Easy clip to treat anal fistula tracts: a word of caution.

BACKGROUND AND AIMS: Closing the internal opening by a clip ovesco has been recently proposed for healing the fistula tract, but, to date, data on benefit are poorly analyzed. The aim was to report a preliminary multicenter experience. MATERIALS AND METHODS: Retrospective study was undertaken in six different French centers: surgical procedure, immediate complications, and follow-up have been collected. RESULTS: Nineteen clips were inserted in 17 patients (M/F, 4/13; median age, 42 years [29-54]) who had an anal fistula: 12 (71%) high fistulas (including 4 rectovaginal fistulas), 5 (29%) lower fistulas (with 3 rectovaginal fistulas), and 6 (35%) Crohn's fistulas. Out of 17 patients, 15 had a seton drainage beforehand. The procedure was easy in 8 (47%) patients and the median operative time was 27.5 min (20-36.5). Postoperative period was painful for 11 (65%) patients. A clip migration was noted in 11 patients (65%) after a median follow-up of 10 days (5.5-49.8). Eleven patients (65%) who failed had reoperation including 10 new drainages within the first month (0.5-5). After a mean follow-up of 4 months (2-7),, closing the tract was observed in 2 patients (12%) following the first insertion of the clip and in another one after a second insertion. CONCLUSION: Treatment of anal fistula by placing a clip on the internal opening is disappointing and deleterious for some patients. A better assessment before dissemination is recommended.

[Risk factors of upper gastrointestinal complications in outpatients on antiplatelet therapy: description and management]. / Facteurs de risque de complications digestives des patients sous antiagrégant plaquettaire suivis en cardiologie de ville : description et prise en charge.

OBJECTIVES: Patients on antiplatelet therapy have a gastrointestinal bleeding risk. It is increased by risk factors. The frequency of those risk factors, the prevalence of upper digestive symptoms and their management in patients on antiplatelet agents is unknown. PATIENTS AND METHODS: We performed an observational multi-centred prospective survey among 560 French cardiologists with private practice. Each cardiologist completed a questionnaire for the first four patients treated with antiplatelet agents in primary or secondary prevention. RESULTS: Among the 2182 patients included, (age = 67 ± 11 years; 74% male), 83% had at least one gastrointestinal bleeding risk factor and 38.9% had a history of upper digestive tract symptom. A history of gastrointestinal bleeding was reported in 3.4% and a history of documented gastro-duodenal ulcer in 5.5%. A proton pump inhibitor was already prescribed in 39% of the patients. At the time of the consultation, upper digestive symptoms were described in 21% of the patients. In those patients with symptoms, 85% had no modification in antiplatelet therapy and 62.7% were prescribed gastro-protective drugs (proton pump inhibitors: 51.8%, H(2)-blockers 3.6% other anti-acid medication: 7.3%). CONCLUSION: Among patients on antiplatelet agents, the prevalence of upper digestive symptoms and risk factors for gastrointestinal bleeding is high. Preventative management needs to be clarified in this population.

Methotrexate for psoriasiform lesions associated with anti-tumour necrosis factor therapy in inflammatory bowel disease.

BACKGROUND: Psoriasiform lesions associated with anti-tumour necrosis factor (TNF) therapy are frequent in patients with inflammatory bowel disease (IBD). While methotrexate is the most frequently used systemic treatment for psoriasis, its efficacy for psoriasiform lesions related to anti-TNF therapy remains unknown. AIMS: To assess the efficacy of methotrexate for psoriasiform lesions associated with anti-TNF therapy refractory to topical therapy in IBD patients. METHODS: The charts of eight patients from the Nancy IBD cohort who developed psoriasiform lesions on anti-TNF therapy were reviewed. Clinical response was defined as a decrease of more than 50% in the lesions covering surface. All patients were followed up by the same experienced dermatologist. RESULTS: Eight women (seven Crohn's disease) were followed up for a median duration of 29 months (range, 20-45). Of the eight patients receiving methotrexate, three were primary responders without discontinuation of anti-TNF agents. Only one patient had a sustained response at final follow-up and was able to continue both methotrexate and anti-TNF therapy. Of the two other primary responders, one patient had to discontinue anti-TNF because of severe psoriasiform lesions, whereas the other one continued anti-TNF therapy despite persistent skin lesions at final follow-up. Among the five primary nonresponders, four patients had to stop anti-TNF treatment due to disabling skin lesions. CONCLUSION: Methotrexate does not appear effective in treating psoriasiform lesions associated with anti-TNF therapy refractory to topical therapy in IBD.

Additional benefit of procalcitonin to C-reactive protein to assess disease activity and severity in Crohn's disease.

BACKGROUND: Serum procalcitonin level may reflect non-infectious inflammation. AIM: To assess the correlation of serum procalcitonin level with clinical, biological, endoscopic and radiological markers of disease activity in inflammatory bowel diseases (IBD), and to evaluate the additional diagnostic benefit of measuring serum procalcitonin level to that of C-reactive protein (CRP) for disease activity appraisal. METHODS: We performed a prospective observational study. Spearman's rank correlation and receiver operating characteristic analysis were used to evaluate correlation and diagnostic accuracy respectively. RESULTS: In Crohn's disease (CD) (n = 30), serum procalcitonin level was strongly correlated with clinical, biological, endoscopic and radiological disease activity markers. In CD, the serum procalcitonin level >0.14 µg/L demonstrated a high accuracy for detecting severe disease (Sensitivity = 100%; Specificity = 96%; AUROC = 0.963; P = 0.0001). The diagnostic accuracy of the 'serum procalcitonin level-CRP strategy' (CRP >5 mg/L and serum procalcitonin level >0.05 µg/L) was significantly superior to that of CRP alone for diagnosing severe CD (AUROC = 0.783 vs. 0.674; P = 0.01). In ulcerative colitis (UC) (n = 27), serum procalcitonin level was correlated with CRP and with endoscopic and radiological disease activity markers. CONCLUSIONS: In CD, the serum procalcitonin level was correlated with all disease activity markers and a cut-off of 0.14 µg/L could distinguish severe forms of the disease. The 'serum procalcitonin level-CRP strategy' was superior to CRP alone for diagnosing active or severe CD.

Infliximab for refractory ulcerative proctitis.

BACKGROUND: Efficacy of infliximab in treating ulcerative proctitis remains unknown. AIM: To evaluate the clinical, biological and endoscopic efficacy of infliximab therapy in refractory proctitis. METHODS: The charts of 420 patients treated with infliximab for ulcerative colitis were reviewed. Thirteen patients were treated with infliximab for refractory ulcerative proctitis in six referral centres between 2005 and 2009. RESULTS: Following infliximab therapy induction, 9/13 patients (69%) had a complete response (defined as absence of diarrhoea and blood), 2/13 (15%) had a partial response and 2/13 (15%) were primary nonresponders. The median follow-up was 17 months (range, 3-48). Among the 11 patients with clinical response after infliximab induction therapy, 9 (82%) patients maintained response at last follow-up. Disappearance of rectal disorders was observed in all nine patients who maintained clinical response at last follow-up. Following infliximab induction therapy, the mean CRP level fell from 12.8 mg/L to 4.7 mg/L. Endoscopic evaluation was performed before and after infliximab in seven patients, showing an improvement in mucosal lesions in four patients, persistent mild endoscopic activity in two patients and no improvement in one patient. One patient underwent proctocolectomy. CONCLUSION: Infliximab therapy seems to be effective in inducing and maintaining a clinical response in refractory ulcerative proctitis.

The efficacy and safety of a third anti-TNF monoclonal antibody in Crohn's disease after failure of two other anti-TNF antibodies.

BACKGROUND: Adalimumab (ADA) and certolizumab pegol (CZP) have demonstrated efficacy in Crohn's disease (CD) patients previously treated with infliximab (IFX). AIM: To assess the efficacy and tolerability of a third anti-TNF in CD after failure of and/or intolerance to two different anti-TNF antibodies. METHODS: Crohn's disease patients who received ADA or CZP after loss of response and/or intolerance to two anti-TNF agent were included in this retrospective study. Data were collected using a standardized questionnaire. Clinical response, duration, safety and reasons for discontinuation were assessed. RESULTS: Sixty-seven patients treated with CZP (n = 40) or ADA (n = 27) were included. A clinical response was observed in 41 (61%) at week 6 and 34 patients (51%) at week 20. The probability of remaining under treatment at 3 months, 6 months and 9 months was 68%, 60% and 45%, respectively. At the end of follow-up, the third anti-TNF had been stopped in 36 patients for intolerance (n = 13), or failure (n = 23). Two deaths were observed. CONCLUSIONS: The treatment with a third anti-TNF (CZP or ADA) agent of CD patients, who have experienced loss of response and/or intolerance to two anti-TNF antibodies, has favourable short-term and long-term efficacy. It is an option to be considered in patients with no other therapeutic options.

Inflammatory bowel disease and hepatitis B and C.

The risk of viral B and C hepatitis has long been considered to be increased in patients with inflammatory bowel disease (IBD). Blood transfusion and surgery have been identified as the two main risk factors, suggesting nosocomial transmission could be involved. However, recent epidemiologic surveys have found that prevalence in IBD patients is similar to or even lower than that in the general population. Part of the explanation of these recent data may lie in the application of protective measures against viral infection (hepatitis B virus [HBV] vaccination and hepatitis C virus [HCV]-free blood transfusions). Sometimes fatal viral reactivations have been reported in patients on immunosuppressive therapy. Two periods can be distinguished: a) during therapy, a rise in viremia associated with a decrease of immune-mediated hepatic lesions; b) after cessation of therapy, an immune rebound with a destruction of virus-infected hepatocytes. For HBV, preemptive strategy consisting of an antiviral analog is efficient in chronic HBs antigen carriers. For HCV, the impact of immunosuppressive drugs on the natural history is unclear. Most studies report improved comfort although no biopsies were performed before and after immunosuppressive treatment. Physicians managing IBD patients should be aware of the need for screening and institute preventive measures against B and C hepatitis.

Tumour necrosis factor antagonists and inflammatory bowel diseases: a national practice survey.

BACKGROUND: Although the use of tumour necrosis factor (TNF) antagonists is increasingly codified, several unresolved issues remain. AIM: To conduct a French national survey on TNF antagonists use in inflammatory bowel disease (IBD). METHODS: A postal questionnaire was sent to all French gastroenterologists among whom 450 prescribe TNF antagonists for IBD. Only anti-TNF prescribers were invited to respond. RESULTS: A total of 333 questionnaires could be analysed, which represented a rate of survey completeness of 74%. Scheduled maintenance infliximab treatment was prescribed by 92% of gastroenterologists. In Crohn's disease in remission after 1 year of TNF antagonists, 77.4% of physicians continued treatment. In luminal Crohn's disease, 97% of hospital practitioners introduced infliximab as first-line anti-TNF therapy vs. 78% of physicians with nonhospital activity (P = 0.002); only 22.5% of gastroenterologists opted for adalimumab as first-line therapy. In Crohn's disease in remission after 6 months of azathioprine in combination with infliximab, 63.8% of practitioners discontinued azathioprine. In case of pregnancy during anti-TNF treatment, 35.1% of physicians discontinued therapy at the time of conception and did not administer anti-TNF therapy during pregnancy. CONCLUSIONS: The attitudes of French gastroenterologists generally reflect the recommendations regarding the use of anti-TNF and concomitant immunosuppressive therapy in IBD.

[Anorectal disease: past, present, future]. / Proctologie: de la statique à la << dynamite >>.

Over the last decade, therapeutic approaches of anorectal disorders have been profoundly modified by new drugs, new procedures and functional considerations. In fact, the primary goals of these procedures emphasize minimal invasive approaches. Less functional postoperative complaints are often preferred over a radical efficacy. As compared to haemorrhoidectomy, haemorrhoidopexy procedure is today advocated to reduce postoperative care and complaints. As compared to lateral sphincterotomy, nitrates and botulinum toxin represent a second line therapy of chronic anal fissure to avoid faecal incontinence. As compared to fistulotmy, both glue and plug may be used to treat a high tract fistulae for the same reasons.

Long-term outcome of non-fistulizing (ulcers, stricture) perianal Crohn's disease in patients treated with infliximab.

BACKGROUND: In Crohn's disease, anal ulcers and stricture can be disabling. AIM: To evaluate long-term outcome of non-fistulizing perianal Crohn's disease under infliximab. METHODS: The medical records of 99 patients with non-fistulizing perianal Crohn's disease at first infliximab infusion were reviewed. Complete responses (ulcer healing or stricture regression) after induction infliximab therapy and at the maximal follow-up were assessed. RESULTS: Ninety-four patients (94.9%) had ulcers, 22 (22.2%) had stricture and 31 (31.3%) had draining perianal fistulas at first infliximab infusion. After infliximab induction therapy, 40/94 (42.5%) patients with ulcers, 4/22 (18.2%) with stricture and 10/31 (32.2%) with fistulas had a complete response. Eight patients were lost to follow-up. After a median follow-up of 175 weeks (range, 13-459), complete response rates for ulcers, stricture and fistulas were 72.3% (68/94), 54.5% (12/22) and 54.8% (20/31) respectively. Long-term response for cavitating ulcer was positively associated with concomitant immunosuppressant use (P = 0.017) and older age (P = 0.049). Among the 12 patients with complete regression of stricture, 6 patients also had anal dilatation. Complete response was associated with perianal pain relief and disappearance of soiling. Three patients with ulcers developed an anal abscess. CONCLUSIONS: Infliximab therapy may be effective in inducing and maintaining response for ulcers.

TNF antagonists in the treatment of inflammatory bowel disease: results of a survey of gastroenterologists in the French region of Lorraine.

BACKGROUND AND OBJECTIVE: We conducted a survey of nonacademic gastroenterologists to evaluate the use of tumor necrosis factor (TNF) antagonists in inflammatory bowel disease (IBD). METHODS: A total of 100 questionnaires were sent by mail to a representative sample of gastroenterologists practicing in the French region of Lorraine. RESULTS: Forty-six practitioners responded to the survey, of whom 95.5% prescribed scheduled infliximab treatment. After 6 months of infliximab in combination with azathioprine, 55% then prescribed infliximab as monotherapy. A complete pretherapeutic assessment was performed by only one fourth of the gastroenterologists. When the PPD skin test measured 7 mm, nearly half of the physicians introduced anti-TNF therapy without chemoprophylaxis (versus only 2.4% when the diameter was 11 mm). In the event of quiescent Crohn's disease (CD) after 1 year of anti-TNF treatment, 35.7% stopped the drug. In refractory CD, 72.7% prescribed infliximab as the first-line therapy (versus 27.3% who used adalimumab). In patients with urinary tract infection, 44.2% initiated antibiotics and delayed anti-TNF treatment, while 46.5% initiated anti-TNF therapy along with antibiotic therapy. CONCLUSION: This study is the first survey upon the use of TNF antagonists by nonacademic gastroenterologists, and the findings suggest that physicians using these drugs may require more information about the pretherapeutic assessment and management of the infectious risk.

Adalimumab for Crohn's disease with intolerance or lost response to infliximab: a 3-year single-centre experience.

BACKGROUND: Adalimumab is effective in inducing clinical remission in patients with Crohn's disease who lost response or became intolerant to infliximab. AIM: To evaluate long-term efficacy and safety of adalimumab as a second line therapy in luminal and fistulizing Crohn's disease. METHODS: We report our single-centre experience in 53 patients. We evaluated maintenance of clinical response defined as the absence of adverse events leading to drug withdrawal, no major abdominal surgery and no loss of clinical response in initial responders. Major abdominal surgery, steroid sparing, complete fistula closure and safety were also assessed. RESULTS: The probability of maintaining clinical response was 77.2%, 67.8% and 50.8% at 26, 52 and 130 weeks respectively. The probability of remaining major abdominal surgery-free was 82.3% at 26, 52 and 130 weeks. Complete fistula closure occurred in six of 10 patients, and eight of 10 patients were able to taper steroid therapy. Adverse events occurred in 31 patients (58.5%) leading to adalimumab withdrawal in nine patients (17%). CONCLUSION: Adalimumab therapy may be effective in the long term in both luminal and fistulizing Crohn's disease in infliximab-failure patients, half of patients maintaining clinical response and potentially avoiding major abdominal surgery in 80% of cases.

[Helminths and inflammatory bowel diseases]. / Helminthes et maladies inflammatoires chroniques intestinales.

The current etiologic model of inflammatory bowel diseases proposes a genetically predisposed host responding to a variety of environmental triggers by exhibiting an abnormal immune response to normal luminal flora. Crohn's disease is common in highly industrialized western countries where helminths are rare and uncommon in less developed areas of the world where most people carry worms. From this observation grew the hygiene hypothesis, which states that our failure to be exposed to previously common infectious agents alters the immune repertoire established in childhood. Helminths diminish immune responsiveness in naturally colonised humans and reduce inflammation in experimental colitis. Crohn's disease involves over reactive T-helper (Th1) pathways, and helminths blunt Th1 responses, inducing production of Th2 cytokines. Helminths also induce regulatory T cells to maintain host mucosal homeostasis. Thus, there is an immunological basis to expect that exposure to helminths such as Trichuris suis will prove beneficial in Crohn's disease. Exposure to helminths may be effective in treating inflammatory bowel diseases and was well tolerated, according to the results of few studies. Its long-term safety remains unknown.

Long-term outcome of adalimumab therapy for ulcerative colitis with intolerance or lost response to infliximab: a single-centre experience.

BACKGROUND: Adalimumab may be effective in inducing remission in patients with mild-to-moderate ulcerative colitis who had secondary failure to infliximab. AIM: To evaluate long-term efficacy and safety of adalimumab in patients with ulcerative colitis who previously responded to infliximab, and then lost response or became intolerant. METHODS: We report our single-centre experience in 13 patients. The patients received a loading dose of 160 mg of adalimumab subcutaneously in week 0, followed by 80 mg at week 2 and then 40 mg every other week starting at week 4. The primary efficacy measure was the proportion of patients on adalimumab therapy during the study. RESULTS: Median duration of follow-up was 42 weeks (range, 10-100). The mean number of adalimumab infusions was 21 (range, 5-50). The probability of maintaining adalimumab was 92.3%, 84.6%, 60.6% and 32.5% at 1, 3, 6 and 23 months respectively. Six of 13 patients (46.2%) underwent colectomy during the study. No serious toxicities occurred in the study. CONCLUSION: Adalimumab is well-tolerated and may be effective in maintaining clinical remission in a subgroup of patients with ulcerative colitis and lost response or intolerance to infliximab, potentially avoiding colectomy in about half of the patients.

Interaction of ribavirin with azathioprine metabolism potentially induces myelosuppression.

BACKGROUND: The interaction of ribavirin, an inosine monophosphate dehydrogenase inhibitor, with azathioprine metabolism, potentially leading to myelotoxicity, remains unexplored. AIM: To underline the interaction of ribavirin, an inosine monophosphate dehydrogenase inhibitor, with azathioprine metabolism, potentially leading to myelotoxicity. METHODS: The medical records of eight patients who developed severe pancytopenia following concomitant use of azathioprine and ribavirin were retrospectively reviewed. RESULTS: Bone marrow suppression reached nadir after a mean interval of 4.6 +/- 1.6 weeks following HCV therapy initiation in seven patients. At the time of pancytopenia, the mean platelet count was 69.75 +/- 82.8 x 10(-3)/mm(3), mean haemoglobin level 7.75 +/- 1.3 g/dL and mean neutrophil count 0.45 +/- 0.26 x 10(-3)/mm(3). All patients had normal thiopurine methyltransferase genotype. In two patients, a prospective monitoring of azathioprine metabolites was available. Myelotoxicity was accompanied by elevated total methylated metabolite levels (16,500 and 15,000 pmol/8 x 10(8) erythrocytes) with a concomitant decrease in 6-tioguanine nucleotide levels; 1 month after azathioprine, pegylated interferon alfa and ribavirin were discontinued and full blood count returned to normal in both patients. No haematological toxicity occurred after the reintroduction of peginterferon plus ribarivin or azathioprine alone in eight patients. CONCLUSION: Collectively, the benefit/risk ratio favours avoidance of inosine monophosphate dehydrogenase inhibitors in purine analogue-treated patients with normal thiopurine methyltransferase activity, a situation frequently encountered in clinical practice.

Adalimumab maintenance therapy for Crohn's disease with intolerance or lost response to infliximab: an open-label study.

BACKGROUND: Adalimumab is effective in inducing remission in patients with active Crohn's disease who had secondary failure to infliximab therapy. AIM: To evaluate the efficacy and safety of adalimumab maintenance therapy in Crohn's disease patients who previously responded to infliximab and then lost response or became intolerant. METHODS: Twenty-four patients with Crohn's disease were enrolled in a 52-week open-label trial. The patients received a loading dose of adalimumab 80-mg at week 0, and then 40 mg every other week starting at week 2. The primary efficacy measure was clinical remission defined as Crohn's Disease Activity Index score < 150 at week 52. RESULTS: Five patients lost response to adalimumab. None of the patients experienced intolerance to adalimumab. Clinical remission rates were higher at weeks 4 (16/24, 67%) and 52 (14/24, 58%) compared with baseline (8/24, 35%) (P=0.043 at week 52). This was accompanied by a decrease in mean C-reactive protein concentration from 31.8 mg/mL at baseline to 9.7 mg/mL at week 52, and 3/4 (75%) patients achieved steroid-free remission. No serious toxicities occurred in the study. CONCLUSIONS: Adalimumab is well tolerated and appears to be effective in maintaining clinical remission in patients with Crohn's disease and lost response or intolerance to infliximab.

Treatment of patients with heartburn without endoscopic evaluation: on-demand treatment after effective continuous administration of lansoprazole 15 mg.

BACKGROUND: Relapse is frequent after initial treatment for gastro-oesophageal reflux. An alternative strategy to intermittent or continuous therapy may be on-demand treatment. AIM: To compare the efficacy and safety of on-demand lansoprazole 15 mg and placebo treatment in patients with gastro-oesophageal reflux. METHODS: This was a multicentre, randomized, double-blind study in two parallel groups of patients. In the acute study phase, all included patients (n = 203) were treated with lansoprazole 15 mg (once per day) for 4 weeks. At week 4, asymptomatic patients entered the 6-month, on-demand, follow-up phase and were randomized to receive either lansoprazole 15 mg (once per day) or placebo. RESULTS: A higher percentage of patients in the lansoprazole group completed the 6-month follow-up than in the placebo group [81% vs. 61% (P = 0.003)]. Only 16% of patients in the lansoprazole group discontinued the study for insufficient control of heartburn vs. 28% in the placebo group (P = 0.046). The mean daily intake in patients who completed the study was 1-5 capsules/day in the lansoprazole 15 mg group. CONCLUSIONS: On-demand treatment with lansoprazole 15 mg in symptomatic patients after short-term, continuous treatment is a promising therapeutic alternative to intermittent and continuous treatment to maintain heartburn control in patients with gastro-oesophageal reflux.

The role of acid suppression in patients with endoscopy-negative reflux disease: the effect of treatment with esomeprazole or omeprazole.

BACKGROUND: Patients with endoscopy-negative reflux disease have reflux symptoms, mainly heartburn, but not mucosal breaks characteristic of erosive oesophagitis. Standard-dose proton pump inhibitors can provide symptom relief in endoscopy-negative reflux disease but the effect of greater acid suppression has not been studied. AIM: To test the hypothesis that esomeprazole produces heartburn resolution in a greater proportion of patients with ENRD than omeprazole. METHODS: Three multi-centre randomized, controlled, double-blind, 4-week acute treatment studies were conducted in endoscopy-negative reflux disease patients. In study A (n = 1282), patients received either esomeprazole 40 mg, esomeprazole 20 mg or omeprazole 20 mg daily; in studies B (n = 693) and C (n = 670) patients received either esomeprazole 40 mg or omeprazole 20 mg (B), and esomeprazole 20 mg or omeprazole 20 mg (C), respectively. RESULTS: Resolution of heartburn at 4 weeks (no heartburn symptoms during the last 7 days) was achieved in similar proportions of patients in each treatment arm in study A (esomeprazole 40 mg, 56.7%; esomeprazole 20 mg, 60.5%; omeprazole 20 mg, 58.1%), study B (esomeprazole 40 mg, 70.3%; omeprazole 20 mg, 67.9%) and study C (esomeprazole 20 mg, 61.9%; omeprazole 20 mg, 59.6%). There were no significant differences between treatment groups within each study. CONCLUSIONS: More than 60% of endoscopy-negative reflux disease patients reported heartburn resolution but, after 4 weeks of therapy, these proportions did not differ significantly between treatments.