Ulcerative Colitis: Cosnes J

Johnson GJ, Cosnes J, Mansfield JC. · Department of Gastroenterology, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP, UK. · Aliment Pharmacol Ther. · Pubmed #15813828 links to  free full text

Abstract: This article aims to offer an updated review of the effects of smoking on inflammatory bowel disease, and provide a review of the methods of achieving smoking cessation. A systematic review of Embase and Medline databases was conducted. Smoking causes opposing effects on ulcerative colitis and Crohn's disease. The odds ratio of developing ulcerative colitis for smokers compared with lifetime non-smokers is 0.41. Conversely, smokers with Crohn's disease have a more aggressive disease requiring more therapeutic intervention. Smoking cessation is associated with a 65% reduction in the risk of a relapse as compared with continued smokers, a similar magnitude to that obtained with immunosuppressive therapy. Although difficult to achieve smoking cessation can best be encouraged by accessing appropriate counselling services, nicotine replacement therapy and bupropion. Using a combination of these treatments there is an improved chance of success of up to 20% compared with an unassisted quit attempt. Smoking cessation unequivocally improves the course of Crohn's disease and should be a primary therapeutic aim in smokers with Crohn's disease.

Gambiez L, Cosnes J, Guedon C, Karoui M, Sielezneff I, Zerbib P, Panis Y. · Service de chirurgie digestive et transplantation, Hôpital Claude Huriez, 59034 Lille. · Gastroenterol Clin Biol. · Pubmed #15672572 No free full text.

This publication has no abstract.

Cosnes J. · Service de Gastroentérologie et Nutrition, Hôpital Saint-Antoine, 184 rue du Faubourg Saint-Antoine, 75571 Paris cedex 12, France. · Best Pract Res Clin Gastroenterol. · Pubmed #15157822 No free full text.

Abstract: Current smoking protects against ulcerative colitis and, after onset of the disease, improves its course, decreasing the need for colectomy. However, smoking increases the risk of developing Crohn's disease and worsens its course, increasing the need for steroids, immunosuppressants and reoperations. Smoking cessation aggravates ulcerative colitis and improves Crohn's disease. The effects of smoking are the sum of contradictory effects of various substances, including nicotine and carbon monoxide, and are modulated by gender, genetic background, disease location and activity, cigarette dose and nicotine concentration. Smokers with ulcerative colitis should not be discouraged from stopping smoking but encouraged to stop, to reduce their risk of cardiopulmonary tobacco-related diseases. In Crohn's disease, smoking cessation has become a major therapeutic goal, particularly in young women and in patients with ileal involvement. A large amount of supportive information, use of nicotine-replacement therapies and antidepressants, and individual counselling might aid the patient in quitting.

Gornet JM, Couve S, Hassani Z, Delchier JC, Marteau P, Cosnes J, Bouhnik Y, Dupas JL, Modigliani R, Taillard F, Lemann M. · Department of Gastroenterology, Hôpital Saint-Louis, Paris, France. · Aliment Pharmacol Ther. · Pubmed #12869077 links to  free full text

Abstract: BACKGROUND: The efficacy of infliximab in ulcerative colitis (UC) and indeterminate colitis has been poorly assessed and preliminary results are conflicting. METHODS: The records of 30 patients treated with infliximab for ulcerative colitis (n=19) or indeterminate colitis (n=11) were reviewed. Infliximab was given because of steroid resistance (n=18), dependence (n=5) or intolerance (n=7); five patients had failed on cyclosporin; 19 patients had a severe flare-up. RESULTS: Median duration of follow-up was 10 months. In 28 patients with active disease, the response rate was 75% at day 7, with 43% having a complete remission, and 50% at month 1, with 32% having a complete remission. Among the 22 responders, the probability of relapse was 73% at month 6. The probability of complete remission without steroids, taking into account the re-treatment for relapse (n=11), was 57% (95% confidence interval (CI): 45% to 69%) at month 6. The probability of colectomy was 33% (95% CI: 23% to 43%) at month 12. In indeterminate colitis, response rate was only 50% at day 7 and 30% at month 1. Concomitant use of antimetabolite agents was associated with better results. CONCLUSIONS: Infliximab was able to induce a rapid response in some patients with UC or indeterminate colitis refractory to conventional treatment. Long-term results were less favourable, with frequent relapses, and about one-third of the patients required a colectomy.

Carbonnel F, Gargouri D, Lémann M, Beaugerie L, Cattan S, Cosnes J, Gendre JP. · Service d'Hépatogastroentérologie et Nutrition, Hôpital Rothschild, Paris, France. · Aliment Pharmacol Ther. · Pubmed #10735919 links to  free full text

Abstract: BACKGROUND: Intensive intravenous treatment remains the first line therapy of severe, uncomplicated attacks of ulcerative colitis. AIM: To predict the failure of intensive intravenous treatment by combining clinical and laboratory parameters with endoscopy findings. METHODS: Retrospective study conducted in a tertiary care referral centre. Failure of intensive intravenous treatment was defined as colectomy before day 30, intravenous cyclosporin, or death. Predictive factors of outcome were assessed using univariate and multivariate prognostic analysis. RESULTS: Between January 1990 and May 1997, 85 consecutive patients were treated with intensive intravenous treatment for non-response to oral corticosteroids (n=59) and/or severe attack of ulcerative colitis (n=26). There were 41 successes and 44 failures (including 1 death, 13 cyclosporin and 30 colectomies before day 30). Multivariate prognostic analysis found that the presence of Truelove and Witts' criteria (P=0.018), an attack that had lasted more than 6 weeks (P=0.001), and severe endoscopic lesions (P=0.007) were associated with an increased risk of failure. Patients with severe endoscopic lesions and Truelove and Witts' criteria, or an attack of more than 6 weeks had a failure rate of 85-86%. CONCLUSION: Clinical, laboratory and endoscopic findings can predict the risk of failure of intensive intravenous treatment. A prospective study is required to confirm these results.

Sokol H, Seksik P, Furet JP, Firmesse O, Nion-Larmurier I, Beaugerie L, Cosnes J, Corthier G, Marteau P, Doré J. · UEPSD, INRA, Jouy-en-Josas, France. · Inflamm Bowel Dis. · Pubmed #19235886 No free full text.

Abstract: BACKGROUND: The intestinal microbiota is suspected to play a role in colitis and particularly in inflammatory bowel disease (IBD) pathogenesis. The aim was to compare the fecal microbiota composition of patients with colitis to that of healthy subjects (HS). METHODS: fecal samples from 22 active Crohn's disease (A-CD) patients, 10 CD patients in remission (R-CD), 13 active ulcerative colitis (A-UC) patients, 4 UC patients in remission (R-UC), 8 infectious colitis (IC) patients, and 27 HS were analyzed by quantitative real-time polymerase chain reaction (PCR) targeting the 16S rRNA gene. Bacterial counts were transformed to logarithms (Log(10) CFU) for statistical analysis. RESULTS: Bacteria of the phylum Firmicutes (Clostridium leptum and Clostridium coccoides groups) were less represented in A-IBD patients (9.7; P = 0.004) and IC (9.4; P = 0.02), compared to HS (10.8). Faecalibacterium prausnitzii species (a major representative of the C. leptum group) had lower counts in A-IBD and IC patients compared to HS (8.8 and 8.3 versus 10.4; P = 0.0004 and P = 0.003). The Firmicutes/Bacteroidetes ratio was lower in A-IBD (1.3; P = 0.0001) and IC patients (0.4; P = 0.002). Compared to HS, Bifidobacteria were less represented in A-IBD and IC (7.9 and 7.7 versus 9.2; P = 0.001 and P = 0.01). CONCLUSIONS: The fecal microbiota of patients with IBD differs from that of HS. The phylum Firmicutes and particularly the species F. prausnitzii, are underrepresented in A-IBD patients as well as in IC patients. These bacteria could be crucial to gut homeostasis since lower counts of F. prausnitzii are consistently associated with a reduced protection of the gut mucosa.

Farhi D, Cosnes J, Zizi N, Chosidow O, Seksik P, Beaugerie L, Aractingi S, Khosrotehrani K. · Department of Dermatology, Hôpital Tenon, AP-HP, Paris, France. · Medicine (Baltimore). · Pubmed #18794711 No free full text.

Abstract: Erythema nodosum and pyoderma gangrenosum are the most common cutaneous manifestations in inflammatory bowel diseases (IBD). We conducted the current study to assess the cumulative prevalence of erythema nodosum and pyoderma gangrenosum in patients with IBD and to appraise their association with demographic, clinical, and prognostic factors related to IBD. Between 2000 and 2005, data for all patients with IBD at our gastroenterology department were prospectively and systematically collected using a standardized protocol.Among 2402 patients (1521 diagnosed with Crohn disease [63.3%] and 744 with ulcerative colitis [31.0%]), 140 (5.8%) had at least 1 skin manifestation. The most frequent dermatologic symptoms were erythema nodosum (4.0%) and pyoderma gangrenosum (0.75%). In multivariate analyses, erythema nodosum was significantly and independently associated with a diagnosis of Crohn disease (p < 0.001), female sex (p < 0.001), eye and joint involvement (p < 0.001), and pyoderma gangrenosum (p < 0.0001).Among patients with Crohn disease, erythema nodosum was associated with isolated colonic involvement (p = 0.0001). Pyoderma gangrenosum was significantly and independently associated with black African origin (p = 0.003), familial history of ulcerative colitis (p = 0.0005), uninterrupted pancolitis as the initial location of IBD (p = 0.03), permanent stoma (p = 0.002), eye involvement (p = 0.001), and erythema nodosum (p < 0.0001). It is noteworthy that the association between pyoderma gangrenosum and permanent stoma persisted after exclusion of patients with peristomal pyoderma gangrenosum (p = 0.07).In conclusion, neither erythema nodosum nor pyoderma gangrenosum was significantly associated with the severity criteria in IBD; however, their occurrence may reflect a peculiar phenotype among affected patients.

Cacheux W, Seksik P, Lemann M, Marteau P, Nion-Larmurier I, Afchain P, Daniel F, Beaugerie L, Cosnes J. · Department of Gastroenterology, Assistance Publique des Hôpitaux de Paris (AP-HP), Saint-Antoine Hospital, Paris, France. · Am J Gastroenterol. · Pubmed #18047542 No free full text.

Abstract: OBJECTIVES: Cyclosporine is an effective rescue therapy in steroid-refractory ulcerative colitis (UC) and may avoid immediate colectomy. However, the individual's response to cyclosporine is poorly predictable. The aim of this study was to identify predictive factors of the response to cyclosporine in steroid-refractory UC. METHODS: One hundred thirty-five patients with steroid-refractory UC, admitted consecutively between 1992 and 2004, were included. Data were collected on the first day of the cyclosporine therapy. Colonoscopy was performed within 2 days preceding or following the cyclosporine treatment in 118 patients for assessing the presence of severe endoscopic lesions. RESULTS: The actuarial rate of colectomy was 0.45 at 6 months. Cox analysis in the whole population selected three predictive criteria of colectomy: body temperature >37.5 degrees C (adjusted hazard ratio = 1.94, 95% confidence interval 1.51-2.49), heart rate >90 bpm (1.86, 1.45-2.38), and C-reactive protein (CRP) >45 mg/L (1.70, 1.34-2.16). In the 118 patients who underwent colonoscopy, the presence of severe endoscopic lesions was an independent predictive factor of colectomy (2.38, 1.80-3.14). Colonoscopy was decisive and changed the therapeutic decision in patients with one or two criteria: 71% of the patients with severe endoscopic lesions were colectomized versus 17% of the patients without severe endoscopic lesions (P < 0.001). Finally, the clinical, biological, and endoscopic criteria allowed the classification of the patients into two different groups (80%vs 20% colectomy at 6 months). CONCLUSION: In patients with steroid-refractory UC, the combination of simple criteria is useful to predict the response to cyclosporine. Colonoscopy is crucial in patients with intermediate clinical and biological severity.

Svrcek M, Cosnes J, Beaugerie L, Parc R, Bennis M, Tiret E, Fléjou JF. · AP-HP Hôpital Saint-Antoine, Service d'Anatomie et Cytologie Pathlogiques, Université Paris, Faculté de Médecine Pierre et Marie Curie, Paris, France. · Histopathology. · Pubmed #17394493 No free full text.

Abstract: AIMS: To determine the clinicopathological features of colorectal cancer (CRC) in Crohn's disease (CD). METHODS AND RESULTS: All histological slides from surgical specimens with inflammatory bowel disease-related colorectal neoplasia examined in our hospital between 1990 and 2005 were reviewed. We identified 18 CRCs in 16 patients with CD and compared them with 57 CRCs in 41 patients with ulcerative colitis (UC). We also studied 25 patients with dysplasia without cancer (CD 2, UC 23). When CD and UC were compared, the median age at diagnosis of cancer (CD 52 years, UC 51 years), the frequency of mucinous adenocarcinoma (CD 16.7%, UC 17.5%) and the frequency of dysplasia adjacent to and distal from cancer (CD 56.3 and 37.5%, UC 65.8 and 39%, respectively) were similar. All neoplastic lesions occurred in areas affected by inflammatory bowel disease. CONCLUSIONS: CRC complicating CD and UC shares many clinicopathological features, in particular similar frequencies of dysplasia, both adjacent and distal, with cancer. Thus, surveillance for patients with Crohn's colitis should be similar to that for patients with UC. Consideration should be given to a more extensive UC-like surgical approach instead of segmental resection of the involved area.

Daniel F, Loriot MA, Seksik P, Cosnes J, Gornet JM, Lémann M, Fein F, Vernier-Massouille G, De Vos M, Boureille A, Treton X, Flourié B, Roblin X, Louis E, Zerbib F, Beaune P, Marteau P. · Department of Gastroenterology, Assistance Publique des Hôpitaux de Paris (AP-HP), Hôpital Européen Georges Pompidou, Paris, France. · Inflamm Bowel Dis. · Pubmed #17206635 links to  free full text

Abstract: 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.

Cosnes J, Seksik P, Nion-Larmurier I, Beaugerie L, Gendre JP. · Service de Gastroentérologie et Nutrition, hôpital St-Antoine, 184 rue du Faubourg St-Antoine, 75571 Paris cedex 12, France. · World J Gastroenterol. · Pubmed #16534877 links to  free full text

Abstract: AIM: To determine whether prior appendectomy modifies the phenotype and severity of Crohn's disease. METHODS: Appendectomy status and smoking habits were specified by direct interview in 2838 patients consecutively seen between 1995 and 2004. Occurrence of complications and therapeutic needs were reviewed retrospectively. Additionally, annual disease activity was assessed prospectively between 1995 and 2004 in patients who had not had ileocecal resection and of a matched control group. RESULTS: Compared to 1770 non-appendectomized patients, appendectomized patients more than 5 years before Crohn's disease diagnosis (n=716) were more often females, smokers, with ileal disease. Cox regression showed that prior appendectomy was positively related to the risk of intestinal stricture (adjusted hazard ratio, 1.24; 95% confidence interval, 1.13 to 1.36; P=0.02) and inversely related to the risk of perianal fistulization (adjusted hazard ratio, 0.75; 95% confidence interval, 0.68 to 0.83; P=0.002). No difference was observed between the two groups regarding the therapeutic needs, except for an increased risk of surgery in appendectomized patients, attributable to the increased prevalence of ileal disease. Between 1995 and 2004, Crohn's disease was active during 50% of years in appendectomized patients (1318 out of 2637 patient-years) and 51% in non-appendectomized patients (1454 out of 2841 patient-years; NS). CONCLUSION: Prior appendectomy is associated with a more proximal disease and has an increased risk of stricture and a lesser risk of anal fistulization. However, the severity of the disease is unaffected.

Cosnes J, Nion-Larmurier I, Afchain P, Beaugerie L, Gendre JP. · Hôpital Saint-Antoine, 184 rue du Faubourg St-Antoine, 75571 Paris cedex 12, France. · Clin Gastroenterol Hepatol. · Pubmed #15017631 No free full text.

Abstract: BACKGROUND AND AIMS: The aim of this study was to examine in parallel the effect of smoking on ulcerative colitis and Crohn's colitis and assess the effect of gender on the response of colitis to smoking. METHODS: Medical charts of 1784 adult consecutive patients (978 patients, ulcerative colitis; 118 patients, indeterminate colitis; and 688 patients, Crohn's colitis), whose smoking habits were specified by direct interview, were reviewed. RESULTS: The proportion of ever smokers was 42% in ulcerative colitis, 43% in indeterminate colitis, and 61% in Crohn's colitis. Smoking cessation preceded the onset of colitis in 279 patients with ulcerative colitis or indeterminate colitis (61%) and only 52 patients (12%) with Crohn's colitis. In ulcerative colitis and indeterminate colitis, current smoking delayed mean age at disease onset in men (from 32 to 41 yr; P < 0.001), but not women (from 33 to 33 yr), and decreased the need for immunosuppressants in men (10-yr cumulative risk, 26% +/- 4% in nonsmokers vs. 8% +/- 4% in smokers; P < 0.01), but not significantly in women. Conversely, in Crohn's colitis, current smoking hastened disease onset in women (from 35 to 29 yr; P < 0.001), but not men (from 32 to 31 yr), and increased the need for immunosuppressants in women (10-yr cumulative risk, 48% +/- 5% in nonsmokers vs. 58% +/- 4% in smokers; P < 0.01), but not men. CONCLUSIONS: The dual effects of smoking in colitis, beneficial in ulcerative colitis and harmful in Crohn's colitis, are modulated importantly by gender, with women having more disadvantage than men.

Cosnes J, Carbonnel F, Beaugerie L, Blain A, Reijasse D, Gendre JP. · Service d'Hépatogastroentérologie et Nutrition, hôpital Rothschild, Paris, France. · Gut. · Pubmed #12427780 links to  free full text

Abstract: BACKGROUND: Appendicectomy reduces the risk of having ulcerative colitis. However, its effect on the natural history of ulcerative colitis remains uncertain. AIM: To determine whether appendicectomy reduces the overall severity of ulcerative colitis. PATIENTS AND METHODS: Appendicectomy status and smoking habits were specified by direct interview in 638 patients seen consecutively between 1997 and 2000. Severity of ulcerative colitis was assessed by reviewing therapeutic needs from the onset of colitis. Additionally, the annual incidence of flare up was assessed prospectively between 1997 and 2000 in patients who had not been colectomised. RESULTS: The 10 year risk of colectomy was 16 (7)% in previously appendicectomised patients (n=49) compared with 33 (2)% in non-appendicectomised patients (n=589, p=0.05). Cox regression showed that previous appendicectomy and current smoking were independent factors protecting against colectomy (adjusted hazard ratio and 95% confidence intervals: 0.40 (0.20-0.78) and 0.60 (0.40-0.95), respectively). The respective proportions of appendicectomised and non-appendicectomised patients who required oral steroids and immunosuppressive therapy were not significantly different (67% v 70% and 27% v 19%, respectively). Between 1997 and 2000, ulcerative colitis was active for 48% of the time in appendicectomised patients (47 of 98 patient years) and for 62% of the time in non-appendicectomised patients (631 of 1024 patient years; p<0.01). CONCLUSION: Previous appendicectomy is associated with a less severe course of ulcerative colitis. The beneficial effect of appendicectomy on the risk of colectomy is additive to that of current smoking.

Beaugerie L, Massot N, Carbonnel F, Cattan S, Gendre JP, Cosnes J. · Department of Gastroenterology, Rothschild Hospital, Paris, France. · Am J Gastroenterol. · Pubmed #11467641 No free full text.

Abstract: OBJECTIVES: The incidence and severity of ulcerative colitis (UC) are higher in nonsmokers than in smokers. The natural course of UC in smokers who stop smoking is not known. The aim of this study was to determine the impact of cessation of smoking on the course of UC among the cohort of patients regularly seen at our institution. METHODS: The severity of UC, as judged by the occurrence of flare-ups and the need for systemic steroids, immunosuppressive drugs and colectomy, was determined in 32 patients with UC who stopped smoking after the diagnosis of UC. We compared the period after cessation of smoking (7-yr mean follow-up) with the period between the onset of the disease and the cessation of smoking (9-yr mean duration). The course of UC in this group was compared with that of 32 nonsmokers and 32 continuing smokers matched for sex, age, and age at onset. RESULTS: In patients who quit, cessation of smoking was followed by an increase in the rate of years with active disease (p < 0.01), years with hospitalization (p < 0.05) and years with major medical therapy (oral steroids, intravenous steroids, and azathioprine, p < 0.01). After cessation of smoking, the rate of years with immunosuppressive therapy was significantly greater in ex-smokers and nonsmokers than in continuing smokers (p < 0.01). The risk of colectomy in ex-smokers after smoking cessation was similar to that of nonsmokers and continuing smokers. CONCLUSIONS: In smokers with UC who stop smoking, the severity of the disease increases after smoking cessation, with an increase in the disease activity and the need for hospital admission and major medical therapy. In addition, the need for azathioprine therapy becomes similar to that of nonsmokers.