Judith E. Baars

The risk of inflammatory bowel disease-related colorectal carcinoma is limited: results from a nationwide nested case-control study.

OBJECTIVES:The risk for inflammatory bowel disease (IBD)-related colorectal cancer (CRC) remains a matter of debate. Initial reports mainly originate from tertiary referral centers, and conflict with more recent studies. Overall, epidemiology of IBD-related CRC is relevant to strengthen the basis of surveillance guidelines. We performed a nationwide nested case–control study to assess the risk for IBD-related CRC and associated prognostic factors in general hospitals.METHODS:IBD patients diagnosed with CRC between January 1990 and July 2006 in 78 Dutch general hospitals were identified as cases, using a nationwide automated pathology database. Control IBD patients without CRC were randomly selected. Clinical data were collected from detailed chart review. Poisson regression analysis was used for univariable and multivariable analyses.RESULTS:A total of 173 cases were identified through pathology and chart review and compared with 393 controls. The incidence rate of IBD-related CRC was 0.04%. Risk factors for IBD-related CRC were older age, concomitant primary sclerosing cholangitis (PSC, relative ratio (RR) per year duration 1.05; 95% confidence interval (CI) 1.01–1.10), pseudopolyps (RR 1.92; 95% CI 1.28–2.88), and duration of IBD (RR per year 1.04; 95% CI 1.02–1.05). Using immunosuppressive therapy (odds ratio (OR) 0.3; 95% CI 0.16–0.56, P<0.001) or anti-tumor necrosis factor (TNF) (OR 0.09; 95% CI 0.01–0.68, P<0.02) was protective.CONCLUSIONS:We found a limited risk for developing IBD-related CRC in The Netherlands. Age, duration of PSC and IBD, concomitant pseudopolyps, and use immunosuppressives or anti-TNF were strong prognostic factors in general hospitals.

Majority of patients with inflammatory bowel disease in clinical remission have mucosal inflammation.

Background: Management of inflammatory bowel disease (IBD) is increasingly focused on mucosal remission. We assessed the prevalence of mucosal inflammation during clinical remission, the clinical consequences, and the impact on disease course. Methods: IBD patients from two referral centers who underwent a surveillance colonoscopy while clinically in remission between January 2001 and December 2003 were included. Follow‐up ended May 1, 2009. Clinical data were collected from patient charts. Statistical analysis was performed using independent t‐tests and nonparametric tests. Results: In total, 152 IBD patients were included (98 [65%] ulcerative colitis, 46 [30%] Crohns disease; 85 [56%] males). Median follow‐up was 6.8 years (interquartile range [IQR] 6–8). Forty‐seven (31%) patients had no signs of inflammation during endoscopy (group A). Of the remaining 105 (68%) patients, 51 (49%) had both endoscopic and histological inflammation (group B), 51 (49%) histological inflammation only (group C), two (2%) endoscopic lesions only (group D). Two years later, 29% of all patients had endoscopic inflammation and another 27% had only microscopic inflammation. In 39% the inflammation had resolved spontaneously. Inflammation was more often found in group B+C (n = 62/102; 61%) than in group A (n = 17/47; 36%; P = 0.21). Inflammation was not associated with more frequent clinical relapses nor with stricture formation, nor with the need for surgery. Conclusions: A large proportion of IBD patients have mucosal inflammation without clinical symptoms. Although one‐third recover spontaneously, mucosal inflammation in patients who are clinically in remission is associated with more severe mucosal disease activity, but not with more complications or symptomatic flares during follow‐up. (Inflamm Bowel Dis 2012)

Patients' preferences regarding shared decision-making in the treatment of inflammatory bowel disease: Results from a patient-empowerment study

Background: Shared decision-making is gaining favor in clinical practice, although the extent to which patients want to be involved in choosing their treatment varies substantially. Because data are lacking on the preferences of patients with chronic diseases such as inflammatory bowel disease (IBD), we wanted to assess IBD patients’ preferences about being involved in such decisions. Methods: Adult IBD patients were asked to anonymously complete an online survey on their preferences. Non-parametric tests (χ2) were used to determine the relationship between responses and respondents. Results: The questionnaire was completed by 1,067 patients, 617 with Crohn’s disease and 450 with ulcerative colitis. Patients’ mean age was 43 (SD 13.7) years; the majority were female (66%). In total, 866 patients (81%) reported it as ‘very important’ to be actively involved in the decision-making process, and another 177 (17%) rated it as ‘quite important’. When asked how their treatment could be improved, 537 patients (50%) wanted close, equitable collaboration with their physician. This preference was significantly associated with a disease duration of ≤8 years (p = 0.03). Gender and type of IBD were not significantly associated with patients’ preferences. Conclusions: This study demonstrates IBD patients’ desire to be actively involved in the decision-making process. Further research is needed on physicians’ perspectives on shared decision-making, and on finding predictive factors for developing a model for shared decision-making in IBD.

Patient's perspectives important for early anti-tumor necrosis factor treatment in inflammatory bowel disease

Background/Aim: We hypothesized that limited information is given to patients on the risks and benefits of individual therapy, and feedback is lacking to verify if patients correctly interpreted the given information. We assessed the perspectives of patients with inflammatory bowel disease (IBD) concerning the treatment-associated risks/benefits of infliximab. Methods: Patients were asked to complete a survey regarding the benefits and risks of infliximab. Results are reported as descriptive statistics. Comparisons between groups were analyzed using independent t tests and the Kruskal-Wallis test. Results: In total, 152 IBD patientscompleted the questionnaire. Fifty-seven percent (78/138) estimated the 1-year remission rate from infliximab to be >50%. Seventy-one percent (104/146) indicated they would not take a drug with risks reflecting those estimated for infliximab if the 1-year remission rate was <75%. Crohn’s disease patients and those recalling a discussion regarding the risks/benefits of infliximab treatment had higher estimates of the 1-year remission rate with infliximab than ulcerative colitis patients (p = 0.03) and patients who did not recall previous information (p = 0.03). Perceptions were independent of age and disease duration. Conclusion: IBD patients misperceive the risks and benefits of infliximab. The majority of patients would not accept treatment-related risks if the 1-year remission rate was <75%. Counseling on treatment-associated risks and benefits should be ameliorated.

High therapy adherence but substantial limitations to daily activities amongst members of the Dutch inflammatory bowel disease patients' organization: a patient empowerment study

Aliment Pharmacol Ther 30, 864–872

A short course of corticosteroids prior to surveillance colonoscopy to decrease mucosal inflammation in inflammatory bowel disease patients: Results from a randomized controlled trial

BACKGROUND Inflammation is a known pitfall of surveillance colonoscopy for inflammatory bowel disease (IBD) as it is difficult to differentiate between inflammation and true dysplasia. This randomized controlled trial assessed the effectiveness of a low dose of corticosteroids prior to surveillance colonoscopy to decrease mucosal inflammation. METHODS IBD-patients scheduled for surveillance colonoscopy between July 2008-January 2010 were eligible to participate. Patients were randomized to either two weeks daily 20mg prednisone and calcium plus vitamin D prior to surveillance colonoscopy or no treatment. All biopsies were reviewed by an expert gastrointestinal pathologist who was blinded for medication-use. Statistics were performed using chi-square tests, non-parametric tests and binary logistic regression. RESULTS Sixty patients (M/F 30/30, UC/CD 31/29) participated: 31 (52%) in the treatment arm and 29 (48%) in the control group. In the treatment arm, 247 biopsies were scored against 262 in the control group. In the treatment arm 27 out of 247 biopsies (10.9%) had a score >1 on the Geboes scale, against 50 out of 262 biopsies (19.1%) in the control group, p=0.013. In total, 58% of the treatment arm against 66% of the control group had endoscopic or histological mucosal inflammation (p=0.6). There was a trend for patients in the treatment arm to have less severe inflammation compared with the control group, however this was not significant (p=0.12). CONCLUSIONS In our cohort, a short course of corticosteroids decreases the overall histological disease activity in individual biopsies without major side-effects. Moreover, there is a trend for corticosteroids to decrease the maximum severity of both endoscopic and histological disease activity per patient.

Increased suppressor of cytokine signaling-3 expression predicts mucosal relapse in ulcerative colitis

Background:Most biomarkers predicting mucosal relapse of ulcerative colitis (UC) patients in clinical remission represent low levels of mucosal inflammation. Since SOCS3 expression may increase the vulnerability of intestinal epithelial cells (IECs) to various insults, we investigated whether its expression predicts mucosal relapse in UC patients in clinical remission without any signs of mucosal inflammation. Methods:UC patients (n = 32) in clinical, endoscopic, and histological remission were followed up for 9 years. IEC expression of SOCS3, p-STAT3, and p-STAT1 were assessed with biopsies from the baseline colonoscopy, last colonoscopy before relapse, and colonoscopy at relapse. Clinical data, endoscopy, and histology reports were collected from patient charts. Results:Twenty-six (81%) patients had histological relapse, 19 (59%) developed an endoscopic relapse, and 17 (53%) had a clinical relapse during follow-up. SOCS3 expression at first colonoscopy during remission correlated with shorter time to histological, endoscopic, and clinical relapse. SOCS3 expression was increased at the last colonoscopy before relapse, approaching relapse levels, whereas p-STAT3 expression was low during the entire remission. A positive correlation between IEC SOCS3 and its inducer p-STAT1 was shown. Conclusions:SOCS3 IEC expression during remission may be useful in predicting mucosal relapse in patients without any signs of mucosal inflammation. These data strengthen our hypothesis that SOCS3 contributes to enhanced vulnerability of IEC during remission. Thus, SOCS3 levels during remission may function as a therapeutic target for clinical monitoring and early induction of mucosal healing.

Disease severity does not affect the interval between IBD diagnosis and the development of CRC: Results from two large, Dutch case series

BACKGROUND The increased risk of colorectal cancer (CRC) in patients with inflammatory bowel disease (IBD) is well established. The incidence of IBD-related CRC however, differs markedly between cohorts from referral centers and population-based studies. In the present study we aimed to identify characteristics potentially explaining these differences in two cohorts of patients with IBD-related CRC. METHODS PALGA, a nationwide pathology network and registry in The Netherlands, was used to search for patients with IBD-associated CRC between 1990 and 2006. Patients from 7 referral hospitals and 78 general hospitals were included. Demographic and disease specific parameters were collected retrospectively using patient charts. RESULTS A total of 281 patients with IBD-associated CRC were identified. Patients from referral hospitals had a lower median age at IBD diagnosis (26 years vs. 28 years (p=0.02)), while having more IBD-relapses before CRC diagnosis than patients from general hospitals (3.8 vs. 1.5 (p<0.01)). In patients from referral hospitals, CRC was diagnosed at a younger age (47 years vs. 51 years (p=0.01)). However, the median interval between IBD diagnosis and diagnosis of CRC was similar in both cohorts (19 years in referral hospitals vs. 17 years in general hospitals (p=0.13)). CONCLUSIONS IBD patients diagnosed with CRC treated in referral hospitals in The Netherlands are younger at both the diagnosis of IBD and CRC than IBD patients with CRC treated in general hospitals. Although patients from referral centers appeared to have a more severe course of IBD, the interval between IBD and CRC diagnosis was similar.

Small bowel carcinoma mimicking a relapse of Crohn's disease: A case series

We describe three patients diagnosed and treated for presumed (relapsing) Crohns disease, but who were subsequently diagnosed with a small bowel carcinoma. This case series underlines the necessity of performing a full work up in the diagnosis of CD and to consider small bowel carcinoma in patients with small bowel CD failing medical therapy.

SOCS3 Expression is a Predictive Factor of Relapse of Mucosal Inflammation in Chronic UC

Background and aims: Ulcerative colitis (UC) is chronic relapsing-remitting disease. Whereas it has been well characterized how various drug induce remission, the mechanisms involved in relapse are not known. We have previously shown that the epithelial expression of SOCS3, a negative regulator of cytokine signaling, was persistently upregulated in both active and inactive UC. Since the expression of SOCS3 during inactive disease may make the epithelial cells more vulnerable to various insults, we investigated whether this expression during remission was associated with the time till relapse. Materials and methods: 41 chronic UC patients in clinical remission underwent a first surveillance colonoscopy between 20012004, and were followed up till 2010. Biopsies from the first surveillance colonoscopy after remission were stained for SOCS3 protein expression and scored according to percentage of positive epithelial cells. Only biopsies from patients with clinical remission and without signs of histological inflammation were included. Clinical data, endoscopy and histology reviews were collected from patient charts. Results: 23 Patients (57.0%) of the 41 chronic UC patients developed histological relapse, and 19 patients (46.3%) had endoscopic relapse of colitis during the course of surveillance. SOCS3 protein expression in colon biopsies of inactive UC patients had a negative correlation with the time till histological (p<0.001) and endoscopic (p=0.007) relapse. Patients with higher epithelial SOCS3 expression at early remission suffered from a significantly more severe colitis during relapse (p=0.001). There was no correlation with CRP levels. Conclusion: Here we found that high levels SOCS3 expression in epithelial cells during remission was associated with a shorter time till relapse and increased severity of inflammation during relapse. These data further strengthen our hypothesis that SOCS3 expression may contribute to enhanced vulnerability of the intestinal epithelial cells during remission. As such, the dynamic changes and the mechanisms involved in this SOCS3 expression during mucosal remission will be further investigated.