The Effectiveness and Safety of First-Line Thioguanine in Thiopurine-Naïve Inflammatory Bowel Disease Patients.

BACKGROUND: Currently thioguanine is solely used as treatment for inflammatory bowel disease after azathioprine and/or mercaptopurine failure. This study aimed to determine the safety, effectiveness, and 12-month drug survival of thioguanine in thiopurine-naïve patients with inflammatory bowel disease. METHODS: A retrospective cohort study was performed in thiopurine-naïve patients with inflammatory bowel disease treated with thioguanine as first thiopurine derivate. Clinical effectiveness was defined as the continuation of thioguanine without the (re)initiation of concurrent biological therapy, systemic corticosteroids, or a surgical intervention. All adverse events were categorized by the Common Terminology Criteria for Adverse Events. RESULTS: A total of 114 patients (male 39%, Crohn's disease 53%) were included with a median treatment duration of 25 months and a median thioguanine dosage of 20 mg/d. Clinical effectiveness at 12 months was observed in 53% of patients, and 78% of these responding patients remained responsive until the end of follow-up. During the entire follow-up period, 26 patients were primary nonresponders, 8 had a secondary loss of response, and 11 patients were unable to cease therapy with systemic corticosteroids within 6 months and were therefore classified as nonresponders. After 12 months, thioguanine was still used by 86% of patients. Fifty (44%) patients developed adverse events (grade 1 or 2) and 9 (8%) patients ceased therapy due to the occurrence of adverse events. An infection was documented in 3 patients, none of them requiring hospitalization and pancytopenia occurred in 2 other patients. No signs of nodular regenerative hyperplasia or portal hypertension were observed. CONCLUSIONS: At 12 months, first-line thioguanine therapy was clinically effective in 53% of thiopurine-naïve inflammatory bowel disease patients with an acceptable safety profile.

After 12 months, first-line thioguanine therapy was still used by 86% of thiopurine-naïve patients with inflammatory bowel disease and clinically effective in 53%. The safety profile was acceptable and only 8% of patients ceased therapy due to adverse events.

Healthy Cotwins Share Gut Microbiome Signatures With Their Inflammatory Bowel Disease Twins and Unrelated Patients.

BACKGROUND & AIMS: It is currently unclear whether reported changes in the gut microbiome are cause or consequence of inflammatory bowel disease (IBD). Therefore, we studied the gut microbiome of IBD-discordant and -concordant twin pairs, which offers the unique opportunity to assess individuals at increased risk of developing IBD, namely healthy cotwins from IBD-discordant twin pairs. METHODS: Fecal samples were obtained from 99 twins (belonging to 51 twin pairs), 495 healthy age-, sex-, and body mass index-matched controls, and 99 unrelated patients with IBD. Whole-genome metagenomic shotgun sequencing was performed. Taxonomic and functional (pathways) composition was compared among healthy cotwins, IBD-twins, unrelated patients with IBD, and healthy controls with multivariable (ie, adjusted for potential confounding) generalized linear models. RESULTS: No significant differences were observed in the relative abundance of species and pathways between healthy cotwins and their IBD-twins (false discovery rate <0.10). Compared with healthy controls, 13, 19, and 18 species, and 78, 105, and 153 pathways were found to be differentially abundant in healthy cotwins, IBD-twins, and unrelated patients with IBD, respectively (false discovery rate <0.10). Of these, 8 (42.1%) of 19 and 1 (5.6%) of 18 species, and 37 (35.2%) of 105 and 30 (19.6%) of 153 pathways overlapped between healthy cotwins and IBD-twins, and healthy cotwins and unrelated patients with IBD, respectively. Many of the shared species and pathways have previously been associated with IBD. The shared pathways include potentially inflammation-related pathways, for example, an increase in propionate degradation and L-arginine degradation pathways. CONCLUSIONS: The gut microbiome of healthy cotwins from IBD-discordant twin pairs displays IBD-like signatures. These IBD-like microbiome signatures might precede the onset of IBD. However, longitudinal follow-up studies are needed to infer a causal relationship.

Associations of Pathogenic Variants in MLH1, MSH2, and MSH6 With Risk of Colorectal Adenomas and Tumors and With Somatic Mutations in Patients With Lynch Syndrome.

BACKGROUND & AIMS: Lynch syndrome is caused by variants in DNA mismatch repair (MMR) genes and associated with an increased risk of colorectal cancer (CRC). In patients with Lynch syndrome, CRCs can develop via different pathways. We studied associations between Lynch syndrome-associated variants in MMR genes and risks of adenoma and CRC and somatic mutations in APC and CTNNB1 in tumors in an international cohort of patients. METHODS: We combined clinical and molecular data from 3 studies. We obtained clinical data from 2747 patients with Lynch syndrome associated with variants in MLH1, MSH2, or MSH6 from Germany, the Netherlands, and Finland who received at least 2 surveillance colonoscopies and were followed for a median time of 7.8 years for development of adenomas or CRC. We performed DNA sequence analyses of 48 colorectal tumors (from 16 patients with mutations in MLH1, 29 patients with mutations in MSH2, and 3 with mutations in MSH6) for somatic mutations in APC and CTNNB1. RESULTS: Risk of advanced adenoma in 10 years was 17.8% in patients with pathogenic variants in MSH2 vs 7.7% in MLH1 (P < .001). Higher proportions of patients with pathogenic variants in MLH1 or MSH2 developed CRC in 10 years (11.3% and 11.4%) than patients with pathogenic variants in MSH6 (4.7%) (P = .001 and P = .003 for MLH1 and MSH2 vs MSH6, respectively). Somatic mutations in APC were found in 75% of tumors from patients with pathogenic variants in MSH2 vs 11% in MLH1 (P = .015). Somatic mutations in CTNNB1 were found in 50% of tumors from patients with pathogenic variants in MLH1 vs 7% in MSH2 (P = .002). None of the 3 tumors with pathogenic variants in MSH6 had a mutation in CTNNB1, but all had mutations in APC. CONCLUSIONS: In an analysis of clinical and DNA sequence data from patients with Lynch syndrome from 3 countries, we associated pathogenic variants in MMR genes with risk of adenoma and CRC, and somatic mutations in APC and CTNNB1 in colorectal tumors. If these findings are confirmed, surveillance guidelines might be adjusted based on MMR gene variants.

Pre-to-post diagnosis weight trajectories in colorectal cancer patients with non-metastatic disease.

PURPOSE: Previous studies have shown that > 50% of colorectal cancer (CRC) patients treated with adjuvant chemotherapy gain weight after diagnosis. This may affect long-term health. Therefore, prevention of weight gain has been incorporated in oncological guidelines for CRC with a focus on patients that undergo adjuvant chemotherapy treatment. It is, however, unknown how changes in weight after diagnosis relate to weight before diagnosis and whether weight changes from pre-to-post diagnosis are restricted to chemotherapy treatment. We therefore examined pre-to-post diagnosis weight trajectories and compared them between those treated with and without adjuvant chemotherapy. METHODS: We included 1184 patients diagnosed with stages I-III CRC between 2010 and 2015 from an ongoing observational prospective study. At diagnosis, patients reported current weight and usual weight 2 years before diagnosis. In the 2 years following diagnosis, weight was self-reported repeatedly. We used linear mixed models to analyse weight trajectories. RESULTS: Mean pre-to-post diagnosis weight change was -0.8 (95% CI -1.1, -0.4) kg. Post-diagnosis weight gain was + 3.5 (95% CI 2.7, 4.3) kg in patients who had lost ≥ 5% weight before diagnosis, while on average clinically relevant weight gain after diagnosis was absent in the groups without pre-diagnosis weight loss. Pre-to-post diagnosis weight change was similar in patients treated with (-0.1 kg (95%CI -0.8, 0.6)) and without adjuvant chemotherapy (-0.9 kg (95%CI -1.4, -0.5)). CONCLUSIONS: Overall, hardly any pre-to-post diagnosis weight change was observed among CRC patients, because post-diagnosis weight gain was mainly observed in patients who lost weight before diagnosis. This was observed independent of treatment with adjuvant chemotherapy.

No Difference in Colorectal Cancer Incidence or Stage at Detection by Colonoscopy Among 3 Countries With Different Lynch Syndrome Surveillance Policies.

BACKGROUND & AIMS: Patients with Lynch syndrome are at high risk for developing colorectal cancer (CRC). Regular colonoscopic surveillance is recommended, but there is no international consensus on the appropriate interval. We investigated whether shorter intervals are associated with lower CRC incidence and detection at earlier stages by comparing the surveillance policies in Germany, which evaluates patients by colonoscopy annually, in the Netherlands (patients evaluated at 1-2-year intervals), and Finland (patients evaluated at 2-3-year intervals). METHODS: We collected data from 16,327 colonoscopic examinations (conducted from 1984 through 2015) of 2747 patients with Lynch syndrome (pathogenic variants in the MLH1, MSH2, or MSH6 genes) from the German HNPCC Consortium, the Dutch Lynch Syndrome Registry, and the Finnish Lynch Syndrome Registry. Our analysis included 23,309 person-years of cumulative observation time. Time from the index colonoscopy to incident CRC or adenoma was analyzed using the Kaplan-Meier method; groups were compared using the log-rank test. We performed multivariable Cox regression analyses to identify factors associated with CRC risk (diagnosis of CRC before the index colonoscopy, sex, mutation, age, and presence of adenoma at the index colonoscopy). RESULTS: The 10-year cumulative CRC incidence ranged from 4.1% to 18.4% in patients with low- and high-risk profiles, respectively, and varied with age, sex, mutation, and prior detection of CRC or adenoma. Observed colonoscopy intervals were largely in accordance with the country-specific recommendations. We found no significant differences in cumulative CRC incidence or CRC stage at detection among countries. There was no significant association between CRC stage and time since last colonoscopy. CONCLUSIONS: We did not find a significant reduction in CRC incidence or stage of detection in Germany (annual colonoscopic surveillance) than in countries with longer surveillance intervals (the Netherlands, with 1-2-year intervals, and Finland, with 2-3-year intervals). Overall, we did not find a significant association of the interval with CRC risk, although age, sex, mutation, and prior neoplasia were used to individually modify colonoscopy intervals. Studies are needed to develop and validate risk-adapted surveillance strategies and to identify patients who benefit from shorter surveillance intervals.

Sex-Related Differences in Patients With Inflammatory Bowel Disease: Results of 2 Prospective Cohort Studies.

Background: The understanding of gender differences in inflammatory bowel disease (IBD) patients is an important step towards tailored treatment for the individual patient. The aim of this study was to compare disease phenotype, clinical manifestations, disease activity, and healthcare utilization between men and women with Crohn's disease (CD) and ulcerative colitis (UC). Methods: Two multicenter observational cohort studies with a prospective design were used to explore the differences between men and women regarding demographic and phenotypic characteristics and healthcare utilization. Detailed data on IBD-phenotype was mainly available from the Dutch IBD Biobank, while the COIN cohort provided healthcare utilization data. Results: In the Dutch IBD Biobank study, 2118 CD patients and 1269 UC patients were analyzed. Female CD patients were more often current smokers, and male UC patients were more often previous smokers. Early onset CD (<16 years) was more frequently encountered in males than in females (20% versus 12%, P < 0.01). Male CD patients were more often diagnosed with ileal disease (28% versus 20%, P < 0.01) and underwent more often small bowel and ileocecal resection. Extraintestinal manifestations (EIMs) were more often encountered in female IBD patients. In the COIN study, 1139 CD patients and 1213 UC patients were analyzed. Male CD patients used prednisone more often and suffered more often from osteopenia. IBD-specific healthcare costs did not differ between male and female IBD patients. Conclusions: Sex differences in patients with IBD include age of onset, disease location, and EIM prevalence. No large differences in therapeutic management of IBD were observed between men and women with IBD. 10.1093/ibd/izy004_video1izy004_Video_15786481854001.

Clinical Predictors of Future Nonadherence in Inflammatory Bowel Disease.

BACKGROUND: Nonadherence to medical therapy is frequently encountered in patients with inflammatory bowel disease (IBD). We aimed to identify predictors for future (non)adherence in IBD. METHODS: We conducted a multicenter prospective cohort study with adult patients with Crohn's disease (CD) and ulcerative colitis (UC). Data were collected by means of 3-monthly questionnaires on the course of disease and healthcare utilization. Medication adherence was assessed using a visual analogue scale, ranging from 0% to 100%. Levels <80% were considered to indicate nonadherence. The Brief Illness Perception Questionnaire was used to identify illness perceptions. We used a logistic regression analysis to identify patient- and disease-related factors predictive of nonadherence 3 months after the assessment of predictors. RESULTS: In total, 1558 patients with CD and 1054 patients with UC were included and followed for 2.5 years. On average, 12.1% of patients with CD and 13.3% of patients with UC using IBD-specific medication were nonadherent. Nonadherence was most frequently observed in patients using mesalazine (CD), budesonide (UC) and rectally administrated therapy (both CD and UC). A higher perceived treatment control and understanding of the disease were associated with adherence to medical therapy. Independent predictors of future nonadherence were age at diagnosis (odds ratio [OR]: 0.99 per year), nonadherence (OR: 26.91), a current flare (OR: 1.30) and feelings of anxiety/depression (OR: 1.17), together with an area under the receiver-operating-characteristics curve of 0.74. CONCLUSIONS: Lower age at diagnosis, flares, feelings of anxiety or depression, and nonadherence are associated with future nonadherence in patients with IBD. Altering illness perceptions could be an approach to improve adherence behavior.

The Polyp Manager: a new tool for optimal polyp documentation during colonoscopy. A pilot study.

BACKGROUND AND STUDY AIMS: Conventional reporting of polyps is often incomplete. We tested the Polyp Manager (PM), a new software application permitting the endoscopist to document polyps in real time during colonoscopy. We studied completeness of polyp descriptions, user-friendliness and the potential time benefit. PATIENTS AND METHODS: In two Dutch hospitals colonoscopies were performed with PM (as a touchscreen endoscopist-operated device or nurse-operated desktop application). Completeness of polyp descriptions was compared to a historical group with conventional reporting (CRH). Prospectively, we compared user-friendliness (VAS-scores) and time benefit of the endoscopist-operated PM to conventional reporting (CR) in one hospital. Duration of colonoscopy and time needed to report polyps and provide a pathology request were measured. Provided that using PM does not prolong colonoscopy, the sum of the latter two was considered as a potential time-benefit if the PM were fully integrated into a digital reporting system. RESULTS: A total of 144 regular colonoscopies were included in the study. Both groups were comparable with regard to patient characteristics, duration of colonoscopy and number of polyps. Using the PM did reduce incomplete documentation of the following items in CRH-reports: location (96 % vs 82 %, P = 0.01), size (95 % vs 89 %, P = 0.03), aspect (71 % vs 36 %, P < 0.001) and completeness of removal (61 % vs 37 %, P < 0.001). In the prospective study 23 PM-colonoscopies where compared to 28 CR-colonoscopies. VAS-scores were significantly higher in the endoscopist-operated PM group. Time to report was 01:27 ± 01:43 minutes (median + interquartile range) in the entire group (PM as CR), reflecting potential time benefit per colonoscopy. CONCLUSIONS: The PM is a user-friendly tool that seems to improve completeness of polyp reporting. Once integrated with digital reporting systems, it is probably time saving as well.

Evolution of Costs of Inflammatory Bowel Disease over Two Years of Follow-Up.

BACKGROUND: With the increasing use of anti-TNF therapy in inflammatory bowel disease (IBD), a shift of costs has been observed with medication costs replacing hospitalization and surgery as major cost driver. We aimed to explore the evolution of IBD-related costs over two years of follow-up. METHODS AND FINDINGS: In total 1,307 Crohn's disease (CD) patients and 915 ulcerative colitis (UC) patients were prospectively followed for two years by three-monthly web-based questionnaires. Changes of healthcare costs, productivity costs and out-of-pocket costs over time were assessed using mixed model analysis. Multivariable logistic regression analysis was used to identify costs drivers. In total 737 CD patients and 566 UC were included. Total costs were stable over two years of follow-up, with annual total costs of €7,835 in CD and €3,600 in UC. However, within healthcare costs, the proportion of anti-TNF therapy-related costs increased from 64% to 72% in CD (p<0.01) and from 31% to 39% in UC (p < 0.01). In contrast, the proportion of hospitalization costs decreased from 19% to 13% in CD (p<0.01), and 22% to 15% in UC (p < 0.01). Penetrating disease course predicted an increase of healthcare costs (adjusted odds ratio (adj. OR) 1.95 (95% CI 1.02-3.37) in CD and age <40 years in UC (adj. OR 4.72 (95% CI 1.61-13.86)). CONCLUSIONS: BD-related costs remained stable over two years. However, the proportion of anti-TNF-related healthcare costs increased, while hospitalization costs decreased. Factors associated with increased costs were penetrating disease course in CD and age <40 in UC.

Equivalent Helicobacter pylori infection rates in Lynch syndrome mutation carriers with and without a first-degree relative with gastric cancer.

BACKGROUND: Patients with Lynch syndrome (LS) are at an increased risk of developing gastric cancer. In 2010, a guideline that recommended to screen all patients for Helicobacter pylori was implemented in the Netherlands. H. pylori is an important risk factor in the development of gastric cancer in the general population, and eradication of the bacterium reduces this risk. We aimed to assess the proportion of LS patients being tested and the yield and also addressed the question whether H. pylori infection is more prevalent in LS families with known cases of gastric cancer. METHODS: Proven mutation carriers from five different Dutch hospitals were included. The implementation of H. pylori screening and its outcome was examined. The observation period was 2008-2013. The presence of first-degree family members with gastric cancer was noted, and it was observed if H. pylori infection was more prevalent in Lynch families with known cases of gastric cancer. Obtainable endoscopy reports were reviewed. RESULTS: Four hundred forty-three (male, 184) proven mutation carriers were included. The proportion of patients screened increased after 2010, from 37 to 68%. Twenty percent of the patients were infected. The 25 patients who had a first-degree family member with gastric cancer did not have a higher infection rate. In 30% of cases, an endoscopy was performed; in four patients, intestinal metaplasia and in eight patients, gastric cancer was found. CONCLUSION: The recommendation to screen for H. pylori is increasingly followed. The prevalence of infection in this patient group does not differ from the general population. Patients who had a first-degree family member with gastric cancer did not have a higher infection rate.

Increased Belching After Sleeve Gastrectomy.

INTRODUCTION: Laparoscopic sleeve gastrectomy (LSG) is considered to be an effective procedure for patients with morbid obesity. Belching is frequently reported after this procedure, but it has not been well studied in the bariatric population. This study aims to assess the changes in belching before and after sleeve gastrectomy, as measured with impedance monitoring. METHODS: In a prospective study, patients underwent 24-h pH-impedance monitoring before and 3 months after LSG. Using this technique, belches can be identified. Preoperative and postoperative upper gastrointestinal symptoms were assessed using the Reflux Disease Questionnaire (RDQ). RESULTS: Fifteen patients (1 M/14 F, mean age 42.2 ± 11.0 years, mean weight 134.5 ± 21.1 kg, mean BMI 46.4 ± 6.0 kg/m(2)) participated in this study. Belching occurred significantly more often after LSG, with an increase in symptom score from 2.9 ± 2.6 before to 5.3 ± 3.5 3 months after LSG (p = 0.04). The total number of gastric belches increased from 29.7 ± 11.7 before to 59.5 ± 38.3/24 h 3 months after LSG (p = 0.03). The total number of supragastric belches did not change after LSG. The number of swallows decreased from 746.9 ± 302.4 before to 555.7 ± 172.5 3 months after the procedure (p = 0.03). The number of air swallows tended to decrease (p = 0.08). Esophageal acid exposure increased significantly, from 3.7 ± 2.9 % before to 12.6 ± 10.5 % after LSG (p = 0.01). CONCLUSION: Subjectively (as reported by patients) and objectively (as measured by impedance monitoring), an increase in gastric belches is seen after LSG, while the number of (air) swallows tends to decrease after the procedure and the incidence of supragastric belches remains constant. The altered anatomy as well as increased gastroesophageal reflux after LSG may play a role in the increase of belching.

Comparison of Costs and Quality of Life in Ulcerative Colitis Patients with an Ileal Pouch-Anal Anastomosis, Ileostomy and Anti-TNFα Therapy.

BACKGROUND AND AIMS: More data are warranted on the economic impact of different treatment strategies in ulcerative colitis (UC) patients. We compared the costs and quality of life of UC patients with a pouch reconstruction, an ileostomy or anti-tumour necrosis factor α (TNFα) therapy. METHODS: UC patients filled out 3-monthly questionnaires for 2 years. Differences in 3-monthly healthcare costs, productivity costs and patient costs were tested using mixed model analysis. Quality of life was assessed employing the ) and the inflammatory bowel disease questionnaire (IBDQ). RESULTS: Out of 915 UC patients, 81 (9%) had a pouch and 48 (5%) an ileostomy, and 34 (4%) were on anti-TNFα therapy. Anti-TNFα-treated patients reported high UC related-healthcare costs per 3 months (€5350). Medication use accounted for 92% of healthcare costs. UC-attributable healthcare costs were 3-fold higher in ileostomy patients compared with pouch patients (€1581 versus €407; p < 0.01). Main cost drivers in ileostomy patients were healthcare costs and ileostomy supplies (2 and 23% of healthcare costs, respectively). In pouch patients, the main cost driver was hospitalization, accounting for 50% of healthcare costs. Productivity loss did not differ between pouch and ileostomy patients (€483 versus €377; p < 0.23), but was significantly higher in anti-TNFα-treated patients (€1085). No difference was found in IBDQ scores, but pouch patients were found to have higher quality-adjusted life years than ileostomy patients and anti-TNFα-treated patients (0.90 [interquartile range 0.78-1.00] versus 0.84 [0.78-1.00] and 0.84 [0.69-1.00], respectively; p < 0.01). CONCLUSION: Patients receiving anti-TNFα therapy reported the highest healthcare cost, in which medication use was the major cost driver. Ileostomy patients were three times more expensive than pouch patients due to frequent hospitalization and ileostomy supplies.

Self-reported disability in patients with inflammatory bowel disease largely determined by disease activity and illness perceptions.

BACKGROUND: The inflammatory bowel disease (IBD) disability index has recently been introduced to measure patients' physical, psychological, familial, and social limitations associated with IBD. We assessed factors related to self-reported disability and the relationship between disability and direct health care costs. METHODS: A large cohort of patients with Crohn's disease (CD) and ulcerative colitis (UC) was prospectively followed for 2 years by 3 monthly web-based questionnaires. At 2 years, patients completed the IBD disability index, with lower score indicating more disability. Linear regression analysis was used to examine the impact of demographics, clinical characteristics, and illness perceptions on self-reported disability. Trends in direct health care costs across the disability severity groups minimal, mild, moderate, and severe, were tested. RESULTS: A total of 554 patients with CD and 424 patients with UC completed the IBD disability index (response rate, 45%). Both clinical characteristics and illness perceptions significantly contributed to self-reported disability (45%-47%, P = 0.000 and 8%-12%, P = 0.000, respectively). Patients with CD scored lower on the self-reported IBD disability index than patients with UC (0.255 versus 3.890, P < 0.000), indicating more disability in patients with CD. Factors independently associated with higher self-reported disability rates were increased disease activity, illness identity (higher number of symptoms attributed to IBD), and stronger emotional response. Disease duration and disease phenotype were not associated with self-reported disability. Direct health care costs increased with the worsening of self-reported disability (P = 0.000). CONCLUSIONS: More disability was reported by patients with CD than by UC. Self-reported disability in IBD was mainly determined by clinical disease activity and illness perceptions but not by disease duration or disease phenotype.

Association between postprandial symptoms and gastric emptying after sleeve gastrectomy.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is an effective bariatric procedure. However, postprandial symptoms can compromise its beneficial effect. It is not known if a changed gastric emptying and these symptoms are related. This study aimed to assess the association between postprandial symptoms and the gastric emptying pattern after LSG. METHODS: A gastric emptying study with a solid and liquid meal component was performed in the second year after LSG. Before the test, symptoms were assessed using a standardized questionnaire, and during the test, symptoms were scored on a visual analog scale (VAS). Gastric emptying results were expressed as lag phase, half time of gastric emptying (T½), and caloric emptying rate/minute. RESULTS: Twenty patients (14 F/6 M; age 45.6 ± 7.7 years, weight 93.4 ± 28.2 kg, BMI 31.6 ± 8.1 kg/m(2)) participated in this study; 13 had a low symptom score (≤9, group I), 7 a high symptom score (≥18, group II). VAS scores for epigastric pain, nausea, and belching were significantly higher in group II. Lag phase (solid) was 6.4 ± 4.5 min in group I, 7.3 ± 6.3 in group II (p = 0.94); T½ (solid) was 40.6 ± 10.0 min in group I, 34.4 ± 9.3 in group II (p = 0.27); caloric emptying rate was 3.9 ± 0.6 kcal/min in group I, 3.9 ± 1.0 kcal/min in group II (p = 0.32). CONCLUSIONS: Patients with postprandial symptoms after LSG reported more symptoms during the gastric emptying study than patients without symptoms. However, there was no difference between gastric emptying characteristics between both groups, suggesting that abnormal gastric emptying is not a major determinant of postprandial symptoms after LSG.

Effect of sleeve gastrectomy on gastroesophageal reflux.

Laparoscopic sleeve gastrectomy (LSG) is effective as a stand-alone bariatric procedure. Despite its positive effect with regard to weight loss and improvement of obesity-related co-morbidities, some patients develop gastroesophageal reflux symptoms postoperatively. The pathogenesis of these symptoms is not completely understood. Hence, this study aimed to assess the effect of sleeve gastrectomy on acid and non-acid gastroesophageal reflux, reflux symptoms and esophageal function. In a prospective study, patients underwent esophageal function tests (high-resolution manometry (HRM) and 24-h pH/impedance metry) before and 3 months after LSG. Preoperative and postoperative symptoms were assessed using the Reflux Disease Questionnaire (RDQ). In total, 20 patients (4 male/16 female, mean age 43 ± 12 years, mean weight 137.3 ± 25 kg, and mean BMI 47.6 ± 6.1 kg/m(2)) participated in this study. GERD symptoms did not significantly change after sleeve gastrectomy, but other upper gastrointestinal symptoms, particularly belching, epigastric pain and vomiting increased. Esophageal acid exposure significantly increased after sleeve gastrectomy: upright from 5.1 ± 4.4 to 12.6 ± 9.8% (p = 0.003), supine from 1.4 ± 2.4 to 11 ± 15% (p = 0.003) and total acid exposure from 4.1 ± 3.5 to 12 ± 10.4% (p = 0.004). The percentage of normal peristaltic contractions remained unchanged, but the distal contractile integral decreased after LSG from 2,006.0 ± 1,806.3 to 1,537.4 ± 1,671.8 mmHg · cm · s (p = 0.01). The lower esophageal sphincter (LES) pressure decreased from 18.3 ± 9.2 to 11.0 ± 7.0 mmHg (p = 0.02). After LSG, patients have significantly higher esophageal acid exposure, which may well be due to a decrease in LES resting pressure following the procedure.

Effect of aging on healthcare costs of inflammatory bowel disease: a glimpse into the future.

BACKGROUND: Population aging is expected to result in a substantial additional burden on healthcare resources in the near future. We aimed to assess the current and future impact of aging on direct healthcare costs (DHC) attributed to inflammatory bowel disease (IBD). METHODS: Patients with IBD from a Dutch multicenter cohort filled out 3-monthly questionnaires for 2 years. Elderly (≥60 yr) and younger patients (18-60 yr) IBD were analyzed for differences in 3-monthly DHC, productivity losses, and out-of-pocket costs. Prevalence rates were obtained from a health insurance database. Estimates of annual DHC and prevalence rates were applied to the total Dutch adult population in 2011 and then projected to 2040, using predicted changes in population demography, prices, and volume. RESULTS: IBD-attributable DHC were lower in elderly than in younger patients with IBD with respect to 3-monthly DHC (&OV0556;359 versus &OV0556;978, P < 0.01), productivity losses (&OV0556;108 versus &OV0556;456, P < 0.01), and out-of-pocket costs (&OV0556;40 versus &OV0556;57, P < 0.01). Between 2011 and 2040, the percentage of elderly IBD patients in the Netherlands has been projected to rise from 24% to 35%. Between 2011 and 2040, DHC of the total IBD population in the Netherlands are projected to increase from &OV0556;161 to &OV0556;661 million. Population aging accounted for 1% of this increase, next to rising prices (29%), and volume growth (70%). CONCLUSIONS: Population aging has a negligible effect on IBD-attributable DHC of the IBD population in the near future, because the average costs incurred by elderly patients with IBD are considerably lower than those incurred by younger patients with IBD.

Nocturnal and daytime esophageal acid exposure in normal-weight, overweight, and obese patients with reflux symptoms.

OBJECTIVES: This study aimed to investigate the association between BMI and esophageal acid exposure in a cohort of patients referred for esophageal pH monitoring. The contributing roles of hiatal hernia, lower esophageal sphincter (LES) pressure, and intragastric pressure (IGP) were investigated, with an emphasis on reflux in the supine position. METHODS: Esophageal manometry and 24-h pH-metry results were extracted from a prospectively collected database, and supplemental data (body mass, endoscopy results) from patient files. RESULTS: In total, 245 patients (mean age 52.2±14 years, 54% men) were included in this study. In the normal-weight subgroup (n=87), the median acid exposure time was 1.1% [0-8.1] in the supine position (with interquartile range 25-75%) and 7.7% [2.5-14.8] in the upright position; the total acid exposure time was 7.4% [2.7-11.7]/24 h. In the overweight subgroup (n=104), the median acid exposure time was 4.9% [0.3-13.3] in the supine position and 11.1% [5.4-16.9] in the upright position; the total acid exposure time was 8.9% [4.7-15.8]/24 h. In the obesity subgroup (n=54), the median acid exposure time was 4.1% [0.7-14.3] in the supine position and 10.5% [5-17.5] in the upright position; the total acid exposure time was 8.3% [5.3-14.7]/24 h. Supine acid exposure was significantly higher in overweight and obese patients than in normal-weight patients (both P=0.02). In overweight patients, a hiatal hernia was predictive of supine and total acid exposure, as was a decreasing LES pressure in both the supine and the upright position. In obese patients, increased IGP contributed toward an increased total acid exposure. Although an association between increasing BMI and acid exposure was observed, BMI was not independently predictive. CONCLUSION: Overweight and obesity is associated with increased reflux, especially in the supine position. The most important factors that contribute toward reflux are the presence of a hiatal hernia and a lower LES pressure in overweight patients and an increased IGP in obese patients.

Healthcare costs of inflammatory bowel disease have shifted from hospitalisation and surgery towards anti-TNFα therapy: results from the COIN study.

OBJECTIVE: The introduction of anti tumour necrosis factor-α (anti-TNFα) therapy might impact healthcare expenditures, but there are limited data regarding the costs of inflammatory bowel diseases (IBD) following the introduction of these drugs. We aimed to assess the healthcare costs and productivity losses in a large cohort of IBD patients. DESIGN: Crohn's disease (CD) and ulcerative colitis (UC) patients from seven university hospitals and seven general hospitals were invited to fill-out a web-based questionnaire. Cost items were derived from a 3 month follow-up questionnaire and categorised in outpatient clinic, diagnostics, medication, surgery and hospitalisation. Productivity losses included sick leave of paid and unpaid work. Costs were expressed as mean 3-month costs per patients with a 95% CI obtained using non-parametric bootstrapping. RESULTS: A total of 1315 CD patients and 937 UC patients were included. Healthcare costs were almost three times higher in CD as compared with UC, €1625 (95% CI €1476 to €1775) versus €595 (95% CI €505 to €685), respectively (p<0.01). Anti-TNFα use was the main costs driver, accounting for 64% and 31% of the total cost in CD and UC. Hospitalisation and surgery together accounted for 19% and <1% of the healthcare costs in CD and 23% and 1% in UC, respectively. Productivity losses accounted for 16% and 39% of the total costs in CD and UC. CONCLUSIONS: We showed that healthcare costs are mainly driven by medication costs, most importantly by anti-TNFα therapy. Hospitalisation and surgery accounted only for a minor part of the healthcare costs.

Risk factors of work disability in patients with inflammatory bowel disease--a Dutch nationwide web-based survey: work disability in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) is associated with high costs to society. Few data on the impact of IBD on work disability and potential predictive factors are available. AIM: To assess the prevalence of and predictive factors for work disability in Crohn's disease (CD) and ulcerative colitis (UC). METHODS: A web-based questionnaire was sent out in seven university hospitals and seven general hospitals in the Netherlands. Initially, 3050 adult IBD patients were included in this prospective, nationwide cohort study, whereof 2629 patients were within the working-age (18-64 years). We used the baseline questionnaire to assess the prevalence rates of work disability in CD and UC patients within working-age. Prevalence rates were compared with the Dutch background population using age- and sex-matched data obtained from Statistics Netherlands. Multivariable logistic regression analyses were performed to identify independent demographic- and disease-specific risk factors for work disability. RESULTS: In CD, 18.3% of patients was fully disabled and 8.8% partially disabled, compared to 9.5% and 5.4% in UC patients (p<0.01), respectively. Compared to Dutch controls, the prevalence was significantly higher, especially in CD patients. Higher age, low education, depression, chronic back pain, joint manifestations and typical disease-related risk factors such as penetrating disease course and surgery in the past were all found to be associated with work disability. CONCLUSION: We report high work disability rates in a large sample of IBD patients in the Netherlands. CD patients suffer more frequently from work disability than UC patients. A combination of demographic and disease-related factors is predictive of work disability.

Quality of life after surgery for colon cancer in patients with Lynch syndrome: partial versus subtotal colectomy.

BACKGROUND: Lynch syndrome is a disorder caused by mismatch repair gene mutations. Mutation carriers have a high risk of developing colorectal cancer. In patients with Lynch syndrome in whom colon cancer has been diagnosed, in general, subtotal colectomy instead of partial colectomy is recommended because of the substantial risk of metachronous colorectal cancer. However, the effect of more extensive surgery on quality of life and functional outcome is unknown. OBJECTIVE: The aim of this study was to investigate quality of life and functional outcome in patients with Lynch syndrome after partial colectomy and subtotal colectomy. DESIGN: This is a nationwide cross-sectional study in the Netherlands. SETTINGS: Two quality-of-life questionnaires (Short Form-36 and The European Organization for Research and Treatment of Cancer Colorectal Cancer-specific Quality of Life Questionnaire Module) and a functional outcome questionnaire (Colorectal Functional Outcome) were used. PATIENTS: Patients with Lynch syndrome who underwent surgery for colon cancer were included. MAIN OUTCOME MEASURES: The primary outcomes measured were quality of life and functional outcome. RESULTS: Questionnaires were sent to 192 patients with Lynch syndrome who underwent surgery for colorectal cancer. A total of 136 patients returned the questionnaire (response rate, 71%). Eighteen patients with rectal cancer, 9 patients with a permanent ileostomy, and 5 patients with an IPAA were excluded. Fifty-one patients underwent partial colectomy, and 53 underwent subtotal colectomy. None of the scales of the Short Form-36 survey showed a significant difference. Analysis of the Colorectal Functional Outcome questionnaire revealed that, after subtotal colectomy, patients have a significantly higher stool frequency (p ≤ 0.01) and a significantly higher score on stool-related aspects (p = 0.06) and social impact (p = 0.03). The European Organization for Research and Treatment of Cancer Colorectal Cancer-specific Quality of Life Questionnaire Module presented more problems with defecation after subtotal colectomy (p ≤ 0.01). LIMITATIONS: Certain selection bias cannot be ruled out. CONCLUSIONS: Although functional outcome is worse after subtotal colectomy than after partial colectomy, generic quality of life does not differ after the 2 types of surgery in Lynch syndrome. When discussing the options for surgery with the patient, all advantages and disadvantages of both surgical procedures, including quality of life and functional outcome, should be discussed.