Lene Riis

Follow-Up of Exocrine Pancreatic Function in Type-1 Diabetes mellitus

In a previous study, mild to moderate exocrine pancreatic insufficiency, as measured by the secretin-pancreozymin test, was found in 23 (43%) of 53 patients with type-1 diabetes mellitus. Of these 53 patients, 20 (7 of whom initially had an abnormal secretin-pancreozymin test) were available for a follow-up examination 11 years later. Of the 7 patients with abnormal exocrine pancreatic function at the first test, 5 remained abnormal and 2 became normal, whereas of the 13 patients with initially normal pancreatic function the test result remained normal in 11 patients and became abnormal in 2. In these 2 groups the test result did not differ significantly between both tests. However, exocrine pancreatic function had returned to normal or had become abnormal in 2 patients, respectively, at the second test. In the 3 patients with exocrine pancreatic insufficiency at the first and second tests, the lipase level had not fallen below 10% or less than the normal level at which steatorrhea occurs and therapy is required. There was no significant correlation between the duration of the diabetes and the test results for both time points of investigation. The data suggest that mild to moderate exocrine pancreatic insufficiency found in type-1 diabetes is due to an early event in the course of the diabetes and does not progress. Therefore, this finding is of minor clinical importance and expensive pancreatic enzyme substitution will not be required.

Scleroderma induced by paclitaxel

Paclitaxel is a standard treatment of a variety of solid tumours. It binds to microtubules at the tubulin ß subunit causing an increase in microtubule polymerisation. The result is inhibition of the normal dynamic reorganisation of the microtubule network essential for normal cell function. As a consequence a miotic arrest is induced eventually leading to apoptosis [1]. Paclitaxel is mainly excreted in the stool via the enterohepatic circulation over approximately fi ve days as parent compound and metabolites. Premedication with steroids is necessary to prevent taxane related hypersensitivity. Nevertheless major hypersensitivity reactions occur in 3% despite prophylaxis. Side effects include bone marrow suppression, pulmonary toxicity, nail disorders and skin toxicity [2]. Scleroderma is an autoimmune systemic connective tissue disease which is characteristic by blood vessel changes and fi brosis of the skin. The fi brosis can appear in any organ. The aetiology and pathogenesis of scleroderma is unknown, however the most important genetic predisposition is female gender [3]. We report a case of possible paclitaxel induced scleroderma in a patient with ovarian/peritoneal cancer and present a review of related literature.

Confocal laser endomicroscopy: a novel method for prediction of relapse in Crohn's disease.

BACKGROUND AND STUDY AIMSnConfocal laser endomicroscopy (CLE) has been shown to predict relapse in ulcerative colitis in remission, but little is currently known about its role in Crohns disease. The aim of this study was to identify reproducible CLE features in patients with Crohns disease and to examine whether these are risk factors for relapse.nnnPATIENTS AND METHODSnThis was a single-center prospective feasibility study of CLE imaging in patients with Crohns disease. CLE imaging was performed in the terminal ileum and four colorectal sites, and was correlated with histopathology and macroscopic appearance. Clinical relapse, defined as the need for treatment escalation or surgical intervention, was recorded during follow-up.nnnRESULTSnThe study included 50 patients: 39 with Crohns disease (20 in remission), and 11 controls. Ileal fluorescein leakage and microerosions were significantly more frequent in patients with endoscopically active Crohns disease compared with patients with inactive Crohns disease and controls (Pu200a=u200a0.005 and (Pu200a=u200a0.006, respectively). The same applied to colorectal fluorescein leakage and vascular alterations ((Pu200a=u200a0.043 and (Pu200a=u200a0.034, respectively). During a 12-month follow-up period, ileal fluorescein leakage and microerosions were significant risk factors for relapse in the subgroup of patients in remission (log rank (Pu200a=u200a0.009 and (Pu200a=u200a0.007, respectively) as well as in the entire group of patients with Crohns disease (log rank (Pu200a=u200a0.006 and (Pu200a=u200a0.01, respectively). Inter- and intraobserver reproducibility was almost perfect (κu200a>u200a0.80) or substantial (κu200a>u200a0.60) for the majority of CLE parameters.nnnCONCLUSIONSnCLE can identify reproducible microscopic changes in the terminal ileum that are risk factors for relapse in patients with otherwise inactive Crohns disease.nnnTRIAL REGISTRATIONnClinicalTrials.gov (NCT01738529).

Confocal laser endomicroscopy in ulcerative colitis: a longitudinal study of endomicroscopic changes and response to medical therapy (with videos)

BACKGROUND AND AIMSnConfocal laser endomicroscopy enables real-time inxa0vivo microscopy during endoscopy and can predict relapse in patients with inflammatory bowel disease in remission. However, little is known about how endomicroscopic features change with time. The aim of this longitudinal study was to correlate colonic confocal laser endomicroscopy (CLE) in ulcerative colitis with histopathology and macroscopic appearance before and after intensification of medical treatment.nnnMETHODSnTwenty-two patients with ulcerative colitis in clinical relapse and 7 control subjects referred for colonoscopy were enrolled. The colonic mucosa was examined with high-definition colonoscopy, histopathology, and CLE at 4 colonic sites. Subsequently, patients requiring medical treatment escalation were referred for repeat endoscopy with CLE after 6 to 8 weeks.nnnRESULTSnThe baseline frequency of fluorescein leakage (Pxa0< .001), microerosions (Pxa0< .001), tortuosity of thexa0crypts (Pxa0= .001), distortion of the crypts openings (Pxa0= .001), presence of inflammatory infiltrates (Pxa0<xa0.001), and decreased crypt density (Pxa0< .001) were significantly higher in active ulcerative colitis compared with inactive ulcerative colitis and control subjects. A decrease in histopathologic score after medical treatment escalation was correlated with improvement in crypt tortuosity (rsxa0= .35, Pxa0= .016), distortion of crypt openings (rsxa0= .30, Pxa0= .045), and decreased crypt density (rsxa0= .33, Pxa0= .026) but not in other features.nnnCONCLUSIONSnCLE is an emerging endoscopic technique that reproducibly identifies mucosal changes in ulcerative colitis. With the exception of crypt changes, endomicroscopic features appear to improve slowly with time after medical treatment. (nnnCLINICAL TRIAL REGISTRATION NUMBERnNCT01684514.).

Confocal Laser Endomicroscopy in Inflammatory Bowel Disease--A Systematic Review.

BACKGROUND AND AIMSnConfocal laser endomicroscopy is an endoscopic method that provides in vivo real-time imaging of the mucosa at a cellular level, elucidating mucosal changes that are undetectable by white light endoscopy. This paper systematically reviews current indications and perspectives of confocal laser endomicroscopy for inflammatory bowel disease.nnnMETHODSnAvailable literature was searched systematically for studies applying confocal laser endomicroscopy in Crohns disease or ulcerative colitis. Relevant literature was reviewed and only studies reporting original clinical data were included. Next, eligible studies were analysed with respect to several parameters, such as technique and clinical aim and definitions of outcomes.nnnRESULTSnConfocal laser endomicroscopy has been used for a wide range of purposes in inflammatory bowel disease, covering assessment of inflammatory severity, prediction of therapeutic response and relapse and adenoma surveillance in patients with ulcerative colitis. Methods for measurement of the histological changes ranged from subjective grading to objective quantification analysed by computer-aided models. The studies derived their conclusions from assessment of histological features such as colonic crypts, epithelial gaps and epithelial leakiness to fluorescein.nnnCONCLUSIONSnConfocal laser endomicroscopy remains an experimental but emerging tool for assessment of inflammatory bowel disease. It is the only method that enables in vivo functional assessment of intestinal barrier function. There is great heterogeneity in the literature and no single approach has been validated and reproduced to the level of general acceptance.

Genetic and Environmental Factors in Monozygotic Twins with Crohn’s Disease and Their First-Degree Relatives: A Case Report

Background/Aims: Familial Crohn’s disease has shown concordance concerning location and clinical type of the disease especially among monozygotic twins. Susceptibility to Crohn’s disease is both based on genetic and environmental factors. We investigated polymorphisms of CARD15, TLR4, and OCTN, and environmental factors in a monozygotic twin pair with Crohn’s disease and their first-degree relatives. Methods: 22-year-old monozygotic female twins with ileocolonic Crohn’s disease and their healthy brother and parents were examined. DNA samples from patients and relatives were genotyped for CARD15, TLR4,and OCTN polymorphisms. ASCA and p-ANCA analyses were performed. Additionally, patients and relatives filled out a questionnaire concerning multiple environmental factors. Results: Both twins presented in the same year with identical Vienna Classification phenotypes: stenotic behavior (B2) and localization in terminal ileum and colon (L3). Both carried a CARD15 R702W variant, but had normal alleles in TLR4 and OCTN. They were smokers since the age of 15, used oral contraceptives and had undergone appendectomy. The healthy father and brother were CARD15 R702W positive, were non-smokers and had not undergone appendectomy. Conclusion: This case report is the first to describe complete concordance in CARD15 status, phenotypic appearance, and smoking, appendectomy and oral contraceptive use in a pair of monozygotic twins with CD.

SMAD4 Protein Expression Is Downregulated in Ileal Epithelial Cells from Patients with Crohn’s Disease with Significant Inverse Correlation to Disease Activity

Background Small mothers against decapentaplegic (SMAD)4 and SMAD7 are key regulatory components in the immunosuppressive transforming growth factor- (TGF-) β signaling pathway, which is defective in inflammatory bowel disease (IBD). SMAD4 may play an important role in the pathogenesis of IBD as indicated in experimental models of colitis. Aims To examine the ileal expression levels of SMAD4 and to correlate these with CD disease activity. Methods The material comprised 29 CD patients (13 with active disease, 16 in remission) and 9 asymptomatic patients referred for ileocolonoscopy as part of an adenoma surveillance program serving as controls. Patients were examined with ileocolonoscopy. Corresponding ileal biopsies were obtained for histological analysis and assessment of SMAD4 and SMAD7 protein expression by immunohistochemistry (IHC). Results The protein expression of SMAD4 was significantly downregulated in ileal tissue sections from CD patients as compared to healthy controls (p < 0.001). Further, luminal SMAD4 expression was inversely correlated with endoscopic (r s = −0.315; p = 0.05) and histopathological activity (r s = −0.40; p = 0.013). Conclusions The SMAD4 epithelial protein level was markedly downregulated in CD patients and inversely correlated with disease activity. This may contribute to defective mucosal TGF-β signaling in active IBD.