Web-based dietary assessment and advice helps inflammatory bowel disease patients to improve their diet quality.

Time to evaluate diet quality and give dietary advice is limited in clinical IBD practice. The Eetscore is a web-based tool that assesses diet quality according to the Dutch dietary guidelines and provides personalised dietary advice. We aimed to assess diet quality of IBD patients using the Eetscore and to study changes in diet quality, health-related quality of life (HRQoL) and clinical disease activity over time. A prospective cohort study was performed in 195 adult IBD patients. Participants were invited to fill out questionnaires (Eetscore-FFQ, short IBDQ and p-HBI/p-SCCAI) at baseline and after 1 and 4 months. The Eetscore calculates diet quality based on 16 food components (10 points per component, total score 0-160; the higher the better) and provides dietary advice per component based on the assessment. At baseline, mean diet quality was 98±19. Diet quality was positively associated with age, female gender and level of education. Component scores were highest for red meat, wholegrain products, and sweetened beverages, and lowest for legumes, nuts, and processed meat. Over time, diet quality increased to 107±21 at 4 months (p<0.001). Each 10-point improvement in diet quality was associated with an increase in HRQoL (ß=0.4 (95%CI 0.02; 0.7), p=0.04). Clinical disease activity did not change. In conclusion, diet quality of IBD patients significantly improved following personalised dietary advice of the Eetscore. Improvement of diet quality was associated with a slight improvement in HRQoL. The Eetscore is a practical and useful tool to monitor and support a healthy diet in IBD patients.

Mobile application to monitor inflammatory bowel disease patients on intravenous biologic treatment: a feasibility study.

BACKGROUND: Monitoring of IBD patients on intravenous biologic treatment is recommended but time-consuming for patients and nurses. We developed a mobile application (app) to promote self-management and studied its feasibility in clinical practice. METHODS: Adult IBD patients treated with intravenous infliximab or vedolizumab used the app over four biologic treatments. The app includes information modules and an interactive timeline with notifications of blood tests and health checks before treatment. RESULTS: In total, 55 patients participated of whom 71% had Crohn's disease and 85% used infliximab. Compliance with health checks and blood tests was 67% before the first biologic treatment and 70, 87, and 80% before the second, third, and fourth treatment, respectively. The median number of times the app was used per treatment varied from 6 to 8 times (≥4 considered sufficient). Patients were satisfied with the app [median VAS score 8 (IQR 7-9)] and remained equally satisfied with IBD care [score 8 (IQR 8-9) before and after app use]. Nurses contacted all patients by telephone before the first biologic treatment, as previous standard care. Before the second, third, and fourth treatment only 47, 35, and 49% of patients were contacted. The majority (92%) wanted to continue using the app after the study. CONCLUSIONS: Monitoring of IBD patients treated with intravenous biologics using an app is feasible. We saw high compliance, sufficient app use, and high patient satisfaction. Moreover, health-care utilization was reduced and almost all patients preferred using the app over previous standard care (ClinicalTrials.gov NCT04254614).

Distribution of mucosal PD-1 expressing T cells in patients with colitis of different etiologies.

BACKGROUND: Immunotherapy, targeting programmed death-1 (PD-1) enhances antitumor T-cell activity in patients with malignancies. Blocking PD-1 or its ligand may lead to fulminant colitis as serious adverse event in these patients. Since little is known of the presence and role of PD-1+T cells in colitis of different etiologies, we determined PD-1+T cells in mucosal specimens of patients with inflammatory bowel disease, infectious colitis (InfC), immunotherapy-related colitis (ImC) and healthy controls (HC). METHODS: Newly diagnosed patients with ulcerative colitis (UC, n = 73), Crohn's disease (CD, n = 50), InfC (n = 5), ImC (n = 8) and HC (n = 8) were included. Baseline inflamed colonic biopsies were studied with immunohistochemistry and flowcytometry. RESULTS: Using immunohistochemistry, PD-1 was not present on lymphocytes in the epithelium of all patients, nor in HC. The percentage PD-1+ of all lymphocytes in the lamina propria was 40% in UC, 5% in InfC, 3% in ImC and 0% in HC. Flowcytometry showed significant higher percentages of PD-1+T cells in inflamed biopsy specimens of UC patients (22%) compared to all other groups: CD patients (13%), InfC (12%), ImC (5%) and HC (6%). CONCLUSION: There are relevant differences in distribution and frequencies of mucosal PD-1+ T-cell subsets in patients with UC, CD, InfC and ImC, supporting the hypothesis that these types of colitis are driven by different immunological pathways. The increased numbers of PD-1+ and PD-L1+ lymphocytes in the colonic mucosa of UC patients suggest that the PD-1/PD-L1 pathway might be more activated in UC than in CD.

Improvement of Fatigue and Quality of Life in Patients with Quiescent Inflammatory Bowel Disease Following a Personalized Exercise Program.

BACKGROUND AND AIMS: Fatigue significantly impacts the quality of life of patients with inflammatory bowel disease (IBD). This study aimed to assess the effect of a personalized, intensive exercise program on fatigue, health-related quality of life (HRQoL), and cardiorespiratory fitness in patients with quiescent IBD and severe fatigue. METHODS: A pilot study was performed including IBD patients in remission with severe fatigue. The 12-week exercise program consisted of three times per week 1-h sessions, including aerobic- and progressive-resistance training at personalized intensity based on a cardiopulmonary exercise test (CPET) and one-repetition maximum. CPET was repeated after 12 weeks. Fatigue and HRQoL were assessed using the checklist individual strength and 32-item IBD questionnaire. RESULTS: Twenty-five IBD patients with mean age of 45 (± 2.6) years were included of which 22 (88%) completed the exercise program. Fatigue significantly improved from 105 (± 17) points on the checklist individual strength before, to 66 (± 20) after completion of exercise program (p < 0.001). Patients' HRQoL significantly improved from 156 (± 21) to 176 (± 19) (p < 0.001). When looking at the subdomains of HRQoL, significant improvement was seen in emotional (58 ± 12 vs. 69 ± 9.1, p = 0.003), systemic (19 ± 3.9 vs. 24 ± 4.7, p < 0.001), and social function (25 ± 5.4 vs. 30 ± 3.9, p < 0.001). Bowel symptoms did not change (53 ± 7.7 vs. 55 ± 7.3, p = 0.208). Repeat CPET showed a significant improvement in maximum power patients were able to deliver (2.4 ± 0.5 vs. 2.7 ± 0.5 W/kg, p = 0.002). CONCLUSIONS: A personalized, intensive exercise program can lead to significant improvement of fatigue, HRQoL, and cardiorespiratory fitness in patients with quiescent IBD and severe fatigue.

Changes in glycemic control and body weight after explantation of the duodenal-jejunal bypass liner.

BACKGROUND AND AIMS: The duodenal-jejunal bypass liner (DJBL) is an endoscopic device that induces weight loss and improves glycemic control in patients with type 2 diabetes mellitus (T2DM). The aim of the current study was to assess the effects of DJBL explantation on glycemic control and body weight. METHODS: This prospective, observational study included only patients with T2DM who had the DJBL implanted for at least 6 months and had a follow-up of at least 12 months after explantation. The primary endpoints were changes in glycosylated hemoglobin A1c (HbA1c) and body weight during the 12 months after explantation. Secondary endpoints were changes in fasting plasma glucose, blood pressure, and plasma lipid levels. RESULTS: In total, 59 patients completed the 12-month follow-up after explantation. During this period body weight increased by 5.6 (standard deviation, 6.4) kg (P < .001) and HbA1c rose from 65 (SD 17) to 70 (SD 20) mmol/mol (P < .001). However, body weight remained 8.0 (SD 8.6) kg (P < .001) lower than before implantation, that is, corresponding to a net total body weight loss of 7.4% (SD 7.6) (P < .001). Although HbA1c was significantly higher 12 months after explantation compared with baseline and the mean daily dose of insulin used was comparable, the number of patients on insulin remained significantly lower than before implantation. CONCLUSIONS: Explantation of the DJBL is associated with weight gain and worsening of glycemic control, although some beneficial effects remained detectable 12 months after explantation. A change in strategy is needed to preserve the beneficial effects of DJBL treatment. (Clinical trial registration number: 746∖100111.).

The value of serum antibodies in differentiating inflammatory bowel disease, predicting disease activity and disease course in the newly diagnosed patient.

BACKGROUND: Data on serum antibodies in untreated adult inflammatory bowel disease (IBD) patients at diagnosis are scarcely available, and results on the stability of antibody presence over time are inconsistent. Our aim was to investigate antibodies in newly diagnosed, untreated IBD patients in relation to disease phenotype and course. Furthermore, we analyzed antibody presence over time. METHODS: Baseline anti-Saccharomyces cerevisiae antibodies (ASCA), anti-chitobioside carbohydrate antibodies (ACCA), anti-laminaribioside carbohydrate antibodies (ALCA) and anti-mannobioside carbohydrate antibodies (AMCA) were measured with enzyme-linked immunosorbent assays and perinuclear anti-neutrophilic cytoplasmic antibodies (pANCA) was measured by indirect immunofluorescence in serum of 120 untreated IBD patients at diagnosis and 19 healthy controls. Antibodies were related to disease outcomes. Serial measurements were available in 71 patients. RESULTS: The combination of pANCA and ASCA enabled good discrimination between UC and CD (p = .004). Antibody presence was relatively stable over time, even though there were significant changes in concentrations. There was a trend towards larger fluctuations in concentration with immunosuppressive medication. Baseline pANCA in UC patients correlated with calprotectin values (rho = .545, p = .019) and change in pANCA status over time was associated with disease activity at that moment. No associations were found with antibodies at diagnosis and disease outcomes. CONCLUSION: Antibody profiles at diagnosis support the distinction between CD and UC. Anti-glycan antibodies are reasonably stable over time, but may fluctuate under the influence of immunosuppressive treatment which may explain the inconsistency in findings hitherto. The appearance or disappearance of pANCA antibodies during follow-up correlated with disease activity in UC and may be used in disease monitoring.

Weight reduction and improvement in diabetes by the duodenal-jejunal bypass liner: a 198 patient cohort study.

BACKGROUND: The duodenal-jejunal bypass liner (DJBL) is an endoscopic treatment for patients with type 2 diabetes mellitus (T2DM) and (morbid) obesity. The aim of the current study was to determine its efficacy and safety profile. METHODS: Inclusion criteria for treatment with a DJBL were: age 18-70 years, BMI 28-45 kg/m2, and T2DM with a HbA1c > 48 mmol/mol. Primary outcomes were changes in HbA1c and body weight. Secondary outcomes included changes in blood pressure, lipids, and anti-diabetic medication. Predictive factors for success of treatment with the DJBL were determined. RESULTS: Between 2011 and 2014, 185 out of 198 patients successfully underwent a DJBL implantation procedure, with an intended implantation time of 12 months. In these 185 patients, body weight decreased by 12.8 ± 8.0 kg (total body weight loss of 11.9 ± 6.9 %, p < 0.001), HbA1c decreased from 67 to 61 mmol/mol (p < 0.001) despite a reduction in anti-diabetic medication, and blood pressure and serum lipid levels all decreased. In total, 57 (31 %) DJBLs were explanted early after a median duration of 33 weeks. Adverse events occurred in 17 % of patients. C-peptide ≥1.0 nmol/L and body weight ≥107 kg at screening were independent predictive factors for success. CONCLUSIONS: Treatment with the DJBL in T2DM patients with (morbid) obesity results in improvement in glucose control, a reduction in anti-diabetic medication, and significant weight loss. The largest changes are observed within the first 3-6 months. Initial C-peptide levels and body weight may help to select patients with the greatest chance of success.

Safety experience with the duodenal-jejunal bypass liner: an endoscopic treatment for diabetes and obesity.

BACKGROUND: The duodenal-jejunal bypass liner (DJBL) is a new, device-based endoscopic treatment for type 2 diabetes mellitus (T2DM) and obesity. OBJECTIVE: To report serious safety events of subjects treated with the DJBL while offering a simple guideline to mitigate risk. DESIGN: Single-center observational study. SETTING: Tertiary referral center. PATIENTS: For commercial use, patients were eligible for implantation of the DJBL when they met the following criteria: age 18 to 65 years, body mass index 28 to 45 kg/m(2), T2DM, and negative serum Helicobacter pylori test. INTERVENTIONS: Endoscopic implantation of the DJBL. MAIN OUTCOME MEASUREMENTS: Adverse events, serious adverse events, early explantation. RESULTS: Between October 2007 and January 2014, 152 of 165 planned implantations (92%) and 94 explantations were performed in our center. Significant weight loss and improvement in T2DM and other cardiovascular parameters were achieved. Early removal of the device occurred because of persistent GI symptoms in 16 patients (11%). Serious adverse events were observed in a subset of patients: 7 GI bleeds, 5 of which required early removal; 2 cases of pancreatitis; 1 case of hepatic abscess; and 1 obstruction of the sleeve. Explantation resulted in an esophageal tear in 2 cases. LIMITATIONS: Single-center study. CONCLUSION: The DJBL improves glycemic control while causing weight loss. The safety profile of the DJBL demonstrates a reasonable tolerability profile. However, serious safety adverse events can occur. Patient selection, expert use of the device at placement and removal, and the supportive care of an experienced multidisciplinary team are key for safe and effective use of the DJBL.

Rising incidence of celiac disease in the Netherlands; an analysis of temporal trends from 1995 to 2010.

OBJECTIVE: According to screening studies, celiac disease (CD) is prevalent in Western Europe. Actual prevalence tends to be much lower. The width of this actual gap is determined by the balance between disease symptoms and the "case-finding" capabilities of the healthcare system. Therefore, we conducted a nationwide study to determine the temporal trends in the incidence in the Netherlands including a focus on demographic aspects. MATERIALS AND METHODS: We performed a nationwide search in the Dutch Pathology Registry (PALGA) to identify all biopsy-proven cases of CD in five different years between 1995 and 2010. Furthermore, demographic profiles and socioeconomic status (SES) of patients were studied. RESULTS: The overall incidence of CD increased from 2.72 (confidence interval [CI] 2.46-2.99) in 1995 to 6.65 (CI 6.27-7.06) per 100,000 inhabitants in 2010. No significant regional differences were noticed. In men, rates increased from 2.28 (CI 1.95-2.65) to 4.71 (CI 4.25-5.20) per 100,000 in 2010. In women, the increase was from 3.27 (CI 2.88-3.70) to 8.66 (CI 8.04-9.31) per 100,000 in 2010. A trend toward leveling of incidence was observed from 2008 to 2010. Patients diagnosed during childhood live in areas with a higher SES compared with patients diagnosed at adult age. CONCLUSION: The incidence of biopsy-proven CD in the Netherlands increased almost threefold between 1995 and 2010. In areas with a higher SES, relatively more children were diagnosed.

Dietary supplement use is not associated with recurrence of colorectal adenomas: a prospective cohort study.

Diet and lifestyle influence colorectal adenoma recurrence. The role of dietary supplement use in colorectal adenoma recurrence remains controversial. In this prospective cohort study, we examined the association between dietary supplement use, total colorectal adenoma recurrence and advanced adenoma recurrence. Colorectal adenoma cases (n = 565) from a former case-control study, recruited between 1995 and 2002, were prospectively followed until 2008. Adenomas with a diameter of ≥1 cm and/or (tubulo)villous histology and/or with high grade dysplasia and/or ≥3 adenomas detected at the same colonic examination were considered advanced adenomas. Hazard ratios (HRs) and 95% confidence intervals (CIs) for dietary supplement users (use of any supplement during the past year) compared to nonusers and colorectal adenoma recurrence were calculated using stratified Cox proportional hazard models for counting processes and were adjusted for age, sex, educational level and number of colonoscopies during follow-up. Robust sandwich covariance estimation was used to adjust for the within subject correlation. A number of 165 out of 565 adenoma patients had at least one colorectal adenoma recurrence during a median person-time of 5.4 years and of these, 37 patients had at least one advanced adenoma. One-third of the total study population (n = 203) used a dietary supplement. Compared to no use, dietary supplement use was neither statistically significantly associated with total colorectal adenoma recurrence (HR = 1.03; 95% CI 0.79-1.34) nor with recurrent advanced adenomas (HR = 1.59; 95% CI 0.88-2.87). This prospective cohort study did not suggest an association between dietary supplement use and colorectal adenoma recurrence.

External Validity and Consistency over Time of Patient Segmentation Based on Disease Acceptance and Perceived Control in Inflammatory Bowel Disease.

BACKGROUND AND AIMS: The patient segmentation model based on disease acceptance and perceived control may guide personalized care in inflammatory bowel disease (IBD). We aimed to investigate the external validity of the segmentation model and its consistency over time. METHODS: This is a multicenter longitudinal cohort study of adult IBD patients with questionnaires on disease acceptance and perceived control (6-items, 7-point Likert scale) and health-related quality of life (HRQoL) (Short IBD questionnaire, range 10-70). Segments were created based on mean scores (cut-off>5): (I) high acceptance, high control; (II) high acceptance, low control; (III) low acceptance, high control and; (IV) low acceptance, low control. RESULTS: The external validation cohort included 921 IBD patients. The acceptance and control scale were unidimensional and internally consistent. Segments differed significantly in gender, disease duration, IBD medication and clinical disease activity. High acceptance and/or high control were significantly associated with a higher HRQoL compared with low acceptance and low control (i.e., segment IV) (Beta (95%CI) segment I=11.7 (10.4-13.1), segment II=9.3 (7.7-10.9) and segment III=3.8 (1.6-6.0), p≤0.001). The follow-up cohort included 783 patients: 58% remained in the same segment while 42% differed in segment over time. Changes in segment were positively correlated with changes in HRQoL over time (Spearman rho 0.38, p<0.001). CONCLUSIONS: The patient segmentation model based on disease acceptance and perceived control was externally valid and showed consistency over time. The different segments were independently associated with HRQoL. Future interventions should aim to personalize care based on segments and improve disease acceptance and perceived control of IBD patients.

Mucosal α4ß7+ Lymphocytes and MAdCAM+ Venules Predict Response to Vedolizumab in Ulcerative Colitis.

BACKGROUND: Therapeutic strategies for patients with ulcerative colitis (UC) are based on patient- and disease-related factors in combination with drug characteristics but fail to predict success in individual patients. A considerable proportion of UC patients do not respond to the biological vedolizumab. Therefore, pretreatment biomarkers for therapeutic efficacy are urgently needed. Mucosal markers related to the integrin-dependent T lymphocyte homing could be potent predictors. METHODS: We prospectively included 21 biological- and steroid-naive UC patients with moderate-to-severe disease activity planned to escalate therapy to vedolizumab. At week 0, before initiating treatment, colonic biopsy specimens were obtained for immunophenotyping and immunohistochemistry. Clinical and endoscopic disease activity were determined at week 16 after 4 infusions of vedolizumab. In addition, we retrospectively included 5 UC patients who were first treated with anti-tumor necrosis factor α before receiving vedolizumab to compare with biological-naive patients. RESULTS: Abundance of α4ß7 on more than 8% of all CD3+ T lymphocytes in colonic biopsies at baseline was predictive for responsiveness to vedolizumab (sensitivity 100%, specificity 100%). The threshold for the proportion of MAdCAM-1+ and PNAd+ of all venules in the biopsies predictive for responsiveness to vedolizumab was ≥2.59% (sensitivity 89%, specificity 100%) and ≥2.41% (sensitivity 61%, specificity 50%), respectively. At week 16, a significant decrease of α4ß7+CD3+T lymphocytes was demonstrated in responders (18% [12%-24%] to 8% [3%-9%]; P = .002), while no difference was seen in nonresponders (4% [3%-6%] to 3%; P = .59). CONCLUSIONS: UC responders to vedolizumab have a higher percentage of α4ß7+CD3+ T lymphocytes and a higher proportion of MAdCAM-1+ venules in colonic biopsies than nonresponders before initiating therapy. Both analyses could be promising predictive biomarkers for therapeutic response and may lead to more patient tailored treatment in the future.

A conservative and minimally invasive approach to necrotizing pancreatitis improves outcome.

BACKGROUND & AIMS: Treatment of patients with necrotizing pancreatitis has become more conservative and less invasive, but there are few data from prospective studies to support the efficacy of this change. We performed a prospective multicenter study of treatment outcomes among patients with necrotizing pancreatitis. METHODS: We collected data from 639 consecutive patients with necrotizing pancreatitis, from 2004 to 2008, treated at 21 Dutch hospitals. Data were analyzed for disease severity, interventions (radiologic, endoscopic, surgical), and outcome. RESULTS: Overall mortality was 15% (n=93). Organ failure occurred in 240 patients (38%), with 35% mortality. Treatment was conservative in 397 patients (62%), with 7% mortality. An intervention was performed in 242 patients (38%), with 27% mortality; this included early emergency laparotomy in 32 patients (5%), with 78% mortality. Patients with longer times between admission and intervention had lower mortality: 0 to 14 days, 56%; 14 to 29 days, 26%; and >29 days, 15% (P<.001). A total of 208 patients (33%) received interventions for infected necrosis, with 19% mortality. Catheter drainage was most often performed as the first intervention (63% of cases), without additional necrosectomy in 35% of patients. Primary catheter drainage had fewer complications than primary necrosectomy (42% vs 64%, P=.003). Patients with pancreatic parenchymal necrosis (n=324), compared with patients with only peripancreatic necrosis (n=315), had a higher risk of organ failure (50% vs 24%, P<.001) and mortality (20% vs 9%, P<.001). CONCLUSIONS: Approximately 62% of patients with necrotizing pancreatitis can be treated without an intervention and with low mortality. In patients with infected necrosis, delayed intervention and catheter drainage as first treatment improves outcome.

Dose-Escalating (50-500 mg) Gluten Administration Leads to Detectable Gluten-Immunogenic-Peptides in Urine of Patients with Coeliac Disease Which Is Unrelated to Symptoms, a Placebo Controlled Trial.

BACKGROUND: To determine the applicability and sensitivity of a urine self-test to detect gluten-immunogenic-peptides (GIP) in daily-life for patients with coeliac disease and correlate the test results with reported symptoms. METHODS: We performed a prospective double-blinded placebo-controlled study, including adults with coeliac disease adhering to a strictly gluten-free diet. Patients were administered gluten in test-cycles of ascending doses of 50, 100, 200, and 500 mg alternated with placebo. Urine portions from 2, 5-17 h after the ingestion were collected and analyzed for GIP using the iVYCHECK-GIP-Urine rapid lateral flow test. Patients completed a diary mapping symptoms (nausea, bloating, diarrhea, abdominal pain, and lower level of energy). RESULTS: We enrolled 15 patients and 7 received all 4 cycles with increasing gluten dosing. GIP was detected from urine in 47% of the patients receiving 50 mg gluten and in 86% with 500 mg gluten. We detected GIP in 20-50% of urine samples after placebo. There was no correlation between symptoms, gluten administration and/or GIP in urine. CONCLUSIONS: Gluten intake, even with a dose as low as 50 mg, leads to detectable urinary GIP concentrations. There is no correlation of coeliac disease ascribed symptoms with detection of urinary GIP.

Improving Care for Recently Diagnosed Inflammatory Bowel Disease Patients: Lessons Learned From a Patient-Centred, Mixed-Method Study.

BACKGROUND AND AIMS: Newly diagnosed inflammatory bowel disease [IBD] patients need to deal with the physical and emotional impact of the disease. We aimed to evaluate care for recently diagnosed IBD patients from the patient perspective and assess themes for improvement. METHODS: A mixed-method study with adult IBD patients 4-15 months after diagnosis was performed. First, relevant themes were identified through semi-structured interviews until data saturation. Next, a questionnaire assessing satisfaction with care [SATI-Q] was developed and validated with 15 items divided into two domains: medical care and information and psychosocial care. Higher scores indicate higher patient satisfaction [0-100]. RESULTS: We interviewed 20 patients. Next, 84/107 patients completed the SATI-Q: 51% female, aged 37 years (interquartile range [IQR 25-58]), 36% Crohn's disease, disease duration 9 months [IQR 6-12] and 74% in clinical remission. The median SATI-Q score was 82 [IQR 72-92]. Patients were more satisfied with medical care than with information and psychosocial care (score 92 [IQR 81-98] vs 74 [IQR 60-90], p < 0.001). Patients were least satisfied with the attention given to IBD-related emotions and information on IBD medication, diet and future perspectives [77, 76, 57 and 54% of patients satisfied]. Patients [81%] preferred spoken information. Only 26-27% preferred brochures and websites. CONCLUSIONS: In this study, the SATI-Q questionnaire was developed and validated to assess patient satisfaction with care in early IBD. Our findings suggest that psychosocial care and information on IBD medication, diet influence and future perspectives for recently diagnosed IBD patients require improvement.

Malignant transformation of perianal and enterocutaneous fistulas is rare: results of 17 years of follow-up from The Netherlands.

OBJECTIVE: Malignant transformation of fistulas has been observed, particularly in perianal fistulas in Crohn's disease (CD) patients. The prevalence of adenocarcinoma in enterocutaneous fistulas and non-CD-related fistulas, however, is unknown. We investigated adenocarcinoma originating from perianal and enterocutaneous fistulas in both CD patients and non-CD patients from nine large, mostly tertiary referral, hospitals in The Netherlands. METHODS: Patients suffering from fistulizing disease and either dysplasia or adenocarcinoma between January 1990 and January 2007 were identified using the nationwide automated pathology database (PALGA). Clinical and histopathological data were collected and verified using hospital patient-charts and reported by descriptive statistics. The total CD-population comprised 6058 patients. RESULTS: In a study-period of 17 years, 2324 patients with any fistula were reported in PALGA. In 542 patients, dysplasia or adenocarcinoma was also mentioned. After initial review and additional detailed chart review, 538 patients were excluded, mainly because the adenocarcinoma was not related to the fistula. In the remaining four patients, all suffering from CD, adenocarcinoma originating from the fistula-tract was confirmed. The malignancies developed 25 years (IQR 10-38) after CD diagnosis, and 10 years (IQR 6-22) after fistula diagnosis. Median age at time of adenocarcinoma diagnosis was 48.3 years (IQR 43-58). Only one patient had clinical symptoms indicative for adenocarcinoma. In three other patients, the adenocarcinoma was found coincidently. CONCLUSIONS: Adenocarcinoma complicating perianal or enterocutaneous fistula-tracts is a rare finding. Only 4 out of 6058 CD patients developed a fistula-associated adenocarcinoma. We could not identify any malignant transformations in non-CD-related fistulas in our 17 years study-period.

Acceptance and Perceived Control are Independently Associated With Quality of Life in Inflammatory Bowel Disease: Introduction of a New Segmentation Model.

BACKGROUND AND AIMS: Segmentation of patients based on psychological determinants of subjective health may provide new ways to personalized care. The cross-disease segmentation model developed by Bloem & Stalpers discriminates patients based on disease acceptance and perceived control. We aimed to validate the segmentation model, compare segments and evaluate whether segments independently correlate with quality of life in inflammatory bowel disease [IBD]. METHODS: A cross-sectional study of adult IBD patients was performed with questionnaires on quality of life [32-item inflammatory bowel disease questionnaire], acceptance and perceived control [six items with 7-point Likert scale]. Four segments were formed [cut-off > 5]: [I] high acceptance, high control; [II] high acceptance, low control [III]; low acceptance, high control and; [IV] low acceptance, low control. RESULTS: We included 686 patients. The acceptance and perceived control scales were unidimensionally structured and internally consistent. Segments differed significantly in age, smoking behaviour, diagnosis, disease duration, extra-intestinal manifestations, IBD medication, clinical disease activity and quality of life. High acceptance (standardized beta coefficient [ß] 0.25, p < 0.001), high perceived control [ß 0.12, p < 0.001] or both [ß 0.53, p < 0.001], were associated with a significantly better health-related quality of life compared with low acceptance and low perceived control. Sociodemographic and clinical factors explained 25% of the variance in quality of life. The explained variance significantly increased to 45% when the patients' segment was added to the model [ΔR2 20%, p < 0.001]. CONCLUSIONS: The segmentation model based on disease acceptance and perceived control is valid in IBD patients and discriminates different segments that correlate independently with quality of life. This may open new strategies for patient care.

Efficacy and Safety of 100 Laparoscopy-Assisted Transgastric Endoscopic Retrograde Cholangiopancreatography Procedures in Patients with Roux-en-Y Gastric Bypass.

PURPOSE: Laparoscopy-assisted transgastric endoscopic retrograde cholangiopancreatography (LAERCP) is an alternative for the anatomically challenging conventional ERCP in patients with a Roux-en-Y gastric bypass (RYGB) as it allows access to the biliary tree via the gastric remnant. We investigated the efficacy and safety of LAERCP. MATERIAL AND METHODS: We retrospectively reviewed all charts from RYGB patients who underwent a LAERCP between January 2009 and August 2019 in a non-academic referral center for bariatric surgery. Patients who underwent pancreatic therapy were excluded. We collected demographic, clinical, and outcome data. An adverse event was defined as any complaint related to the LAERCP up to 30 days after the procedure and graded according to the ASGE lexicon. RESULTS: We identified 100 LAERCP in 86 patients with RYGB (70% female, median age 54 years). Same-session cholecystectomy was performed in 35 LAERCP (35%). The papilla of Vater was visualized in 100% of LAERCP with a therapeutic success rate of 94%. Stone extraction succeeded in 88.8% and sphincterotomy was performed in 96.7%. We identified 30 adverse events in 28 procedures, of which eight endoscopy-related, 14 laparoscopy-related, and eight non-specified (f.i. fever, allergic reaction). In total, six severe adverse events were reported concerning post-ERCP pancreatitis (n = 2), laparoscopy-related hemorrhage (n = 1), abscess (n = 1), shock (n = 1), and pneumonia (n = 1). No patient died due to LAERCP. CONCLUSION: LAERCP is an effective and relatively safe procedure for biliary diseases in patients with RYGB.

Development of Mucosal PNAd+ and MAdCAM-1+ Venules during Disease Course in Ulcerative Colitis.

PNAd and MAdCAM-1 addressins on venules are of importance in T-cell homing and potential therapeutic targets in ulcerative colitis (UC). Normally, PNAd+ high endothelial venules (HEVs) are only present in lymphoid organs, whereas small numbers of MAdCAM-1+ venules can be seen in non-lymphoid tissue. We aimed to study their presence in the intestinal mucosa of UC patients at diagnosis and during follow-up, and their correlation with disease activity. Colonic biopsy specimens of 378 UC patients were analyzed by immunohistochemistry for CD3, CD20, ERG, MECA-79 (PNAd) and MECA-376 (MAdCAM-1) and compared to healthy controls (HC). The proportion of PNAd+HEVs in UC at diagnosis was 4.9% (IQR 2.0%-8.3%), while none were detected in HC. During follow-up, PNAd+HEVs completely disappeared in remission (n = 93), whereas the proportion in active disease was similar to baseline (n = 285, p = 0.39). The proportion of MAdCAM-1+venules in UC at baseline was 5.8% (IQR 2.6-10.0). During follow-up, the proportion in remission was comparable to diagnosis, but upregulated (7.5% (IQR 4.4-10.9), p = 0.001) in active disease. In conclusion, PNAd+HEVs appear in UC during active inflammation which could thus serve as a marker for disease activity, whereas MAdCAM-1+venules remain present after inflammation is resolved and increase after subsequent flares, reflecting chronicity and potentially serving as a therapeutic target.

Early endoscopic retrograde cholangiopancreatography in predicted severe acute biliary pancreatitis: a prospective multicenter study.

SUMMARY BACKGROUND DATA: The role of early endoscopic retrograde cholangiopancreatography (ERCP) in acute biliary pancreatitis (ABP) remains controversial. Previous studies have included only a relatively small number of patients with predicted severe ABP. We investigated the clinical effects of early ERCP in these patients. METHODS: We performed a prospective, observational multicenter study in 8 university medical centers and 7 major teaching hospitals. One hundred fifty-three patients with predicted severe ABP without cholangitis enrolled in a randomized multicenter trial on probiotic prophylaxis in acute pancreatitis were prospectively followed. Conservative treatment or ERCP within 72 hours after symptom onset (at discretion of the treating physician) were compared for complications and mortality. Patients without and with cholestasis (bilirubin: >2.3 mg/dL [40 mumol/L] and/or dilated common bile duct) were analyzed separately. RESULTS: Of the 153 patients, 81 (53%) underwent ERCP and 72 (47%) conservative treatment. Groups were highly comparable at baseline. Seventy-eight patients (51%) had cholestasis. In patients with cholestasis, ERCP (52/78 patients: 67%), as compared with conservative treatment, was associated with fewer complications (25% vs. 54%, P = 0.020, multivariate adjusted odds ratio [OR]: 0.35, 95% confidence interval [CI]: 0.13-0.99, P= 0.049). This included fewer patients with >30% pancreatic necrosis (8% vs. 31%, P = 0.010). Mortality was nonsignificantly lower after ERCP (6% vs. 15%, P = 0.213, multivariate adjusted OR: 0.44, 95% CI: 0.08-2.28, P = 0.330). In patients without cholestasis, ERCP (29/75 patients: 39%) was not associated with reduced complications (45% vs. 41%, P = 0.814, multivariate adjusted OR: 1.36; 95% CI: 0.49-3.76; P = 0.554) or mortality (14% vs. 17%, P = 0.754, multivariate adjusted OR: 0.78; 95% CI: 0.19-3.12, P = 0.734). CONCLUSIONS: Early ERCP is associated with fewer complications in predicted severe ABP if cholestasis is present.