Roeland A. Veenendaal

Quality of web-based information on inflammatory bowel diseases.

Background: The Internet is the largest source of health information and is widely used by inflammatory bowel disease (IBD) patients. As information is largely unregulated, our objective was to evaluate the quality, readability, accuracy, and accessibility of the information concerning IBD available on the World Wide Web. Methods: The phrases “inflammatory bowel disease,” “Crohns disease,” and “Ulcerative Colitis” were entered separately as search terms into the 6 most commonly used search engines. Sites were categorized as institutional, pharmaceutical, nonpharmaceutical commercial sites, charitable, support, or alternative medicine. Websites were evaluated for content quality using the validated DISCERN rating instrument. Readability was graded by the Flesch Reading Ease and the Flesch‐Kincaid Grade Level score. Results: Of the 76 websites evaluated by DISCERN, 43% of the sites were rated as excellent to good and 57% as fair to poor. Alternative medicine sites scored significant lower (P > 0.05) than institutional, pharmaceutical, and nonpharmaceutical commercial sites. There was no relation between a rating score and the position of a website on the search engine ranking. The median Flesch Reading Ease Score was 41.65 (range, 2.6‐77.7) and 11.85 (range, 6.2‐21.1) for the Flesch‐Kincaid Grade Level. Conclusions: The quality of websites containing information on IBD varies widely. Most of the online material available is too difficult to comprehend for a substantial portion of the patient population, and good quality information may be beyond reach of the average information seeker. Inflamm Bowel Dis 2009

Azathioprine: an Update on Clinical Efficacy and Safety in Inflammatory Bowel Disease

BACKGROUND The approval of azathioprine (AZA) for the long-term therapy of patients with Crohns disease in The Netherlands. METHODS Review and update of the literature on clinical efficacy and safety of AZA in inflammatory bowel disease. RESULTS AZA and its metabolite 6-mercaptopurine (6-MP) are effective in the treatment of active Crohns disease. However, the onset of the clinical response is delayed, requiring combination with other active medication in the early phase of treatment. Maintenance therapy with AZA/6-MP is also effective in the prevention of relapses in patients with Crohns disease in remission. Indications for AZA/6-MP therapy further include refractory, fistulizing and steroid-dependent Crohns disease. It is not known whether or when AZA/6-MP can be withdrawn in patients in long-term remission, but most clinicians discontinue therapy after 3-5 years. Although fewer data are available, AZA/6-PM appears to be effective also in the therapy of patients with ulcerative colitis. Side effects of AZA/6-MP occur in about 15% of patients and include skin rash, pancreatitis and hepatitis, dose-related neutropenia and thrombocytopenia, and risk of increased occurrence and severity of infections. Recent data suggest that the risk of malignancy, other than colorectal cancer, is not increased. Safety in pregnancy has not been studied extensively, but no increased prevalence of birth defects has been reported. CONCLUSIONS AZA/6-MP therapy is efficacious in patients with active Crohns disease, but the drug is especially valuable in the long-term treatment of patients with Crohns disease and ulcerative colitis. Drug-related side effects are frequent and require discontinuation or dose-reduction of the AZA/6-MP therapy. Due to an increased risk of infections secondary to myelosuppression, careful follow-up is mandatory. Insufficient data are available on safety in pregnancy and on the risk of malignancies, but the limited data available in patients with inflammatory bowel disease appear to be reassuring.

Proximal Crohn's disease: review of the clinicopathologic features and therapy.

Crohns disease in the proximal region of the digestive tract is uncommon. Better diagnostically procedures and more careful histologic examination has led to a higher detection of proximal Crohns disease. The diagnosis is based on symptoms, endoscopy with serial sections, or double contrast radiography. The most common histologic finding for this diagnosis are granulomas in the mucosa in Helicobacter pylori-negative patients, but the granulomas are not always frequently detected. Endoscopic lesions in the proximal regions look like the lesions that could be found in the distal regions. Notching in the duodenal folds could be a strong indication for Crohns desease. Radiological lesions are not always characteristic, but should be used in combination with endoscopy. Stenosis is an important complication, but fistula formation and pseudodiverticular formation is possible. There is no uniform medical therapy, but the regular anti-inflammatory management for Crohns disease is most often used. Sometimes surgery is needed.

Classification, epidemiology and aetiology

Intestinal failure and its most important cause, short-bowel syndrome (SBS), are rare clinical entities leading to a vast complex of symptoms and complications with significant morbidity and mortality. Both conditions occur as the result of a massive reduction in enteral nutrient absorptive capacity. Disease manifestation is based on aetiological and anatomical characteristics such as remaining intestinal length and the presence of a functionally intact colon. Congenital and perinatal conditions, for example, intestinal atresia, necrotizing enterocolitis (NEC) and intestinal volvulus are the most important causes in children. The aetiology in adults is based on diseases inducing loss of intestinal function or loss of intestinal surface area after extensive surgical resections. The most frequent causes are mesenteric infarction, radiation enteritis and Crohns disease. Knowledge of the epidemiology of intestinal failure and SBS is limited, being mainly based on the extrapolated figures of home parenteral nutrition centres and single-centre studies. At present, the incidence of SBS is estimated to be 2-5 per million.

Crohn's Disease of the Upper Gastrointestinal Tract: the Value of Endoscopic Examination

The involvement of the upper gastrointestinal (GI) tract has been considered to be a rare manifestation of Crohns disease (CD). Retrospective studies have reported prevalence figures of 0.5-13%. The diagnosis of CD of the upper GI tract is based on clinical, radiological, endoscopic and histologic features. In contrast to the retrospective studies, prospective studies, in which patients with CD underwent routine endoscopic evaluation with biopsies, revealed a much higher frequency of endoscopic and histologic abnormalities. Since Helicobacter pylori is the most frequent cause of gastritis and the most important etiologic factor in peptic ulcer disease, it is important to assess the contribution of H. pylori in the interpretation of the abnormalities observed in the upper GI tract in patients with CD. Therapy for CD of the upper GI tract consists of drug therapy and endoscopic or surgical interventions and is in fact similar to that for distal CD. Corticosteroids are still the most important drugs in the treatment of CD of the upper GI tract. Sometimes adjunctive therapy, e.g. gastric antisecretory drugs and mucosa protective agents, is beneficial. Endoscopic evaluation of the upper GI tract with biopsies should be part of the work-up of CD patients.

Colonic stenting as bridge to surgery versus emergency surgery for management of acute left-sided malignant colonic obstruction: a multicenter randomized trial (Stent-in 2 study)

BackgroundAcute left-sided colonic obstruction is most often caused by malignancy and the surgical treatment is associated with a high mortality and morbidity rate. Moreover, these operated patients end up with a temporary or permanent stoma. Initial insertion of an enteral stent to decompress the obstructed colon, allowing for surgery to be performed electively, is gaining popularity. In uncontrolled studies stent placement before elective surgery has been suggested to decrease mortality, morbidity and number of colostomies. However stent perforation can lead to peritoneal tumor spill, changing a potentially curable disease in an incurable one. Therefore it is of paramount importance to compare the outcomes of colonic stenting followed by elective surgery with emergency surgery for the management of acute left-sided malignant colonic obstruction in a randomized multicenter fashion.Methods/designPatients with acute left-sided malignant colonic obstruction eligible for this study will be randomized to either emergency surgery (current standard treatment) or colonic stenting as bridge to elective surgery. Outcome measurements are effectiveness and costs of both strategies. Effectiveness will be evaluated in terms of quality of life, morbidity and mortality. Quality of life will be measured with standardized questionnaires (EORTC QLQ-C30, EORTC QLQ-CR38, EQ-5D and EQ-VAS). Morbidity is defined as every event leading to hospital admission or prolonging hospital stay. Mortality will be analyzed as total mortality as well as procedure-related mortality. The total costs of treatment will be evaluated by counting volumes and calculating unit prices. Including 120 patients on a 1:1 basis will have 80% power to detect an effect size of 0.5 on the EORTC QLQ-C30 global health scale, using a two group t-test with a 0.05 two-sided significance level. Differences in quality of life and morbidity will be analyzed using mixed-models repeated measures analysis of variance. Mortality will be compared using Kaplan-Meier curves and log-rank statistics.DiscussionThe Stent-in 2 study is a randomized controlled multicenter trial that will provide evidence whether or not colonic stenting as bridge to surgery is to be performed in patients with acute left-sided colonic obstruction.Trial registrationCurrent Controlled Trials ISRCTN46462267.

Treatment of Helicobacter pylori infection favourably affects gastric mucosal superoxide dismutases.

BACKGROUND AND AIMS: Excessive production of reactive oxygen metabolites (ROMs) by phagocytic cells is thought to contribute to the mucosal pathology of Helicobacter pylori infection. Previously, H pylori infection was shown to have a differential effect on some gastric mucosal scavenger enzymes of ROMs-namely, mitochondrial and cytoplasmic superoxide dismutases-reflected by a large increase in the cytokine inducible manganese superoxide dismutase and a marginal decrease in the constitutive copper/zinc superoxide dismutase. The present study was performed to evaluate whether these altered mucosal superoxide dismutase concentrations and activities in H pylori associated gastritis are reversed to normal by successful treatment of the infection. PATIENTS AND METHODS: In two different treatment groups-namely, omeprazole or ranitidine, in combination with clarithromycin and metronidazole (OME/AB (n = 33) and RAN/AB (n = 30))-manganese superoxide dismutase and copper/zinc superoxide dismutase concentrations were evaluated by enzyme linked immunosorbent assays in homogenates of gastric antrum and corpus biopsy specimens obtained before and eight weeks after successful treatment of H pylori infection. Superoxide dismutase activities in these homogenates were determined spectrophotometrically in eight patients of both groups before and after successful treatment. The concentrations of gastric mucosal superoxide dismutases were also determined in 12 patients with a persistent H pylori infection, with (n = 4) or without (n = 8) eradication therapy. Infection and eradication of H pylori were confirmed by a combination of culture and histology. RESULTS: Concentrations of manganese superoxide dismutase were significantly lower after than before therapy in antral (p < 0.001 in both treatment groups) and corpus (p < 0.001 in both treatment groups) mucosa. By contrast, copper/zinc superoxide dismutase concentrations were significantly higher (p < 0.001) only in antral mucosa of the OME/AB treated group. Manganese superoxide dismutase activity was significantly lower after than before treatment in antral (OME/AB p < 0.01, RAN/AB p < 0.001), but not in corpus mucosa. Copper/zinc superoxide dismutase activity was not significantly altered by therapy. In the 12 patients with a persistent H pylori infection no major changes in the gastric mucosal superoxide dismutase concentrations were found. CONCLUSIONS: The raised manganese superoxide dismutase and reduced copper/ zinc superoxide dismutase concentrations and activities in H pylori associated gastritis were reversed towards normal by successful treatment of the infection.

Influence of Combination Therapy with Immune Modulators on Anti-TNF Trough Levels and Antibodies in Patients with IBD

Background:It is important to identify factors that can reduce the incidence of immunogenicity against anti-tumor necrosis factor medication in patients with inflammatory bowel disease. The objective of our study was to evaluate the influence of cotreatment with immune modulators (IMs) on trough levels (TLs) and antidrug antibodies. Methods:The records of all patients with inflammatory bowel disease at the Leiden University Medical Center who received either adalimumab or infliximab (IFX) in the year 2011 and/or 2012 (n = 352) were retrospectively evaluated about the assessment of TL and antibodies and use of IM. Results:Two hundred seventeen patients were included (108 patients IFX; 109 patients adalimumab). Mean TL in the IFX group was higher in the combination therapy group compared with the monotherapy group, 4.6 versus 7.5 µg/mL, P = 0.04. In the adalimumab group, the difference was not significant. In patients with IFX monotherapy, the incidence of antibody formation was higher compared with patients with combination therapy (29.8% versus 5.7%, P = 0.001). IFX patients with a suboptimal dose of IM had a higher TL compared with patients who had an optimal dose, P = 0.02. The incidence of antibody formation was lower in IFX patients who immediately started with IMs compared with patients who did not (33.3% versus 66.7%, P = 0.04). Conclusions:The influence of combination therapy with IM on TL and antibodies to anti-tumor necrosis factor medication was significant for IFX-treated patients. Patients who started combination therapy immediately developed antibodies less often than patients who started later with concomitant medication.

IgG subclass response to Helicobacter pylori in patients with chronic active gastritis and duodenal ulcer.

The IgG subclass response is determined by the type of bacteria producing the infection and by genetic factors of the host. Patients with a Helicobacter pylori infection develop a specific immune response that is mainly of the IgA and IgG class. We measured the IgG subclass response in 20 patients with chronic active gastritis without a history of duodenal ulcer and 20 patients with chronic active gastritis and duodenal ulcer diagnosed by endoscopy and histology. A control group included 20 H. pylori-negative patients and 60 H. pylori-positive blood transfusion donors. Systemic IgG subclass response was measured with a modified enzyme-linked immunosorbent assay technique, using as antigen a sonicate of six different H. pylori strains. Mouse monoclonal antibodies against each of the four human IgG subclasses (IgG1, IgG2, IgG3, and IgG4) were used. The total IgG anti-H. pylori antibody titres were equal in all three H. pylori-positive groups and significantly different from that of the negative control group (p less than 0.01). The IgG subclass response in persons infected with H. pylori involved all four subclasses but was predominantly of the IgG1 and IgG2 subclasses. All of the groups with H. pylori infection had significantly higher levels of IgG1 than the negative control group, but no differences were detected among the three groups. However, the duodenal ulcer group had a significantly higher IgG2 response than the gastritis group (mean optical density +/- SEM, 0.382 +/- 0.047 versus 0.200 +/- 0.025, respectively; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Serum Gastrin and Mucosal Somatostatin in Helicobacter pylori-Associated Gastritis

AIMS The aims were to study gastrin concentrations and gastric mucosal somatostatin and gastrin concentrations in relation to the extent of gastritis in Helicobacter infection. METHODS We measured basal serum gastrin concentrations in antral mucosal biopsy specimens and somatostatin concentrations in corpus biopsy specimens in 88 consecutive dyspeptic subjects undergoing endoscopy. These subjects were divided into three categories on the basis of histology, serology, and culture: H. pylori-positive pangastritis, H. pylori positive antral gastritis with normal body histology, and H. pylori-negative controls. Statistical evaluation was done with the Wilcoxon rank sum test. RESULTS Basal serum gastrin concentrations were significantly increased only in subjects with pangastritis and not in those with antral gastritis only, as compared with controls (mean +/- SEM: 72 +/- 7, 46 +/- 10, and 42 +/- 7 ng/l, respectively). Subjects with pangastritis or antral gastritis had significantly lower antral somatostatin concentrations than controls (mean +/- SEM: 0.80 +/- 0.07, 1.03 +/- 0.15, and 2.40 +/- 0.31 micrograms/g(protein), respectively). We also found significantly lower antral gastritis only as compared with controls (mean +/- SEM: 62 +/- 13, 78 +/- 16, and 165 +/- 25 micrograms/g(protein), respectively). In subjects with pangastritis a significantly lower concentration of somatostatin was found in the corpus biopsy specimens than in those with antral gastritis only and controls. CONCLUSIONS These results suggest that hypergastrinemia in H. pylori gastritis is not caused by antral gastritis and antral somatostatin deficiency alone but that corpus inflammation plays a key role in the origin of hypergastrinemia. Furthermore, in patients with pangastritis a corpus mucosal somatostatin deficiency was found.