Distribution of histopathological features along the colon in microscopic colitis.

PURPOSE: The diagnosis microscopic colitis (MC) consisting of collagenous colitis (CC) and lymphocytic colitis (LC) relies on histological assessment of mucosal biopsies from the colon. The optimal biopsy strategy for reliable diagnosis of MC is controversial. The aim of this study was to evaluate the distribution of histopathological features of MC throughout the colon. METHODS: Mucosal biopsies from multiple colonic segments of patients with MC who participated in one of the three prospective European multicenter trials were analyzed. Histological slides were stained with hematoxylin-and-eosin, a connective tissue stain, and CD3 in selected cases. RESULTS: In total, 255 patients were included, 199 and 56 patients with CC and LC, respectively. Both groups exhibited a gradient with more pronounced inflammation in the lamina propria in the proximal colon compared with the distal colon. Similarly, the thickness of the subepithelial collagenous band in CC showed a gradient with higher values in the proximal colon. The mean number of intraepithelial lymphocytes was > 20 in all colonic segments in patients within both subgroups. Biopsies from 86 to 94% of individual segments were diagnostic, rectum excluded. Biopsies from non-diagnostic segments often showed features of another subgroup of MC. CONCLUSION: Conclusively, although the severity of the histological changes in MC differed in the colonic mucosa, the minimum criteria required for the diagnosis were present in the random biopsies from the majority of segments. Thus, our findings show MC to be a pancolitis, rectum excluded, questioning previously proclaimed patchiness throughout the colon.

Quantifying intraepithelial lymphocytes and subepithelial collagen band in microscopic colitis, extracting insights into the interrelationship of lymphocytic and collagenous colitis.

Microscopic colitis (MC) is the umbrella term for the conditions termed lymphocytic colitis (LC) and collagenous colitis (CC). LC with thickening of the subepithelial collagen band or CC with increased number of intraepithelial T- lymphocytes (IELs) is often seen in MC and may lead to difficulties in correct histological classification. We investigated the extent of overlapping features of CC and LC in 60 cases of MC by measuring the exact thickness of the subepithelial collagen band in Van Gieson stained slides and quantifying number of IELs in CD3 stained slides by digital image analysis. A thickened collagen band was observed in nine out of 29 cases with LC (31%) and an increased number of IELs in all 23 cases of CC (100%). There was no correlation between the thickness of the collagen band and number of IELs. Due to the increased number of IELs in all cases of CC we consider the lymphocytic inflammatory infiltration of the mucosa to be the essential histopathological feature of MC. However, although LC and CC are related due to the lymphocytic inflammation, the non-linear correlation of number of IELs and thickness of the collagenous band indicate differences in their pathogenesis.

Biochemical Diagnosis of Bile Acid Diarrhea: Prospective Comparison With the 75Seleno-Taurohomocholic Acid Test.

INTRODUCTION: The diagnosis of bile acid diarrhea is often missed because the availability of the seleno-taurohomocholic acid (SeHCAT) test is limited. We aimed to compare the biomarkers 7α-hydroxy-4-cholesten-3-one (C4) and fibroblast growth factor 19 (FGF19) with the SeHCAT test. METHODS: Patients with chronic diarrhea without intestinal resection referred for SeHCAT were prospectively recruited for this diagnostic accuracy study. Blood was sampled at fasting and after a stimulation meal with chenodeoxycholic acid. SeHCAT retention ≤10% defined bile acid diarrhea and >10% defined miscellaneous diarrhea. Receiver operating characteristics (ROC) were analyzed with SeHCAT as the gold standard. www.clinicaltrials.gov (NCT03059537). RESULTS: Patients with bile acid diarrhea (n = 26) had mean C4 of 30 ng/mL (95% confidence interval: 19-46) vs 8 (7-11; P < 0.001) in the miscellaneous diarrhea group (n = 45). Area under the ROC curve (ROCAUC) for C4 was 0.83 (0.72-0.93). C4 < 15 ng/mL had 85% (74%-96%) negative predictive value; C4 > 48 ng/mL had 82% (59%-100%) positive predictive value. Twenty patients had C4 values 15-48 ng/mL, of whom 11/20 had SeHCAT ≤10%. Median fasting FGF19 was 72 pg/mL (interquartile range: 53-146) vs 119 (84-240) (P = 0.004); ROCAUC was 0.71 (0.58-0.83). Stimulated FGF19 responses did not differ (P = 0.54). DISCUSSION: We identified C4 thresholds with clinically useful predictive values for the diagnosis of and screening for bile acid diarrhea in patients with chronic watery diarrhea. Further validation of the cutoff values with the placebo-controlled effect of sequestrant therapy is warranted (see Visual Abstract, Supplementary Digital Content 2, http://links.lww.com/AJG/B603).

An investigation of European pathologists' approach to diagnose microscopic colitis.

Microscopic colitis (MC) comprising lymphocytic colitis (LC), collagenous colitis (CC) and the incomplete forms of microscopic colitis (MCi) are frequent causes of chronic watery diarrhea. The diagnosis is based on specific histological features in colonic biopsies. Especially regarding MCi, the histological features may be subtle. The PRO-MC collaboration was established in 2016 with the aims to systematically describe the disease course and to validate the diagnostic criteria of MC. In the present study, we analysed pathologists' initial approach to diagnose MC. Five pathologists with expertise in gastro-intestinal pathology reviewed the first 10 cases enrolled in the PRO-MC registry in six of the participating centres. Despite considerable differences in strategies in biopsy sampling, in choice of stains and in minimum number of biopsies and segments required for diagnosing MC, inter-observer agreement between the participating centres and expert pathologists as well as among the latter was substantial. Disagreed cases most often related to difficulties in distinguishing between MC subgroups. We recommend that pathologists as well as clinicians reach consensus in their diagnostic approach to MC, which is a prerequisite to compare MC cohorts internationally and to facilitate clinical MC trials and follow-up studies.

Efficacy and Safety of Budesonide, vs Mesalazine or Placebo, as Induction Therapy for Lymphocytic Colitis.

BACKGROUND & AIMS: Lymphocytic colitis is a common cause of chronic, nonbloody diarrhea. However, the effects of treatment are unclear and randomized placebo-controlled trials were requested in a Cochrane review. We performed a randomized, placebo-controlled, multicenter study to evaluate budesonide and mesalazine as induction therapy for lymphocytic colitis. METHODS: Patients with active lymphocytic colitis were randomly assigned to groups given budesonide 9 mg once daily (Budenofalk granules), mesalazine 3 g once daily (Salofalk granules), or placebo for 8 weeks in a double-blind, double-dummy design. The primary endpoint was clinical remission, defined as ≤21 stools (including ≤6 watery stools), in the 7 days before week 8. RESULTS: The final analysis included 57 patients (19 per group). Most patients were female (72%) and the mean age was 59 years. The proportion of patients in clinical remission at week 8 was significantly higher in the budesonide group than in the placebo group (intention-to-treat analysis, 79% vs 42%; P = .01). The difference in proportions of patients in clinical remission at week 8 between the mesalazine (63%) and placebo groups was not significant (P = .09). The proportion of patients with histologic remission at week 8 was significantly higher in the budesonide group (68%) vs the mesalazine (26%; P = .02) or placebo (21%; P = .008) groups. The incidence of adverse events was 47.4% in the budesonide group, 68.4% in the mesalazine group, and 42.1% in the placebo group. CONCLUSIONS: In a randomized multicenter study, we found oral budesonide 9 mg once daily to be effective and safe for induction of clinical and histologic remission in patients with lymphocytic colitis, compared with placebo. Oral mesalazine 3 g once daily was not significantly better than placebo. ClinicalTrials.gov no: NCT01209208.

An altered composition of the microbiome in microscopic colitis is driven towards the composition in healthy controls by treatment with budesonide.

Background and aim: Microscopic colitis (MC) is an inflammatory disease of the bowel, hypothetically induced by an immunologic response to a luminal microbial agent. We aimed to characterize the microbiome composition in MC and subtypes collagenous colitis (CC) and lymphocytic colitis (LC) and to identify a possible microbial effect of treatment. Method: Stool samples were collected from MC patients prior to treatment, at 8 weeks (during treatment) and at 16 weeks (after treatment), and from healthy controls, not receiving treatment, at matched time-points. Microbiome composition was analyzed by sequencing of the 16S and 18S genes. Differences between patients and controls were analyzed by Shannon's diversity index (mean, standard deviation (SD)) and principal coordinate analysis (PCoA) complemented with a permanova test of UniFrac distances. Results: Ten LC patients, 10 CC patients and 10 controls were included. By PCoA, the bacterial composition in MC patients differed from controls at baseline (p = .02), but not during and after treatment (p = .09 and p = .33, respectively). At baseline, bacterial diversity was lower in MC patients compared to controls (2.5, SD: 0.5 vs 3.5, SD: 0.3, p < .05). Diversity in MC patients increased during (3.0, SD: 0.6) and after treatment and (2.9, SD: 0.5) compared with baseline (p < .01). Eukaryotes were detected in fewer samples from MC patients compared with controls (11/20 (55%) vs. 9/10 (90%), p = .06) with no effect of treatment. Conclusion: Microbiome composition is altered in MC patients. During and after treatment with budesonide the microbiome composition in MC patients was driven towards the composition in healthy controls.

Microscopic colitis in Denmark and Sweden: incidence, putative risk factors, histological assessment and endoscopic activity.

OBJECTIVE: The significantly higher incidence rates of microscopic colitis (MC) in Denmark compared to Sweden remains unexplained. METHODS: Consecutive patients with newly diagnosed MC in the neighbouring regions of Skåne in 2011-2015 and Zealand in 2010-2016 were prospectively identified. Data on large bowel endoscopies and biopsies rates were retrieved. Information on putative factors were obtained from registers and literature. Interobserver agreement between pathologists from both regions on 40 blinded hematoxylin and eosin (H&E)-stained colon biopsies (collagenous colitis (CC), lymphocytic colitis (LC), non-specific inflammation and normal) was evaluated using kappa statistics. RESULTS: The mean annual incidence per 105 inhabitants in Skåne and Zealand 2010-2015 was 5.9 (95% CI 4.6-7.3) versus 16.4 (95% confidence intervals (95% CI) 13.6-19.2) for CC and 2.7 (95% CI 1.0-4.3) versus 11.1 (95% CI 8.8-13.4) for LC, respectively. Number of endoscopies with biopsy per 1000 and the rate of MC per endoscopy with biopsy was higher in Zealand (34-52/1000) than in Skåne (12-21/1000). The kappa value for overall agreement between pathologists was good (0.72; 95% CI 0.64-0.79). Prescription of proton pump inhibitors and selective serotonin reuptake inhibitors was higher in Skåne in the relevant age groups and prescription of non-steroidal anti-inflammatory drugs and smoking rate higher in Zealand. Alcohol consumption was higher in Denmark than in Sweden. CONCLUSION: The incidence of MC and number of cases per colonic biopsy was higher in Zealand and could not be readily explained by endoscopy or biopsy rates, differences in histological assessment or putative risk factors.

Parenteral therapy and complications in patients with intestinal failure in a regional unit.

OBJECTIVE: To describe a cohort of patients with intestinal failure (IF) and tunnelled catheters in a regional IF unit, treatment and catheter-related complication rates, and to compare the quality of care with previously published results from specialised IF centres in Denmark. METHODS: A retrospective chart review of an adult IF patient cohort receiving parenteral therapy through tunnelled catheters in a regional IF unit from 2005 to 2014. Demographics, indication, type and frequency of parenteral therapy, dwell time, cause of removal and complications were recorded. RESULTS: Parenteral therapy was provided to 78 patients with a median age of 64 (25-86) years. Numbers increased from seven patients in 2005 to 40 in 2014. The cause of IF was surgical complications (33%), cancer (28%), inflammatory bowel disease (IBD, 15%) and other causes (24%). The median duration of parenteral therapy was 453 days (range: 16-3651 days). One hundred and forty-two tunnelled catheters were inserted. The incidence of catheter-related blood stream infection (CRBSI) was 1.51/1000 days (95% CI: 1.20-1.90) and the incidence of thrombosis was 0.10/1000 days (0.04-0.25). Seventy-two episodes of CRBSI occurred with 89 microorganisms cultured, the most common being coagulase-negative Staphylococcus (n = 25, 28%). CONCLUSION: The rate of CRBSI did not differ from larger centres in Denmark but the rate of thrombotic events was higher than expected. Parenteral therapy can safely and effectively be offered to patients with IF in smaller centres.

Individualized Therapy Is a Long-Term Cost-Effective Method Compared to Dose Intensification in Crohn's Disease Patients Failing Infliximab.

BACKGROUND: In Crohn's disease patients failing infliximab therapy, interventions defined by an algorithm based on infliximab and anti-infliximab antibody measurements have proven more cost-effective than intensifying the infliximab regimen. AIM: This study investigated long-term economic outcomes at the week 20 follow-up study visit and after 1 year. Clinical outcomes were assessed at week 20. METHODS: Follow-up from a 12-week, single-blind, clinical trial where patients with infliximab treatment failure were randomized to infliximab intensification (5 mg/kg every 4 weeks) (n = 36), or algorithm-defined interventions (n = 33). Accumulated costs, expressed as mean costs per patient, were based on the Danish National Patient Registry. RESULTS: At the scheduled week 20 follow-up study visit, response and remission rates were similar in all study subpopulations between patients treated by the algorithm or by infliximab intensification. However, the sum of healthcare costs related to Crohn's disease was substantially lower (31 %) for patients randomized to algorithm-based interventions than infliximab intensification in the intention-to-treat population: $11,940 versus $17,236; p = 0.005. For per-protocol patients (n = 55), costs at the week 20 follow-up visit were even lower (49 %) in the algorithm group: $8,742 versus $17,236; p = 0.002. Figures were similar for patients having completed the 12-week trial as per protocol (50 % reduction in costs) (n = 45). Among patients continuing the allocated study intervention throughout the entire 20-week follow-up period (n = 29), costs were reduced by 60 % in algorithm-treated patients: $7,056 versus $17,776; p < 0.001. Cost-reduction percentages remained stable throughout one year. CONCLUSION: Economic benefit of algorithm-based interventions at infliximab failure is maintained throughout 1 year.

Individualised therapy is more cost-effective than dose intensification in patients with Crohn's disease who lose response to anti-TNF treatment: a randomised, controlled trial.

OBJECTIVE: Although the reasons for secondary loss of response to infliximab (IFX) maintenance therapy in Crohn's disease vary, dose intensification is usually recommended. This study investigated the cost-effectiveness of interventions defined by an algorithm designed to identify specific reasons for therapeutic failure. DESIGN: Randomised, controlled, single-blind, multicentre study. 69 patients with secondary IFX failure were randomised to IFX dose intensification (5 mg/kg every 4 weeks) (n=36) or interventions based on serum IFX and IFX antibody levels using the proposed algorithm (n=33). Predefined co-primary end points at week 12 were proportion of patients responding (Crohn's Disease Activity Index (CDAI) decrease ≥ 70, or ≥ 50% reduction in active fistulas) and accumulated costs related to treatment of Crohn's disease, expressed as mean cost per patient, based on the Danish National Patient Registry for all hospitalisation and outpatient costs in the Danish healthcare sector. RESULTS: Costs for intention-to-treat patients were substantially lower (34%) for those treated in accordance with the algorithm than by IFX dose intensification: € 6038 vs € 9178, p<0.001. However, disease control, as judged by response rates, was similar: 58% and 53%, respectively, p=0.81; difference 5% (-19% to 28%). For per-protocol patients, treatment costs were even lower (56%) in the algorithm-treated group (€ 4062 vs € 9178, p<0.001) and with similar response rates (47% vs 53%, p=0.78; difference -5% (-33% to 22%)). CONCLUSIONS: Treatment of secondary IFX failure using an algorithm based on combined IFX and IFX antibody measurements significantly reduces average treatment costs per patient compared with routine IFX dose escalation and without any apparent negative effect on clinical efficacy. TRIAL REGISTRATION NO: NCT00851565.

Risk of cancer in patients with bile acid diarrhoea: a Danish nationwide matched cohort study.

OBJECTIVE: Bile acid diarrhoea is a common cause of chronic diarrhoea. Increased levels of potentially carcinogenic bile acids in faeces, theoretically, may increase the risk of colorectal cancer in particular, but the long-term disease course is unknown. We aimed to investigate the overall and site-specific cancer risk in bile acid diarrhoea. DESIGN: Adult patients with bile acid diarrhoea were identified using nationwide Danish registries from 2003 to 2020 by a diagnostic gold-standard 75-selenium tauroselcholic acid procedure followed within 6 months by sequestrant prescription. The risk of overall and site-specific cancers in cases with bile acid diarrhoea was compared with sex, age and comorbidity-adjusted matched controls. A competing risk model estimated cumulative incidence functions and cause-specific HRs. RESULTS: We identified 2260 patients with bile acid diarrhoea with a mean follow-up of 5.5 years (SD 4.2). The overall cancer risk was increased by an HR of 1.32 (95% CI 1.12 to 1.54). The risk of site-specific cancer was increased in 3 of 10 cancer groups: haematological, HR 2.41 (1.36 to 4.02); skin, HR 1.33 (1.01 to 1.71); and male genital cancers, HR 1.85 (1.11 to 2.92). No increased risk of colorectal cancer was detected in patients with bile acid diarrhoea, HR 0.73 (0.34 to 1.63). CONCLUSIONS: Bile acid diarrhoea was associated with an increased overall risk of cancer, especially haematological cancers, but the risk of colorectal cancer was not increased. The lack of a diagnostic code for bile acid diarrhoea and potential residual confounding are limitations, and the findings should be replicated in other cohorts.

Number of intraepithelial lymphocytes and presence of a subepithelial band in normal colonic mucosa differs according to stainings and evaluation method.

Chronic watery diarrhea is a frequent symptom. In approximately 10% of the patients, a diagnosis of microscopic colitis (MC) is established. The diagnosis relies on specific, but sometimes subtle, histopathological findings. As the histology of normal intestinal mucosa vary, discriminating subtle features of MC from normal tissue can be challenging and therefore auxiliary stainings are increasingly used. The aim of this study was to determine the variance in number of intraepithelial lymphocytes (IELs) and presence of a subepithelial band in normal ileum and colonic mucosa, according to different stains and digital assessment. Sixty-one patients without diarrhea referred to screening colonoscopy due to a positive feacal blood test and presenting with endoscopically normal mucosa were included. Basic histological features, number of IELs, and thickness of a subepithelial band was manually evaluated and a deep learning-based algorithm was developed to digitally determine the number of IELs in each of the two compartments; surface epithelium and cryptal epithelium, and the density of lymphocytes in the lamina propria compartment. The number of IELs was significantly higher on CD3-stained slides compared with slides stained with Hematoxylin-and-Eosin (HE) (p<0.001), and even higher numbers were reached using digital analysis. No significant difference between right and left colon in IELs or density of CD3-positive lymphocytes in lamina propria was found. No subepithelial band was present in HE-stained slides while a thin band was visualized on special stains. Conclusively, in this cohort of prospectively collected ileum and colonic biopsies from asymptomatic patients, the range of IELs and detection of a subepithelial collagenous band varied depending on the stain and method used for assessment. As assessment of biopsies from patients with diarrhea constitute a considerable workload in the pathology departments digital image analysis is highly desired. Knowledge provided by the present study highlight important differences that should be considered before introducing this method in the clinic.

Prospective comparison of diagnostic tests for bile acid diarrhoea.

BACKGROUND: Bile acid diarrhoea is often missed because gold standard nuclear medicine tauroselcholic [75-Se] acid (SeHCAT) testing has limited availability. Empirical treatment effect has unknown diagnostic performance, whereas plasma 7α-hydroxy-4-cholesten-3-one (C4) is inexpensive but lacks sensitivity. AIMS: To determine diagnostic characteristics of empirical treatment and explore improvements in diagnostics with potential better availability than SeHCAT. METHODS: This diagnostic accuracy study was part of a randomised, placebo-controlled trial of colesevelam. Consecutive patients with chronic diarrhoea attending SeHCAT had blood and stool sampled. Key thresholds were C4 > 46 ng/mL and SeHCAT retention ≤10%. A questionnaire recorded patient-reported empirical treatment effect. We analysed receiver operating characteristics and explored machine learning applied logistic regression and decision tree modelling with internal validation. RESULTS: Ninety-six (38%) of 251 patients had SeHCAT retention ≤10%. The effect of empirical treatment assessed with test results for bile acid studies blinded had 63% (95% confidence interval 44%-79%) sensitivity and 65% (47%-80%) specificity; C4 > 46 ng/mL had 47% (37%-57%) and 92% (87%-96%), respectively. A decision tree combining C4 ≥ 31 ng/mL with ≥1.1 daily watery stools (Bristol type 6 and 7) had 70% (51%-85%) sensitivity and 95% (83%-99%) specificity. The logistic regression model, including C4, the sum of measured stool bile acids and daily watery stools, had 77% (58%-90%) sensitivity and 93% (80%-98%) specificity. CONCLUSIONS: Diagnosis of bile acid diarrhoea using empirical treatment was inadequate. Exploration suggested considerable improvements in the sensitivity of C4-based testing, offering potential widely available diagnostics. Further validation is warranted. CLINICALTRIALS: gov: NCT03876717.

Efficacy and safety of colesevelam for the treatment of bile acid diarrhoea: a double-blind, randomised, placebo-controlled, phase 4 clinical trial.

BACKGROUND: Bile acid diarrhoea is a common but overlooked cause of chronic watery diarrhoea. Plasma 7α-hydroxy-4-cholesten-3-one (C4) is an alternative to the gold standard tauroselcholic [75Se] acid (SeHCAT) test. Low-certainty evidence supports sequestrant treatment, including colesevelam. We aimed to determine the efficacy and safety of colesevelam in bile acid diarrhoea. METHODS: In this randomised, double-blind, placebo-controlled, investigator-initiated phase 4 trial of the sequestrant colesevelam in bile acid diarrhoea (SINBAD), we enrolled consecutive patients aged 18-79 years without inflammatory bowel disease attending SeHCAT testing for suspected bile acid diarrhoea at four Danish secondary care centres. Participants were randomly allocated 1:1 to receive 12 days of treatment with colesevelam (overencapsulated tablets of 625 mg) or placebo, with the starting dose of two capsules twice daily and titrated to effect during the first 5 days of treatment. A pharmacist independent of the clinical investigators generated a randomisation list on the web page randomization.com using block randomisation (randomisation was not stratified). C4 and SeHCAT diagnostic results were blinded during treatment. We treated all patients with diarrhoea, with a daily mean of 3·0 or more bowel movements or 1·0 or more watery bowel movements (Bristol stool scale type 6 and 7). Remission was defined as the absence of both these criteria during treatment days 6-12. The primary outcome was the intention-to-treat remission rate in bile acid diarrhoea diagnosed by C4 concentration greater than 46 ng/mL. A secondary outcome was the intention-to-treat remission rate in bile acid diarrhoea diagnosed by SeHCAT retention of 10% or less. This trial is registered with ClinicalTrials.gov, NCT03876717. FINDINGS: Between Oct 25, 2018, and July 1, 2021, 168 patients were randomly assigned to receive colesevelam (n=84) or placebo (n=84). 41 patients had C4 concentration greater than 46 ng/mL (22 assigned to the colesevelam group and 19 to the placebo group). For the C4-defined primary outcome, 14 (64%) of 22 participants receiving colesevelam versus three (16%) of 19 participants receiving placebo achieved remission (adjusted odds ratio 9·1, 95% CI 1·9-62·8; p=0·011). For the SeHCAT-defined secondary outcome, 75 of the 168 participants had retention of less than 10% (37 assigned to the colesevelam group and 38 assigned to the placebo group); 22 (59%) of 37 participants receiving colesevelam achieved remission versus five (13%) of 38 participants receiving placebo (adjusted odds ratio 11·1, 95% CI 3·4-45·6; p=0·00020). There were no serious adverse events. Common adverse events were transient. For patients receiving colesevelam within the primary outcome population, five had abdominal pain, nine had bloating, and four had nausea. For patients receiving placebo, four had abdominal pain, four had bloating, and one had nausea. No participants with bile acid diarrhoea withdrew due to adverse events. INTERPRETATION: Colesevelam was superior to placebo at inducing remission of bile acid diarrhoea diagnosed with C4 concentration greater than 46 ng/mL. Secondary outcome data suggest similar efficacy treating SeHCAT-defined bile acid diarrhoea. Colesevelam was safe during the treatment. FUNDING: Fabrikant Vilhelm Pedersen og hustrus mindelegat; recommended by the Novo Nordisk Foundation.

The Process of Developing a Disease Activity Index in Microscopic Colitis.

BACKGROUND AND AIMS: Patient-reported outcome measures [PROMs] aim to measure patients' perception of how their disorder influences everyday functioning. The objective of this study was to develop a PROM to assess disease activity in microscopic colitis [MC] fulfilling the requirements of the Food and Drug Administration [FDA]. METHODS: The European Microscopic Colitis Activity Index [E-MCAI] was developed in four steps. [1] A list of symptoms associated with active MC was created by a group of experts in the field. [2] Content validity of the symptoms was performed by experts [n = 14] and patients [n = 79] using the Content Validity Index. [3] Questions and response alternatives were created for each symptom, and validity of the E-MCAI was evaluated with cognitive interviews with patients [n = 7] and by the experts. [4] A pilot postal survey was performed to ensure usability. RESULTS: Seven of the symptoms related to active MC fulfilled the criteria for content validity and were included in the E-MCAI: stool consistency, stool frequency, stools at night, feel a need to pass more stools shortly after a bowel movement, urgent need to empty the bowel, leakage of stool and abdominal pain. The development and validation process resulted in the current version of the E-MCAI consisting of six questions related to MC. CONCLUSIONS: The E-MCAI was developed using the methods advocated by the FDA. The evaluation indicates good content validity. Further evaluation will be performed to achieve construct validity, reliability and responsiveness in future cross-sectional and longitudinal studies.

High morbidity after laparoscopic emergency colectomy for inflammatory bowel disease.

INTRODUCTION: Only limited data are available on subtotal laparoscopic colectomy (STC) in patients with in inflammatory bowel disease. We present the first Danish experiences with intended laparoscopic STC for inflammatory bowel disease (IBD). The primary outcome was 30-day morbidity. MATERIAL AND METHODS: The present study is a retrospective single-centre study with consecutive enrolment of patients undergoing intended STC for IBD from 1 January 2005 to 31 July 2009. The results were analysed as either emergency or elective operations. Only the most severe complication was noted for each patient. Data on medical treatment, blood tests and complications and death within 30 days were registered. RESULTS: A total of 32 patients underwent surgery (15 elective and 17 emergency procedures). Patients in the emergency group had significantly more severe disease activity than elective patients. Severe complications were recorded in 47% and 20% of the patients undergoing emergency and elective STC, respectively (p = 0.15). The overall morbidity was 72%. One emergency patient died. Five of eight emergency patients and one of three elective patients underwent conversion and experienced a major complication (p = 0.55). The overall conversion rate was 32% (p = 0.15). CONCLUSION: We found high morbidity and conversion rates in patients undergoing SLC for IBD. A prospective national Danish survey on early postoperative outcome is suggested. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

[Healing of severe morbus Crohn-related pyoderma gangrenosum after colectomy].

This case report describes a patient with colonic Crohn's disease and perianal disease. The patient experienced extensive and severe pyoderma gangrenosum after colectomy. Steroids and anti-inflammatory medication had no effect on pyoderma or the persistent perianal and rectal disease. All pyoderma lesions eventually healed after proctectomy and excision of perianal fistulae. The relevance and effect of surgically induced remission on medically resistant inflammatory bowel disease-associated pyoderma gangrenosum is highlighted.