Fecal microbiota dynamics during disease activity and remission in newly diagnosed and established ulcerative colitis.

Patients with ulcerative colitis (UC) have an altered gut microbiota composition, but the microbial relationship to disease activity needs to be further elucidated. Therefore, temporal dynamics of the fecal microbial community during remission and flare was determined. Fecal samples were collected at 2-6 time-points from UC patients during established disease (cohort EST) and at diagnosis (cohort NEW). Sampling range for cohort EST was 3-10 months and for cohort NEW 36 months. Relapses were monitored for an additional three years for cohort EST. Microbial composition was assessed by Genetic Analysis GA-map Dysbiosis Test, targeting ≥ 300 bacteria. Eighteen patients in cohort EST (8 with maintained remission and 10 experiencing a flare), provided 71 fecal samples. In cohort NEW, 13 patients provided 49 fecal samples. The microbial composition showed no clustering related to disease activity in any cohort. Microbial dissimilarity was higher between than within patients for both cohorts, irrespective of presence of a flare. Microbial stability within patients was constant over time with no major shift in overall composition nor modification in the abundance of any specific species. Microbial composition was not affected by intensified medical treatment or linked to future disease course. Thus in UC, the gut microbiota is highly stable irrespective of disease stage, disease activity or treatment escalation. This suggests that prolonged dietary interventions or repeated fecal transplantations are needed to be able to induce permanent alterations of the gut microbiota.

Fecal microbiota composition is linked to the postoperative disease course in patients with Crohn's disease.

BACKGROUND: The role of the fecal microbiota composition for the postoperative disease course of patients with Crohn's disease (CD) who have undergone ileocecal resection remains to be established. In this study, we investigated if the fecal microbiota composition, determined by a high throughput test quantifying a pre-selected set of bacteria, is associated with the postoperative disease course of CD patients. METHODS: Fecal samples were obtained from healthy subjects as well as from CD patients, 3-10 weeks and 1 year after ileocaecal resection. The fecal microbial composition was analyzed by Genetic Analysis GA-map Dysbiosis test, targeting ≥300 bacteria on different taxonomic levels. Postoperative disease status was assessed endoscopically according to Rutgeerts scoring system 1 year after surgery. Differences in fecal microbiota composition between groups were analyzed by multivariate factor analyses and cluster analysis. Microbial stability over time was determined using Bray-Curtis dissimilarity. RESULTS: One year after surgery, the fecal microbiota composition differed between CD patients (n = 21) and healthy subjects (n = 7). At this time point, the microbiota composition of CD patients was associated with disease course, clearly separating patients with disease relapse (n = 8) and patients in remission (n = 13). Further, the microbial within-patient stability was high during the first year after surgery, irrespective of disease course. CONCLUSION: The fecal microbiota composition of CD patients, analyzed by GA-map Dysbiosis test, is subject to little variation over time, and may potentially be used as a non-invasive diagnostic tool for the postoperative disease course.

Psychological distress, iron deficiency, active disease and female gender are independent risk factors for fatigue in patients with ulcerative colitis.

BACKGROUND: Patients with ulcerative colitis often report fatigue. OBJECTIVES: To investigate prevalence of and risk factors for fatigue in patients with ulcerative colitis with active disease and during deep remission. METHODS: In this cross-sectional study, disease activity was evaluated with endoscopy and calprotectin, and patients were classified as having active disease (n = 133) or being in deep remission (n = 155). Blood samples were analysed to assess anaemia, iron deficiency and systemic immune activity. Patients completed questionnaires to assess fatigue, psychological distress, gastrointestinal symptoms and quality of life. RESULTS: The prevalence of high fatigue (general fatigue ≥ 13, Multidimensional Fatigue Inventory) was 40% in the full study population. Among patients with high fatigue, female gender and iron deficiency were more prevalent, and these patients had more severe disease activity and reported higher levels of anxiety, depression and decreased quality of life compared with patients with no/mild fatigue. A logistic regression analysis identified probable psychiatric disorder (odds ratio (OR) (confidence interval) 6.1 (3.1-12.2)), iron deficiency (OR 2.5 (1.2-5.1)), active disease (OR 2.2 (1.2-3.9)) and female gender (OR 2.1 (1.1-3.7)) as independent risk factors for high fatigue. Similar results were found concerning psychological distress, gender and quality of life, but immune markers did not differ in patients in deep remission with high vs. no/mild fatigue. CONCLUSIONS: Probable psychiatric disorder, iron deficiency, active disease and female gender are independent risk factors for high fatigue in patients with ulcerative colitis. Low-grade immune activity does not seem to be the cause of fatigue among patients in deep remission.

Anti-TNF Therapy Response in Patients with Ulcerative Colitis Is Associated with Colonic Antimicrobial Peptide Expression and Microbiota Composition.

BACKGROUND AND AIMS: Anti-tumour necrosis factor [TNF] therapy is used in patients with ulcerative colitis [UC], but not all patients respond to treatment. Antimicrobial peptides [AMPs] and the gut microbiota are essential for gut homeostasis and may be important for treatment outcome. The aim of this study was to determine AMP and microbiota profiles in patients with UC before anti-TNF therapy start and correlate these data to treatment outcome. METHODS: Serum and biopsies were obtained from UC patients naïve to biological therapy [n = 56] before anti-TNF therapy start [baseline]. Fecal samples were taken at baseline and Weeks 2 and 6. Quantitative proteomic analysis was performed in mucosal biopsies. Expression of AMPs and cytokines was determined in biopsies and serum. Microbiota analysis of fecal samples was performed using GA-map™ Dysbiosis Test and real-time quantitative polymerase chain reaction [rtPCR]. Treatment response was evaluated 12-14 weeks after baseline. RESULTS: At baseline, proteomic analysis of biopsies showed that treatment responders and non-responders had differential expression of AMPs. Eleven AMP and AMP-related genes were analysed by rtPCR in mucosal biopsies and could together discriminate responders from non-responders at baseline. The most important nominators for response were increased expression of defensin 5 and eosinophilic cationic protein. Microbiota analysis revealed lower dysbiosis indexes and higher abundance of Faecalibacterium prausnitzii in responders compared with non-responders at baseline. Also, abundance of F. prausnitzii increased during induction therapy in responders. CONCLUSIONS: Anti-TNF therapy responders and non-responders display distinctly separate patterns of mucosal AMP expression and gut microbiota before treatment start. This indicates that intestinal antimicrobial/microbial composition can influence treatment outcome.

Diagnostic Performance of Five Assays for Anti-Hepatitis E Virus IgG and IgM in a Large Cohort Study.

Determination of anti-hepatitis E virus (anti-HEV) antibodies is still enigmatic. There is no gold standard, and results obtained with different assays often diverge. Herein, five assays were compared for detection of anti-HEV IgM and IgG. Serum samples from 500 Swedish blood donors and 316 patients, of whom 136 had suspected HEV infection, were analyzed. Concordant results for IgM and IgG with all assays were obtained only for 71% and 70% of patients with suspected hepatitis E, respectively. The range of sensitivity for anti-HEV detection was broad (42% to 96%); this was reflected in the detection limit, which varied up to 19-fold for IgM and 17-fold for IgG between assays. HEV RNA was analyzed in all patients and in those blood donors reactive for anti-HEV in any assay, and it was found in 26 individuals. Among all of the assays, both anti-HEV IgG and IgM were detected in 10 of those individuals. Twelve had only IgG and, in 7 of those 12, IgG was only detected with the two most sensitive assays. Three of the HEV-RNA-positive samples were negative for anti-HEV IgM and IgG in all assays. With the two most sensitive assays, anti-HEV IgG was identified in 16% of the blood donor samples and in 66% of patients with suspected HEV infection. Because several HEV-RNA-positive samples had only anti-HEV IgG without anti-HEV IgM or lacked anti-HEV antibodies, analysis for HEV RNA may be warranted as a complement in the laboratory diagnosis of ongoing HEV infection.

The severity of inflammation at onset of ulcerative colitis is not associated with IBS-like symptoms during clinical remission.

BACKGROUND AND AIMS: Symptoms compatible with irritable bowel syndrome (IBS) are common in patients with ulcerative colitis (UC) in clinical remission. It has been suggested that these symptoms might arise due to post-inflammatory changes comparable with post-infectious IBS. The aim was to study factors at new onset of UC that predict development of IBS-like symptoms during clinical remission. METHODS: In total, 98 patients with new onset of UC were followed prospectively for 3 years with yearly follow-up visits. Data from the first visit at the onset of UC were compared between a group of patients who fulfilled the criteria for IBS while in remission (UCR+IBS) during follow-up and a group who did not (UCR-IBS). RESULTS: Among the UC patients, 87 met the criteria for clinical remission and 25 (29%) of these reported IBS-like symptoms in remission during follow-up. There was no difference in inflammatory disease activity at the initial flare or in the prevalence of previous IBS symptoms when comparing UCR+IBS and UCR-IBS patients. The UCR+IBS patients reported more severe gastrointestinal symptoms, including abdominal pain, during their primary flare. CONCLUSION: The severity and extent of inflammation at onset of UC do not seem to affect the development of IBS-like symptoms in UC patients during clinical remission. The high prevalence of IBS-like symptoms is not explained by pre-existing IBS. UCR+IBS patients reported more severe gastrointestinal symptoms at disease onset, which might indicate a more sensitive gastrointestinal tract in this category of patients.

Global mucosal and serum cytokine profile in patients with ulcerative colitis undergoing anti-TNF therapy.

BACKGROUND AND OBJECTIVE: The knowledge of the effects of anti-tumour necrosis factor (TNF) treatment on the global cytokine profile in patients with ulcerative colitis (UC) is limited. A better understanding of these mechanisms could improve the ability to select patients that should undergo the therapy. Therefore, the aim was to determine the global mucosal and serum cytokine profile before and during induction therapy with anti-TNF in UC patients. MATERIALS AND METHODS: In total, mucosal biopsies (n = 28) and serum samples (n = 42) were collected from UC patients (total n = 48) before anti-TNF therapy. At week 14 response to the therapy was evaluated and again mucosal biopsies (n = 14) and serum samples (n = 42) were collected. Quantitative real-time PCR was used to determine mucosal cytokine mRNA expression and the MSD MULTI-ARRAY assay system platform was used for analysis of cytokines in serum. The global cytokine profile was evaluated by multivariate factor analysis. RESULTS: At baseline, the global profile of mucosal cytokine mRNA expression and serum cytokines discriminated therapy responders from non-responders. Responders had lower mucosal mRNA expression of interleukin 1ß (IL-1ß), IL-17A, IL-6 and interferon γ (IFN-γ) than non-responders. Fourteen weeks after therapy start mucosal IL-1ß and IL-6 were down-regulated in therapy responders but not in non-responders. At week 14, serum levels of IL-6 were decreased in therapy responders whereas IFN-γ and IL-12p70 were increased in non-responders. CONCLUSIONS: Our data suggest that patients with a therapy failure have a more severe pro-inflammatory cytokine profile before start of anti-TNF treatment, which is less well suppressed by the treatment as compared to therapy responders.

Pharmacological intervention based on fecal calprotectin levels in patients with ulcerative colitis at high risk of a relapse: A prospective, randomized, controlled study.

BACKGROUND: Targeted therapy, using biomarkers to assess disease activity in ulcerative colitis (UC), has been proposed. OBJECTIVE: The objective of this study was to evaluate whether pharmacological intervention guided by fecal calprotectin (FC) prolongs remission in patients with UC. METHODS: A total of 91 adults with UC in remission were randomized to an intervention group or a control group. Analysis of FC was performed monthly, during 18 months. A FC value of 300 µg/g was set as the cut-off for intervention, which was a dose escalation of the oral 5-aminosalicylate (5-ASA) agent. The primary study end-point was the number of patients to have relapsed by month 18. RESULTS: There were relapses in 18 (35.3%) and 20 (50.0%) patients in the intervention and the control groups, respectively (p = 0.23); and 28 (54.9%) patients in the intervention group and 28 (70.0%) patients in the control group had a FC > 300 µg/g, of which 8 (28.6%) and 16 (57.1%) relapsed, respectively (p < 0.05). CONCLUSION: Active intervention significantly reduced relapse rates, although no significant difference was reached between the groups overall. Thus, FC-levels might be used to identify patients with UC at risk for a flare, and a dose escalation of their 5-ASA agent is a therapeutic option for these patients.

Response to infliximab therapy in ulcerative colitis is associated with decreased monocyte activation, reduced CCL2 expression and downregulation of Tenascin C.

BACKGROUND AND AIMS: The cellular mechanisms leading to infliximab therapy response in patients with ulcerative colitis (UC) are incompletely known. We therefore investigated early effects of infliximab therapy on monocytes and associated chemokines linked to clinical therapy response in UC patients. METHODS: Blood and biopsies were obtained from anti-TNF therapy-naïve UC patients (n = 43) before (baseline) and during induction therapy with infliximab. Therapy response was evaluated at Week 14. Expression of monocyte activation markers and levels of chemokines in serum and biopsies were determined. Quantitative proteomic analysis was performed in cultured mucosal biopsies, and obtained data was validated in serum. RESULTS: In therapy responders, but not in non-responders, infliximab reduced blood monocyte expression of CD14 and CD86, 2 weeks after therapy commenced, relative to baseline. Serum CCL2 levels were decreased only among therapy responders at Week 2 and Week 14, relative to baseline. These data corresponded with lower levels of CD14, CD86 and CCL2 in intestinal tissue in responders as compared with non-responders at Week 14. Proteomic analysis of cultured biopsies showed that infliximab induced a reduction in Tenascin C that predicted downregulation of CCL2. Therapy responders, but not non-responders, had decreased serum Tenascin C levels at Week 2 and Week 14, relative to baseline. CONCLUSIONS: Infliximab therapy response in UC patients is associated with reduced monocyte activation and serum levels of CCL2 2 weeks after therapy commencement. In therapy responders, infliximab influenced Tenascin C, which might be a regulator of CCL2 expression and important for induction of the clinical therapy response.

The intra-individual variability of faecal calprotectin: a prospective study in patients with active ulcerative colitis.

BACKGROUND AND AIMS: Leukocyte-derived proteins in faeces, especially calprotectin, are increasingly used to assess disease activity in ulcerative colitis. The objectives of the present study were to assess the importance of factors related to the stool sampling procedure. METHODS: For 2 days, patients with active ulcerative colitis collected two stool samples at each bowel movement. The time of defecation, consistency and presence of blood were self-recorded in a diary. The variability in the concentrations of calprotectin during the day and between two consecutive days was assessed, as was the stability of calprotectin concentrations in samples stored at room temperature. RESULTS: Altogether, 18 patients collected 287 stool samples. The intraclass correlation coefficient in pairs of samples from 132 bowel movements was 0.79 (95% CI 0.48-0.90). The median individual coefficient of variation in samples collected during the same day was 52% (4-178). There was a correlation between the level of calprotectin and the time between bowel movements (r = 0.5; p = 0.013). After 3 days at room temperature the calprotectin concentrations in stool samples were unchanged, but after 7 days a significant (p < 0.01) decrease was found (mean 28%; 95% CI 0.10-0.47). CONCLUSION: The present data reveal a great variability in the concentrations of calprotectin in stool samples collected during a single day. Since the levels of calprotectin increased with longer time between the bowel movements, it seems most appropriate to analyse stool from the first bowel movement in the morning. Moreover, storage of stool samples at room temperature for more than 3 days is not advisable.

Fecal calprotectin one year after ileocaecal resection for Crohn's disease--a comparison with findings at ileocolonoscopy.

BACKGROUND AND AIMS: Ileocaecal resection for Crohn's disease is commonly performed. The severity of endoscopic lesions in the anastomotic area one year postoperatively is considered to reflect the subsequent clinical course. Fecal calprotectin (FC) has been shown to correlate with the findings at ileocolonoscopy in Crohn's disease. The objectives of this study were to assess whether the concentration of FC reflects the endoscopic findings one year after ileocaecal resection and to evaluate the variation of FC in individual patients during 6months prior to the ileocolonoscopy. METHODS: Thirty patients with Crohn's disease and ileocaecal resection performed within one year were included. Stool samples were delivered monthly until an ileocolonoscopy was performed one year postoperatively. RESULTS: One year after surgery the median values of FC were not significantly different between the patients in endoscopic remission (n=17) and the patients with an endoscopic recurrence (189 (75-364) vs 227 (120-1066)µg/g; p=0.25). However, most patients with low values were in remission and all patients with high (>600µg/g) calprotectin values had recurrent disease. The variability of the FC concentration was most pronounced in patients with diarrhea. CONCLUSIONS: We found no statistical difference in the concentrations of calprotectin between patients in endoscopic remission and patients with a recurrent disease one year after ileocaecal resection for Crohn's disease. However, among the minority of patients with low or high values, FC indicated remission and recurrence, respectively. There was significant variation of the fecal calprotectin concentrations over time, which affects the utility of calprotectin in clinical practice.

Fecal chromogranins and secretogranins are increased in patients with ulcerative colitis but are not associated with disease activity.

BACKGROUND: Little is known of the importance of chromogranins (Cg) and secretogranins (Sg) in ulcerative colitis (UC). We therefore investigated fecal levels of CgA, CgB, SgII and SgIII, and their association with inflammatory activity, disease duration and medical therapy in UC. METHODS: Analyses of CgA, CgB, SgII, SgIII and calprotectin in stool samples from 41 UC patients and 29 healthy controls were performed. Two stool samples, during relapse and remission, respectively, were obtained from each UC patient. RESULTS: The levels of fecal CgA and SgII were higher in UC patients with active disease as compared to healthy controls. CgB and SgII were positively correlated with disease duration, but none of the granins were positively correlated with calprotectin, Mayo score, CRP or serum concentrations of TNF in UC patients with active disease. Also UC patients in remission had higher levels of CgA, CgB, SgII, and SgIII as compared to healthy controls. However, levels of fecal CgA, CgB, SgII and SgIII were lower during active disease relative to remission. Moreover, fecal levels of CgA and SgII were higher in UC patients in remission treated with thiopurines than in thiopurine-naïve patients in remission. CONCLUSION: Fecal chromogranins and secretogranins are increased in UC but are not associated with disease activity, but seem to increase with duration of the disease. Thus, fecal granins might reflect structural changes associated with chronicity of disease, or medical therapy.

Fecal calprotectin levels predict the clinical course in patients with new onset of ulcerative colitis.

BACKGROUND: The clinical course of ulcerative colitis (UC) is unpredictable. During recent years, the ability of fecal biomarkers to predict relapse in inflammatory bowel disease has been evaluated. The objective of this study was to assess fecal calprotectin (FC) as a predictor of disease recurrence in patients with new onset of UC. METHODS: Sixty-nine patients were included. After the initial treatment, patients were followed up after 3 months and then yearly for 3 years. The prognostic role of FC 3 months after the initial therapy was evaluated. RESULTS: The FC levels 3 months after the diagnosis were higher in patients experiencing a relapsing disease course compared with those with a mild disease course during 1 year (median, 263; interquartile range [IQR], 100-634 µg/g versus median, 102; IQR, 38-225 µg/g; P = 0.009) and 3 years of follow-up (median, 280; IQR, 102-622 µg/g versus median, 118; IQR, 39-219 µg/g; P = 0.01). The area under the receiver operating characteristic curves using calprotectin to predict a relapsing disease course during 1 year and 3 years were 0.69 (95% confidence interval, 0.56-0.82) and 0.70 (95% confidence interval, 0.57-0.83), respectively. In the Kaplan-Meier survival analysis, a FC level >262 µg/g was associated with an increased risk of a relapsing disease course during the study period (P = 0.003). In logistic regression analysis, only FC and age were found to be independent predictors of having a relapsing disease course. CONCLUSIONS: Levels of FC 3 months after the initial therapy in patients with new onset of UC predict the disease course over the following years, and they are of value in the clinical management of these patients.

CD25 and TNF receptor II reflect early primary response to infliximab therapy in patients with ulcerative colitis.

BACKGROUND: Although infliximab treatment is an option for patients with ulcerative colitis (UC), not all patients do respond to therapy, and cellular mechanisms leading to therapy response are incompletely known. OBJECTIVE: The objective of this article is to determine early effects of infliximab therapy on T cells in the blood of UC patients and if effects differed in therapy responders and nonresponders. METHODS: Blood samples were obtained before and two weeks post-treatment start from 34 anti-tumor necrosis factor (TNF) therapy-naïve UC patients undergoing infliximab therapy. Response to therapy was evaluated prior to the fourth treatment dose. Expression of T cell surface markers and levels of soluble receptors and cytokines in serum were determined. RESULTS: At baseline, there were no differences in cellular, biochemical or clinical parameters between therapy responders and nonresponders. Infliximab therapy reduced frequencies of CD25(+) T cells and increased frequencies of annexin V(+) T cells in patients responding to infliximab, but not in nonresponding patients, two weeks after therapy start. Only therapy responders had decreased serum levels of sCD25 and sTNFRII two weeks after treatment start. In contrast, clinical parameters did not reflect therapy outcome already two weeks after therapy start. CONCLUSION: Soluble and membrane-bound T cell receptors may be early indicators of infliximab therapy response in UC, which can be of clinical importance for the decision when to continue or to stop the treatment.

Diagnostic yield of colonoscopy based on symptoms.

OBJECTIVE: There are only a few data on the diagnostic yield of colonoscopy in different symptoms. The aim of this study was to assess the outcome of colonoscopy in patients with various gastrointestinal symptoms and to estimate the relation between the findings and the presenting symptoms. MATERIAL AND METHODS: 1121 consecutive colonoscopies were registered during 1 year. Asymptomatic subjects and patients with known inflammatory bowel disease (IBD) were excluded, leaving 767 eligible for the study. Symptoms, findings and clinical judgement about their relation were recorded. RESULTS: In patients with bleeding symptoms (n=405), serious colonic pathology--cancers and adenomas >1 cm, IBD and angiodysplasia--was found in 54 (13.3%), 83 (20.5%) and 20 (4.9%) patients, respectively; 162 (40%) patients had findings that could be related to the symptom. In 173 subjects with non-bloody diarrhoea, the diagnostic yield was 31.2%, i.e. mostly IBD and microscopic colitis. In 189 subjects with other gastrointestinal symptoms, the diagnostic yield was 13.2%. Serious colonic pathology was found in 8 of 362 (2.2%) subjects examined because of non-bleeding symptoms. CONCLUSION: The diagnostic yield of colonoscopy is high in patients with bleeding symptoms or diarrhoea, while the prevalence of significant findings is equal to a screening population in patients with other symptoms.

Extracolonic and incidental findings on CT colonography (virtual colonoscopy).

OBJECTIVE: The objective of our study was to prospectively determine the frequency and clinical importance of extracolonic findings on CT colonography in symptomatic patients. SUBJECTS AND METHODS. One hundred eleven symptomatic patients referred for colonoscopy underwent CT colonography before colonoscopy. Helical CT from the diaphragm to the symphysis was performed with the patient in the supine and prone positions after rectal air insufflation. Image interpretation was done on a digital workstation. Extracolonic findings were classified as minor, moderate, or major according to potential clinical importance. Patient records, with a follow-up time of about 3 years, were reviewed to determine final diagnoses. RESULTS: Twenty-six (23%) of the patients had CT findings of major importance such as lymphadenopathy (n = 7), aortic aneurysm (n = 6), suspected solid hepatic masses (n = 5), and suspected solid renal masses (n = 4). Fifty-eight patients (52%) had findings of moderate importance such as gallstones (n = 16), indeterminate renal masses (n = 9), adrenal masses with benign appearance (n = 8), and hiatal hernia (n = 7). Forty-six patients (41%) had no or only minor findings, such as renal cysts (n = 34), renal calcifications (n = 19), and hepatic cysts (n = 14). Review of patient records showed that CT colonography contributed to the detection of major, previously unknown extracolonic disorders in 14 (13%) of the 111 patients. CONCLUSION: Potentially important extracolonic findings were revealed in 23% of the patients, leading to additional diagnostic or therapeutic considerations. Some of these findings were clinically important, whereas others were previously known or led to unnecessary workup. This finding must be taken into account when CT colonography is considered for routine diagnostic workup or screening.

Patient acceptance of CT colonography and conventional colonoscopy: prospective comparative study in patients with or suspected of having colorectal disease.

PURPOSE: To prospectively evaluate, by means of self-assessed questionnaires, patient acceptance of computed tomographic (CT) colonography compared with that of conventional colonoscopy, when performed in patients with or suspected of having colorectal disease. MATERIALS AND METHODS: One hundred eleven patients underwent CT colonography followed immediately by conventional colonoscopy. Patient acceptance was evaluated with questionnaires, and the proportions of patients who favored one examination were compared. The main variables were overall impression, discomfort during air filling or instrumentation, and perceived pain, evaluated by using ordered verbal descriptor scales after each examination. The preference for either examination was evaluated after completion of both examinations. RESULTS: Of the 68 patients who favored one examination, 56 (82%) preferred CT colonography (P <.00001). Concerning overall impression of problems or discomfort in connection with the examination, 49 (69%) of 71 with a preference considered colonoscopy to be more difficult (P =.002). CT colonography was regarded as "not painful" by 62 (57%) of 108 patients compared with 28 (26%) for colonoscopy, and a larger proportion of patients rated pain as higher during colonoscopy than during CT colonography (95% CI: 30%, 56%). Discomfort from air filling of the colon was the major complaint about CT colonography. CONCLUSION: CT colonography was considered less painful and less difficult overall than colonoscopy and was the preferred examination.