Findings From Current Research

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Leukocytapheresis (LCAP) in the Management of Chronic Active Ulcerative Colitis-Results of a Randomized Pilot Trial.

Authors: Emmrich J, Petermann S, Nowak D, Beutner I, Brock P, Klingel R, Mausfeld-Lafdhiya P, Liebe S, Ramlow W.

Division of Gastroenterology, Department of Internal Medicine, University Hospital of Rostock, Ernst-Heydemann-Str. 6, 18057, Rostock, Germany, joerg.emmrich@med.uni-rostock.de.

Recent studies suggest that leukocytapheresis with Cellsorba is a valuable therapy for ulcerative colitis after failure of conventional treatment. In this study the potential of leukocytapheresis to induce remission in refractory chronic colitis under the conditions of European treatment guidelines was investigated. The therapeutic benefit of leukocytapheresis in the maintenance of remission was additionally elucidated. Twenty patients were treated weekly for 5 weeks. A significant decrease in the activity index was observed. Fourteen patients achieved clinical remission, and mucosal healing was observed endoscopically in six patients. After randomization these 14 patients in remission entered a second period of either monthly leukocytapheresis or no further treatment. In both groups steroids were tapered down. After 6 months, only one patient in the control group remained in remission, in contrast to five of eight patients in the leukocytapheresis group. In conclusion, leukocytapheresis may offer a therapeutic option in the induction and the maintenance of remission in chronic active ulcerative colitis.

Journal: Dig Dis Sci. 2007 Apr 5;
Adapted from PubMed; click here to access full journal article.

Altered Cryptal Expression of Luminal Potassium (BK) Channels in Ulcerative Colitis.

Authors: Sandle G, Perry M, Mathialahan T, Linley J, Robinson P, Hunter M, Maclennan K.

Institute for Molecular Medicine, St James's University Hospital, Leeds, UK.

Decreased sodium (Na(+)), chloride (Cl(-)), and water absorption, and increased potassium (K(+)) secretion, contribute to the pathogenesis of diarrhoea in ulcerative colitis. The cellular abnormalities underlying decreased Na(+) and Cl(-) absorption are becoming clearer, but the mechanism of increased K(+) secretion is unknown. Human colon is normally a K(+) secretory epithelium, making it likely that K(+) channels are expressed in the luminal (apical) membrane. Based on the assumption that these K(+) channels resembled the high conductance luminal K(+) (BK) channels previously identified in rat colon, we used molecular and patch clamp recording techniques to evaluate BK channel expression in normal and inflamed human colon, and the distribution and characteristics of these channels in normal colon. In normal colon, BK channel alpha-subunit protein was immunolocalized to surface cells and upper crypt cells. By contrast, in ulcerative colitis, although BK channel alpha-subunit protein expression was unchanged in surface cells, it extended along the entire crypt irrespective of whether the disease was active or quiescent. BK channel alpha-subunit protein and mRNA expression (evaluated by western blotting and real-time PCR, respectively) were similar in the normal ascending and sigmoid colon. Of the four possible beta-subunits (beta(1-4)), the beta(1)- and beta(3)-subunits were dominant. Voltage-dependent, barium-inhibitable, luminal K(+) channels with a unitary conductance of 214 pS were identified at low abundance in the luminal membrane of surface cells around the openings of sigmoid colonic crypts. We conclude that increased faecal K(+) losses in ulcerative colitis, and possibly other diseases associated with altered colonic K(+) transport, may reflect wider expression of luminal BK channels along the crypt axis. Copyright (c) 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Journal: J Pathol. 2007 Apr 3;
Adapted from PubMed; click here to access full journal article.

Altered Intestinal Permeability is Predictive of Early Relapse in Children with Steroid-Responsive Ulcerative Colitis.

Authors: Miele E, Pascarella F, Quaglietta L, Giannetti E, Greco L, Troncone R, Staiano A.

Department of Pediatrics, University of Naples "Federico II", Naples, Italy.

Aim To determine if small bowel involvement at diagnosis could predict early relapse in children with ulcerative colitis. Methods Children with newly diagnosed ulcerative colitis were evaluated prospectively at three time points: within 1 month, 6 months and 1 year after diagnosis. Clinical activity indices were used to measure disease activity. Laboratory studies were performed at each visit and/or at the time of relapse. At diagnosis, all patients underwent colonoscopy and a cellobiose/mannitol small intestinal permeability study. Some children were further investigated with an upper gastrointestinal endoscopy. Results Thirty-three patients completed the 1-year study. Overall, nine patients (27.3%) relapsed within 6 months of diagnosis, one patient (3%) within 1 year, whereas 23 patients (69.7%) did not relapse. The mean clinical activity indices, laboratory parameters, extent of colonic involvement, upper and lower gastrointestinal histological features were not predictive of early relapse. Results of the cellobiose/mannitol small intestinal permeability study were significantly higher in children who relapsed within 6 months compared with children who did not relapse (P < 0.013). The cellobiose/mannitol small intestinal permeability study was abnormal in 77.8% of early relapsers compared with only 8.3% of non-relapsers. Conclusion Abnormal small intestinal permeability in children with ulcerative colitis could predict a more relapsing disease.

Journal: Aliment Pharmacol Ther. 2007 Apr 15;25(8):933-9.
Adapted from PubMed; click here to access full journal article.

Narrow-Band Imaging Compared with Conventional Colonoscopy for the Detection of Dysplasia in Patients with Longstanding Ulcerative Colitis.

Authors: Dekker E, van den Broek FJ, Reitsma JB, Hardwick JC, Offerhaus GJ, van Deventer SJ, Hommes DW, Fockens P.

Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands. e.dekker@amc.uva.nl

BACKGROUND AND STUDY AIM: Patients with longstanding ulcerative colitis are at increased risk of developing colorectal cancer. Colonoscopic surveillance is advised, but the detection of neoplasia by conventional colonoscopy is difficult. The aim of this study was to compare the accuracy of narrow-band imaging (NBI), a new imaging technique, with standard colonoscopy for the detection of neoplasia in patients with longstanding ulcerative colitis. PATIENTS AND METHODS: This was a prospective, randomized, crossover study of 42 patients with longstanding ulcerative colitis. All participants underwent NBI and conventional colonoscopy with at least 3 weeks between the procedures. Randomization determined the order of the examinations. Targeted biopsies were taken during both procedures; additional random biopsies were taken at conventional colonoscopy only. The number of patients with neoplasia detected by targeted biopsies was used to assess the sensitivity for each technique. RESULTS: With NBI, 52 suspicious lesions were detected in 17 patients, compared with 28 suspicious lesions in 13 patients detected during conventional colonoscopy. Histopathological evaluation of targeted biopsies revealed 11 patients with neoplasia: in four patients the neoplasia was detected by both techniques, in four patients neoplasia was detected only by NBI, and in three patients neoplasia was detected only by conventional colonoscopy ( P = 0.705). Aside from targeted biopsies, 1522 random biopsies were taken. These revealed one additional patient with dysplasia that was not detected by either technique. CONCLUSIONS: The sensitivity of the studied first-generation NBI system for the detection of patients with neoplasia seems to be comparable to conventional colonoscopy, although more suspicious lesions were found during NBI. We believe that it is still too early to stop taking additional random biopsies at surveillance colonoscopy in patients with ulcerative colitis.

Journal: Endoscopy. 2007 Mar;39(3):216-21.
Adapted from PubMed; click here to access full journal article.

One Bite or Two? A Prospective Trial Comparing Colonoscopy Biopsy Technique in Patients with Chronic Ulcerative Colitis.

Authors: Hookey LC, Hurlbut DJ, Day AG, Manley PN, Depew WT.

Queen's University, Kingston, Canada.

BACKGROUND AND STUDY AIMS: Surveillance for mucosal dysplasia in patients with chronic ulcerative colitis requires numerous biopsies (often over 40). The aim of the present study was to determine if two biopsies could be obtained with jumbo forceps before removing them from the instrument (double biopsy technique), as opposed to one biopsy per pass, without sacrificing the histological quality of the biopsy material. METHODS: Twelve patients with chronic ulcerative colitis underwent colonoscopy, and four-quadrant biopsies were obtained at 10 cm intervals. For biopsies at each interval, two quadrants were obtained using the double biopsy technique and the other two quadrants were obtained individually. Two pathologists blinded to the biopsy technique examined each biopsy for technical and diagnostic qualities. The primary outcome was the histological adequacy in the evaluation of dysplasia. RESULTS: A total of 468 biopsies were obtained. A higher proportion of double-biopsy specimens were inadequate for dysplasia assessment compared with single-biopsy specimens (OR=2.78, 95% CI 1.37 to 5.59; P=0.005). In the double biopsy technique group, 14 samples were deemed inadequate due to actual tissue specimen loss, compared with eight samples in the single biopsy technique. However, when analysis was repeated using only the retrieved specimens, the double biopsy technique continued to be at higher risk of obtaining inadequate specimens (OR=14.5, 95% CI 2.1 to 98.7; P=0.006). CONCLUSIONS: The results of the present study suggest that the double biopsy technique is vulnerable to specimen loss and reduced histological quality, and the adoption of this technique as an equivalent method for tissue sampling may be premature.

Journal: Can J Gastroenterol. 2007 Mar;21(3):164-8.
Adapted from PubMed; click here to access full journal article.

New Treatments and Diagnostic Approaches in Ulcerative Colitis.

Authors: Nos Mateu P.

Servicio de Medicina Digestiva. Hospital La Fe. Valencia. Espana. nos_pil@gva.es.

Ulcerative colitis is a chronic inflammatory bowel disease with periods of flares and remission. The main symptom is rectorrhagia. The aim of medical treatment is to induce and maintain clinical remission. At the last congress of the American Gastroenterological Association: Digestive Diseases Week (DDW) in 2006, new data were presented on salicylates, the ASCEND I&II studies evaluating the new formulation of mesalazine, and prebiotics. Also presented were various findings related to cyclosporin and infliximab therapy in severe steroid-refractory flares, such as an early response - which is greater with infliximab - and late response. The factors associated with the possible lack of response to corticoids were analyzed. Several studies evaluating the efficacy of granulocytapheresis in ulcerative colitis, including its use as an alternative to corticoids, were presented.

Journal: Gastroenterol Hepatol. 2006 Nov;29 Suppl 3:52-6.
Adapted from PubMed; click here to access full journal article.