Marlene L. Bambrick

A Randomized Clinical Trial of Ciprofloxacin and Metronidazole to Treat Acute Pouchitis

Metronidazole is effective for the treatment of acute pouchitis after ileal pouch–anal anastomosis, but it has not been directly compared with other antibiotics. This randomized clinical trial was designed to compare the effectiveness and side effects of ciprofloxacin and metronidazole for treating acute pouchitis. Acute pouchitis was defined as a score of 7 or higher on the 18-point Pouchitis Disease Activity Index (PDAI) and symptom duration of 4 weeks or less. Sixteen patients were randomized to a 2-week course of ciprofloxacin 1,000 mg/d (n = 7) or metronidazole 20 mg/kg/d (n = 9). Clinical symptoms, endoscopic findings, and histologic features were assessed before and after therapy. Both ciprofloxacin and metronidazole produced a significant reduction in the total PDAI score as well as in the symptom, endoscopy, and histology subscores. Ciprofloxacin lowered the PDAI score from 10.1 ± 2.3 to 3.3 ± 1.7 (p = 0.0001), whereas metronidazole reduced the PDAI score from 9.7 ± 2.3 to 5.8 ± 1.7 (p = 0.0002). There was a significantly greater reduction in the ciprofloxacin group than in the metronidazole group in terms of the total PDAI (6.9 ± 1.2 versus 3.8 ± 1.7; p = 0.002), symptom score (2.4 ± 0.9 versus 1.3 ± 0.9; p = 0.03), and endoscopic score (3.6 ± 1.3 versus 1.9 ± 1.5; p = 0.03). None of patients in the ciprofloxacin group experienced adverse effects, whereas three patients in the metronidazole group (33%) developed vomiting, dysgeusia, or transient peripheral neuropathy. Both ciprofloxacin and metronidazole are effective in treating acute pouchitis with significant reduction of the PDAI scores. Ciprofloxacin produces a greater reduction in the PDAI and a greater improvement in symptom and endoscopy scores, and is better tolerated than metronidazole. Ciprofloxacin should be considered as one of the first-line therapies for acute pouchitis.

Modified Pouchitis Disease Activity Index A Simplified Approach to the Diagnosis of Pouchitis

AbstractPURPOSE: Pouchitis is the most common complication of ileal pouch-anal anastomosis for ulcerative colitis. Our previous study suggested that symptoms alone are not reliable for the diagnosis of pouchitis. The most commonly used diagnostic instrument is the 18-point pouchitis disease activity index consisting of three principal component scores: symptom, endoscopy, and histology. Despite its popularity, the pouchitis disease activity index has mainly been a research tool because of costs of endoscopy (especially with histology), complexity in calculation, and time delay in determining histology scores. It is not known whether pouch endoscopy without biopsy can reliably diagnose pouchitis in symptomatic patients. The aim of the present study was to determine whether omitting histologic evaluation from the pouchitis disease activity index significantly affects the sensitivity and specificity of diagnostic criteria for pouchitis. METHODS: Ulcerative colitis patients with an ileal pouch-anal anastomosis and symptoms suggestive of pouchitis were evaluated. Patients with chronic refractory pouchitis and Crohn’s disease were excluded. Patients with pouchitis disease activity index scores of seven or more were diagnosed as having pouchitis. Different diagnostic criteria were compared on the basis of the pouchitis disease activity index component scores. Nonparametric receiver-operating-characteristic curves were used to measure proposed pouchitis scores’ diagnostic accuracy compared with diagnosis from the pouchitis disease activity index. The receiver-operating-characteristic area under the curve measured how much these diagnostic strategies differed from each other. RESULTS: Fifty-eight consecutive symptomatic patients were enrolled; 32 (55 percent) patients were diagnosed with pouchitis. With the use of the pouchitis disease activity index as a criterion standard, the use of only symptom and endoscopy scores (modified pouchitis disease activity index) produced an area under the curve of 0.995. Establishing a cut-point of five or more for diseased patients resulted in a sensitivity equal to 97 percent and specificity equal to 100 percent. CONCLUSIONS: Diagnosis based on the modified pouchitis disease activity index offers similar sensitivity and specificity when compared with the pouchitis disease activity index for patients with acute or acute relapsing pouchitis. Omission of endoscopic biopsy and histology from the standard pouchitis disease activity index would simplify pouchitis diagnostic criteria, reduce the cost of diagnosis, and avoid delay associated with determining histology score, while providing equivalent sensitivity and specificity.

Treatment of Rectal Cuff Inflammation (Cuffitis) in Patients with Ulcerative Colitis Following Restorative Proctocolectomy and Ileal Pouch-Anal Anastomosis

BACKGROUND:Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the treatment of choice in the majority of patients with ulcerative colitis (UC) who require surgery. To ease the construction of the IPAA and improve functional outcome by minimizing sphincter related stretch injury, a stapling technique is being commonly used in the pouch-anal anastomosis. Despite its advantages, the procedure normally leaves a 1–2 cm of anal transitional zone or rectal cuff, which is susceptible to recurrence of residual UC or cuffitis. Cuffitis can cause symptoms mimicking pouchitis.AIM:To conduct an open-labeled trial of topical mesalamine in patients with cuffitis.METHODS:We treated 14 consecutive patients with cuffitis by giving mesalamine suppositories 500 mg b.i.d. (mean 3.2 months, range 1–9 months). The Cuffitis Activity Index (adapted from the Pouchitis Disease Activity Index) scores and improvement in symptoms of bloody bowel movements and arthralgias were measured as primary and secondary outcomes.RESULTS:All patients had surgery for medically refractory UC. There were significant reductions in the total Cuffitis Activity Index scores after the therapy (11.93 ± 3.17 vs 6.21 ± 3.19, p < 0.001). Symptom (3.24 ± 1.28 vs 1.79 ± 1.31), endoscopy (3.14 ± 1.29 vs 1.00 ± 1.52), and histology (4.93 ± 1.77 vs 3.57 ± 1.39) scores each were significantly reduced (p < 0.05). Ninety-two percent of patients with bloody bowel movements and 70% of patients with arthralgias improved after the therapy. No systemic or topical adverse effects were reported.CONCLUSION:Topical mesalamine appears well tolerated and effective in treating patients with cuffitis, with improvement in symptom as well as endoscopic and histologic inflammation.

Sexual function following restorative proctocolectomy in women

PURPOSE: This study was undertaken to identify the incidence and type of sexual dysfunction experienced by women after undergoing restorative proctocolectomy. METHODS: A questionnaire was sent to 262 females who underwent restorative proctocolectomy by a single surgeon from 1984 to 1993. The response rate was 35 percent (92/262). Additional information was gained from our pelvic pouch data base. Mean follow-up was 43 (6–130) months. RESULTS: Following surgery, a significant increase was found in vaginal dryness, dyspareunia, pain interfering with sexual pleasure, and limiting of sexual activity because of concerns of stool leakage. There was no significant change in sexual desire, arousal, sensitivity, frequency of intercourse, or satisfaction with sexual relationship. CONCLUSION: Potential sexual dysfunction following restorative proctocolectomy in women merits discussion in preoperative counseling with the patient.

In vivo colonoscopic optical coherence tomography for transmural inflammation in inflammatory bowel disease.

BACKGROUND & AIMS Transmural inflammation, a distinguishing feature of Crohns disease (CD), cannot be assessed by conventional colonoscopy with mucosal biopsy. Our previous ex vivo study of histology-correlated optical coherence tomography (OCT) imaging on colectomy specimens of CD and ulcerative colitis (UC) showed that disruption of the layered structure of colon wall on OCT is an accurate marker for transmural inflammation of CD. We performed an in vivo colonoscopic OCT in patients with a clinical diagnosis of CD or UC using the previously established, histology-correlated OCT imaging criterion. METHODS OCT was performed in 40 patients with CD (309 images) and 30 patients with UC (292 images). Corresponding endoscopic features of mucosal inflammation were documented. Two gastroenterologists blinded to endoscopic and clinical data scored the OCT images independently to assess the feature of disrupted layered structure. RESULTS Thirty-six CD patients (90.0%) had disrupted layered structure, whereas 5 UC patients (16.7%) had disrupted layered structure (P < .001). Using the clinical diagnosis of CD or UC as the gold standard, the disrupted layered structure on OCT indicative of transmural inflammation had a diagnostic sensitivity and specificity of 90.0% (95% CI: 78.0%, 96.5%) and 83.3% (95% CI: 67.3%, 93.3%) for CD, respectively. The kappa coefficient in the interpretation of OCT images was 0.80 (95% CI: 0.75, 0.86, P < .001). CONCLUSIONS In vivo colonoscopic OCT is feasible and accurate to detect disrupted layered structure of the colon wall indicative of transmural inflammation, providing a valuable tool to distinguish CD from UC.

Ex Vivo Histology-Correlated Optical Coherence Tomography in the Detection of Transmural Inflammation in Crohn's Disease

BACKGROUND AND AIMS Distinguishing Crohns disease (CD) from ulcerative colitis (UC) can be difficult. Transmural inflammation, a key feature of CD, cannot be assessed by conventional colonoscopy with biopsy. Optical coherence tomography (OCT) provides high-resolution, cross-sectional images of the gut wall and might become a new diagnostic tool. The aims of this study were to perform histology-correlated OCT on surgical specimens of CD and UC and to determine its diagnostic accuracy. METHODS Colectomy specimens from patients with a preoperative diagnosis of CD (N = 24) or UC (N = 24) were studied with OCT in the operating room. OCT and histopathology were assessed blindly, and diagnostic accuracy of OCT was assessed. RESULTS Eight preoperatively identified UC patients (33%) with transmural inflammation on postoperative histology were diagnosed with CD, and all 8 had a disrupted layered structure on OCT, a characteristic feature of transmural disease. Sixteen UC patients (67%) had superficial inflammation on histology; of them, 13 (81%) had an intact layered structure on OCT. All 24 preoperative CD patients had transmural inflammation on histology, and 23 (96%) had a disrupted layered structure on OCT. Of 585 histology-OCT image sets from the 48 patients, 152 sets (26%) had transmural inflammation on histology. The sensitivity and specificity for OCT to detect transmural disease were 86% and 91%, respectively. CONCLUSIONS Transmural inflammation, as characterized by disruption of the layered structure of colon wall on OCT, is an accurate marker for the diagnosis of CD. Ex vivo OCT predicted transmural inflammation on postoperative histopathology.

Clinical features and quality of life in patients with different phenotypes of Crohn's disease of the ileal pouch.

PurposeCrohn’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.MethodsA 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.ResultsDemographic 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.ConclusionsPredominant 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.

Association between immune-associated disorders and adverse outcomes of ileal pouch-anal anastomosis.

OBJECTIVES:Autoimmune disorders (ADs) frequently coexist with inflammatory bowel disease. The aim of the study was to determine whether coexisting AD in patients with ileal pouches increases the risk for chronic antibiotic-refractory pouchitis (CARP) and other inflammatory conditions of the pouch.METHODS:A total of 622 patients seen in our Pouchitis Clinic were enrolled. We compared the prevalence of adverse outcomes of the pouch (including CARP, Crohns disease of the pouch, and pouch failure) in patients with or without concurrent AD and assessed the factors for these adverse outcomes.RESULTS:There were seven pouch disease categories: normal (N=60), irritable pouch syndrome (N=112), active pouchitis (N=131), CARP (N=67), Crohns disease (N=131), cuffitis (N=83), surgical complications (N=36), and anismus (N=2). The prevalence of AD in these pouch disease categories was 4.5%, 12.5%, 9.2%, 13.4%, 10.7%, 3.8%, 1.5%, and 0%, respectively. The presence of at least one AD at time of pouch surgery was shown to be associated with a twofold increase in the risk for CARP (hazard ratio=2.29; 95% CI: 1.52, 3.46; P<0.001) and for pouch-associated hospitalization (hazard ratio=2.39; 95% CI: 1.59, 3.58; P<0.001). The presence of AD was not associated with increased risk for irritable pouch syndrome, active pouchitis, Crohns disease, cuffitis, surgical complications, or pouch failure. Patients with Crohns disease of the pouch had a 2.42 times higher risk for pouch failure (P=0.042) than these without. Active smoking or a history of smoking was shown to be associated with an increased risk for pouch-associated hospitalization and pouch failure.CONCLUSIONS:AD appears to be associated with an increased risk for CARP, and the presence of the association between these AD and pouch disorders may stimulate further research on the link of these organ systems on an immunological basis.

A cost-effectiveness analysis of diagnostic strategies for symptomatic patients with ileal pouch-anal anastomosis

A cost-effectiveness analysis of diagnostic strategies for symptomatic patients with ileal pouch–anal anastomosis

Fecal lactoferrin distinguishes inflammatory from non-inflammatory causes of symptoms in patients with ileal-pouch anal anastomosis (IPAA)

plicated in small bowel ulceration and stricture formation, which are difficult to detect. We report on 12 patients referred either for obscure gastrointestinal bleeding [10] or abdominal pain [2] in which NSAID associated strictures and ulcers were detected by CE and/or intra-operative endoscopy. Methods: In the study population, the mean age was 60.2 yrs [range 18-77]; 3 were male and 9 were female. 9 had iron deficiency anemia and had received an average of 4 units of blood (range 2–20). 11 of 12 patients underwent CE after a prior workup that included a minimum of upper endoscopy [mean 1.41]; colonoscopy [mean 2.0] and all had enteroclysis or a SBFT. Reported NSAID consumption was from 1 to 30 years. 2 took NSAIDs for more than 10 years prior to CE. Results: Strictures with associated ulceration were found in all patients using CE while 2 had findings on radiography. The number of strictures per patient varied from 1 to 23. 10 of 11 patients had transient capsule retention of up to 2 weeks duration, 3 of 11 patients had capsule retention requiring surgical retrieval. 6 of 11 required surgical treatment consisting of intraoperative enteroscopy [6], small intestinal resection [6] and/or stricturoplasty [1] based on CE findings. Pathological exam of surgical specimens revealed strictures comprised of circumferential webs associated with a few discrete ulcers. Macroscopically, the most common findings were short concentric ring-like stenoses, with clearly demarcated ulceration, usually at the innermost margin of the web. In addition some strictures had no serosal representation, and were only located by CE and confirmed by intraoperative enteroscopy. The most frequent histological finding was fibromuscular hyperplasia that broadened the plica circularis. This was associated with disruption and disappearance of the muscularis propria, particularly towards the top of the plica. This was limited to the submucosa and was remarkable for the lack of inflammatory infiltrate. Conclusions: NSAID injury to the small intestine is more common than previously appreciated. CE provides a sensitive means of detecting NSAID lesions in the small intestine. Complete surgical treatment requires intraoperative enteroscopy to detect all stenoses. The pathology of these lesions may be characteristic for NSAID lesions of the small intestine and is distinct from Crohn’s disease.