Endoscopic Recurrence Rate Research Articles

Meta-Analysis of the Placebo Rates of Clinical Relapse and Severe Endoscopic Recurrence in Postoperative Crohn's Disease

The benefit of therapy for prevention of postoperative recurrence of Crohn's disease (CD) is limited. Clinical relapse and severe endoscopic recurrence are the main outcomes in the evaluation of trials on prevention of recurrence. The aim of this meta-analysis was to focus on knowledge of the placebo rates of relapse and recurrence in postoperative CD and to identify factors influencing these rates. We performed a meta-analysis of placebo-controlled, randomized clinical trials, evaluating therapies for postoperative maintenance of CD identified on MEDLINE from 1990 to 2006. Primary outcomes were clinical relapse and severe endoscopic recurrence. The pooled estimate of the placebo relapse rate was 23.7% (95% confidence interval [CI], 13-35; range 0-78). There was a statistically significant heterogeneity among studies (P < .0001). Heterogeneity in clinical relapse was present even if the trials were stratified according to the time of outcome. The pooled estimate of the severe endoscopic recurrence rate was 50.2% (95% CI, 28-73; range, 30-79). There was significant heterogeneity among the studies (P = .00038). This heterogeneity was less apparent in studies carried out within 12 months. The logistic analysis identified only duration of follow-up as a variable associated with different placebo relapse rates. No variable was identified as a predictor of a placebo endoscopic recurrence rate. There is significant heterogeneity among placebo rates in postoperative CD. No single design variable was identified that explained the heterogeneity in placebo outcomes for clinical or endoscopic recurrence.

Meta‐analysis: factors predicting post‐operative recurrence with placebo therapy in patients with Crohn’s disease

The use of placebo in randomized clinical trials (PC-RCTs) is often required to evaluate drug efficacy in maintenance of Crohn's disease (CD). To determine pooled estimates of placebo rates of maintaining clinical remission and endoscopic recurrence following surgery for CD and identify factors that influenced placebo outcomes. We performed a systematic review and meta-analysis of PC-RCTs evaluating post-operative maintenance therapies for CD identified from MEDLINE from 1966 to 2005. Twelve studies met our inclusion criteria. The pooled placebo rate of maintaining clinical remission was 56% (95% CI 47-64%; range 34-89%) during a median follow-up of 52 weeks (range 12-156 weeks), but significant heterogeneity existed among the studies (P < 0.001). Prior steroid therapy was the only factor found to be associated with maintaining remission (P = 0.04). The pooled placebo endoscopic recurrence rate was 58% (95% CI 51-65%; range 36-80%) during a median follow-up of 52 weeks (range 12-156 weeks), with significant heterogeneity noted (P = 0.0003). Prior surgery, concomitant small bowel and colonic disease, fistulizing phenotype, or prior immunomodulator therapy influenced endoscopic recurrence (P < 0.05). Placebo rates in PC-RCTs evaluating post-operative clinical and endoscopic recurrence demonstrate significant variability, which is influenced by specific study characteristics.

Therapy of Metronidazole With Azathioprine to Prevent Postoperative Recurrence of Crohn's Disease: A Controlled Randomized Trial

More than 80% of Crohn's disease (CD) patients undergoing resection suffer recurrence of their disease. Therapy with aminosalicylates, antimetabolites, or antibiotics leads to a modest reduction in the incidence of recurrence. We sought to examine whether metronidazole for 3 months together with azathioprine (AZA) for 12 months is superior to metronidazole alone to reduce recurrence of postoperative CD in "high-risk" patients. CD patients undergoing curative ileocecal resection with >or=1 risk factor for recurrence received metronidazole (3 months) and AZA/placebo (12 months). The primary end point was the proportion of patients with significant endoscopic recurrence 3 and 12 months after surgery. Secondary end points included clinical recurrence, safety, and tolerability of treatment. Eighty-one patients were randomized; 19 discontinued the study early. Significant endoscopic recurrence was observed in 14 of 32 (43.7%) patients in the AZA group and in 20 of 29 (69.0%) patients in the placebo group at 12 months postsurgery (P = .048). Intention-to-treat analysis revealed endoscopic recurrence in 22 of 40 (55%) in the AZA group and 32 of 41 (78%) in the placebo group at month 12 (P = .035). At month 12, 7 of 32 patients had no endoscopic lesions in the AZA group, versus 1 of 29 in the placebo group (P = .037). Despite the enhanced risk of recurrence, the overall incidence of significant recurrence was rather low, probably owing to the metronidazole treatment that all patients received. Concomitant AZA resulted in lower endoscopic recurrence rates and less severe recurrences 12 months postsurgery, predicting a more favorable clinical outcome. This combined treatment seems to be recommendable to all operated CD patients with an enhanced risk for recurrence.

Multicenter randomized-controlled clinical trial of probiotics (Lactobacillus johnsonii, LA1) on early endoscopic recurrence of Crohnʼs disease after ileo-caecal resection

Seventy percent of Crohn's disease (CD) patients exhibit anastomotic recurrence within 1 year after ileo-caecal surgery. Recent clinical trials suggest the beneficial use of probiotics in the control of intestinal inflammation in pouchitis and ulcerative colitis. This study is a multicenter clinical trial evaluating the efficacy of an oral administration of the probiotic LAl on early post-operative endoscopic recurrence of CD. Seventy patients with CD were enrolled prior to elective ileo-caecal resection and randomly assigned after surgery to daily treatment with either Lactobacillus johnsonii, LA1, Nestle (1010 colony-forming units, CFU) (group A, n = 34) or placebo (group B, n = 36) for 12 weeks. The primary objective was to assess the effect of LAl on the endoscopic recurrence rate at 12 weeks. Stratification was performed according to smoking status at randomization. Seven and 14 patients were excluded in the LA1 and placebo groups, respectively. In intention-to-treat analysis, the mean endoscopic score was not significantly different between the two treatment groups at 3 months (LA1 versus placebo: 1.50 +/- 1.32 versus 1.22+/-1.37, treatment effect: P = 0.48, smoke effect: P = 0.72). The percentage of patients with severe recurrence (i3 + i4) was 21% and 15% in the LAl and placebo groups, respectively (P = 0.33). Using a per-protocol (PP) analysis, the mean endoscopic score was not significantly different between the two treatment groups (LAl versus placebo groups: 1.44 +/-1.31 versus 1.05 +/- 1.21, P = 0.32). The percentage of patients with severe recurrence (i3 + i4) was 19% and 9% in the LAl and placebo groups, respectively (P = 0.054). Clinical relapse rate (CDAI [CD activity index] > 150, with an increase of CDAI > 70 points or greater from baseline) in the LAl and placebo groups was 15% (4/27) and 13.5% (3/22), respectively (PP analysis: chi-square test, P = 0.91 and log-rank test: P = 0.79). Oral administration of the probiotic LA1 in patients with CD failed to prevent early endoscopic recurrence at 12 weeks after ileo-caecal resection.

This Month in Gastroenterology

This Month in Gastroenterology

The Role of Endoscopy in the Management of Postoperative Patients with Crohn’s Disease

The Role of Endoscopy in the Management of Postoperative Patients with Crohn’s Disease

Long-term results of highly selective vagotomy: a prospective study with implications for future laparoscopic surgery.

Between 1979 and 1984, 141 patients (110 men, 31 women) underwent highly selective vagotomy (HSV) by a standard open technique for duodenal ulcer. All patients had received preoperative treatment with full-dose H2-receptor antagonists. Some 107 of these patients underwent HSV for persistent relapse on withdrawal of H2-receptor antagonists (relapsing responders) and 30 because of non-response to such drugs. After 4 years of follow-up, non-responders were found to be more likely to have symptoms after operation (P < 0.001), but did not have a higher rate of recurrent ulceration. At a median of 11 (range 8-14) years after operation 126 patients were still alive; 115 (91 per cent) of these were followed up. Ten patients (9 per cent) were found to have had endoscopically proven recurrence and eight (7 per cent) still had symptoms without evidence of recurrence. The endoscopic recurrence rate and symptom rate at 11 years were no longer significantly different between relapsing responders and non-responders. The preoperative response to H2-receptor antagonist therapy does not help in predicting the likelihood of ulcer recurrence or long-term symptoms after HSV. Post-operative symptoms do not necessarily predict long-term ulcer recurrence. The long-term endoscopic recurrence rate after HSV is low and, if equally good results can be obtained laparoscopically, this will be an important and cost-effective option in the management of duodenal ulcer.

Postoperative maintenance of Crohn’s disease remission with 6-mercaptopurine, mesalamine, or placebo: A 2-year trial

No therapy has been shown to reliably prevent the evolution of postoperative recurrence of Crohn's disease. The aim of the current trial was to compare 6-mercaptopurine (6-MP) and mesalamine with placebo for the prevention of clinical, endoscopic, and radiographic recurrence of Crohn's disease after resection and ileocolic anastomosis. Five centers randomized 131 patients to receive 6-MP (50 mg), mesalamine (3 g), or placebo daily in a double-blind, double-dummy trial. Patients had clinical assessments at 7 weeks and then every 3 months; colonoscopy at 6, 12, and 24 months; and small bowel series at 12 and 24 months. End points were clinical, endoscopic, and radiographic recurrence rates at 24 months. Clinical recurrence rates (intent to treat) by life-table analysis at 24 months were 50% (95% confidence interval [CI], 34%-68%), 58% (95% CI, 41%-75%), and 77% (95% CI, 61%-91%) in patients receiving 6-MP, mesalamine, and placebo, respectively. Endoscopic recurrence rates were 43% (95% CI, 28%-63%), 63% (95% CI, 47%-79%), and 64% (95% CI, 46%-81%), and radiographic recurrence rates were 33% (95% CI, 19%-54%), 46% (95% CI, 29%-66%), and 49% (95% CI, 30%-72%), respectively. 6-MP was more effective than placebo ( P < 0.05) at preventing clinical and endoscopic recurrence over 2 years. Patient withdrawals resulted in 69% of the study population evaluable for the clinical recurrence end point. 6-MP, 50 mg daily, was more effective than placebo at preventing postoperative recurrence of Crohn's disease and should be considered as a maintenance therapy after ileocolic resection.

Probiotics and Crohn's disease

Antibiotics are often employed in the treatment of Crohn's disease, with interesting results. However, indiscriminate suppression of intestinal bacteria may be harmful and long-term use of antibiotics is burdened by side-effects and by the risk of developing bacterial resistance. Manipulation of enteric flora with probiotic compounds would be a possible and appealing alternative. First aim of our study has been to investigate the efficacy of this probiotic in reducing the endoscopic recurrence rate or in reducing the severity of recurrent lesions at 1 year after surgery. Secondary goal has been the reduction of the clinical recurrence rate. Forty-five patients have been randomised to receive Lactobacillus rhamnosus strain GG or placebo for 12 months. The results have shown no differences in endoscopic and clinical remission between the two groups.

Azathioprine for prevention of postoperative recurrence in Crohn's disease: a retrospective study.

The efficacy of azathioprine (AZA) in chronically active Crohn's disease (CD) is well established. Whether this drug is also useful to prevent recurrences after surgery is unknown. We report here our experience of AZA in this therapeutic goal. Between 1987 and 1996, 38 patients with CD were treated with AZA to prevent postoperative recurrence. Twenty-three of these had undergone a curative resection with removal of all previously involved parts of the gut. In the other 15 patients, resection was limited to the parts of the gut macroscopically abnormal at the time of surgery; those parts that were previously involved but normal at this time were conserved. The operative procedures were ileocolonic resection (n = 18), subtotal colectomy with ileorectal anastomosis (n = 12), coloproctectomy with ileo-anal anastomosis (n = 4) or ileostomy (n = 2), ileal resection (n = 1) and segmental colectomy (n = 1). Twelve patients had been treated previously with AZA before surgery; in 26 patients, AZA was started within the 2 months following surgery. The median duration of postoperative follow-up was 29 months. Probabilities of clinical recurrence according to the Kaplan-Meier method were 9, 16 and 28% at 1, 2 and 3 years, respectively. For the 25 patients who had a colonoscopy or a small bowel barium X-ray during the follow-up, probabilities of anatomical recurrence were 16, 36 and 59% at 1, 2 and 3 years, respectively. The probability of anatomical recurrence was significantly higher in patients who had segments of the gut previously involved but not removed because they were macroscopically normal at the time of surgery. In patients treated with AZA, the rate of postoperative endoscopic recurrence was lower than that previously reported in untreated patients. Our results suggest that AZA should be evaluated prospectively for prevention of postoperative CD recurrence, at least in high-risk patients.

Prediction of the clinical course of Behçet's colitis according to macroscopic classification by colonoscopy.

The lesions in Behçet's colitis show aphthoid or punched-out ulceration, but the macroscopic types of lesion found have not been defined. To predict the clinical outcome in patients with Behçet's colitis according to the colonoscopic findings, we classified the characteristic colonic ulcers, evaluated the efficacy of medical treatment on colonoscopic lesions, and calculated the operation rates and recurrence rates relative to the macroscopic types. The medical records and colonoscopic photographs of 50 patients with Behçet's colitis were reviewed. The colonic lesions were examined by colonoscopy in patients with Behçet's disease and gastrointestinal symptoms. The colonoscopic findings were categorized into three types of ulceration: volcano-like, geographic, and aphthous. The efficacy of medical treatment was assessed by follow-up colonoscopy or double-contrast barium enema four to eight weeks after treatment, and recurrence of the lesions was evaluated during the follow-up periods. Cumulative surgery rates were obtained using the Kaplan-Meier method. The macroscopic classification of colonic ulcers identified 25 of 50 patients (50%) with volcano-type lesions, 11 (22%) with the geographic type, and 14 (28%) with the aphthous type. The rates of complete remission after medical treatment and surgery, respectively, were six of 25 (24%) and 13 of 25 (52%) with volcano-type ulcerations; eight of 11 (73%) and one of 11 (9%) with the geographic type; and nine of 14 (64%) and two of 14 (14%) with the aphthous type. The endoscopic and clinical recurrence rates were nine of 19 (47%) in volcano-type ulcerations, one of nine (11%) in the geographic type, and one of 11 (9%) in the aphthous type. Volcano-type ulcerations in Behçet's colitis showed a less favorable response to medical treatment, a more frequent requirement for surgery, and more frequent recurrences than the geographic and aphthous types of ulcerations.

Oral budesonide for prevention of postsurgical recurrence in Crohn's disease

Background & Aims: Prevention of postoperative recurrence after resection for Crohn's disease (CD) would be of great clinical benefit. The efficacy of oral budesonide for prevention of endoscopic recurrence was evaluated in patients undergoing resection for ileal or ileocecal CD. Methods: Sixty-three patients received budesonide and 66 received placebo in a double-blind, randomized trial with parallel groups. Ileocolonoscopy, including biopsy, was performed after 3 and 12 months. Indications for surgery were fibrostenosis (78 patients), disease activity (41), and other reasons (10). Results: The frequency of endoscopic recurrence did not differ between the groups at 3 and 12 months. In patients with disease activity as indication for surgery, the endoscopic recurrence rate at the anastomosis was lower in the budesonide group at 3 months, although not significantly (21% vs. 47%; P = 0.11), and at 12 months (32% vs. 65%; P = 0.047). There was no such difference with respect to fibrostenosis as indication for surgery. No differences in adverse event patterns were found between the two groups. Conclusions: Oral budesonide, 6 mg daily, offered no benefit in prevention of endoscopic recurrence after surgery for ileal/ileocecal fibrostenotic CD but decreased the recurrence rate in patients who had undergone surgery for disease activity. GASTROENTEROLOGY 1999;116:294-300

Is it possible to prevent recurrent Crohn's disease with medical or surgical interventions?

While surgery for Crohn's disease is usually effective initially, its long-term benefits may be diminished by the risk of recurrent disease. In our studies, we have observed symptomatic recurrence rates of 47% and endoscopic recurrence rates of 75% at 3 years. As a result, there has been considerable interest in strategies aimed at decreasing recurrence. Unfortunately, surgical manoeuvers have had little effect on recurrence rates. There are conflicting data on the effect of resection margin length and microscopic disease at the resection margin, probably due to the fact that most data are derived from retrospective studies. Differences in anastomotic technique also appear to have little effect on the recurrence rate. On the other hand, there are now data from two randomized controlled trials supporting the use of 5-aminosalicylic acid postoperatively. In a study performed at the University of Toronto and Mayo Clinic, of 163 patients who were randomized to 5-aminosalicylic acid (Salofalk®) 3.0 g/day or placebo, the relative risk of a symptomatic recurrence was 0.628 in the treatment group compared to those in the control group. For compliant patients, the risk reduction was even greater with a RR of 0.532. A similar reduction in the endoscopic recurrence rate was observed. Caprilli and colleagues reported similar results in patients receiving 2.4 g Asacol® per day. Postoperative recurrence is a significant problem but is significantly reduced by the prophylactic use of 5-aminosalicylic acid.

Videothoracoscopic Appearance of First and Recurrent Pneumothorax

Comparison of the videothoracoscopic appearance of first and recurrent pneumothorax, and assessment of a relation between endoscopic appearance and recurrence rate. University hospital. Eighty-two patients, 64 men (mean age, 32.7 years) and 18 women (mean age, 31.5 years), were included. Patients with known underlying pulmonary disease at the time of hospital admission were excluded. There were 61 patients (74%) with first pneumothorax, and 21 patients (26%) with recurrent pneumothorax. All patients underwent videothoracoscopy under general anesthesia, with double-lumen intubation. Blebs or bullae were found in 47 patients (77%) with first pneumothorax, and in 14 patients (67%) with recurrent pneumothorax. Bullae > 2 cm were found in 34 patients (56%) with first pneumothorax and 10 patients (48%) with recurrent pneumothorax. Patients with blebs or bullae were significantly older than patients with normal videothoracoscopic appearance (mean age, 36.5 +/- 15.7 years vs 25.3 +/- 5.8 years, p < 0.05). Adhesions were significantly more frequently found in patients with blebs or bullae compared with patients with normal thoracoscopic appearance of the lung (p < 0.05). Seventeen of 21 patients (81%) with normal thoracoscopic appearance were smokers. Of nonsmoking patients (n = 22), 82% had blebs and bullae. No significant differences in videothoracoscopic appearance were found between first and recurrent pneumothorax. These results suggest that recurrence after the first event of spontaneous pneumothorax cannot be predicted by thoracoscopic findings. Smoking and blebs or bullae are independent risk factors for development of spontaneous pneumothorax.

Scanning electron-microscopic lesions in Crohn's disease: Relevance for the interpretation of postoperative recurrence

Background/Aims: Endoscopic postoperative recurrence often occurs a few months after surgical therapy for Crohn's disease, even if the resection margins were macroscopically free of disease. Why the disease primarily recurs at the anastomotic site is not known. This study investigated resection margins in Crohn's disease in an attempt to clarify whether early lesions are relevant to the interpretation of postoperative recurrence. Methods: Specimens of surgically resected bowel from 29 patients with Crohn's disease and tissue from 11 controls were studied with a scanning electron microscope. Results: In Crohn's disease, a triad of early lesions occurring in both histopathologically unaffected and affected mucosa was revealed; the triad consisted of mucosal architectural alterations, epithelial bridge formation, and goblet-cell hyperplasia or hypertrophy or both. Seventy-three percent of patients showed early alterations within histopathologically unaffected margins in the small bowel, and 71% had such alterations in the large bowel. Conclusions: The findings provide further evidence for the concept of diffuse involvement of the whole gastrointestinal tract by the disease process. The endoscopic recurrence rate in the first year after the operative procedure is almost identical to the number of early lesions present during surgery. The term “postoperatively recurrent disease” should be used only if relevant clinical parameters change.

Prevention of early recurrence of Crohnʼs disease after ileal resection with ileocolonic anastomosis

The evolution of the recurrence of Crohn's disease after ileal resection and ileocolonic anastomosis closely mimics the natural history of the disease. The pattern of disease does not change after resection compared with that before surgery. New lesions develop within weeks to months after resection in the neoterminal ileum and the severity of these early lesions determine when symptoms and complications recur. This model of early recurrence of Crohn's disease lesions is rather new and drug prevention studies are scarce. A 3-month course of metronidazole (20 m/kg) has been shown to decrease the rate of severe recurrence. Data on 5-aminosalicylic acid therapy are controversial. Claversal seems to be ineffective in preventing recurrence, whereas Pentasa 3 g/day and Asacol 2.4 g/day decreased the rate of endoscopic recurrence, with less symptomatic recurrence observed with the latter drug

Factors Influencing the Relapse of Gastric Ulcers During H2‐Receptor Antagonist Maintenance Therapy

Abstract: We performed H2‐receptor antagonist maintenance therapy for 2 years on 146 patients with healed gastric ulcers (including those with concurrent duodenal ulcers), and determined the cumulative endoscopic and symptomatic recurrence rates. We also investigated the factors involved in ulcer recurrence in the first 12 months of maintenance therapy. The cumulative endoscopic non‐recurrence rate was 70.0% at 12 months and 57.2% at 24 months, while the cumulative symptomatic non‐recurrence rate was 84.8% at 12 months and 75.0% at 24 months. The factors contributing to endoscopic recurrence were the presence of a concomitant disease, the presence of duodenal ulcer, the type of ulcer, and the endoscopic stage at healing. The factors related to symptomatic recurrence were smoking and the type of ulcer. Multivariate analysis showed that the type of ulcer, smoking, and the endoscopic stage at healing influenced the risk of recurrence.

Predictability of the postoperative course of Crohn's disease

Eighty-nine patients who had been treated by ileal resection for Crohn's disease between 1979 and 1984 were included in a prospective cohort follow up to study the natural course of early postoperative lesions. Recurrent lesions were observed endoscopically in the neoterminal ileum within 1 year of surgery in 73% of the patients, although only 20% of the patients had symptoms. Three years after surgery, the endoscopic recurrence rate had increased to 85% and symptomatic recurrence occurred in 34%. The ultimate course of the disease was best predicted by the severity of the early postoperative lesions, as observed at ileoscopy. Clinical parameters that influenced outcome were preoperative disease activity, the indication for surgery, and the number of surgical resections. When patients were stratified for preoperative disease activity, the severity of lesions found at endoscopy remained a strong predictive factor for symptomatic recurrence. In 22 other patients submitted to “curative” ileal resection and ileocolonic anastomosis, the segment to be used as neoterminal ileum was carefully examined during surgery, and two large biopsies were taken before making the anastomosis. An ileoscopy was performed 6 months after surgery. Although all patients had a macroscopically normal neoterminal ileum and 19 had entirely normal biopsies at the time of surgery, 21 patients were found at ileoscopy to have developed ileitis involving a 15-cm segment (range, 4–30 cm), and 20 had unequivocal microscopic lesions on biopsies. These studies suggest that early lesions in the neoterminal ileum after Crohn's resection do not originate from microscopic inflammation present in this bowel segment at the time of surgery. The early postoperative lesions in the neoterminal ileum seem to be a suitable model to study the pathogenesis of Crohn's disease and also to evaluate new therapeutic modalities, either to prevent development of these early lesions or to treat progressive recurrence.