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Biomedical subjects

J Bruix

Publications and source records attributed to J Bruix.

At least 37 records · Page 2Linked to original sources
PubMed2000

The current status of liver transplantation for primary hepatic malignancy.

Several advances have been achieved during the last years in the management of patients with liver cancer. The refinement of the imaging techniques and the better knowledge of the biology of this neoplasm have facilitated the establishment of useful criteria to select patients for transplantation. Following a strict selection policy (solitary tumors < or = 5 cm or up to 3 foci each one < or = 3 cm) patients with liver cancer may achieve the same survival as nonneoplastic subjects. Currently, the main problem is how to diminish the risk of tumor progression while waiting for a liver. Although at present the benefits of invasive treatments are ill-defined, the ongoing studies exploring new treatment options hopefully will succeed in preventing this complication and further improve the current results.

Carcinoma, Hepatocellular↗
PubMed2000

Early diagnosis and treatment of hepatocellular carcinoma.

The incidence of hepatocellular carcinoma is increasing world-wide. Although there are no randomized controlled trials showing benefits from surveillance programmes, these strategies have been widely practised by hepatologists, and most early tumours are diagnosed in the setting of such a policy. In this chapter we summarize the surveillance schedule and recall the policy applied in our Unit. Diagnosis at an early stage is crucial to allow the application of curative treatments that are the only hope for increasing the life expectancy of the patient. Surgical resection and liver transplantation are considered the first-line options for early tumours, although there is no agreement on which is the best approach. Resection is limited by the high recurrence rate, whereas the increasing waiting times have decreased the intention-to-treat outcomes of transplantation. Percutaneous treatments are reserved for patients with single non-surgical tumours. Clinical trials assessing treatments for patients with advanced tumours have not shown any survival benefits.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Nonsurgical treatment of hepatocellular carcinoma.

1. Outcome from nonsurgical treatment is directly related to stage of hepatocellular cancer (HCC) and degree of liver function impairment. 2. Ablative percutaneous procedures, such as alcohol injection or radiofrequency thermal therapy, are most effective in the destruction of solitary tumors of 3 cm or less. 3. In most cases, nonsurgical treatments are not curative, but may slow tumor progression and can provide palliation. 4. Arterial embolization or chemoembolization has an antitumor effect, but it has not been shown to affect patient outcome. 5. Radiation therapy, chemotherapy, hormonal manipulation, and interferon have not been consistently effective in HCC. 6. Ablative procedures, embolization, and systemic chemotherapy should be avoided in patients with advanced cirrhosis.

Antineoplastic Agents↗
PubMed1999

Natural history of untreated nonsurgical hepatocellular carcinoma: rationale for the design and evaluation of therapeutic trials.

This study analyzed the natural history and prognostic factors of patients with nonsurgical hepatocellular carcinoma (HCC). Twenty variables from 102 cirrhotic patients with HCC who were not treated within prospective randomized controlled trials (RCT) were investigated through uni- and multivariate analyses. None of them was suitable for radical therapies (surgical resection, liver transplantation, or ethanol injection) or presented end-stage disease as reflected by an Okuda stage 3 or a Performance Status >/=3. Sixty-five patients were Child-Pugh A, 34 were B, and 3 were C. Most of them exhibited a preserved Performance Status Test (PST) (0 = 56; 1 = 38; 2 = 8). Tumor was solitary in 26 (</=5 cm in 16) and multinodular/massive in 76. After a median follow-up of 17 months, 79 patients died, the 1-, 2-, and 3-year survival being 54%, 40%, and 28%. The multivariate study identified PST (P =.01), constitutional syndrome (P =.04), vascular invasion (P =.001), and extrahepatic spread (P =.04) as independent predictors for mortality. The 1-, 2-, and 3-year survival for the 48 patients without adverse factors (Stage 0) was 80%, 65%, and 50%, respectively, and 29%, 16%, and 8% in the 54 patients with at least one adverse parameter (Stage I). Therefore, Stage 0 would correspond to an intermediate stage, while Stage I would represent an advanced status, before reaching an end-stage phase. In conclusion, the outcome of nonsurgical HCC is not homogeneously grim and may be predicted by assessing the presence of symptoms and of an invasive tumoral pattern. Therapeutic trials should be designed and evaluated considering these characteristics.

Adult↗
PubMed1999

Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation.

Liver transplantation is proposed as the best therapy for early hepatocellular carcinoma in cirrhotic patients. However, the confrontation with the results obtained by surgical resection has never been done on an intention-to-treat basis. Between 1989 and 1997, 164 out of 1,265 patients with hepatocellular carcinoma were evaluated for surgery. Seventy-seven (48 men, mean 61 years of age, 74 Child-Pugh class A, size 33 +/- 18 mm) were resected (first line option) and 87 (65 men, mean 55 years of age, 50 Child-Pugh class B/C, size 24 +/- 14 mm) were selected for transplantation. The 1-, 3-, and 5-year "intention-to-treat" survival was 85%, 62%, and 51% for resection and 84%, 69%, and 69% for transplantation (8 drop-outs on waiting list). Bilirubin and clinically relevant portal hypertension were independent survival predictors after resection. Thereby, the 5-year survival of the best candidates (absence of clinically relevant portal hypertension, n = 35) was 74%, whereas it was 25% for the worst candidates (portal hypertension and bilirubin >/=1 mg/dL, n = 27) (P <.00001). The variable "drop-out on waiting list" was the sole survival predictor after transplantation. The 2-year survival rate of patients evaluated for transplantation was 84% in the 1989 to 1995 period (mean waiting time, 62 days; no drop-outs) and 54% during 1996 to 1997 (mean waiting time, 162 days; 8 drop-outs)(P <.003). This outcome was significantly lower than that of the best candidates for resection (P =.002). In conclusion, a proper selection of candidates for resection promotes better results than transplantation, in which the results are significantly hampered by the growing incidence of drop-outs because of the increasing waiting time.

Bilirubin↗
PubMed1999

Infection with a novel human DNA virus (TTV) has no pathogenic significance in patients with liver diseases.

BACKGROUND/AIMS: A recently identified DNA virus, termed TT virus (TTV), has been associated with post-transfusional hepatitis, and a high prevalence of TTV infection in patients with acute or chronic liver disease of unknown etiology has been reported from Japan, but few data are available about TTV infection in other countries. METHODS: Using hemi-nested-PCR amplification to detect TTV-DNA sequences in serum, we investigated TTV infection in blood donors and in patients with liver diseases of varied etiology. RESULTS: The prevalence of TTV infection was 13.7% in blood donors (23/168), 18.6% in chronic hepatitis C (19/102), 28.6% in chronic hepatitis B (16/56), 29.9% in hepatocellular carcinoma (20/67), 9.1% in cryptogenic chronic liver disease (2/22) and 39.6% in fulminant hepatitis (19/48). The prevalence of TTV infection in patients with virus-induced or idiopathic fulminant hepatitis was similar. Comparison of TTV-infected and non-infected patients did not reveal significant differences concerning demographic, epidemiological or histopathological features. In patients with hepatitis C, response to interferon therapy was not related to TTV infection. Phylogenetic analysis of TTV isolates showed that at least three different types of TTV are present in Spain. CONCLUSIONS: Our data suggest that TTV infection is frequent among blood donors and patients with acute liver disease. However, pathogenic effects associated with TTV infection were not observed.

Acute Disease↗
PubMed1999

Locoregional treatments for hepatocellular carcinoma.

Improvements in diagnostic techniques have enhanced our understanding of the natural history of hepatocellular carcinoma (HCC). This has facilitated a proper evaluation of the available treatment options for this neoplasm through both phase II studies and randomized controlled trials. Surgical resection and liver transplantation constitute the first two radical options, and when they are contra-indicated, patients may benefit from percutaneous ethanol injection or thermal ablation by radiofrequency current. These options may also achieve a complete response and constitute the last potentially radical therapies for small HCC. In contrast, for large multinodular tumours, the available treatment options have not been shown to improve survival. Arterial embolization with or without associated chemotherapy has been widely used. However, randomized controlled trials have failed to show a survival benefit, emphasizing the need to develop new treatment strategies.

Antineoplastic Agents↗
PubMed1999

Prognosis of hepatocellular carcinoma: the BCLC staging classification.

The classifications of hepatocellular carcinoma (HCC) currently used are based on prognostic factors obtained from studies performed years ago when most tumors were diagnosed at advanced stages and the survival rates were substantially poor. Recent investigations have reviewed the survival of early tumors properly selected to receive radical therapies and the natural outcome of nonsurgical HCC patients. These data enable a new staging system to be proposed, the Barcelona Clinic Liver Cancer (BCLC) staging classification, that comprises four stages that select the best candidates for the best therapies currently available. Early stage (A) includes patients with asymptomatic early tumors suitable for radical therapies--resection, transplantation or percutaneous treatments. Intermediate stage (B) comprises patients with asymptomatic multinodular HCC. Advanced stage (C) includes patients with symptomatic tumors and/or an invasive tumoral pattern (vascular invasion/extrahepatic spread). Stage B and C patients may receive palliative treatments/new agents in the setting of phase II investigations or randomized controlled trials. End-stage disease (D) contain patients with extremely grim prognosis (Okuda stage III or PST 3-4) that should merely receive symptomatic treatment.

Carcinoma, Hepatocellular↗
PubMed1998

Liver transplantation for small hepatocellular carcinoma: the tumor-node-metastasis classification does not have prognostic power.

Tumoral recurrence rate and survival of patients with hepatocellular carcinoma (HCC) treated by orthotopic liver transplantation (OLT) depend on tumor stage. Thereby, from the beginning of our program, we selected only patients with solitary tumors < or = 5 cm without vascular invasion, thus avoiding the use of the tumor-node-metastasis (TNM) staging system as a selection tool. The present study reports the results obtained in 58 consecutive patients (52 +/- 8 years, 47 males) with HCC (7 incidentals) transplanted between 1989 and 1995. Transplantation was indicated because of tumor diagnosis in 40 cases and advanced liver failure in 18. Mean tumor size at staging was 28.2 +/- 12.1 mm. No adjuvant treatment was applied during the waiting period (58.9 +/- 45.1 days). The pathological tumor-node-metastasis (pTNM) classification allocated 15 patients to stage I, 19 to stage II, 11 to stage IIIA, and 13 to stage IVA showing preoperative understaging in 43% of the cases with known tumor. After a median follow up of 31 months, only two patients have shown tumor recurrence and fifteen have died, the 1-, 3-, and 5-year survival being 84%, 74%, and 74%. All HCV+ patients remain infected and 94% showed significant liver disease (6 cirrhosis). Six patients have had a second transplant. In conclusion, the application of restrictive criteria not following the TNM staging system prompts excellent results for liver transplantation in patients with HCC, both in terms of survival and disease recurrence, even without applying adjuvant treatment; however, the survival data should be tempered by the appearance of complications that may worsen the long-term prognosis.

Adult↗
PubMed1998

Transarterial embolization versus symptomatic treatment in patients with advanced hepatocellular carcinoma: results of a randomized, controlled trial in a single institution.

This randomized, controlled trial assessed the effect of transarterial embolization (TAE) (without associated chemotherapy) on the survival of patients with nonsurgical hepatocellular carcinoma (HCC). Eighty consecutive patients were randomized to treatment with embolization (Group A, n = 40), or to symptomatic treatment (Group B, n = 40), there being no differences between both groups regarding the degree of liver function impairment and tumor stage. Eighty-two percent of the patients presented a self-limited postembolization syndrome, without treatment-related mortality. Fifty-five percent of the treated cases exhibited a partial response, which resulted in a lower probability of tumor progression during follow-up (57% vs. 77% at 1 year; P < .005). However, after a median follow-up of 24 months (30 deaths in each group), there are no differences in survival (Group A: 49% and 13%; Group B: 50% and 27%, at 2 and 4 years, respectively; P = .72). The absence of differences was maintained even when dividing patients according to Child-Pugh's grade, Okuda stage, or performance status test (PST). Furthermore, there were no differences in the probability of complications or in the need of hospital admissions. In conclusion, TAE has a marked antitumoral effect associated to a slower growth of the tumor, but it does not improve the survival of patients with nonsurgical HCC.

Aged↗
PubMed1998

Tumor necrosis factor primes hepatocytes for DNA replication in the rat.

Signaling through tumor necrosis factor receptor type 1 (TNFR-1) using a pathway that involves nuclear factor kappaB (NF-kappaB), interleukin-6 (IL-6), and STAT3 is required for the initiation of liver regeneration. We have proposed that TNF primes hepatocytes to respond to the mitogenic effect of growth factors, but so far, there has been no experimental demonstration that TNF enhances growth factor responses of hepatocytes. To test this hypothesis, we infused hepatocyte growth factor (HGF) and transforming growth factor (TGF-) (40 microgram/24 h) directly into the portal vein of rats for 24 hours using osmotic pumps and determined whether TNF injection (5 microgram per rat) would significantly increase hepatocyte DNA labeling in these animals. All rats received 5-bromo-2'-deoxyuridine (BrdU) by intraperitoneal delivery during a 48-hour period (i.e., BrdU infusion continued for 24 hours after the end of growth factor administration). BrdU labeling in the liver was measured by both immunohistochemistry and flow cytometry, and the results obtained by these methods showed excellent concordance. The results demonstrate that TNF transiently activates NF-kappaB and STAT3 and increases the proliferative response of hepatocytes to HGF or TGF- by fourfold. Priming effects on hepatocyte DNA replication were also obtained with injection of lipopolysaccharide (LPS) and gadolinium chloride (GdCl3), agents that release TNF in the liver. Similarly to TNF, GdCl3 injection caused the activation of NF-kappaB and STAT3, reaching a maximum 8 to 12 hours after the injection. The results show that TNF acts as a primer to sensitize hepatocytes to the proliferative effects of growth factors and offers a mechanism to explain the initiation and progression phases of liver regeneration after partial hepatectomy (PH).

Animals↗
PubMed1998

Impact of HBV, HCV and GBV-C/HGV on hepatocellular carcinomas in Europe: results of a European concerted action.

BACKGROUND/AIMS: To investigate the impact of hepatitis B (HBV) and C (HCV) infections on hepatocellular carcinoma (HCC) in Europe. METHODS: Five hundred and three patients with HCC, from six liver centers, were included. All 503 sera and 80 liver samples were tested for HBV DNA and HCV RNA by polymerase chain reaction. GBV-C/HGV RNA was also tested in 57 sera. RESULTS: HBsAg and anti-HCV were detected in 19% and 40.1% of the patients, respectively. Serum and liver HBV DNA were detected in 82% and 91% of the HBsAg positive subjects. HBV DNA was also detected in the serum and liver of 33% and 47% of HBsAg negative patients. In this group, serum HBV DNA was more prevalent in anti-HBs and/or anti-HBc patients (47.9%), compared to those without any HBV marker (25.1%). HCV RNA was detected in 89% and 7% of anti-HCV positive and negative cases, respectively, HCV 1b being the most prevalent genotype (80%). Coinfection with HBV and HCV was shown in 20.4% of patients, while only 29% had neither HBV nor HCV GBV-C/HGV RNA was detected in only 4/57 sera. CONCLUSIONS: This study offers the first large analysis of HCC in Europe, based on both serology and molecular tests. It demonstrates the major impact of HBV and HCV, but not of GBV-C/HGV, in liver carcinogenesis in Northern as well as Southern Europe. It also stresses the need to use viral genome detection in epidemiological studies when serological tests are negative.

Aged↗
PubMed1998

Hepatitis G virus infection in chronic liver disease.

BACKGROUND: The hepatitis G virus (HGV), a recently identified member of the Flaviviridae family, can cause chronic infection in man but the role of this agent in chronic liver disease is poorly understood. AIMS: To evaluate the prevalence and meaning of HGV infection in a large series of patients with chronic liver disease. SUBJECTS: Two hundred volunteer blood donors, 179 patients with chronic hepatitis C, 111 with chronic hepatitis B, 104 with alcoholic liver disease, 136 with hepatocellular carcinoma, and 24 with cryptogenic chronic liver disease were studied. METHODS: HGV RNA was investigated in serum samples by reverse transcription and polymerase chain reaction amplification of the 5' non-coding region of HCV and hybridisation to a specific probe. The main features of HGV RNA seropositive and seronegative patients were compared. RESULTS: The prevalence of HGV infection was 3% in blood donors, 7% in chronic hepatitis C, 8% in chronic hepatitis B, 2% in alcoholic liver disease, 4% in hepatocellular carcinoma, and 8% in cryptogenic chronic liver disease. HGV infected patients tended to be younger than non-infected patients but no differences concerning sex, possible source of infection, clinical manifestations, biochemical and virological parameters, or severity of liver lesions were found. CONCLUSIONS: The prevalence of HGV infection in chronic liver disease seems to be relatively low in our area. Infection with HGV does not seem to play a significant pathogenic role in patients with chronic liver disease related to chronic HBV or HCV infection or to increased alcohol consumption, or in those with cryptogenic chronic liver disease.

Adult↗
PubMed1997

Hepatitis C virus (HCV) genotypes in Spanish patients with HCV infection: relationship between HCV genotype 1b, cirrhosis and hepatocellular carcinoma.

BACKGROUND/AIMS: The influence of the infecting virus genotype on the progression of the underlying liver disease in patients with chronic hepatitis C virus (HCV) infection remains controversial. The aim of this study was to investigate the prevalence of HCV genotypes in Spanish patients with chronic HCV infection and to elucidate the relationship between the infecting genotype and the severity of the disease. METHODS: A cross-sectional, retrospective analysis of frequency distribution of HCV genotypes was carried out in 414 Spanish patients with chronic HCV infection, including 243 patients with asymptomatic or minimally symptomatic chronic hepatitis, 112 patients with cirrhosis and hepatocellular carcinoma and 59 patients with decompensated cirrhosis. HCV genotype was determined by restriction fragment length polymorphisms of the 5' non-coding region. RESULTS: Infection with HCV genotype 1b was found in 72% of patients with chronic hepatitis and in more than 90% of patients with cirrhosis, with or without hepatocellular carcinoma. Older age, infection with genotype 1b and absence of overt parenteral exposure as a possible source of infection were associated with cirrhosis and hepatocellular carcinoma by univariate analysis and this association was confirmed by regression analysis. CONCLUSIONS: HCV genotype 1b is associated with advanced liver disease in our geographical area. However, this may be related to a cohort-effect caused by over-representation of genotype 1b in older patients with more advanced disease, because, in our country, this HCV genotype appeared earlier in time and is therefore associated with more prolonged periods of infection.

Adult↗
PubMed1997

Serum levels of C-erbB-2 (HER-2/neu) in patients with malignant and non-malignant diseases.

The diagnostic value of a new tumor marker, c-erbB-2, was studied in the sera of 50 controls, 112 patients with benign diseases and 534 patients with malignancies. Using 15 U/ml as the cutoff, no healthy subjects, patients with benign diseases (excluding liver cirrhosis) or patients with no evidence of disease (45 patients) had serum levels higher than this limit. Abnormal c-erbB-2 levels were found in 38.5% (10 of 26) of the patients with liver cirrhosis and in 26.7% (8 of 30) of those patients with primary liver cancer. No differences were found between the c-erbB-2 serum concentrations in liver cirrhosis or primary liver cancer, suggesting the possible catabolism of this antigen in the liver. Abnormal levels of this antigen were found in 20% (56 of 278) of the patients with breast carcinoma (locoregional 7%, metastases 41.5%), in 21% (6 of 28) of ovarian carcinomas (stage I-II 0%, stage III-IV 42.8%), in 21% (3 of 14) of the colorectal tumors (locoregional 0%, metastases 30%), and in 13.3% (11 of 83) of the patients with lung cancer (locoregional 11.5%, metastases 16%). C-erbB-2 sensitivity in other patients with advanced disease was: 25% (9 of 36) in prostatic cancer, 22% (2 of 9) in gastric cancer, and 11% (1 of 9) in vesical tumors. When patients with liver metastases were excluded abnormal c-erbB-2 serum levels were only found in breast, lung, prostatic and ovarian carcinomas. C-erbB-2 sensitivity in patients with lung cancer was related to tumor histology with significantly higher value in non-small cell lung cancer (mainly adenocarcinomas) than in patients with small cell lung cancer (p < 0.013). C-erbB-2 concentrations in patients with breast cancer were significantly higher in patients with recurrence (mainly bone and liver metastases) and in patients with progesterone receptor-negative (< 15 fmol/mg) tumors (p < 0.01). In conclusion, c-erbB-2 is not a specific tumor marker and abnormal serum levels may be found in patients with liver pathologies. Its sensitivity suggests its possible application as a tumor marker in breast, ovarian, lung (mainly adenocarcinomas) and prostatic tumors.

Adult↗