Low prevalence of colonoscopic surveillance of inflammatory bowel disease patients with longstanding extensive colitis: a clinical practice survey nested in the CESAME cohort

International audienceBackground: Surveillance colonoscopy is recommended for inflammatory bowel disease (IBD) patients with longstanding extensive colitis (LEC). Aims: To assess modalities and results of colonoscopic surveillance in a subset of CESAME cohort patients at high risk of colorectal cancer (CRC) and followed in university French hospitals. Methods: Among 910 eligible patients with more than a 7-year history of extensive colitis at CESAME enrolment, 685 patients completed a questionnaire on surveillance colonoscopy and 102 were excluded because of prior proctocolectomy. Finally, 583 patients provided information spanning a median period of 41 months (IQR 38-43) between cohort enrolment and the end of follow-up. Details of the colonoscopic procedures and histological findings were obtained for 440 colonoscopies in 270 patients. Results: Only 53.5% (n=312) of the patients with LEC had at least one surveillance colonoscopy during the study period, with marked variations across the 9 participating centres (27.3% to 70.0%, p= < 0.0001). Surveillance rate was significantly lower in Crohn's colitis than in ulcerative colitis (UC) (47.6% vs 68.5%, p=< 0.0001). Independent predictors of colonoscopic surveillance were male sex, UC IBD subtype, longer disease duration, previous history of CRC, and disease management in a centre with large IBD population. Random biopsies, targeted biopsies and chromoendoscopy were performed during respectively 70.7%, 26.6 and 30.0% of surveillance colonoscopies. Two cases of high-grade dysplasia were detected in patients undergoing colonoscopic surveillance. Two advanced-stage CRC were diagnosed in patients who did not have colonosocopic surveillance. Conclusions: Colonoscopic surveillance rate is low in IBD patients with longstanding extensive colitis

From array-based hybridization of Helicobacter pylori isolates to the complete genome sequence of an isolate associated with MALT lymphoma

<p>Abstract</p> <p>Background</p> <p><it>elicobacter pylori </it>infection is associated with several gastro-duodenal inflammatory diseases of various levels of severity. To determine whether certain combinations of genetic markers can be used to predict the clinical source of the infection, we analyzed well documented and geographically homogenous clinical isolates using a comparative genomics approach.</p> <p>Results</p> <p>A set of 254 <it>H. pylori </it>genes was used to perform array-based comparative genomic hybridization among 120 French <it>H. pylori </it>strains associated with chronic gastritis (n = 33), duodenal ulcers (n = 27), intestinal metaplasia (n = 17) or gastric extra-nodal marginal zone B-cell MALT lymphoma (n = 43). Hierarchical cluster analyses of the DNA hybridization values allowed us to identify a homogeneous subpopulation of strains that clustered exclusively with <it>cag</it>PAI minus MALT lymphoma isolates. The genome sequence of B38, a representative of this MALT lymphoma strain-cluster, was completed, fully annotated, and compared with the six previously released <it>H. pylori </it>genomes (i.e. J99, 26695, HPAG1, P12, G27 and Shi470). B38 has the smallest <it>H. pylori </it>genome described thus far (1,576,758 base pairs containing 1,528 CDSs); it contains the <it>vacA</it>s2m2 allele and lacks the genes encoding the major virulence factors (absence of <it>cag</it>PAI, <it>bab</it>B, <it>bab</it>C, <it>sab</it>B, and <it>hom</it>B). Comparative genomics led to the identification of very few sequences that are unique to the B38 strain (9 intact CDSs and 7 pseudogenes). Pair-wise genomic synteny comparisons between B38 and the 6 <it>H. pylori </it>sequenced genomes revealed an almost complete co-linearity, never seen before between the genomes of strain Shi470 (a Peruvian isolate) and B38.</p> <p>Conclusion</p> <p>These isolates are deprived of the main <it>H. pylori </it>virulence factors characterized previously, but are nonetheless associated with gastric neoplasia.</p

Inhibition of anti-tuberculosis T-lymphocyte function with tumour necrosis factor antagonists

Reactivation of latent Mycobacterium tuberculosis (Mtb) infection is a major complication of anti-tumour necrosis factor (TNF)-α treatment, but its mechanism is not fully understood. We evaluated the effect of the TNF antagonists infliximab (Ifx), adalimumab (Ada) and etanercept (Eta) on anti-mycobacterial immune responses in two conditions: with ex vivo studies from patients treated with TNF antagonists and with the in vitro addition of TNF antagonists to cells stimulated with mycobacterial antigens. In both cases, we analysed the response of CD4(+ )T lymphocytes to purified protein derivative (PPD) and to culture filtrate protein (CFP)-10, an antigen restricted to Mtb. The tests performed were lymphoproliferation and immediate production of interferon (IFN)-γ. In the 68 patients with inflammatory diseases (rheumatoid arthritis, spondylarthropathy or Crohn's disease), including 31 patients with a previous or latent tuberculosis (TB), 14 weeks of anti-TNF-α treatment had no effect on the proliferation of CD4(+ )T lymphocytes. In contrast, the number of IFN-γ-releasing CD4(+ )T lymphocytes decreased for PPD (p < 0.005) and CFP-10 (p < 0.01) in patients with previous TB and for PPD (p < 0.05) in other patients (all vaccinated with Bacille Calmette-Guérin). Treatments with Ifx and with Eta affected IFN-γ release to a similar extent. In vitro addition of TNF antagonists to CD4(+ )T lymphocytes stimulated with mycobacterial antigens inhibited their proliferation and their expression of membrane-bound TNF (mTNF). These effects occurred late in cultures, suggesting a direct effect of TNF antagonists on activated mTNF(+ )CD4(+ )T lymphocytes, and Ifx and Ada were more efficient than Eta. Therefore, TNF antagonists have a dual action on anti-mycobacterial CD4(+ )T lymphocytes. Administered in vivo, they decrease the frequency of the subpopulation of memory CD4(+ )T lymphocytes rapidly releasing IFN-γ upon challenge with mycobacterial antigens. Added in vitro, they inhibit the activation of CD4(+ )T lymphocytes by mycobacterial antigens. Such a dual effect may explain the increased incidence of TB in patients treated with TNF antagonists as well as possible differences between TNF antagonists for the incidence and the clinical presentation of TB reactivation

Chronic Hepatitis C Virus and Gastric MALT Lymphoma Congenital Erythropoietin-Dependent Erythrocytosis Responsive to Theophylline Treatment

Cases of lymphocytic monoclonal B-cell proliferation such as non-Hodgkin&apos;s lymphomas have been reported in chronically hepatitis C virus (HCV)-infected patients. Lymphomas of the mucosa-associated lymphoid tissue (MALT) type are due to monoclonal proliferation of B cells showing characteristic histopathological features of MALT. Luppi et al 1 recently reported an unexpectedly high prevalence of HCV infection in a series of patients with low-grade lymphomas of the MALT type in various body sites. This study showed the presence of both anti-HCV antibodies and HCV-RNA in the serum of 8 of 16 MALT lymphoma patients (50%). 1 In another study, Pioltelli et al 2 also observed a high prevalence of HCV infection in low-grade lymphomas of the MALT type (36.4%), although they did not mention the number of cases examined. The aim of the present study was to assess the prevalence of HCV infection in a well-characterized series of 46 patients with gastric MALT lymphoma. Of the 46 patients, 25 had a low-grade lymphoma (14 women, 11 men, mean age 54.2 years, range 30 to 75) and 21 had a high-grade lymphoma (8 women, 13 men, mean age 56.3 years, range 23 to 85). Helicobacter pylori infection was demonstrated by serological and/or histological tests in 37 of 46 patients (80.4%). One hundred sixty-five patients with gastroduodenal disease were recruited to compose the control group. There were 84 patients with duodenal ulcer, 43 with gastric ulcer, and 38 with dyspepsia. The two groups were comparable in terms of the sex ratio, age, prevalence of H pylori, risk factors for HCV infection (previous parenteral exposure to blood products, intravenous drug misuse, nosocomial exposure), and geographical origin. Diagnosis of gastric MALT lymphoma was based on gastric biopsy specimens evaluated according to Isaacson&apos;s classification 3 and by immunophenotypic analysis of surface T-and B-lymphocyte markers. Anti-HCV antibodies were determined by third-generation enzymelinked immunosorbent assay and confirmed by third-generation recombinant immunoblot assay (RIBA) in all patients (Ortho Clinical Systems, Raritan, NJ). There was no significant difference between the prevalence of HCV infection in the MALT lymphoma group and the control group: among the patients with gastric MALT lymphoma, only 1 had anti-HCV antibodies (2.2%), compared with 4 in the control group (2.4%) (not significant). The only MALT patient who tested anti-HCV Ab-positive was also positive for H pylori and belonged to the low-grade MALT lymphoma group. Thus, we found no higher prevalence of HCV infection among patients with gastric MALT lymphoma than in a control group composed of subjects with a gastroduodenal disease similarly related to H pylori infection, with the same risk factors for hepatitis C and deriving from the same geographical region. Our data contrast with those of the Italian teams 1,2 and are more in keeping with those of the American and British teams, 4,5 who did not specifically study gastric MALT lymphoma but found no evidence of a relationship between HCV infection and non-Hodgkin&apos;s lymphoma. To our knowledge, this is the first study to evaluate the prevalence of HCV infection in a large, well-characterized series of patients with gastric lymphomas of the MALT type. Our results indicate that there is no link between HCV infection and gastric MALT lymphoma in France