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Denis Heresbach

Publications and source records attributed to Denis Heresbach.

14 recordsLinked to original sources
PubMed2006

[Cost-effectiveness of colorectal cancer screening].

Colorectal cancer (CRC) screening in France is based on a faecal occult blood test every two years in average risk subjects 50-74 years of age while other endoscopic or non-endoscopic screening methods are used in Europe and in the USA. Beside the reduced incidence of and mortality from CRC found in available studies, cost-effectiveness data need to be taken into account. Because of the delay between randomized controlled trials and clinical results, transitional probabilistic models of screening programs are useful for public health policy makers. The aim of the present review was to promote the implementation of cost-effectiveness studies, to provide a guide to analyze cost-effectiveness studies on CRC screening and, to propose a French cost effectiveness study comparing CRC screening strategies. Most of these trials were performed by US or UK authors and demonstrate that the incremental cost-effectiveness ratio varies between 5 000 and 15 000 US dollars/one year life gained, with wide variations: these results were highly dependent on the unit costs of the different devices as well as the predictive values of the screening tests. Although CRC screening programs have been implemented in several administrative districts of France since 2002, and the results of these randomized controlled trials using fecal occult blood have been updated, cost-effectiveness criteria need to be integrated; especially since the results of screening campaigns based on other tools such as flexible sigmoidoscopy should be available in 2007.

Aged↗
PubMed2006

Review in depth and meta-analysis of controlled trials on colorectal cancer screening by faecal occult blood test.

BACKGROUND: Several randomized studies have shown that colorectal cancer (CRC) screening by faecal occult blood test (FOBT) reduces CRC mortality. These trials have different designs, especially concerning FOBT frequency and duration, as well as the length of follow-up after stopping FOBT campaigns. AIMS: To review the effectiveness of screening for CRC with FOBT, to consider the reduction in mortality during or after screening or to identify factors associated with a significant mortality reduction. METHODS: A systematic review of trials of FOBT screening with a meta-analysis of four controlled trials selected for their biennial and population-based design. The main outcome measurements were mortality relative risk (RR) and 95% confidence interval (CI) of biennial FOBT during short (10 years, i.e. five or six rounds) or long-term (six or more rounds) screening periods, as well as after stopping screening and follow-up during 5-7 years. The meta-analysis used the Mantel-Haenszel method with fixed effects when the heterogeneity test was not significant, and used 'intent to screen' results. RESULTS: Although the quality of the four trials was high, only three were randomized, and one used rehydrated biennial FOBT associated with a high colonoscopy rate (28%). A meta-analysis of mortality results showed that subjects allocated to screening had a reduction of CRC mortality during a 10-year period (RR 0.86; CI 0.79-0.94) although CRC mortality was not decreased during the 5-7 years after the 10-year (six rounds) screening period, nor in the last phase (8-16 years after the onset of screening) of a long-term (16 years or nine rounds) biennial screening. Whatever the design of the period of ongoing FOBT, CRC incidence neither decreased nor increased, although it was reduced for 5-7 years after the 10-year screening period. Neither the design nor the clinical or demographic parameters of these trials were independently associated with CRC mortality reduction. CONCLUSION: Biennial FOBT decreased CRC mortality by 14% when performed over 10 years, without evidence-based benefit on CRC mortality when performed over a longer period. No independent predictors of CRC mortality reduction have been identified in order to allow a CRC screening programme in any subgroups of subjects at risk.

Aged↗
PubMed2005

Regulation by allergens of chemokine receptor expression on in vitro-generated dendritic cells.

Immature dendritic cells (DCs) derived from CD34+ progenitor cells or peripheral monocytes, are used as in vitro sensitization models in many chemical allergen treatment studies. During the sensitization, DCs follow maturation process and gain the capacity to migrate to lymph nodes where they stimulate T cells. Chemokine receptor allows DCs to migrate along chemotactic gradients. In this work, we used immature DCs from peripheral monocytes to evaluate the influence of allergens on chemokine receptor and surface-marker expression. We tested the sensitizers dinitrochlorobenzene, Bandrowski's base, and coumarin, as well as the tolerogen dichloronitrobenzene, the irritant sodium dodecyl sulfate and the solvent dimethyl sulfoxide. All skin sensitizers up-regulated the co-stimulatory molecule CD86 and increased the CD83+ cell population. No expression of the chemokine receptors CCR2, CCR3, CCR6, or CXCR5 was observed on DCs exposed to the tested chemicals. The strong allergen dinitrochlorobenzene slightly increased CCR7 expression on DCs but down-regulated CCR1 surface expression. CCR1 down-regulation was not mediated by a classical maturation pathway, as it was unaffected by the corticosteroid dexamethasone.

Allergens↗
PubMed2005

Does the "Suspected Blood Indicator" improve the detection of bleeding lesions by capsule endoscopy?

BACKGROUND: The "Suspected Blood Indicator" (SBI), a feature included in the software for interpretation of capsule endoscopy (CE), is designed to facilitate detection of bleeding lesions in the small bowel. This study evaluated the sensitivity and the specificity of the SBI in patients who underwent CE for obscure GI bleeding (OGIB). METHODS: CE recordings from patients with OGIB recruited in 7 centers were read by experts blinded to the red SBI tags. They classified lesions of interest as bleeding or as having a potential for bleeding that was high (P2), low (P1), or absent (P0). The SBI tags then were marked by a another investigator. Concordance was acknowledged when frames selected by the expert reader, and those tagged by the SBI had the same time code. RESULTS: A total of 156 recordings were evaluated. In 83, there was either no lesion (n = 71) or a P0 lesion (n = 12); these CE recordings were regarded as normal. Among the 73 abnormal recordings, 114 P2 and 92 P1 lesions were identified. A total of 154 red tags were analyzed. Sensitivity, specificity, and positive and negative predictive values of SBI were 37%, 59%, 50%, and 46%, respectively, for detection of the presence of a P2 or P1 lesion in front of a red tag. CONCLUSIONS: SBI-based detection of intestinal lesions with the potential for bleeding is of limited clinical value in practice and does not reduce the time required for interpretation of CE.

Endoscopes, Gastrointestinal↗
PubMed2005

RBC 6-TGN and hematological parameters in patients with Crohn's disease treated by azathioprine.

OBJECTIVE: The immunosuppressive properties of azathioprine (AZA) are mediated by intracellular metabolism of 6-MP into its active metabolites 6-thiguanine nucleotide (6-TGN) and 6-methylmercaptopurine (6-MMP). The aims of this study were to correlate red blood cell (RBC) 6-TGN and hematological parameters and their change in adult patients with Crohn's disease (CD) treated by AZA and to determine independent factors enabling determination of RBC 6-TGN. METHODS: RBC 6-TGN concentration was determined with high performance liquid chromography (HLPC) performed on 74 hepa-rinized blood samples from 32 patients. Changes of hematological parameters were measured for each RBC 6-TGN concentration. RBC 6-TGN concentration above 235 pmol/8x108 RBC was proposed as the therapeutic level in patients treated by AZA. Correlations between the various parameters were assessed as appropriate. Logistic regression analysis was used to determinate independent variables. P<0.05 was considered significant. RESULTS: There was a positive correlation between RBC 6-TGN and decreased red cell count (DeltaRBC) (r=0.314; P=0.006), platelet count (DeltaPlatelets) (r=0.314; P=0.007), White cell count (DeltaWC) (r=0.241; P=0.04) and neutrophil count (DeltaPMN) (r=0.292; P=0.02). RBC 6-TGN in the therapeutic zone was positively correlated with mean corpuscular volume (MCV) (r=0.527; P=0.01), mean corpuscular hemoglobin concentration (MCHC) (r=0.437; P=0.04), increase in MCV (DeltaMCV) (r=0.512; P=0.012), decrease in White cell count (DeltaWC) (r=0451; P=003) and in neutrophil count (DeltaPMN) (r=0.463; P=0.03). Multivariate analysis showed that low activity of CD (P<0.02), young age at onset of treatment by AZA (P<0.03) and a low red cell distribution width (RDW) (P=0.003) were independent factors for RBC 6-TGN situated in therapeutic zone. RBC 6-TGN could be determined by logistic regression from AZA dose (mg/kg/d) and MCV increase. CONCLUSION: This study confirms that hematological parameters or their change can be used to determine whether RBC 6-TGN concentration has reached the therapeutic level. Logistic regression analysis showed that decreased RDW and increased MCV were independent factors for RBC 6-TGN level.

Adult↗
PubMed2004

NOD2/CARD15 gene polymorphisms in Crohn's disease: a genotype- phenotype analysis.

OBJECTIVES: Three recently identified NOD2/CARD15 mutations have been described associated with an increased susceptibility Crohn's disease (CD). Our aim was to examine the potential association of these NOD2 mutations with CD and different subsets of CD phenotypes in our population. METHODS: Two hundred and five well-defined CD patients from north-western France and 95 ethnically matched healthy controls were genotyped for mutations R702W, G908R and Leu1007insC by DNA sequencing. Allele and genotype frequencies of NOD2 variants were examined in the whole series of CD and in different subgroups of CD phenotypes defined by the clinical characteristics of the Vienna classification (age at diagnosis, location and behaviour) or by histological features (granuloma). RESULTS: Carriers of at least one NOD2/CARD15 variant were significantly more frequent in CD than in controls (38.0% versus 20.0%, P < 0.002), and the R702W allele was the most significant contributor to this NOD2 association with CD. Homozygotes and compound heterozygotes combined had a higher risk of CD (odds ratio = 12.0, P < 0.0026) than simple heterozygotes for any variant (odds ratio = 2.2, P < 0.013) compared with subjects with no variant. Univariate analysis revealed that carriage of at least one NOD2 mutation was significantly associated with ileal involvement (P < 0.03), and stricturing evolution (P < 0.0015). Granuloma was associated with an excess of the R702W allele (16.1% versus 8.0%, Pc < 0.035), and was correlated with a young age at diagnosis, whatever the NOD2/CARD15 genotype. Multivariate analysis demonstrated that carriage of NOD2/CARD15 mutants, especially R702W, was primarily and independently associated both with stricturing evolution of CD and the presence of granuloma. CONCLUSIONS: In our population, all NOD2/CARD15 mutant genotypes, especially compound heterozygosity, were found to increase the risk of CD, but R702W was the sole allele showing a significant association with CD. In addition, we confirm the positive and independent association of the R702W mutation with stricturing behaviour and describe a second one with the presence of granuloma.

Adolescent↗
PubMed2004

Crohn's disease in the over-60 age group: a population based study.

OBJECTIVES: Late-onset Crohn's disease (CD) may show a distinctive pattern of expression. The aim of our study was to describe the incidence or presentation of CD in the elderly and compare the outcomes in patients < 60 years or > or = 60 years at diagnosis. METHODS: The study included a population based inception cohort of all incident CD cases diagnosed in Brittany (France) between 1994 and 1997. Sixty-three patients were > or = 60 years and 201 were < 60 years at diagnosis. The physicians managing the patients used standardized questionnaires to collect the study data. The questionnaires on outcomes and treatments were completed in 2002. RESULTS: In patients > or = 60 years, the annual incidence was 2.5 per 10 persons and clinical features were similar to those in younger patients, except for a higher rate of colon involvement. Among older patients, those with diverticula (29/63, 46%) were more likely to have granulomas (58% vs 33% of patients without diverticula, P < 0.04), but the diagnosis of CD was confirmed by lesions remote from the diverticula in most cases (23/29). Early resection rates were not higher in older patients, who were less likely to require immunosuppressants or re-admission for CD flares, as compared to younger patients. Five year mortality in older patients was 16% but was unrelated to CD. CONCLUSIONS: In Brittany, the age specific incidence, clinical features, and prognosis of CD among the elderly are comparable to those in younger individuals. Colon involvement is more common. Concomitant diverticular disease is common and should prompt a search for CD lesions at other sites to confirm the diagnosis. Older patients are less likely to require immunosuppressants or admission for flares.

Adult↗
PubMed2003

[Endoscopic and pathological aspect of small bowel and colonic involvement in Whipple's disease: a case report].

We describe a case of Whipple's disease confirmed by clinical, histological, bacteriological and molecular criteria. The duodenal involvement was associated with the presence of an endoscopic and histological enterocolitis. Final diagnosis of small bowel and colonic involvement by Whipple's disease was confirmed by histology and molecular biology. We review the literature on extra duodenal involvement. We underline the fact that enterocolitis in Whipple's disease is non-specific. We also discuss the other causes of intestinal mucosal infiltration by macrophages.

Adult↗
PubMed2003

[Paroxysmal nocturnal hemoglobinuria associated with intestinal ischemia leading to small bowel perforation].

Paroxysmal nocturnal hemoglobinuria is rarely associated with intestinal complications. We report a case of paroxysmal nocturnal hemoglobinuria with small bowel ischemia leading to ileal perforation. In the literature, an ulcerative jejuno-ileitis has been reported in 6 cases of intestinal ischemia, due to thrombosis of mucosal small vessels. This disease is usually revealed by abdominal pain. Based on published cases and our observation of intestinal ischemia leading to small bowel perforation, surgery should be considered as the first-line treatment, especially when small bowel lesions are limited.

Adult↗
PubMed2003

[Selective COX-2 inhibitor-associated colitis: two case reports].

Non-steroidal anti-inflammatory drugs (NSAIDs) reduce prostaglandin synthesis by inhibiting cyclo-oxygenase 1 (COX-1) and/or cyclo-oxygenase 2 (COX-2). Different groups of NSAIDs, defined by their action on either COX-1 or COX-2, have been developed. Whether intestinal toxicity of preferential or selective COX-2 inhibitors is reduced compared with that of standard NSAIDs is controversial. We report the cases of two patients with self-limited colitis induced by preferential COX-2. We discuss the mechanisms of intestinal toxic effects of COX-2 preferential inhibitors from endoscopic and histological features of colitis.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2002

Serum measurements of pancreatitis associated protein in active Crohn's disease with ileal location.

BACKGROUND AND AIMS: Pancreatitis-associated protein (PAP) is a pancreatic stress protein also expressed in the ileum but not in the colon. Its serum concentration is increased in patients with small bowel inflammation due to untreated celiac disease. We searched to determine whether PAP could be a serum marker for ileal location of active Crohn's disease (CD). METHODS: A multicenter prospective study was conducted, including 54 healthy controls and 124 patients with CD of whom 38 had quiescent ileal or ileocolonic disease (group A), 45 had active ileal or ileocolonic disease (group B), 18 had quiescent colon-only CD (group C), and 28 had active colonic disease (group D). Active disease was defined by a Crohn's disease activity index > 150 and serum C-reactive protein (CRP) > 10 mg/mL. Location of lesions was assessed by endoscopy. PAP was assayed in serum, the upper threshold for normal values being 50 ng/mL. RESULTS: In group B, 27 patients (60%) had elevated serum PAP, compared to one in group A (2.5%), one in group C (5.3%), three in group D (10.7%) and none in the control group (P<0.01). By contrast, serum levels of C-reactive protein did not differ between patients with active CD and either ileal location (group B) or pure colonic location (group D) (38 +/-10.5 vs 41.6 +/- 6.4 mg/mL, NS). Within group B, serum PAP concentration was correlated with none of the epidemiological, clinical or biological data available. Increased serum level of PAP diagnosed ileal location in active CD with a sensitivity of 60%, a specificity of 94%, a positive predictive value of 84% and a negative predictive value of 81%. CONCLUSION: Elevated serum PAP (> 50 ng/mL ) is significantly associated with disease activity and ileal location

Acute-Phase Proteins↗
PubMed2002

[Treatment of Crohn's disease with anti-TNF alpha antibodies (infliximab): results of a multicentric and retrospective study].

OBJECTIVE: To evaluate the results of infliximab therapy, an anti-TNF-alpha antibody, in patients with severe and refractory Crohn's disease or with fistulas, treated outside the setting of a therapeutic trial. METHODS: All Crohn's disease patients treated at the Departments of Gastroenterology of the University Hospitals of Bordeaux, Nantes, Poitiers, Rennes and Tours were retrospectively analyzed. RESULTS: Sixty-nine patients were treated with a total of 170 infusions of infliximab, 32 patients being treated for refractory Crohn's disease and 37 for fistulas. The median follow-up was 8 months (extremes 1-20). An objective response was observed in 79% of refractory Crohn's disease patients and 78% of fistulazing patients. A remission was observed in 72% and 70% of the patients respectively. Forty-five percent of patients had relapsed within 4 months (extremes 2-7). Immunosuppressive therapy was associated with a lower relapse rate (18% with versus 56% without, P=0.004). Infliximab resulted in a steroid-sparing effect in 73% of patients. Forty adverse events, none of severe grade, were observed in 22% of the patients, without any influence of steroids or immunosuppressive therapy. CONCLUSION: This study confirms that infliximab is very effective in steroid-dependent and fistulazing Crohn's disease. Infliximab has a steroid-sparing effect and immunosuppressive therapy is associated with a reduced relapse rate. Although the tolerance is good in the short term, long term safety remains to be established by further studies.

Adult↗