Surveillance of CDNK2A mutation carriers is relatively successful, detecting most PDACs at a resectable stage. The benefit of surveillance in families with FPC is less evident.

Background: Enteric glia protect the integrity of the gut, as loss of enteric glial fibrillary acidic protein (GFAP) positive (+) glia leads to a haemorrhagic jejunoileitis. Crohn's disease (CD) and necrotising enterocolitis (NEC) show pathological changes in enteric glia. Therefore, factors controlling GFAP+ enteric glia are of great interest. The aim of the present study was to characterise enteric glia and determine the effect of interleukin 1b (IL-1b), interleukin 4 (IL-4), tumour necrosis factor a (TNF-a), and lipopolysaccharides (LPS) on cultured enteric glia. Methods: Dissected rat colon and cultured enteric glia cells were double labelled with anti-GFAP and anti-S-100 antibodies. For regulatory studies, enteric glia cells were treated with cytokines and LPS. Proliferation was assayed using bromodeoxyuridine (BrdU) and mitosis of enteric glia was blocked by demecolcine. Results: We were able to distinguish GFAP negative (2) from GFAP+ glia subtypes in situ and in primary cultures. Incubation of cells with IL-1b, TNF-a, and LPS led to a significant increase in GFAP+ enteric glia while IL-4 had no effect on GFAP expression. After incubation with IL-1b, total intracellular GFAP of enteric glia cells was increased. Upregulation of GFAP+ enteric glia could also be observed after stimulation with IL-1b on blocking mitosis. BrdU uptake in stimulated enteric glia showed no increased proliferation rate. Conclusions: Two different types of enteric glia based on GFAP expression exist in the gut. Proinflammatory cytokines and LPS cause a dramatic increase in GFAP+ enteric glia. This suggests that cytokines play an important role in controlling GFAP+ enteric glia which might in turn be involved in modulating the integrity of the bowel during inflammation.

BackgroundThe enteric glia network may be involved in the pathogenesis of inflammatory bowel disease (IBD). Enteric glia cells (EGCs) are the major source of glial-derived neurotrophic factor (GDNF), which regulates apoptosis of enterocytes. The aim of the study was to determine the distribution of EGCs and GDNF during gut inflammation and to elucidate a possible diminished enteric glia network in IBD.MethodsThe expression of glial fibrillary acidic protein (GFAP) in colonic biopsies of patients with IBD, controls and patients with infectious colitis was detected by immunohistochemistry and Western blot. Tissue GDNF levels were measured by ELISA.ResultsThe expression of GFAP and GDNF in the mucosal plexus is highly increased in the inflamed colon of patients with ulcerative colitis (UC) and infectious colitis. Although the GDNF and GFAP content are increased in Crohn's disease (CD), it is significantly less. Additionally the non-inflamed colon of CD patients showed a reduced GFAP and no GDNF expression compared to controls and the non-inflamed colon of UC patients.ConclusionsGFAP and GDNF as signs of activated EGCs are increased in the inflamed mucosa of patients with UC and infectious colitis, which underline an unspecific role of EGC in the regulation of intestinal inflammation. The reduced GFAP and GDNF content in the colon of CD patients suggest a diminished EGC network in this disease. This might be a part of the pathophysiological puzzle of CD.

Background and aims: Osteopenia and osteoporosis are frequent in Crohn's disease. However, there are few data on related vertebral fractures. Therefore, we evaluated prospectively the prevalence of osteoporotic vertebral fractures in these patients. Methods: A total of 293 patients were screened with dual energy x ray absorptiometry of the lumbar spine (L1-L4) and proximal right femur. In 156 patients with lumbar osteopenia or osteoporosis (T score <−1), x ray examinations of the thoracic and lumbar spine were performed. Assessment of fractures included visual reading of x rays and quantitative morphometry of the vertebral bodies (T4-L4), analogous to the criteria of the European Vertebral Osteoporosis Study. Results: In 34 (21.8%; 18 female) of 156 Crohn's disease patients with reduced bone mineral density, 63 osteoporotic vertebral fractures (50 fx. (osteoporotic fracture with visible fracture line running into the vertebral body and/or change of outer shape) and 13 fxd. (osteoporotic fracture with change of outer shape but without visible fracture line)) were found, 50 fx. in 25 (16%, 15 female) patients and 13 fxd. in nine (5.8%, three female) patients. In four patients the fractures were clinically evident and associated with severe back pain. Approximately one third of patients with fractures were younger than 30 years. Lumbar bone mineral density was significantly reduced in patients with fractures compared with those without (T score −2.50 (0.88) v −2.07 (0.66); p<0.025) but not at the hip (−2.0 (1.1) v −1.81 (0.87); p=0.38). In subgroups analyses, no significant differences were observed. Conclusions: In patients with Crohn's disease and reduced bone mineral density, the prevalence of vertebral fractures-that is, manifest osteoporosis-was strikingly high at 22%, even in those aged less than 30 years, a problem deserving further clinical attention.