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Background: The liver is the most frequently injured solid intra-abdominal organ. The major cause of early death following severe liver trauma is exsanguination. Although perihepatic packing improves survival in severe liver trauma, this leaves parenchymal damage untreated, often resulting in post-traumatic biliary leakage and a subsequent rise in morbidity. The aim of this study was to analyze the incidence and treatment of biliary leakage following the operative management of liver trauma. Methods: Patients presenting between 2000 and 2009 to Erasmus University Medical Centre with traumatic liver injury were identified. Data from 125 patients were collected and analyzed. Sixty-eight (54 %) patients required operation. All consecutive patients with post-operative biliary complications were analyzed. Post-operative biliary complications were defined as biloma, biliary fistula, and bilhemia. Results: Ten (15 %) patients were diagnosed with post-operative biliary leakage following liver injury. Three patients with a biloma were treated with percutaneous drainage, without further intervention. Seven patients with significant biliary leakage were managed by endoscopic stenting of the common bile duct to decompress the internal biliary pressure. One patient had a relaparotomy and right hemihepatectomy to control biliary leakage and injury of the right hepatic duct. Conclusion: Biliary complications continue to occur frequently following damage control surgery for liver trauma. The majority of biliary complications can be managed without an operation. Endoscopic retrograde cholangiopancreatography (ERCP) and internal stenting represent a safe strategy to manage post-operative biliary leakage and bilhemia in patients following liver trauma. Minor biliary leakage should be managed by percutaneous drainage alone. [ABSTRACT FROM AUTHOR]

Objectives: Computed tomography (CT) colonography cost assumptions so far ranged from €346 to €594 per procedure, based on clinical CT reimbursement rates. The aim of our study was to estimate the costs in a screening situation. Methods: Data were collected within an invitational population-based CRC screening trial ( n = 2,920, age 50-75 years) with a dedicated CT-screening setting. Unit costs were calculated per action, per invitee and per participant (depending on adherence) and per individual with detected advanced neoplasia. Sensitivity analyses were performed, and alternative scenarios were considered. Results: Of the invitees, 47.2 % were reminded, 38.8 % scheduled for an intake, 37.2 % scheduled for CT colonography, 33.6 % underwent CT colonography and 1.1 % needed a re-examination. Lesions ≥10 mm were detected in 2.9 % of the invitees. Invitation costs were €5.57. Costs per CT colonography (intake to results) were €144.00. Extra costs of communication of positive results were €9.00. Average costs of invitational-based CT colonography screening were €56.97 per invitee, €169.40 per participant and €2,772.51 per individual with detected advanced neoplasia. Conclusions: Dutch costs of CT-screening were substantially lower than the cost assumptions that were used in published cost-effectiveness analyses on CT colonography screening. This finding indicates that previous cost-effectiveness analyses should be updated, at least for the Dutch situation. Key Points: • CT colonography screening costs have historically been based on (local) clinical reimbursement rates • Estimates ranged from €346-€594, based on abdominal and/or pelvic computed tomography • Average costs per participant within an invitational population-based screening program: €169.40 • Average CT colonography costs per individual with detected advanced neoplasia: €2,772.51 • Previous cost-effectiveness analyses should probably be updated [ABSTRACT FROM AUTHOR]

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is an invasive procedure that proves burdensome to patients. Nevertheless, very little data are available on patient tolerance of this procedure that may improve practice guidelines and could aid in decreasing the burden of ERCP. This study therefore investigated the burden of ERCP performed with the patient under conscious sedation. Methods: Consecutive patients receiving ERCP under conscious sedation between November 2007 and December 2008 at the University Medical Center Utrecht and Erasmus MC Rotterdam (The Netherlands) were asked to participate in this study. The patients completed questionnaires on demographics, medical history, burden of ERCP (mental health, discomfort, and pain), symptoms and the EuroQol-5D (EQ-5D), including the EQ-VAS (lower EQ-5D scores and higher EQ-VAS scores represent a better quality of life). The paired t-test, the Kruskal-Wallis test, Pearson correlation, and logistic regression were used to evaluate the results. Results: The questionnaire was returned by 149 (54%) of 276 eligible patients, 139 of whom completed the entire questionnaire (54% males; mean age, 60 ± 14 years). Throat ache ( p < 0.001) was the only symptom higher than baseline value 1 day after the ERCP. On day 1, about one-tenth of the patients experienced moderate to severe mental health problems, which were associated with a higher EQ-5D score before ERCP ( p = 0.01). Slightly fewer than half of the patients experienced pain and discomfort during and immediately after ERCP. More discomfort was experienced by patients who underwent therapeutic ERCP ( p < 0.05) and those with a higher EQ-5D score ( p < 0.001) or lower VAS ( p < 0.01). Pain was associated with younger age ( p < 0.01), higher EQ-5D score ( p < 0.001), and lower VAS ( p < 0.01). Conclusion: One-third to one-half of patients experience pain and discomfort during and immediately after ERCP when it is performed with conscious sedation for the patient. Other sedation strategies, such as the use of general anesthesia or propofol, may well reduce the burden of ERCP, particularly for patients with a higher EQ-5D score, younger age, or therapeutic ERCP treatment. However, randomized trials are warranted. [ABSTRACT FROM AUTHOR]

The treatment of choice of H. pylori infections is a 7-day triple-therapy with a proton pump inhibitor (PPI) plus amoxicillin and either clarithromycin or metronidazole, depending on local antibiotic resistance rates. The data on efficacy of eradication therapy in a group of rheumatology patients on long-term NSAID therapy are reported here. This study was part of a nationwide, multicenter RCT that took place in 2000-2002 in the Netherlands. Patients who tested positive for H. pylori IgG antibodies were included and randomly assigned to either eradication PPI-triple therapy or placebo. After completion, follow-up at 3 months was done by endoscopy and biopsies were sent for culture and histology. In the eradication group 13% (20/152, 95% CI 9-20%) and in the placebo group 79% (123/155, 95% CI 72-85%) of the patients were H. pylori positive by histology or culture. H. pylori was successfully eradicated in 91% of the patients who were fully compliant to therapy, compared to 50% of those who were not (difference of 41%; 95% CI 18-63%). Resistance percentages found in isolates of the placebo group were: 4% to clarithromycin, 19% to metronidazole, 1% to amoxicillin and 2% to tetracycline. [ABSTRACT FROM AUTHOR]

Over the 15-year period 1989–2003, the incidence of oesophagus–cardia adenocarcinoma in the Netherlands rose annually by 2.6% for males and 1.2% for females. This was the net outcome of annual increases in the incidence of adenocarcinoma of the oesophagus (ACO) of 7.2% for males and 3.5% for females and annual declines in the incidence of adenocarcinoma of the gastric cardia (AGC) of more than 1% for both genders. Nonlinear cohort patterns were found in females with ACO and for both genders in AGC; a nonlinear period pattern was observed only in males with AGC. These differing epidemiological patterns for ACO and AGC do not support a common aetiology. Proposed underlying factors for the rise in ACO incidence appear to have little effect on AGC incidence. This and the secular decline in smoking among males may have led to the decline in AGC incidence.British Journal of Cancer (2007) 96, 1767–1771. doi:10.1038/sj.bjc.6603798 www.bjcancer.com Published online 15 May 2007 [ABSTRACT FROM AUTHOR]

In the United States (USA), a correlation has been demonstrated between socio-economic status (SES) of patients on the one hand, and tumour histology, stage of the disease and treatment modality of various cancer types on the other hand. It is unknown whether such correlations are also involved in patients with oesophageal cancer in The Netherlands. Between 1994 and 2003, 888 oesophageal cancer patients were included in a prospective database with findings on the diagnostic work-up and treatment of oesophageal cancer. Socio-economic status of patients was defined as the average net yearly income. Linear-by-linear association testing revealed that oesophageal adenocarcinoma was more frequently observed in patients with higher SES and squamous cell carcinoma in patients with lower SES (P=0.02). Multivariable logistic regression analysis showed no correlation between SES and staging procedures and preoperative TNM stage. The adjusted odds ratio (OR) for stent placement was 0.82 (95% CI 0.71-0.95), indicating that with an increase in SES by 1200 [euro], the likelihood that a stent was placed declined by 18%. Patients with a higher SES more frequently underwent resection or were treated with chemotherapy (OR: 1.15; 95% CI 1.01-1.32 and OR: 1.16; 95% CI 1.02-1.32, respectively). Socio-economic factors are involved in oesophageal cancer in The Netherlands, as patients with a higher SES are more likely to have an adenocarcinoma and patients with a lower SES a squamous cell carcinoma. Moreover, the correlations between SES and different treatment modalities suggest that both patient and doctor determinants contribute to the decision on the most optimal treatment modality in patients with oesophageal cancer. [ABSTRACT FROM AUTHOR]

Background Proton pump inhibitors are widely used, but little is known about the usage pattern in different indications. Aim To analyse proton pump inhibitor usage patterns in the general population. Methods A cohort of 16 311 incident proton pump inhibitor users was identified in the Integrated Primary Care Information database, a Dutch general practice research database. Persistence and adherence were calculated by indication. Risk factors were identified by logistic regression analysis. Results One-year persistence was 31% in patients using proton pump inhibitors for gastro-oesophageal reflux. Persistence was higher in oesophagitis grade A/B (54%), grade C/D (73%) and Barrett's oesophagus (72%), compared to patients with only reflux symptoms (27%). Approximately 25% of patients with non-reflux dyspepsia or Helicobacter pylori-associated indications used proton pump inhibitors for more than 6 months. Half of all patients used proton pump inhibitors <80% of time indicating intermittent use, which was independent of indication. Exception were patients with Barrett's oesophagus, who were most adherent. Conclusions A substantial proportion of patients with indications not requiring long-term treatment use proton pump inhibitors for an extended period. Half of the patients used proton pump inhibitors on-demand or intermittently. Such usage pattern is probably sufficient for most patients, but may be inadequate if proton pump inhibitors are used for serious diseases, such as severe oesophagitis or Barrett's oesophagus. [ABSTRACT FROM AUTHOR]

Background Despite reports of decreasing hospitalizations and mortality due to peptic ulcer, it is unclear whether the incidence has truly declined over time. Aim To investigate time trends in the incidence of and in hospital admission rates for peptic ulcer in the Netherlands. Methods The nationwide registry of pathology reports (PALGA) and the national registry of hospital admissions ( Landelijke Medische Registratie) were used. Standardized morbidity ratios were calculated to assess the magnitude of the changes. Results The age-adjusted incidence of gastric ulcer halved for both men (standardized morbidity ratio 0.48; CI 0.46–0.49) and women (standardized morbidity ratio 0.49; CI 0.47–0.51). Although the number of gastric biopsies obtained at endoscopy increased, the proportion with a diagnosis of peptic ulcer decreased by more than 50% (standardized morbidity ratio 0.47; CI 0.46–0.49). The admission rate for peptic ulcer more than halved between 1980 and 2003. In contrast, admission rates for complicated ulcers barely changed and slightly increased among women. Conclusions The incidence of histopathologically confirmed gastric ulcer halved between 1992 and 2003 in the Netherlands. As the number of gastric biopsies increased in this period, a true decrease is likely. Hospital admissions for peptic ulcer declined dramatically between 1980 and 2003, but remained unchanged or slightly increased for complicated ulcers. [ABSTRACT FROM AUTHOR]

Successful treatment of Helicobacter pylori infection is becoming compromised by emerging resistance. We report the prevalence rates of H. pylori resistance to metronidazole, clarithromycin, amoxycillin, tetracycline and trovafloxacin in The Netherlands. A total of 231 H. pylori clinical isolates were collected throughout the country over a period of 6 months during 1997-1998. The MICs of the above-mentioned antibiotics were determined in a single laboratory. The overall percentage of resistance for clarithromycin and metronidazole was 1.7% and 21.2%, respectively. None of the strains was resistant to amoxycillin or tetracycline. The primary resistance rate of trovafloxacin was as high as 4.7%. Since trovafloxacin has not yet been introduced on to the Dutch market, the resistance is probably induced by the use of other quinolones. Our data indicate that treatment outcome would benefit from susceptibility testing before starting therapy, especially when prescribing metronidazole. [ABSTRACT FROM PUBLISHER]

Objectives: The prevalence of Helicobacter pylori infection varies in the Netherlands from 5% in children to about 50% in the elderly. In the institutionalized intellectually disabled, a high prevalence of infection has been reported. It is unknown whether there are specific risk factors to obtain H. pylori infection in this population, and whether employees of such institutes are at risk for H. pylori infection. Methods: Therefore, we analyzed the seroprevalence of H. pylori antibodies by ELISA among 338 intellectually disabled inhabitants and 254 employees of two institutes. H. pylori-positive patients were compared with H. pylori-negative controls. The intellectually disabled and the employees were evaluated for possible risk factors. Results: Of the 338 intellectually disabled, 280 (82.8%, median age 51 yr) were infected with H. pylori. This rate is significantly higher than the prevalence of H. pylori in the Dutch population. The presence of H. pylori was significantly associated with male gender, longer duration of institutionalization, an IQ < 50, rumination, and a history of upper abdominal symptoms. Of the 254 employees, 69 (27.2%) were infected, which is equal to the rate for the total Dutch population. The presence of H. pylori infection among employees was, however, significantly associated with a higher level of physical contact with the intellectually disabled, longer duration of employment, and having upper abdominal symptoms. Conclusions: Intellectually disabled persons are at high risk of developing H. pylori infection. Employees with close physical contact to the intellectually disabled population for a considerable period of time are also at increased risk. H. pylori infection should he considered a job attributable risk in this profession. [ABSTRACT FROM AUTHOR]

Aim: Suboptimal self-management with controller inhalation therapy in asthma and COPD is frequently observed with poor treatment outcomes. The developed 'Respiratory Adherence Care Enhancer' (RACE) instrument identifies and addresses individual barriers to self-management with a theoretical underpinning. This study investigates the feasibility of pharmaceutical support with this instrument., Methods: An implementation trial was conducted with asthma and COPD patients in 5 community pharmacies in the Netherlands. Patients were allocated to standard care or add-on support with the RACE instrument. Patients were invited to complete the RACE questionnaire at baseline, 5-week and 10-week follow-up. Barrier profiles were accessible for the intervention group with subsequent consultations at baseline and 5-weeks. Experiences were collected from patients and consultants with a questionnaire and reported findings. Primary endpoints focused on the acceptability, practicality and implementation process. Secondary endpoints included between-group differences in barrier and disease control outcomes from baseline at 10-weeks follow-up., Results: In total, 84 patients were included; 48 were assigned to intervention and 36 to standard care. Patient satisfaction of support with the RACE instrument was high (71%). Patients felt motivated, reassured and more confident about their disease management. Consultants reported an increase in awareness of patient barriers. Patient recognition of barrier profiles was 83.9% (±12.9%). The barrier inhaler techniques decreased significantly for the intervention group at follow-up with odds ratio 0.30 (95% confidence interval, 0.10-0.91). No significant differences were observed for changes in number of barriers and disease control., Conclusion: Self-management support with the RACE instrument is feasible and appreciated, facilitating behaviour change with patient-centred pharmaceutical care in asthma and COPD., (© 2024 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Objective: To evaluate the impact of the COVID-19 pandemic on the outcome of major trauma patients in the Netherlands., Summary Background Data: Major trauma patients highly rely on immediate access to specialized services, including ICUs, shortages caused by the impact of the COVID-19 pandemic may influence their outcome., Methods: A multi-center observational cohort study, based on the Dutch National Trauma Registry was performed. Characteristics, resource usage, and outcome of major trauma patients (injury severity score ≥16) treated at all trauma-receiving hospitals during the first COVID-19 peak (March 23 through May 10) were compared with those treated from the same period in 2018 and 2019 (reference period)., Results: During the peak period, 520 major trauma patients were admitted, versus 570 on average in the pre-COVID-19 years. Significantly fewer patients were admitted to ICU facilities during the peak than during the reference period (49.6% vs 55.8%; P=0.016). Patients with less severe traumatic brain injuries in particular were less often admitted to the ICU during the peak (40.5% vs 52.5%; P=0.005). Moreover, this subgroup showed an increased mortality compared to the reference period (13.5% vs 7.7%; P=0.044). These results were confirmed using multivariable logistic regression analyses. In addition, a significant increase in observed versus predicted mortality was recorded for patients who had a priori predicted mortality of 50% to 75% (P=0.012)., Conclusions: The COVID-19 peak had an adverse effect on trauma care as major trauma patients were less often admitted to ICU and specifically those with minor through moderate brain injury had higher mortality rates., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Autophagy is a cellular degradation mechanism, which is triggered by the bacterium Helicobacter pylori . A single nucleotide polymorphism (SNP) in the autophagy gene ATG16L1 (rs2241880, G-allele) has been shown to dysregulate autophagy and increase intestinal endoplasmic reticulum (ER) stress. Here, we investigate the role of this SNP in H. pylori -mediated gastric carcinogenesis and its molecular pathways. ATG16L1 rs2241880 was genotyped in subjects from different ethnic cohorts (Dutch and Australian) presenting with gastric (pre)malignant lesions of various severity. Expression of GRP78 (a marker for ER stress) was assessed in gastric tissues. The effect of ATG16L1 rs2241880 on H. pylori -mediated ER stress and pro-inflammatory cytokine induction was investigated in organoids and CRISPR/Cas9 modified cell lines. Development of gastric cancer was associated with the ATG16L1 rs2241880 G-allele. Intestinal metaplastic cells in gastric tissue of patients showed increased levels of ER-stress. In vitro models showed that H. pylori increases autophagy while reducing ER stress, which appeared partly mediated by the ATG16L1 rs2241880 genotype. H. pylori -induced IL-8 production was increased while TNF-α production was decreased, in cells homozygous for the G-allele. The ATG16L1 rs2241880 G-allele is associated with progression of gastric premalignant lesions and cancer. Modulation of H. pylori -induced ER stress pathways and pro-inflammatory mediators by ATG16L1 rs2441880 may underlie this increased risk.

Objectives: The aim of this study was to explore pharmacists' barriers and facilitators regarding participation in pharmacy practice research., Methods: We conducted an online cross-sectional survey in 1974 community pharmacies in the Netherlands., Key Findings: A total of 252 pharmacists completed the questionnaire. The majority agreed that participation in research should be part of daily practice. Efficient time investment and a clear benefit for general professional knowledge, patient care and pharmacy organisation were the most important facilitating factors., Conclusions: To encourage pharmacists' participation, researchers should offer clear instructions, possibilities for flexible time management, simple patient inclusion, task delegation and no additional contacts with healthcare professionals due to the research., (© 2019 The Authors. International Journal of Pharmacy Practice published by John Wiley & Sons Ltd on behalf of Royal Pharmaceutical Society.)

Pharmaceutical care guidelines aim to provide recommendations for pharmaceutical care, reduce unwanted pharmacy practice variation and ultimately improve the quality of healthcare. This study evaluated community pharmacists' adherence to recommendations for the provision of care to asthma patients with first dispensing and follow-up refill encounters in The Netherlands. Data were pharmacists' self-assessment of adherence to guideline recommendations, independent observations of dispensing encounters and a nationwide questionnaire on pharmacists' views on the desirable (clinical) necessity of applying guideline recommendations to their patient population. The 21 pharmacists who performed self-assessment judged their adherence concerning inhalation instructions as high. The lowest scores were reported for recommendations to collect additional information on the type of lung disease and for asking patients' expectations, wishes and concerns. Sixty-eight dispensing encounters were observed. In 83% of the 35 first dispensing observations, inhalation instruction was provided. This percentage was lower (62%) at refill dispensings. During all encounters, pharmacy staff seldom explored patients' perceptions or responded to patients' expectations, wishes and concerns. One hundred and four pharmacists completed the feasibility questionnaire. Pharmacists judged that all patients should receive inhalation instruction at first dispensing. They regarded it necessary to check on patients' expectations, wishes and concerns regarding the treatment for only up to 70% of the patients. More efforts on guideline implementation are needed, especially on follow-up dispensings and on gaining relevant information from patients and other healthcare professionals. Pharmacists still have opportunities to grow in applying a patient-tailored approach and exploring patients' individual needs, rather than providing practical information.

Background: Helicobacter pylori prevalence in Western countries has been declining simultaneously with increases in childhood asthma and allergic diseases; prior studies have linked these phenomena., Aims: To examine the association between H. pylori colonisation in children and risk of asthma and related conditions at school age. We secondly examined additional effects of maternal H. pylori status by pairing with children's status., Methods: This study was embedded in a multi-ethnic population-based cohort in Rotterdam, The Netherlands. We measured anti-H. pylori and anti-CagA antibodies in serum of children obtained at age 6 years, and of their mothers obtained during midpregnancy. Asthma or related conditions were reported for children at age 6 years. We used multivariate logistic regression analyses among 3797 subjects., Results: In children, the H. pylori positivity rate was 8.7%, and 29.2% of these were CagA-positive. A child's colonisation with a CagA-negative-H. pylori strain was associated with an increased risk of asthma (Odds ratio 2.11; 95% CI 1.23-3.60), but this differed for European (3.64; 1.97-6.73) and non-European (0.52; 0.14-1.89) children. When taking into account maternal H. pylori status, only H. pylori-positive children with an H. pylori-negative mother had increased risk of asthma (2.42; 1.11-5.27), accounting for 3.4% of the asthma risk., Conclusions: Colonisation of a European child with a CagA-negative-H. pylori strain at age 6 was associated with an increased prevalence of asthma, but there was no association for non-European children. The underlying mechanisms for the observed risk differences require further research., (© 2016 John Wiley & Sons Ltd.)

Background and Study Aims: The assessment of indications for follow-up colonoscopy may help to improve the allocation of available endoscopy resources. The aim of this study was to assess the timing of early follow-up colonoscopy and surveillance utilization in relation to adenoma detection rate (ADR) at follow-up., Methods: An assessment of the timing and yield of follow-up colonoscopies was performed in patients with non-inflammatory bowel disease (IBD) in a Dutch multicenter study. The primary outcome was the number of patients with a prior (index) colonoscopy. The necessity for follow-up procedures was assessed using the ADR., Results: Of 4800 consecutive patients undergoing a colonoscopy, 1249 non-IBD patients had undergone an index colonoscopy. Of these, follow-up procedures were performed within 1 year in 27 % (331/1249). Excluding incomplete colonoscopy, incomplete polypectomy, or poor bowel preparation on index, the ADR on early follow-up was 4 % for symptomatic and 26 % for asymptomatic patients. Among the asymptomatic patients with a follow-up colonoscopy at > 1 year (n = 463), an ADR of 23 % (108/463) was found. In 27 % of these patients, the observed surveillance intervals were in accordance with American Gastroenterological Association (AGA) surveillance recommendations; 60 % were classified as over-utilization and 13 % as under-utilization according to the AGA. Optimal utilization follow-up colonoscopies had higher ADRs on follow-up compared with over-utilized procedures (31 % vs. 17 %; P < 0.001)., Conclusions: Follow-up colonoscopy in symptomatic patients within a year has limited value in terms of adenoma detection. A considerable proportion of surveillance colonoscopies are performed too early according to current guidelines, resulting in low detection rates. Both aspects can be targeted for optimal usage in endoscopic capacity., (© Georg Thieme Verlag KG Stuttgart · New York.)

Importance: Helicobacter pylori is a major cause of gastritis and gastroduodenal ulcer disease and can cause cancer. H. pylori prevalence is as high as 90% in some developing countries but 10% of a given population is never colonized, regardless of exposure. Genetic factors are hypothesized to confer H. pylori susceptibility., Objective: To identify genetic loci associated with H. pylori seroprevalence in 2 independent population-based cohorts and to determine their putative pathophysiological role by whole-blood RNA gene expression profiling., Design, Setting, and Participants: Two independent genome-wide association studies (GWASs) and a subsequent meta-analysis were conducted for anti-H. pylori IgG serology in the Study of Health in Pomerania (SHIP) (recruitment, 1997-2001 [n = 3830]) as well as the Rotterdam Study (RS-I) (recruitment, 1990-1993) and RS-II (recruitment, 2000-2001 [n = 7108]) populations. Whole-blood RNA gene expression profiles were analyzed in RS-III (recruitment, 2006-2008 [n = 762]) and SHIP-TREND (recruitment, 2008-2012 [n = 991]), and fecal H. pylori antigen in SHIP-TREND (n = 961)., Main Outcomes and Measures: H. pylori seroprevalence., Results: Of 10,938 participants, 6160 (56.3%) were seropositive for H. pylori. GWASs identified the toll-like receptor (TLR) locus (4p14; top-ranked single-nucleotide polymorphism (SNP), rs10004195; P = 1.4 × 10(-18); odds ratio, 0.70 [95% CI, 0.65 to 0.76]) and the FCGR2A locus (1q23.3; top-ranked SNP, rs368433; P = 2.1 × 10(-8); odds ratio, 0.73 [95% CI, 0.65 to 0.81]) as associated with H. pylori seroprevalence. Among the 3 TLR genes at 4p14, only TLR1 was differentially expressed per copy number of the minor rs10004195-A allele (β = -0.23 [95% CI, -0.34 to -0.11]; P = 2.1 × 10(-4)). Individuals with high fecal H. pylori antigen titers (optical density >1) also exhibited the highest 25% of TLR1 expression levels (P = .01 by χ2 test). Furthermore, TLR1 exhibited an Asn248Ser substitution in the extracellular domain strongly linked to the rs10004195 SNP., Conclusions and Relevance: GWAS meta-analysis identified an association between TLR1 and H. pylori seroprevalence, a finding that requires replication in nonwhite populations. If confirmed, genetic variations in TLR1 may help explain some of the observed variation in individual risk for H. pylori infection.

Background: Data on clinical characteristics of patients with inflammatory bowel disease (IBD)-related colorectal cancer (CRC) are scarce and mainly originate from tertiary referral centres. We studied patient and disease characteristics of IBD-related CRC in a nationwide IBD cohort in general hospitals. Main outcome parameters were time to develop CRC, and factors associated with early CRC development., Methods: All IBD patients diagnosed with CRC between 1 January 1990 and 1 July 2006 were identified using a nationwide automated pathology database (PALGA). Patient charts were assessed to confirm diagnosis and collect clinical data. Early CRC was defined as CRC diagnosed less than 8 years after IBD diagnosis. Statistical analysis was performed using descriptive statistics, independent t tests, binary logistic regression and Cox-regression analysis., Results: Diagnosis of IBD-related CRC was confirmed in 251 patients (171 ulcerative colitis, 77 Crohn's disease, 3 unclassified colitis), 161 males (64 %). Median time from IBD diagnosis to CRC diagnosis was 12 years (IQR 4-20); 89 patients (35 %) developed early CRC. Type of IBD, gender, concomitant PSC, pseudopolyps, extent of inflammation, and medication use were not related to early CRC (p > 0.05). IBD diagnosis at older age (HR for 10 years older age 2.25; 95 % CI 1.92-2.63) was related to early CRC. Twenty-three patients (12 %) had been included in a surveillance programme prior to CRC diagnosis. Patients in the surveillance group had a significantly better tumor stage (p = 0.004)., Conclusions: We emphasize the problem of a high proportion of IBD-associated CRCs developing before the recommended start of surveillance. Therefore, we suggest that older age at IBD onset could be an additional factor to start surveillance in IBD patients.

Background and Study Aims: Colonoscopy is increasingly performed by nurse endoscopists. We aimed to assess the endoscopic quality and patient experience of these procedures., Patients and Methods: This prospective multicenter study analyzed 100 consecutive colonoscopies each for 10 trained nurse endoscopists with respect to endoscopic quality and patient experience. Colonoscopies were performed under the supervision of a gastroenterologist, using the techniques and protocols of the participating hospitals. Patient experience was assessed using a questionnaire., Results: Most nurse endoscopists were female (90 %; median age 43 [range 35 - 49]). Before the start of the study, they had performed a median of 528 colonoscopies (range 208 - 2103). For the 1000 patients, mean age was 56 ± 15 years; 55 % were women; and 96 % were in class I or II according to the American Society of Anesthesiologists' physical status classification system. Colonoscopies were performed for screening or surveillance in 42 %; for symptomatic indications in 58 % of patients. The unassisted cecal intubation rate was 94 %; the mean withdrawal time was 10 ± 5 minutes. The adenoma detection rate was 26.7 %. In 229 of the colonoscopies (23 %), the nurse endoscopists required assistance from the supervising gastroenterologist. The complication rate was 0.2 %: one perforation and one cardiopulmonary complication. The questionnaire was completed by 734 /1000 patients (73 %) and of these 694 /734 (95 %) were satisfied with the endoscopic procedure. Among the respondents 530 /734 (72 %) had no specific preference for a physician or nurse endoscopist, whereas 113 /734 (15 %) preferred a physician endoscopist, and 91 /734 (12 %) preferred a nurse endoscopist., Conclusion: The nurse endoscopists performed colonoscopies according to the internationally recognized quality standards and with high patient satisfaction., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: Fecal immunochemical testing (FIT) is increasingly used for colorectal cancer (CRC) screening. We aimed to estimate its diagnostic accuracy in invitational population screening measured against colonoscopy., Methods: Participants (50-75 years) in an invitational primary colonoscopy screening program were asked to complete one sample FIT before colonoscopy. We estimated FIT sensitivity, specificity, and predictive values in detecting CRC and advanced neoplasia (carcinomas and advanced adenomas) for cutoff levels of 50 (FIT50), 75 (FIT75), and 100 (FIT100) ng hemoglobin (Hb)/ml, corresponding with, respectively, 10, 15 and 20 μg Hb/g feces., Results: A total of 1,256 participants underwent a FIT and screening colonoscopy. Advanced neoplasia was detected by colonoscopy in 119 (9%), 8 (0.6%) of them had CRC. At FIT50, 121 (10%) had a positive test result; 45 (37%) had advanced neoplasia and 7 (6%) had CRC. A total of 74 of 1,135 FIT50 negatives (7%) had advanced neoplasia including 1 (0.1%) CRC. FIT50 had a sensitivity of 38% (95% confidence interval (CI): 29-47) for advanced neoplasia and 88% (95% CI: 37-99) for CRC at a specificity of 93% (95% CI: 92-95) and 91% (95% CI: 89-92), respectively. The positive and negative predictive values for FIT50 were 6% (95% CI: 3-12) and almost 100% (95% CI: 99-100) for CRC, and 37% (95% CI: 29-46) and 93% (95% CI: 92-95) for advanced neoplasia. The sensitivity and specificity of FIT75 for advanced neoplasia were 33% (95% CI: 25-42) and 96% (95% CI: 94-97). At FIT100, 71 screenees (6%) had a positive test result. The sensitivity and specificity of FIT100 were for advanced neoplasia 31% (95% CI: 23-40) and 97% (95% CI: 96-98), and for CRC 75% (95% CI: 36-96) and 95% (95% CI: 93-96). The area under curve for detecting advanced neoplasia was 0.70 (95% CI: 0.64-0.76). FIT had a similar sensitivity for proximal and distal advanced neoplasia at cutoffs of 50 (38% vs. 37%; P=0.99), 75 (33% vs. 31%; P=0.85) and 100 (33% vs. 29%; P=0.68) ng Hb/ml., Discussion: Nine out of ten screening participants with CRC and four out of ten with advanced neoplasia will be detected using one single FIT at low cutoff. Sensitivity in detecting proximal and distal advanced neoplasia is comparable.

Introduction: The Global Rating Scale (GRS) is a quality assurance program that was developed in England to assess patient-centered care in endoscopy. The aim of the current study was to evaluate patient experiences of colonoscopy using the GRS in order to compare different departments and to provide benchmarks. The study also evaluated factors associated with patient satisfaction., Methods: A GRS questionnaire was used both before and after the procedure in outpatients undergoing colonoscopy. The questionnaire assessed the processes associated with the colonoscopy, from making the appointment up until discharge. Mean values and ranges of 12 endoscopy departments were calculated together with P values in order to assess heterogeneity., Results: In total, 1904 pre-procedure and 1532 (80 %) post-procedure questionnaires were returned from 12 endoscopy departments. The mean time patients had to wait for their procedure was 4.3 weeks (range 3.1 - 5.8 weeks), and 54 % (range 35 - 64 %; P < 0.001) reported being given a choice of appointment dates/times. Discomfort during colonoscopy was reported by 20 % (range 8 - 40 %; P < 0.001). Recovery room privacy was satisfactory for 76 % of patients (range 66 - 90 %; P < 0.05). The majority of patients reported being sufficiently informed about what to do in case of problems after discharge (79 %, range 43 - 98 %; P < 0.001), and 85 % of individuals stated that they would be willing to repeat the colonoscopy procedure (range 72 - 92 %; P < 0.001). Factors associated with a decreased willingness to return were the burdensome bowel preparation (odds ratio [OR] = 0.25; P < 0.001), "rushing staff" attitude (OR = 0.57; P < 0.05), low acceptance of the procedure (OR = 0.42; P < 0.01), and more discomfort than expected (OR = 0.54; P < 0.05)., Conclusion: Overall patient experiences with colonoscopy were satisfactory, but they also showed considerable variation. This study shows that use of a GRS patient questionnaire is feasible in the Dutch endoscopy setting for the assessment of patient experience. The significant variability between endoscopy units can be used to benchmark services and enable shortcomings to be identified., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objectives: The standard approach to benign esophageal perforations consists of conservative treatment or surgery. In this study, we investigated the efficacy of short-term stent placement for nonmalignant esophageal perforations., Methods: This is a prospective single-center study of patients with benign esophageal perforations in whom a removable self-expandable stent was placed. Data were collected from a prospective database, endoscopy records, and operation reports. To obtain follow-up data, we contacted the patients, their relatives, or their general practitioner., Results: A total of 33 patients underwent stent insertion owing to an iatrogenic perforation (n=19), Boerhaave's syndrome (n=10), or other causes (n=4); this resulted in an immediate and complete sealing of the lesion in 32 patients (97%). Stents migrated in 11 patients (33%). Four patients required an esophageal resection for failed stent therapy (n=3) and failed stent removal (n=1). The 90-day mortality rate was 15%. A total of 33 endoscopic stent extractions were attempted. Overall, 23 stents were extracted within 6 weeks (group I) and 10 stents between 6 and 84 weeks (group II). Extractions were uncomplicated in all patients in group I (100%) vs. in 5 patients in group II (50%) (P=0.001). Six extraction-related complications occurred in group II, including two self-limiting bleedings, three stent fractures, and one impacted stent., Conclusions: In patients with a benign esophageal perforation, temporary stent therapy is effective and provides a good alternative to surgery. Complications due to stent removal can be prevented by removal of the prosthesis within 6 weeks after insertion, without compromising the efficacy of treatment.

Background: Perceived burden of colorectal cancer (CRC) screening is an important determinant of participation in subsequent screening rounds and therefore crucial for the effectiveness of a screening programme. This study determined differences in perceived burden and willingness to return for a second screening round among participants of a randomised population-based trial comparing a guaiac-based faecal occult blood test (gFOBT), a faecal immunochemical test (FIT) and flexible sigmoidoscopy (FS) screening., Methods: A representative sample of the Dutch population (aged 50-74years) was randomised to be invited for gFOBT, FIT and FS screening. A random sample of participants of each group was asked to complete a questionnaire about test burden and willingness to return for CRC screening., Results: In total 402/481 (84%) gFOBT, 530/659 (80%) FIT and 852/1124 (76%) FS screenees returned the questionnaire. The test was reported as burdensome by 2.5% of gFOBT, 1.4% of FIT and 12.9% of FS screenees (comparing gFOBT versus FIT p=0.05; versus FS p<0.001). In total 94.1% of gFOBT, 94.0% of FIT and 83.8% of FS screenees were willing to attend successive screening rounds (comparing gFOBT versus FIT p=0.84; versus FS p<0.001). Women reported more burden during FS screening than men (18.2% versus 7.7%; p<0.001)., Conclusions: FIT slightly outperforms gFOBT with a lower level of reported discomfort and overall burden. Both FOBTs are better accepted than FS screening. All three tests have a high level of acceptance, which may affect uptake of subsequent screening rounds and should be taken into consideration before implementing a CRC screening programme., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Background and Study Aim: Double-balloon enteroscopy (DBE) has proven to be a relatively safe method for small-bowel evaluation, with a complication rate of 1 %. The main concern after diagnostic DBE is acute pancreatitis. Single-balloon enteroscopy (SBE) has emerged as a viable alternative to DBE. Until now, no incidence of pancreatitis has been reported for SBE. The aims were to evaluate complication rate and occurrence of hyperamylasemia and to identify the risk factors for hyperamylasemia after SBE., Patients and Methods: Prospectively, consecutive patients undergoing peroral ("proximal") or combined approach SBE were included. Complications were assessed at 1 and 30 days afterwards. Serum amylase and C-reactive protein (CRP) were assessed immediately before and 2 - 3 hours after SBE., Results: 166 SBE procedures were performed in 105 patients (53-male; mean age 51 years, range 9 - 87). The indications for SBE were: anemia (n = 55), Crohn's disease (n = 31) and abdominal complaints suspicious for inflammatory bowel disease (n = 5), Peutz-Jeghers syndrome (n = 1) and other (n = 13). Therapeutic interventions were performed during 21 procedures (13 %). One perforation (1 / 21 therapeutic interventions, 4.8 %) occurred after dilation of a benign stricture. While 13 patients (16 %) had post-SBE hyperamylasemia, none had complaints suggesting acute pancreatitis. Factors such as sex, indication, procedure duration, number of passes, route of SBE, findings, and/or treatment showed no significant correlation with presence of hyperamylasemia., Conclusions: SBE appears to be a safe diagnostic endoscopic procedure. The incidence of hyperamylasemia and pancreatitis after peroral SBE seems comparable to that after DBE., (Georg Thieme Verlag KG Stuttgart.New York.)

Introduction: In many countries uptake of colorectal cancer (CRC) screening remains low., Aim: To assess how procedural characteristics of CRC screening programmes determine preferences for participation and how individuals weigh these against the perceived benefits from participation in CRC screening., Methods: A discrete choice experiment was conducted among subjects in the age group of 50-75 years, including both screening-naïve subjects and participants of a CRC screening programme. Subjects were asked on their preferences for aspects of CRC screening programmes using scenarios based on pain, risk of complications, screening location, preparation, duration of procedure, screening interval and risk reduction of CRC-related death., Results: The response was 31% (156/500) for screening-naïve and 57% (124/210) for CRC screening participants. All aspects proved to significantly influence the respondents' preferences. For both groups combined, respondents required an additional relative risk reduction of CRC-related death by a screening programme of 1% for every additional 10 min of duration, 5% in order to expose themselves to a small risk of complications, 10% to accept mild pain, 10% to undergo preparation with an enema, 12% to use 0.75l of oral preparation combined with 12h fasting and 32% to use an extensive bowel preparation. Screening intervals shorter than 10 years were significantly preferred to a 10-year screening interval., Conclusion: This study shows that especially type of bowel preparation, risk reduction of CRC related death and length of screening interval influence CRC screening preferences. Furthermore, improving awareness on CRC mortality reduction by CRC screening may increase uptake.

Background: Adherence is important for successful treatment in inflammatory bowel disease (IBD) patients. Previous studies demonstrated high prevalence of non-adherence., Aim: To assess IBD-patients' perceptions of therapy adherence and disease-related functional status in members of the Dutch patients' association of Crohn's disease and ulcerative colitis (CCUVN)., Methods: Inflammatory bowel disease-patients completed anonymously a survey at the website of the CCUVN. Statistical analysis was performed using principal component analysis, univariate and multivariate logistic regression., Results: The questionnaire was completed by 1067 patients [617 (58%) Crohn's disease (CD) and 450 (42%) ulcerative colitis (UC)]. Mean age was 43 years (s.d. 13.7); women (66%). Of 920 patients currently using medication, 797 (87%) were adherent. Of the patients using 5-ASA, 91% were adherent (527/582), vs. 96% using corticosteroids (316/330) and 97% (414/425) using immunosuppressives. CD patients (OR 1.54; 95% CI 1.05-2.27), patients with duration of disease

Background and Study Aims: Gastrointestinal endoscopy investigations are frequently requested by gastroenterologists, general practitioners and other physicians. In addition to the classic methods of report writing, several electronic endoscopic report systems are currently available. The aim of the study was to evaluate the costs of three different ways of producing reports; by hand, by dictation, or by computer., Methods: Three methods of report writing were compared, with special attention to costs. The endoscopy process was analyzed, from arrival of the patient to sending the report to the referring doctor, and including production of endoscopic images or video, logging of used endoscopes and their disinfection, and storage costs for endoscopy data., Results: During the first 5 years, the mean costs per procedure were Euro 4.78 for handwritten, Euro 6.39 for dictated and Euro 8.90 for computerized reports. Due to depreciation, after this initial period, the respective costs declined to Euro 4.37, Euro 5.20 and Euro 5.13, respectively. Despite high initial costs, a cost-benefit analysis already revealed a financial benefit from a computerized system after 3 years., Conclusions: The electronic production of an endoscopic report turned out to be the most expensive way of report writing during the first 5 years, due to high initial costs. After 5 years the costs of the different systems were comparable with each other. Cost-benefit analysis showed a positive financial benefit for computerized reports after 3 years.

Objective: To simultaneously assess cardiovascular (CV) and gastrointestinal (GI) risk with traditional non-steroidal anti-inflammatory drugs (tNSAIDs) and cyclo-oxygenase 2 (COX-2) inhibitors., Methods: Using the PHARMO Record Linkage System, including drug-dispensing and hospitalisation data of >2 million residents of The Netherlands, subjects with first hospitalisation for acute myocardial infarction (AMI), CV and GI events were identified. Use of COX-2 inhibitors and traditional non-selective NSAIDs was classified into remote, recent and current. Cases were matched to controls in a 1:4 ratio on age and event date. Multivariate analyses adjusted for gender, history of hospitalisations and medications., Results: Compared to remote use, AMI risk was increased among current users of COX-2 inhibitors combined (adjusted odds ratio (OR) 1.73, 95% CI 1.37 to 2.19) and tNSAIDs combined (OR 1.41, 95% CI 1.23 to 1.61). AMI risk with celecoxib (OR 2.53, 95% CI 1.53 to 4.18), rofecoxib (OR 1.60, 95% CI 1.22 to 2.10), ibuprofen (OR 1.56, 95% CI 1.19 to 2.05) and diclofenac (OR 1.51, 95% CI 1.22 to 1.87) was significantly increased. CV risk with current use of individual COX-2 inhibitors and tNSAIDs was significantly increased (OR from 1.17 to 1.64), as was GI risk with current use of rofecoxib (OR 1.99, 95% CI 1.51 to 2.63), naproxen (OR 4.44, 95% CI 3.36 to 5.86), ibuprofen (OR 1.90, 95% CI 1.40 to 2.58), diclofenac (OR 4.77, 95% CI 3.94 to 5.76), other tNSAIDs (OR 2.59, 95% CI 2.08 to 3.21), but not celecoxib (OR 1.36, 95% CI 0.70 to 2.66). Compared to current use of celecoxib and AMI risk was significantly decreased with current use of naproxen (OR 0.48, 95% CI 0.26 to 0.87) only. GI risk was increased with current naproxen (OR 3.26, 95% CI 1.59 to 6.70) and diclofenac (OR 3.50, 95% CI 1.76 to 6.98)., Conclusions: AMI and CV risk increased similarly with individual COX-2 inhibitors and tNSAIDs, whereas GI risk was found to be greater with naproxen and diclofenac. Residual confounding and "channelling" cannot be excluded.

Background: Nurse endoscopists may provide a solution for the insufficient endoscopic capacity in colorectal cancer (CRC) screening., Aim: To determine the views of gastroenterologists about the potential role of nurse endoscopists in gastrointestinal endoscopy., Methods: A postal questionnaire was sent to all registered gastroenterologists (n = 301) and gastroenterology residents (n = 79) in the Netherlands., Results: Two hundred and thirty five of 380 (62%) gastroenterologists and residents completed the questionnaire. Overall, 48% were positive towards introduction of nurse endoscopists, whereas 18% were neutral and 34% negative. Respondents expected no major differences in endoscopic quality between physicians and nurse endoscopists. Nevertheless, 69% expected that patient experiences would be better met by physicians. Multivariate analysis showed that actual experience with nurse endoscopists and beliefs that nurse endoscopists are able to provide adequate endoscopic quality and good patient experiences, were independent predictors for a positive attitude towards introduction of nurse endoscopists [OR 6.6 (2.3-18.4), OR 1.9 (1.2-3.5) and OR 2.1 (1.2-2.9), respectively]. Respectively 89% and 66% of the respondents considered sigmoidoscopy and colonoscopy for CRC screening as appropriate procedures to be performed by nurse endoscopists. Diagnostic and therapeutic endoscopies were considered less appropriate., Conclusion: A majority of gastroenterologists have a positive attitude towards introduction of nurse endoscopists, especially for CRC screening endoscopies.

We aimed to separate the influence of radiologist experience from that of CT quality in the evaluation of CT examinations of patients with esophageal or gastric cardia cancer. Two radiologists from referral centers ('expert radiologists') and six radiologists from regional non-referral centers ('non-expert radiologists') performed 240 evaluations of 72 CT examinations of patients diagnosed with esophageal or gastric cardia cancer between 1994 and 2003. We used conditional logistic regression analysis to calculate odds ratios (OR) for the likelihood of a correct diagnosis. Expert radiologists made a correct diagnosis of the presence or absence of distant metastases according to the gold standard almost three times more frequently (OR 2.9; 95% CI 1.4-6.3) than non-expert radiologists. For the subgroup of CT examinations showing distant metastases, a statistically significant correlation (OR 3.5; 95% CI 1.4-9.1) was found between CT quality as judged by the radiologists and a correct diagnosis. Both radiologist experience and quality of the CT examination play a role in the detection of distant metastases in esophageal or gastric cardia cancer patients. Therefore, we suggest that staging procedures for esophageal and gastric cardia cancer should preferably be performed in centers with technically advanced equipment and experienced radiologists.

Background: Gastric marginal zone non-Hodgkin lymphomas MALT type (gMALT) and gastric adenocarcinomas (GC) are long-term complications of chronic Helicobacter pylori gastritis, however, the incidence of gMALT and the GC risk in these patients is unclear., Objective: To evaluate epidemiological time trends of gMALT in the Netherlands and to estimate GC risk., Methods: Patients with a first diagnosis of gMALT between 1991 and 2006 were identified in the Dutch nation-wide histopathology registry (PALGA). Age-standardised incidence rates were calculated. The incidences of GC in patients with gMALT and in the Dutch population were compared. Relative risks were calculated by a Poisson Model., Results: In total, 1419 patients were newly diagnosed with gMALT, compatible with an incidence of 0.41/100,000/year. GC was diagnosed in 34 (2.4%) patients of the cohort. Patients with gMALT had a sixfold increased risk for GC in comparison with the general population (p<0.001). This risk was 16.6 times higher in gMALT patients aged between 45 and 59 years than in the Dutch population (p<0.001)., Conclusions: GC risk in patients with gMALT is six times higher than in the Dutch population and warrants accurate re-evaluation after diagnosis and treatment for gMALT.

Background and Study Aims: Simulators are increasingly used in skills training for physicians; however data on systematic evaluation of the performance of these simulators are scarce compared with those used in aviation. The objectives of this study were to determine the expert validity, the construct validity, and the training value of the novel Olympus simulator as judged by experts., Patients and Methods: Participants were novices and experts. Novices had no prior experience in flexible endoscopy; experts had all performed more than 1000 colonoscopies. Participants filled out a questionnaire on their impression of the realism of the colonoscopy exercises performed. These included a dexterity exercise and a virtual colonoscopy. Test parameters used were points acquired in a game, time to reach the cecum, maximum insertion force, and "patient pain.", Results: Novices (n = 26) scored a median of 973 points (range--118-1393), experts (n = 23) scored 1212 points (range 89-1375). This difference did not reach significance (P = 0.073). Experts performed virtual colonoscopy significantly faster than novices (220 vs. 780 s, P < 0.001) but used more insertion force (11.8 vs. 11.6 N; P = 0.147). Maximum pain score was higher in the expert group: 86% vs. 73%. (P = 0.018). The realism was graded 6.5 on a 10-point scale. Experts considered the Olympus simulator beneficial for the training of novice endoscopists., Conclusions: The novel Olympus simulator discriminates excellently between the measured levels of expertise. The prototype offers a good realistic representation of colonoscopy according to experts. Although the software development is continuing, the device can already be implemented in the training program of novice endoscopists.

The main options for secondary prevention of gastrooesophageal variceal bleeding are endoscopic therapy and treatment with propranolol. Creation ofa transjugular intrahepatic portosystemic shunt (TIPS) is currently considered a valuable secondary 'rescue' treatment when other therapies fail. Recent data suggest that the use of covered stents markedly increases the efficacy of TIPS, compared with conventional uncovered stents. Therefore, a multicentre randomised trial was designed to compare the effects of TIPS using covered stents with those of endoscopic therapy plus propranolol in patients with a first or second episode ofgastro-oesophageal variceal bleeding. TIPS will be performed in 4 university centres with relevant expertise. The trial will hopefully gain nationwide support, and all centres in The Netherlands are cordially invited to participate.

Background: The pre-malignant gastric lesions atrophic gastritis (AG), intestinal metaplasia (IM) and dysplasia (DYS) have long been identified as principal risk factors for gastric cancer., Objective: To evaluate epidemiological time trends of pre-malignant gastric lesions in the Netherlands., Methods: Patients with a first diagnosis of AG, IM or DYS between 1991 and 2005 were identified in the Dutch nationwide histopathology registry. The number of new diagnoses per year were evaluated relative to the total number of patients with a first gastric biopsy. Time trends were evaluated with age-period-cohort models using logistic regression analysis., Results: In total, 23 278 patients were newly diagnosed with AG, 65 937 patients with IM, and 8517 patients with DYS. The incidence of AG declined similarly in men and women with 8.2% per year [95% CI 7.9% to 8.6%], and DYS with 8.1% per year [95% CI 7.5% to 8.6%]. The proportional number of new IM cases declined with 2.9% per year [95% CI 2.7% to 3.1%] in men and 2.4% [95% CI 2.2% to 2.6%] in women. With age-period-cohort models a cohort phenomenon was demonstrated for all categories of pre-malignant gastric lesions in men and in women with IM and DYS. Period phenomena with a larger decline in number of diagnoses after 1996 were also demonstrated for AG and IM., Conclusions: The incidence of pre-malignant gastric lesions is declining. Period and cohort phenomena were demonstrated for diagnoses of AG and IM. These findings imply that a further decrease of at least 24% in the incidence of gastric cancer in the coming decade may be anticipated in Western countries without specific intervention.

Background: Upper gastrointestinal (UGI) complications are a well-recognized risk of NSAID treatment, requiring preventive measures in high-risk patients. Adherence to gastroprotective agents (GPAs) in NSAID users has been suggested to be suboptimal., Aim: To investigate the association between adherence to GPAs (proton pump inhibitors or H(2)-receptor antagonists) and the risk of NSAID-related UGI ulcers or haemorrhage in high-risk patients., Methods: A population-based nested case-control study was conducted within a cohort of new NSAID users with at least one risk factor for a NSAID-related UGI complication, identified in the Dutch IPCI database during 1996-2005. Adherence to GPAs was calculated as the proportion of NSAID treatment days covered (PDC) by a GPA prescription. Multivariate conditional logistic regression analysis was used to calculate odds ratios with 95% confidence intervals (95% CI)., Results: Fifteen percent of the non-selective NSAID users received GPAs. The risk of a NSAID-related UGI complication among NSAID users increased 16% for every 10% decrease in adherence. Compared to patients with a PDC of >80%, patients with PDCs of 20-80% and <20% had a 2.5-fold (95% CI: 1.0-6.7) respectively 4.0-fold (95% CI: 1.2-13.0) increased risk., Conclusion: There is a strong inverse relationship between adherence to GPAs and the risk of UGI complications in high-risk NSAID users.

Aims: To determine interobserver variation in grading of dysplasia in Barrett's oesophagus (BO) between non-expert general pathologists and expert gastrointestinal pathologists on the one hand and between expert pathologists on the other hand., Methods and Results: In this prospective multicentre study, non-expert and expert pathologists graded biopsy specimens of 920 patients with endoscopic BO, which were blindly reviewed by one member of a panel of expert pathologists (panel experts) and by a second panel expert in case of disagreement on dysplasia grade. Agreement between two of three pathologists was established as the final diagnosis. Analysis was performed by kappa statistics. Due to absence of intestinal metaplasia, 127/920 (14%) patients were excluded. The interobserver agreement for dysplasia [no dysplasia (ND) versus indefinite for dysplasia/low-grade dysplasia (IND/LGD) versus high-grade dysplasia (HGD)/adenocarcinoma (AC)] between non-experts and first panel experts and between initial experts and first panel experts was fair (kappa = 0.24 and kappa = 0.27, respectively), and substantial for differentiation of HGD/AC from ND/IND/LGD (kappa = 0.62 and kappa = 0.58, respectively)., Conclusions: There was considerable interobserver variability in the interpretation of ND or IND/LGD in BO between non-experts and experts, but also between expert pathologists. This suggests that less subjective markers are needed to determine the risk of developing AC in BO.

Background: Presently, no evidence-based guidelines for the follow-up of patients after surgery for gastrointestinal cancer are available. As a consequence, follow-up strategies may differ between hospitals depending on preference of physicians. We investigated which follow-up procedures are currently employed after surgery for gastrointestinal cancer in the Netherlands., Method: A questionnaire was sent to all surgical departments in the Netherlands. The questionnaire focused on frequency of follow-up visits and diagnostic procedures after surgical treatment for oesophageal, gastric, pancreatic and colorectal cancer and psychosocial issues during follow-up., Results: The response rate was 90% (83/92). In the majority of hospitals, surgeons treated patients with colorectal (100%) and gastric (96%) cancer in their own centre, whereas patients with pancreatic (64%) and oesophageal (61%) cancer were more often referred to a tertiary centre. For all patients treated for gastrointestinal cancer, three to four follow-up visits were made in the first year, followed by at least two annual visits thereafter. After colorectal surgery, blood tests (78%), colonoscopy (75%) and abdominal ultrasound (57%) were frequently performed. In other gastrointestinal malignancies, procedures were in most cases only performed if symptoms occurred. In almost three-quarters of patients, psychosocial problems were observed, which were dealt with by surgeons in two-thirds of patients. The majority of patients treated for gastrointestinal cancer were pre- and postoperatively discussed in a multidisciplinary setting. Oncologists, gastroenterologists and dieticians were the most frequently consulted specialists after surgery for gastrointestinal cancer., Conclusion: Patients frequently visit the outpatient clinic after surgery for gastrointestinal cancer in the Netherlands. Whereas follow-up after colorectal cancer surgery focuses on finding recurrent disease and metachronous lesions in the colorectum, this is less clear after oesophageal, gastric and pancreatic cancer surgery. Further studies are needed to establish what is the most effective follow-up protocol after different types of gastrointestinal cancer surgery.

Background: The widespread use of gastrointestinal endoscopy for diagnosis and treatment requires effective, standardised report systems. This need is further increased by the limited storage of images, and by the need for structured databases for surveillance and epidemiology. We therefore aimed for a report system which would be quick, easy to learn, and suitable for use in busy daily practice., Methods: Endobase III is an endoscopy information system offering three different ways of report writing, i.e. standard reports, text blocks and Minimal Standard Terminology (MST). A working group of two university and four general hospitals worked as a reference group for the development of standard reports and text blocks. Guidelines from various gastrointestinal endoscopy societies were followed to compose the reports., Results: Standard reports were based on a list of distinct diagnoses; text blocks were based on anatomic landmarks and individual procedures. As such, 316 standard reports were developed for upper and lower gastrointestinal endoscopy, and endoscopic retrograde cholangiopancreatography (ERCP). In this way selecting one diagnosis produces a complete report. A total of 1571 different text blocks were additionally developed for each part of the gastrointestinal tract and for procedures during endoscopy. This module allowed generation of a full report on the combination of text blocks. Reports could be composed and printed within two minutes for 90% of cases., Conclusion: Standard reports and text blocks are a quick, user-friendly way of report writing accepted and used by a number of gastroenterologists in the Netherlands.

Four patients, two women aged 29 and 42 years and two men aged 45 and 34 years, with longstanding complaints of (watery) diarrhoea were referred for a second opinion after extensive and costly analysis, including numerous examinations. An accurate medical history revealed deviant food patterns with abundant intake of coffee and sugar or sugar-containing products like cola or sweeteners in all four patients. Coffee (and caffeine) has a stimulating effect on both intestinal motility and net secretion, possibly leading to diarrhoea. Over-consumption of sugars and sweeteners (sometimes added to medication) can also cause osmotic diarrhoea. In all four patients, dietary advice was sufficient to resolve the diarrhoea, thus emphasizing once more the importance of an accurate and complete medical history.

Background: Barrett's oesophagus (BO) predisposes to oesophageal adenocarcinoma. Epidemiological data suggest that the incidence of BO is rising but it is unclear whether this reflects a true rise in incidence of BO or an increase in detection secondary to more upper gastrointestinal endoscopies performed. This study aimed to examine the changes in BO incidence relative to the number of upper gastrointestinal endoscopies performed in the general population., Methods: We conducted a cohort study using the Integrated Primary Care Information database. This general practice research database contains the complete and longitudinal electronic medical records of more than 500,000 persons., Results: In total, 260 incident cases of BO were identified during the study period. The incidence of BO increased from 14.3/100,000 person years in 1997 (95% confidence interval (CI) 8.6-22.4) to 23.1/100,000 person years (95% CI 17.2-30.6) in 2002 (r2 = 0.87). The number of upper gastrointestinal endoscopies decreased from 7.2/1000 person years (95% CI 6.7-7.7) to 5.7/1000 person years (95% CI 5.4-6.1) over the same time period. This resulted in an overall increase in detected BO per 1000 endoscopies from 19.8 (95% CI 12.0-31.0) in 1997 to 40.5 (95% CI 30.0-53.5) in 2002 (r2 = 0.93). The incidence of adenocarcinoma increased from 1.7/100,000 person years (95% CI 0.3-5.4) in 1997 to 6.0/100,000 person years (95% CI 3.3-10.2) in 2002 (r2 = 0.87)., Conclusion: The incidence of diagnosed BO is increasing, independent of the number of upper gastrointestinal endoscopies that are being performed. This increase in BO incidence will likely result in a further increase in the incidence of oesophageal adenocarcinomas in the near future.

Background and Aims: Interleukin-10 is an anti-inflammatory and immunomodulatory cytokine. Interleukin-10 deficient mice are prone to develop chronic colitis. Administration of recombinant human interleukin-10 has been proposed to have a beneficial effect in a subgroup of patients with Crohn's disease. Recently, we found an interleukin-10 Gly15Arg mutation in a family with Crohn's disease which is associated with reduced interleukin-10 secretion by in vitro stimulated monocytes and lymphocytes. We hypothesised that this interleukin-10 mutation plays a role in maintaining the inflammatory process in Crohn's disease in some families., Patients and Methods: We evaluated interleukin-10 Gly15Arg in 379 patients with Crohn's disease, and 75 unrelated healthy controls. Also, first degree family members of interleukin-10 Gly15Arg carriers were evaluated. Additionally, mutation carriers and their relatives were evaluated for CARD15 R702W, G908R, and 1007fs., Results: Two patients with Crohn's disease were heterozygous for the interleukin-10 Gly15Arg mutation. No homozygotes were found. The Gly15Arg mutation was not observed in the controls. In first degree family members of the Crohn's disease-affected interleukin-10 Gly15Arg carriers, the mutation was found in Crohn's disease-affected as well as in their apparently healthy individuals. All family members carried one or two CARD15 mutation(s)., Conclusion: The interleukin-10 Gly15Arg mutation is rare in patients with Crohn's disease, and is not associated with the disease in the Netherlands.

Colorectal cancer incidence after adenoma removal has been studied in selected populations of adenoma patients. Our study estimates the trend in colorectal cancer incidence after adenoma removal in actual clinical practice. From PALGA, a nationwide network and registry of histo- and cytopathology in the Netherlands, we extracted data of all patients diagnosed with colorectal adenomas between 1 January 1988 and 1 October 1998. The data were used to calculate population-based colorectal cancer incidence rates after adenoma removal. A total of 78,473 adenoma patients were followed for a mean of 4.5 years after the first adenoma removal. The colorectal cancer incidence ratio compared with the general population matched by age and gender was 38.4 (37.3-39.5) in the first year after adenoma removal and 1.5 (95% confidence interval (CI): 1.4-1.6) after Year 1. The incidence ratio decreased from 2.8 (2.5-3.1) in Year 2 to 0.9 (0.6-1.2) in Years 9-11. This time trend is the opposite of the upward time trend that was expected after adenoma removal. Adenoma patients in the Netherlands are at increased risk for colorectal cancer compared to the general population. The high cancer incidence in Years 1-5 after polypectomy can be explained by a colonoscopic sensitivity for cancer of approximately 90%., (Copyright 2004 Wiley-Liss, Inc.)

Objective: To survey the diagnostic procedures and treatment strategies currently employed in hospitals for patients with oesophageal cancer., Design: Questionnaire., Method: A questionnaire was sent to all clinicians working in the field of gastroenterology in the Netherlands. This questionnaire focused on clinical preferences regarding diagnostic procedures and treatment strategies for oesophageal cancer. Also, six hypothetical patient vignettes were presented in order to investigate which factors affected choice of treatment, in particular surgical treatment., Results: The response rate was 64% (426/667); 336 questionnaires were relevant to the investigation. Almost 90% of the clinicians treated fewer than 20 patients annually, usually in their own hospital. CT was the most frequently used staging procedure; endoscopic ultrasound was less frequently used (42% used it in less than half the patients). The treatment choice for the patient vignettes varied widely among clinicians. Factors influencing the choice to operate or not were: metastases, loco-regional tumour ingrowth, poor general health, and advanced age with 8, 22, 20, and 53%, respectively, of the clinicians still considering surgery in the presence of one of these factors as opposed to 99% if none of these factors were present. Surgeons opted for operation more often than internists and gastroenterologists. Stent placement was the most frequently chosen method to palliate malignant dysphagia., Conclusion: There is a wide variation in the use of diagnostic procedures and treatment strategies for patients with oesophageal cancer in the Netherlands. This stresses the need for scientifically based practice guidelines, taking into account specific patient and tumour characteristics.

Four patients with gastroduodenal ulcers in the absence of Helicobacter pylori illustrate the decreasing prevalence of this microorganism. One was a 19-year-old boy with nausea, diarrhoea and weight loss caused by multiple gastroduodenal ulcers due to the Zollinger-Ellison syndrome. Another was a 36-year-old man with abdominal discomfort caused by an ulcer due to Crohn's disease. The other two cases concerned a 29-year-old man and a 68-year-old woman with relapsing ulcer disease and active bleeding, in whom no causal factors could be determined. Recent studies suggest a decreasing prevalence of H. pylori leading to both a relative and an absolute decrease of gastroduodenal ulcers attributed to H. pylori. Future treatment strategies will have to take these altered prevalence rates into consideration.

Objective: To investigate whether the decrease in rate of Helicobacter pylori infection in subsequent birth cohorts has continued during the last decades., Methods: Determination by ELISA of IgG H. pylori antibodies in 314 serum samples from Dutch children (age 6-8 yr, n = 154) and young adolescents (age 12-15 yr, n = 160), collected in 1978 and 1993., Results: The prevalence of H. pylori declined from 19% to 9% at age 6-8 yr and from 23% to 11% at age 12-15 yr. For the whole study population, a decline from 21% to 10% (p = 0.01) was observed between 1978 and 1993. On the basis of these data and an incidence of infection with H. pylori of 0.3% per year during the same period, a model for both past and future prevalence rates of H. pylori in the Dutch population was calculated. The outcome demonstrates a decrease from more than 50% around World War II to less than 20% for the whole population around year 2040., Conclusions: H. pylori infection rates in childhood have continued to decline until recent decades, demonstrating a persistent birth cohort effect. This decline will result in a very low prevalence of H. pylori infection in the Dutch population during the next decades, becoming even lower as the observed decline in children and young adolescents continues.

Helicobacter pylori strains may be either cagA+ or cagA-, and in logitudinal studies, infection with a cagA+ strain has been associated with increased risk for the development of atrophic gastritis and cancer of the distal stomach. We sought to determine the relative proportion of strains producing CagA in different geographic locales, and the extent to which CagA seroprevalence varied in countries with different gastric and esophageal cancer rates. Using an enzyme-linked immunosorbent assay (ELISA) to detect serum IgG to CagA, we examined sera from 468 asymptomatic H. pylori-infected adults from Canada, Peru, China, Thailand, The Netherlands and 3 different ethnic groups in New Zealand. The CagA seroprevalence in Peru and Thailand (82.2% and 78.8%, respectively) were each substantially higher than for the Chinese (37.9%), Canadian (41.9%), Dutch (39.0%) and New Zealand (28.2%) subjects, but within each population, rates were relatively constant across gender and age groups. Reported gastric but not esophageal cancer rates for the 8 studied populations were significantly associated with H. pylori seroprevalence. Variation in CagA positivity rates was not significantly associated with variation in either gastric or esophageal cancer rates. Our data suggest that CagA seroprevalence is not the major factor influencing gastric cancer rates.