Belgian guidelines for pathology reporting of neuroendocrine neoplasms of the pancreaticobiliary and gastrointestinal tract.

Since neuroendocrine neoplasms are rare tumors, registration of patient data in national and multinational registries is recommended. Indeed, this will facilitate multicenter studies on the epidemiology, efficacy and safety of diagnostic and therapeutic strategies for well-differentiated neuroendocrine tumors as well as for neuroendocrine carcinomas. In Belgium, data on patient and tumor characteristics of all newly diagnosed malignancies have been collected in the Belgian Cancer Registry since 2004 including anonymized full pathological reports. The Digestive Neuroendocrine Tumor (DNET) registry collects information on classification, staging, diagnostic tools and treatment in a prospective national online database. However, the terminology, classification and staging systems of neuroendocrine neoplasms have changed repeatedly over the past 20 years as a result of a better understanding of these rare tumors, by joining forces internationally. These frequent changes make it very difficult to exchange data or perform retrospective analyses. For optimal decision making, for a clear understanding and to allow reclassification according to the latest staging system, several items need to be described in the pathology report. This paper provides an overview of the essential items in reporting neuroendocrine neoplasms of the pancreaticobiliary and gastrointestinal tract.

Kinetics of butyrate metabolism in the normal colon and in ulcerative colitis: the effects of substrate concentration and carnitine on the ß-oxidation pathway.

BACKGROUND: Butyrate, a colonic metabolite of carbohydrates, is considered as the major energy source for the colonic mucosa. An impaired butyrate metabolism has been reported in ulcerative colitis (UC), however, the cause still remains unknown. AIM: In the present study, we investigated whether higher butyrate concentrations could normalise the oxidation rate in UC. Furthermore, it was investigated whether carnitine could enhance the butyrate oxidation. METHODS: Mucosal biopsies from a total of 26 UC patients and 25 controls were incubated with (14)C-labelled Na-butyrate and the produced (14)CO(2) was measured. First, the rate of oxidative metabolism was compared at three different concentrations of Na-butyrate (0.05 mm, 1 mm and 10 mm). Then, incubations of biopsies were performed with carnitine alone or combined with ATP. RESULTS: Overall, butyrate oxidation in UC was significantly lower than that in controls. The maximum rate of butyrate oxidation was achieved in UC and control subjects from 1 mm onwards. Increasing the butyrate concentration to a level to be present in the colonic lumen, i.e. 10 mm, did not increase the rate of butyrate oxidation in UC to the rate observed in controls. Addition of carnitine alone or combined with ATP caused no effects. CONCLUSIONS: Saturation of butyrate kinetics was achieved from 1 mm in UC and control subjects. The rate of butyrate metabolism was significantly impaired in active ulcerative colitis. The addition of compounds interfering with the ß-oxidation pathway had no effect on the butyrate metabolism in UC.

EGFR-immunohistochemistry in colorectal cancer and non-small cell lung cancer: comparison of 3 commercially available EGFR-antibodies.

BACKGROUND: Epidermal Growth Factor Receptor (EGFR)-targeted therapies are currently used for the treatment of metastasized colorectal cancer (CRC) and non small cell lung cancer (NSCLC). Patient selection for this treatment is based on immunohistochemical (IHC) testing for EGFR. The rising amount of commercially available EGFR-antibodies makes standardisation of EGFR-IHC necessary. The goal of this study was to analyse possible discrepancies between 3 antibodies against EGFR. PATIENTS AND METHODS: 36 formalin-fixed samples of CRC (n = 26) and NSCLC (n = 10) were stained with 3 antibody-clones: 2-18C9 (Dako); 31G7 (VentanaTM) and 111.6 (Labvision Neomarkers). Interpretation of stains includes assessment of % positive cells, evaluation of cut off values and staining intensity. RESULTS: With a 1% cut-off, the 2-18C9 clone stained 86% of the cases positive, the 31G7-clone 77% and the 111.6-clone 52%. With a 10% cut-off, percentages declined to 77%, 61% and 30% respectively. The 2-18C9-clone showed the highest staining intensity. The 2-18C9 clone and the 31G7-clone showed a concordance rate of 90%. CONCLUSIONS: IHC staining with 3 different antibody clones directed against EGFR shows indeed differences in staining results: the percentage of positive cells and staining intensity are variable. A correct cut-off value for a positive result is important and can be different depending upon the antibody. Appropriate validation of an antibody is essential before it can be used for selection of patients.

Contribution of morphology for the comprehension of mechanisms of fibrosis in inflammatory enterocolitis.

Strictures are a common complication of Crohn's disease and an indication for surgery in approximately 50% of patients. Morphologic studies have shown that fibrosis of the submucosa and muscularis propria are common in Crohn's disease, especially in strictures. Immunohistochemical and in situ hybridization studies have demonstrated a marked increase of various subtypes of collagens in Crohn's disease. Collagens type I and III are present in ulcerated areas where they appear around capillaries and in a linear deposition at the junction between the granulation tissue and the necrotic debris. Collagens type IV and V show a prominent perivascular expression, increased deposition in the muscularis propria and increased expression around ganglia. Initiation and maintenance of the connective tissue changes are related with the inflammatory infiltrate. Inflammatory cells can further alter smooth muscle proliferation and migration and promote the formation of myofibroblasts. These alterations together with increased collagen deposition are involved in the complex process of strictures and bowel wall alterations in Crohn's disease.

Effects of 'contact laxatives' on intestinal and colonic epithelial cell proliferation.

Experimental studies indicate that laxatives may induce epithelial damage. In addition, some laxatives induce the release of prostaglandins. Epithelial cell damage and release of prostaglandins are two pathways by which epithelial cell proliferation could be influenced. Furthermore, fermentable laxatives like lactulose may influence large intestine cell proliferation by the trophic effect of the fermentation products such as short-chain fatty acids. For these reasons an in vivo study in rats was performed to compare the short- and long-term effect of sennosides, bisacodyl, sodium picosulfate and lactulose on epithelial cell proliferation in the ileum and large intestine. Cell proliferation was examined by the BrdUrd labelling technique after 2, 6 and 12 weeks of continuous treatment. Studies in control animals show that the Labeling Index (LI) is higher in the cecum compared with other segments of the colon, and higher in the ileum than in the colon. Treatment with sennosides, bisacodyl and sodium picosulfate does not influence the LI in the ileum and induces no statistically significant increase of the LI when the treated groups are compared with the control group. The proliferative pattern along the crypts remains unchanged with all the laxatives throughout the study. It appears therefore that 'contact' laxatives have no major influence on ileal and colonic epithelial cell proliferation and should not be regarded as tumor-promoting substances.