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Background & Aims: Little is known about progression of ischemic colitis (IC) among unselected patients. We aimed to estimate the incidence, risk factors, and natural history of IC in a population-based cohort in Olmsted County, Minnesota., Methods: We performed a retrospective population-based cohort and nested case-control study of IC. Each IC case was matched to 2 controls from the same population on the basis of sex, age, and closest registration number. Conditional logistic regression, the Kaplan-Meier method, and proportional hazards regression were used to assess comorbidities, estimate survival, and identify characteristics associated with survival, respectively., Results: Four hundred forty-five county residents (median age, 71.6 years; 67% female) were diagnosed with IC from 1976 through 2009 and were matched with 890 controls. The age-adjusted and sex-adjusted incidence rates of IC nearly quadrupled from 6.1 cases/100,000 person-years in 1976-1980 to 22.9/100,000 in 2005-2009. The odds for IC were significantly higher among subjects with atherosclerotic diseases; odds ratios ranged from 2.6 for individuals with coronary disease to 7.9 for individuals with peripheral vascular disease. Of IC cases, 59% survived for 5 years (95% confidence interval, 54%-64%), compared with 90% of controls (95% confidence interval, 88%-92%). Age >40 years, male sex, right-sided colon involvement, concomitant small bowel involvement, and chronic obstructive pulmonary disease were all independently associated with mortality (P < .05)., Conclusions: The incidence of IC increased during the past 3 decades in a population-based cohort in Minnesota. IC typically presents in older patients with multiple comorbidities and is associated with high in-hospital mortality (11.5%) and rates of surgery (17%)., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Anti-TNFα biologics induce and maintain remission in inflammatory bowel disease (IBD). Also, they have been reported to induce or unmask idiopathic inflammatory demyelinating disease of the central nervous system (IIDD)., Aim: To determine if anti-TNFα biologics increased the risk of IIDD in a large cohort of patients with IBD., Methods: We retrospectively identified adult patients referred to the Mayo Clinic, Rochester, MN for management of IBD from a five state capture area (Minnesota, Wisconsin, North Dakota, South Dakota and Iowa) between 1996 and 2010. IIDDs were identified in both Crohn's disease (CD) and ulcerative colitis (UC) patients with and without anti-TNFα exposure using the 2010 McDonald MRI criteria. The risk of IIDDs in patients with and without anti-TNFα exposure was estimated for IBD; CD and UC groups separately., Results: A total of 9095 patients with IBD were identified (4342 CD and 4753 UC). Four patients with CD with exposure to anti-TNFα agents (4/2054) and five patients with CD without anti-TNFα exposure (5/2288) developed a confirmed IIDD. One patient with UC with exposure to anti-TNFα agents (1/1371) and five patients with UC without anti-TNFα agents developed a confirmed IIDD (5/3382). The per cent of IIDDs in patients with and without anti-TNFα exposure was; IBD: 0.15% and 0.18% (RR = 0.83, 95% CI: 0.28-2.42; P = 0.729); CD: 0.19% and 0.22% (RR = 0.89, 95% CI: 0.24-3.31; P = 0.863); UC: 0.07% and 0.15% (RR = 0.49, 95% CI: 0.06-4.22; P = 0.510)., Conclusion: Anti-TNFα biologics do not appear to impact the risk of developing clinical idiopathic inflammatory demyelinating disease in patients with inflammatory bowel disease., (© 2014 John Wiley & Sons Ltd.)

Background & Aims: The increasing incidence of microscopic colitis has been partly attributed to detection bias. We aimed to ascertain recent incidence trends and the overall prevalence of microscopic colitis in a population-based study., Methods: Using data from the Rochester Epidemiology Project, we identified residents of Olmsted County, Minnesota, who were diagnosed with collagenous colitis or lymphocytic colitis from January 1, 2002, through December 31, 2010, based on biopsy results and the presence of diarrhea (N = 182; mean age at diagnosis, 65.8 years; 76.4% women). Poisson regression analyses were performed to evaluate associations between incidence and age, sex, and calendar period., Results: The age- and sex-adjusted incidence of microscopic colitis was 21.0 cases per 100,000 person-years (95% confidence interval [CI], 18.0-24.1 cases per 100,000 person-years). The incidence of lymphocytic colitis was 12.0 per 100,000 person-years (95% CI, 9.6-14.3 per 100,000 person-years) and collagenous colitis was 9.1 per 100,000 person-years (95% CI, 7.0-11.1 per 100,000 person-years). The incidence of microscopic colitis and its subtypes remained stable over the study period (P = .63). Increasing age (P < .001) and female sex (P < .001) were associated with increasing incidence. On December 31, 2010, the prevalence of microscopic colitis was 219 cases per 100,000 persons (90.4 per 100,000 persons for collagenous colitis and 128.6 per 100,000 persons for lymphocytic colitis)., Conclusion: The incidence of microscopic colitis in Olmsted County residents has stabilized and remains associated with female sex and increasing age., (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.)

The optimal care of patients with inflammatory bowel disease depends on adherence to standards of care regarding diagnosis, informing the patient of potential risks of treatment, obtaining recommended baseline studies, and monitoring the patient for efficacy and adverse effects. In clinical research as well as practice, financial conflicts of interest must be disclosed and managed to insure that patients have sufficient information to make a decision regarding participation in a study and to insure their safety. Medical education of care-givers in training carries the obligation and liability to oversee the care of the IBD patient and insure that safe and optimal care. This review addresses medicolegal issues that can arise in the care of the patient with IBD. Clinicians who provide optimal care for patients with inflammatory bowel diseases (IBD) must employ appropriate diagnostic and therapeutic options and also adhere to standards of care and ethical principles. Ethical and medicolegal issues can arise from the failure to adhere to the standards of medical care, clinical research and education. In a report in the New England Journal of Medicine in 2011, gastroenterologists in the U.S. ranked 6th out of 26 subspecialities as the most commonly sued for malpractice, with the mean payment to the plaintiff of just under $200,000 [1]. It is noteworthy that two other specialties that involve invasive procedures ranked lower on the list than Gastroenterology. For example, Cardiology and Anesthesiology ranked 11th and 17th, respectively. In this review, nine of the pitfalls to adherence to the standards of practice for IBD are reviewed.

Background: Data on the differences in inpatient treatment approaches and outcomes between younger and older patients with inflammatory bowel disease (IBD) are limited. Therefore, we used a parallel cohort study design to compare outcomes between younger and older patients with IBD., Methods: All anti-tumor necrosis factor (TNF)-naive patients aged 60 years and older hospitalized at our institution between 2003 and 2011 and treated with corticosteroids for an IBD flare were matched 1:1 to younger patients aged 18 to 50 years. Rates of corticosteroid response, colectomy, and initiation of anti-TNF therapy were compared., Results: Sixty-five patients were identified in each cohort. Median ages were 70 years (range, 60-94) and 30 years (range, 18-50) for the older and younger groups, respectively. Twenty-three percent of older patients were refractory to corticosteroids compared with 38% of the younger cohort (odds ratio, 0.5; 95% confidence intervals, 0.2-1.1). Older corticosteroid-refractory patients had surgery (80% versus 72%) and were started on anti-TNF therapy (20% versus 12%; P = 0.71), at a similar frequency as younger patients. Older steroid-responsive patients were less likely to start an anti-TNF agent during the first year of follow-up than younger patients (7% versus 31%, P = 0.006), but there was no difference in 1-year colectomy rates (27% versus 28%, P = 0.63)., Conclusions: Corticosteroid response was similar in older and younger patients hospitalized for IBD. Inpatient treatment for corticosteroid-refractory patients was similar between cohorts. Older corticosteroid-responsive patients were less likely to be treated with an anti-TNF than younger patients.

Background: Up to 30% of cases of pouchitis are felt to have a secondary cause. Cytomegalovirus (CMV) may represent a possible etiopathological agent. Here, we report our experience with CMV involvement of the pouch, including risk factors, clinical features, and pouch outcomes in patients with inflammatory bowel disease after proctocolectomy with ileal pouch-anal anastomosis., Methods: The pathology database at Mayo Clinic in Rochester was searched between January 1995 and October 2012 for patients with a tissue diagnosis of CMV of the pouch following ileal pouch-anal anastomosis., Results: Seven patients with CMV inclusions of the pouch were identified. The median age was 35 (range, 10-53) years, and the majority were female (71%). Five patients (71%) were on immunosuppressive medications including 4 who had undergone orthotopic liver transplantation for primary sclerosing cholangitis. The clinical presentation was similar among all patients: the majority had diarrhea (86%), fever (71%), and abdominal pain (57%). All had mucosal inflammation, with 71% having focal ulcerations in the pouch and 60% having inflammatory changes in the prepouch ileum. All patients improved with ganciclovir. None required pouch excision or had recurrent CMV infection. Three patients had recurrent nonspecific pouchitis., Conclusions: A high index of suspicion is needed to diagnose CMV of the pouch. An increase in stool frequency and fever in patients on immune suppression or in those who have failed empiric antibiotics should prompt assessment for CMV infection. Antiviral therapy seems to be effective, and postinfection pouch outcomes seem favorable, particularly in those presenting with their first episode of pouchitis.

Background: We sought to identify clinical and demographic features influencing hospitalization and colectomy in a population-based inception cohort of ulcerative colitis., Methods: Between 1970 and 2004, a total of 369 patients (58.5% males) from Olmsted County, MN, were followed from diagnosis for 5401 person-years. The cumulative probability of hospitalization and colectomy were estimated using the Kaplan-Meier method. Cox proportional hazards regression was used to identify factors associated with hospitalization and colectomy., Results: The cumulative probability of first hospitalization was 29.4% at 5 years (95% confidence interval [CI], 24.5%-34.1%), 38.7% at 10 years (33.1%-43.8%), 49.2% at 20 years (42.7%-55.2%), and 52.3% at 30 years (45.1%-59.7%). The incidence rate of hospitalizations decreased over the last 4 decades, although cumulative probability of first hospitalization increased with successive decades of diagnosis. Early need for corticosteroids (hazard ratio [HR], 1.8; 95% CI, 1.1%-2.7%) and early need for hospitalization (HR, 1.5; 95% CI, 1.02-2.4) were independent predictors of hospitalization after 90 days of illness. The cumulative probability of colectomy from the time of diagnosis was 13.1% at 5 years (95% CI, 9.4%-16.6%), 18.9% at 10 years (95% CI, 14.4%-23.2%), and 25.4% at 20 years (95% CI, 19.8%-30.8%). Male gender (HR, 2.1; 95% CI, 1.3-3.5), diagnosis in the 1990s (HR, 2.0; 95% CI, 1.01-4.0), and diagnosis in 2000 to 2004 (HR, 3.7; 95% CI, 1.7-8.2) were significantly associated with colectomy risk., Conclusions: Colectomy rates were comparable to reports from northern Europe. The numbers of hospitalizations show a decreasing trend. Male gender and being diagnosed in the 2000 to 2004 period predicted colectomy while extensive colitis predicted future hospitalizations.

Objective: Spondyloarthritis (SpA) is an important extraintestinal manifestation of inflammatory bowel disease (IBD). We assessed the cumulative incidence and clinical spectrum of SpA in a population-based cohort of patients with ulcerative colitis (UC)., Methods: The medical records of a population-based cohort of residents of Olmsted County, Minnesota, USA, diagnosed with UC from 1970 through 2004 were reviewed. Patients were followed longitudinally until moving from Olmsted County, death, or June 30, 2011. We used the European Spondylarthropathy Study Group, Assessment of Spondyloarthritis International Society (ASAS) criteria, and modified New York criteria to identify patients with SpA., Results: The cohort included 365 patients with UC, of whom 41.9% were women. The median age at diagnosis of UC was 38.6 years (range 1.2-91.4). Forty patients developed SpA based on the ASAS criteria. The cumulative incidence of a diagnosis of SpA after an established diagnosis of UC was 4.8% at 10 years (95% CI 95% CI 2.2%-7.3%), 13.7% at 20 years (95% CI 9.0%-18.1%), and 22.1% at 30 years (95% CI 4.3%-29.1%)., Conclusion: The cumulative incidence of all forms of SpA increased to about 22% by 30 years from UC diagnosis. This value is slightly greater than what we previously described in a population-based cohort of Crohn disease diagnosed in Olmsted County over the same time period. SpA and its features are associated with UC, and heightened awareness on the part of clinicians is needed for diagnosing and managing them.

Institutional review boards are charged with overseeing that human studies research is conducted in accordance with federal and state regulations and with their own policies and procedures, with the goal of minimizing risks to participants and maximizing the quality of the research data. Nutrition research often involves vulnerable populations, including children and the cognitively impaired, for whom there are specific regulations. Ethical issues are common in nutrition research, and both the investigative team and the institutional review board should seek input regarding ethical issues that arise.

Background: Microscopic colitis and irritable bowel syndrome (IBS) are the common causes of watery diarrhea, abdominal discomfort, and other gastrointestinal symptoms. Previous retrospective data and post hoc analysis of information from a randomized controlled trial have suggested that there is considerable overlap between the symptoms seen in patients with microscopic colitis and the symptom-based criteria for IBS. We sought to study this overlap in a prospective cohort., Methods: A random cohort of patients with biopsy-proven microscopic colitis seen at our institution were administered a symptom questionnaire. Based on their responses, the proportion of patients who met various definitions for IBS was determined. Clinical characteristics of those meeting IBS criteria were compared with those who did not., Results: In the 120 patients who were included, 38% to 58% met the diagnostic criteria for IBS. These patients tended to be younger and more likely female than those who did not meet IBS criteria., Conclusions: Patients with microscopic colitis frequently meet the diagnostic criteria for IBS. Therefore, these criteria are not specific enough to exclude the presence of microscopic colitis. In patients with watery diarrhea, colonoscopy with mucosal biopsies should be performed if symptoms are not controlled by antidiarrheal medications.

Objectives: To evaluate the outcomes of corticosteroid-treated microscopic colitis (MC) in a population-based cohort, and to compare these outcomes in patients treated with prednisone or budesonide., Methods: A historical cohort study of Olmsted County, Minnesota residents diagnosed with collagenous or lymphocytic colitis (LC) between 1986 and 2010 was performed using the Rochester Epidemiology Project., Results: Of 315 patients with MC, 80 (25.4%) were treated with corticosteroids. The median age at colitis diagnosis was 66.5 years (range: 16-95) and 78.7% were female. Forty patients (50%) had LC and 40 (50%) had collagenous colitis. Prednisone was used in 17 patients (21.2%) and budesonide in 63 (78.8%); 56 (75.6%) had complete response and 15 (20.3%) had partial response. Patients treated with budesonide had a higher rate of complete response than those treated with prednisone (82.5 vs. 52.9%; odds ratio, 4.18; 95% CI, 1.3-13.5). Six patients were lost to follow-up. The remaining 74 had a median follow-up of 4 years (range 0.2-14). Fifty patients out of the 71 who responded (70.4%) had a recurrence after corticosteroid discontinuation. Patients treated with budesonide were less likely to recur than those treated with prednisone (hazard ratio, 0.38; 95% CI, 0.18-0.85; P=0.02). After 397 person years of follow-up in the 73 patients with long-term data, 47 (64.4%) required maintenance with corticosteroids., Conclusion: Patients with MC often respond to corticosteroid therapy, but with a high relapse rate. Budesonide had a higher response rate and a lower risk of recurrence than prednisone.

Background & Aims: Endoscopic healing is likely to become an important goal for treatment of patients with ulcerative colitis (UC). A simple validated endoscopic index is needed. We validated the previously developed UC Colonoscopic Index of Severity (UCCIS)., Methods: In a prospective study, 50 patients with UC were examined by colonoscopy; we analyzed videos of rectum and sigmoid, descending, transverse, and cecum/ascending colon. Eight gastroenterologists blindly rated 4 mucosal lesions (for vascular pattern, granularity, friability, ulceration) and severity of damage to each segment and overall. The global assessment of endoscopic severity (GAES) was based on a 4-point scale and 10-cm visual analogue scale. Correlation of the UCCIS score with clinical indexes (clinical activity index and simple clinical colitis activity index), patient-defined remission, and laboratory measures of disease activity (levels of C-reactive protein, albumin, and hemoglobin and platelet counts) were estimated by using the Pearson (r) or Spearman (r(s)) method., Results: Interobserver agreement was good to excellent for the 4 mucosal lesions evaluated by endoscopy and the GAES. The UCCIS calculated for our data accounted for 74% (R(2) = 0.74) and 80% (R(2) = 0.80) of the variation in the GAES and visual analogue scores, respectively (P < .0001). The UCCIS also correlated with clinical activity index (r = 0.52, P < .001), simple clinical colitis activity index (r = 0.62, P < .0001), and patient-defined remission (r = 0.43, P < .01). The UCCIS also correlated with levels of C-reactive protein (r(s) = 0.56, P < .001), albumin (r = -0.55, P < .001), and hemoglobin (r = -0.39, P < .01). A rederivation of the equation for the UCCIS by using the data from a previous study combined with those of the current study (n = 101) yielded similar results., Conclusions: The UCCIS is a simple tool that provides reproducible results in endoscopic scoring of patients with UC., (Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Not all patients with Crohn's disease (CD) respond or maintain response to anti-tumor necrosis factor (TNF) agents and alternative treatment is necessary. Natalizumab, a monoclonal antibody to alpha-4 integrin approved for CD, has demonstrated efficacy in randomized clinical trials. We describe our experience with natalizumab in clinical practice at Mayo Clinic Rochester., Methods: Consecutive patients prescribed natalizumab for active CD were invited to participate and were followed prospectively. Incidence of infection, hospitalization, neoplasm, or other adverse events were recorded. Clinical activity was assessed using the Harvey-Bradshaw Index at each 30-day infusion visit., Results: Between April 2008 and September 2010, 36 patients were prescribed natalizumab and 30 (83.3%) agreed to participate. Median disease duration was 9 years (range, 3-43). Twenty-three patients had prior exposure to two anti-TNF agents, seven to one agent. All patients experienced at least one adverse event; none of the 13 patients in whom natalizumab was stopped (43%) discontinued due to adverse events. Five patients had infusions held for infection. No patient developed progressive multifocal leukoencephalopathy (PML). Fourteen patients (46%) had clinical response. The cumulative probability of achieving complete response within 1 year was 56% (28%-73%). Four of seven patients were weaned off corticosteroids., Conclusions: In our experience with natalizumab in clinical practice, adverse events were manageable and did not result in treatment cessation. No PML cases were seen and clinical response was similar to that in clinical trials. Natalizumab results in clinical benefit in patients who have active disease and have failed anti-TNF therapy., (Copyright © 2012 Crohn's & Colitis Foundation of America, Inc.)

Objectives: We sought to estimate the need for surgery in an American population-based cohort of Crohn's disease., Methods: The medical records of 310 incident cases of Crohn's disease from Olmsted County, Minnesota, diagnosed between 1970 and 2004, were reviewed through March 2009. Cumulative incidence was estimated using the Kaplan-Meier method, and associations between baseline factors and time to first event were assessed using proportional hazards regression and expressed as hazards ratios (HRs) with 95% confidence intervals., Results: Median follow-up per patient was 12 years. One hundred and fifty-two patients underwent at least 1 major abdominal surgery, 65 had at least 2 surgeries, and 32 had at least 3 surgeries. The cumulative probability of major abdominal surgery was 38, 48, and 58% at 5, 10, and 20 years after diagnosis, respectively. Baseline factors significantly associated with time to major abdominal surgery were: ileocolonic (HR, 3.3), small bowel (HR, 3.4), and upper gastrointestinal (HR, 4.0) extent, relative to colonic alone; current cigarette smoking (HR, 1.7), male gender (HR, 1.6), penetrating disease behavior (HR, 2.7), and early corticosteroid use (HR=1.6). Major abdominal surgery rates remained stable, with 5-year cumulative probabilities in 1970-1974 and 2000-2004 of 37.5 and 35.1%, respectively., Conclusions: The cumulative probability of major abdominal surgery in this population-based cohort of Crohn's disease approached 60% after 20 years of disease, and many patients required second or third surgeries. Non-colonic disease extent, current smoking, male gender, penetrating disease behavior, and early steroid use were significantly associated with major abdominal surgery.

Objective: Spondyloarthritis (SpA) is an extraintestinal manifestation of inflammatory bowel disease with significant clinical effects, although the frequency is uncertain. We assessed the cumulative incidence and clinical spectrum of SpA in patients with Crohn's disease (CD) in a population-based cohort., Methods: The medical records of a population-based cohort of Olmsted County, Minnesota, residents diagnosed with CD between 1970 and 2004 were reviewed. Patients were followed longitudinally until migration, death, or December 31, 2010. We used the European Spondylarthropathy Study Group, Assessment of Spondyloarthritis international Society (ASAS) criteria and modified New York criteria to identify patients with SpA. The Kaplan-Meier method was used to estimate the cumulative incidence of SpA following diagnosis of CD., Results: The cohort included 311 patients with CD (49.8% females; median age 29.9 yrs, range 8-89). Thirty-two patients developed SpA based on ASAS criteria. The cumulative incidence of SpA after CD diagnosis was 6.7% (95% CI 2.5%-6.7%) at 10 years, 13.9% (95% CI 8.7%-18.8%) at 20 years, and 18.6% (95% CI 11.0%-25.5%) at 30 years. The 10-year cumulative incidence of ankylosing spondylitis was 0, while both the 20-year and 30-year cumulative incidences were 0.5% (95% CI 0-1.6%)., Conclusion: We have for the first time defined the actual cumulative incidence of SpA in CD using complete medical record information in a population-based cohort. The cumulative incidence of all forms of SpA increased to approximately 19% by 30 years from diagnosis of CD. Our results emphasize the importance of maintaining a high level of suspicion for SpA when following patients with CD.

About 10% of patients with colitis due to inflammatory bowel disease have indeterminate colitis. Despite newer diagnostic tools, the frequency has not diminished over the past 33 years. The current preferred term among academicians is colonic inflammatory bowel disease unclassified(IBDU), although indeterminate colitis is the term endorsed for inclusion in the ICD-10 coding system. Indeterminate colitis is more frequent among children. Theanti-Saccharomyces cerevisiae (ASCA) and perinuclear anti-cytoplasmic antibody (pANCA) are useful in distinguishing IBDU from ulcerative colitis and Crohn’s disease. However, current serologic and genetic studies, as well as endoscopic and imaging studies lack sufficient positive predictive values to make a definite diagnosis of Crohn’s colitis or ulcerative colitis. Patients with IBDU who undergo proctocolectomy with ileal pouch-anal anastomosis have more complications than patients with ulcerative colitis. Although some patients with indeterminate colitis eventually develop characteristic ulcerative colitis or Crohn’s disease, a subgroup are durably indeterminate.

We review the principal methods and issues in the governance of clinical research: oversight of human research by federal offices, certification of clinical trial centers, management of conflict of interest in clinical research, and trial registration and reporting.

Background: Computed tomographic enterography (CTE) has been shown to have a high sensitivity and specificity for active small bowel inflammation. There are only sparse data on the effect of CTE results on Crohn's disease (CD) patient care., Methods: We prospectively assessed 273 patients with established or suspected CD undergoing a clinically indicated CTE. Providers were asked to complete pre- and postimaging questionnaires regarding proposed clinical management plans and physician level of confidence (LOC) for the presence or absence of active small bowel disease, fistula(s), abscess(es), or stricturing disease. Correlative clinical, serologic, and histologic data were recorded. Following revelation of CTE results, providers were questioned if CTE altered their management plans, and whether LOC changes were due to CTE findings (on a 5-point scale)., Results: CTE altered management plans in 139 cases (51%). CTE changed management in 70 (48%) of those with established disease, prompting medication changes in 35 (24%). Management changes were made post-CTE in 69 (54%) of those with suspected CD, predominantly due to excluding CD (36%). CTE-perceived changes in management were independent of clinical, serologic, and histologic findings (P < 0.0001). Clinically meaningful LOC changes (2 or more points) were observed in 212 (78%)., Conclusions: CTE is a clinically useful examination, altering management plans in nearly half of patients with CD, while increasing physician LOC for the detection of small bowel inflammation and penetrating disease. These findings further support the use of CTE in CD management algorithms., (Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.)

Background: The cumulative incidence of and risk factors for perianal Crohn's disease (CD) for findings other than fistulas are unknown., Methods: The medical records of 310 incident cases of CD from Olmsted County, Minnesota, diagnosed between 1970 and 2004, were reviewed for evidence of perianal disease findings other than fistulas. Cumulative incidence was estimated using the Kaplan-Meier method, and associations between baseline factors and time to first event were assessed using proportional hazards regression. Four types of lesions were studied: anorectal strictures, deep anal canal ulcers, anal fissures, and perianal skin tags., Results: The 10-year cumulative probability from time of diagnosis was 5.8% (95% confidence interval [CI], 2.6%-8.8%) for anorectal strictures, 6.6% (3.6%-9.6%) for deep anal canal ulcers, 10.5% (6.8%-14.1%) for anal fissures, and 18.7% (13.9%-23.3%) for perianal skin tags. The cumulative probability for any perianal lesion other than fistulas was 21.3% (16.5%-25.8%) at 5 years and 29.2% (23.5%-34.5%) at 10 years. Baseline factors associated with time to first perianal lesion other than fistulas were age (hazard ratio [HR] per 10 years, 0.9; 95% CI, 0.8-0.98; P = 0.026), female gender (HR, 1.7; 95% CI, 1.1-2.7; P = 0.013), and presence of extraintestinal manifestations (HR, 1.7; 95% CI, 1.03-2.8; P = 0.038)., Conclusions: Perianal lesions other than fistulas occurred frequently during the clinical course of CD. Female gender and extraintestinal manifestations were associated with increased risks for perianal lesions other than fistulas, while older age at diagnosis was associated with a slightly decreased risk., (Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.)

Background: Endoscopic evaluation plays a pivotal role in the assessment of treatment response in ulcerative colitis (UC). This study aimed to determine the interobserver agreement (IOA) for assessment of mucosal lesions, and to determine lesions predictive of global assessment of endoscopic severity (GAES)., Methods: Fifty-one UC patients had digital videorecording of their colonoscopic examinations, edited into videoclips representative of five colonic segments (rectum, sigmoid, descending, transverse, ascending/cecum). Seven gastroenterologists specializing in inflammatory bowel disease (IBD) independently and blindly rated individual lesions and endoscopic severity for each segment and globally. Edema, erythema, stricture, loss of haustral folds, rigidity, and pseudopolyps were scored as absent or present while vascular pattern, granularity, ulceration, and bleeding-friability were scored using a predefined severity scale. The GAES was based on a 4-point scale and a 10-cm visual analog scale (VAS). The IOA among raters was estimated using Lin's concordance correlation coefficient (CCC). Strength of agreement was categorized as excellent (0.81-1.00), good (0.61-0.80), moderate (0.41-0.60), and fair (0.21-0.40). Linear regression analysis was used to identify lesions predictive of overall endoscopic severity and develop a scoring system for clinical use., Results: Granularity, vascular pattern, ulceration, bleeding/friability, and pseudopolyps had good IOA in most segments. There was excellent agreement for VAS and good agreement for GAES and the VAS was significantly associated with GAES (P < 0.001). Granularity, vascular pattern, ulceration, and bleeding-friability were significant predictors of overall endoscopic severity., Conclusions: Granularity, vascular pattern, ulceration, and bleeding-friability demonstrated good reproducibility and were predictors of the GAES in UC patients., (Copyright © 2010 Crohn's & Colitis Foundation of America, Inc.)

We examined the effect of a controlled diet and two probiotic preparations on urinary oxalate excretion, a risk factor for calcium oxalate kidney stone formation, in patients with mild hyperoxaluria. Patients were randomized to a placebo, a probiotic, or a synbiotic preparation. This tested whether these probiotic preparations can increase oxalate metabolism in the intestine and/or decrease oxalate absorption from the gut. Patients were maintained on a controlled diet to remove the confounding variable of differing oxalate intake from food. Urinary oxalate excretion and calcium oxalate supersaturation on the controlled diet were significantly lower compared with baseline on a free-choice diet. Neither study preparation reduced urinary oxalate excretion nor calcium oxalate supersaturation. Fecal lactobacilli colony counts increased on both preparations, whereas enterococcal and yeast colony counts were increased on the synbiotic. Total urine volume and the excretion of oxalate and calcium were all strong independent determinants of urinary calcium oxalate supersaturation. Hence, dietary oxalate restriction reduced urinary oxalate excretion, but the tested probiotics did not influence urinary oxalate levels in patients on a restricted oxalate diet. However, this study suggests that dietary oxalate restriction is useful for kidney stone prevention.

Background: We sought to assess the effectiveness and safety of adalimumab for the treatment of Crohn's disease (CD) in clinical practice., Methods: Demographic, clinical, and treatment data were abstracted from the medical record. The primary outcome was clinical response to induction therapy with adalimumab for CD (complete, partial, or nonresponse)., Results: In all, 118 patients were prescribed adalimumab for CD between January 2003 and June 2007. All but five subjects (96%) had received prior infliximab and 50 were on systemic corticosteroids at the time of initial adalimumab dose (44%). A complete response was achieved in 53 patients and 20 patients had no response. The cumulative probability of any response (complete or partial) was 81.3% at 1 year. Dose escalation was required in 59 patients (1-year cumulative probability, 54.0%). Among patients with complete response, 18 lost response during follow-up (1-year cumulative probability, 21.4%). Among 50 patients on corticosteroids at baseline the median daily dose was 20 mg, which decreased to a median of 0 mg during treatment. Sixty-four patients (54%) experienced a total of 117 adverse events. Thirteen patients (11%) experienced 15 serious adverse events. Sixteen patients (14%) discontinued adalimumab due to an adverse event., Conclusions: Adalimumab was both effective and well tolerated for the treatment of CD in this tertiary practice with a high prevalence of past infliximab exposure. This experience largely predates FDA approval of adalimumab for CD.

Background: The aim of this study was to assess the clinical benefit and tolerability of adalimumab, a fully human monoclonal antibody to tumor necrosis factor (TNF), in patients with ulcerative colitis (UC)., Methods: Patients with active UC, including those who had lost response or developed intolerance to the chimeric anti-TNF antibody infliximab, were enrolled in a 24-week uncontrolled trial. Patients were treated with subcutaneous adalimumab 160 mg at week 0, 80 mg at week 2, and 40 mg every other week starting at week 4. After week 8 the dose could be escalated to 40 mg weekly for incomplete response. Outcome measures included clinical response and remission and mucosal healing., Results: Twenty patients were enrolled, of whom 13 had previously received infliximab. Seven patients had dose escalation of adalimumab between weeks 8 and 16, from 40 mg every other week to 40 mg weekly, due to incomplete response. The rates of clinical response were 25% at week 8 and 50% at week 24. The rates of clinical remission were 5% at week 8 and 20% at week 24. The rate of mucosal healing was 30% at week 8. The rates of clinical response and remission and mucosal healing were similar in infliximab-naïve and previously exposed patients. None of the patients experienced hypersensitivity reactions during treatment with adalimumab., Conclusions: Adalimumab is well tolerated and appears to be a clinically beneficial option for patients with UC, including those who have previously lost their response to or cannot tolerate infliximab.

Bile acid malabsorption (BAM) is reported in up to 50% of patients with functional diarrhoea and irritable bowel syndrome with diarrhoea (IBS-D). Serum 7alpha-hydroxy-4-cholesten-3-one (7alphaHCO or 7alphaC4), an indirect measurement of hepatic bile acid synthesis, has been validated as a measurement of BAM relative to the (75)SeHCAT retention test. Our aim was to develop a serum 7alphaC4 assay, normal values, and compare results from healthy controls, patients with ileal Crohn's disease or resection, and patients with IBS-D or IBS with constipation (IBS-C). Stored serum samples were used from adult men and women in the following groups: 111 normal healthy controls, 15 IBS-D, 15 IBS-C, 24 with distal ileal Crohn's disease and 20 with distal ileal resection for Crohn's disease. We adapted a published high pressure liquid chromatography, tandem mass spectrometry (HPLC-MS/MS) assay. The HPLC-MS/MS assay showed good linearity in concentration range 0-200 ng mL(-1), sensitivity (lowest limit of detection 0.04 ng mL(-1)), and high analytical recovery (average 99%, range 93-107%). The 5th to 95th percentile for 111 normal healthy controls was 6-60.7 ng mL(-1). There were significant overall group differences (anovaon ranks, P < 0.001), with significantly higher values for terminal ileal disease or resection. There were significant differences between health and IBS (anova, P = 0.043) with higher mean values in IBS-D relative to controls (rank sum test, P = 0.027). We have established a sensitive non-isotopic assay based on HPLC-MS/MS, determined normal 7alphaC4 values, and identified increased 7alphaC4 in IBS-D and in distal ileal resection and disease. This assay has potential as a non-invasive test for BAM in IBS.

Background: This study was conducted to determine the prevalence of penetrating disease and extraintestinal manifestations of Crohn's disease (CD) identified by computed tomography enterography (CTE). We also sought to examine the percentage of clinically significant new noninflammatory bowel disease (IBD) related findings in these patients., Methods: We analyzed the records of 357 consecutive patients with previously diagnosed CD evaluated at our institution who underwent a CTE between August 2004 and October 2005. Radiology reports were reviewed for the presence of penetrating disease (abscess, fistula, or phlegmon) or extraintestinal IBD manifestations (nephrolithiasis, cholelithiasis, sacroiliitis, avascular necrosis, deep vein thrombosis, or primary sclerosing cholangitis). Additional non-IBD-related abnormalities were also recorded, including any mass or cystic lesion. Urgent findings were defined as those that were deemed by the radiologist or ordering physician to require medical follow-up within 3 months., Results: Of 357 patients identified (51% female) the median age was 41.6 years and median disease duration was 9.9 years. Of this cohort, 20.7% had penetrating disease (new finding in 58.1%) and 18.8% had extraintestinal IBD manifestations (new finding in 67.2%). Six patients had primary sclerosing cholangitis and portal/mesenteric vein thrombosis, respectively. In addition, 45.1% had non-IBD findings including 2 unsuspected malignancies. Most of these extraenteric non-IBD abnormalities were benign, with only 13.0% requiring urgent follow-up., Conclusions: CT enterography is a valuable diagnostic modality for detecting both penetrating disease and extraintestinal IBD manifestations. These data add to a growing body of evidence that supports the use of CTE in CD diagnostic and management algorithms.

Background: With the introduction of new techniques to image the small bowel, there remains uncertainty about their role for diagnosing Crohn's disease., Objective: To assess the sensitivity and specificity of capsule endoscopy (CE), CT enterography (CTE), ileocolonoscopy, and small-bowel follow-through (SBFT) in the diagnosis of small bowel Crohn's disease., Methods: Prospective, blinded trial., Setting: Inflammatory bowel disease clinic at an academic medical center., Patients: Known or suspected Crohn's disease. Exclusion criteria included known abdominal abscess and non-steroidal anti-inflammatory drug (NSAID) use. Partial small-bowel obstruction (PSBO) at CTE excluded patients from subsequent CE., Interventions: Patients underwent all 4 tests over a 4-day period., Main Outcome Measurements: Sensitivity, specificity, and accuracy of each test to detect active small-bowel Crohn's disease. The criterion standard was a consensus diagnosis based upon clinical presentation and all 4 studies., Results: Forty-one CTE examinations were performed. Seven patients (17%) had an asymptomatic PSBO. Forty patients underwent colonoscopy, 38 had SBFT studies, and 28 had CE examinations. Small-bowel Crohn's disease was active in 51%, absent in 42%, inactive in 5%, and suspicious in 2% of patients. The sensitivity of CE for detecting active small-bowel Crohn's disease was 83%, not significantly higher than CTE (83%), ileocolonoscopy (74%), or SBFT (65%). However, the specificity of CE (53%) was significantly lower than the other tests (P < .05). One patient developed a transient PSBO due to CE, but no patients had retained capsules., Limitation: Use of a consensus clinical diagnosis as the criterion standard-but this is how Crohn's disease is diagnosed in practice., Conclusions: The sensitivity of CE for active small-bowel Crohn's disease was not significantly different from CTE, ileocolonoscopy, or SBFT. However, lower specificity and the need for preceding small-bowel radiography (due to the high frequency of asymptomatic PSBO) may limit the utility of CE as a first-line test for Crohn's disease.

Physicians often take on responsibilities beyond medical care regarding their patients with ulcerative colitis and Crohn's disease: they serve as the patients' advocates to nonmedical entities and individuals, including insurance companies, schools, employers, companions, and family members. These responsibilities create a more complex relationship between the patient and their IBD physician. In addition, these responsibilities may accentuate ethical issues for the physician who is also engaged in clinical treatment trials for inflammatory bowel disease (IBD). Ethical issues include therapeutic misconception, clinical equipoise, and financial and nonfinancial conflicts of interest. Physicians who refer patients with IBD to enroll in treatment trials, as well as clinician investigators who conduct studies should consider measures to clarify the separation between clinical care and participation in a therapeutic study, and to ensure the ethical treatment of patients. These precautionary measures may include payment of participants to emphasize that the research study is different from clinical care, consent by an investigator other than the treating physician, and care to disclose conflicts of interest to the patient and the medical community in presentations and publications. If the financial conflict is too great, a physician should not participate in the clinical trial.

Background: There is conflicting data regarding the response to medical and surgical therapy for inflammatory bowel disease with respect to age at disease onset., Aim: To determine if the age at onset of Crohn's disease and ulcerative colitis is a risk factor for surgery for non-neoplastic bowel disease., Methods: This was a case-control study of patients evaluated between 1998 and 2001. Cases had undergone an initial operation for bowel disease. Controls were matched 1:1 for gender, disease subtype, date of first visit (+/-2 years), time from diagnosis prior to first visit (+/-3 years) and duration of follow-up. Association with age, disease extent, smoking history, medication use and co-morbidities vs. case/control status was assessed using multiple variable conditional logistic regression to estimate the odds ratio (OR) and 95% confidence intervals (CI) for undergoing surgery., Results: Among 132 Crohn's patients, older patients had lower odds for surgery (OR per 5 years, 0.86; 95% CI: 0.75-0.98). The rate of surgery for non-neoplastic bowel disease was not significantly associated with disease distribution, co-morbidities or cigarette smoking. Among 234 ulcerative colitis patients, the rate of surgery was unrelated to age, disease extent, co-morbidities or cigarette smoking,, Conclusions: For Crohn's disease, but not ulcerative colitis, the risk of surgery for non-neoplastic bowel disease decreases with increasing age at diagnosis, irrespective of disease distribution and history of cigarette smoking.

Objective: Although the epidemiology of microscopic colitis has been described in Europe, no such data exist from North America. We studied the incidence, prevalence and temporal trends of microscopic colitis in a geographically defined US population., Design and Setting: In this population based cohort study, residents of Olmsted County, Minnesota, with a new diagnosis of microscopic colitis, and all who had colon biopsies for evaluation of diarrhoea, between 1 January 1985 and 31 December 2001 were identified. Biopsies were reviewed for confirmation (cases) and to identify missed cases (diarrhoea biopsies)., Main Outcome Measures: Incidence rates, age and sex adjusted to the 2000 US white population. Poisson regression assessed the association of calendar period, age and sex with incidence., Results: We identified 130 incident cases for an overall rate of 8.6 cases per 100,000 person-years. There was a significant secular trend, with incidence increasing from 1.1 per 100,000 early in the study to 19.6 per 100,000 by the end (p<0.001). Rates increased with age (p<0.001). By subtype, the incidence was 3.1 per 100,000 for collagenous colitis and 5.5 per 100,000 for lymphocytic colitis. Collagenous colitis was associated with female sex (p<0.001) but lymphocytic colitis was not. Prevalence (per 100,000 persons) on 31 December 2001 was 103.0 (39.3 for collagenous colitis and 63.7 for lymphocytic colitis)., Conclusions: The incidence of microscopic colitis has increased significantly over time, and by the end of the study, the incidence and prevalence were significantly higher than reported previously. Microscopic colitis is associated with older age, and collagenous colitis is associated with female sex.

Objectives: Population-based data on risk factors and protective factors for colorectal dysplasia and cancer in patients with inflammatory bowel disease (IBD) are sparse. We conducted a nested case-control study of such factors in two well-described IBD cohorts from Copenhagen County, Denmark and Olmsted County, Minnesota., Methods: Forty-three neoplasia cases were matched on six criteria to 1-3 controls (N = 102). Medical records were scrutinized for demographic and clinical data. For each variable, the odds of neoplasia were estimated using conditional logistic regression., Results: Primary sclerosing cholangitis (PSC) (odds ratio [OR] 6.9, 95% confidence interval [CI] 1.2-40), percentage of disease course with clinically active disease (OR [per 5% increase] 1.2, 95% CI 0.996-1.4), and >or=1 yr of continuous symptoms (OR 3.2, 95% CI 1.2-8.6) were associated with neoplasia, whereas a borderline association with median number of small-bowel x-rays (OR 1.3, 95% CI 0.96-1.6) was observed. We did not observe a protective effect of frequency of physician visits (OR 1.4, 95% CI 0.96-2.0), number of colonoscopies (OR 1.4, 95% CI 1.0-2.1), cumulative dose of sulfasalazine (OR [per 1,000 g] 1.1, 95% CI 1.0-1.3) and mesalamine (OR [per 1,000 g] 1.3, 95% CI 0.9-1.9), or partial intestinal resections (OR 1.5, 95% CI 0.3-7.1)., Conclusions: Subgroups of IBD patients-those with PSC, severe long-standing disease, and exposure to x-ray-were at greater risk of colorectal neoplasia. The protective effect of close follow-up, colonoscopy, and treatment with 5-aminosalicylates was questionable.

Background: We previously reported that the prevalence of Crohn's disease (CD) and ulcerative colitis (UC) in Olmsted County, Minnesota, had risen significantly between 1940 and 1993. We sought to update the incidence and prevalence of these conditions in our region through 2000., Methods: The Rochester Epidemiology Project allows population-based studies of disease in county residents. CD and UC were defined by previously used criteria. County residents newly diagnosed between 1990 and 2000 were identified as incidence cases, and persons with these conditions alive and residing in the county on January 1, 2001, were identified as prevalence cases. All rates were adjusted to 2000 US Census figures for whites., Results: In 1990-2000 the adjusted annual incidence rates for UC and CD were 8.8 cases per 100,000 (95% confidence interval [CI], 7.2-10.5) and 7.9 per 100,000 (95% CI, 6.3-9.5), respectively, not significantly different from rates observed in 1970-1979. On January 1, 2001, there were 220 residents with CD, for an adjusted prevalence of 174 per 100,000 (95% CI, 151-197), and 269 residents with UC, for an adjusted prevalence of 214 per 100,000 (95% CI, 188-240)., Conclusion: Although incidence rates of CD and UC increased after 1940, they have remained stable over the past 30 years. Since 1991 the prevalence of UC decreased by 7%, and the prevalence of CD increased about 31%. Extrapolating these figures to US Census data, there were approximately 1.1 million people with inflammatory bowel disease in the US in 2000.

Background: Microscopic colitis is diagnosed on the basis of histologic criteria, and irritable bowel syndrome (IBS) is diagnosed by symptom-based criteria. There has been little investigation into the symptomatic overlap between these conditions. Our aim was to assess the prevalence of symptoms of irritable bowel syndrome in a population-based cohort of patients with microscopic colitis., Methods: The Rochester Epidemiology Project (REP), a medical records linkage system providing all health care data for the defined population of Olmsted County, Minnesota, was used to identify all county residents with a diagnosis of microscopic colitis between 1985 and 2001. The medical records of these individuals were reviewed to ascertain symptoms consistent with Rome, Rome II, and Manning criteria for irritable bowel syndrome., Results: One hundred thirty-one cases of microscopic colitis were identified. Median age at diagnosis was 68 years (range, 24-95); 71% were women. Sixty-nine (53%) and 73 (56%) met Rome and Rome II criteria for irritable bowel syndrome, respectively. Fifty-four (41%) had three or more Manning criteria. Forty-three (33%) had previously been diagnosed with irritable bowel syndrome., Conclusions: In this population-based cohort of histologically confirmed microscopic colitis, approximately one-half met symptom-based criteria for the diagnosis of irritable bowel syndrome. The clinical symptom-based criteria for irritable bowel syndrome are not specific enough to rule out the diagnosis of microscopic colitis. Therefore, patients with suspected diarrhea-predominant irritable bowel syndrome should undergo biopsies of the colon to investigate for possible microscopic colitis if symptoms are not well controlled by antidiarrheal therapy.

Background: The term indeterminate colitis is imprecise and without a generally accepted definition. Nevertheless, it is a term that is commonly used by gastroenterologists, pathologists and surgeons., Aim: To offer an opinion supported by published data, about the appropriate use of the term indeterminate colitis by addressing a series of questions., Methods: A PubMed database search was performed using the keywords, 'colitis' and 'inflammatory bowel disease' each combined individually with the following adjectives: 'indeterminate', 'unclassified', 'undefined', 'undiagnosed' and 'non-specific'., Results: There is no generally accepted definition of indeterminate colitis. All current applications of the term rely on exclusionary criteria and there is no confirmatory diagnostic test. Nevertheless, the diagnosis of indeterminate colitis appears to be durable in a subgroup of patients, suggesting that this group represents a unique phenotype., Conclusions: Indeterminate colitis has expanded from a strictly defined, postcolectomy pathological diagnosis to become, in addition, a clinical diagnosis without generally accepted criteria. A diagnosis of indeterminate colitis should be qualified with descriptors for the diagnostic criteria applied.

Biologics are a primary focus for research and development of new treatments for IBD and other immune disorders. CDER, which is a branch of the FDA, oversees most of the biologics that are being used or tested for IBD, and it regulates nonbiologic medications for IBD. The approval process for most biologics for IBD is similar to the process for nonbiologics. FDA regulation of a new drug or biologic can be divided into three stages: the commercial IND, the NDA, and postmarketing (phase 4) studies. It is unclear if generic versions of biologics can be approved within the current legislation.

Background and Aims: We followed a population based cohort of patients with inflammatory bowel disease (IBD) from Olmsted County, Minnesota, in order to analyse long term survival and cause specific mortality., Material and Methods: A total of 692 patients were followed for a median of 14 years. Standardised mortality ratios (SMRs, observed/expected deaths) were calculated for specific causes of death. Cox proportional hazards regression was used to determine if clinical variables were independently associated with mortality., Results: Fifty six of 314 Crohn's disease patients died compared with 46.0 expected (SMR 1.2 (95% confidence interval (CI) 0.9-1.6)), and 62 of 378 ulcerative colitis (UC) patients died compared with 79.2 expected (SMR 0.8 (95% CI 0.6-1.0)). Eighteen patients with Crohn's disease (32%) died from disease related complications, and 12 patients (19%) died from causes related to UC. In Crohn's disease, an increased risk of dying from non-malignant gastrointestinal causes (SMR 6.4 (95% CI 3.2-11.5)), gastrointestinal malignancies (SMR 4.7 (95% CI 1.7-10.2)), and chronic obstructive pulmonary disease (COPD) (SMR 3.5 (95% CI 1.3-7.5)) was observed. In UC, cardiovascular death was reduced (SMR 0.6 (95% CI 0.4-0.9)). Increased age at diagnosis and male sex were associated with mortality in both subtypes. In UC but not Crohn's disease, a diagnosis after 1980 was associated with decreased mortality., Conclusions: In this population based study of IBD patients from North America, overall survival was similar to that expected in the US White population. Crohn's disease patients were at increased risk of dying from gastrointestinal disease and COPD whereas UC patients had a decreased risk of cardiovascular death.

Background: Microscopic colitis is a common cause of chronic watery diarrhea of unknown origin. Some patients develop diarrhea after cholecystectomy, and some patients with microscopic colitis have evidence of bile acid malabsorption. However, the association between cholecystectomy and microscopic colitis has not been studied. A protective effect of appendectomy on the development of ulcerative colitis also has been reported, but its relationship with microscopic colitis has not been studied. The aim of this study was to assess cholecystectomy and appendectomy as potential risk factors for the development of microscopic colitis in a nested case-control study., Materials and Methods: Using the Rochester Epidemiology Project, we identified all Olmsted County (Minnesota) residents with an initial diagnosis of microscopic colitis between January 1, 1985, and December 31, 2001. Rates of antecedent cholecystectomy or appendectomy in patients with microscopic colitis were compared with age-, gender-, and calendar year-matched community controls through conditional logistic regression., Results: Microscopic colitis was identified in 130 cases. Cholecystectomy preceded the diagnosis of microscopic colitis in 12 cases (9%) compared with 17 (13%) in the control group (odds ratio [OR] 0.7; 95% CI 0.3-1.5). Appendectomy preceded the diagnosis of microscopic colitis in 39 subjects (30%) compared with 28 (22%) in the control group (OR 1.6; 95% CI 0.9-2.7). Similar results were obtained when the analysis was restricted to microscopic colitis subtype (lymphocytic colitis or collagenous colitis)., Conclusions: In this population-based nested case-control study, no significant association was seen between cholecystectomy or appendectomy and the development of microscopic colitis or its subtypes.

Background and Aims: The risk, fate, and ideal management of colorectal dysplasia in inflammatory bowel disease (IBD) remain debated. We estimated the incidence, long-term outcome, and risk factors for progression of colorectal dysplasia (adenomas [adenoma-associated lesions or masses (ALMs)], flat dysplasia, and dysplasia-associated lesions or masses [DALMs]) in a population-based IBD cohort from Olmsted County, Minnesota., Materials and Methods: The Rochester Epidemiology Project was used to identify cohort patients with colorectal dysplasia. Medical records were reviewed for demographic and clinical characteristics. Histology slides were reviewed by a pathologist blinded to previous pathology reports. The cumulative incidence of dysplasia was estimated, and the association between patient characteristics and recurrence/progression of dysplasia was assessed using proportional hazards regression., Results: Twenty-nine (4%) IBD patients developed flat dysplasia (n = 8), DALMs (n = 1), ALMs in areas of IBD (n = 18), or ALMs outside areas of IBD (n = 2). Among 6 patients with flat low-grade dysplasia (fLGD) who did not undergo colectomy, none progressed during a median of 17.8 (range 6-21) years of observation with a median of 3 (range 0-12) surveillance colonoscopies. Four (22%) patients with ALMs in areas of IBD who did not undergo surgery developed LGD or DALMs. Primary sclerosing cholangitis and dysplasia located proximal to the splenic flexure were significantly associated with risk for recurrence/progression of dysplasia., Conclusions: This population-based cohort study from Olmsted County, Minnesota did not confirm an increased risk of cancer related to fLGD, whereas 22% of patients with ALMs in areas of IBD developed fLGD or DALMs.

Background & Aims: Predictive and protective factors associated with colorectal cancer in chronic ulcerative colitis are not well described. Surveillance colonoscopy and 5-aminosalicylic acid therapy may mitigate cancer risk, but there is debate because these variables have not been evaluated in the same study. The presence of postinflammatory pseudopolyps and use of other anti-inflammatory medications may be important variables that influence risk, but data are sparse., Methods: Variables associated with colorectal cancer were registered in 188 patients with ulcerative colitis-related cancer and matched controls. Conditional logistic regression, adjusted for age at colitis diagnosis and colitis duration, identified a final set of variables independently associated with colorectal cancer., Results: In the final multiple variable model, the most important factors associated with colorectal cancer were a history of pseudopolyps (OR, 2.5; 95% CI: 1.4-4.6), 1 or 2 surveillance colonoscopies (OR, 0.4; 95% CI: 0.2-0.7), smoking (OR, 0.5; 95% CI: 0.2-0.9) and use of corticosteroids (OR, 0.4; 95% CI: 0.2-0.8), aspirin (OR, 0.3; 95% CI: 0.1-0.8), nonsteroidal anti-inflammatory drugs (OR, 0.1; 95% CI: 0.03-0.5), and 5-aminosalicylic acid agents (OR, 0.4; 95% CI: 0.2-0.9), although the latter was not statistically significant after 5 years. Primary sclerosing cholangitis and immunosuppressive use were not statistically significant., Conclusions: These results suggest that, in a population matched for extent and duration of chronic ulcerative colitis, surveillance colonoscopy and use of anti-inflammatory medications may reduce the risk of colorectal cancer. A history of postinflammatory pseudopolyps appears to be a predictive factor for cancer.

Background & Aims: The risk for colorectal cancer in Crohn's disease and ulcerative colitis patients from the United States currently is unknown. We estimated the risk for small-bowel and colorectal cancer in a population-based cohort of 692 inflammatory bowel disease patients from Olmsted County, Minnesota, from 1940 to 2001., Methods: The Rochester Epidemiology Project was used to identify cohort patients with colorectal and small-bowel cancer. The cumulative probability of cancer and standardized incidence ratios (SIR) were estimated using expected rates from Surveillance, Epidemiology, and End Results, white patients from Iowa, from 1973 to 2000, and Olmsted County, from 1980 to 1999., Results: Colorectal cancer was observed in 6 ulcerative colitis patients vs 5.38 expected (SIR, 1.1; 95% confidence interval [CI], 0.4-2.4), but 4 of these occurred among those with extensive colitis or pancolitis (SIR, 2.4; 95% CI, 0.6-6.0). Six Crohn's disease patients (vs 3.2 expected) developed colorectal cancer (SIR, 1.9; 95% CI, 0.7-4.1). Three Crohn's disease patients developed small-bowel cancer vs 0.07 expected (SIR, 40.6; 95% CI, 8.4-118)., Conclusions: The risk for colorectal cancer was not increased among ulcerative colitis patients overall, but appeared to be increased among those with extensive colitis. The colorectal cancer risk was increased slightly among Crohn's disease patients, who also had a 40-fold excess risk for small-bowel cancer.

Purpose: Previous studies have reported high morbidity and mortality in mothers and their offspring after colectomy for ulcerative colitis during pregnancy. This study was designed to assess the maternal and fetal outcomes of pregnant females undergoing colectomy for ulcerative colitis in the current era., Methods: A retrospective analysis was performed at our institution of all pregnant females undergoing operation for ulcerative colitis between 1980 and 2004. To compare this data to that of past literature, a MEDLINE search from 1951 to 2004 reviewed all cases reported on this topic., Results: Between 1980 and 2004, five females underwent an operation at our institution for fulminant ulcerative colitis while pregnant. All five patients underwent subtotal colectomy with Brooke ileostomy. Postoperative maternal morbidity included a superficial wound infection and a small asymptomatic intra-abdominal abscess. All females had successful pregnancies, and no maternal or fetal deaths occurred. Two patients went on to have an ileal pouch-anal anastomosis, one had a completion proctectomy and end ileostomy, one is scheduled for an ileal pouch-anal anastomosis, and one patient is lost to follow-up. The literature review revealed 37 cases. The overall fetal and maternal mortality was 49 and 22 percent respectively. Postoperative maternal morbidity was reported in 24 percent., Conclusions: In contrast to historic data, the maternal and fetal mortality from our series was zero and maternal morbidity was low. Subtotal colectomy and Brooke ileostomy for ulcerative colitis during pregnancy is safe. A multidisciplinary team that includes a gastroenterologist, high-risk obstetrician, and experienced surgeon is necessary for an optimal outcome.

Background: Delayed release budesonide was approved by the FDA for the treatment of mildly to moderately active Crohn's disease involving the ileum and ascending colon. Controlled trials have demonstrated that budesonide is effective in inducing remission and for maintenance of remission, with less frequent steroid side effects than conventional steroids. We sought to determine the benefit of this medication in clinical practice and to identify any non-FDA-approved uses that may warrant further study., Methods: Patients in whom oral budesonide was prescribed between November 1, 2001 and October 31, 2002, were identified and medical records were reviewed. Patients were categorized by indication for therapy: ileocolonic Crohn's disease (group 1), Crohn's disease elsewhere (group 2), and other conditions (group 3)., Results: A total of 225 patients were identified (108 in group 1, 62 in group 2, and 55 in group 3). Group 3 included patients with microscopic colitis (n = 28), pouchitis (n = 13), ulcerative colitis (n = 12), and celiac disease (n = 2). A favorable outcome occurred in 61% of group 1 patients but only 24% of patients in group 2. In group 3, only microscopic colitis patients and pouchitis patients experienced response rates >50% (77% and 60%, respectively)., Conclusion: Budesonide is effective in a majority of patients with ileocolonic Crohn's disease and microscopic colitis, which is consistent with results reported from clinical trials. A majority of patients with pouchitis also benefit from budesonide therapy, but prospective controlled trials are necessary to clarify the benefit in this group.

Background: Acute pancreatitis has occasionally been associated with Crohn's disease (CD), but whether a causal association exists remains unclear. We sought to determine the frequency of etiologies in a consecutive series of patients with CD with acute pancreatitis., Methods: A centralized diagnostic index was used to identify all patients with CD with acute pancreatitis that were evaluated at Mayo Clinic Rochester between 1976 and 2001. Both diagnoses were made or confirmed at our institution. Records were abstracted for demographics, presenting symptoms, diagnostic tests, risk factors of pancreatitis, treatment, and follow-up., Results: Forty-eight patients with CD with pancreatitis were identified. The median age at diagnosis of acute pancreatitis was 47 years (range, 31-91 yr). Forty-six (96%) met biochemical criteria for acute pancreatitis. The most sensitive radiographic tests were abdominal computed tomography (70%) and abdominal ultrasound (46%). The etiology of pancreatitis was considered to be gallstones (21%), significant alcohol intake (15%), use of purine analogs (13%), duodenal Crohn's involvement (12%), postendoscopic retrograde cholangiopancreatography complications (10%), postoperative complications (12%), use of other medications (4%) and idiopathic (8%). The median length of hospitalization was 7 days (range, 0-40 d). Ten patients (21%) had recurrence of acute pancreatitis. Three patients (6%) were subsequently diagnosed with pancreatic cancer., Conclusions: A definite etiology could be identified in most patients with CD with acute pancreatitis. Gallstones and alcohol accounted for more than one third of cases, whereas CD, either because of duodenal involvement or medications used for its treatment, accounted for more than one quarter of the cases. A small proportion of patients remained idiopathic.

Published in 1974, the Belmont Report established the ethical principles for conducting clinical research in the United States. The essential concepts are respect for the research participant, beneficence for society at large, and justice (equal access to participation and equal treatment) toward subjects in a research study. These principles are applied through the use of informed consent, risk/benefit assessment, and the impartial selection of study subjects. Strict adherence to these criteria often results in conflicts of interest, which the investigator must anticipate and manage. Investigators must also be thoroughly acquainted with the principles of Good Clinical Practice and regulatory requirements. Recent implementation of the Privacy Rule now requires the investigator to protect not only the safety but the privacy of the research subject. While the regulatory obligations can appear onerous, strict compliance results in clinical research that is safe, scientifically sound, and ethical.

Introduction: We sought to examine the relationship between C-reactive protein (CRP) and clinical, endoscopic, histologic, and radiographic activity in inflammatory bowel disease (IBD)., Methods: All IBD patients at our institution between January 2002 and August 2003 who had a CRP, colonoscopy, and either small bowel follow-through (SBFT) or CT enterography (CTE) performed within 14 days were identified. Clinical activity was assessed retrospectively through review of the medical record. Logistic regression was used in Crohn's disease (CD) patients to estimate the odds ratio (OR) with 95% confidence intervals for an elevated CRP. Associations were assessed using Fisher exact test in ulcerative colitis (UC) patients due to small sample size., Results: One-hundred four CD patients (46% males) and 43 UC and indeterminate colitis patients (44% males) were identified. In CD patients, moderate-severe clinical activity (OR, 4.5; 95% CI, 1.1-18.3), active disease at colonoscopy (OR, 3.5; 95% CI, 1.4-8.9), and histologically severe inflammation (OR, 10.6; 95% CI; 1.1-104) were all significantly associated with CRP elevation. Abnormal small bowel radiographic imaging was not significantly associated with CRP elevation. In UC patients, CRP elevation was significantly associated with severe clinical activity, elevation in sedimentation rate, anemia, hypoalbuminemia, and active disease at ileocolonoscopy, but not with histologic inflammation., Conclusions: CRP elevation in IBD patients is associated with clinical disease activity, endoscopic inflammation, severely active histologic inflammation (in CD patients), and several other biomarkers of inflammation, but not with radiographic activity.