Endoscopic and histological healing with infliximab anti-tumor necrosis factor antibodies in Crohn's disease: A European multicenter trial

BACKGROUND & AIMS: Tumor necrosis factor (TNF) is a pivotal cytokine in intestinal inflammation. Controlled trials using a chimeric anti-TNF antibody (infliximab) have shown its efficacy in refractory Crohn's disease. METHODS: Endoscopic and histological response to infliximab was investigated in a multicenter, randomized, double-blind, and placebo-controlled trial including 30 patients with active Crohn's disease undergoing ileocolonoscopy before and 4 weeks after intravenous administration of 5, 10, or 20 mg/kg of infliximab or placebo as a single infusion. Lesions were scored by means of the validated Crohn's Disease Endoscopic Index of Severity (CDEIS). Endoscopic biopsy specimens were taken during both procedures from 9 of 30 patients and scored by a single gastrointestinal pathologist. RESULTS: CDEIS scores decreased significantly in most infliximab-treated patients without an apparent dose response. No endoscopic improvement was observed in the placebo group. The changes in CDEIS correlated highly with those of the Crohn's Disease Activity Index. At a histological level, disappearance of the inflammatory infiltrate was observed in infliximab-treated patients but not in placebo-treated ones; however, architectural changes persisted in most patients. Strictures developed in several patients. CONCLUSIONS: Clinical improvement after infliximab therapy in active Crohn's disease is accompanied by significant healing of endoscopic lesions and disappearance of the mucosal inflammatory infiltrate.     

Rifabutin and ethambutol do not help recurrent Crohn's disease in the neoterminal ileum.

We tested the efficacy of rifabutin and ethambutol in combination in healing severe recurrent Crohn's disease in the neoterminal ileum. Sixteen patients who had undergone an ileal resection with partial colectomy and ileocolonic anastomosis and who had severe recurrent lesions in the neoterminal ileum at baseline ileocolonoscopy were included in the study. The patients received rifabutin in a dose of 5 mg/kg together with ethambutol, 20 mg/kg. Ten patients were treated for 6 months; six patients dropped out because of adverse events. As no effect was observed after 6 months, five patients completed a 12-month therapy course. Follow-up ileocolonoscopy was performed at 3, 6, and 12 months. In none of the 10 patients who completed the 6-month trial and in none of the five patients who completed 12 months of therapy was endoscopic improvement of the lesions observed. In four patients the disease was clinically progressive, and two patients underwent a reresection after 6 and 8 months, respectively. This study shows that long-term therapy with rifabutin and ethambutol does not heal Crohn's disease in the neoterminal ileum and does not prevent recurrence of symptoms and complications.     

Infliximab heals intestinal inflammatory lesions and restores growth in children with Crohn’s disease

BACKGROUND: Infliximab has recently emerged as an efficacious agent for patients with severe Crohn's disease. There are only few studies on the use of infliximab in children with Crohn's disease: most of them are retrospective and deal only with the clinical response to the drug. AIM: We aimed at assessing the efficacy of infliximab in children and adolescents with severe Crohn's disease recruited consecutively and followed up prospectively at a single centre. Clinical response, intestinal inflammation and growth pattern were evaluated. PATIENTS: Eighteen patients entered into the trial (median age: 13 years, range: 6-18). They were referred because of severe symptoms with unsatisfactory response to conventional drugs. METHODS: All patients received a baseline schedule of three intravenous infusions of infliximab (0, 2 and 6 weeks), 5 mg/kg. Paediatric Crohn's Disease Activity Index, nutritional and activity serum variables, and ileocolonoscopy (with histology) were evaluated before and 8 weeks after beginning the therapy. All patients had long-term administration of azathioprine (2 mg/kg per day). After the baseline schedule, eight patients had a retreatment infusion of infliximab (5 mg/kg) every 8 weeks. Weight and height Z scores were measured before starting the baseline infusion programme and after 6 months. RESULTS: After 8 weeks of therapy, there was a dramatic improvement in Paediatric Crohn's Disease Activity Index, in nutritional and activity blood parameters, as well as in endoscopic and histological scores; 10 patients had a clinical remission (Paediatric Crohn's Disease Activity Index < or = 10), 12 patients had an inflammatory remission (decrease in both endoscopic and histological scores for > or = 50% as compared to baseline values). In all patients corticosteroids were stopped within 4 weeks after beginning infliximab therapy. After 6 months of therapy, Paediatric Crohn's Disease Activity Index was markedly lower than the pre-treatment value; however, it was significantly lower in patients on retreatment than in those who received only three infusions of infliximab. Furthermore, a significant increase in both weight and height Z scores was observed 6 months after beginning of the baseline infusion programme. Moreover, weight and height gain was significantly higher in patients on retreatment rather than in those treated only with three baseline infusions of infliximab. Mild infusion reactions controlled by slowing infusion rate were observed in four patients. No delayed hypersensitivity-like reactions were seen. CONCLUSIONS: In children with severe Crohn's disease, infliximab is a safe and valuable treatment in inducing remission, in healing inflammatory lesions of the gut, as documented by endoscopy and histology, and in promoting growth. Retreatment infusions of infliximab may be suggested in childhood-onset Crohn's disease to maintain remission and reverse growth failure.     

Capsule endoscopy findings in patients with established and suspected small-bowel Crohn's disease: correlation with radiologic, endoscopic, and histologic findings

BACKGROUND: Little is known about the accuracy of capsule endoscopy (CE) in evaluation of small-bowel Crohn's disease. METHODS: Symptomatic eligible patients had ileocolonoscopy and biopsies from the terminal ileum, followed by small-bowel radiologic studies before CE. Endoscopic, radiologic, CE, and histologic findings were compared. Histology (terminal ileum biopsy specimens or a tissue sample after small-bowel resection) served as a criterion standard. RESULTS: Fifty-four patients were enrolled; 15 of the 54 patients were excluded from data analysis (critical small-bowel strictures, 14, identified on radiology; incomplete CE, 1). Data were analyzed for 39 patients. All patients had histologic evaluation of the small bowel. Final diagnosis of active small-intestine Crohn's disease was made in 29/39 patients (74.4%). When calculated, CE yielded a sensitivity and a specificity of 89.6% and 100.0%, respectively, and a positive predictive value and a negative predictive value of 100.0% and 76.9%, respectively, whereas small-bowel series were 27.6%/100.0% and 100.0%/32.3%. CONCLUSIONS: CE is more accurate in detecting small-bowel inflammatory changes suggestive of Crohn's disease than conventional studies. CE, combined with ileocolonoscopy, may be proposed as a first-line investigation of the small intestine in cases of uncomplicated known or suspected Crohn's disease.     

Wireless capsule endoscopy versus ileocolonoscopy for the diagnosis of postoperative recurrence of Crohn's disease: a prospective study

BACKGROUND AND AIMS: Following ileocolonic resection for Crohn's disease (CD), early endoscopic recurrence predicts recurrence of symptoms. The aim of the study was to compare ileocolonoscopy and wireless capsule endoscopy (WCE) for the detection of postoperative recurrence in CD. METHODS: WCE and ileocolonoscopy were performed within six months following surgery in 32 prospectively enrolled patients. Two independent observers interpreted the results of WCE. Recurrence in the neoterminal ileum was defined by a Rutgeerts score>or=1. When observers at WCE did not concur, WCE results were considered as either true negative or true positive and sensitivity and specificity were calculated according to both assumptions. RESULTS: Recurrence occurred in 21 patients (68%) and was detected by ileocolonoscopy in 19 patients. Sensitivity was 90% and specificity 100%. Sensitivity of WCE was 62% and 76% and specificity was 100% and 90%, respectively, depending on assumptions. There was a correlation between the severity of the lesions measured by both methods (p<0.05). Lesions located outside the scope of conventional endoscopy were detected by WCE in two thirds of patients with excellent interobserver agreement (kappa>0.9) for all lesions with the exception of ulceration (kappa=0.7). CONCLUSIONS: The sensitivity of WCE in detecting recurrence in the neoterminal ileum was inferior to that of ileocolonoscopy. In contrast, WCE detected lesions outside the scope of ileocolonoscopy in more than two thirds of patients. Additional follow up studies are needed to assess the clinical relevance of such lesions. At the present time, it seems that WCE cannot systematically replace ileocolonoscopy in the regular management of patients after surgery.     

A report on efficacy and safety of azathioprine in a group of inflammatory bowel disease patients in northwest Greece

BACKGROUND/AIMS: Inflammatory bowel disease has a variable severity and in a group of patients a second-line treatment with immunosuppressive agents, such as azathioprine is required. The aim of the present study was to determine the efficacy and safety of long-term azathioprine treatment in inflammatory bowel disease patients unresponsive to steroids. METHODOLOGY: We investigated the efficacy of azathioprine in controlling the disease relapse (in combination with other drugs) in 29 patients with inflammatory bowel disease (16 with ulcerative colitis and 13 with Crohn's disease). Patients, who were started on azathioprine in combination with steroids, were those who were resistant to steroids. After controlling the acute phase, steroids were discontinued or reduced in very low doses (up to 4 mg methylprednisone per day) and azathioprine was administered in combination with mesalamine for a period of 12-48 months. RESULTS: Azathioprine (in combination with 5-ASA products and steroids) succeeded in controlling the acute relapse in 24 of 29 patients [82.75%, 15/16 (93.7%) with ulcerative colitis and 9/13 (69.2%) with Crohn's disease]. Of the patients who achieved remission, this was maintained for 1 year at least. Only one case of pancreatitis and one with vomiting and diarrhea were noted a few months after the initiation of therapy and azathioprine was discontinued. CONCLUSIONS: Azathioprine is an effective agent which controls acute relapse of inflammatory bowel disease in many cases in combination with other drugs. Long-term remission can be achieved. Side effects are uncommon.     

Natural course of Crohn's disease after ileocolic resection: endoscopically visualised ileal ulcers preceding symptoms.

Forty two Crohn's disease patients were followed up after ileocolic resection with regard to symptoms and endoscopic appearance of the ileocolic anastomosis. Twenty eight patients resected because of colonic neoplasm served as controls. In all the Crohn's disease patients the ileal resection margin was disease free macroscopically at operation. In addition, intraoperative ileoscopy was performed in 13 and no sign of residual inflammation in the neoterminal ileum was seen. Endoscopy soon after surgery often showed preanastomotic ileal ulceration before symptoms appeared, whereas no anastomotic lesions were observed in the controls. Thus, 22 of 30 Crohn's disease patients examined had ulceration of the anastomotic area after three months, but only 10 had developed symptoms indicating relapse (73 v 33%). Corresponding figures in the 30 patients examined after one year were 93 v 37%, and in 14 patients after three years they were 100 and 86% respectively. The inflammatory lesions in all cases were preanastomotic, in the neoterminal ileum, and showed time related progression from aphthae to larger ulcers and stricture. The study suggests that endoscopically observed inflammatory lesions that appear soon after ileocolic resection for Crohn's disease signify new inflammation and not residual, persistent disease or incomplete anastomotic healing. The data further suggest that despite clinical remission after apparently radical intestinal resection, the bowel is permanently inflamed in Crohn's disease.     

Impacts of long-term enteral nutrition on clinical and endoscopic disease activities and mucosal cytokines during remission in patients with Crohn's disease: a prospective study

BACKGROUND: Long-term enteral nutrition may maintain clinical and endoscopic remission in patients with Crohn's disease (CD). The aim of this prospective study was to investigate the impacts of long-term enteral nutrition on clinical and endoscopic disease activities and mucosal tissue cytokines in patients with quiescent CD.METHODS: Forty patients with CD who achieved clinical remission were included. Of these, 20 received continuous elemental diet (Elental) infusion during the nighttime and a low-fat diet during the daytime (EN group) and 20 received neither nutritional therapy nor food restriction (non-EN group). With these regimens, all 40 patients were monitored for 1 year. Further, ileocolonoscopy was performed at entry, at 6 and 12 months, and mucosal biopsies were taken for cytokine assays.RESULTS: On an intention-to-treat basis, 5 patients (25%) in the EN group and 13 (65%) in the non-EN group had a clinical relapse during the 1-year observation (P = 0.03). The mean endoscopic inflammation (EI) scores were not significantly different between the groups at both entry and 6 months, but at 12 months EI scores were significantly higher in the non-EN group than in the EN group (P = 0.04). Additionally, the mucosal tissue interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha levels significantly increased with time in the non-EN group (entry versus 12 months, IL-1beta, P = 0.02; IL-6, P = 0.002; TNF-alpha, P = 0.001). In the EN group these cytokines did not show a significant increase.CONCLUSIONS: Long-term enteral nutrition in patients with quiescent CD has a clear suppressive effect on clinical and endoscopic disease activities and the mucosal inflammatory cytokine levels.     

The diagnostic value of endoscopic terminal ileum biopsies

OBJECTIVES: Biopsy of the terminal ileum (TI) is commonly performed during colonoscopy. The primary utility of this is to diagnose or rule out Crohn's disease in patients with symptoms and/or radiographic findings suggesting this diagnosis. We see many such biopsies in our gastrointestinal pathology service and have been impressed by the subjectively low yield of TI biopsies. Therefore, we studied this to obtain objective data. METHODS: We retrospectively reviewed 414 consecutive patients with terminal ileal biopsies. Histologic parameters evaluated were primarily those changes diagnostic of chronic inflammation or its sequelae. Histologic findings were then compared with the indication(s) and endoscopic findings. RESULTS: The TI was histologically normal in 82% and endoscopically normal in 81% with most endoscopic abnormals having "ileitis" (13%). Known or strongly suspected inflammatory bowel disease was the most common indication (38%) with Crohn's disease accounting for 20% and ulcerative colitis 16% followed by diarrhea (33%), anemia/hematochezia (15%), abdominal pain (6%), and abnormal imaging (5%). Diagnostic yield varied, with indication and endoscopic findings being highest with known suspected Crohn's disease (40%), abnormal imaging (32%), and with endoscopic "ileitis" (84%) or ulcers/erosions (69%). CONCLUSIONS: Diagnostic yield of TI biopsy varied with indication and endoscopic findings. Our study indicates that biopsy is of greatest value in patients undergoing endoscopy for known or strongly suspected Crohn's disease, or with an abnormal imaging study of the TI. Biopsy of endoscopically normal mucosa is unlikely to yield diagnostically useful information, and is not encouraged as routine. However, when "ileitis," ulcers, or erosions are identified, biopsies can be very helpful.     

Nipple valve anastomosis for preventing recurrence of Crohn disease in the neoterminal ileum after ileocolic resection. A prospective pilot study

BACKGROUND: Crohn disease may recur within months in the neoterminal ileum after ileocolic resection. Coloileal reflux may be a factor contributing to recurrence. This study tests the effect of a nipple valve anastomosis in preventing symptomatic and endoscopic neoileal recurrence. METHODS: Between January 1993 and April 1997, 25 patients with Crohn disease were resected and anastomosed with an ileocolic nipple valve. Postoperatively, the patients were given 5-aminosalicylic acid, 0.75-3 g/daily. Regular follow-up included the Harvey-Bradshaw index, ileocolonoscopy, and hydrocolonic sonography. RESULTS: After 1 year 2 of 25 patients (8%) had a symptomatic and 3 of 23 patients (13%) an endoscopic recurrence. There was no symptomatic neoileal recurrence between 1 and 5 years. After 3 years 6 of 13 patients (46%) had an endoscopic recurrence. After 5 years 4 of 11 patients (36%) had a symptomatic recurrence. CONCLUSIONS: These results may suggest that a nipple valve anstomosis delays and perhaps prevents symptomatic recurrence of Crohn disease in the neoterminal ileum.     

Nipple Valve Anastomosis for Preventing Recurrence of Crohn Disease in the Neoterminal Ileum after Ileocolic Resection: A Prospective Pilot Study

Background: Crohn disease may recur within months in the neoterminal ileum after ileocolic resection. Coloileal reflux may be a factor contributing to recurrence. This study tests the effect of a nipple valve anastomosis in preventing symptomatic and endoscopic neoileal recurrence. Methods: Between January 1993 and April 1997, 25 patients with Crohn disease were resected and anastomosed with an ileocolic nipple valve. Postoperatively, the patients were given 5-aminosalicylic acid, 0.75-3 g/daily. Regular follow-up included the Harvey-Bradshaw index, ileocolonoscopy, and hydrocolonic sonography. Results: After 1 year 2 of 25 patients (8%) had a symptomatic and 3 of 23 patients (13%) an endoscopic recurrence. There was no symptomatic neoileal recurrence between 1 and 5 years. After 3 years 6 of 13 patients (46%) had an endoscopic recurrence. After 5 years 4 of 11 patients (36%) had a symptomatic recurrence. Conclusions: These results may suggest that a nipple valve anstomosis delays and perhaps prevents symptomatic recurrence of Crohn disease in the neoterminal ileum.     

Concordance between abdominal scintigraphy using technetium-99m hexamethylpropylene amine oxime-labelled leucocytes and ileocolonoscopy in patients with spondyloarthropathies and without clinical evidence of inflammatory bowel disease.

OBJECTIVE: To study the concordance between abdominal scintigraphy using technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO)-labelled leucocytes (ASTLL) and ileocolonoscopy in patients with spondyloarthropathies (SpA) and without clinical evidence of inflammatory bowel disease (IBD). PATIENTS AND METHODS: Fifteen patients with SpA (European Spondylarthropathy Study Group 1991 criteria) without clinical evidence of IBD were studied prospectively with ASTLL and ileocolonoscopy. RESULTS: This cohort consisted of seven men and eight women aged 31.8+/-10.5 yr (18-47) [mean age +/- S.D. (range)] and with a disease duration of 6.0+/-4.4 yr (0.4-15). ASTLL showed abnormal uptake in four patients. Ileocolonoscopy was abnormal in five patients, showing acute inflammatory lesions in one patient with reactive arthritis, undifferentiated chronic inflammatory lesions in two cases, and features indistinguishable from those of Crohn's disease in two cases. ASTLL was negative in two cases in which ileocolonoscopy showed inflammatory lesions and was positive (terminal ileum) in one case with normal ileocolonoscopy. The concordance between the two examinations was statistically significant (kappa = 0.53; P = 0.008). CONCLUSION: ASTLL may be an interesting tool to detect subclinical gut inflammation in patients with SpA.     

Evaluation of criteria for the activity of Crohn's disease by power Doppler sonography

BACKGROUND/AIM: In recent years, power Doppler sonography has been proposed as a method to assess disease activity in patients with Crohn's disease. The aim of this prospective study was to evaluate diagnostic criteria for power Doppler sonography by blinded comparison with ileocolonoscopy. METHODS: Twenty-two patients with confirmed Crohn's disease were prospectively investigated with B-mode and power Doppler sonography (HDI 5000, Philips Ultrasound) as well as ileocolonoscopy. Sonography was performed within 3 days before endoscopy. All procedures were performed by experienced examiners who were blinded to the clinical data and other results. Defined ultrasound parameters (bowel wall thickness, vascularization pattern) were used to determine a sonographic score of the activity. The degree of activity was scored from 1 (none) to 4 (high) by both ultrasound and ileocolonoscopy (pattern, extent of typical lesions). For each patient all segments of the colon and the terminal ileum were evaluated by both ultrasound and endoscopy. The weighted kappa test was used (StatXact software) for statistical analysis. RESULTS: In total, 126 bowel segments were evaluated by both ultrasound and endoscopy. The study showed a high concordance of power Doppler sonography and ileocolonoscopy (weighted kappa by region: sigmoid colon: 0.81; transverse colon: 0.78; ascending colon: 0.75; cecum: 0.84; terminal ileum: 0.82). Highest concordance was found in the descending colon (weighted kappa: 0.91; 95% CI: 0.83-0.98). CONCLUSIONS: Combination of B-mode and power Doppler sonography has a high accuracy in the determination of disease activity in Crohn's disease when compared to ileocolonoscopy. The diagnostic criteria established in this study can be useful for the evaluation of inflammatory bowel diseases by ultrasound.     

Experience with the use of low-dose methotrexate for inflammatory bowel disease

BACKGROUND: Thiopurine drugs (azathioprine and 6-mercaptopurine) are well established in the treatment of patients with inflammatory bowel disease. However, some patients are intolerant or resistant to thiopurine drugs and their management remains a challenge. Several studies have suggested methotrexate is effective for the induction and maintenance of remission in Crohn's disease. OBJECTIVE: This study was conducted because the overall data on clinical efficacy of methotrexate in inflammatory bowel disease remain limited and there are no data regarding fistulating Crohn's disease or concomitant use of methotrexate with thiopurine drugs in inflammatory bowel disease. METHODS: This study was a retrospective review of medical notes. Clinical response was defined as sustained withdrawal of oral steroids or fistula improvement. New episodes of steroid therapy, infliximab or surgery during the first 6 months were considered as failure to achieve clinical response. RESULTS: Seventy-two patients were studied (66 Crohn's disease and six ulcerative colitis). The mean dose of methotrexate used was 18.2 mg/week. Clinical response was achieved in 22 of 54 patients (40.7%) who completed 6 months of methotrexate treatment. For patients with Crohn's disease, fistula improvement was achieved in eight of 18 (44.4%) patients compared with 11 of 30 (36.7%) receiving methotrexate for steroid withdrawal. Clinical response was achieved in six of 15 patients (40%) treated with methotrexate and azathioprine at the same time compared with 16 of 39 patients (41%) treated with methotrexate alone. CONCLUSIONS: Methotrexate is reasonably effective in clinical practice as a steroid sparing agent in inflammatory bowel disease. The efficacy in fistulating Crohn's disease justifies its use as an immunomodulator in these patients. Combined azathioprine and methotrexate treatment appears to offer no advantage over methotrexate alone.     

Effective maintenance of inflammatory bowel disease remission by azathioprine does not require concurrent 5-aminosalicylate therapy.

OBJECTIVES: To assess the effect of 5-aminosalicylate treatment in conjunction with azathioprine on remission maintenance in inflammatory bowel disease patients. METHOD: This retrospective study was based on a total of 186 inflammatory bowel disease patients (104 with Crohn's disease; 82 with ulcerative colitis), who were stable on azathioprine for a minimum of 6 months. The median duration of follow-up was 4.3 years (range 0.6-15.5 years). Relapse rates per year of follow-up were compared in an azathioprine + 5-aminosalicylate group (n = 103) and an azathioprine alone group (n = 83); survival curves for cumulative remission rates were compared by log-rank test. Discontinuation of azathioprine in both groups was also recorded, as was the incidence of malignancy. RESULTS: In ulcerative colitis patients (n = 82), mean relapse rates for the azathioprine + 5-aminosalicylate group were 0.21/year compared with 0.19/year for the azathioprine alone group (P = not significant). In Crohn's disease patients (n = 104), mean relapse rates for the azathioprine + 5-aminosalicylate group were 0.27/year compared with 0.3/year for the azathioprine alone group (P = not significant). The cumulative remission percentage (determined from time to first relapse) was used in Kaplan-Meier survival analysis and showed no difference between the azathioprine + 5-aminosalicylate group and the azathioprine alone group by log-rank analysis, for ulcerative colitis and Crohn's disease as well as for all inflammatory bowel disease patients. Concurrent use of 5-aminosalicylates was no more frequent in patients who discontinued azathioprine due to adverse events. The only malignancy recorded was Waldenstr?m's macroglobulinaemia after 7 years of azathioprine therapy. CONCLUSION: Concurrent use of 5-aminosalicylate drugs did not reduce the relapse rates of inflammatory bowel disease patients who were established on azathioprine therapy. The use of 5-aminosalicylate drugs did not lead to any increase in discontinuation of azathioprine due to adverse events.     

Efficacy and safety of azathioprine maintenance therapy in a group of Crohn's disease patients in China.

OBJECTIVE: To evaluate the efficacy and the safety of long-term azathioprine maintenance therapy in a group of Chinese patients with Crohn's disease. METHODS: The efficacy of azathioprine (2.0 mg/kg/day) in controlling the disease relapse in 13 patients with Crohn's disease following clinical remission by prednisone or surgery were investigated. The Crohn's disease activity index (CDAI) and the Harvey-Bradshaw index, the reduction of steroid dosage and side-effects for an average of 18 months follow up were analyzed. RESULTS: Azathioprine was effective in controlling the disease relapse in 10 (by CDAI scores) or 11 (by Harvey -Bradshaw index) of 13 patients (76.9% and 84.6%, respectively) for at least 6 months. Azathioprine was not discontinued in a patient who experienced a temporary and mild elevation of aminotransferases 14 months after the initiation of therapy. However one patient who was co-administered with azathioprine and mesalamine (Pentasa) developed an episode of bone marrow suppression that ultimately required the withdrawal of both medications. CONCLUSION: Azathioprine is an effective agent which controls the relapse of Crohn's disease in most patients. Long-term remission can be achieved. Side-effects, including severe leukopenia, myelo-suppression and the mild elevation of hepatic enzymes, may occur in a small number of patients.     

Azathioprine and 6-mercaptopurine for the treatment of perianal Crohn's disease in children

Numerous adult studies show a 30-65% response rate to azathioprine (AZA) or 6-mercaptopurine (6-MP) for significant perianal Crohn's disease. The aim of this study was to evaluate whether these drugs healed pediatric perianal Crohn's disease. Records of pediatric Crohn's patients were retrospectively reviewed for significant perianal disease treated with AZA or 6-MP for > or =6 months. The patient's perianal disease was reviewed and evaluated for fistulas, drainage, induration, and tenderness. In addition, the patients were given a score using the Irvine Perianal Disease Activity Index (PDAI). Patients were retrospectively scored upon initiation of treatment and after six months of therapy. Possible scores ranged from 0-20. Twenty patients met the study criteria. Five patients were considered treatment failures. One patient required a colostomy after 1.5 months of therapy, one developed pancreatitis, and three were noncompliant with therapy. Of the remaining 15 patients who were treated for > or =6 months, 67% had an improvement in drainage, 73% in tenderness, 60% in induration, and 40% in fistula closure. The mean Irvine PDAI was 7.67 +/- 2.19 initially and 4.40 +/- 1.72 after six months of therapy. The improvement was statistically significant (p < 0.001). AZA and 6-MP are effective treatments for healing significant perianal Crohn's disease in pediatrics.     

Consensus of the Chronic Inflammatory Bowl Disease Study Group of the Austrian Society of Gastroenterology and Hepatology on the topic of "diagnosis and therapy of chronic inflammatory bowel diseases in adolescence"

Although up to 20% of patients with Crohn's disease have their first flare during childhood or adolescence, there are no or only a few randomized, controlled studies. However, big differences and uncertainty may be observed between the diagnosis and therapy of pediatricians and gastroenterologists specialized for adults. In addition, special problems result from the enormous somatic and psychological evolution during adolescence. The diagnosis is done as in adult patients by enteroclysm and ileocolonoscopy (including multiple biopsies) whereas a deep sedoanalgesia or anesthesia should be performed routinely. Corticosteroids are the gold standard for therapy of Crohn's disease in the adolescence (especially in cases with high inflammatory activity), but also enteral nutrition over 4-12 weeks--or a combination of both. A recent randomized controlled study demonstrates the positive effect of 6-mercaptopurine in newly diagnosed patients with Crohn's disease in the adolescence. 5-aminosalicylates or the probably more effective azathioprine/6-mercaptopurine could be used for prevention of recurrence in Crohn's disease. The therapy of ulcerative colitis is performed as in adults including the very effective local rectal applications. An accompanying psychosomatic therapy is recommended especially in young patients with disturbed separation from the parents and inadequate coping. The indication for surgery is similar to adults. However, a specific indication for earlier surgery is given, if severe malabsorption and delay of growth takes place in spite of adequate therapy, because this delay of growth could be only caught up before puberty. A conservative therapeutic regimen is recommended in young patients with perianal Crohn's disease.     

胶囊内镜、CT小肠成像、小肠造影及回结肠镜对克罗恩病诊断价值的比较

目的 比较4种影像技术方法在小肠克罗恩病(CD)诊断中的应用价值.方法 57例经临床病理诊断为小肠CD的患者伴有不同程度腹痛、消瘦、腹泻或发热、大便潜血阳性等症状体征,进行回结肠镜、CT小肠成像(CTE)、胶囊内镜(CE)、小肠造影(SBFT)检查,发现异常患者则具体记录病变部位、性质,并对单项检杳及两项检查联合的阳性检出率进行比较.结果 57例CD患者中50例完成了回结肠镜检查,33例发现回肠末端溃疡(66.00%),17例回肠末端正常;CTE 34例,发现小肠病变29例(85.29%);CE 27例,其中1例发生CE在胃内潴留未达小肠,发现小肠病变26例(96.30%);SBFT 39例,发现小肠病变26例(66.67%).CE诊断CD的阳性率最高(96.30%),而回结肠镜最低(66.0%),4种检查方法的阳性率差异有统计学意义(P=0.006).两种检查方法联合的诊断CD的阳性检出率:CE+CTE为92.86%(13/14),SBFT+CTE为90.91%(20/22),CE+回结肠镜为95.65%(22/23),CE+SBFT为100%(17/17),回结肠镜+CTE为89.66%(26/29),回结肠镜+SBFT为77.78%(28/36),两种检查联合的组间比较,差异无统计学意义(P=0.140).结论 CE、CTE诊断轻度、中度CD的阳性率比SBFT高,CE发现早期黏膜病变较好,CTE发现肠壁及肠外病变较好,最重要的是CE及CTE可应用于非梗阻性小肠CD患者,传统技术如SBFT或回结肠镜阴性或不能明确诊断时,CE还可用于解释临床症状、随访及指导治疗.     

6-mercaptopurine in patients with inflammatory bowel disease and previous digestive intolerance of azathioprine

OBJECTIVE: Azathioprine and 6-mercaptopurine are useful therapies in inflammatory bowel diseases. Despite their efficacy, their use is limited owing to treatment intolerance or toxicity in 10-15% of patients. It has been suggested that both drugs could be interchangeable. MATERIAL AND METHODS: All patients treated with 6-mercaptopurine because of previous digestive intolerance of azathioprine in four Spanish hospitals were reviewed. Tolerance of 6-mercaptopurine therapy was assessed. RESULTS: Fifteen patients (11 Crohn's disease, 4 ulcerative colitis) were included. Immunosuppressant therapy was prescribed for steroid-dependent disease in 13 cases, and for perianal disease in 2. Main symptoms of digestive intolerance were epigastric pain, nausea and vomiting, which developed within the first weeks of treatment. Acute pancreatitis was ruled out in all the cases. Five patients commenced 6-mercaptopurine immediately after azathioprine discontinuation and 7 patients within the first month. Eleven patients (73.3%) tolerated 6-mercaptopurine and reached the therapeutic goals; only two patients had to discontinue 6-mercaptopurine because of adverse effects. CONCLUSIONS: Treatment with 6-mercaptopurine is a safe alternative in patients with inflammatory bowel diseases and previous digestive intolerance of azathioprine.