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Biomedical subjects

S Naveau

Publications and source records attributed to S Naveau.

At least 19 recordsLinked to original sources

Meta-analysis: evaluation of adjuvant therapy after curative liver resection for hepatocellular carcinoma.

AIM: To evaluate adjuvant modalities after curative resection for hepatocellular carcinoma using a meta-analysis of randomized and non-randomized controlled trials. METHODS: In a first step, a meta-analysis of randomized controlled trials was carried out. Sensitivity analyses after inclusion of non-randomized controlled trials were performed. Four therapeutic modalities were evaluated: pre-operative transarterial chemotherapy, post-operative transarterial chemotherapy, systemic chemotherapy and a combination of systemic and transarterial chemotherapy. RESULTS: Only post-operative transarterial chemotherapy improved survival significantly at 2 years [difference, 22.8%; confidence interval (CI), 8.6-36.9%; P = 0.002] and 3 years (difference, 27.6%; CI, 8.2-47.1%; P = 0.005), and decreased the probability of no recurrence at 1 year (difference, 28.8%; CI, 16.7-40.8%; P < 0.001), 2 years (difference, 27.6%; CI, 8.2-47.1%; P = 0.005) and 3 years (difference, 28%; CI, 8.2-47.9%; P = 0.006). In a sensitivity analysis after inclusion of non-randomized controlled trials, post-operative transarterial chemotherapy still improved survival at 1 year (difference, 9.6%; CI, 0.8-18.3%; P = 0.03), 2 years (difference, 13.5%; CI, 0.9-26%, P = 0.04) and 3 years (difference, 18%; CI, 7-28.9%; P < 0.001), and decreased the probability of no recurrence at 1 year (difference, 20.3%; CI, 7.7-33%; P = 0.002), 2 years (difference, 35%; CI, 21.4-46.3%; P < 0.001) and 3 years (difference, 34.5%; CI, 18.7-50.3%; P < 0.001). CONCLUSION: Post-operative transarterial chemotherapy improved survival and decreased the cumulative probability of no recurrence. New randomized controlled trials evaluating this modality are required.

Antineoplastic Agents↗

Reinforced interferon alpha-2b and ribavirin is more effective than standard combination therapy in the retreatment of chronic hepatitis C previously nonresponsive to interferon: a randomized trial.

Interferon-alpha (IFN) monotherapy results in sustained virological clearance in a minority of patients with chronic hepatitis C. The aim of this study was to assess the effect of a reinforced regimen combining ribavirin and high-dose IFN for 48 weeks compared with a nonreinforced regimen combining a standard IFN regimen and ribavirin for 24 weeks in nonresponders with chronic hepatitis C. A total of 231 patients with chronic hepatitis C and previous nonresponse to IFN monotherapy were randomized. The reinforced group (n = 114) received IFN-2b 6 million units (MU) thrice weekly (TIW) and ribavirin for 48 weeks, and the nonreinforced group (n = 117) received IFN-2b 3 MU TIW and ribavirin for 24 weeks. The main outcome measure was a sustained virological response, defined as negative serum hepatitis C virus (HCV)-RNA 24 weeks following the end of treatment. This endpoint was determined in 98 patients of the reinforced group and 105 patients of the nonreinforced group. At the end of follow-up, a sustained virological response was observed in 29 of the 98 patients (29.6%) in the reinforced group vs 16 of the 105 patients (15.2%) in the nonreinforced group (P = 0.014). In multivariate analysis, factors associated with a sustained virological response were treated with a reinforced regimen [odds ratio (OR) 2.9; P = 0.06] and genotype 2 or 3 (OR 8.8; P < 0.0002). A total of 160 patients had paired biopsies before and after treatment. Histological activity improvement was observed in 32 of 80 patients (40%) and fibrosis worsening in 26 of 80 patients (33%) in the reinforced group vs 13 of 80 (16%) and 19 of 80 (24%) in the nonreinforced group (P = 0.30 and 0.20, respectively). Hence in nonresponders, a high-dose 48-week regimen of IFN and ribavirin combination was more effective than a regimen with interferon at lower dose and ribavirin for 24 weeks only.

Adolescent↗

Excessive alcohol consumption favours high risk polyp or colorectal cancer occurrence among patients with adenomas: a case control study.

BACKGROUND AND AIMS: Excessive alcohol consumption is a risk factor for developing colorectal adenomas. This study aimed to investigate the influence of excessive alcohol consumption on the occurrence of high risk polyps (adenoma > or = 10 mm, villous component, high grade dysplasia) or colorectal cancer among patients with at least one colonic adenoma. PATIENTS AND METHODS: Three groups of patients with at least one colorectal adenoma were included in a case control study: 401 heavy drinkers (group HD, mean daily alcohol intake 117 (SD 4) g/day for a mean duration of 22 (SD 0.6) years), aged 57 (0.5) years (78% men); 152 patients suffering from irritable bowel syndrome (IBS), aged 61 (0.9) years (57% male); and 108 patients with a family history (FH) of colorectal adenoma or cancer, aged 55 (1) years (64% male). Exclusion criteria were: anaemia, haematochezia, personal history of colorectal adenoma or cancer, and for groups HD and IBS a family history of colorectal adenoma and/or cancer. Relative risks were estimated by the odds ratio (OR) using a logistic regression model and were expressed with 95% confidence interval (CI). RESULTS: After age and sex adjustment, the likelihood of having an adenoma > or = 10 mm was higher in group HD than in the IBS group (OR 1.8, 95% CI (1.2-2.7)) and the likelihood of having high risk adenomas or cancer was higher in group HD compared with the IBS group (OR 1.6, 95% CI (1.2-2.1)) and the FH group although this was not significant (OR 1.6, 95% CI (0.97-2.6) (p=0.081); 90% CI (1.03-2.4)). After age and sex adjustment, the likelihood of having an adenoma with high grade dysplasia or cancer was higher in group HD than in the IBS group (OR 1.7, 95% CI (1.02-2.8)) or group FH, although this was not significant (OR 3.7, 95% CI (0.98-15) (p=0.076); 90% CI (1.10-12.47)). CONCLUSION: In patients with at least one colorectal adenoma, excessive alcohol consumption increases the likelihood of developing high risk adenomas or colorectal cancer.

Adenoma↗

[Acute alcoholic hepatitis: treatments].

PROGNOSIS: Acute alcoholic hepatitis (AAH) is a severe form of alcohol-related liver disease with a high short-term mortality that can reach 50%. Long-term outcome depends on definitive weaning from alcohol and the development of cirrhosis. ESSENTIAL THERAPEUTIC STEP: Abstention from alcohol is the number one therapeutic measure required for treating AAH. Abstention must be total and definitive. THERAPEUTIC STRATEGIES: The pathogenic mechanisms involved in AAH have led to close assessment of numerous treatment protocols. Thirty-three randomized trials have evaluated drug treatments based on various strategies: antiinflammatory action using corticosteroids or colchicine; reduction of the hypermetabolism using propylthiouracil; hepatoprotective effect against oxidative stress using cyanidalol, alpha lipoid acid, silymarine, amlopidine, malotilate; vasodilatation to improve oxygenation of the centrolublular region using a calcium channel inhibitor, amlopidine; increased liver regeneration using anabolism steroids, intravenous perfusion combining insulin and glucagon; antifibrosis action using colchicine, D penicillamine; improved microcirculation due to increased deformability of the red cells and inhibition of TNF-alpha using pentoxifyllin. Eleven therapeutic trials have investigated the effect of parenteral or enteral artificial nutrition. GOLD STANDARD TREATMENT: Among all these strategies, the only one with a proven efficacy is corticosteroid therapy. Four trials have demonstrated the effect of corticosteroid therapy on short-term survival and 3 of the 4 meta-analyses devoted to the topic have demonstrated the usefulness of corticosteroid therapy in severe forms defined by a Maddrey index > or = 32: bilirubin in mumol per liter/17 + 4.6 (patient's PT in seconds--control PT in seconds) and the presence or not of encephalopathy. The gold standard treatment for severe AAH is oral prednisolone 40 mg/d for 1 month (excluding contraindications). PERSPECTIVES: Despite the effect of corticosteroid therapy, mortality at 2 months in severe AAH is still about 30%. Recent experimental data suggest that monoclonal anti-TNF alpha antibodies could be useful.

Acute Disease↗

[Regenerative nodular hyperplasia: variable clinical aspects].

BACKGROUND: Regenerative nodular hyperplasia can take on very misleading aspects making diagnosis difficult. CASE REPORTS: We report three cases of regenerative nodular hyperplasia (RNH). In the first patient rupture of esophageal varices was associated with myelofibrosis. In the second, extensive portal thrombus formation was associated with consumption coagulopathy and essential thrombocytemia. The third patient had systemic sclerodermia, hepatic macronodules, refractory exsudative ascitis and chronic hepatic encephalopathy following surgery for a porto-cava anastomosis. DISCUSSION: The diagnosis of RNH should be suspected in a variety of clinical situations with search for associated diseases in all cases. The prognosis is related to the consequences of portal hypertension and the severity of the associated diseases.

Adult↗

Abnormal von Willebrand factor in bleeding angiodysplasias of the digestive tract.

BACKGROUND & AIMS: Involvement of an abnormal von Willebrand factor in the bleeding expression of gastrointestinal angiodysplasias has been suggested but not assessed by prospective studies. METHODS: To address this issue, 27 patients with either nonbleeding (group A, n = 9) or bleeding (group B, n = 9) digestive angiodysplasias or telangiectasias or diverticular hemorrhage (group C, n = 9) were enrolled. In all patients, an analysis of von Willebrand factor and a screening for the most common disorders associated with an acquired von Willebrand disease were performed. RESULTS: In all patients from groups A and C, von Willebrand factor was normal, and no underlying disease could be found. In contrast, all but 1 patient from group B had a variable selective loss of the largest multimeric forms of von Willebrand factor, associated in 7 cases with a stenosis of the aortic valve. CONCLUSIONS: This study indicates that most patients with bleeding angiodysplasia or telangiectasia have a deficiency of the largest multimers of von Willebrand factor induced by a latent acquired von Willebrand disease. Because these multimers are the most effective in promoting primary hemostasis at the very high shear conditions related to these vascular malformations, we suggest that their deficiency is likely to contribute to the bleeding diathesis.

Adult↗

Tumor necrosis factor soluble receptor p55 and lipid peroxidation in patients with acute alcoholic hepatitis.

OBJECTIVES: In experimental models, liver injury induced by ethanol, cytotoxic activity of tumor necrosis factor (TNF) -alpha is principally mediated by TNF receptor p55 (TNFRp55). Among the various mechanisms underlying the toxic effects of TNF-alpha, overproduction of reactive oxygen species seems to play a key role in mediating TNF-alpha-induced cytotoxicity. The aim of this study was to evaluate, in patients with alcoholic liver disease, whether alcohol TNFRp55-mediated hepatotoxicity could account for lipid peroxidation expressed by significant increase in serum thiobarbituric reactive acid substances (TBARS) content, and could be amplified by decrease in blood total glutathione content and decrease in plasma antioxidant protective capacity. METHODS: We studied 27 patients with histological alcoholic liver disease (five fibrosis, six acute alcoholic hepatitis (AAH) without cirrhosis, four cirrhosis without AAH, and 12 cirrhosis with AAH. TNFsRp55 and TNFsRp75 plasma levels were measured using ELISA assays. Plasma lipid peroxidation was evaluated by the content of TBARS. Total glutathione (tGSH) content in blood was determined by a kinetic assay. The sensitivity of erythrocytes to an oxidative stress and the plasma antioxidant protective capacity were simultaneously determined by a simple method. RESULTS: In the 18 patients with mild or severe AAH, the plasma levels of TNFsRp55 were negatively correlated with tGSH and were positively correlated with TBARS, with total bilirubin and with discriminant function. tGSH was positively correlated with plasma selenium. The plasma levels of TNFsRp75 were positively correlated with TBARS and with total bilirubin. There was no significant correlation with the mean inhibitory 50% plasma volume or with the percentage of hemolyzed erythrocytes. CONCLUSIONS: Our data support the notions that, in patients with AAH, TNFsRp55 probably mediates cytotoxicity of TNF-alpha, and that cytotoxic effect could be amplified by tGSH depletion in enhancing lipid peroxidation.

Acute Disease↗

[Patients with alcoholic liver disease hospitalized in gastroenterology. A national multicenter study].

OBJECTIVES: To describe the characteristics of in-patients with alcoholic liver disease in Hepatogastroenterology and to evaluate whether geographic location was a risk factor for cirrhosis. METHODS: A French, national, multicenter, prospective investigation was performed in the last quarter of 1997. To be included in the study, patients had to have drunk at least 50 g of alcohol per day for the past year or to have cirrhosis. RESULTS: Seventeen centers included 802 patients, 20% had histologically proven cirrhosis or probable cirrhosis. Thirty-five percent had undergone liver biopsy. Twenty five percent of these patients had cirrhosis without acute alcoholic hepatitis and 37% had cirrhosis with acute alcoholic hepatitis. After dividing France along a Bordeaux-Strasbourg axis, there was more histologically proven or probable cirrhosis in the North (46%) than in the South (36%) (P<0.005) while daily alcohol intake was greater the South (150 +/- 6 g) than in the North (129 +/- 4 g) (P<0.0001). When the six variables (age, sex, daily consumption of alcohol over the past 5 years, presence of hepatitis B surface antigen and antibodies to hepatitis C virus, total duration of alcohol abuse) were considered together in stepwise logistic regression analysis, geographic location changed the prediction of cirrhosis. The odds ratio for cirrhosis in patients living to the North of the Bordeaux-Strasbourg axis was 1.9 (95% confidence interval range 1.1-3.2) (P<0.02), suggesting the role of nutritional factors.

Age Distribution↗

[Ulceronecrotic tracheobronchial involvement in Crohn's disease].

We report the case of a young female patient hospitalized for the first episode of a colonic Crohn's disease with specific ulceronecrotic tracheobronchial involvement leading to chronic and invalidant cough. Symptomatic bronchopulmonary manifestations are very rare in the course of inflammatory bowel diseases and usually not mentioned in Gastroenterology textbooks.

Adolescent↗

[Abdominal tuberculosis: deceptive and still encountered].

BACKGROUND: Extrapulmonary manifestations of tuberculosis are increasing in incidence. Abdominal tuberculosis may mimic a variety of gastrointestinal disorders. The diagnosis of abdominal tuberculosis is still difficult to establish before surgery. CASE REPORTS: We report 3 cases of abdominal tuberculosis in immunocompetent individuals. One patient presented with an ileocecal mass mimicking cancer. The second one presented with fever, ileocecal mass and ascites leading to the diagnosis of appendiceal peritonitis. The last patient was admitted for ascites, ovarian mass and high CA 125 serum level simulating ovarian cancer with peritoneal carcinomatosis. COMMENTS: In cases of abdominal tuberculosis when standard investigations are unhelpful, a PCR should be performed. Estimation of adenosine deaminase in ascitic fluid is an easy and reliable method for diagnosing tuberculous ascites. With these non invasive diagnostic procedures, surgery should be reserved only to patients with complications.

Adenosine Deaminase↗

Pretreatment expression of the perforin gene by circulating CD8(+) T lymphocytes predicts biochemical response to interferon-alpha in patients with chronic hepatitis C.

It would be of great value to be able to predict, before the initiation of treatment, which patients with hepatitis C virus-induced chronic hepatitis will be cured by interferon-alpha (IFN-alpha). Competitive RT-PCR was used to evaluate spontaneous expression of the perforin gene, a marker of cytotoxic cell activation, by circulating mononuclear cells in 17 patients undergoing IFN-alpha treatment. IFN-alpha increased perforin gene expression (p < 0.003), but this was not correlated with outcome. In contrast, pretreatment perforin gene expression levels were higher in the 8 patients with a sustained biochemical response after treatment than in the 9 non-responsive patients (p = 0.01). This factor predicted favorable clinical outcome with a sensitivity of 75% and a specificity of 89%. Thus, pretreatment immunological status has a major influence on the ability of IFN-alpha to cure chronic hepatitis C, and the evaluation of perforin gene expression may help to select patients that will benefit from IFN-alpha treatment.

Adult↗

Detection of the fluorescence of GI vessels in rats using a CCD camera or a near-infrared video endoscope.

BACKGROUND: Choroidal near-infrared fluorescent angiography can detect vessels in the eye with high resolution. Observation of fluorescent gastrointestinal (GI) vessels by endoscopy may be useful in portal hypertension and bleeding ulcer. We here describe a technique for the detection of fluorescent GI vessels with a CCD camera or a near-infrared video endoscope. METHODS: Laparotomy was performed on rats. A tissue target was excited by means of a laser diode. We took pictures of tissue under both white and near-infrared light, both before and after intravenous injection of indocyanine green. Fluorescent light was selected by means of filters placed in front of the lens of a CCD camera or a near-infrared video endoscope. RESULTS: Under near-infrared light and after dye injection, we observed fluorescent vessels in real time and distinguished arterial from venous fluorescence. CONCLUSIONS: This device permits visualization of GI vessels, which could be useful for diagnosis of vascular abnormalities during endoscopy and surgery.

Animals↗

Evaluation of efficacy of liver transplantation in alcoholic cirrhosis using matched and simulated controls: 5-year survival. Multi-centre group.

BACKGROUND/AIMS: Alcoholic cirrhosis is the most common cause of liver transplantation in US males. The limited number of donor livers calls for "prioritisation", favouring those patients who will benefit most. The aim was to assess the efficacy of liver transplantation in patients with alcoholic cirrhosis. METHODS: We compared the survival of 169 transplanted patients with two conservatively treated control groups, one of 169 patients matched for prognostic factors (age, cirrhosis severity, bleeding history) and one of 169 simulated patients. RESULTS: The probability of survival to 5 years in the transplanted group was 66% (95% confidence interval 58-74%) vs. 52% (44-60; p = 0.03) in the matched group and 54% (51-57; p = 0.01) in the simulated controls. Transplantation was associated with survival (relative risk = 1.51; p = 0.02), independently of risk score (risk = 2.07; p<0.001), indication, period of inclusion, centre experience, and alcohol abstinence. Patients with severe disease (Pugh C11-15) benefited most in terms of 5-year survival: 58% (44-72) vs. 31% (17-45; p = 0.008) in the matched and 35% (30-40; p<0.001) in the simulated control groups. For patients at lower risk there was no significant difference. CONCLUSIONS: Liver transplantation increases the 5-year survival of patients with severe alcoholic cirrhosis. In patients at lower risk, efficacy of transplantation should be confirmed by longer follow-up or by randomised trial.

Case-Control Studies↗

Prognostic value of the soluble interleukin-2 receptor in chronic hepatitis C treated with interferon-alfa. Multicenter GER-CYT 04 Group.

BACKGROUND/AIMS: High serum levels of the soluble interleukin 2 receptor (sIL-2R) have been reported in patients with chronic hepatitis C. The aims of this study were to determine the evolution of sIL-2R considered as an indicator of activation of T cells in patients with hepatitis C virus (HCV) treated with IFN-alpha and to correlate sIL-2R serum levels with parameters reflecting ongoing liver disease and with outcome of interferon treatment. METHODS: In a case-control study, we studied patients enrolled in a multicenter randomized clinical trial which had demonstrated the benefit of a reinforced regimen of interferon alpha. Each of the 26 sustained virological responders (SVR) was paired for treatment regimen with two non-responders (NR). RESULTS: Prior to treatment, higher levels of sIL-2R were found in the sera of 78 patients compared with healthy controls (3791+/-210 pg/ml versus 956+/-88 pg/ml (p<0.001)). In the 78 patients after 4 weeks of treatment, the levels of sIL-2R were higher than pretreatment levels (4308+/-206 pg/ml (p<0.01)). In the NR, levels of sIL-2R increased significantly after 4 weeks of treatment compared with pretreatment levels (p<0.01), and levels of sIL-2R at week 72 were not significantly different from those at pretreatment. Conversely, in the SVR, levels of sIL-2R at week 4 did not significantly increase compared to pretreatment values, and thereafter gradually decreased. At week 72, levels of sIL-2R were significantly lower than before treatment (p<0.001). The difference between levels of sIL-2R at week 4 and before initiation of treatment (delta s IL-2R) was smaller in the SVR than in the NR (142+/-219 pg/ml versus 704+/-107 pg/ml (p<0.02). The disappearance of HCV RNA from the serum at week 4 showed a sensitivity of 92% (95% confidence interval 86-98) and a specificity of 60% (95% confidence interval 49-71), delta sIL-2R had a sensitivity of 42% (95% confidence interval 31-53) and a specificity of 81% (95% confidence interval 79-90) for the prediction of a sustained virological response 6 months after stopping treatment. The disappearance of HCV RNA from serum at week 4 and delta sIL-2R were independent and early predictive factors for a sustained virological response 6 months after stopping treatment. CONCLUSIONS: At week 4, delta sIL-2R may be a more specific parameter than the disappearance of HCV RNA for assessing total, and hence more sustained, elimination of HCV infection 6 months after stopping treatment.

Adult↗

Prothrombin 20210G/A mutation in two patients with mesenteric ischemia.

Primary cases of splanchnic vein thrombosis are now less common since a systematic screening for hypercoagulability is performed. In 1996, a sequence variation in the 3'-untranslated region of the prothrombin gene (F.II 20210G/A mutation) has been linked to a threefold increased risk for venous thrombosis. The role of this thrombophilic disorder is not documented in patients with thrombosis of the splanchnic veins. This report presents two patients with a mesenteric ischemia associated with a heterozygous state for the F.II 20210G/A mutation. The first patient developed an ischemic colitis and the second one an ischemic necrosis of the terminal ileum related to a thrombosis of the superior mesenteric vein. In both cases, another thrombotic risk factor was associated: either a general prothrombic state (primary antiphospholipid syndrome) or a focal factor (abnormal hemodynamic conditions related to a liver cirrhosis). It has recently been proposed that several conditions need to be combined for deep vein thrombosis to develop. Screening for the combination of multiple underlying prothrombotic conditions thus appears justified in patients with splanchnic thrombosis. The role of the F.II 20210G/A mutation as a predisposing factor for thrombosis of the digestive vessels should be considered and needs further investigation.

Adult↗