Diagnosis and Differential Diagnosis of Crohn’s Disease of the Ileal Pouch

Approximately 20%-30% of patients with ulcerative colitis will eventually require colectomy despite recent advances in medical therapy. Ileal pouch-anal anastomosis has become the surgical treatment of choice. A subset of patients with ileal pouches can develop Crohn's disease or a Crohn's-disease-like condition of the ileal pouch after surgery. Diagnosis, differential diagnosis, and management of Crohn's disease of the ileal pouch have been challenging. A combined assessment of clinical history, endoscopy, histology, abdominal/pelvic imaging, and examination under anesthesia is often necessary for accurate diagnosis, disease classification, management, and prognosis. A multidisciplinary approach with gastroenterologists, colorectal surgeons, gastrointestinal pathologists, and radiologists is advocated.     

Safety and Efficacy of Strictureplasty for Crohn’s Disease: A Systematic Review and Meta-Analysis

Purpose This study was designed to review safety and efficacy of strictureplasty for Crohn’s disease. Methods A literature search was performed to identify studies published between 1975 and 2005 that reported the outcome of strictureplasty. Systematic review was performed on the following subjects separately: 1) overall experience of strictureplasty; 2) postoperative complications; 3) postoperative recurrence and site of recurrence; 4) factors affecting postoperative complications and recurrence; 5) short-bowel syndrome; and 6) cancer risk. Meta-analysis of recurrence rate after strictureplasty was performed by using random-effect model and meta-regressive techniques. Results A total of 1,112 patients who underwent 3,259 strictureplasties (Heineke-Mikulicz, 81 percent; Finney, 10 percent; side-to-side isoperistaltic, 5 percent) were identified. The sites of strictureplasty were jejunum and/or ileum (94 percent), previous anastomosis (4 percent), duodenum (1 percent), and colon (1 percent). After jejunoileal strictureplasty, including ileocolonic strictureplasty, septic complications (leak/fistula/abscess) occurred in 4 percent of patients. Overall surgical recurrence was 23 percent (95 percent confidence interval, 17–30 percent). Using meta-regressive analysis, the five-year recurrence rate after strictureplasty was 28 percent. In 90 percent of patients, recurrence occurred at nonstrictureplasty sites, and the site-specific recurrence rate was 3 percent. Two patients developed adenocarcinoma at the site of previous jejunoileal strictureplasty. The experience of duodenal or colonic strictureplasty was limited. Conclusions Strictureplasty is a safe and effective procedure for jejunoileal Crohn’s disease, including ileocolonic recurrence, and it has the advantage of protecting against further small bowel loss. However, the place for strictureplasty is less well defined in duodenal and colonic diseases.     

The Fate of the Ileal Pouch in Patients Developing Crohn’s Disease

PURPOSE Recent studies have suggested that a subset of patients with Crohns colitis may have a favorable outcome after ileal pouch-anal anastomosis and have advocated elective ileal pouch-anal anastomosis in selected patients with Crohns disease. We have not offered ileal pouch-anal anastomosis to patients with known Crohns disease, but because of the overlap in clinical presentation of ulcerative colitis and indeterminate colitis, some patients receiving an ileal pouch-anal anastomosis are subsequently found to have Crohns disease. We review our experience with these patients to identify potential preoperative predictors of ultimate pouch failure.METHODS Patients with a final diagnosis of Crohns disease were identified from an ileal pouch-anal anastomosis registry. These patients are followed prospectively. Preoperative and postoperative clinical and pathologic characteristics were evaluated as predictors of outcome. Median (range) values are listed.RESULTS Thirty-two (18 females) patients (4.1 percent) with a final diagnosis of Crohns disease were identified from a registry of 790 ileal pouch-anal anastomosis patients (1980–2002). Patients underwent ileal pouch-anal anastomosis in two stages (11 patients) or three stages (21 patients). The preoperative diagnosis was ulcerative colitis in 24 patients and indeterminate colitis in 8 patients. Median follow-up was 153 (range, 13–231) months. The median time from ileal pouch-anal anastomosis to diagnosis of Crohns disease was 19 (range, 0–188) months. Complications occurred in 93 percent, including perineal abscess/fistula (63 percent), pouchitis (50 percent), and anal stricture (38 percent). Pouch failure (excision or current diversion) occurred in nine patients (29 percent) at a median of 66 (range, 6–187) months. Two of these 9 patients had preoperative anal disease (not significant). Comparing patients with failed pouches (n = 9) to patients with functioning pouches (n = 23), post-ileal pouch-anal anastomosis perineal abscess (67 vs. 26 percent, P = 0.05) and pouch fistula (89 vs. 30 percent, P = 0.01) were more commonly associated with pouch failure. Preoperative clinical, endoscopic, and pathologic features were not predictive of pouch failure or patient outcome. For those with a functional pouch, 50 percent have been or are currently on medication to treat active Crohns disease. This group had six bowel movements in 24 (range, 3–10) hours, with leakage in 60 percent and pad usage in 45 percent.CONCLUSIONS Patients who undergo ileal pouch-anal anastomosis and are subsequently found to have Crohns disease experience significant morbidity. Preoperative characteristics, including the presence of anal disease, were not predictive of subsequent pouch failure. We choose not to recommend the routine application of ileal pouch-anal anastomosis in any subset of patients with known Crohns disease.Reprints are not available.     

Is Pyloric Gland Metaplasia in Ileal Pouch Biopsies a Marker for Crohn’s Disease?

Background

Approximately 5–10 % of ulcerative colitis (UC) patients who undergo ileal pouch-anal anastomosis (IPAA) will develop postoperative complications such as refractory pouchitis or a change in diagnosis to Crohn’s disease (CD). Serological markers and histologic aspects of the pouch such as pyloric gland metaplasia (PGM) have been associated with a risk for these complications.

Methods

Twenty-eight IPAA patients with either CD of the pouch or chronic pouchitis (cases) and 36 IPAA controls who experienced a normal postoperative course were originally consented. Of these 64 subjects, 22 cases and 17 controls had histopathologic and serologic data available and were subsequently enrolled. Demographic and clinical data were entered into a database, blood analyzed for serological markers (Prometheus Labs, San Diego, CA) and biopsies of the pouch and the afferent limb reviewed by two GI pathologists.

Results

Of the cases, 55 % (12/22) had evidence of PGM in their pouch and/or small bowel biopsies, as compared to 12 % (2/17) of the controls (p = 0.006). Of 13 subjects with CD, 77 % (10/13) were found to have PGM versus subjects with chronic pouchitis in which 22 % (2/9) were found to have PGM (p = 0.03). There was a trend of ASCA positivity (both IgG and IgA, p = 0.20) and of higher ASCA titer levels (p = 0.07) with postoperative complications.

Conclusion

This study suggests that the presence of ileal pouch PGM is associated with postoperative complications and favors a diagnosis of CD over UC with chronic pouchitis.     

Efficacy of Mesenchymal Stromal Cells for Fistula Treatment of Crohn’s Disease: A Systematic Review and Meta-Analysis

Background and Aim

The introduction of mesenchymal stromal cells (MSCs) has changed the management of Crohn’s fistula, while it remains controversial. The aim of this study was to provide an overview of efficacy and optimum state of MSCs treatment on Crohn’s fistula.

Methods

Studies reporting MSCs treatment on Crohn’s fistula were searched and included. A fixed-effects model was used to assess the efficacy of MSCs, and outcomes of healing and recurrence were used to evaluate the best states of MSCs intervention.

Results

Fourteen articles were enrolled (n = 477). Pooled analysis showed MSCs had a significant efficacy compared to other treatments [risk difference: 0.21 (0.09, 0.32), P = 0.000]. Notably, after MSCs treatment, the group of Crohn’s disease activity index (CDAI) baseline >150 group had a higher healing rate (HR) and a clinical response (a change in CDAI of >50 points) (79.17 ± 8.78 vs. 47.54 ± 15.90, P = 0.011) compared to CDAI baseline of <150. The duration time of CD and fistulas had a negative correlation with HR accompanied by MSC therapy (r = ?0.900, ?0.925). Then, a moderate dose MSCs (2–4 × 10⁷ cells/ml) had a higher HR (80.07%) and lower recurrence rate (RR 13.98%) compared to other dosages. Moreover, adipose-derived MSCs therapy had an advantage over bone marrow-derived MSCs in terms of low RR (7.4 ± 4.28 vs. 13.39 ± 0.89).

Conclusions

The evidence supported the effect of MSCs at a more appropriate time of Crohn’s fistula. And CDAI baseline (the points >150) has been a candidate for evaluating effectiveness of MSCs application on Crohn’s fistula.

     

Ustekinumab for the treatment of Crohn’s disease

Introduction: Ustekinumab is a human monoclonal antibody directed against the shared p40 subunit of interleukins 12 and 23. Ustekinumab is currently approved for the treatment of psoriatic arthritis (PsA) and moderate to severe plaque psoriasis, and is being evaluated in Crohn’s disease (CD).

Areas covered: The first evidence supporting the efficacy of ustekinumab in the treatment of moderate to severe CD was published in 2008. Results from subsequent phase II and phase III randomized controlled trials (RCTs) have shown promising data on the clinical efficacy of induction and remission of moderate to severe CD. These data and the safety profile of ustekinumab will be reviewed.

Expert commentary: As a significant proportion of individuals with CD have ongoing symptoms and inflammation despite existing therapies, there is a clinical need for new agents like ustekinumab directed at different targets on the inflammatory pathway. Looking forward, more studies are needed to evaluate dosing escalation or de-escalation in addition to timing of therapy switches. In addition, further data is required to gauge the comparative effectiveness of ustekinumab to the biologic agents that are currently used in the treatment of CD.     

Adalimumab Treatment in Children with Refractory Crohn’s Disease

Information on safety and efficacy of adalimumab in children with Crohn’s disease (CD) is limited. We present a case-series of 14 children with severe CD treated with adalimumab during a 3.5-year period. Fourteen children (nine boys, five girls), aged 13.9 years (range 1.9–19.1) were treated with adalimumab during 12.5 months (range 7–42). All had steroid or immunosuppression-drugs refractory disease. Ten patients (71%) had been previously treated with infliximab, 13/14 were treated with different immunosuppressive drugs and all were steroid-dependent or resistant. Seven children (50%) showed full clinical response and 5/14 (35%) improved partially. Two children (15%) had loss of response after a period of transient improvement. Adalimumab treatment enabled complete steroids withdrawal in 8/14 (57%) of steroid-dependent children. Currently, five children are in complete remission with adalimumab monotherapy for a median 14 months (range 9–24). Adalimumab may induce and maintain remission in children with severe, refractory CD. Prospective safety and efficacy confirmation of this data in children is necessary.     

Clinical Features and Quality of Life in Patients with Different Phenotypes of Crohn’s Disease of the Ileal Pouch

Purpose Crohn’s disease of the pouch can occur in patients with colectomy and ileal pouch-anal anastomosis performed for ulcerative colitis. The clinical features of inflammatory, fibrostenotic, and fistulizing Crohn’s disease have not been characterized. Methods A total of 73 eligible patients with Crohn’s disease of the pouch, who were seen in the Pouchitis Clinic, were enrolled: 25 with inflammatory Crohn’s disease, 17 with fibrostenotic Crohn’s disease, and 31 with fistulizing Crohn’s disease. The clinical phenotypes of Crohn’s disease were based on a combined assessment of clinical, endoscopic, radiographic, and histologic features. Clinical symptoms, endoscopic and histologic features, and health-related quality-of-life scores were assessed. Results Demographic and clinical features, including preoperative and postoperative parameters, were similar between the three phenotypes of Crohn’s disease of the pouch. The use of nonsteroidal anti-inflammatory drugs, neuropsychiatric drugs, antidiarrheal agents, and Crohn’s disease medicines was not different between the three groups. Predominant symptoms, as expected, were significantly different between the three phenotypes: diarrhea and/or pain in 92 percent of patients with inflammatory Crohn’s disease, obstructive symptoms in 64.7 percent of patients with fibrostenotic Crohn’s disease, and fistular drainage in 51.6 percent of those with fistulizing Crohn’s disease (P < 0.0001). There was no statistical difference in quality-of-life scores between the three phenotypes, adjusted for disease activity. There was no significant correlation between quality-of-life and symptom scores in any of the three groups. Although not statistically significant, patients with fistulizing Crohn’s disease (16.1 percent) tended to have an increased risk for pouch failure compared with inflammatory (8 percent) or fibrostenotic (5.9 percent) Crohn’s disease. Conclusions Predominant symptoms were different in clinical phenotypes of Crohn’s disease. Each of the three phenotypes of Crohn’s disease similarly affected quality-of-life. Fistulizing Crohn’s disease may be associated with a higher risk for pouch failure. Supported by NIH R03 DK 067275 and an American College of Gastroenterology Clinical Research Award. Reprints are not available.