Prospective multicentre clinical study on inter- and intrapatient genetic variability for antimicrobial resistance of Helicobacter pylori.

OBJECTIVES: We report on a large prospective, multicentre clinical investigation on inter- and intrapatient genetic variability for antimicrobial resistance of Helicobacter pylori. METHODS: Therapy-naive patients (n = 2004) who had undergone routine diagnostic gastroscopy were prospectively included from all geographic regions of Austria. Gastric biopsy samples were collected separately from antrum and corpus. Samples were analysed by histopathology and real-time PCR for genotypic resistance to clarithromycin and quinolones. Clinical and demographic information was analysed in relation to resistance patterns. RESULTS: H. pylori infection was detected in 514 (26%) of 2004 patients by histopathology and confirmed in 465 (90%) of 514 patients by real-time PCR. PCR results were discordant for antrum and corpus in 27 (5%) of 514 patients, indicating inhomogeneous infections. Clarithromycin resistance rates were 17% (77/448) and 19% (84/455), and quinolone resistance rates were 12% (37/310) and 10% (32/334) in antrum and corpus samples, respectively. Combination of test results per patient yielded resistance rates of 21% (98/465) and 13% (50/383) for clarithromycin and quinolones, respectively. Overall, infection with both sensitive and resistant H. pylori was detected in 65 (14%) of 465 patients. CONCLUSIONS: Anatomically inhomogeneous infection with different, multiple H. pylori strains is common. Prospective clinical study design, collection of samples from multiple sites and microbiologic methods that allow the detection of coinfections are mandatory for collection of reliable data on antimicrobial resistance patterns in representative patient populations. (ClinicalTrials.gov identifier: NCT02925091).

[Non-cirrhotic portal hypertension presented by acute upper gastrointestinal bleeding 7 years after oxaliplatin-chemotherapy]. / Nicht zirrhotische portale Hypertension mit bedrohlicher Blutungskomplikation 7 Jahre nach Oxaliplatin-Chemotherapie.

After having received adjuvant FOLFOX treatment consisting of oxaliplatin, folinic acid and fluoruracil following hemicolectomy in colon cancer 7 years ago, the findings of non-cirrhotic portal hypertension presented by acute upper gastrointestinal bleeding in a 49-year old woman were interpreted as oxaliplatin-associated. Imaging techniques, hepatic venous pressure measurement and liver biopsy supported pre-sinusoidal damage due to NRH (nodular regenerative hyperplasia) as the underlying cause, even though histological findings were moderate. Following primary endoscopic treatment, a stable condition has thus far been achievable with standard drug therapy.

[Cystic echinococcosis and hepatocellular carcinoma--a coincidence? A case report]. / Zystische Echinokokkose und hepatozelluläres Karzinom--zufällige Koinzidenz? Ein Fallbericht.

INTRODUCTION: The coincidence of echinococcosis and hepatocellular carcinoma (HCC) is quite rare. We report the case of a 45-year-old man who was admitted to our hospital because of abdominal pain in the right upper quadrant and jaundice. Clinical features and diagnostics: There was no history of weight loss or fever. No abdominal mass was palpable. The laboratory reports showed increased transaminase levels. Ultrasonography revealed an inhomogenous, cystic lesion measuring 6 cm in diameter in the segments VI and VII. Serology for echinococcosis was negative, alpha-fetoprotein (AFP) was considerably increased. CT scan showed a solid mass of 3,7 cm in diameter adjacent to the cystic lesion. THERAPY AND COURSE: Anthelminthic therapy with albendazole caused a massive increase of cholestasis parameters and treatment had to be stopped. The simultaneous occurrence of serologically negative cystic echinococcosis and HCC was suspected and partial liver resection was performed. Histological examination confirmed both diagnoses and tumor resection in healthy tissue. 5 months after resection CT scan showed multicentric HCC affecting the whole liver. Palliative therapy with sorafenib was established. DISCUSSION: The coincidence of HCC and cystic echinococcosis in the non-cirrhotic liver of a young man is a rare event. Despite resection in healthy tissue multicentric HCC was diagnosed 5 months later. Only few cases of simultaneous occurrence of HCC and echinococcosis have been published so far. Some authors considered echinococcosis as a trigger for HCC. A causal link between both entities has not been demonstrated until now.

[Adalimumab for the treatment of ulcerative colitis--a consensus report by the working group inflammatory bowel diseases of the Austrian Society of Gastroenterology and Hepatology]. / Adalimumab in der Behandlung der Colitis ulcerosa--ein Konsensus der Arbeitsgruppe Chronisch Entzündliche Darmerkrankungen der Österreichischen Gesellschaft für Gastroenterologie und Hepatologie.

TNF alpha antibodies have clearly improved the outcome of moderately to severely active ulcerative colitis. Adalimumab is the first fully human, monoclonal TNF alpha antibody, which is administered subcutaneously. Since April 2012 adalimumab is approved for the treatment of moderately to severely active ulcerative colitis in patients who have not responded despite a full and adequate course of therapy with a corticosteroid and an immunosuppressant or who are intolerant to or have medical contraindications for such therapies. Adalimumab can induce and maintain clinical remission and mucosal healing compared to placebo in moderately to severely active ulcerative colitis, can reduce the rate of ulcerative colitis related hospitalisations and improve health-related quality of life. The response can be observed after two weeks of treatment. The safety profile of adalimumab is comparable to those of other TNF alpha inhibitors. Studies on the treatment of ulcerative colitis with adalimumab did not reveal new safety aspects. The present consensus report by the Working Group Inflammatory Bowel Diseases of the Austrian Society of Gastroenterology and Hepatology presents the existing evidence of adalimumab for the treatment of ulcerative colitis and is aimed to assist as code of its practice.

[Adalimumab for the treatment of adult Crohn's disease--update of a consensus report by the Working Group Inflammatory Bowel Disease of the Austrian Society of Gastroenterology and Hepatology]. / Adalimumab in der Behandlung des adulten Morbus Crohn--Update eines Konsensus der Arbeitsgruppe Chronisch Entzündliche Darmerkrankungen der Österreichischen Gesellschaft für Gastroenterologie und Hepatologie.

TNF alpha antibodies have clearly improved the outcome of moderate to severe Crohn's disease. Adalimumab is the first fully human, monoclonal TNF alpha antibody, which can be self-administered subcutaneously. Since August 2012 adalimumab is approved for the treatment of moderately to severely active Crohn's disease, in patients who have not responded despite a full and adequate course of therapy with a corticosteroid and/or an immunosuppressant or who are intolerant to or have medical contraindications for such therapies. Compared to placebo adalimumab can induce significantly more often steroid-free remission and mucosal healing in patients with moderate to severe Crohn's disease, reduce the rate of Crohn's disease-related hospitalisations and surgery and improve health-related quality of life. Adalimumab is clinically efficacious both in patients with Crohn's disease naïve to previous exposure to TNF-alpha antibodies and in those previously exposed with a rapid onset of action within days and confirmed maintenance performance over 3 years. The safety profile of adalimumab is comparable to those of other TNF alpha inhibitors. Due to its low immunogenicity allergic reactions are rare. The update of a consensus report by the Working Group Inflammatory Bowel Disease of the Austrian Society of Gastroenterology and Hepatology presents the existing evidence on adalimumab for the treatment of Crohn's disease and is aimed to assist as a code of practice in its applications.

Prevalence of flat lesions in a large screening population and their role in colonoscopy quality improvement.

BACKGROUND AND STUDY AIMS: Flat lesions pose new challenges for endoscopists, but the importance of detecting them is still controversial. Most screening studies do not survey macroscopic polyp morphology. The aims were to evaluate the percentage of flat polyp findings in a large asymptomatic adult screening population (n = 52 521), to assess the impact of shape and size on malignant transformation, and to assess the role of flat lesions regarding quality assurance in colorectal cancer prevention. MATERIAL AND METHODS: Retrospective analysis of screening colonoscopies performed between 2007 and 2011 according to the Austrian "Quality management for colon cancer prevention" program. RESULTS: 17 771 patients with polyps were included in the study. Patients with flat polyps represented 24.2 % (n = 4293), 62.4 % (n = 11 097) were classified as having sessile and 13.4 % (n = 2381) as pedunculated polyps. Among those with flat polyps 51.4 % had adenomas (n = 2207). High grade dysplasia (HGD) was found in 2.1 % (n = 47) of flat adenomas, in 1.5 % (n = 89) of sessile adenomas and 4.7 % (n = 92) of pedunculated adenomas (P < 0.0001. The risk for containing HGD was 1.0 % for flat lesions ≤ 10 mm in size compared with 10.3 % for lesions > 10 mm, and 1.0 % for polypoid lesions ≤ 10 mm compared with 9.3 % for lesions > 10 mm (P < 0.0001). Multivariable logistic regression showed that polyp size (P < 0.0001) but not polyp shape (P = 0.438) is an independent predictor for HGD. Adenoma detection rate (ADR) correlated weakly with the flat polyp detection rate (Pearson r = 0.24). CONCLUSION: Malignant potential of polyps is mostly affected by size but not by shape. Since flat polyp detection rate only correlates poorly with ADR we do not recommend its incorporation in quality assured screening colonoscopy.

[Diagnosis and treatment of iron deficiency and anaemia in inflammatory bowel diseases. Consensus of the Austrian IBD Working Party]. / Diagnose und Behandlung von Eisenmangel und Anämie bei chronisch entzündlichen Darmerkrankungen. Konsensus der österreichischen Arbeitsgruppe für CED.

Iron deficiency with and without anaemia is a common burden of patients with inflammatory bowel diseases (IBD) and has considerable impact on their quality of life and the ability to perform. The IBD working group of the Austrian Society of Gastroenterology and Hepatology developed five consensus statements on the following topics: (i) diagnosis of iron deficiency and (ii) anaemia, (iii) screening of iron deficiency, (iv) treatment of iron deficiency and (v) therapeutic goals. The clinical importance of intravenous iron replacement therapy in IBD with regard to effectiveness and compliance was discussed.

[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.

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.

[Colocutaneous fistula after a PEG procedure with introducer technique and gastropexy]. / Kolokutane Fistel nach PEG-Anlage mittels Introducer-Technik mit Gastropexie.

INTRODUCTION: The pull-PEG (percutaneous endoscopic gastrostomy) is the most commonly used procedure for PEG placement. Alternative methods may be used in patients with an obstructed oesophagus. We here present the case of an unusual complication during PEG placement with the new introducer technique and gastropexy. CASE REPORT: A 74-year-old men with progressive thymus cell carcinoma was referred for a PEG procedure. Since the tumour stenosis in the oesophagus was only passable with a slim-sight endoscope (5,9 mm), we decided in favour of the direct PEG method with gastropexy. The procedure was performed without any complications. 35 days later we changed the balloon catheter and were able to easily inflate the balloon. Surprisingly, the X-ray performed thereafter, revealed a misplacement of the catheter in the colon without any notable contrast medium in the stomach. Although the patient expressed no complaints, he underwent surgery on the same day proving the colocutaneous fistula. There were no signs of peritonitis. The patient's postoperative recovery was uneventful. DISCUSSION: Pull-PEG requires an intact oesophageal passage. The spread of bacteria and tumour cells is a possible risk factor. Direct punction PEG might be better in these cases. This method is not a standard procedure, but the recent implementation of an additional gastropexy represents a significant improvement. We experienced a rare complication, which was first described in 1987. However, this case is the first documented complication in association with gastropexy. This case shows that even gastropexy does not prevent colon interposition. Therefore, an endoscopic or radiological control of the tube placement after changing seems to be necessary.

[Adalimumab for the treatment of Crohn's disease - consensus paper of the Working Group "chronic inflammatory bowel diseases" of the Austrian Society for Gastroenterology and Hepatology]. / Adalimumab in der Behandlung des Morbus Crohn - ein Konsensus der Arbeitsgruppe Chronisch Entzündliche Darmerkrankungen der Osterreichischen Gesellschaft für Gastroenterologie und Hepatologie.

The advent of anti-TNF alpha antibodies has clearly improved the outcome of patients with Crohn's disease. With adalimumab, the first fully human, monoclonal anti-TNF alpha antibody, which can be administered subcutaneously by means of a pen, became available in 2007. In Europe adalimumab is approved for the treatment of severe, active Crohn's disease, in patients who have not responded despite a full and adequate course of therapy with a corticosteroid and/or an immunosuppressant; or who are intolerant to or have medical contraindications for such therapies. Adalimumab is clinically efficacious both in patients with Crohn's disease naïve to previous exposure to anti-TNF alpha antibodies and in those previously exposed with a rapid onset of action and a confirmed maintenance performance over 3 years. A reduction in the rate of hospitalisation and an improvement of health-related quality of life are associated with this treatment. The safety profile of adalimumab is comparable to those of other TNF alpha inhibitors. Due to low immunogenicity, allergic reactions are rare. A careful screening of patients before and during treatment with adalimumab is of key importance. The presented therapy guidelines based on existing evidence are aimed to assist in the efficient and safe use of adalimumab in the treatment of Crohn's disease.

[Use of infliximab in ulcerative colitis]. / Infliximab in der Therapie der Colitis ulcerosa.

Infliximab, a chimeric monoclonal anti-tumour necrosis factor alpha (TNF) antibody has dramatically changed the management of various chronic inflammatory disorders such as Crohn's disease (CD), rheumatoid arthritis, ankylosing spondylitis or psoriasis. This drug is well established for the treatment of CD in case of steroid-refractoriness, failure to respond to an immunosuppressant agent or fistulizing disease. The immunological concept that ulcerative colitis (UC) reflects primarily a T-helper cell type-2 mediated disease prevented the earlier use of anti-TNF agents in this disease. Promising initial pilot studies in steroid-refractory UC patients led to two large placebo-controlled trials in patients with moderate to severe UC. These studies clearly showed a benefit for infliximab treatment in UC with mucosal healing and improved life quality. Infliximab therefore can be used in patients not responding adequately to steroids and/or immunosuppressants. Furthermore, one study showed evidence that infliximab might also be effective in severe, intravenous steroid-refractory UC. Therefore, infliximab might be used alternatively to cyclosporine A or tacrolimus in this patient group. Infliximab has now been established as an additional treatment option in patients with chronic-active UC not responding to an immunosuppressive agent and/or in case of severe acute UC. Experienced gastroenterologists should be involved in the decision making for such a therapy to balance thoroughly the benefit/risk ratio for our patients.

[Endoscopy in IBD. A Consensus Report of the IBD Working of the Austrian Association of Gastroenterology and Hepatology]. / Endoskopie bei CED.

Ileocolonoscopy including biopsies is the first line investigation in suspected inflammatory bowel disease (IBD). In up to 90 % of the cases ulcerative colitis and Crohn's disease are differentiated on endoscopic presentation. Standardised reporting of endoscopic results increases the validity and comparability of IBD findings. When there is a firm diagnosis of IBD, colonoscopy should only be performed for specific questions. An upper gastrointestinal endoscopy is only indicated in patients with upper gastrointestinal symptoms. Push and capsule endoscopy should also be limited to specific questions and situations. IBD with extended colitis is associated with an increased risk for colorectal cancer. Endoscopic surveillance with accurate biopsy sampling is a valuable tool for the prevention of colorectal cancer.

[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.

6-Thioguanine treatment in inflammatory bowel disease: a critical appraisal by a European 6-TG working party.

Recently, the suggestion to use 6-thioguanine (6-TG) as an alternative thiopurine in patients with inflammatory bowel disease (IBD) has been discarded due to reports about possible (hepato) toxicity. During meetings arranged in Vienna and Prague in 2004, European experts applying 6-TG further on in IBD patients presented data on safety and efficacy of 6-TG. After thorough evaluation of its risk-benefit ratio, the group consented that 6-TG may still be considered as a rescue drug in stringently defined indications in IBD, albeit restricted to a clinical research setting. As a potential indication for administering 6-TG, we delineated the requirement for maintenance therapy as well as intolerance and/or resistance to aminosalicylates, azathioprine, 6-mercaptopurine, methotrexate and infliximab. Furthermore, indications are preferred in which surgery is thought to be inappropriate. The standard 6-TG dosage should not exceed 25 mg daily. Routine laboratory controls are mandatory in short intervals. Liver biopsies should be performed after 6-12 months, three years and then three-yearly accompanied by gastroduodenoscopy, to monitor for potential hepatotoxicity, including nodular regenerative hyperplasia (NRH) and veno-occlusive disease (VOD). Treatment with 6-TG must be discontinued in case of overt or histologically proven hepatotoxicity.

[Weight loss, abdominal pain and anemia after a holiday abroad--case report of lead poisoning]. / Gewichtsverlust, Bauchschmerzen und Anämie als Folgen einer Urlaubsreise -- Fallbericht einer Bleiintoxikation.

HISTORY AND ADMISSION FINDINGS: A 58-year-old woman with type 1 diabetes and coronary artery disease was admitted to hospital because of diminished appetite, weight loss, abdominal pain and anemia. Earlier treatment of duodenal ulcer and cholecystectomy had not achieved sustained relief. On physical examination paleness and general weakness was noted. INVESTIGATIONS: Laboratory tests showed a normocytic, normochromic anemia, anisocytosis, polychromasia and basophilic stippling of erythrocytes. Bone marrow examination revealed a hyperreactive erythropoesis with basophilic stippling of erythrocytes and incomplete differentiation of erythroid progenitor cells. Inherited or acquired enzymopathies of erythrocytes were ruled out. Urinary collection showed remarkable elevation of porphyrin concentration. DIAGNOSIS, TREATMENT AND COURSE: Suspected poisoning was confirmed by elevated lead concentrations in whole-blood (85.8 microg/dl) and urine (106.3 microg/l). A souvenir of Rhodes, a ceramic mug with lead-containing glaze, was identified as the source of the lead poisoning, the lead dissolving into hot tea put in the mug. Treatment with D-penicillamine was begun, and within five weeks anemia disappeared and the patient achieved complete resolution of symptoms. CONCLUSION: Recognition of the cause of lead poisoning is of critical importance. This case report demonstrates difficulties in diagnosing and identifying the source of poisoning.

Lansoprazole-associated collagenous colitis: a case report.

A 57-year-old man developed chronic, watery diarrhea four weeks after Helicobacter pylori eradication therapy including lansoprazole followed by lansoprazole monotherapy for gastroesophageal reflux disease. Four weeks later the patient was admitted to our hospital. By repeated testing other causes of diarrhea, e. g., infectious diarrhea including Clostridium difficile colitis were excluded. Endoscopy showed a normal colon, histopathology of random biopsies of all sections of the colon demonstrated the characteristic features of collagenous colitis. Withdrawal of lansoprazole lead to prompt and sustained relief. Two months later repeat colonoscopy with biopsies showed no evidence of collagenous colitis. Collagenous colitis as a subtype of microscopic colitis is a rare cause of chronic diarrhea with unknown pathogenesis. The reported case represents an unusual association between medication with the proton pump inhibitor lansoprazole and the development of collagenous colitis suggesting the importance of evaluation of drug use in patients with microscopic colitis.

[Immunosuppressive therapy for inflammatory bowel disease: consensus by the Austrian working group on IBD]. / Immunsuppressiva in der Therapie chronisch entzündlicher Darmerkrankungen. Konsensus der Arbeitsgruppe Chronisch Entzündliche Darmerkrankungen der OGGH.

Azathioprine (AZA) or 6-mercaptopurine (6-MP) are the immunosuppressive drugs of choice in the treatment of inflammatory bowel disorders (IBD). Optimal dosage for AZA is around 2.5 mg/kg body weight and induction of remission by these drugs may take 6 - 7 months. Intramuscularly applied Methotrexate (MTX) is the second choice, while its efficacy starts earlier than that of AZA; studies assessing oral low-dose MTX treatment are lacking. Cyclosporin is the standard treatment in case of steroid-refractory severe ulcerative colitis. This drug may also be used in patients with severe extraintestinal manifestations of IBD. Regarding other immunosuppressive drugs such as mycophenolic acid or 6-thioguanine respective controlled clinical study data are not available. The risk of malignancy using immunosuppressive drugs such as AZA is low and furthermore, especially AZA and 6-MP can be used rather safely during pregnancy.