NOD2/CARD15 mutations and the risk of reoperation in patients with Crohns disease.

INTRODUCTION: Three NOD2/CARD15 gene variants (3020insC, R702W, G908R) have been identified as genetic risk factors for Crohns disease patients. However the diagnostic and therapeutic relevance for clinical practice remains limited. The aim of this study was to evaluate the association between these variants, the risk of reoperation and disease phenotype. METHODS: In 76 Crohns disease patients (41 female, 35 male) with a minimum 5 year follow-up, three polymorphisms of the NOD2/CARD15 gene (R702W, G908R, 3020insC) were tested. Detailed clinical and medical history including surgical procedures and reoperations were obtained by reviewing the medical charts and completed prospectively. Association between the need for reoperation, disease phenotypes and gene variants were analyzed. RESULTS: 24 patients (32%) showed at least one NOD2/CARD15 mutation. 25 patients (33%) required reoperation, 51 (67%) represented the control group. The expected trend that patients with NOD2/CARD15 variants have a higher frequency of reoperations was not confirmed to a level of statistical significance (p=0.2688). Two of the four patients (50%) with the 3020insC variant required further surgery. We did not confirm any association between NOD2/CARD15 mutations and age at diagnosis (p=0.4356), behavior (p=0.6610), or localization (p=0.4747) according to the Montreal classification. CONCLUSION: NOD2/CARD15 polymorphisms did not significantly affect the reoperation rate. Homozygosity for the 3020insC variant in the NOD2/CARD15 gene is associated with a high risk of reoperation. NOD2/CARD15 gene variants are not significantly associated with specific disease phenotypes.

Differentiating autoimmune pancreatitis from pancreatic cancer.

Differential diagnosis between autoimmune pancreatitis (AIP) and pancreatic cancer can be very difficult. The main clinical symptoms in patients with autoimmune pancreatitis are jaundice, weight loss, abdominal pain and new onset of diabetes mellitus. Unfortunately, the same symptoms could be observed in patients with pancreatic carcinoma too. Imaging methods as computed tomography (CT) scan, magnetic resonance imaging (MRI) and endosonography (EUS); together with serological examination (IgG4 and Ca 19-9) play the important role in differentiation autoimmune pancreatitis from pancreatic cancer. Extrapancreatic findings are distinctive in patients with autoimmune pancreatitis. In some cases the pancreatic biopsy is indicated, mainly in patients with focal or multifocal form of autoimmune pancreatitis. Response to steroids (decreased pancreatic or extrapancreatic lesion or damage) is distinctive to AIP. In clinical practice, CT scan seems to be the most reasonable tool for examining the patients with obstructive jaundice with or without present pancreatic mass. Stratification the patients with possible AIP versus pancreatic cancer is important. In patients with AIP it may avoid pancreatic resection, as well as incorrect steroid treatment in patients with pancreatic carcinoma.

[Specificities of the diagnostics and therapy of exocrine pancreatic insufficiency]. / Zvlástnosti diagnostiky a terapie exokrinní pankreatické nedostatecnosti

Exocrine pancreatic insufficiency develops steadily; however, the initial reduction in secretion is practically not diagnosable. More advanced stages, which usually replicate morphological changes, can be determined with tests which asses the exocrine pancreatic capacity. Substantial damage of the pancreas and replacement of viable parenchyma with connective tissue is accompanied by the occurrence of steatorrhoea. This corresponds to a reduction in exocrine pancreatic secretion below 10% of physiological secretion. Exocrine pancreatic secretion tests are still not sufficiently sensitive for diagnosing early stages of pancreas defects and thus are not suitable for diagnostics. Furthermore, detecting reduced exocrine secretion does not provide any information about the aetiology of the disease, e.g. inflammation/tumor. The most precise test is a costly examination, including a stimulation of the gland with enterohormones; however, breath tests are usually recommended for the assessment of exocrine insufficiency therapy. Exocrine pancreatic insufficiency therapy consists of administering drugs containing pancreatin (amylase, lipase, and peptidase) to patients diagnosed with steatorrhoea, manifest pancreatic insufficiency. As standard, capsules containing microparticles of 1-2mm are recommended. They have a protective coating that prevents inactivation in the microparticles of the contained enzymes by gastric hydrochloric acid. The drug should be administered during each meal, i.e. several times a day. The most common mistake during pancreatic enzyme therapy is under dosage. The following rule applies to patients with digestive insufficiency: 40,000-50,000 UNT of lipase are to be administered during "main meals" and 25,000 UNT of lipase during morning or afternoon snacks. The drug should be taken during the meal; insufficient treatment and dosage are associated with insufficient digestion and absorption ofa number of substances and also with pancreatic malabsorption.