ICCs derived from a different level of biliary ducts were related to different premalignant conditions and different tumor progression. Some ICCs arising from the large biliary duct are likely to exhibit an aggressive course even in cases of small tumor size. The recognition of the above events induces the proper therapy.
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PMID:Proposal of progression model for intrahepatic cholangiocarcinoma: clinicopathologic differences between hilar type and peripheral type. 1759 73

Hepatocellular carcinoma (HCC) generally develops as a consequence of underlying liver disease, most commonly viral hepatitis. The development of HCC follows an orderly progression from cirrhosis to dysplastic nodules to early cancer development, which can be reliably cured if discovered before the development of vascular invasion (typically occurring at a tumor diameter of approximately 2 cm). The identifiable population at risk makes screening a realistic possibility, and liver imaging is recommended every 6 months for patients with cirrhosis. For patients with preserved liver function and no portal hypertension who develop HCC that is confined to one region of the liver, resection is the preferred treatment. If resection is not possible because of poor liver function, and the HCC is within the Milan criteria (1 nodule > or =5 cm, 2-3 nodules > or =3 cm), liver transplantation is the treatment of choice. To prevent tumor progression while waiting, nonsurgical treatments including percutaneous ethanol injection, radiofrequency ablation, and transarterial chemoembolization are employed, but drop-out from the waiting list remains a problem. Living donor transplantation is an alternative that can eliminate drop-out and enable liver transplantation for patients with HCC whose disease does not fall within the Milan criteria. There is a need for more effective adjuvant therapies after resection and liver transplantation; newer antiangiogenic agents offer hope for improved outcomes in the future.
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PMID:Strategies for the management of hepatocellular carcinoma. 1759 7


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