[Colorectal cancer: screening and surveillance in inflammatory bowel diseases - consensus of the working group for inflammatory bowel diseases of the Austrian Society of Gastroenterology and Hepatology]. / Kolorektales Karzinom: Screening und Surveillance bei chronisch entzündlichen Darmerkrankungen - Konsensus der Arbeitsgruppe für chronisch entzündliche Darmerkrankungen der ÖGGH.

Patients with ulcerative colitis and Crohn's colitis are at increased risk of colorectal cancer (CRC). This risk is dependent on the duration and extent of disease, inflammatory activity and possible additional risk factors. Thus, the aim is to reduce this risk and to detect dysplastic and malignant lesions at an early stage. The working group for Inflammatory Bowel Diseases (IBD) of the Austrian Society of Gastroenterology and Hepatology (ÖGGH) has developed consensus statements on the following topics: risk of colorectal cancer, screening and surveillance, procedure of surveillance colonoscopy, dysplasia and its management, and chemoprevention. This consensus is intended to increase awareness of the increased risk of CRC in IBD and to support a standardised approach in cancer prevention.

[Infliximab therapy for Crohn's disease - a practical guideline: actualised consensus of the working group for chronic inflammatory bowel diseases of the Austrian Society for Gastroenterology and Hepatology]. / Infliximab in der Therapie des Morbus Crohn - ein praktischer Leitfaden: aktualisierter ÖGGH-Konsensus der Arbeitsgruppe Chronisch-entzündliche Darmerkrankungen der ÖGGH.

Infliximab is a monoclonal antibody against tumor necrosis factor alpha (TNF-α), which is approved for the treatment of chronic inflammatory bowel disease (IBD) such as Crohn's disease (CD), fistulating Crohn's disease (FCD), ulcerative colitis (UC), and paediatric ulcerative colitis (PUC) from 6 years onwards. Besides its therapeutic efficacy, this antibody therapy is characterised by its side effects profile, which has been addressed in a seperate consensus statement by the Working Group for chronic inflammatory bowel diseases within the Austrian Society for Gastroenterology and Hepatology. Infliximab is an effective treatment option for the above-mentioned indications; however, use of this agent requires special knowledge to assess the benefit-risk profile for each patient individually.

Effect of virtual endoscopy simulator training on performance of upper gastrointestinal endoscopy in patients: a randomized controlled trial.

BACKGROUND: Skills in gastrointestinal endoscopy mainly depend on experience and practice. Patients upon whom trainees perform their first endoscopic examinations are likely to suffer more discomfort and prolonged procedures. Training on endoscopy simulators may reduce the time required to reach competency in patient endoscopy. PATIENTS AND METHODS: Residents in internal medicine without experience of endoscopy were randomized to a group who trained on a simulator before conventional training (group S) or one that received conventional training only (group C) before starting upper gastrointestinal endoscopy in patients. After endoscopy, discomfort and pain were evaluated by patients, who were blind to the beginners' training status. Results in terms of time, technique (intubation, pyloric passage, J-maneuver), and diagnosis of pathological entities were evaluated by experts. RESULTS: From 2003 to 2007, 28 residents were enrolled. Comparing group S with group C in their first ten endoscopic examinations in patients, time taken to reach the duodenum (239 seconds (range 50 - 620) vs. 310 seconds (110 - 720; P < 0.0001) and technical accuracy ( P < 0.02) were significantly better in group S. Diagnostic accuracy did not differ between the groups. Fourteen residents (7 simulator-trained, 7 not simulator-trained) continued endoscopy training. After 60 endoscopic examinations, investigation time was still shorter in group S. Technical and diagnostic accuracy improved during on-patient training in both groups; here differences between groups were no longer observable. There were no significant differences in discomfort and pain scores between the groups after 10 and after 60 endoscopies. Discomfort and pain were higher than for endoscopy performed by experts. CONCLUSION: This randomized controlled trial shows that virtual simulator training significantly affects technical accuracy in the early and mid-term stages of endoscopic training. It helps reduce the time needed to reach technical competency, but clinically the effect is limited. Simulator training could be useful in an endoscopy training curriculum but cannot replace on-patient training.

Impact of different therapeutic regimens on the outcome of patients with Crohn's disease of the upper gastrointestinal tract.

BACKGROUND: To follow-up clinical and biochemical features in patients with Crohn's disease (CD) of the upper gastrointestinal (GI) tract and to evaluate the impact of different therapeutics on the outcome of these patients. METHODS: 32 CD patients with endoscopically and histologically proven CD of the upper GI tract were included into this retrospective study. Gastroduodenal and intestinal permeability tests, inflammatory parameters, Crohn's Disease Activity Index (CDAI), and upper gastrointestinal complaint profile were sequentially assessed. These parameters were assessed at the beginning and followed up during therapies with antisecretory drugs, mesalamine, prednisolone, and azathioprine. RESULTS: Symptoms responded to antisecretory drugs. Gastroduodenal permeability increased under mesalamine. Gastroduodenal and intestinal permeability as well as CDAI decreased under prednisolone. Under azathioprine, gastroduodenal and intestinal permeability, CDAI, and C-reactive protein decreased.

An open-label trial of the selective cyclo-oxygenase-2 inhibitor, rofecoxib, in inflammatory bowel disease-associated peripheral arthritis and arthralgia.

BACKGROUND: Conventional non-steroidal anti-inflammatory drugs have been associated with an increased risk of exacerbation of inflammatory bowel disease. AIM: To evaluate, in a prospective, open-label study, the safety and efficacy of a 20-day regimen of the selective cyclo-oxygenase-2 inhibitor, rofecoxib, 12.5-25 mg/day, in inflammatory bowel disease patients with associated peripheral arthropathy and/or arthritis. METHODS: Patients with clinically inactive to mild inflammatory bowel disease and a joint pain score of at least two points on a scale ranging from zero (none) to four (very poor) were eligible. Response was defined by a decrease of at least two points in the arthralgia score. RESULTS: Of the 32 patients included, 26 (81%) were treated with rofecoxib, 25 mg/day, and six (19%) with rofecoxib, 12.5 mg/day. In three patients (9%), rofecoxib had to be withdrawn after a few days due to gastrointestinal complaints which ceased immediately after drug discontinuation. No flare of inflammatory bowel disease occurred. Thirteen of the 32 patients (41%) were responders and, overall, the arthralgia score decreased from two to one (P = 0.0001). CONCLUSIONS: This is the first prospective study on the use of a selective cyclo-oxygenase-2 inhibitor in inflammatory bowel disease patients with peripheral arthropathy and/or arthralgia. The promising safety and efficacy profile warrants further evaluation in controlled trials.

Antibiotics and azathioprine for the treatment of perianal fistulas in Crohn's disease.

BACKGROUND: Antibiotics and thiopurines have been employed in the management of fistulizing Crohn's disease, although evidence of their efficacy is rare. AIM: To evaluate, in a prospective, open-label study, the influence of antibiotics and azathioprine on the clinical outcome of perianal fistulas in patients with Crohn's disease. METHODS: Fifty-two patients entered the study, starting with an 8-week regimen of ciprofloxacin (500-1000 mg/day) and/or metronidazole (1000-1500 mg/day). Seventeen patients had already received daily azathioprine (2-2.5 mg/kg) at enrollment, whereas in 14 patients azathioprine was initiated after 8 weeks of antibiotic treatment. Outcome was evaluated by Fistula Drainage Assessment and the Perianal Disease Activity Index at weeks 8 and 20. RESULTS: Overall, 26 patients (50%) responded to antibiotic treatment, with complete healing in 25% of patients at week 8. The Perianal Disease Activity Index decreased significantly from 8.4 +/- 2.9 to 6.0 +/- 4.0 (P < 0.0001). At week 20, the outcome was assessed in 49 patients (94%), 29 of whom (59%) had received azathioprine. Response was noted in 17 of the 49 patients (35%), with complete healing in nine patients (18%). Patients who received azathioprine were more likely to achieve a response (48%) than those without immunosuppression (15%) (P = 0.03). The Perianal Disease Activity Index was closely associated with treatment response and perianal disease activity. CONCLUSION: Antibiotics are useful to induce a short-term response in perianal Crohn's disease, and may provide a bridging strategy to azathioprine, which seems to be essential for the maintenance of fistula improvement.

Prevalence and clinical importance of hypertransaminasaemia in coeliac disease.

OBJECTIVE: To assess the prevalence and potential pathogenetic factors of hypertransaminasaemia in patients with coeliac disease prior to initiation of a gluten-free diet (GFD) and to assess the course of transaminases on a GFD. PATIENTS: A retrospective study was made of 178 patients with coeliac disease (130 women, 48 men; median age 36 years; range 17-84 years) at the gastroenterological department of a university hospital. METHODS: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured prior to initiation of a GFD and at 3, 6 and 12 months of GFD. Intestinal permeability, a test for functional integrity of the small bowel, was investigated before starting a GFD in 116 patients by an oral test using lactulose and mannitol. RESULTS: In 72 patients (40.4%) AST and/or ALT were increased prior to initiation of a GFD. Within 1 year on a GFD ALT and AST normalized except in eight cases (4.6%). The intestinal permeability index (% lactulose/% mannitol in 5 h urine) was higher in patients with elevated (median 0.34; range 0.03-1.43) than in patients with normal transaminases (0.11; 0.02-1.28) (P < 0.0001) and correlated with AST (tau = 0.34; P < 0.0001) and ALT (tau = 0.32; P < 0.0001). In five cases with hypertransaminasaemia a liver biopsy was performed prior to initiation of a GFD. Two patients had mild to moderate hepatitis with septal fibrosis. The other three had minimal lymphocytic infiltrates of the portal tracts. Inflammatory alterations of the bile ducts were not found. CONCLUSION: Hypertransaminasaemia before GFD is frequent in coeliac patients, correlates with intestinal permeability and normalizes on a GFD in most patients. In cases of persistently elevated liver function tests of unknown origin underlying coeliac disease should be considered.

A decade of infliximab: The Austrian evidence based consensus on the safe use of infliximab in inflammatory bowel disease.

Infliximab (IFX) has tremendously enriched the therapy of inflammatory bowel diseases (IBD) and other immune mediated diseases. Although the efficacy of IFX was undoubtedly proven during the last decade numerous publications have also caused various safety concerns. To summarize the immense information concerning adverse events and safety issues the Austrian Society of Gastroenterology and Hepatology launched this evidence based consensus on the safe use of IFX which covers the following topics: infusion reactions and immunogenicity, skin reactions, opportunistic infections (including tuberculosis), non-opportunistic infections (bacterial and viral), vaccination, neurological complications, hepatotoxicity, congestive heart failure, haematological side effects, intestinal strictures, stenosis and bowel obstruction (SSO), concomitant medication, malignancy and lymphoma, IFX in the elderly and the young, mortality, fertility, pregnancy and breast feeding. To make the vast amount of information practicable for routine application the consensus was finally condensed into a checklist for a safe use of IFX which consists of two parts: issues to be addressed prior to anti-TNF therapy and issues to be addressed during maintenance. Both parts are further divided into obligatory and facultative items.

[Aminosalicylates and steroids in the treatment ot chronic inflammatory bowel diseases--consensus paper of the Working Group for Chronic Inflammatory Bowel Diseases of the OGGH]. / Aminosalicylate und Steroide in der Behandlung von chronisch entzündlichen Darmerkrankungen -- Konsensuspapier der Arbeitsgruppe für chronisch entzündliche Darmerkrankungen der OGGH.

5-aminosalicylates (5-ASA) and steroids constitute a cornerstone of medical therapy in patients with inflammatory bowel diseases (IBD). Whereas the efficacy of 5-ASA in Crohn's disease (CD) is equivocal, ulcerative colitis (UC) is the main indication for this drug. In UC, 5-ASA is effective in the treatment of mild to moderate acute disease and in maintenance of remission. Furthermore, 5-ASA topical therapy is an important treatment option in patients with mild to moderate proctitis and/or left-sided UC and shows additive efficacy to oral therapy. From retrospective data a chemo-preventative activity of long-term 5-ASA therapy in UC is delineated. Steroids are treatment of first choice for moderate to severe cases of CD and UC. Budesonide, a modified steroid with less side effects, plays a major role in the treatment of ileocolonic CD +/- involvement of the right colon and is used as treatment of choice in mild-to-moderate cases. In case of acute, severe disease conventional steroids are superior compared to budesonide and therefore budesonide should only be used after considerable improvement of disease activity. The necessity to apply steroids in a given patient represents a negative prognostic indicator for the course of disease and should incite the early introduction of immunosuppressive therapy in this case. Steroids are only effective as short term therapy of IBD and are to be avoided for maintenance treatment. In all cases of steroid therapy an osteoporosis prophylaxis with calcium and vitamin D is recommended. Topical steroid treatment is less effective in left-sided UC compared to 5-ASA.

Mechanic intestinal obstruction--a possible presentation of perforated appendicitis.

A 61-year-old man presented with diffuse abdominal pain, diarrhea, vomiting and fever. On the initial diagnosis of gastroenteritis the patient received the antibiotic ofloxacine for one week. On admission plain abdominal radiograph suggested a mechanic intestinal obstruction. In computed tomography a conglomerate tumor in the ileocecal region was seen and the patient underwent laparotomy. The conglomerate tumor was mobilized and an abscess opened, which was caused by a perforated appendicitis. After the operation the patient improved immediately and had an uneventful postoperative course. He was released and did not suffer from gastrointestinal symptoms the following 16 months of follow-up. The present case shall set forth that perforated appendicitis can clinically present as intestinal obstruction. Although a rare complication, perforated appendicitis should therefore even be considered in cases of mechanic intestinal obstruction of unknown cause.

Is mycophenolate mofetil an effective alternative in azathioprine-intolerant patients with chronic active Crohn's disease?

OBJECTIVES: Up to 50% of patients with Crohn's disease (CD) develop steroid-dependent or refractory disease requiring immunosuppression. Azathioprine (AZA) is usually used for this purpose but must be withdrawn in up to 10% of patients because of adverse events. Mycophenolate mofetil (MMF) is of proven efficacy and safety in transplantation and in some autoimmune disorders. The aim of the present study was to investigate the effect of MMF, especially in AZA-intolerant patients with chronic active CD, in comparison to a matched control group treated with AZA. METHODS: In a retrospective study, 15 patients treated with MMF and 30 randomly chosen, matched patients treated with AZA for chronic active CD were compared over a period of 1 yr. Intolerance to AZA was the indication for MMF. Crohn's Disease Activity Index (CDAI), steroid demand, extraintestinal manifestations, and hematological and biochemical parameters were assessed at the start of therapy and 1, 2, 3, 6, 9, and 12 months thereafter. RESULTS: All patients who completed the 12 months of treatment (77% AZA, 60% MMF) achieved remission. Under MMF, the cumulative prednisolone dose could be reduced by 1 g in the first half year, whereas, under AZA, this reduction was possible only in the second half year. MMF patients had almost twice as many flare-ups (80% vs 47%). Adverse events prompted the withdrawal of AZA in five patients (17%) and of MMF in three (20%). CONCLUSIONS: Both drugs are effective in inducing remission. AZA seems to be more effective in maintaining remission. The onset of therapeutic effect is delayed less under MMF. Both drugs have steroid sparing potential, which is delayed under AZA. It seems that AZA still is the immunouppressant of choice in chronic active CD, but MMF is a reasonable alternative in patients who do not tolerate AZA.

Thromboembolism and resistance to activated protein C in patients with inflammatory bowel disease.

OBJECTIVE: Thromboembolic events are serious complications in patients with inflammatory bowel disease (IBD). Resistance of factor V to degradation by activated protein C (APC) is a major cause for venous thrombosis and is found in approximately 30% of patients with thromboembolism. The aim of the present study was to assess the prevalence of APC resistance and clinical risk factors in patients with IBD. METHODS: One-hundred-two patients with IBD (64 women and 38 men; median age, 35 yr; range, 17-77 yr; 77 with Crohn's disease, 25 with ulcerative colitis) and 102 gender- and age-matched healthy control subjects were investigated prospectively for the presence of APC resistance. None of the healthy controls but 16 patients with IBD had a history of thromboembolism. RESULTS: Patients with IBD and thromboembolism were young, with a median age of 37 yr (range, 17-61 yr). Five (31.3%) of them had APC resistance, which was more common than in patients with IBD without thromboembolism (7%) and in controls (5.9%) (p < 0.01). Three patients had two thromboembolic events, the other 13 each had one. Deep vein thrombosis of the leg and pulmonary emboli were the most common thromboembolic complications (84.2%). Active disease, fistula, or bowel stenosis were found in 10 (52.6%) of 19 thromboembolic events; in three (15.8%) cases thromboembolism happened postoperatively. CONCLUSIONS: APC resistance is not associated with IBD but, when present, increases the risk of thromboembolism. Patients with IBD and thromboembolism are mostly young and clinical risk factors can be found in one-half of cases.

Is inflammatory bowel disease an independent and disease specific risk factor for thromboembolism?

BACKGROUND: Patients with inflammatory bowel disease (IBD) are thought to be at increased risk of venous thromboembolism (TE). However, the extent of this risk is not known. Furthermore, it is not known if this risk is specific for IBD or if it is shared by other chronic inflammatory diseases or other chronic bowel diseases. AIMS: To compare the risk of TE in patients with IBD, rheumatoid arthritis, and coeliac disease with matched control subjects. PATIENTS AND METHODS: Study subjects answered a questionnaire assessing the history of TE, any cases of which had to be confirmed radiologically. A total of 618 patients with IBD, 243 with rheumatoid arthritis, 207 with coeliac disease, and 707 control subjects were consecutively included. All three patient groups were compared with control subjects matched to the respective group by age and sex. RESULTS: Thirty eight IBD patients (6.2%) had suffered TE. This was significantly higher compared with the matched control population with only 10 cases reported (1.6%) (p<0.001; odds ratio (OR) 3.6 (95% confidence interval (CI) 1.7-7.8)). Five patients with rheumatoid arthritis (2.1%) had suffered TE compared with six subjects (2.5%) in the control population matched to patients with rheumatoid arthritis (NS; OR 0.7 (95% CI 0.2-2.9)). TE had occurred in two patients with coeliac disease (1%) compared with four subjects (1.9%) in the control population matched to the coeliac disease group (NS; OR 0.4 (95% CI 0.1-2.5)). In 60% of TE cases in the IBD group, at least one IBD specific factor (active disease, stenosis, fistula, abscess) was present at the time TE occurred. CONCLUSIONS: IBD is a risk factor for TE. It seems that TE is a specific feature of IBD as neither rheumatoid arthritis, another chronic inflammatory disease, nor coeliac disease, another chronic bowel disease, had an increased risk of TE.