Risk of impaired nutritional status and flare occurrence in IBD outpatients.

BACKGROUND: Inflammatory bowel disease (IBD) patients are at risk of an impaired nutritional status. The impact thereof on the IBD relapse risk is clinically relevant, though sparsely investigated. AIM: The aim was to explore the association between an impaired nutritional status risk and the occurrence of disease flares in IBD outpatients participating in a longitudinal telemedicine study. METHODS: IBD outpatients were recruited from the myIBDcoach study cohort, with one year clinical follow-up. Through myIBDcoach, a telemedicine tool, patients reported on disease activity and risk of impaired nutritional status (i.e. Short Nutritional Assessment Questionnaire >1 and/or BMI < 18.5 kg/m2) every one to three months. Data was analysed by generalized estimating equation modelling. RESULTS: In total, 417 patients were included. During follow-up, 49 patients (11.8%) flared after initial clinical remission and 53 patients (12.7%) showed an increased risk of impaired nutritional status. The risk of impaired nutritional status was associated with flare occurrence (OR 2.61 (95% CI 1.02-6.69)). CONCLUSIONS: The risk of an impaired nutritional status was associated with subsequent flares in IBD outpatients. This emphasizes the importance of monitoring disease activity in IBD patients at risk of impaired nutritional status.

Corticosteroid Sparing in Inflammatory Bowel Disease is More Often Achieved in the Immunomodulator and Biological Era-Results from the Dutch Population-Based IBDSL Cohort.

OBJECTIVES: Corticosteroid-free remission is an emerging treatment goal in the management of inflammatory bowel disease (IBD). In the population-based Inflammatory Bowel Disease South Limburg cohort, we studied temporal changes in corticosteroid use and assessed the corticosteroid-sparing effects of immunomodulators and biologicals in real life. METHODS: In total, 2,823 newly diagnosed patients with Crohn's disease (CD) or ulcerative colitis (UC) were included. Corticosteroid exposure and cumulative days of use were compared between patients diagnosed in 1991-1998 (CD: n=316, UC: n=539), 1999-2005 (CD: n=387, UC: n=527), and 2006-2011 (CD: n=459, UC: n=595). Second, the corticosteroid-sparing effects of immunomodulators and biologicals were assessed. RESULTS: Over time, the corticosteroid exposure rate was stable (54.0% in CD and 31.4% in UC), even as the cumulative corticosteroid use in the first disease year (CD: 83 days (interquartile range (IQR) 35-189), UC: 62 days (IQR 0-137)). On the long-term, a gradual decrease in cumulative corticosteroid use was seen in CD (era '91-'98: 366 days (IQR 107-841), era '06-'11: 120 days (IQR 72-211), P<0.01), whereas in UC an initial decrease was observed (era '91-'98: 184 days (IQR 86-443), era '99-'05: 166 days (IQR 74-281), P=0.03), and stabilization thereafter. Immunomodulator and biological users had a lower risk of requiring corticosteroids than matched controls in CD only (33.6% vs. 49.9%, P<0.01, and 25.7% vs. 38.2%, P=0.04, respectively). CONCLUSIONS: In a real-world setting, more recently diagnosed IBD patients used lower amounts of corticosteroids as of the second year of disease. For CD, a significant association was found with the use of immunomodulators and biologicals. These conclusions support the increasing use of these treatment modalities.

Telemedicine for management of inflammatory bowel disease (myIBDcoach): a pragmatic, multicentre, randomised controlled trial.

BACKGROUND: Tight and personalised control of inflammatory bowel disease in a traditional setting is challenging because of the disease complexity, high pressure on outpatient clinics, and rising incidence. We compared the effects of self-management with a telemedicine system, which was developed for all subtypes of inflammatory bowel disease, on health-care utilisation and patient-reported quality of care versus standard care. METHODS: We did this pragmatic, randomised trial in two academic and two non-academic hospitals in the Netherlands. Outpatients aged 18-75 years with inflammatory bowel disease and without an ileoanal or ileorectal pouch anastomosis, who had internet access and Dutch proficiency, were randomly assigned (1:1) to care via a telemedicine system (myIBDcoach) that monitors and registers disease activity or standard care and followed up for 12 months. Randomisation was done with a computer-generated sequence and used the minimisation method. Participants, health-care providers, and staff who assessed outcome measures were not masked to treatment allocation. Primary outcomes were the number of outpatient visits and patient-reported quality of care (assessed by visual analogue scale score 0-10). Safety endpoints were the numbers of flares, corticosteroid courses, hospital admissions, emergency visits, and surgeries. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02173002. FINDINGS: Between Sept 9, 2014, and May 18, 2015, 909 patients were randomly assigned to telemedicine (n=465) or standard care (n=444). At 12 months, the mean number of outpatient visits to the gastroenterologist or nurse was significantly lower in the telemedicine group (1·55 [SD 1·50]) than in the standard care group (2·34 [1·64]; difference -0·79 [95% CI -0·98 to -0·59]; p<0·0001), as was the mean number of hospital admissions (0·05 [0·28] vs 0·10 [0·43]; difference -0·05 [-0·10 to 0·00]; p=0·046). At 12 months, both groups reported high mean patient-reported quality of care scores (8·16 [1·37] in the telemedicine group vs 8·27 [1·28] in the standard care group; difference 0·10 [-0·13 to 0·32]; p=0·411). The mean numbers of flares, corticosteroid courses, emergency visits, and surgeries did not differ between groups. INTERPRETATION: Telemedicine was safe and reduced outpatient visits and hospital admissions compared with standard care. This self-management tool might be useful for reorganising care of inflammatory bowel disease towards personalised and value-based health care. FUNDING: Maastricht University Medical Centre and Ferring.

A 20-Year Temporal Change Analysis in Incidence, Presenting Phenotype and Mortality, in the Dutch IBDSL Cohort-Can Diagnostic Factors Explain the Increase in IBD Incidence?

BACKGROUND: The aim was to study temporal changes in incidence, disease phenotype at diagnosis, and mortality of adult inflammatory bowel disease [IBD] patients in South Limburg, The Netherlands, diagnosed between 1991 and 2010. In addition, the 2010 IBD prevalence was estimated. METHODS: A multi-faceted approach including hospital administrations, the national pathology registry [PALGA], and general practitioners led to the identification of 1162 patients with Crohn's disease [CD], 1663 with ulcerative colitis [UC], and 84 with unclassified IBD [IBD-U]. Temporal changes in incidence, disease phenotype, and mortality were studied using linear, multinomial regression analyses, and standardised mortality rates [SMR], respectively. RESULTS: The annual incidences increased from 17.90/100000 in 1991 to 40.36/100000 in 2010 for IBD, from 5.84/100000 to 17.49/100000 for CD, and from 11.67/100000 to 21.47/100000 for UC [p < 0.01 for all]. A shift towards milder disease at diagnosis was observed over time [eg decrease of complicated disease in CD, increase of proctitis in UC]. IBD mortality was similar to that in the general population (SMR 0.92; 95% confidence interval [CI] 0.81-1.05), and did not change over time. The estimated IBD prevalence was 830/100000. CONCLUSIONS: The IBD incidence in South Limburg increased significantly between 1991 and 2010. The shift towards milder disease at diagnosis in parallel with the improved diagnostics and ability to detect low-grade inflammation was suggestive of an important role of diagnostic factors in this increase. Environmental factors probably played a role as well. The mortality was low and, together with the increasing incidence, led to the high prevalence of IBD in South Limburg.

Development and Feasibility Study of a Telemedicine Tool for All Patients with IBD: MyIBDcoach.

BACKGROUND: Tight control of disease activity, medication side effects, and adherence are crucial to prevent disease complications and improve quality of life in patients with inflammatory bowel disease (IBD). The chronic nature and increasing incidence of IBD demand health care innovations to guarantee future high-quality care. Previous research proved that integrated care by telemedicine can improve outcomes of chronic diseases. Currently available IBD telemedicine tools focus on specific patient subgroups. Therefore, we aimed to (1) develop a telemedicine system suitable for all patients with IBD in everyday practice and (2) to test this system's feasibility. METHODS: With a structured iterative process between patients, dietitians, IBD nurse-specialists, and gastroenterologists, myIBDcoach was developed. During 3 months, myIBDcoach's feasibility was tested by 30 consecutive outpatients with IBD of 3 hospitals. Thereafter, patients and health care providers completed a questionnaire covering satisfaction, accessibility, and experiences with myIBDcoach. RESULTS: MyIBDcoach enables continuous home-monitoring of patients with IBD and optimizes disease knowledge and communication between patients and health care providers. Besides disease activity, medication adherence, and side effects, myIBDcoach monitors malnutrition, smoking, quality of life, fatigue, life-events, work participation, stress, and anxiety and depression and provides e-learnings for patient empowerment. Patients graded the system with a mean of 7.8 of 10, and 93% would recommend myIBDcoach to other patients. CONCLUSIONS: We developed myIBDcoach, which enables integrated care for all patients with IBD, regardless of disease severity or medication use. The feasibility study showed high satisfaction and compliance of patients and health care providers. To study myIBDcoach's efficacy, a multicenter randomized controlled trial has been initiated.

High Percentage of IBD Patients with Indefinite Fecal Calprotectin Levels: Additional Value of a Combination Score.

BACKGROUND AND AIM: Monitoring mucosal inflammation in inflammatory bowel disease (IBD) is of major importance to prevent complications and improve long-term disease outcome. The correlation of clinical activity indices with endoscopic disease activity is, however, moderate. Fecal calprotectin (FC) is a better predictor of mucosal inflammation, but values between 100 and 250 µg/g are difficult to interpret in clinical practice. We aimed to evaluate the occurrence of indefinite FC levels in a real-life IBD cohort and study the additional value of a combination of biochemical markers and clinical activity indices. METHODS: In total, 148 Crohn's disease (CD) and 80 ulcerative colitis (UC) patients visiting the outpatient clinic were enrolled. FC, clinical disease activity scored by the Harvey-Bradshaw index or Simple Clinical Colitis Activity Index, and C-reactive protein (CRP) were assessed. In a subset of patients, endoscopic activity was scored by the simple endoscopic score-Crohn's disease and Mayo endoscopic subscore. Clinical activity index, CRP, and FC were integrated in a combination score and compared with endoscopy. RESULTS: Indefinite FC values were present in 24% of CD and 15% of UC. In the cohort of patients with endoscopy scores available, the combination score predicted endoscopic disease activity in CD with a sensitivity of 83% and specificity of 69% [positive predictive value (PPV) 58%, negative predictive value (NPV) 89%]. In UC, this was 88 and 75% (PPV 93%, NPV 60%). CONCLUSIONS: A combination of FC with clinical activity indices or CRP may aid in classifying patients with indefinite disease activity according to FC alone.

Improvements in the Long-Term Outcome of Crohn's Disease Over the Past Two Decades and the Relation to Changes in Medical Management: Results from the Population-Based IBDSL Cohort.

OBJECTIVES: Medical treatment options and strategies for Crohn's disease (CD) have changed over the past decades. To assess its impact, we studied the evolution of the long-term disease outcome in the Dutch Inflammatory Bowel Disease South Limburg (IBDSL) cohort. METHODS: In total, 1,162 CD patients were included. Three eras were distinguished: 1991-1998 (n=316), 1999-2005 (n=387), and 2006-2011 (n=459), and patients were followed until 2014. Medication exposure and the rates of hospitalization, surgery, and phenotype progression were estimated using Kaplan-Meier survival analyses and compared between eras by multivariable Cox regression models. Second, propensity score matching was used to assess the relation between medication use and the long-term outcome. RESULTS: Over time, the immunomodulator exposure rate increased from 30.6% in the era 1991-1998 to 70.8% in the era 2006-2011 at 5 years. Similar, biological exposure increased from 3.1% (era 1991-1998) to 41.2% (era 2006-2011). In parallel, the hospitalization rate attenuated from 65.9% to 44.2% and the surgery rate from 42.9% to 17.4% at 5 years, respectively (both P<0.01). Progression to a complicated phenotype has not changed over time (21.2% in the era 1991-1998 vs. 21.3% in the era 2006-2011, P=0.93). Immunomodulator users had a similar risk of hospitalization, surgery, or phenotype progression as propensity score-matched nonusers (P>0.05 for all analyses). Similar results were found for biological users (P>0.05 for all analyses). CONCLUSIONS: Between 1991 and 2014, the hospitalization and surgery rates decreased, whereas progression to complicated disease is still common in CD. These improvements were not significantly related to the use of immunomodulators and biologicals.

Inflammatory bowel disease, cancer and medication: Cancer risk in the Dutch population-based IBDSL cohort.

The management of inflammatory bowel disease (IBD) has changed since the mid-1990s (e.g., use of thiopurines/anti-TNFα agents, improved surveillance programs), possibly affecting cancer risk. To establish current cancer risk in IBD, updates are warranted from cohorts covering this time span, and detailed enough to study associations with phenotype and medication. We studied intestinal-, extra-intestinal- and overall cancer risk in the Dutch population-based IBDSL cohort. In total, 1,157 Crohn's disease (CD) and 1,644 ulcerative colitis (UC) patients were diagnosed between 1991 and 2011, and followed until 2013. Standardized incidence ratios (SIRs) were calculated for CD and UC separately, as well as for gender-, phenotype-, disease duration-, diagnosis era- and medication groups. We found an increased risk for colorectal cancer in CD patients with colon involvement (SIR 2.97; 95% CI 1.08-6.46), but not in the total CD or UC population. In addition, CD patients were at increased risk for hematologic- (2.41; 1.04-4.76), overall skin- (1.55; 1.06-2.19), skin squamous cell- (SCC; 3.83; 1.83-7.04) and overall cancer (1.28; 1.01-1.60), whereas UC patients had no increased risk for extra-intestinal- and overall cancer. Finally, in a medication analysis on CD and UC together, long-term immunosuppression exposure (>12 months) was associated with an increased risk for hematologic cancer, non-Hodgkin lymphoma, SCC and overall cancer, and this increase was mainly attributed to thiopurines. IBD patients with long-term immunosuppression exposure can be considered as having a higher cancer risk, and our data support the advice in recent IBD guidelines to consider skin cancer screening in these patients.

Epidemiology and Long-term Outcome of Inflammatory Bowel Disease Diagnosed at Elderly Age-An Increasing Distinct Entity?

BACKGROUND: Elderly onset (EO) inflammatory bowel disease (IBD) may become a more common entity as a result of population aging and the rising IBD incidence. Its management is challenging, because of multimorbidity, polypharmacy, and frailty. Insight into the long-term outcome is essential for optimal patient counseling and treatment. We studied the incidence and disease outcome of elderly-onset IBD in direct comparison to adult-onset (AO) IBD. METHODS: All 2823 cases with IBD from the Dutch population-based IBD South Limburg cohort, diagnosed between 1991 and 2011, were included. Long-term outcome (hospitalization, surgery, and disease phenotype) was compared between AO (<60 years at diagnosis) and EO (≥60 years at diagnosis) disease, for Crohn's disease (CD) and ulcerative colitis (UC) separately. RESULTS: In total, 1162 patients with CD (136 EO/1026 AO) and 1661 patients with UC (373 EO/1288 AO) were included. The EO IBD incidence increased from 11.71 per 100,000 persons in 1991 to 23.66 per 100,000 persons in 2010, P < 0.01. Immunomodulators were less often used in EO CD (61.8% versus 77.1%, P = 0.03) and EO UC (22.8% versus 35.4%, P < 0.01), even as biologicals (25.1% versus 55.1%, P = 0.03 and 7.8% versus 18.0%, P < 0.01, respectively). No differences were observed in surgery risk (CD: hazard ratio [HR] 1.19; 95% confidence interval [CI], 0.85-1.67 and UC: HR, 0.88; 95% CI, 0.53-1.46), or in CD phenotype progression (HR, 0.81; 95% CI, 0.52-1.25), but more patients with EO UC required hospitalization (HR, 1.29; 95% CI, 1.01-1.63). CONCLUSIONS: EO IBD is rising, warranting physicians' alertness for IBD in elderly patients. The long-term outcome was not different from AO disease, despite a less frequent use of immunomodulators and biologicals.

Plasma intestinal fatty acid-binding protein fails to predict endoscopic disease activity in inflammatory bowel disease patients.

BACKGROUND: Monitoring disease activity in inflammatory bowel disease (IBD) is of major importance to prevent long-term complications. Intestinal fatty acid-binding protein (I-FABP) has been identified as a marker for intestinal damage and correlates with the degree of inflammation. The aim of the present study was to evaluate whether I-FABP can predict active disease or remission in Crohn's disease (CD) and ulcerative colitis (UC) in a real-life IBD cohort. METHODS: In total, 70 patients with endoscopic disease activity available and 194 patients with disease activity on the basis of a stringent combi-score of clinical activity index, C-reactive protein, and fecal calprotectin were included. Plasma I-FABP was compared between patients with active disease and remission. In a small subgroup of CD patients, follow-up samples were analyzed. RESULTS: In CD (139.2 vs. 119.2 pg/ml; P=0.37) and UC (107.8 vs. 151.8 pg/ml; P=0.33), the median I-FABP did not differ in endoscopic active disease versus remission. In UC patients with active disease on the basis of the combi-score, the median I-FABP (106.8 vs. 172.0 pg/ml; P=0.03) was significantly lower than in patients in remission, but not in CD (145.5 vs. 157.5 pg/ml; P=0.29). Neither disease location in CD nor extent of disease in UC influenced I-FABP significantly. I-FABP was not different (P=0.78) in CD patients with a change in disease activity over time. CONCLUSION: Plasma I-FABP did not differ between endoscopic active disease and remission in both CD and UC. I-FABP was lower in active UC but not CD on the basis of the combi-score. On the basis of these findings, I-FABP has no potential as a novel noninvasive biomarker for disease activity in IBD.

Disease Outcome of Ulcerative Colitis in an Era of Changing Treatment Strategies: Results from the Dutch Population-Based IBDSL Cohort.

BACKGROUND AND AIMS: In the past decades, treatment options and strategies for ulcerative colitis [UC] have radically changed. Whether these developments have altered the disease outcome at population level is yet unknown. Therefore, we evaluated the disease outcome of UC over the past two decades in the South-Limburg area of The Netherlands. METHODS: In the Dutch population-based IBDSL cohort, three time cohorts were defined: cohort 1991-1997 [cohort A], cohort 1998-2005 [cohort B], and cohort 2006-2010 [cohort C]. The colectomy and hospitalisation rates were compared between cohorts by Kaplan-Meier survival analyses. Hazard ratios [HR] for early colectomy [within 6 months after diagnosis], late colectomy [beyond 6 months after diagnosis], and hospitalisation were calculated using Cox regression models. RESULTS: In total, 476 UC patients were included in cohort A, 587 patients in cohort B, and 598 patients in cohort C. Over time, an increase in the use of immunomodulators [8.1%, 22.8% and 21.7%, respectively, p < 0.01] and biological agents [0%, 4.3% and 10.6%, respectively, p < 0.01] was observed. The early colectomy rate decreased from 1.5% in cohort A to 0.5% in cohort B [HR 0.14; 95% confidence interval 0.04-0.47], with no further decrease in cohort C [0.3%, HR 0.98; 95% confidence interval 0.20-4.85]. Late colectomy rate remained unchanged over time [4.0% vs 5.2% vs 3.6%, respectively, p = 0.54]. Hospitalisation rate was also similar among cohorts [22.3% vs 19.5% vs 18.3%, respectively, p = 0.10]. CONCLUSION: Over the past two decades, a reduction in early colectomy rate was observed, with no further reduction in the most recent era. Late colectomy rate and hospitalisation rate remained unchanged over time.

Pancreatitis-associated protein has no additional value as a marker of disease activity in a real-life cohort of IBD patients.

BACKGROUND AND AIM: Monitoring of mucosal inflammation in inflammatory bowel disease (IBD) is of major importance. New noninvasive markers for intestinal inflammation are needed. Previous studies have reported that pancreatitis-associated protein (PAP) correlates with clinical activity in IBD subgroups. Our aim was to investigate the correlation of serum and fecal PAP with clinical and biochemical parameters of disease activity in a real-life IBD cohort. PATIENTS AND METHODS: Two hundred and five consecutive IBD patients were enrolled. Clinical disease activity was scored by the Harvey-Bradshaw Index or the Simple Clinical Colitis Activity Index; also, C-reactive protein (CRP), erythrocyte sedimentation rate, and fecal calprotectin were determined. As surrogate for endoscopy, a combination score of clinical indices with CRP or calprotectin was used to define active disease. Fecal and serum PAP were measured by ELISA. RESULTS: The median serum and fecal PAP did not differ in Crohn's disease (CD) or ulcerative colitis (UC) patients with active compared with inactive disease according to clinical activity indices. Defining active disease by a combination score of Harvey-Bradshaw Index of more than 4 and CRP of more than 5 mg/l or calprotectin more than 250 µg/g, serum PAP (P=0.01), but not fecal PAP (P=0.32), was significantly higher in active than inactive CD patients. Area under the curve of the corresponding receiver operating curve (ROC) was 0.64. No differences were found in serum or fecal PAP levels using the combination score for active disease in UC. CONCLUSION: Serum but not fecal PAP was higher in active compared with nonactive CD and may reflect mucosal inflammation in CD, but not in UC. However, the accuracy of serum PAP for the diagnosis of active disease was poor, and therefore, serum PAP does not seem to have additional value compared with the current noninvasive markers.

Real-time in vivo imaging of early mucosal changes during ischemia-reperfusion in human jejunum.

BACKGROUND AND STUDY AIMS: Small intestinal ischemia-reperfusion (IR) is a frequent, potentially life threatening phenomenon. There is a lack of non-invasive diagnostic modalities. For many intestinal diseases, visualizing the intestinal mucosa using endoscopy is gold standard. However, limited knowledge exists on small intestinal IR-induced, early mucosal changes. The aims of this study were to investigate endoscopic changes in human jejunum exposed to IR, and to study concordance between endoscopic appearance and histology. PATIENTS AND METHODS: In 23 patients a part of jejunum, to be removed for surgical reasons, was isolated and selectively exposed to ischemia with 0, 30 or 120 minutes of reperfusion. In 3 patients, a videocapsule was inserted in the isolated segment before exposure to IR, to visualize the mucosa. Endoscopic view at several time points was related to histology (Heamatoxylin & Eosin) obtained from 20 patients. RESULTS: Ischemia was characterized by loss of villous structure, mucosal whitening and appearance of punctate lesions. This was related to appearance of subepithelial spaces and breaches in the epithelial lining in the histological view. Early during reperfusion, the lumen filled with IR-damaged, shed cells and VCE showed mucosal erosions, hemorrhage and intraluminal debris. At 60 minutes of reperfusion, the only remaining signs of IR were loss of villous structure and small erosions, indicating rapid mucosal healing. CONCLUSIONS: This study shows a unique, real-time in vivo endoscopic view of early mucosal changes during IR of the human small intestine. Future studies should evaluate its usefulness in diagnosis of patients suspected of IR.

Transoral incisionless fundoplication for treatment of gastroesophageal reflux disease in clinical practice.

BACKGROUND: Transoral incisionless fundoplication is a recently introduced endoluminal technique for the treatment of gastroesophageal reflux disease (GERD). The objective of this study was to determine outcomes in chronic GERD patients who were referred for surgical management. METHODS: A cohort of 38 patients underwent transoral incisionless fundoplication (TIF) in a tertiary care setting. Pre- and post-procedure assessment included GERD-related quality of life questionnaires, proton pump inhibitor (PPI) usage, 24-h pH measurements, upper gastrointestinal endoscopy, esophageal manometry, and registration of adverse events. Duration of follow-up was 36 months. RESULTS: Gastroesophageal valves were constructed of 4 cm (range, 4-6) in length and 220° (range, 180-240) in circumference. One serious adverse event occurred, consisting of intraluminal bleeding at a fastener site. Hiatal hernia was completely reduced in 56 % and esophagitis was cured in 47 % of patients. Postprocedure esophageal acid exposure did not significantly improve (p > 0.05). At 36 (range, 29-41) months follow-up 14 patients (36 %) had undergone revisional laparoscopic fundoplication. Quality of life scores of the remaining cohort showed significant improvement (p < 0.0001) and daily use of antisecretory medication was discontinued by 74 %. CONCLUSIONS: Endoluminal fundoplication improved quality of life and reduced the need for PPIs in only a subgroup of patients at 3 years follow-up. The amount of patients requiring additional medication and revisional surgery was high.

A multicenter, randomized efficacy study of the EndoBarrier Gastrointestinal Liner for presurgical weight loss prior to bariatric surgery.

BACKGROUND: The endoscopically placed duodenal-jejunal bypass sleeve or EndoBarrier Gastrointestinal Liner has been designed to achieve weight loss in morbidly obese patients. We report on the first European experience with this device. METHODS: A multicenter, randomized clinical trial was performed. Forty-one patients were included and 30 underwent sleeve implantation. Eleven patients served as a diet control group. All patients followed the same low-calorie diet during the study period. The purpose of the study was to determine the safety and efficacy of the device. RESULTS: Twenty-six devices were successfully implanted. In 4 patients, implantation could not be achieved. Four devices were explanted prior to the initial protocol end point because of migration (1), dislocation of the anchor (1), sleeve obstruction (1), and continuous epigastric pain (1). The remaining patients all completed the study. Mean procedure time was 35 minutes (range: 12-102 minutes) for a successful implantation and 17 minutes (range: 5-99 minutes) for explantation. There were no procedure related adverse events. During the study period the 26 duodenal-jejunal bypass sleeve patients (100%) had at least one adverse event, mainly abdominal pain and nausea during the first week after implantation. Initial mean body mass index (BMI, kg/m2) was 48.9 and 47.4 kg/m2 for the device and control patients, respectively. Mean excess weight loss after 3 months was 19.0% for device patients versus 6.9% for control patients (P < 0.002). Absolute change in BMI at 3 months was 5.5 and 1.9 kg/m2, respectively. Type 2 diabetes mellitus was present at baseline in 8 patients of the device group and improved in 7 patients during the study period (lower glucose levels, HbA1c, and medication requirements). CONCLUSION: The EndoBarrier Gastrointestinal Liner is a feasible and safe noninvasive device with excellent short-term weight loss results. The device also has a significant positive effect on type 2 diabetes mellitus. Long-term randomized and sham studies for weight loss and treatment of diabetes are necessary to determine the role of the device in the treatment of morbid obesity.This study was registered at www.clinicaltrials.gov (registration number: NCT00830440).

Mortality in inflammatory bowel disease in the Netherlands 1991-2002: results of a population-based study: the IBD South-Limburg cohort.

BACKGROUND: The aim was to evaluate overall and disease-specific mortality in a population-based inflammatory bowel disease (IBD) cohort in the Netherlands, as well as risk factors for mortality. METHODS: IBD patients diagnosed between 1 January 1991 and 1 January 2003 were included. Standardized mortality ratios (SMRs) were calculated overall and with regard to causes of death, gender, as well as age, phenotype, smoking status at diagnosis, and medication use. RESULTS: At the censoring date, 72 out of 1187 patients had died (21 Crohn's disease [CD], 47 ulcerative colitis [UC], and 4 indeterminate colitis [IC] patients). The SMR (95% confidence interval [CI]) was 1.1 (0.7-1.6) for CD, 0.9 (0.7-1.2) for UC and 0.7 (0.2-1.7) for IC. Disease-specific mortality risk was significantly increased for gastrointestinal (GI) causes of death both in CD (SMR 7.5, 95% CI: 2.8-16.4) and UC (SMR 3.4, 95% CI: 1.4-7.0); in CD patients, especially in patients <40 years of age at diagnosis. For UC, an increased SMR was noted in female patients and in patients <19 years and >80 years at diagnosis. In contrast, UC patients had a decreased mortality risk from cancer (SMR 0.5, 95% CI; 0.2-0.9). CONCLUSIONS: In this population-based IBD study, mortality in CD, UC, and IC was comparable to the background population. The increased mortality risk for GI causes might reflect complicated disease course, with young and elderly patients at diagnosis needing intensive follow-up. Caution in interpreting the finding on mortality risk from cancer is needed as follow-up was probably to short to observe IBD-related cancers.

In vivo diagnosis and classification of colorectal neoplasia by chromoendoscopy-guided confocal laser endomicroscopy.

BACKGROUND & AIMS: Colorectal cancer surveillance guidelines rely on clinicohistologic features of adenomas. Unfortunately, in common practice, recording of these features lacks precision and uniformity, which might hamper appropriate follow-up decisions. Confocal laser endomicroscopy (CLE) is a novel technology that allows real-time in vivo microscopy of the mucosa and provides accurate histopathology. The aims of this study were (1) to define and validate differential features of adenomatous and nonadenomatous colorectal polyps by chromoendoscopy-guided CLE (C-CLE) and (2) to assess predictive value of this technique for diagnosis of colorectal neoplasia. METHODS: Patients at risk for colorectal cancer were prospectively investigated by using CLE. During extubation, fluorescein 10% was used in conjunction with acriflavine hydrochloride 0.05% to characterize global tissue architecture as well as cytonuclear features of colorectal epithelium. Ex vivo histology was used as gold standard. Reproducibility tests were performed. RESULTS: In total, 116 colorectal polyps from 72 patients were examined. Ex vivo histology showed 68 adenomas, 6 invasive carcinomas, 30 hyperplastic polyps, and 12 inflammatory polyps. C-CLE of adenomas revealed lack of epithelial surface maturation, crypt budding, altered vascular pattern, and loss of cell polarity. In contrast, C-CLE of nonadenomatous polyps revealed epithelial surface maturation, and minor abnormalities of crypt architecture and of vascular pattern, and maintained cell polarity. Adenoma dysplasia score reliably discriminated high-grade dysplasia from low-grade dysplasia (accuracy, 96.7%). Interobserver agreement was high (K coefficients: pathologist, 0.92; endomicroscopist, 0.88). In vivo histology predicted ex vivo data with sensitivity of 97.3%, specificity of 92.8%, and accuracy of 95.7%. CONCLUSIONS: C-CLE accurately discriminates adenomatous from nonadenomatous colorectal polyps and enables evaluation of degree of dysplasia during ongoing endoscopy. This technology might offer considerable potential to ultimately fine-tune surveillance programs, particularly in high-risk groups.

Inflammatory Bowel Disease in South Limburg (the Netherlands) 1991-2002: Incidence, diagnostic delay, and seasonal variations in onset of symptoms.

BACKGROUND AND AIMS: Increasing incidence in Inflammatory Bowel Disease (IBD) has been suggested. Recent data on population based incidence rates within Europe are however scarce. Primary aim was to investigate prospectively the incidence of IBD within a well-defined geographical and administrative area of the Netherlands, the South Limburg IBD registry. Secondary aims were to study the duration of symptoms before diagnosis (lag time) and seasonal influences on the incidence of IBD. METHODS: The incidence was examined using standardized registration of all newly diagnosed IBD patients, between 1-1-1991 and 1-1-2003. Medical records were reviewed to verify the diagnosis. At inclusion, diagnostic lag time was registered in months. RESULTS: Age standardized incidence rates per 100,000 person-years (p-y) were: Crohn's Disease, male 4.84, female 7.58; Ulcerative Colitis, male 8.51, female 6.92; and Indeterminate Colitis, male 1.05, female 0.93. Incidence rates did not significantly changes over time in either Crohn's Disease, Ulcerative Colitis or Indeterminate Colitis. Lag time was 5 (0-360) months in Crohn's Disease, 3.0 (0-480) months in Ulcerative Colitis and 3.0 (0-180) months in Indeterminate Colitis. Lag time was not significantly different between the periods 1991-1993 and 2000-2002, and no statistical differences in the onset of symptoms per calendar month or season were found. CONCLUSIONS: Our results, from the South Limburg region (the Netherlands), show no significant change in incidence rates of IBD. The incidence found is relatively high compared to other European countries. Lag time did not change during the study period, and seasonal influence of incidence rates could not be confirmed.

Azathioprine induced pneumonitis in a patient with ulcerative colitis.

Immunomodulator therapy with the thiopurine analogues azathioprine (AZA) or 6-mercaptopurine (6-MP) is commonly prescribed for maintenance of remission in inflammatory bowel disease (IBD). Ten to twenty-five percent of patients have to withdraw from AZA or 6-MP due to adverse events that are partly explained by the relative activity of the drug metabolizing enzymes. Most of the potential major adverse events (myelosuppression, hepatotoxicity and pancreatitis) are well known. Pulmonary toxicity is rare but severe and may lead to respiratory insufficiency and even death. We describe a case of a young woman with ulcerative colitis (UC) who developed respiratory symptoms and fever combined with nodular densities and ground glass areas in both lungs on CT scan. An infection was ruled out and the diagnosis azathioprine induced pneumonitis was made. The drug was stopped and within one week her fever and respiratory symptoms resolved. Clinicians should be alert to this serious adverse event when treating patients with thiopurines.