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Biomedical subjects

A Craxì

Publications and source records attributed to A Craxì.

82 records · Page 5Linked to original sources

Preoperative radiotherapy for resectable rectal cancer: A meta-analysis.

CONTEXT: The benefit of adjuvant radiotherapy for resectable rectal cancer has been extensively studied, but data on survival are still equivocal despite a reduction in the rate of local recurrence. OBJECTIVE: To assess the effectiveness of preoperative radiotherapy followed by surgery in the reduction of overall and cancer-related mortality and in the prevention of local recurrence and distant metastases. DATA SOURCES: Computerized bibliographic searches of MEDLINE and CANCERLIT (1970 to December 1999), including non-English sources, were supplemented with hand searches of reference lists. The medical subject headings used were rectal cancer, radiotherapy, surgery, RCT, randomized, and clinical trial. STUDY SELECTION: Studies were included if they were randomized controlled trials (RCTs) comparing preoperative radiotherapy plus surgery with surgery alone and if they included patients with resectable histologically proven rectal adenocarcinoma, without metastatic disease. Fourteen RCTs were analyzed. DATA EXTRACTION: Data on population, intervention, and outcomes were extracted from each RCT according to the intention-to-treat method by 3 independent observers and combined using the DerSimonian and Laird method. DATA SYNTHESIS: Radiotherapy plus surgery compared with surgery alone significantly reduced the 5-year overall mortality rate (odds ratio [OR] 0.84; 95% confidence interval [CI], 0.72-0.98; P =.03), cancer-related mortality rate (OR, 0.71; 95% CI, 0.61-0.82; P<.001), and local recurrence rate (OR, 0.49; 95% CI, 0.38-0.62; P<.001). No reduction was observed in the occurrence of distant metastases (OR, 0.93; 95% CI, 0.73-1.18; P =.54). CONCLUSIONS: In patients with resectable rectal cancer, preoperative radiotherapy significantly improved overall and cancer-specific survival compared with surgery alone. The magnitude of the benefit is relatively small and criteria are needed to identify patients most likely to benefit from adjuvant radiotherapy. JAMA. 2000;284:1008-1015

Humans↗

A retrospective study of the role of delta agent infection in children with HBsAg-positive chronic hepatitis.

The prevalence of intrahepatic delta antigen and/or anti-delta antibody was retrospectively investigated in 102 children with chronic HBsAg-positive hepatitis who were seen consecutively in three medical institutions between 1974 and 1982. Delta infection markers were found in 13 patients (12.7%) who exhibited high serum titers of anti-delta antibody; intrahepatic delta antigen was detected in ten. Eleven of the 13 children had severe progressive liver disease associated in all but one with absence of hepatitis B virus replication as evaluated by analysis of serum hepatitis B virus DNA. The factors which seem to increase the risk of delta infection in children who are hepatitis B virus carriers are geographic origin, a history of exposure to blood derivatives and age. A further 37 of 102 children had chronic active hepatitis (20 patients) or cirrhosis (17 patients) without evidence of delta infection. These results indicate that delta infection occurs in children with chronic hepatitis. This possibility should be considered in investigation of children with HBsAg-positive chronic liver disease. Although the delta agent is an important cause of progressive liver disease in children who are chronic HBsAg carriers, severe liver injury and especially cirrhosis can occur without evidence of delta infection.

Adolescent↗

Host and viral features in chronic HCV infection: relevance to interferon responsiveness.

Host and viral variables interact in determining the course and responsiveness to therapy of any viral infection. Presence of cirrhosis, serum levels of hepatitis C virus (HCV) RNA and the genotype of infecting virus are considered predictive of response to interferon (IFN) in chronic HCV infection. We evaluated these parameters in relation to IFN therapy in a cohort of anti-HCV-positive subjects with chronic hepatitis or cirrhosis. HCV RNA was detected by polymerase chain reaction (PCR) and by the branched DNA assay (bDNA), to quantify viraemia. HCV typing was performed by reverse-hybridization line probe assay. HCV RNA was detected in almost all anti-HCV-positive subjects with liver disease, PCR being more sensitive than bDNA. Hepatitis C viraemia was lowest in cirrhosis. Low pretreatment viraemia selected for those patients with chronic hepatitis obtaining a high rate of sustained response to IFN. The role of HCV type was less clearcut, due to the high prevalence in our population of type 1 (especially subtype 1b, accounting for 80% of cases). A trend towards a better response of non-1b genotypes was confirmed. This may be related to higher HCV RNA levels in type 1b-infected subjects. Cirrhosis remains however, independently from virological features, the strongest predictor of non-response to IFN.

Chronic Disease↗

Heterogeneity of HVR-1 quasispecies is predictive of early but not sustained virological response in genotype 1b-infected patients undergoing combined treatment with PEG- or STD-IFN plus RBV.

ISDR mutation pattern and HVR-1 quasispecies were analyzed in HCV genotype 1b-infected patients treated with either PEG- or STD-IFN plus ribavirin, in order to find virological correlates of therapy outcome. ISDR region analysis, performed at baseline (T0) and at 4 weeks of therapy (T1), indicated that ISDR mutation pattern was not predictive of response to treatment. Moreover, no selection of putative resistant strains in the first month of therapy was observed. Viral load was not correlated with any parameter of HVR-1 heterogeneity. Among the HVR-1 heterogeneity parameters considered, complexity was inversely correlated to viral load decline at T1. In univariate analysis, complexity, proportion of non synonymous substitutions (NS) and NS/S ratio were lower in patients showing virological response at 6 months of treatment. Complexity was the only parameter independently associated with both decline of viral load at T1 and virological response after 6 months, even after adjustment for confounding variables. At the end of treatment or later, these correlations were lost. Evolution pattern of the HVR-1 quasispecies indicated a strong selective pressure in sustained responders, with complete substitution of pre-existing quasispecies, while minor changes occured in non responders. In relapsers both patterns were present at a similar rate. In conclusion, this study shows that HVR-1 heterogeneity may be involved in the early response to combined IFN-RBV therapy. The loss of correlation between viral heterogeneity and therapy outcome at 6 months of therapy, or later, suggests that other factors may play a role in maintaining sustained response to treatment.

Antiviral Agents↗

Occult HBV infection and suppression of HCV replication in the early phase of combination therapy for chronic hepatitis C.

BACKGROUND: Occult HBV infection in subjects with chronic hepatitis C is related to more severe disease outcome. It has been suggested that it might reduce sensitivity to antiviral treatment. AIMS: To assess in HBsAg negative subjects with chronic hepatitis C any effect of the presence of HBV genomes in the liver on the early kinetics of HCV-RNA under PEG-IFN plus ribavirin. PATIENTS AND METHODS: Twenty-two anti-HCV and HCV-RNA positive subjects, with biopsy-proven chronic hepatitis C (M/F 15/7; 50 +/- 8.6 years, 16 genotype 1b) were given PEG-IFN alpha 2b 1.0 microg qw plus ribavirin (800 to 1,200 mg daily according to body weight) for an intended 52 week period. Early virological response was assessed over the first 4 weeks of therapy by quantifying HCV-RNA. Occult HBV infection was assessed by testing for HBV-DNA in the liver before therapy. RESULTS: HBV genomes were found in the liver of 7 of 22 (31.4%) patients, unrelated to anti-HBc status. Kinetics of HCV-RNA during the first 4 weeks of antiviral treatment was unaffected by occult HBV infection, both in terms of absolute reduction of viral load and of number of cases with a reduction of > or = 2 log10 on treatment. CONCLUSIONS: Occult HBV infection does not affect the early phase of response to combination therapy. Further follow-up of patients into the maintenance phase of antiviral treatment and after stopping it will clarify if and when occult HBV has a role in reducing sustained virological response.

Adult↗

Features of autoimmunity in cryptogenic chronic hepatitis.

The presence of autoantibodies in 125 patients with cryptogenic chronic hepatitis (CH) was assessed by indirect immunofluorescence (IFL) on standard tissue sections and on Hep-2 cells. Smooth muscle antibodies (SMA) were found in a high percentage of patients without any difference between the anti-HBc positive and the anti-HBc negative subsets, but the antiactin pattern, suggestive of autoimmunity, was detected only in a small number of cases. Low-titer antinuclear antibodies (ANA) were found in CH but also in healthy controls on Hep-2 cells. No significant differences were found in the prevalence of SMA and ANA positivity in various histologic subgroups of CH. Amongst 37 patients with primary biliary cirrhosis (PBC) the use of Hep-2 cells allowed better evaluation of ANA patterns and identified the multiple nuclear dots (MND) pattern, unrecognisable on tissue sections, in 9 cases.

Adult↗