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Jordi Bruix

Publications and source records attributed to Jordi Bruix.

13 recordsLinked to original sources
PubMed2003

Identification of novel tumor markers in hepatitis C virus-associated hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common primary cancer associated frequently with hepatitis C virus (HCV). To gain insight into the molecular mechanisms of hepatocarcinogenesis, and to identify potential HCC markers, we performed cDNA microarray analysis on surgical liver samples from 20 HCV-infected patients. RNA from individual tumors was compared with RNA isolated from adjacent nontumor tissue that was cirrhotic in all of the cases. Gene expression changes related to cirrhosis were filtered out using experiments in which pooled RNA from HCV-infected cirrhotic liver without tumors was compared with pooled RNA from normal liver. Expression of approximately 13,600 genes was analyzed using the advanced analysis tools of the Rosetta Resolver System. This analysis revealed a set of 50 potential HCC marker genes, which were up-regulated in the majority of the tumors analyzed, much more widely than common clinical markers such as cell proliferation-related genes. This HCC marker set contained several cancer-related genes, including serine/threonine kinase 15 (STK15), which has been implicated in chromosome segregation abnormalities but which has not been linked previously with liver cancer. In addition, a set of genes encoding secreted or plasma proteins was identified, including plasma glutamate carboxypeptidase (PGCP) and two secreted phospholipases A2 (PLA2G13 and PLA2G7). These genes may provide potential HCC serological markers because of their strong up-regulation in more than half of the tumors analyzed. Thus, high throughput methods coupled with high-order statistical analyses may result in the development of new diagnostic tools for liver malignancies.

Aged↗
PubMed2003

p27(Kip1) is an independent predictor of recurrence after surgical resection in patients with small hepatocellular carcinoma.

BACKGROUND/AIMS: Alterations in p27(Kip1) (p27) and cyclin E (cycE) expression are found in tumors and are related to poor prognosis. This study assesses the role of these cell cycle regulators in the development of recurrence after surgical resection in 46 cirrhotic patients (age: 61.3+/-7 years, 30 males, 44 Child-Pugh's A, 30 HCV-positive) with small hepatocellular carcinoma (HCC, size: 3.1+/-1.5cm, 40 solitary at pathological examination). METHODS: p27 and cycE expression in tumoral and non-tumoral liver were analyzed by Western blot (WB). p27 was also assessed by immunohistochemistry (IHC). RESULTS: Tumor p27 underexpression (50% decreased vs. non-tumoral liver) occurred in 12 cases. Throughout follow-up, 26 patients developed recurrence, which was significantly higher in patients with p27 underexpression than in those without (3-year recurrence: 80 vs. 44%, respectively, P=0.026). IHC showed concordant inverse findings: 13 tumors showed high p27 staining that was related to lower recurrence rate (P=0.019). Multivariate analysis identified p27 measured by WB as an improved predictor of recurrence (OR: 3.09, 95% CI: 1.26-7.08, P=0.016). By contrast, cycE, increased in 66% of the tumors, had no impact on recurrence but was associated to poor differentiation (P=0.015) and microvascular invasion (P=0.016). CONCLUSIONS: p27 underexpression is frequent in relatively early stages of HCC and constitutes an independent predictor of recurrence after surgical resection.

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PubMed2003

Treatment of hepatocellular carcinoma: is there an optimal strategy?

The incidence of hepatocellular carcinoma is increasing worldwide and now it accounts for as many as 1 million deaths annually, representing the third cause of cancer-related death. Surveillance programmes in the population at risk, namely cirrhotic patients, aim to detect tumours at an early stage when benefit from effective therapy may be provided. Patients with early tumours (single tumours measuring less than 5 cm or with less than 3 nodules measuring less than 3 cm in size) constitute the early stage category. These patients may be treated with surgical resection, transplantation, or percutaneous ablation, and the 5-year survival rate will exceed 50%. Patients with more advanced disease constitute the intermediate-advanced stage. Intermediate stage includes individuals without cancer-related symptoms and absence of vascular invasion and/or extrahepatic spread. They may achieve a 50% survival rate at 3 years that can be expanded by transarterial chemoembolization. Symptomatic patients with more advanced disease have a survival rate of less than 20% at 3 years. In this group of patients the efficacy of new agents should be assessed in phase II trials or randomized controlled trials versus no treatment to determine the impact of any therapy on survival. Finally, patients with end-stage disease with heavily impaired liver function (Child-Pugh class C) or severe physical impairment (performance status 3-4) die within 6 months and should receive only symptomatic treatment.

Carcinoma, Hepatocellular↗
PubMed2003

Systematic review of randomized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival.

There is no standard treatment for patients with unresectable hepatocellular carcinoma (HCC). Survival benefits derived from medical interventions are controversial. The aim of this systematic review was to assess the evidence of the impact of medical treatments on survival. Randomized controlled trials (RCTs) that were published as full papers assessing survival for primary treatments of HCC were included. MEDLINE, the Cochrane Library, CANCERLIT, and a manual search from 1978 to May 2002 were used. The primary end point was survival, and the secondary end point was response to treatment. Estimates of effect were calculated according to the random effects model. Sensitivity analysis included methodological quality. We identified 61 randomized trials, but only 14 met the criteria to perform a meta-analysis assessing arterial embolization (7 trials, 545 patients) or tamoxifen (7 trials, 898 patients). Arterial embolization improved 2-year survival compared with control (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.32-0.89; P =.017). Sensitivity analysis showed a significant benefit of chemoembolization with cisplatin or doxorubicin (OR, 0.42; 95% CI, 0.20-0.88) but none with embolization alone (OR, 0.59; 95% CI, 0.29-1.20). Overall, treatment induced objective responses in 35% of patients (range, 16%-61%). Tamoxifen showed no antitumoral effect and no survival benefits (OR, 0.64; 95% CI, 0.36-1.13; P =.13), and only low-quality scale trials suggested 1-year improvement in survival. In conclusion, chemoembolization improves survival of patients with unresectable HCC and may become the standard treatment. Treatment with tamoxifen does not modify the survival of patients with advanced disease.

Carcinoma, Hepatocellular↗
PubMed2002

Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial.

BACKGROUND: There is no standard treatment for unresectable hepatocellular carcinoma. Arterial embolisation is widely used, but evidence of survival benefits is lacking. METHODS: We did a randomised controlled trial in patients with unresectable hepatocellular carcinoma not suitable for curative treatment, of Child-Pugh class A or B and Okuda stage I or II, to assess the survival benefits of regularly repeated arterial embolisation (gelatin sponge) or chemoembolisation (gelatin sponge plus doxorubicin) compared with conservative treatment. 903 patients were assessed, and 112 (12%) patients were finally included in the study. The primary endpoint was survival. Analyses were by intention to treat. FINDINGS: The trial was stopped when the ninth sequential inspection showed that chemoembolisation had survival benefits compared with conservative treatment (hazard ratio of death 0.47 [95% CI 0.25-0.91], p=0.025). 25 of 37 patients assigned embolisation, 21 of 40 assigned chemoembolisation, and 25 of 35 assigned conservative treatment died. Survival probabilities at 1 year and 2 years were 75% and 50% for embolisation; 82% and 63% for chemoembolisation, and 63% and 27% for control (chemoembolisation vs control p=0.009). Chemoembolisation induced objective responses sustained for at least 6 months in 35% (14)of cases, and was associated with a significantly lower rate of portal-vein invasion than conservative treatment. Treatment allocation was the only variable independently related to survival (odds ratio 0.45 [95% CI 0.25-0.81], p=0.02). INTERPRETATION: Chemoembolisation improved survival of stringently selected patients with unresectable hepatocellular carcinoma.

Aged↗
PubMed2002

Expected developments in hepatology.

It is very difficult to predict new developments in hepatology so we have decided to analyse the most important issues related to three clinical conditions in hepatology. The first is chronic hepatitis. Here, we discuss the relevance of occult forms of hepatitis B virus infection in the development of cryptogenic liver disease and hepatocellular carcinoma. In addition, the role of genotyping in hepatitis B is analysed, indicating that patients with genotype A have a better prognosis than those with genotype D. The treatment of hepatitis B virus infection is also reviewed, and it has been suggested that research should be directed towards the development of new anti-viral agents to suppress virus replication. The natural history of hepatitis C virus infection is considered, emphasizing the need to know the progression of fibrosis in these patients. The chapter also suggests that treatment of hepatitis C virus infection with pegilated interferon and ribavirin is currently relatively effective. New therapeutic strategies will be required in the future, the most important challenge being the development of a hepatitis C virus vaccine. The second section is on chronic cholestasis. The role of anti-mitochondrial antibodies in primary biliary cirrhosis is considered. The possible infectious agents implicated as potential triggers of primary biliary cirrhosis are also discussed, suggesting that several infections may play a role in the pathogenesis of this condition. Other aetiopathogenic factors, for example organic compounds, drugs and chemicals, are indicated. It is possible that, in the near future, the precise sequence and molecular basis by which infectious agents or xenobiotics may initiate the cascade of the autoimmune response will be defined. One of the most important challenges in primary sclerosing cholangitis concerns the mechanisms that may induce the development of this disease. Up until now, genetic factors have been suggested, recent data reporting a clear-cut association between primary sclerosing cholangitis and the tumour necrosis factor-alpha(2) allele. The third part of this chapter includes recent progress achieved in hepatocellular carcinoma, discussing developments in the knowledge of hepatocellular carcinogenesis. Hepatocellular carcinomas appear so far to be genetically heterogeneous neoplasms, and this heterogeneity may correlate with the variety of aetiological factors involved. The risk factors and primary, secondary and tertiary prevention of the condition are also analysed. Finally, the development of new therapeutic strategies for hepatocellular carcinoma is evaluated by evidence-based studies.

Antiviral Agents↗
PubMedDate not supplied

Contrast-enhanced power Doppler sonography and helical computed tomography for assessment of vascularity of small hepatocellular carcinomas before and after percutaneous ablation.

PURPOSE: We compared the usefulness of Levovist-enhanced power Doppler imaging (PDI) and helical CT in the depiction of tumor vascularity before and after percutaneous ablation of small hepatocellular carcinomas (HCCs). METHODS: Thirty-one cirrhotic patients with solitary unresectable HCCs smaller than 5 cm (mean size, 2.7 +/- 0.8 cm; range, 1.5-5.0 cm) recruited over a 15-month period were treated with percutaneous ethanol injection (n = 9) or radiofrequency ablation (n = 22). PDI, contrast-enhanced PDI (using Levovist), and multiphase contrast-enhanced helical CT were performed before and after percutaneous ablation, and vascularity findings were compared. RESULTS: Levovist significantly increased baseline intratumoral Doppler signals on PDI compared to non-contrast PDI. The most frequent tumor vascularity pattern was heterogeneous (45%). Vascularity was identified in all tumors by both contrast-enhanced PDI and helical CT before ablation. After percutaneous ablation, intratumoral vascularity was detected in 11 tumors by contrast-enhanced PDI and in 15 tumors by CT. The sensitivity, specificity, and diagnostic accuracy of contrast-enhanced PDI in demonstrating intratumoral vascularity, with CT being the gold standard, were 66%, 93%, and 81%, respectively. There was significant agreement between the 2 modalities in the depiction of tumor vascularity after ablation (kappa = 0.6, p = 0.001). However, there were 5 false negatives and 1 false positive with contrast-enhanced PDI. Complete tumor necrosis was achieved in 21 patients (68%). CONCLUSIONS: There was a good concordance between contrast-enhanced PDI and helical CT in the depiction of HCC vascularity before and after percutaneous ablation. However, although contrast-enhanced PDI may be useful for real-time guidance of treatment, its low sensitivity makes it inadequate to accurately assess the completeness of ablation.

Aged↗
PubMedDate not supplied

Prognostic assessment and evaluation of the benefits of treatment.

Prognosis estimation in patients with hepatocellular carcinoma (HCC) can provide information at diagnosis and can indicate therapy. Because cirrhosis underlies HCC in most individuals, their outcome is related to both entities, which determine the applicability and efficacy of therapy. Accordingly, prognostic modelling should consider tumor stage, liver function impairment, the patient's general condition, and treatment efficacy. We have developed a system that stratifies patients into four categories, simultaneously setting prognosis and guiding the therapy. Patients with HCC (single HCC < or =5 cm or three or fewer nodules < or =3 cm) benefit from curative/effective therapies (resection, transplantation, and percutaneous ablation), expert application of which provides a 50% to 75% 5-year survival. Those with more advanced disease present a heterogenous outcome. Patients who do not present with cancer-related symptoms and whose tumor has not invaded vascular vessels or disseminated outside the liver may reach 50% survival at 3 years, and they benefit from chemoembolization. Those who present with symptoms (pain, deterioration of physical condition) and/or an aggressive tumor pattern do not reach a 10% survival at 3 years, and there is no effective therapy for them. Finally, those with severe liver function or health status impairment constitute the end-stage category and cannot be expected to survive more than 1 year.

Carcinoma, Hepatocellular↗
PubMedDate not supplied

Prognosis of hepatocellular carcinoma.

The prognosis of patients with hepatocellular carcinoma is related to the stage of the tumor at diagnosis and to the degree of liver function impairment induced either by the tumor itself or by the underlying cirrhosis. Any prognostic prediction should also take into account the potential impact of therapeutic interventions. Only surgical resection, liver transplantation and percutaneous ablation achieve a relatively high rate of complete responses in patients with tumors diagnosed at an early stage and may improve survival. By contrast, patients diagnosed at an advanced stage will receive palliative treatment with unproven survival benefits. Each stage and each treatment have their specific prognostic predictors. Thus, the most accurate prognostic system will have to use a specific model for each strata at which patients may be diagnosed: early, intermediate-advanced and terminal. Patients at an early stage may achieve a 5-year survival rate above 50%, those at intermediate-advanced present a 20-50% survival at 3 years and those at terminal stage die within six months. In addition to predicting prognosis, the staging system should also guide the selection of treatment and this is the major advantage of the classification applied in the Barcelona-Clinic Liver Cancer Group.

Algorithms↗