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BACKGROUND: It remains unclear whether urgent endoscopic retrograde cholangiopancreatography (ERCP) with biliary sphincterotomy improves the outcome of patients with gallstone pancreatitis without concomitant cholangitis. We did a randomised trial to compare urgent ERCP with sphincterotomy versus conservative treatment in patients with predicted severe acute gallstone pancreatitis.METHODS: In this multicentre, parallel-group, assessor-masked, randomised controlled superiority trial, patients with predicted severe (Acute Physiology and Chronic Health Evaluation II score ≥8, Imrie score ≥3, or C-reactive protein concentration >150 mg/L) gallstone pancreatitis without cholangitis were assessed for eligibility in 26 hospitals in the Netherlands. Patients were randomly assigned (1:1) by a web-based randomisation module with randomly varying block sizes to urgent ERCP with sphincterotomy (within 24 h after hospital presentation) or conservative treatment. The primary endpoint was a composite of mortality or major complications (new-onset persistent organ failure, cholangitis, bacteraemia, pneumonia, pancreatic necrosis, or pancreatic insufficiency) within 6 months of randomisation. Analysis was by intention to treat. This trial is registered with the ISRCTN registry, ISRCTN97372133.FINDINGS: Between Feb 28, 2013, and March 1, 2017, 232 patients were randomly assigned to urgent ERCP with sphincterotomy (n=118) or conservative treatment (n=114). One patient from each group was excluded from the final analysis because of cholangitis (urgent ERCP group) and chronic pancreatitis (conservative treatment group) at admission. The primary endpoint occurred in 45 (38%) of 117 patients in the urgent ERCP group and in 50 (44%) of 113 patients in the conservative treatment group (risk ratio [RR] 0·87, 95% CI 0·64-1·18; p=0·37). No relevant differences in the individual components of the primary endpoint were recorded between groups, apart from the occurrence of cholangitis (two [2%] of 117 in the urgent ERCP group vs 11 [10%] of 113 in the conservative treatment group; RR 0·18, 95% CI 0·04-0·78; p=0·010). Adverse events were reported in 87 (74%) of 118 patients in the urgent ERCP group versus 91 (80%) of 114 patients in the conservative treatment group.INTERPRETATION: In patients with predicted severe gallstone pancreatitis but without cholangitis, urgent ERCP with sphincterotomy did not reduce the composite endpoint of major complications or mortality, compared with conservative treatment. Our findings support a conservative strategy in patients with predicted severe acute gallstone pancreatitis with an ERCP indicated only in patients with cholangitis or persistent cholestasis.FUNDING: The Netherlands Organization for Health Research and Development, Fonds NutsOhra, and the Dutch Patient Organization for Pancreatic Diseases.

Background: Diet plays an important role in symptom management of irritable bowel syndrome (IBS). However, current diet therapies are not optimal nor successful for everyone. Objective: To investigate whether subgroups based on IBS subtypes or severity identify different self-reported dietary triggers, and whether these are associated with severity and psychological factors. Design: Online cross-sectional surveyParticipantsPatients with IBS (n = 1601) who fulfilled the Rome IV criteria or had an IBS diagnosis. Main outcomes: Self-reported response to 44 preselected dietary triggers, IBS quality of life, and anxiety and depression. Subgroups were based on subtypes or severity.Statistical analysisResponse to dietary triggers was analyzed using multiple correspondence analysis. Moreover, a food score was calculated to quantify the number and severity of responses to dietary triggers. Results: Response to greasy foods, onions, cabbage, and spicy and fried foods were mentioned most often (ranging between 55% and 65%). Response to dietary triggers differed between subtypes and severity groups, but absolute differences were small. Multiple correspondence analysis did not reveal clustering between dietary triggers, and ellipses for the subtypes overlapped. Some clustering was seen when ellipses were drawn for severity, which indicates that severity explained a fraction of the variation in response to dietary triggers, and subtypes did not. The food score was not significantly different between subtypes but was significantly higher with higher levels of severity (mild = 20.9 ± 17, moderate = 29.2 ± 19, severe = 37.9 ± 20, P < .001), having depressive (no = 31.4 ± 20, yes = 37.4 ± 20, P < .001) or anxious symptoms (no = 30.7 ± 20, yes = 35.2 ± 20, P < .001), and lower quality of life (lower quality of life = 38.5 ± 19, higher quality of life = 26.5 ± 19, P < .001). Conclusion: Patients with different IBS subtypes or IBS severity do not identify different self-reported dietary triggers. Patients with more severe IBS and who experience anxiety or depression tend to have severe responses to more dietary triggers. IBS severity seems a better classifier than Rome IV criteria regarding diet. Dietary treatment needs to be individualized under guidance of a dietitian.

Contains fulltext : 238641.pdf (Publisher’s version ) (Open Access) BACKGROUND: Since 1999, international guidelines recommend fasting from solid foods up to 6 hours and clear liquids up to 2 hours before surgery. Early recovery after surgery programs recommend restoration of oral intake as soon as possible. This study determines adherence to these guidelines up to 20 years after its introduction. METHODS: A 2-center observational study with a 10-year interval was performed in the Netherlands. In period 1 (2009), preoperative fasting time was observed as primary outcome. In period 2 (2019), preoperative fasting and postoperative restoration of oral intake were observed. Fasting times were collected using an interview-assisted questionnaire. RESULTS: During both periods, 311 patients were included from vascular, trauma, orthopedic, urological, oncological, gastrointestinal, and ear-nose-throat and maxillary surgical units. Duration of preoperative fasting was prolonged in 290 (90.3%) patients for solid foods and in 208 (67.8%) patients for clear liquids. Median duration of preoperative fasting from solid foods and clear liquids was respectively 2.5 and 3 times the recommended 6 and 2 hours, with no improvements from one period to another. Postoperative food intake was resumed within 4 hours in 30.7% of the patients. Median duration of perioperative fasting was 23:46 hours (interquartile range 20:00-30:30 hours) for solid foods and 11:00 hours (interquartile range 7:53-16:00 hours) for clear liquids. CONCLUSION: Old habits die hard. Despite 20 years of fasting guidelines, surgical patients are still exposed erroneously to prolonged fasting in 2 hospitals. Patients should be encouraged to eat and drink until 6 and 2 hours, respectively, before surgery and to restart eating after surgery.

Contains fulltext : 220980.pdf (Publisher’s version ) (Closed access) AIMS AND OBJECTIVES: To analyse oral care delivery in one hospital through exploring experiences from both nurses' and patients' perspectives and examining patients' oral health. BACKGROUND: Oral health problems are associated with undernutrition and other general health outcomes. Although oral care belongs to the essentials of nursing, it is often neglected. Improving oral health may require behaviour change of both nurses and patients. Defining tailored strategies need a clear view on the context. DESIGN: A context analysis in one hospital using a convergent parallel mixed-methods design was reported following the EQUATOR guidelines using two checklists: COnsolidated criteria for REporting Qualitative research (qualitative research) and STROBE (observational research). METHODS: Semi-structured interviews were conducted with 19 nurses and 11 patients. The topic list was based on the Integrated Change Model. Prospective oral examination was performed among 91 surgical patients using the Oral Health Assessment Tool (OHAT). RESULTS: Nurses acknowledged that they did not prioritise oral care in daily practice. Furthermore, they lacked knowledge and skills to identify and provide care for oral problems. Nurses mentioned helpful resources to perform oral care, like standardised language and instruments. However, they had no access to or were unaware of them. Patients admitted that they did not prioritise oral care due to their sickness during hospitalisation, were unaware of the importance of oral care, but felt responsible for their oral care. The most prominent oral problems identified with the OHAT were unclean mouths (n = 75, 82%), unhealthy gum and tissues (n = 55, 60%) and dry mouth (n = 42, 46%). CONCLUSIONS: This context analysis identified inadequate oral care due to lack of positive attitude and knowledge in both nurses and patients, skills for nurses, and resources. RELEVANCE TO CLINICAL PRACTICE: The behavioural factors indicate strategies for development of a multicomponent intervention to improve oral care in this hospital, nutritional status and general health outcomes.

Introduction: After standard diagnostic work-up, the aetiology of acute pancreatitis remains unknown in 16–27% of cases, a condition referred to as idiopathic acute pancreatitis (IAP). Determining the aetiology of pancreatitis is essential, as it may direct treatment in the acute phase and guides interventions to prevent recurrent pancreatitis. Methods: Between 2008 and 2015, patients with acute pancreatitis were registered prospectively in 19 Dutch hospitals. Patients who had a negative initial diagnostic work-up with regard to the underlying aetiology of their pancreatitis were labelled ‘presumed’ IAP. The aim of this study was to assess the use of diagnostic modalities and their yield to establish an aetiology in ‘presumed’ IAP, and to assess recurrence rates both with and without treatment. Results: Out of the 1632 registered patients, 191 patients had a first episode of ‘presumed’ IAP, of whom 176 (92%) underwent additional diagnostic testing: CT (n = 124, diagnostic yield 8%), EUS (n = 62, yield 35%), MRI/MRCP (n = 56, yield 33%), repeat ultrasound (n = 97, yield 21%), IgG4 (n = 54, yield 9%) and ERCP (n = 15, yield 47%). In 64 of 176 patients (36%) an aetiological diagnosis was established, mostly biliary (n = 39). In 13 out of 176 of patients (7%) a neoplasm was diagnosed. If additional diagnostic workup revealed an aetiology, the recurrence rate was lower in the treated patients than in the patients without a definite aetiology (15% versus 43%, p = 0.014). Conclusion: Additional diagnostic testing revealed an aetiology in one-third of ‘presumed’ IAP patients. The aetiology found was mostly biliary, but occasionally neoplasms were found. Identification of an aetiology with subsequent treatment reduced the rate of recurrence.

Background & aims: To improve the nutritional status of surgical patients before hospital admission, an Outpatient Nursing Nutritional Intervention (ONNI) was developed. The ONNI comprehends five components: determining causes of undernutrition, performing a nutritional care plan including tailored and general advice, self-monitoring of nutritional intake and eating patterns, counselling and encouragement, and conducting a follow-up telephone call to discuss improvements in nutritional behaviour. Here, we evaluate the feasibility and effectiveness of the ONNI. Methods: In a multi-centred, cluster-randomised pilot study, nurses from outpatient clinics were randomly allocated to usual care (UC) or the ONNI. Patients planned for elective surgery were included if they were at increased risk for undernutrition based on the Malnutrition Universal Screening Tool (MUST) and hospital admission was not planned within seven days. Feasibility outcomes included participation rate, extent of intervention delivery, and patient satisfaction. Nutritional intake was monitored for two days before admission. Body weight, BMI and MUST scores at hospital admission were compared to measurements from the outpatient clinic visit. Data were analysed on an intention-to-treat basis by researchers who were blinded for patients and caregivers. Results: Forty-eight patients enrolled the feasibility phase. Participation rate was 72%. Nurses delivered all intervention components adequately in the end of the implementation period. Finally, 152 patients (IG: n = 66, 43%) participated in the study. A significant difference in mean energy intake (870 kcal/d, 95%CI:630-1109 p < 0.000) and mean protein intake (34.1 g/d, 95%CI: 25.0–43.2; p < 0.000) was observed in favour of the IG. Nutritional energy requirements were achieved in 74% (n = 46) of the IG and in 17% (n = 13) of the UC group (p < 0.000), and protein requirements were achieved in 52% (n = 32) of the IG, compared to 8% (n = 6) of the UC group (p < 0.000). Body weight, BMI and MUST scores did not change in either group. Conclusions: The ONNI is a feasible and effective intervention tool for nurses at outpatient clinics. Patients in the IG had more nutritional intake and fulfilled nutritional requirements significantly more often than patients receiving UC. Further research is required to determine the optimal pre-operative timing of nutritional support and to measure its effect on other patients groups. Clinical trial registration: The study protocol was registered at the ClinicalTrial.gov website with the following identifier: NCT02440165.

Contains fulltext : 229788.pdf (Publisher’s version ) (Open Access) BACKGROUND: Prehabilitation might attenuate common surgery-induced losses in muscle mass and physical performance. Beneficial effects of physical exercise with protein supplementation have been reported in older adults, but typically after an intervention of at least 12 weeks. The time-window for pre-surgery training is often limited to around 30 days, and it is not known if it is possible to achieve comparable results in such a short time window. OBJECTIVES: The aim of this study was to pilot-test the effectiveness of a controlled four-week combined exercise and protein supplementation program on skeletal muscle-related outcomes in a Dutch older adult population. DESIGN: This study was a one-armed pilot trial. PARTICIPANTS: Seventeen older men and women, aged 55-75y, not scheduled for surgery. INTERVENTION: A 4-week intervention program consisting of a twice-weekly supervised resistance and high-intensity aerobic exercise training of 75 min, combined with daily protein supplementation (2 doses of 15.5 g/day at breakfast and lunch). MEASUREMENT: After two and four weeks, isometric quadriceps maximal voluntary contraction (MVC) was assessed via Biodex and quadriceps cross-sectional area (CSA) via magnetic resonance imaging. Other outcome measures were handgrip strength, chair rise time and maximal aerobic capacity (VO(2)-max), as assessed from a submaximal exercise test. RESULTS: Compliance to the supervised training sessions (99.3%) and the protein supplementation (97%) was very high. The 4-week exercise and protein program led to an increase in quadriceps CSA of 2.3 ± 0.7 cm(2) (P = 0.008) in the dominant leg and 3.2 ± 0.7 cm(2) (P

Item does not contain fulltext BACKGROUND AND AIMS: Individuals with inflammatory bowel disease (IBD) often hold strong beliefs on how diet impacts their disease. This study aimed to compare dietary intakes between IBD patients and individuals from the general population and to assess associations of dietary factors with relapse in patients with IBD. METHODS: Patients with longstanding Crohn's disease and ulcerative colitis (n = 165) filled out food frequency questionnaires, as did individuals participating in a Dutch population-based study (controls) (n = 1469). Multivariable regression analyses were used to assess differences in habitual dietary intake between IBD patients and controls, and to estimate associations of dietary factors in patients in remission with the development of disease relapse at follow-up. RESULTS: IBD patients had higher intakes of animal protein (3.50 g/d, 95% confidence interval (CI) 1.67-5.34) and carbohydrate (10.1 g/d, 95% CI 5.23-14.9) than controls and lower intakes of (unsaturated) fat (-3.53 g/d, 95% CI -5.57- -1.50), dietary fiber (-2.19 g/d, 95% CI -3.05- -1.32) and alcohol (-0.84 g/d, 95% CI -1.46- -0.22). This was explained by a higher consumption of carbonated beverages, meat and poultry and lower consumption of fruit, vegetables and dairy products (except cheese) by IBD patients compared with controls. Several dietary factors, particularly (saturated) fat and fiber, appeared to be associated with risk of relapse. CONCLUSIONS: IBD patients had higher dietary intakes of (animal) protein and carbohydrate and lower intakes of (unsaturated) fat, dietary fiber and alcohol compared with a general Dutch population. The results further underscore that dietary factors may have a role in disease course.

Background/Objectives:Migraine, associated with several gastrointestinal disorders, may result from increased intestinal permeability, allowing endotoxins to enter the bloodstream. We tested whether probiotics could reduce migraine through an effect on intestinal permeability and inflammation.Subjects/Methods:In total, 63 patients were randomly allocated to the probiotic (n=31) or the placebo group (n=32). Participants ingested a multispecies probiotic (5x10 9 colony-forming units) or placebo daily for 12 weeks. Migraine was assessed with the Migraine Disability Assessment Scale (MIDAS), the Headache Disability Inventory (HDI) and headache diaries. At baseline and 12 weeks, intestinal permeability was measured with the urinary lactulose/mannitol test and fecal and serum zonulin; inflammation was measured from interleukin (IL) -6, IL-10, tumor necrosis factor-α and C-reactive protein in serum.Results:The MIDAS migraine intensity score significantly decreased in both groups (P

Objectives: Sufficient protein intake and habitual physical activity are key factors in the prevention and treatment of sarcopenia. In the present study, we assessed habitual dietary protein intake and the contribution of animal proteins in male versus female physically active elderly and identified determinants of protein intake. Design: a cross-sectional study. Setting: the study was performed within the Nijmegen Exercise Study. Participants: physically active elderly ≥ 65 yrs. Measurements: Physical activity was assessed using the SQUASH questionnaire and expressed in Metabolic Equivalent of Task hours per week (METhr/wk). Dietary protein intake was determined using a validated food frequency questionnaire (FFQ). Multivariate linear regression analysis was used to determine whether age, sex, educational level, smoking, alcohol intake and physical activity were associated with protein intake (g/kg/d). Results: A total of 910 participants (70±4 yrs, 70% male) were included and reported a habitual physical activity level of 85.0±53.5 METhr/wk. Protein intake was 1.1±0.3 g/kg/d with 57% animal-based proteins for males, and 1.2±0.3 g/kg/d with 59% animalbased proteins for females (both P

Background and Aims: Large non-pedunculated rectal polyps are most commonly resected by endoscopic mucosal resection (EMR) or transanal endoscopic microsurgery (TEM). Despite pre-procedural diagnostics, unexpected rectal cancer is incidentally encountered within the resected specimen. This study aimed to compare the diagnostic assessment and procedural characteristics of lesions with and without unexpected submucosal invasion. Methods: A post-hoc analysis of a multicenter randomized trial (TREND study) was performed in which patients with a non-pedunculated rectal polyp of >= 3 cm without endoscopic suspicion of invasive growth were randomized between EMR and TEM. Results: Unexpected rectal cancer was detected in 13% (27/203) of patients; 15 after EMR and 12 after TEM. Most consisted of low-risk T1 cancers (78%, n = 18). There were no differences in the diagnostic assessment between lesions with and without unexpected submucosal invasion. Diagnostic biopsies revealed similar rates of high-grade dysplasia (28%[7/25] vs 18% [26/144]). When compared with EMR of adenomas, EMR procedures of unexpected cancers had a lower success rate of submucosal lifting (60% vs 93%, P

Item does not contain fulltext BACKGROUND: Undernutrition is a common complication of disease and a major determinant of hospital stay outcome. Dutch hospitals are required to screen for undernutrition on the first day of admission. OBJECTIVE: We sought to determine the prevalence of the screening score "undernourished" with use of the Short Nutritional Assessment Questionnaire (SNAQ) or Malnutrition Universal Screening Tool (MUST) and its relation to length of hospital stay (LOS) in the general hospital population and per medical specialty. DESIGN: We conducted an observational cross-sectional study at 2 university, 3 teaching, and 8 general hospitals. All adult inpatients aged >/=18 y with an LOS of at least 1 d were included. Between 2007 and 2014, the SNAQ/MUST score, admitting medical specialty, LOS, age, and sex of each patient were extracted from the digital hospital chart system. Linear regression analysis with ln(LOS) as an outcome measure and SNAQ >/=3 points/MUST >/=2 points, sex, and age as determinant variables was used to test the relation between SNAQ/MUST score and LOS. RESULTS: In total, 564,063 patients were included (48% males and 52% females aged 62 +/- 18 y). Of those, 74% (419,086) were screened with SNAQ and 26% (144,977) with MUST, and 13.7% (SNAQ) and 14.9% (MUST) of the patients were defined as being undernourished. Medical specialties with the highest percentage of the screening score of undernourished were geriatrics (38%), oncology (33%), gastroenterology (27%), and internal medicine (27%).Patients who had an undernourished screening score had a higher LOS than did patients who did not (median 6.8 compared with 4.0 d; P < 0.001). Regression analysis showed that a positive SNAQ/MUST score was significantly associated with LOS [SNAQ: +1.43 d (95% CI: 1.42, 1.44 d), P < 0.001; MUST: +1.47 d (95% CI: 1.45, 1.49 d), P < 0.001]. CONCLUSIONS: This study provides benchmark data on the prevalence of undernutrition, including more than half a million patients. One out of 7 patients was scored as undernourished. For geriatrics, oncology, gastroenterology, and internal medicine, this ratio was even greater (1 out of 3-4). Hospital stay was 1.4 d longer among undernourished patients than among those who were well nourished.

BackgroundScreening of patients with familial adenomatous polyposis (FAP) have led to a substantial reduction in mortality due to colorectal cancer (CRC). Recent guidelines suggest that surveillance of non-intestinal malignancies should also be considered in those patients. However, the value of these surveillance programmes is unknown. The aims of this study were (1) to assess the occurrence of extracolonic malignancies in a large series of adenomatous polyposis coli (APC) mutation carriers and (2) to evaluate the causes of death.MethodsAll APC mutation carriers were selected from the Dutch polyposis registry. Data on causes of death were collected. Pathology reports were retrieved from the Dutch Pathology Registry.ResultsA total of 85 extracolonic malignancies were diagnosed in 74 of 582 APC mutation carriers. Duodenal and skin cancers were the most prevalent cancers. Thyroid cancer was observed in only 1.5% of the cases. The main cause of death was cancer (59% of all deaths), with 42% due to CRC and 21% due to duodenal cancer. One patient died from thyroid cancer. The second and third most common causes of death were cardiovascular disease (13% of all deaths) and desmoid tumours (11% of all deaths), respectively.ConclusionExtending surveillance programmes to other cancers will not contribute significantly to the survival of patients with FAP.

Contains fulltext : 181861.pdf (Publisher’s version ) (Closed access) BACKGROUND: Infected necrotising pancreatitis is a potentially lethal disease and an indication for invasive intervention. The surgical step-up approach is the standard treatment. A promising alternative is the endoscopic step-up approach. We compared both approaches to see whether the endoscopic step-up approach was superior to the surgical step-up approach in terms of clinical and economic outcomes. METHODS: In this multicentre, randomised, superiority trial, we recruited adult patients with infected necrotising pancreatitis and an indication for invasive intervention from 19 hospitals in the Netherlands. Patients were randomly assigned to either the endoscopic or the surgical step-up approach. The endoscopic approach consisted of endoscopic ultrasound-guided transluminal drainage followed, if necessary, by endoscopic necrosectomy. The surgical approach consisted of percutaneous catheter drainage followed, if necessary, by video-assisted retroperitoneal debridement. The primary endpoint was a composite of major complications or death during 6-month follow-up. Analyses were by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN09186711. FINDINGS: Between Sept 20, 2011, and Jan 29, 2015, we screened 418 patients with pancreatic or extrapancreatic necrosis, of which 98 patients were enrolled and randomly assigned to the endoscopic step-up approach (n=51) or the surgical step-up approach (n=47). The primary endpoint occurred in 22 (43%) of 51 patients in the endoscopy group and in 21 (45%) of 47 patients in the surgery group (risk ratio [RR] 0.97, 95% CI 0.62-1.51; p=0.88). Mortality did not differ between groups (nine [18%] patients in the endoscopy group vs six [13%] patients in the surgery group; RR 1.38, 95% CI 0.53-3.59, p=0.50), nor did any of the major complications included in the primary endpoint. INTERPRETATION: In patients with infected necrotising pancreatitis, the endoscopic step-up approach was not superior to the surgical step-up approach in reducing major complications or death. The rate of pancreatic fistulas and length of hospital stay were lower in the endoscopy group. The outcome of this trial will probably result in a shift to the endoscopic step-up approach as treatment preference. FUNDING: The Dutch Digestive Disease Foundation, Fonds NutsOhra, and the Netherlands Organization for Health Research and Development.

Background: Chronic pancreatitis is a complex disease with many unanswered questions regarding the natural history and therapy. Prospective longitudinal studies with long-term follow-up are warranted.Methods: The Dutch Chronic Pancreatitis Registry (CARE) is a nationwide registry aimed at prospective evaluation and follow-up of patients with chronic pancreatitis. All patients with (suspected) chronic or recurrent pancreatitis are eligible for CARE. Patients are followed-up by yearly questionnaires and review of medical records. Study outcomes are pain, disease complications, quality of life, and pancreatic function. The target sample size was set at 500 for the first year and 1000 patients within 3 years.Results: A total of 1218 patients were included from February 2010 until June 2013 by 76 participating surgeons and gastroenterologist from 33 hospitals. Participation rate was 90% of eligible patients. Eight academic centers included 761 (62%) patients, while 25 community hospitals included 457 (38%). Patient centered outcomes were assessed by yearly questionnaires, which had a response rate of 85 and 82% for year 1 and 2, respectively. The median age of patients was 58 years, 814 (67%) were male, and 38% had symptoms for less than 5 years.Discussion: The CARE registry has successfully recruited over 1200 patients with chronic and recurrent pancreatitis in about 3 years. The defined inclusion criteria ensure patients are included at an early disease stage. Participation and compliance rates are high. CARE offers a unique opportunity with sufficient power to investigate many clinical questions regarding natural course, complications, and efficacy and timing of treatment strategies. Copyright (C) 2014, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved.

The recent addition of immunoglobulin (Ig)G4-associated cholangitis (IAC), also called IgG4-related sclerosing cholangitis (IRSC), to the spectrum of chronic cholangiopathies has created the clinical need for reliable methods to discriminate between IAC and the more common cholestatic entities, primary (PSC) and secondary sclerosing cholangitis. The current American Association for the Study of Liver Diseases practice guidelines for PSC advise on the measurement of specific Ig (sIg)G4 in PSC patients, but interpretation of elevated sIgG4 levels remains unclear. We aimed to provide an algorithm to distinguish IAC from PSC using sIgG analyses. We measured total IgG and IgG subclasses in serum samples of IAC (n=73) and PSC (n=310) patients, as well as in serum samples of disease controls (primary biliary cirrhosis; n=22). sIgG4 levels were elevated above the upper limit of normal (ULN=>1.4 g/L) in 45 PSC patients (15%; 95% confidence interval [CI]: 11-19). The highest specificity and positive predictive value (PPV; 100%) for IAC were reached when applying the 4× ULN (sIgG4>5.6 g/L) cutoff with a sensitivity of 42% (95% CI: 31-55). However, in patients with a sIgG4 between 1× and 2× ULN (n=38/45), the PPV of sIgG4 for IAC was only 28%. In this subgroup, the sIgG4/sIgG1 ratio cutoff of 0.24 yielded a sensitivity of 80% (95% CI: 51-95), a specificity of 74% (95% CI: 57-86), a PPV of 55% (95% CI: 33-75), and a negative predictive value of 90% (95% CI: 73-97). Conclusion: Elevated sIgG4 (>1.4 g/L) occurred in 15% of patients with PSC. In patients with a sIgG4 >1.4 and

Objective To determine to what extent the Rome III criteria for irritable bowel syndrome can contribute towards safely reducing unnecessary referrals for colonoscopy in primary care patients with lower gastrointestinal (GI) complaints. Design Data from the CEDAR study were used: a cross-sectional study in 810 patients with lower GI complaints suggestive for organic bowel disease who were referred by their general practitioner for secondary care colonoscopy. Fulfilment of the Rome III criteria was ascertained by a questionnaire. General practitioners recorded the presence or absence of alarm symptoms. Outcome was determined by colonoscopy and histology. Results Of 810 participants, 222 fulfilled the Rome III criteria [27%, 95% confidence interval (CI) 24-31%]. The majority of these patients presented with alarm symptoms. Only 39 participants fulfilled the Rome III criteria and lacked alarm symptoms (overall frequency 5%, 95% CI 4-7). Overall, organic bowel disease was diagnosed in 141 participants (17%). Participants who fulfilled the Rome III criteria had a significantly lower risk of organic bowel disease compared with participants who did not [12% (95% CI 8-17) vs. 20% (95% CI 17-23), P

Objective For palliation of extrahepatic bile duct obstruction, self-expandable metal stents (SEMS) are superior to plastic stents in terms of stent patency and occurrence of stent dysfunction. We assessed health-related quality of life (HRQoL) after stent placement to investigate whether this also results in a difference in HRQoL between patients treated with a plastic stent or SEMS.Patients and methods This randomized multicenter trial included 219 patients who were randomized to receive plastic stent (n = 73) or SEMS [uncovered (n = 75) and covered (n = 71); n = 146] placement. HRQoL was assessed with two general questionnaires (EQ-5D-3L and QLQ-C30) and one disease-specific questionnaire (PAN-26). Scores were analyzed using linear mixed model regression and included all patients with baseline and at least one follow-up measurement.Results HRQoL data were available in 140 of 219 patients (64%); 71 patients (32%) declined participation and in eight patients (4%) only baseline questionnaires were available. On the QLQ-C30, the interaction between follow-up time and type of stent was significantly different on two of five functional scales [physical functioning (P = 0.004) and emotional functioning (P = 0.01)] in favor of patients with a SEMS. In addition, patients with SEMS reported significantly less frequent symptoms of fatigue (P = 0.01), loss of appetite (P = 0.02), and nausea and vomiting (0.04) over time. The EQ-VAS score decreased with time in both treatment groups, indicating a statistically significant decrease in HRQoL over time.Conclusion In patients with inoperable malignant extrahepatic bile duct obstruction, SEMS placement results in better scores for general and disease-specific HRQoL over time compared with plastic stent placement. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

Background and study aims Endoscopic drainage [i.e. conventional, endoscopic ultrasonography (EUS)-assisted, or EUS-guided] is an accepted treatment modality for symptomatic peripancreatic fluid collections (PFC), but data on the efficacy and safety of EUS-guided drainage performed in a large patient cohort are not widely available. Our aim was to evaluate the clinical success and complication rate of EUS-guided drainage of PFCs and to identify prognostic factors for complications and recurrence of PFCs. Patients and methods A retrospective analysis was carried out of consecutive patients undergoing EUS-guided drainage of a symptomatic PFC in the period 2004-2011. Technical success was defined as the ability to enter and drain a PFC by the placement of one or more double-pigtail stents, whereas clinical success was defined as complete resolution of a PFC on follow-up computed tomography. Results In total, 108 patients [56% men, mean age 55 (SD 14) years], underwent EUS-guided drainage of a symptomatic PFC. The procedure was technically successful in 105/108 (97%) patients and a median of 2 (range 1-3) pigtail stents were placed. Clinical success was observed in 87/104 (84%) patients after a median follow-up of 53 (interquartile range 21-130) weeks, whereas PFC recurrence was noted in 15/83 (18%) patients. Complications occurred in 21/105 (20%) patients and procedure-related mortality was not observed. Prognostic factors for complications and recurrence of PFCs could not be identified. Conclusion EUS-guided drainage of PFCs is effective in the majority of patients. Although the complication rate of the procedure is not negligible (20%), they could be managed in almost all patients by conservative and/or endoscopic means and did not result in mortality. (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins

Objective: To validate published diagnostic models for their ability to safely reduce unnecessary endoscopy referrals in primary care patients suspected of significant colorectal disease.Study Design and Setting: Following a systematic literature search, we independently validated the identified diagnostic models in a cross-sectional study of 810 Dutch primary care patients with persistent lower abdominal complaints referred for endoscopy. We estimated diagnostic accuracy measures for colorectal cancer (N = 37) and significant colorectal disease (N = 141; including colorectal cancer, inftammatory bowel disease, diverticulitis, or > 1-cm adenomas).Results: We evaluated 18 models-12 specific for colorectal cancer, of which most were able to safely rule out colorectal cancer: the best model (National Institute for Health and Care Excellence-1) prevented 59% of referrals (95% confidence interval [CI]: 56-63%), with 96% sensitivity (95% CI: 83-100%), 100% negative predictive value (NPV; 95% CI: 99-100%), and an area under the receiver operating characteristics curve (AUC) of 0.86 (95% CI: 0.80-0.92). The models performed less for significant colorectal disease: the best model (Brazer) prevented 23% of referrals (95% CI: 20-26%), with 95% sensitivity (95% CI: 90-98%), 96% NPV (95% CI: 92-98%), and an AUC of 0.73 (95% CI: 0.69-0.78).Conclusion: Most models safely excluded colorectal cancer in many primary care patients with lower gastrointestinal complaints referred for endoscopy. Models performed less well for significant colorectal disease. (C) 2016 Elsevier Inc. All rights reserved.

BACKGROUNDFecal biomarker tests that differentiate between organic bowel disease (OBD) and non-OBD in primary care patients with persistent lower-abdomen complaints could reduce the number of unnecessary referrals for endoscopy. We quantified the accuracy of fecal calprotectin and immunochemical occult blood (iFOBT) point-of-care (POC) tests and a calprotectin ELISA in primary care patients with suspected OBD.METHODSWe performed biomarker tests on fecal samples from 386 patients with lower-abdomen complaints suggestive for OBD. Endoscopic and histological diagnosis served as reference.RESULTSOBD was diagnosed in 99 patients (prevalence 25.9%); 19 had adenocarcinoma, 53 adenoma, and 27 inflammatory bowel disease. Sensitivity for OBD was 0.64 (95% CI 0.54–0.72) for calprotectin POC, 0.56 (0.46–0.66) for iFOBT POC, and 0.74 (0.65–0.82) for calprotectin ELISA; specificities were 0.53 (0.48–0.59), 0.83 (0.78–0.87), and 0.47 (0.41–0.53), respectively. Negative predictive values (NPVs) were 0.81 (0.74–0.86), 0.85 (0.80–0.88), and 0.84 (0.78–0.89); positive predictive values (PPVs) varied from 0.32 (0.26–0.39) and 0.33 (0.27–0.39) (calprotectin tests) to 0.53 (0.44–0.63) (iFOBT POC). Combining the 2 POC tests improved sensitivity [0.79 (0.69–0.86)] and NPV [0.87 (0.81–0.91)] but lowered specificity [0.49 (0.44–0.55)] and PPV [0.35 (0.29–0.42)]. When adenomas ≤1 cm were considered non-OBD, the NPV of all tests improved to >0.90 [combined POC tests, 0.97 (0.93–0.99)].CONCLUSIONSDiagnostic accuracy of the tests alone or combined was insufficient when all adenomas were considered OBD. When only adenomas >1 cm were considered OBD, all tests could rule out OBD to a reasonable extent, particularly the combined POC tests. The tests were less useful for inclusion of OBD.

Contains fulltext : 108111.pdf (Publisher’s version ) (Open Access) Esophageal cancer (EC) has a globally increasing incidence with poor curative treatment options and survival rates. Environmental and dietary factors have crucial roles in esophageal carcinogenesis. Polymorphisms in the UGT genes, a superfamily of enzymes essential for the detoxification of carcinogens, may alter enzyme activity and subsequently may play a role in EC etiology. Rather than solely establishing differences in genotype distribution, we investigated whether functional polymorphisms in UGT genes that can predict enzyme activity in vivo, may influence EC risk. A case-control study including 351 Caucasian EC patients and 592 Caucasian controls was conducted and polymorphisms in seven UGT genes were determined, using the polymerase chain reaction. On the basis of allelic in vitro enzyme activity measurements, genotypes were categorized according to their predicted in vivo enzyme activity into high, medium and low categories. Predicted enzyme activity groups were combined and compared between patients and controls. The UGT1A1 and UGT1A8 predicted high enzyme activity genotypes were significantly more (OR=1.62; 95% CI, 1.02-2.56) and less frequent (OR=0.36; 95% CI, 0.15-0.84) among patients with esophageal squamous cell carcinoma (ESCC), respectively. High (OR=0.42; 95% CI, 0.22-0.84) and medium (OR=0.25; 95% CI, 0.12-0.52) activity UGT2B4 genotypes were significantly less often present in ESCC patients. No association was detected between UGT genotypes and esophageal adenocarcinoma (EAC) risk. Polymorphisms in UGT genes, resulting in altered enzyme activity genotypes, do not seem modifiers of EAC risk. However, the predicted high activity UGT1A1 genotype, associated with low serum levels of the antioxidant bilirubin, was associated with an increased ESCC risk. The UGT1A8 and UGT2B4 genotypes associated with decreased predicted enzyme activities, were significantly associated with an increased risk of ESCC, probably by a decreased detoxification of carcinogens. 01 juni 2012

Item does not contain fulltext BACKGROUND: Primary sclerosing cholangitis (PSC) is strongly associated with inflammatory bowel disease (IBD). The aim of this study was to assess the IBD phenotype associated with PSC in a large well-phenotyped population-based PSC cohort using endoscopic and histopathologic criteria. METHODS: PSC cases were identified and ascertained, fulfilling well-established criteria, in 39 hospitals in a geographically defined region of The Netherlands. IBD location was recorded according to the Montreal Classification. As this classification does not consider segmental inflammation, backwash ileitis, or rectal sparing, an additional subgroup analysis was performed in 80 cases and 80 age- and sex-matched IBD controls, reviewing all endoscopy and pathology reports filed between 2000 and 2010. RESULTS: In all, 380 (66%) of a total of 579 PSC patients had coexistent IBD, mainly ulcerative colitis (UC) (75%). Overall, 207 (83%) of the PSC-UC patients had a pancolitis, 32 (13%) a left-sided colitis, and 9 (4%) a proctitis only. Seventy (95%) PSC-Crohn's disease (CD) patients had an (ileo)colitis and four (5%) ileitis only. In the subgroup analysis 53 (66%) PSC-UC patients were identified, 24 (30%) PSC-CD patients, and three (4%) PSC-IBD-U patients. Fifty (94%) PSC-UC patients had a pancolitis, compared with 32 (62%) matched UC patients (P < 0.001). Left-sided colitis was seen in 16 (31%) UC controls and in one PSC-UC patient (P < 0.001). Backwash ileitis and rectal sparing were rare findings (

Background Self-expanding metal stents (SEMS) are known to have a significantly higher patency rate than plastic stents. We aimed to identify prognostic factors, besides stent type, for stent patency and to develop a score model that could further aid in guiding stent choice for the palliation of a malignant biliary stricture. Methods A retrospective multicenter study was conducted. Data on consecutive patients who had a stent placed between January 2002 and July 2009 were collected. Cumulative stent occlusion rates were analyzed by Kaplan-Meier curves and log rank testing, and prognostic factors were assessed by Cox regression analysis. Results A total of 690 stents (512 plastic stents, 174 SEMS) were endoscopically placed in 390 patients. At 8 weeks, stent occlusion had occurred in 32% of the plastic stents and 11% of the SEMS. Multivariate analysis indicated that plastic stents (hazard ratio [HR] 2.5, 95% confidence interval [CI] 1.9-3.5), a tight stricture requiring preceding dilation (HR 1.8, 95% CI 1.3-2.5), and a high initial bilirubin level (>50 mu mol/L (HR 1.3, 95% CI 1.0-1.7) were independently associated with an increased risk of stent occlusion. A score model based on these 3 factors was able to distinguish between stent procedures with a relatively high and low risk of stent occlusion (median 14 vs. 26 weeks, respectively). Conclusion Besides plastic stents, stricture severity requiring preceding dilation, and initial higher bilirubin level were associated with a shorter period of stent patency. A simple score model based on these factors was able to predict stent occlusion and may aid in choosing the most appropriate stent type in individual patients.

Contains fulltext : 70440.pdf (Publisher’s version ) (Closed access) BACKGROUND & AIMS: Antidepressants could be effective in the treatment of functional gastrointestinal disorders through their anticholinergic and pain-modulating effects. Previous studies with these drugs lacked sufficient power and were predominantly conducted in patients with irritable bowel syndrome. This study aimed to assess the effectiveness of the serotonin and norepinephrine reuptake inhibitor venlafaxine in patients with functional dyspepsia. METHODS: This was a multi-center, randomized, double-blind, placebo-controlled trial. Participants had persistent dyspeptic symptoms and underwent upper gastrointestinal endoscopy in a secondary care hospital to exclude organic abnormalities. They were randomly assigned to receive 8 weeks of treatment with either venlafaxine XR (2 weeks 75 mg once daily, 4 weeks 150 mg once daily, and 2 weeks 75 mg once daily) or placebo. Symptoms, health-related quality of life, anxiety, and depression were assessed before and at 4, 8, 12, and 20 weeks after inclusion. RESULTS: One hundred sixty patients were randomized; 56% and 73% of participants completed treatment with venlafaxine or placebo, respectively, according to protocol. There was no difference in proportions of symptom-free patients after 8 weeks of treatment or at 20 weeks after inclusion, with venlafaxine in comparison to placebo (37% and 39%, respectively; odds ratio [OR], 0.8; 95% confidence interval [CI], 0.3-2.1; and 42% and 41%, respectively; OR, 3.1; 95% CI, 0.9-12.6). Per-protocol analysis did not reveal any differences between venlafaxine and placebo either (38% and 39% symptom-free, respectively; OR, 1.0; 95% CI, 0.4-2.4 at 8 weeks). CONCLUSIONS: Treatment with the selective serotonin and norepinephrine reuptake inhibitor venlafaxine is not more effective than placebo in patients with functional dyspepsia.

OBJECTIVE: To determine (a) the incidence of restless legs syndrome (RLS) in patients with Crohn's disease (CD), (b) whether and how the occurrence and severity of RLS is related to severity of CD, and (c) how RLS influences the quality of life of CD patients. BASIC METHODS: We carried out a cross-sectional questionnaire study in a random selection of 144 CD patients and 80 controls. Differences were calculated using a χ-test (categorical data), an independent T-test (continuous data, normal distribution), or a Mann-Whitney U-test (continuous data, non-normal distribution). Logistic regression analysis was carried out to establish the relation between CD and RLS after adjusting for risk factors. MAIN RESULTS: The prevalence of RLS was 25.7% (37/144) in CD patients compared with 12.5% (10/80) in the control group (P=0.02). CD patients using caffeine and patients with arthralgias had a higher risk for RLS. A higher score on the modified Harvey Bradshaw Index and CD-related surgery were also associated with a higher risk for RLS. CD-related surgery was also associated with a more severe course of RLS. Patients and controls with RLS had a lower score on 'physical functioning', one of the subcategories of the RAND-36 quality-of-life questionnaire. PRINCIPAL CONCLUSION: RLS occurs more frequently in patients with CD compared with healthy individuals. A more severe course of CD seems to be associated with a higher risk for RLS. The presence of RLS has a negative influence on quality of life, mainly interfering with physical activities of daily life

Background & aims: In several rat infection experiments, we have shown that dietary calcium inhibits intestinal colonization and translocation of invasive salmonella. The aim of the present study was to find out whether calcium is also protective against enterotoxigenic Escherichia coli (ETEC) infection. This was first tested in our rat model and subsequently verified in a human infection study. Methods: Rats were fed a purified diet with either a low or a high amount of calcium phosphate and orally infected with ETEC. In addition, a parallel, double-blind, placebo-controlled intervention study of 3 weeks was performed with 32 healthy men. Subjects largely maintained their habitual diet and consumed either regular milk products (calcium supply, 1100 mg/day) or placebo milk products (calcium supply, 60 mg/day). On day 10, subjects ingested a live but attenuated ETEC strain (strain E1392/75-2A), able to induce mild although short-lived symptoms. Primary outcomes studied were infection-induced diarrhea (total fecal output and relative fecal dry weight) and fecal mucin excretion. Results: In humans, ETEC induced diarrhea in both groups, in that total fecal output doubled and mean relative fecal dry weight dropped from 25% to 20%. Additionally, fecal mucin excretion was increased in both groups. All these fecal parameters were completely normalized in the calcium group on the second infection day, in contrast to the placebo group, which recovered on the third infection day. Likewise, supplemental calcium inhibited ETEC colonization and diarrhea in rats. Conclusions: Calcium in milk products improves human resistance to ETEC infection as it inhibits infectious diarrhea.

Contains fulltext : 152695.pdf (Publisher’s version ) (Closed access) BACKGROUND: In patients with mild gallstone pancreatitis, cholecystectomy during the same hospital admission might reduce the risk of recurrent gallstone-related complications, compared with the more commonly used strategy of interval cholecystectomy. However, evidence to support same-admission cholecystectomy is poor, and concerns exist about an increased risk of cholecystectomy-related complications with this approach. In this study, we aimed to compare same-admission and interval cholecystectomy, with the hypothesis that same-admission cholecystectomy would reduce the risk of recurrent gallstone-related complications without increasing the difficulty of surgery. METHODS: For this multicentre, parallel-group, assessor-masked, randomised controlled superiority trial, inpatients recovering from mild gallstone pancreatitis at 23 hospitals in the Netherlands (with hospital discharge foreseen within 48 h) were assessed for eligibility. Adult patients (aged >/=18 years) were eligible for randomisation if they had a serum C-reactive protein concentration less than 100 mg/L, no need for opioid analgesics, and could tolerate a normal oral diet. Patients with American Society of Anesthesiologists (ASA) class III physical status who were older than 75 years of age, all ASA class IV patients, those with chronic pancreatitis, and those with ongoing alcohol misuse were excluded. A central study coordinator randomly assigned eligible patients (1:1) by computer-based randomisation, with varying block sizes of two and four patients, to cholecystectomy within 3 days of randomisation (same-admission cholecystectomy) or to discharge and cholecystectomy 25-30 days after randomisation (interval cholecystectomy). Randomisation was stratified by centre and by whether or not endoscopic sphincterotomy had been done. Neither investigators nor participants were masked to group assignment. The primary endpoint was a composite of readmission for recurrent gallstone-related complications (pancreatitis, cholangitis, cholecystitis, choledocholithiasis needing endoscopic intervention, or gallstone colic) or mortality within 6 months after randomisation, analysed by intention to treat. The trial was designed to reduce the incidence of the primary endpoint from 8% in the interval group to 1% in the same-admission group. Safety endpoints included bile duct leakage and other complications necessitating re-intervention. This trial is registered with Current Controlled Trials, number ISRCTN72764151, and is complete. FINDINGS: Between Dec 22, 2010, and Aug 19, 2013, 266 inpatients from 23 hospitals in the Netherlands were randomly assigned to interval cholecystectomy (n=137) or same-admission cholecystectomy (n=129). One patient from each group was excluded from the final analyses, because of an incorrect diagnosis of pancreatitis in one patient (in the interval group) and discontinued follow-up in the other (in the same-admission group). The primary endpoint occurred in 23 (17%) of 136 patients in the interval group and in six (5%) of 128 patients in the same-admission group (risk ratio 0.28, 95% CI 0.12-0.66; p=0.002). Safety endpoints occurred in four patients: one case of bile duct leakage and one case of postoperative bleeding in each group. All of these were serious adverse events and were judged to be treatment related, but none led to death. INTERPRETATION: Compared with interval cholecystectomy, same-admission cholecystectomy reduced the rate of recurrent gallstone-related complications in patients with mild gallstone pancreatitis, with a very low risk of cholecystectomy-related complications. FUNDING: Dutch Digestive Disease Foundation.

Contains fulltext : 136543.pdf (Publisher’s version ) (Open Access) INTRODUCTION: Numerous factors influence the development of gastrointestinal (GI) cancer. The insulin-like growth factor (IGF) axis plays a role in embryonic and postnatal growth and tissue repair. Elevated levels of IGFs, low levels of IGF binding proteins (IGFBPs) and over-expression of IGF receptor (IGFR-I) were associated with several stages of cancer. Here, the prevalence of the single nucleotide polymorphisms (SNPs) rs6214 in the IGF type I (IGF-I) gene and rs6898743 in the growth hormone receptor (GHR) gene in patients with GI cancer and controls was studied. MATERIALS & METHODS: In this Dutch case-control study, DNA isolated from blood of 1,457 GI cancer patients; 438 patients with head and neck cancer (HNC), 475 with esophageal cancer (EC) and 544 with colorectal cancer (CRC) and 1,457 matched controls, was used to determine the rs6214 and rs6898743 genotypes by polymerase chain reaction. The association between these SNPs and GI cancer, HNC, esophageal adenocarcinoma (EAC), esophageal squamous-cell carcinoma (ESCC) and proximal or distal CRC was studied. Odds ratios (ORs) with 95% confidence interval (95% CI) were calculated via unconditional logistic regression. RESULTS: Overall for GI cancer, the ORs for SNPs rs6214 and rs6898743 were approximately 1.0 (p-value>0.05), using the most common genotypes GG as reference. An OR of 1.54 (95% CI, 1.05-2.27) was found for EC for genotype AA of rs6214. The ORs for EAC were 1.45 (95% CI, 1.04-2.01) and 1.71 (95% CI, 1.10-2.68), for genotypes GA and AA, respectively. Genotype GC of rs6898743 showed an OR of 0.47 (95% CI, 0.26-0.86) for ESCC. CONCLUSION: The A allele of SNP rs6214 in the IGF-I gene was associated with EAC, and with HNC in women. The GC genotype of rs6898743 in the GHR gene was negatively associated with ESCC.

Contains fulltext : 138087.pdf (Publisher’s version ) (Closed access) Gastrointestinal (GI) cancer is responsible for the majority of deaths among all types of cancer. Lifestyle factors may not only be the main risk factor for GI cancer but reactive oxygen species (ROS) may also be involved. The single-nucleotide polymorphisms (SNPs) 609C>T (rs1800566) and 465C>T (rs1131341) in the NAD(P)H: quinone oxidoreductase 1 (NQO1) gene lead to a decline in NQO1 enzyme activity. NQO1 catalyzes the two-electron reduction of quinones to hydroquinones, thereby preventing the formation of ROS. Such polymorphisms in NQO1 may increase the risk of GI cancer. The aim of this study was to evaluate the influence of the SNPs rs1800566 and rs1131341 in the NQO1 gene on the risk of GI cancer in the Netherlands. Real-time polymerase chain reaction techniques were conducted to determine the NQO1 genotypes of 1457 patients with GI cancer and 1457 age- and gender-matched controls in a case-control study. Binary logistic regression analyses showed no statistically significant difference in genotype distributions between patients and controls: odds ratios (ORs) with 95% confidence interval (CI) for rs1800566 were 1.09 (0.93-1.28) and 1.17 (0.77-1.77) for the CT and TT genotypes, respectively. ORs for rs1131341 CT and TT genotypes were 1.21 (0.90-1.63) and 0.54 (0.05-5.94), respectively. For rs1800566, a significant association between the CT genotype and proximal colon cancer was detected (OR=1.60; 95% CI=1.09-2.35). The NQO1*2 T allele of SNP rs1800566 was found associated with an increased risk for proximal colorectal cancer, whereas SNP rs1131341 was rare in our Dutch population and was not associated with GI cancer.

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. What's new? People take vitamins and other dietary supplements for many reasons, but could your supplements be harmful? Heine-Bröring et al. investigated the effects of dietary supplements on colorectal adenomas, to better advise those at risk. Colorectal cancer is one of the most common types of cancer in the Western world, and one red flag for clinicians is the presence of colorectal adenomas. Patients who develop these asymptomatic growths have an increased risk of colorectal cancer. As more and more people have begun taking multivitamin supplements, it is important to know how to advise patients with recurrent colorectal adenomas regarding dietary supplements. The researchers conducted a cohort study, including 203 dietary supplement users and 362 nonusers, and looked at the relative frequency of colorectal adenomas in each group. Their results showed that taking dietary supplements such as vitamin C, calcium, or multivitamins did not reduce or increase a person's risk of colorectal adenoma recurrence. Use of B-vitamin supplements, however, were associated with an increase in total recurrent colorectal adenomas, but not with recurrent adenomas that showed advanced pathology. © 2012 UICC.

Contains fulltext : 125778.pdf (Publisher’s version ) (Closed access) Esophageal cancer (EC), mainly consisting of squamous cell carcinoma (ESCC) in the Eastern world and adenocarcinoma (EAC) in the Western world, is strongly associated with dietary factors such as alcohol use. We aimed to clarify the modifying role in EC etiology in Caucasians of functional genotypes in alcohol-metabolizing enzymes. In all, 351 Caucasian patients with EC and 430 matched controls were included and polymorphisms in CYP2E1, ADH and near ALDH2 genes were determined. In contrast to the results on ESCC in mainly Asian studies, we found that functional genotypes of alcohol-metabolizing enzymes were not significantly associated with EAC or ESCC in an European population.

Contains fulltext : 118871.pdf (Publisher’s version ) (Open Access) BACKGROUND: Identifying and monitoring high-risk patients can aid the prevention of esophageal cancer (EC). The interaction of environmental risk factor exposure and genetic susceptibility may contribute to the etiology of EC. Biotransformation enzymes such as Glutathione S-Transferases (GSTs ) detoxify mutagenic and genotoxic compounds and therefore control the rate of detoxification of carcinogens. Functional polymorphisms in the genes coding for GSTs alter their enzyme activity in vitro, and were reported to modify EC risk in Asians. We hypothesized that altered enzyme activity GST genotypes influence the susceptibility for esophageal adeno- (EAC) and squamous cell carcinoma (ESCC) in Caucasians. METHODS: We performed a case-control study including 440 Caucasian patients with EC and 592 healthy Caucasian controls matched for age and sex. Functional polymorphisms were selected and genotypes were determined in GST classes Alpha, Mu, Theta and Pi by means of polymerase chain reaction. Genotypes were classified into predicted high, intermediate and low enzyme activity categories based on in vitro activity data. The distribution of the activity genotypes were compared between patients with EAC or ESCC, and controls. Odds ratios (OR) with 95% confidence intervals (CI) were calculated by logistic regression analyses. Gene-gene interactions were tested and for comparison purposes, the predicted low and intermediate activity genotypes were combined. Genotypes with similar risks for EAC or ESCC were combined and analyzed for multiplicative effects. RESULTS: Our analyses includes 327 patients with EAC and 106 patients with ESCC. Low or intermediate activity enzyme genotypes for GSTM1, GSTA1, GSTP1 I105V and A114V as well as for GSTT1, did not significantly modify the risk for ESCC or EAC in our Dutch population. CONCLUSION: Functional genotypes in GST genes are not involved in EAC or ESCC susceptibility in Caucasians, in contrast to results on ESCC from Asia or Africa.

To determine whether long vagal cholinergic pathways are involved in erythromycin-induced pancreatic polypeptide release, erythromycin was administered as an intravenous bolus injection to 9 healthy volunteers (group A) and to 13 patients (group B) with impaired vagal function as a result of truncal vagotomy or accidental vagotomy after antireflux surgery. In 7 of these patients (group B1) an antrectomy was also performed, while in the other 6 patients (group B2) the antrum was not removed. Pancreatic polypeptide was measured by radioimmunoassay at 5-min intervals twice before and at 2, 5, 10, 15, 30, 45 and 60 min after a 3.5 mg/kg bolus injection of erythromycin. On another day, a standard meal was administered and plasma pancreatic polypeptide was measured at 10-min intervals for 1 h. Erythromycin injection resulted in a lower integrated pancreatic polypeptide response in the patients of group B1 (247 +/- 89 pmol/l x 15 min; p = 0.005) and group B2 (497 +/- 111 pmol/l x 15 min; p = 0.05) when compared to the healthy subjects of group A (1,136 +/- 227 pmol/l x 15 min). The pancreatic polypeptide response to erythromycin in group B1 was reduced when compared to group B2, but the difference just failed to reach statistical significance (0.05 < p < 0.10). In the first 30 min after ingestion of a meal (cephalic phase) pancreatic polypeptide release was also markedly lower in group B1 (1,461 +/- 304 pmol/l x 30 min; p < 0.005) and group B2 (1,452 +/- 215 pmol/l x 30 min; p < 0.005) when compared to group A (3,541 +/- 452 pmol/l x 30 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Contains fulltext : 111001.pdf (Publisher’s version ) (Closed access) Esophageal cancer (EC) has a globally increasing incidence with poor curative treatment options and survival rates. Crucial risk factors are exposure to toxins or carcinogens. Microsomal epoxide hydrolase (mEH) is a biotransformation enzyme essential for the detoxification of xenobiotics. Polymorphisms in exon 3 and exon 4 of the microsomal epoxide hydrolase gene (EPHX1) modify catalytic activity of this enzyme and subsequently may play a role in EC etiology. This case-control study investigated whether these polymorphisms in the EPHX1 gene influence esophageal cancer susceptibility in a Dutch Caucasian population. A case-control study including 349 Caucasian EC patients and 581 Caucasian healthy controls was conducted and the polymorphisms Tyr113His (exon 3) and His139Arg (exon 4) in the EPHX1 gene were determined, using polymerase chain reaction. The distribution of exon 3 and exon 4 genotypes were compared between cases and controls. Analyses included a stratification according to tumor histology; esophageal adenocarcinoma (EAC) or squamous cell carcinoma (ESCC). Furthermore, on the basis of allelic in vitro enzyme activity assays, exon 3 and 4 genotypes were combined and categorized according to their predicted high, medium or low enzyme activity. Homozygosity and heterozygosity for both exon 3 and 4 polymorphisms were correlated with a decreased esophageal squamous cell carcinoma risk. Heterozygosity and homozygosity for both polymorphisms correlated with an increased and a decreased esophageal adenocarcinoma risk, respectively. Predicted intermediate and high activity genotypes were risk and protective factors for esophageal squamous cell carcinoma and esophageal adenocarcinoma, respectively. However, none of these associations were statistically significant. In conclusion, the polymorphisms in exon 3 and exon 4 of the EPHX1 gene do not seem to be modifiers of esophageal squamous cell carcinoma or esophageal adenocarcinoma risk in Dutch Caucasians. 01 juni 2012

Changes in gallbladder contraction and plasma cholecystokinin release were studied following modified sham feeding of 3 different isocaloric meals rich in either fat, protein or carbohydrates in healthy volunteers, and results were compared with those following real feeding of comparable meals. In contrast to carbohydrate-rich meals (8 +/- 19 ml/120 min), fat- (-412 +/- 46 ml/120 min) and protein-rich meals (-352 +/- 42 ml/120 min) reduced integrated gallbladder volume (P < 0.05) in response to modified sham feeding. Plasma cholecystokinin levels were not significantly influenced by modified sham feeding of fat, protein or carbohydrates. Real feeding of a carbohydrate-rich meal also failed to significantly reduce gallbladder volume and to stimulate cholecystokinin release (-45 +/- 40 ml/120 min and 51 +/- 11 pmol/120 min, respectively), while real feeding of both fat- and protein-rich meals distinctly reduced gallbladder volume (-679 +/- 76 and -564 +/- 53 ml/120 min, respectively; P < 0.05) and increased cholecystokinin release (651 +/- 72 and 504 +/- 43 pmol/120 min, respectively; P < 0.05). This study demonstrates that gallbladder contraction during the cephalic phase of meal stimulation is dependent on the fat, protein and carbohydrate percentages of a meal, and is activated by different mechanisms than the intestinal phase of a meal.

Item does not contain fulltext Fish consumption is associated with a reduced colorectal cancer risk. A possible mechanism by which fish consumption could decrease colorectal cancer risk is by reducing inflammation. However, thus far, intervention studies investigating both systemic and local gut inflammation markers are lacking. Our objective in this study was to investigate the effects of fatty and lean fish consumption on inflammation markers in serum, feces, and gut. In an intervention study, participants were randomly allocated to receive dietary advice (DA) plus either 300 g of fatty fish (salmon) or 300 g of lean fish (cod) per week for 6 mo, or only DA. Serum C-reactive protein (CRP) concentrations were measured pre- and postintervention (n = 161). In a subgroup (n = 52), we explored the effects of the fish intervention on fecal calprotectin and a wide range of cytokines and chemokines in fecal water and in colonic biopsies. Serum CRP concentrations were lower in the salmon (-0.5 mg/L; 95% CI -0.9, -0.2) and cod (-0.4 mg/L; 95% CI -0.7, 0.0) groups compared with the DA group. None of the inflammation markers in fecal water and colonic biopsies differed between the DA group and the groups that consumed extra fish. In conclusion, increasing salmon or cod consumption for 6 mo resulted in lower concentrations of the systemic inflammation marker CRP. However, exploratory analysis of local markers of inflammation in the colon or feces did not reveal an effect of fish consumption.

Contains fulltext : 79521.pdf (Publisher’s version ) (Open Access) AIM: To determine whether -1195 A-->G and/or -765 G-->C polymorphisms in Cyclooxygenase-2 (COX-2) may have a risk modifying effect on the development of esophageal carcinoma in a Dutch Caucasian population. METHODS: Two study groups were recruited, 252 patients with esophageal carcinoma and 240 healthy controls, matched for race, age, gender and recruiting area. DNA was isolated from whole blood and used for genotyping. PCR products were digested with restriction enzymes and products were analyzed by agarose gel electrophoresis. Odds ratios (OR) and 95% confidence intervals (CI) were estimated. RESULTS: The distribution of the -1195 A-->G polymorphism was significantly different in esophageal cancer patients compared to controls. The -1195 GG genotype resulted in a higher risk of developing esophageal adenocarcinoma (OR = 3.85, 95% CI: 1.45-10.3) compared with the -1195 AA genotype as a reference. The -765 G-->C genotype distribution was not different between the two groups. The GG/GG haplotype was present more often in esophageal adenocarcinoma patients than in controls (OR = 3.45, 95% CI: 1.24-9.58; with AG/AG as a reference). The same trends were observed in patients with squamous cell carcinomas, however, the results did not reach statistical significance. CONCLUSION: Presence of the COX-2 -1195 GG genotype and of the GG/GG haplotype may result in a higher risk of developing esophageal carcinoma.

Item does not contain fulltext CONTEXT: The insulin-like growth factor (IGF)-system has been implicated in colorectal tumor carcinogenesis. Although both tumor expression levels and serum concentrations of IGF-system components are related to colorectal cancer risk, it is unknown whether IGF levels in tissue and serum are correlated. OBJECTIVE: The objective of this study was to determine expression levels of various IGF-system components in different locations of the colorectum, and to investigate whether normal tissue IGF expression levels are correlated with serum IGF-I and IGF-II concentrations. DESIGN: Biopsies from macroscopically normal mucosa at four locations in the colorectum (ascending, transverse, sigmoid colon, and rectum) and a fasting serum sample were obtained from 48 asymptomatic patients at increased risk of colorectal cancer. Expression levels of IGF-I, IGF-II, IGF-IR, IGF-IIR, and IGFBP-3 messenger RNA (mRNA) in tissue were quantitatively evaluated using real-time RT-PCR. Expression of IGF-IR protein in the ascending colon and rectum tissue specimens was assessed semi-quantitatively by immunohistochemistry. Serum IGF-I and IGF-II concentrations were determined using immunometric assays. RESULTS: With the exception of IGF-IIR, mRNA levels of all the IGF-system components investigated, as well as IGF-IR protein expression, were significantly higher in the rectum compared with the ascending colon (p

Contains fulltext : 71360.pdf (Publisher’s version ) (Closed access) BACKGROUND: Infectious complications and associated mortality are a major concern in acute pancreatitis. Enteral administration of probiotics could prevent infectious complications, but convincing evidence is scarce. Our aim was to assess the effects of probiotic prophylaxis in patients with predicted severe acute pancreatitis. METHODS: In this multicentre randomised, double-blind, placebo-controlled trial, 298 patients with predicted severe acute pancreatitis (Acute Physiology and Chronic Health Evaluation [APACHE II] score > or =8, Imrie score > or =3, or C-reactive protein >150 mg/L) were randomly assigned within 72 h of onset of symptoms to receive a multispecies probiotic preparation (n=153) or placebo (n=145), administered enterally twice daily for 28 days. The primary endpoint was the composite of infectious complications--ie, infected pancreatic necrosis, bacteraemia, pneumonia, urosepsis, or infected ascites--during admission and 90-day follow-up. Analyses were by intention to treat. This study is registered, number ISRCTN38327949. FINDINGS: One person in each group was excluded from analyses because of incorrect diagnoses of pancreatitis; thus, 152 individuals in the probiotics group and 144 in the placebo group were analysed. Groups were much the same at baseline in terms of patients' characteristics and disease severity. Infectious complications occurred in 46 (30%) patients in the probiotics group and 41 (28%) of those in the placebo group (relative risk 1.06, 95% CI 0.75-1.51). 24 (16%) patients in the probiotics group died, compared with nine (6%) in the placebo group (relative risk 2.53, 95% CI 1.22-5.25). Nine patients in the probiotics group developed bowel ischaemia (eight with fatal outcome), compared with none in the placebo group (p=0.004). INTERPRETATION: In patients with predicted severe acute pancreatitis, probiotic prophylaxis with this combination of probiotic strains did not reduce the risk of infectious complications and was associated with an increased risk of mortality. Probiotic prophylaxis should therefore not be administered in this category of patients.

Ruling out somatic bowel disease, such as inflammatory bowel disease (IBD), is an important goal in the management of abdominal complaints. Endoscopy is commonly used but is invasive and expensive. Mucosal inflammation in IBD can be detected through fecal biomarkers, though the present enzyme-linked immunoabsorbent assay (ELISA) tests require laboratory facilities. We validated the diagnostic performance of two new fecal rapid tests (FRTs) for the detection of calprotectin and lactoferrin and assessed their potential to differentiate IBD from irritable bowel syndrome (IBS).: The calprotectin and lactoferrin FRTs and ELISA tests were performed on the fecal samples of 114 patients referred for endoscopy, 80% of whom had IBS and 20% IBD, and validated against the endoscopic diagnosis.: The sensitivity and negative predictive value of the calprotectin FRT were both 100%, whereas they were 78% and 95%, respectively, for the lactoferrin FRT. The specificity and positive predictive value were slightly higher for the lactoferrin FRT. Both FRTs had similar diagnostic accuracy as the corresponding ELISA tests.: The calprotectin and lactoferrin rapid tests are as good as the ELISA tests in detecting colonic inflammation. Given their simple use, FRTs can support the non-invasive exclusion of IBD, notably in primary care.Clin Chem Lab Med 2008;46:1275–80.

Item does not contain fulltext BACKGROUND: Higher circulating insulin-like growth factor I (IGF-I) concentrations have been related to a greater risk of cancer. Lycopene intake is inversely associated with cancer risk, and experimental studies have shown that it may affect the IGF system, possibly through an effect on IGF-binding proteins (IGFBPs). OBJECTIVE: The objective of our study was to investigate the effect of an 8-wk supplementation with tomato-derived lycopene (30 mg/d) on serum concentrations of total IGF-I, IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3. DESIGN: We conducted a randomized, placebo-controlled, double-blinded crossover study in 40 men and 31 postmenopausal women with a family history of colorectal cancer, a personal history of colorectal adenoma, or both. RESULTS: Lycopene supplementation significantly (P = 0.01) increased serum IGFBP-1 concentrations in women (median relative difference between serum IGFBP-1 concentrations after lycopene supplementation and after placebo, 21.7%). Serum IGFBP-2 concentrations were higher in both men and women after lycopene supplementation than after placebo, but to a lesser extent (mean relative difference 8.2%; 95% CI: 0.7%, 15.6% in men and 7.8%; 95% CI: -5.0%, 20.6% in women). Total IGF-I, IGF-II, and IGFBP-3 concentrations were not significantly altered by lycopene supplementation. CONCLUSIONS: This is the first study known to show that lycopene supplementation may increase circulating IGFBP-1 and IGFBP-2 concentrations. Because of high interindividual variations in IGFBP-1 and IGFBP-2 effects, these results should be confirmed in larger randomized intervention studies.

Methylation of the promoter region of tumor suppressor genes is increasingly recognized to play a role in cancer development through silencing of gene transcription. We examined the associations between dietary folate intake, MTHFR C677T genotype, and promoter methylation of six tumor suppressor and DNA repair genes. Patients with colorectal adenoma (n = 149) and controls (n = 286) with folate intake in the upper or lower tertile with the CC or TT genotype were selected from a case-control study. Methylation-specific PCRs were conducted on colorectal adenoma specimens. The percentages of promoter methylation ranged from 15.7% to 64.2%. In case-case comparisons, folate was inversely associated with promoter methylation, especially among TT homozygotes. Case-control comparisons suggested that folate was not associated with the occurrence of adenomas with promoter methylation, and increased the risk of unmethylated adenomas, especially in TT homozygotes. The interactions between folate and MTHFR genotype were most pronounced for O6-MGMT: compared with CC homozygotes with low folate intake, the adjusted odds ratios (95% confidence interval) of having a methylated O6-MGMT promoter were 3.39 (0.82-13.93) for TT homozygotes with low folate intake and 0.37 (0.11-1.29) for TT homozygotes with high folate intake (P interaction = 0.02); the odds ratios for the occurrence of adenomas without methylation were 0.57 (0.16-2.11) for TT homozygotes with low folate intake and 3.37 (1.17-9.68) for TT homozygotes with high folate intake (P interaction = 0.03). In conclusion, folate intake seems to be inversely associated with promoter methylation in colorectal adenomas in case-case comparisons, and was positively associated with the occurrence of adenomas without promoter methylation in case-control comparisons, especially for TT homozygotes. (Cancer Epidemiol Biomarkers Prev 2007;16(2):327–33)

Item does not contain fulltext Epidemiological studies show that increased insulin-like growth factor (IGF)-I concentrations are related to increased colorectal cancer risk. A reduced colorectal cancer risk has been associated with isoflavones, which might affect the IGF-system because of their weak estrogenic activity. We conducted a randomized, placebo-controlled, double-blind crossover study to investigate the effect of an 8-wk isolated isoflavone supplementation (84 mg/d) on serum concentrations of total IGF-I, free IGF-I, total IGF-II, IGF binding protein (BP)-1, IGFBP-2, and IGFBP-3. Additionally, we investigated whether IGF-system component differences were related to concentrations of the more potent estrogenic isoflavone metabolite, equol. Our study population consisted of 37 men with a family history of colorectal cancer or a personal history of colorectal adenomas. Isoflavone supplementation did not significantly affect serum total IGF-I concentrations (relative difference between serum total IGF-I concentrations after isoflavone supplementation and after placebo: -1.3%, 95% CI -8.6 to 6.0%). Neither free IGF-I, nor total IGF-II, IGFBP-1, IGFBP-2, or IGFBP-3 concentrations were significantly altered. Interestingly, the change in serum IGF-I concentrations after isoflavone supplementation was negatively associated with serum equol concentrations (r=-0.49, P=0.002). In conclusion, isolated isoflavones did not affect the circulating IGF-system in a male high-risk population for colorectal cancer. However, to our knowledge, this is the first study that suggests isoflavones might have an IGF-I lowering effect in equol producers only. This underlines the importance of taking into account equol status in future isoflavone intervention studies.

Contains fulltext : 59301.pdf (Publisher’s version ) (Closed access) OBJECTIVE: We studied the association between meat consumption and colorectal adenomas, and potential influence of genetic susceptibility to heterocyclic aromatic amines (HCAs) formed during meat cooking at high temperatures. METHODS: We studied HCA concentration in relation to preparation habits among 63 volunteers. Associations of meat consumption, meat preparation habits, and genetic susceptibility with colorectal adenoma risk were investigated among 431 adenoma cases and 433 polyp-free controls recruited at endoscopy. Participants completed a meat consumption and preparation questionnaire and provided blood for DNA isolation. Polymorphisms of N-acetyltransferases (NAT) 1 and 2, sulfotransferase (SULT) 1A1, and glutathione-S-transferases (GST) M1 and T1 were determined. RESULTS: HCAs were present in habitually prepared meat, although meat consumption (7 versus < 5x/week) did not increase the risk of colorectal adenomas (odds ratio (OR) 1.2, 95% confidence interval (CI) 0.8-1.9). Also, presumed unfavorable preparation habits (e.g., use of lid, preference for darkly browned meat) did not increase adenoma risk (OR 0.8 and 0.9, respectively). Only the combination of NAT2 slow acetylation and frequent meat consumption (> 5x/week) slightly increased adenoma risk (OR 1.6, 95% CI 1.1-2.3). CONCLUSIONS: In this Dutch population, unfavorable meat consumption and preparation habits did not increase colorectal adenoma risk, and these associations were not influenced by relevant genetic polymorphisms.