Jean-Marc Gornet

Infliximab for refractory ulcerative colitis or indeterminate colitis: an open-label multicentre study.

Background : The efficacy of infliximab in ulcerative colitis (UC) and indeterminate colitis has been poorly assessed and preliminary results are conflicting.

Prospective, Randomized, Multicenter, Phase III Study of Fluorouracil, Leucovorin, and Irinotecan Versus Epirubicin, Cisplatin, and Capecitabine in Advanced Gastric Adenocarcinoma: A French Intergroup (Fédération Francophone de Cancérologie Digestive, Fédération Nationale des Centres de Lutte Contre le Cancer, and Groupe Coopérateur Multidisciplinaire en Oncologie) Study

PURPOSE To compare epirubicin, cisplatin, and capecitabine (ECX) with fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatments in patients with advanced gastric or esophagogastric junction (EGJ) adenocarcinoma. PATIENTS AND METHODS This open, randomized, phase III study was carried out in 71 centers. Patients with locally advanced or metastatic gastric or EGJ cancer were randomly assigned to receive either ECX as first-line treatment (ECX arm) or FOLFIRI (FOLFIRI arm). Second-line treatment was predefined (FOLFIRI for the ECX arm and ECX for the FOLFIRI arm). The primary criterion was time-to-treatment failure (TTF) of the first-line therapy. Secondary criteria were progression-free survival (PFS), overall survival (OS), toxicity, and quality of life. RESULTS In all, 416 patients were included (median age, 61.4 years; 74% male). After a median follow-up of 31 months, median TTF was significantly longer with FOLFIRI than with ECX (5.1 v 4.2 months; P = .008). There was no significant difference between the two groups in median PFS (5.3 v 5.8 months; P = .96), median OS (9.5 v 9.7 months; P = .95), or response rate (39.2% v 37.8%). First-line FOLFIRI was better tolerated (overall rate of grade 3 to 4 toxicity, 69% v 84%; P < .001; hematologic adverse events [AEs], 38% v 64.5%; P < .001; nonhematologic AEs: 53% v 53.5%; P = .81). CONCLUSION FOLFIRI as first-line treatment for advanced gastric and EGJ cancer demonstrated significantly better TTF than did ECX. Other outcome results indicate that FOLFIRI is an acceptable first-line regimen in this setting and should be explored as a backbone regimen for targeted agents.

Hydrostatic balloon dilatation of Crohn's strictures.

Aim : To evaluate the safety and long‐term efficacy of per‐endoscopic hydrostatic balloon dilatation in a retrospective series of patients with Crohns disease.

anal Carcinomas in Hiv-positive Patients: High-dose Chemoradiotherapy Is Feasible in the Era of Highly Active Antiretroviral Therapy

BACKGROUNDAnal carcinoma, a common disease in HIV-positive patients, is usually treated with chemoradiotherapy. Generally tolerance was poor before the availability of highly active antiretroviral therapies. We report our experience of treating anal carcinoma in the era of new antiviral drugs.PATIENTS AND METHODSBetween 1997 and 2001, nine men on highly active antiretroviral therapies with good immune status before chemoradiotherapy received concomitant chemoradiotherapy consisting of 5-fluorouracil and cisplatinum, and high-dose radiotherapy (60–70 Gy) for anal carcinoma. Six cancers were Stage I, two were Stage II, and one was Stage III. CD4+ cell counts were <200/ml for four patients, between 200/ml and 500/ml for four, and >500/ml for one.RESULTSAll patients received the planned dose of radiation (≥60 Gy). The chemotherapy dose was reduced 25 percent in six patients. Overall treatment time was 58 days. Grade 3 hematologic or skin toxicity occurred in four patients. No association was observed between high-grade toxicity and CD4+ cell count. None of the patients developed opportunistic infections during follow-up. Eight patients were disease-free after a median follow-up of 33 months. Among them, four had no or minor anal function impairment at the last follow-up visit. One patient with T4N2 disease relapsed locally one year after treatment and underwent salvage abdominoperineal excision.CONCLUSIONHigh-dose chemoradiotherapy for anal carcinomas is feasible with low toxicity in HIV-positive patients treated with highly active antiretroviral therapies. Local control is similar to that obtained for HIV-negative patients.

Impact of pregnancy on the clinical activity of Crohn's disease

Background : The impact of pregnancy on Crohns disease activity has been poorly investigated.

Enteropathy associated T cell lymphoma in celiac disease: A large retrospective study

Abstract Introduction Prognosis of enteropathy-associated T cell lymphoma is poor but predictors of survival remain ill-defined. How clinical presentation, pathological features and therapies influence outcome was evaluated in 37 thoroughly characterized patients with celiac disease and T-cell lymphoma. Patients and methods Medical files were studied retrospectively. Lymphoma and intestinal mucosa were analysed by histopathology, multiplex PCR and intestinal intraepithelial lymphocytes phenotyping. Survival and prognostic factors were analysed using Kaplan–Meier curves with Logrank test and Cox Model. Results Lymphoma complicated non clonal enteropathy, celiac disease (n =15) and type I refractory celiac disease (n =2) in 17 patients and clonal type II refractory celiac disease in 20 patients. Twenty-five patients underwent surgery with resection of the main tumour mass in 22 cases. In univariate analysis, non clonal celiac disease, serum albumin level>21.6g/L at diagnosis, chemotherapy and surgical resection predicted good survival (p =0.0007, p <0.0001, p <0.0001, p <0.0001, respectively). In multivariate analysis, serum albumin level>21.6g/L, chemotherapy and reductive surgery were all significantly associated with increased survival (p <0.002, p <0.03, p <0.03, respectively). Conclusions Our study underlines the prognostic value of celiac disease type in patients with T-cell lymphoma, and suggests that a combination of nutritional, chemotherapy and reductive surgery may improve survival.

Genotype/Phenotype Analyses for 53 Crohn’s Disease Associated Genetic Polymorphisms

Background & Aims Recent studies reported a role for more than 70 genes or loci in the susceptibility to Crohn’s disease (CD). However, the impact of these associations in clinical practice remains to be defined. The aim of the study was to analyse the relationship between genotypes and phenotypes for the main 53 CD-associated polymorphisms. Method A cohort of 798 CD patients with a median follow up of 7 years was recruited by tertiary adult and paediatric gastroenterological centres. A detailed phenotypic description of the disease was recorded, including clinical presentation, response to treatments and complications. The participants were genotyped for 53 CD-associated variants previously reported in the literature and correlations with clinical sub-phenotypes were searched for. A replication cohort consisting of 722 CD patients was used to further explore the putative associations. Results The NOD2 rare variants were associated with an earlier age at diagnosis (p = 0.0001) and an ileal involvement (OR = 2.25[1.49–3.41] and 2.77 [1.71–4.50] for rs2066844 and rs2066847, respectively). Colonic lesions were positively associated with the risk alleles of IL23R rs11209026 (OR = 2.25 [1.13–4.51]) and 6q21 rs7746082 (OR = 1.60 [1.10–2.34] and negatively associated with the risk alleles of IRGM rs13361189 (OR = 0.29 [0.11–0.74]) and DEFB1 rs11362 (OR = 0.50 [0.30–0.80]). The ATG16L1 and IRGM variants were associated with a non-inflammatory behaviour (OR = 1.75 [1.22–2.53] and OR = 1.50 [1.04–2.16] respectively). However, these associations lost significance after multiple testing corrections. The protective effect of the IRGM risk allele on colonic lesions was the only association replicated in the second cohort (p = 0.03). Conclusions It is not recommended to genotype the studied polymorphisms in routine practice.

Anal carcinoma in HIV-infected patients in the era of antiretroviral therapy: a comparative study.

BACKGROUND: Before the introduction of highly active antiretroviral therapy, prognosis of anal squamous-cell carcinoma was worse when patients were infected with HIV. Since then, contradictory results have been reported. OBJECTIVE: To compare the results of chemoradiotherapy in HIV-infected and uninfected patients with anal carcinoma. DESIGN: Retrospective analysis of medical records. SETTING: Tertiary care center in France. PATIENTS: Patients with invasive anal carcinoma treated from 2001 through 2006. INTERVENTIONS: Chemoradiotherapy included 60 Gy pelvic irradiation and cisplatin-based chemotherapy. Surgery was performed for local failures or complications. MAIN OUTCOME MEASURES: Tolerance for chemoradiotherapy, tumor control, and survival were evaluated. RESULTS: A total of 46 patients (20 HIV-infected and 26 uninfected) were treated for nonmetastatic anal carcinoma. Median follow-up was 32.5 (range, 7–84) months. HIV-infected patients were more likely to be men (95% vs 23%, P < .001) and were younger (median age, 46 vs 62 years, P < .001) than uninfected patients. The viral load was less than 200 copies/mL in 15 (75%) of the HIV-infected patients. The duration of chemoradiotherapy was longer in HIV-infected than in uninfected patients (median, 103 vs 84 days, P = .027). Chemoradiotherapy failed to achieve local control in 10 (50%) HIV-infected and in 6 (23%) uninfected patients (P = .057). In HIV-infected patients, failure rates were higher in patients who required prolonged chemoradiotherapy than in those who received treatment as scheduled (7/11, 64% vs 1/7, 14%; P = .039). During follow-up, 7 (35%) of the HIV-infected and 3 (12%) of the uninfected patients died, all from anal carcinoma. The 5-year overall survival rate was 39% for HIV-infected and 84% for uninfected patients (P = .026); 5-year disease-free survival was 37% in HIV-infected and 75% in uninfected patients (P = .06). LIMITATIONS: Retrospective design, lack of data regarding precise toxicity grading, and use of cisplatin-based chemoradiotherapy. CONCLUSIONS: Even in the era of highly active antiretroviral therapy, HIV-infected patients with anal squamous-cell carcinoma show impaired tolerance to chemoradiotherapy, have a lower survival rate, and may have a higher rate of local failure compared with uninfected patients.

Exacerbation of Crohn's colitis with severe colonic hemorrhage in a patient on rofecoxib

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Multidrug resistance gene-1 polymorphisms and resistance to cyclosporine a in patients with steroid resistant ulcerative colitis

Background: Cyclosporine A (CsA) is inconstantly effective in inducing remission in acute attacks of ulcerative colitis (UC) not responding to steroids. This study aimed to establish whether multidrug resistance gene (MDR)1 polymorphisms would be associated with CsA failure. Patients and Methods: The distribution of the different genotypes of single nucleotide polymorphisms (SNP) G2677T/A and C3435T of MDR1 exons 21 and 26, respectively, was studied in 154 patients (mean age, 44 yr) who had received CsA to treat severe attacks of steroid resistant UC in 11 centers in France and Belgium. Patients were classified as CsA failure (n = 50) when they needed colectomy within 30 days after CsA initiation. The SNPs were detected by use of a 5′ nuclease allelic discrimination assay. Results: There was a significant association between the G2677T/A polymorphism distribution (exon 21) and the risk for CsA failure (P = 0.0001). The TT genotype of exon 21 was significantly associated with the risk compared with the two other genotypes (odds ratio, 3.77; 95% confidence interval, 1.42–9.97, P = 0.007). There was no significant association between the genotype C3435T distribution (exon 26) and the risk of CsA failure (P = 0.23). Conclusion: The TT genotype of exon 21 MDR1 polymorphisms is associated with a higher risk of CsA failure in patients with steroid resistant UC. Further studies should be performed to establish whether other treatments could be more efficient to avoid surgery in this subset of patients.