Important Note: The following information is provided for your education. It should not be relied upon for personal diagnosis or treatment. If you believe that a particular therapy applies to you or someone you care about, be sure to consult a doctor before trying it.
   

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Previous Ulcerative Colitis Research:
2002-2006   
The Ulcerative Colitis File also contains summaries of past research that has shown promise and may still be standard practice among many physicians. To download earlier research findings on Ulcerative Colitis, click HERE.
 

Latest Research on
Ulcerative Colitis
     
Int J Cancer. 2008 Sep 15;123(6):1417-21.
Cancer risks in ulcerative colitis patients.
Hemminki K, Li X, Sundquist J, Sundquist K.
Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, D-69120 Heidelberg, Germany. k.hemminki@dkfz.de

Patients diagnosed with ulcerative colitis (UC) are known to be at an increased risk of colorectal and liver cancers and leukemia. UC is an autoimmune disease, which may present a wider spectrum of cancers. We wanted to examine the risk of cancer in a large population of UC patients in order to reach high statistical power. A UC research database was constructed by identifying UC patients from the Swedish Hospital Discharge Register and cancer patients from the Cancer Registry. Follow-up of 27,606 UC patients hospitalized for the first time during the years 1964-2004 identified 2,058 patients with cancer. Standardized incidence ratios were calculated for cancer in UC patients by comparing to subjects without hospitalization for UC. The novel tumor sites in UC patients included small intestinal (carcinoid), pancreatic, breast and prostate cancers, nonthyroid endocrine gland tumors, non-Hodgkin lymphoma and multiple myeloma. A total of 11 sites showed an increased risk, which remained at 6 sites when tumors diagnosed in the year of UC hospitalization were excluded; even chronic myeloid leukemia was in excess. Cancer risks depended on the age at first hospitalization for UC. The SIRs for colon, rectal, liver and pancreatic cancers declined by age at hospitalization for UC, while for endocrine tumors the older patients were at higher risk. Our large study identified novel subsequent cancers in UC patients. However, some of these, including small intestinal carcinoids, prostate cancers and nonthyroid endocrine tumors, may be in excess because of intensified medical surveillance of the patients. Copyright 2008 Wiley-Liss, Inc.

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Expert Rev Mol Diagn. 2008 Jul;8(4):465-77.
Apical junction complex proteins and ulcerative colitis: a focus on the PTPRS gene.
Muise A, Rotin D.
Department of Pediatrics, Division of Gastroenterology, Hepatology & Nutrition, Program in Cell Biology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada. aleixo.muise@sickkids.ca

Inflammatory bowel disease is a complex multifactorial disease with a strong genetic component. Recent studies have identified innate immunity (NOD2), autophagy (ATG16L1) and Th17 pathway (IL23R) genes in the pathogenesis of Crohn's disease. The pathogenesis of ulcerative colitis (UC) is less clear; however, there is growing evidence that proteins involved in the apical junction complex are involved in UC. Here we review the up-to-date studies on the genetic basis for IBD and explore the newly described UC-associated apical junction complex pointing to a primary defect in barrier defense. We will focus on the PTPRS (encoding PTPsigma) gene and discuss its and other apical junction complex proteins' role in the pathogenesis of UC.

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Ugeskr Laeger. 2008 Jun 9;170(24):2152-6.
[Biological therapy as treatment of inflammatory bowel diseases]
[Article in Danish]
Agnholt J.
Arhus Universitetshospital, Arhus Sygehus, Medicinsk Hepato-gastroenterologisk Afdeling V, Arhus C. jorge@as.aaa.dk

Biological therapy as treatment of inflammatory bowel diseases has been one of the major achievements since the introduction of steroids. Infliximab has been approved for the treatment of Crohn's disease and ulcerative colitis, and adalimumab for the treatment of Crohn's disease. Both treatments have documented effect for induction of clinical response and remission, and can be used to maintain remission. However, it is important to define the treatment goals before initiation, and whether biologicals should be used alone or together with immunosuppressants as azathioprine.

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Am J Gastroenterol. 2008 Jun;103(6):1460-9. Epub 2008 May 28.
The effect of hypnosis on systemic and rectal mucosal measures of inflammation in ulcerative colitis.
Mawdsley JE, Jenkins DG, Macey MG, Langmead L, Rampton DS.
Centre for Gastroenterology, Institute of Cell and Molecular Science, Barts and the London, Queen Mary School of Medicine and Dentistry, London, UK.

OBJECTIVES: Hypnotherapy is effective in several diseases with a psychosomatic component. Our aim was to study the effects of one session of hypnosis on the systemic and rectal mucosal inflammatory responses in patients with active ulcerative colitis (UC). METHODS: In total, 17 patients with active UC underwent a 50-min session of gut-focused hypnotherapy. Before and after each procedure, the systemic inflammatory response was assessed by serum interleukin (IL)-6 and IL-13 concentrations, tumor necrosis factor-alpha (TNF-alpha) and IL-6 production by lipopolysaccharide (LPS)-stimulated whole blood, leukocyte count, natural killer (NK) cell number, platelet activation, and platelet-leukocyte aggregate formation. Rectal inflammation was assessed by mucosal release of substance P (SP), histamine, IL-13 and TNF-alpha, reactive oxygen metabolite production, and mucosal blood flow. Eight patients with active UC underwent a control procedure. RESULTS: Hypnosis decreased pulse by a median 7 beats per minute (bpm) (P= 0.0008); it also reduced the median serum IL-6 concentration by 53% (P= 0.001), but had no effect on the other systemic variables assessed. Hypnosis reduced rectal mucosal release of SP by a median 81% (P= 0.001), histamine by 35% (P= 0.002) and IL-13 by 53% (P= 0.003), and also, blood flow by 18% (P= 0.0004). The control protocol had no effect on any of the variables assessed. CONCLUSIONS: Hypnosis reduced several components of the systemic and mucosal inflammatory response in active ulcerative colitis toward levels found previously in the inactive disease. Some of these effects may contribute to the anecdotally reported benefits of hypnotherapy and provide a rationale for controlled trials of hypnotherapy in UC.

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Med Wieku Rozwoj. 2007 Oct-Dec;11(4):401-7.
[Inflammatory bowel disease in children--an analysis of the clinical symptoms and selected biochemical parameters]
[Article in Polish]
Landowski P, Liberek A, Szlagatys-Sidorkiewicz A, Radys W, Brodzicki J, Szarszewski A, Marek A, Łuczak G, Kamińska B.
Katedra i Klinika Pediatrii, Gastroenterologii i Onkologii Dzieciecej Akademii Medycznej w Gdańsku. pland@amg.gda.pl

AIM OF THE STUDY: an analysis of clinical symptoms and laboratory tests in children with inflammatory bowel disease (IBD). PATIENTS AND METHODS: eighty-nine children with IBD (58 with ulcerative colitis (UC) and 31 with Crohn's disease (CD) diagnosed on the basis of clinical symptoms, endoscopic and histopathological examination, were qualified into the studied group. Disease activity was evaluated by using Truelowe-Witts scale for UC and PCDA9 scale for CD cases. Forty-two children without acute or chronic inflammatory diseases constituted the control group. RESULTS: the frequency of such clinical symptoms as: diarrhea, fever, weight loss, abdominal pain, weakness, constipations, anemia, joints pain, vomits, and jaundice was comparable in children with UC and CD while intestinal bleeding was significantly more frequently observed in patients with UC than with CD (P<0.05). There was no statistically significant difference in BMI between patients with UC and CD. Cole's index was significantly higher in children with UC than with CD (P<0.05). Hemoglobin level and serum iron level were statistically significantly lower in patients with CD than in the control group (P<0.05). Mean leukocyte count in children with CD was significantly higher than in the control group (P<0.05). Neutrophils percentage in patients with UC and CD was significantly higher than in the control group (P<0.05). Platelet count was significantly higher in all children with IBD than in the control group (P<0.05). Mean serum CRP level was significantly higher only in children with CD while ESR was significantly higher in both groups of IBD patients. Mean serum gamma-globulin level was statistically significantly higher in children with UC and with CD but no significant differences were observed in serum IgA, IgG, and IgM levels among the analyzed groups. Serum GT level was higher in children with CD than in the control group while serum ALT and AST level did not differ significantly among the analyzed groups of patients. CONCLUSIONS: 1. Serum C-reactive protein level is one of the most valuable markers for monitoring the course of IBD, especially CD, in children. 2. In patients with IBD systematic monitoring of liver function parameters (especially parameters of cholestasis) is necessary as severe hepatic complications may occur. 3. Further search for new sensitive and specific markers monitoring the course of inflammatory bowel diseases is needed.

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Lung. 2008 Mar 11 [Epub ahead of print]
Increased Risk of Both Ulcerative Colitis and Crohn's Disease in a Population Suffering from COPD.
Ekbom A, Brandt L, Granath F, Löfdahl CG, Egesten A.
Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation of the airways. In the majority of cases, the inflammation is triggered by tobacco smoke. Smoking also affects the pathogenesis of inflammatory bowel disease (IBD), protecting against ulcerative colitis (UC) and promoting development of Crohn's disease (CD). The present study was undertaken to investigate occurrence of IBD among COPD patients, indicating common inflammatory pathways and shared vulnerability on a genetic basis. The study was designed as a population-based cohort study. All individuals discharged with a diagnosis of COPD from 1987 to 2002 were identified in the Swedish Inpatient Register (n = 180,239). Controls and first-degree relatives of both cases and controls were identified using the Multi-Generation Register. Finally, all individuals (n = 1,174,557) were compared with the Inpatient Register, identifying discharges with a diagnosis of UC or CD. Hazard ratios (HR) for IBD were determined by Cox proportional hazards regression analysis. COPD patients had a significantly higher risk of both UC (HR 1.83; 95% CI 1.61-2.09) and CD (HR 2.72; 95% CI 2.33-3.18). Among first-degree relatives of COPD patients, there was also an overall increased risk of CD (HR 1.25; 95% CI 1.09-1.43) but not of UC (HR 1.09; 95% CI 0.96-1.23). The kinship of first-degree relatives displayed an increased risk of both UC and CD among siblings (HR 1.49; 95% CI 1.15-1.91 and HR 1.46; 95% CI 1.12-1.89, respectively). The results suggest that COPD and IBD may have inflammatory pathways in common, including genetic variants of genes predisposing for disease.

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Gastroenterology. 2008 Mar;134(3):688-95. Epub 2007 Dec 7.
Rosiglitazone for active ulcerative colitis: a randomized placebo-controlled trial.
Lewis JD, Lichtenstein GR, Deren JJ, Sands BE, Hanauer SB, Katz JA, Lashner B, Present DH, Chuai S, Ellenberg JH, Nessel L, Wu GD; Rosiglitazone for Ulcerative Colitis Study Group.
Division of Gastroenterology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA. lewisjd@mail.med.upenn.edu

BACKGROUND & AIMS: Thiazolidinedione ligands for the gamma subtype of peroxisome proliferator-activated receptors (PPARgamma), widely used to treat type 2 diabetes mellitus, have been proposed as novel therapies for ulcerative colitis (UC). METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial compared the efficacy of rosiglitazone (Avandia; GlaxoSmithKline, Philadelphia, PA) 4 mg orally twice daily vs placebo twice daily for 12 weeks in 105 patients with mild to moderately active UC. Disease activity was measured with the Mayo score. The primary end point was clinical response (>/=2-point reduction) at week 12. Clinical remission (Mayo score </=2), endoscopic remission, and quality of life were secondary outcomes. RESULTS: After 12 weeks of therapy, 23 patients (44%) treated with rosiglitazone and 12 patients (23%) treated with placebo achieved clinical response (P = .04). Remission was achieved in 9 patients (17%) treated with rosiglitazone
and 1 patient (2%) treated with placebo (P = .01). Endoscopic remission was uncommon in either treatment arm (8% rosiglitazone vs 2% placebo; P = .34). Clinical improvement was evident as early as 4 weeks after beginning treatment (P = .049). Quality of life was improved significantly at week 8 (P = .01), but not at week 4 (P = .48) or week 12 (P = .14). Serious adverse events were rare. CONCLUSIONS: Rosiglitazone was efficacious in the treatment of mild to moderately active UC.

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Med J Aust. 2008 Mar 3;188(5):304-308.
Probiotics: sorting the evidence from the myths.
Pham M, Lemberg DA, Day AS.
Department of Gastroenterology, Sydney Children’s Hospital, Sydney, NSW, Australia. andrew.day@unsw.edu.au.

Probiotics consist of yeast or bacteria, especially lactic acid bacteria. They are available as capsules, powder, fermented milks or yoghurts. Probiotics exhibit strain-specific differences in their resistance to acid and bile, ability to colonise the gastrointestinal tract, clinical efficacy, and benefits to the health of the host. There is level I evidence for the use of probiotics in treating acute infectious diarrhoea and preventing antibiotic-associated diarrhoea, with Lactobacillus rhamnosus GG and Saccharomyces boulardii having the most evidence to support their use for these conditions. There is level II evidence that S. boulardii combined with high-dose vancomycin is more effective than the antibiotic alone in preventing recurrent Clostridium difficile diarrhoea. There is level I evidence that probiotics prevent traveller's diarrhoea. There is level I evidence for use of the high-potency probiotic VSL#3 in preventing pouchitis, and level II evidence for this agent in
preventing relapse in patients with ulcerative colitis. Probiotics are generally regarded as safe and well tolerated. Some probiotics may be contraindicated in patients who are immunocompromised or have severe underlying illness, as they have been reported to cause fungaemia and bacteraemia.

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Intern Med J. 2008 Feb;38(2):114-9.
Management of distal ulcerative colitis: frequently asked questions analysis.
James SL, Irving PM, Gearry RB, Gibson PR.
Department of Gastroenterology and Monash University Department of Medicine, Box Hill Hospital, Melbourne, Victoria, Australia.

The majority of patients with ulcerative colitis have disease involving only the distal colon. Although 5-aminosalicylic acid (5-ASA, mesalazine) and corticosteroids remain the important drugs used in the management of distal colitis and proctitis, recent expansion of delivery options of 5-ASA and high level evidence regarding efficacy have led to a shift in treatment strategies. The availability of 5-ASA in enema, foam and suppository formulations has enabled optimization of delivery of 5-ASA to the affected mucosa. Such therapy has superior efficacy and fewer adverse effects compared with those of topical corticosteroids. Furthermore, rectal delivery is effective in the maintenance of remission. Consequently, new guidelines for the management of distal colitis have focused more on rectal delivery and on optimizing 5-ASA dosage than previously. However, corticosteroids remain an important remission-inducing agent, and immune-modulating drugs play a clear role in prevention of relapse and in managing chronically active disease. The changes in guidelines have raised several management questions, many of which are addressed in this review.

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J Clin Gastroenterol. 2008 Feb 13 [Epub ahead of print]
Oral 5-ASA Therapy in Ulcerative Colitis: What are the Implications of the New Formulations?
Sandborn WJ.
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.

5-aminosalicylic acid (5-ASA) is the standard first-line treatment for mild-to-moderate ulcerative colitis. A variety of 5-ASA delivery systems are available and in development, including both oral and rectal formulations; all of which aim to deliver the active drug to the colon while minimizing systemic absorption. Because the efficacy of most oral 5-ASA therapies is broadly similar, the appropriate selection of a given formulation often relies on other factors. This article explores the differences between oral 5-ASA formulations in terms of their delivery system, reviews the available data on oral 5-ASA treatment efficacy and tolerability, and examines the rationale for changing from one 5-ASA formulation to another if a patient does not respond to, or worsens on, their existing agent.

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Gut. 2008 Feb 13 [Epub ahead of print]
Randomised trial of once- or twice-daily MMXTM mesalazine for maintenance of remission in ulcerative colitis.
Kamm MA, Lichtenstein GR, Sandborn WJ, Schreiber S, Lees KH, Barrett K, Joseph RE.
Australia.

AIM: Maintenance treatment in ulcerative colitis should be as convenient as possible, to increase the chance of compliance. MMX mesalazine is a once daily, high-strength (1.2 g/tablet) formulation of 5 aminosalicylic acid. This study evaluated the safety and efficacy of MMX mesalazine dosed once or twice daily as maintenance therapy in patients with ulcerative colitis. METHODS: This multicentre, randomised, open-label trial enrolled patients with strictly defined clinical and endoscopic remission, immediately following an episode of mild-to-moderate ulcerative colitis. Patients were randomised to MMX mesalazine 2.4 g/day as a single (2 x 1.2 g tablet) or divided dose (1 x 1.2 g tablet twice daily) for 12 months. RESULTS: 174 patients (37.9%; safety population n=459) experienced 384 adverse events, the majority of which were mild or moderate in intensity. Eighteen patients (3.9%), 9 in each group, experienced a total of 22 serious adverse events (10 in the once-daily and 12 in the twice-daily group). Most serious adverse events were gastrointestinal, experienced by 5 patients in the once-daily and 4 in the twice-daily group. At month 12, 64.4% (efficacy population, n=451) of patients in the once-daily and 68.5% of patients in the twice-daily group were in clinical and endoscopic remission (p=0.351). At month 12, 88.9% and 93.2% in each group, respectively, had maintained clinical remission (were 'relapse-free'). CONCLUSIONS: MMX mesalazine 2.4 g/day administered as a single or divided dose demonstrated a good safety profile, was well tolerated and was effective as maintenance treatment. High clinical and endoscopic remission rates can be achieved with once-daily dosing.

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J Manag Care Pharm. 2008 Jan;14(1 Suppl A):s2-12; quiz s13-5.
The challenge of compliance and persistence: focus on ulcerative colitis.
Kane SV, Brixner D, Rubin DT, Sewitch MJ.
Mayo Clinic College of Medicine, Division of Gastroenterology and Hepatology, 200 First Street, Sw, 19th Floor, Rochester, MN 55905, USA. kane.sunanda@mayo.edu

BACKGROUND: Non-adherence to therapy is a widespread problem, with typical adherence rates for prescribed medications being approximately 50%. An estimated 20% to 50% of patients with ulcerative colitis (UC) do not take their medications as prescribed, resulting in higher disease-recurrence rates and potentially higher health care costs. OBJECTIVE: To characterize the problem of non-adherence in UC, to review the many factors affecting compliance and persistence in this population, and to discuss practical strategies to improve adherence in these patients. SUMMARY: Adherence to and persistence with medication are complex and multifactorial behaviors. Factors shown to affect adherence in UC patients include disease extent and duration, cost of medications, fear of adverse effects, individual psychosocial variables, and the patient-physician relationship. In contrast, recent data do not support an important role for treatment-related factors such as daily dose, regimen, and formulation in influencing adherence in this population, particularly with longer duration of use. Strategies to improve adherence should involve the patient, the provider, and the health care delivery system. For UC patients, knowledge and discussion of the rationale for supporting persistence, such as recent data regarding agents that have a potential chemoprotective benefit, may encourage persistence, even during periods of quiescence. The patient-physician relationship is critical in encouraging adherence, particularly with respect to education, open communication, and agreement regarding the value of the assigned treatment. Health care delivery systems can improve adherence by encouraging the participation of multidisciplinary teams, providing reporting and tracking systems, and eliminating financial barriers where possible.

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Inflamm Bowel Dis. 2008 Jan 31 [Epub ahead of print]
Probiotic administration in patients with ileal pouch-anal anastomosis for ulcerative colitis is associated with expansion of mucosal regulatory cells.
Pronio A, Montesani C, Butteroni C, Vecchione S, Mumolo G, Vestri A, Vitolo D, Boirivant M.
Department of General Surgery, “P. Stefanini,” University “La Sapienza,” Roma, Italy.

Background: Probiotics have anti-inflammatory effects in patients with inflammatory bowel disease and appear to regulate mucosal immune response through reductions in proinflammatory cytokines. The probiotic VSL#3 prevents pouchitis if started within a week of ileostomy closure and maintains remission following antibacterial treatment in patients with refractory or recurrent pouchitis. However, the efficacy of probiotics and their effects on regulatory cells if started at a greater time after surgery in patients undergoing ileal pouch anal anastomosis (IPAA) for ulcerative colitis are unknown. Methods: We conducted an open-label study in which 31 patients at different periods from surgery without signs and symptoms of pouchitis were randomized to 2 sachets of VSL#3 once daily or no treatment for 12 months. Pouchitis disease activity index (PDAI) was evaluated at baseline and after 3, 6, and 12 months. The percentage of CD4+ T lymphocytes expressing CD25 and the inactive form o
f transforming growth factor-beta [latency-associated peptide (LAP)] were evaluated at baseline and after 3 and 6 months in peripheral-blood mononuclear cells and mucosal biopsies. Variation in tissue interleukin-1beta and Foxp3 mRNA expression was also evaluated. Results: During the study period, VSL#3-treated patients showed a significant reduction in PDAI score and a significant increase in the percentage of mucosal CD4+CD25(high) and CD4+ LAP-positive cells compared with baseline values. Tissue samples at different points showed a significant reduction in IL-1beta mRNA expression, and a significant increase in Foxp3 mRNA expression.Conclusions: We conclude that VSL#3 administration in patients with IPAA modulates the PDAI and expands the number of mucosal regulatory T cells.(Inflamm Bowel Dis 2008).

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Z Gastroenterol. 2007 Dec;45(12):1235-40.
Successful Treatment of Steroid Refractory Active Ulcerative Colitis with Natural Interferon-beta - an Open Long-Term Trial.
Musch E, Andus T, Malek M, Chrissafidou A, Schulz M.
Department of Internal Medicine, Marienhospital Bottrop, Germany.

INTRODUCTION: In some steroid refractory patients with active ulcerative colitis (UC), treatment with immunosuppressive agents, such as cyclosporin, azathioprine or 6-mercaptopurin is effective. However, there are patients who fail to respond to these treatment options or who cannot tolerate them. Application of natural interferon-beta (nIFN-beta) may offer an alternative. Following our positive results with nIFN-beta in a previously published open-labeled study, the present study was designed as an extension with the hypothesis that administration of higher dosage of nIFN-beta (1.0 vs. 0.5 MIU) could result in fewer relapse events. PATIENTS AND METHODS: 46 steroid refractory patients with active UC and a mean clinical activity index (CAI) of 13.2 +/- 3.7 (range 9 - 23) were treated with nIFN-beta in addition to existing basic medication (5-ASA/SASP plus corticosteroids). During an induction period of eight weeks, 18 patients (group A) received 0.5 MIU nIFN-beta daily and 28 patients (group B), 1.0 MIU nIFN-beta daily intravenously as a bolus injection. Patients who achieved complete remission (decrease of CAI to </= 4) during the induction period received maintenance therapy with nIFN-beta at the same dose level three times a week and corticosteroids were withdrawn. Remissions and maintenance of remissions were evaluated. RESULTS: In both groups, a comparable number of complete remissions occurred during the induction period: in 16 / 18 patients (89 %) in group A and in 24 / 28 patients (86 %) in group B. Duration of maintenance treatment was 60.0 +/- 90.0 weeks in group A and 52.7 +/- 9.6 weeks in group B. Under this treatment, relapses (increase of CAI to >/= 6) occurred in 5 / 16 patients (31 %) vs. 1 / 24 patients (4 %) (p </= 0.05). Hence, regarding maintaining remissions, the 1.0 MIU group outscored the 0.5 MIU group. Apart from known flu-like side effects, the therapy was well tolerated by all patients in both groups. CONCLUSION: nIFN-beta may be a safe and effective alternative to induce and maintain remissions in patients with steroid refractory active UC. To validate the presented results, its effect has to be investigated in a randomized, placebo-controlled dose-finding trial.

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Can J Gastroenterol. 2007 Dec;21(12):827-34.
Delayed-release oral mesalamine 4.8 g/day (800 mg tablets) compared to 2.4 g/day (400 mg tablets) for the treatment of mildly to moderately active ulcerative colitis: The ASCEND I trial.
Hanauer SB, Sandborn WJ, Dallaire C, Archambault A, Yacyshyn B, Yeh C, Smith-Hall N.
University of Chicago School of Medicine, Chicago, USA.

BACKGROUND: Delayed-release oral mesalamine 2.4 g/day to 4.8 g/day has been shown to be effective in treating mildly to moderately active ulcerative colitis (UC), but it is unknown whether an initial dose of 4.8 g/day is more effective than 2.4 g/day in patients with mildly to moderately active UC and in the subgroup with moderate disease. PATIENTS AND METHODS: A six-week, multicentre, randomized, double-blind, controlled trial assessing the safety and clinical efficacy of a new dose (ASCEND I) of medication randomly assigned 301 adults with mildly to moderately active UC to delayed-release oral mesalamine 2.4 g/day (400 mg tablet [n=154]) or 4.8 g/day (800 mg tablet [n=147]). The primary efficacy end point was overall improvement (ie, treatment success), defined as complete remission or response to therapy from baseline to week 6. Primary safety end points were adverse events and laboratory evaluations. Data were also analyzed separately for the prespecified subgroup of patients with moderate UC at baseline. RESULTS: Treatment success was not statistically different between the treatment groups at week 6; 51% of the group (77 of 150) who received delayed-release oral mesalamine 2.4 g/day and 56% of the group (76 of 136) who received 4.8 g/day reached the efficacy end point (P=0.441). Among the moderate disease subgroup, however, the higher initial dose was more effective; 57% of patients (53 of 93) given delayed-release oral mesalamine 2.4 g/day and 72% of patients (55 of 76) given 4.8 g/day achieved treatment success (P=0.0384). Both regimens were well tolerated. CONCLUSIONS: Delayed-release oral mesalamine is an effective and well-tolerated initial therapy in patients with mildly to moderately active UC, and a 4.8 g/day dose may enhance treatment success rates in patients with moderate disease compared with mesalamine 2.4 g/day.

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Neth J Med. 2007 Dec;65(11):411-8.
Probiotics and remission of ulcerative colitis: a systematic review.
Zigra PI, Maipa VE, Alamanos YP.
Department of Hygiene and Epidemiology, Medical School, University of Ioannina, Greece.

Background: Ulcerative colitis (UC) is an acute and inflammatory disease of the large bowel of unknown aetiology. The use of probiotics for this disease remains controversial. The objective of this systematic review was to identify studies based on randomised controlled trials comparing the effect of probiotics to the effect of anti-inflammatory drugs or placebo in the remission of UC. Methods: We conducted a systematic review of clinical trials comparing the effect of probiotics to the effect of anti-inflammatory treatment or placebo in the remission of UC. PubMed, sciencedirect, Cochrane, Google scholar, metaregister of Controlled Trials and National institutes of Health were searched. results: Nine studies met the inclusion criteria. These studies present a significant heterogeneity concerning their methodology and their results. The improvement in UC remission and the frequency of adverse effects do not differ significantly between probiotic and control groups. Conclusions: There are a limited number of randomised trials published in the field of probiotics used for the remission of UC, and they present many methodological differences. The existing studies suggest a similar safety and efficacy of probiotics in comparison with anti-inflammatory drugs.

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Inflamm Bowel Dis. 2007 Nov 29 [Epub ahead of print]
Steroid-refractory ulcerative colitis: Predictive factors of response to cyclosporine and validation in an independent cohort.
Aceituno M, García-Planella E, Heredia C, Zabana Y, Feu F, Domènech E, Gassull MA, Panés J.
Gastroenterology Department, Hospital Clínic de Barcelona, IDIBAPS, CIBER-EHD, Barcelona, Spain.

Background: One-third of patients with steroid-refractory ulcerative colitis (UC) do not respond to cyclosporine and require colectomy. Since alternative pharmacological treatments for this condition are available, it is pertinent to identify factors that predict response. The objective of this study was to determine predictive factors of response prior to cyclosporine administration, with validation in an independent cohort.Methods: The 2 cohorts of patients were identified from prospectively established databases. All patients had received 1 mg/kg/day prednisolone or equivalent for at least 5 days before cyclosporine. The efficacy measure was need of early surgery (within 3 months).Results: From 1998 to 2005, 34 patients were treated in 1 institution (derivation cohort) and 38 patients in the second institution (validation cohort). Eleven patients in the derivation cohort and 9 patients in the validation cohort underwent early colectomy. Univariate analysis in the derivation cohort demonstrated a significant association of colectomy with C-reactive protein (P = 0.012) and the Ho index before initiation of cyclosporine (P = 0.013). Regression analysis showed that only the Ho index (P = 0.011) had an independent predictive value. The Ho index predicted need of colectomy, with an area under the characteristic receiver operating curve of 0.79 (95% confidence interval [CI], 0.59-0.99) in the derivation cohort and 0.74 (95% CI, 0.53-0.96) in the validation cohort. The cutoff point with the best sensitivity and specificity ratio was >/=5.Conclusions: The Ho-based predictive score is a good predictor of response to cyclosporine and avoidance of colectomy, and may aid in the indication of this treatment for management of steroid-resistant UC.(Inflamm Bowel Dis 2007).

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Recenti Prog Med. 2007 Nov;98(11):560-4.
[Infliximab in moderate to severe steroid-dependent or steroid-refractory ulcerative colitis]
[Article in Italian]
Mocciaro F, Orlando A, Scimeca D, Cottone M.
Università, Bologna. mocciaro@neomedia.it

Tumor Necrosis Factor alpha plays a main role in ulcerative colitis. Thirteen male and 8 female affected by moderate to severe steroid-dependent or refractory-severe ulcerative colitis were treated with 5 mg/kg of infliximab (Remicade). At 12 week efficacy, steroid-sparing, colectomy and side effects were evaluated. In steroid-dependent group (13 patients): 8 patients had a clinical benefit (7 obtained a clinical remission, 54%), 8 (61.5%) discontinued steroids, 1 patient underwent surgery. In steroid-severe refractory group (8 patients): 3 patients (37.5%) had a clinical remission, 2 (25%) had a clinical response and 3 (37.5%) underwent colectomy. One mild infusion reaction and one adverse event (itch) were observed. Infliximab is an effective and safe therapy in patients with moderate to severe steroid dependent and refractory ulcerative colitis.

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Am Fam Physician. 2007 Nov 1;76(9):1323-30.
Ulcerative colitis: diagnosis and treatment.
Langan RC, Gotsch PB, Krafczyk MA, Skillinge DD.
St. Luke's Family Medicine Residency, Bethlehem, Pennsylvania 18017, USA. langanr@slhn.org

Ulcerative colitis is a chronic disease with recurrent symptoms and significant morbidity. The precise etiology is still unknown. As many as 25 percent of patients with ulcerative colitis have extraintestinal manifestations. The diagnosis is made endoscopically. Tests such as perinuclear antineutrophilic cytoplasmic antibodies and anti-Saccharomyces cerevisiae antibodies are promising, but not yet recommended for routine use. Treatment is based on the extent and severity of the disease. Rectal therapy with 5-aminosalicylic acid compounds is used for proctitis. More extensive disease requires treatment with oral 5-aminosalicylic acid compounds and oral corticosteroids. The side effects of steroids limit their usefulness for chronic therapy. Patients who do not respond to treatment with oral corticosteroids require hospitalization and intravenous steroids. Refractory symptoms may be treated with azathioprine or infliximab. Surgical treatment of ulcerative colitis is reserved for patients who fail medical therapy or who develop severe hemorrhage, perforation, or cancer. Longstanding ulcerative colitis is associated with an increased risk of colon cancer. Patients should receive an initial screening colonoscopy eight years after the onset of pancolitis and 12 to 15 years after the onset of left-sided disease; follow-up colonoscopy should be repeated every two to three years.

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Aliment Pharmacol Ther. 2007 Aug 1;26(3):411-9.
A retrospective analysis of the efficacy and safety of infliximab as rescue therapy in acute severe ulcerative colitis.
Lees CW, Heys D, Ho GT, Noble CL, Shand AG, Mowat C, Boulton-Jones R, Williams A, Church N, Satsangi J, Arnott ID; ON BEHALF OF THE SCOTTISH SOCIETY OF GASTROENTEROLOGY INFLIXIMAB GROUP.
Gastrointestinal Unit, Western General Hospital, Edinburgh, UK.

Background Forty per cent of patients with acute severe ulcerative colitis will not respond to intravenous corticosteroids and require second-line medical therapy or colectomy. A recent controlled trial has suggested that infliximab may be effective as rescue therapy. Aim To assess the value of infliximab as rescue therapy for acute severe colitis in a retrospective cohort of ulcerative colitis patients in Scotland. Methods All patients satisfied Truelove and Witts criteria on admission, failed to respond to intravenous corticosteroids and received infliximab (5 mg/kg) as rescue therapy. Response was defined as need for colectomy at hospital discharge and by 90 days. Results A total of 39 patients (median age 31.7 years) were treated. 26/39 (66%) responded, avoiding colectomy during the acute admission, and were followed up for a median of 203 days (Interquartile range = 135.5-328.5). Hypoalbuminaemia was a consistent predictor of non-response on univariate and multivariate analysis. At day 3 of intravenous steroids, 9/18 (50.0%) with serum albumin <34 g/L had urgent colectomy vs. 1/13 (7.7%) >/=34 g/L (P = 0.02, OR = 12.0, C.I. 1.28-112.7). Two serious adverse events occurred - one death due to Pseudomonas pneumonia, and one post-operative fungal septicaemia. Conclusions Infliximab represents a moderately effective rescue therapy for patients with acute severe ulcerative colitis. Serious adverse events, including death, do occur and should be discussed with patients prior to therapy.

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J Clin Pharmacol. 2007 Aug;47(8):930-41. Epub 2007 Jun 13.
The Role of TNF{alpha} in Ulcerative Colitis.
Sands BE, Kaplan GG.
MGH Crohn's and Colitis Center, 165 Cambridge Street, 9th Floor, Boston, MA 02114; e-mail: bsands@partners.org.

Standard of care for ulcerative colitis involves long-term pharmacotherapy or colectomy. Approximately 20% to 30% of patients eventually require a colectomy because patients either do not respond or cannot tolerate the currently available pharmacotherapies. Advances in our knowledge of the pathophysiology of ulcerative colitis have highlighted the importance of cytokines such as tumor necrosis factor alpha (TNFalpha) in the inflammatory process. TNFalpha is a proinflammatory mediator that plays an integral role in the pathogenesis of inflammatory bowel disease. In addition, mounting evidence indicates a genetic association between TNFalpha and ulcerative colitis. Furthermore, increased TNFalpha levels have been demonstrated in studies of patients with ulcerative colitis. TNFalpha is likely an important component in the pathophysiology of ulcerative colitis, and thus agents targeting TNFalpha in ulcerative colitis have been studied. Recent randomized controlled trials have confirmed that biologic anti-TNFalpha therapy is effective in ulcerative colitis. Soluble TNFalpha receptors or biologic agents that suppress or inhibit TNFalpha production may also show therapeutic promise.

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Cochrane Database Syst Rev. 2007 Jul 18;(3):CD006443.
Omega 3 fatty acids (fish oil) for maintenance of remission in ulcerative colitis.
Turner D, Steinhart A, Griffiths A.

BACKGROUND: Omega-3 fatty acids (n-3, fish oil) have been shown to have anti-inflammatory properties. Therefore, n-3 therapy may be beneficial in chronic inflammatory disorders such as ulcerative colitis. OBJECTIVES: To systematically review the efficacy and safety of n-3 for maintaining remission in ulcerative colitis (UC). SEARCH STRATEGY: The following databases were searched from their inception without language restriction: Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Healthstar, PubMed, and ACP journal club. Experts were contacted for unpublished data. SELECTION CRITERIA: Randomized placebo-controlled trials (RCT) of fish oil for maintenance of remission in UC were included. Studies must have enrolled patients (of any age group) who were in remission at the time of recruitment, and were followed for at least six months. The intervention must have been fish oil given in pre-defined dosage. Co-interventions were allowed only if they were balanced between the study groups. The primary outcome was relapse rate and the secondary outcome was frequency of adverse events. Other outcomes to assess efficacy were change in disease activity scores and time to first relapse. DATA COLLECTION AND ANALYSIS: Two independent investigators reviewed studies for eligibility, extracted the data and assessed study quality. Meta-analysis weighted by the Mantel-Haenszel method was performed using RevMan 4.2.8 software. Random or fixed effect models were used according to degree of heterogeneity and subgroup analyses were performed to explore heterogeneity. A sensitivity analysis was performed excluding a study of questionable quality . MAIN RESULTS: The three studies that were included used different formulation and dosing of n-3 but none used enteric coated capsules. The pooled analysis showed a similar relapse rate in the n-3 treated patients and controls (RR 1.02; 95% CI 0.51 to 2.03; P = 0.96). Combining the studies resulted in virtually no statistical heterogeneity (P = 0.93, I(2) = 0%). Various subgroup and sensitivity analyses showed similar results. However, the total number of patients enrolled in these studies was small (n = 138). No significant adverse events were recorded in any of the studies and not enough data were available to pool the other secondary outcomes for meta-analysis. AUTHORS' CONCLUSIONS: No evidence was found that supports the use of omega 3 fatty acids for maintenance of remission in UC. Further studies using enteric coated capsules may be justified.

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World J Gastroenterol. 2007 Jun 28;13(24):3288-300.
Ileal pouch surgery for ulcerative colitis.
Bach SP, Mortensen NJ.
Nuffield Department of Surgery, University of Oxford, United Kingdom. simon.bach@nds.ox.ac.uk

Ulcerative colitis (UC) is a relapsing and remitting disease characterised by chronic mucosal and submucosal inflammation of the colon and rectum. Treatment may vary depending upon the extent and severity of inflammation. Broadly speaking medical treatments aim to induce and then maintain remission. Surgery is indicated for inflammatory disease that is refractory to medical treatment or in cases of neoplastic transformation. Approximately 25% of patients with UC ultimately require colectomy. Ileal pouch-anal anastomosis (IPAA) has become the standard of care for patients with ulcerative colitis who ultimately require colectomy. This review will examine indications for IPAA, patient selection, technical aspects of surgery, management of complications and long term outcome following this procedure.

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Inflamm Bowel Dis. 2007 Jun 13; [Epub ahead of print]
Quality of life after restorative proctocolectomy for ulcerative colitis: Preoperative status and long-term results.
Tariverdian M, Leowardi C, Hinz U, Welsch T, Schmidt J, Kienle P.
Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.

Background: Restorative proctocolectomy has become the surgical procedure of choice in patients with ulcerative colitis. Only smaller studies have compared postoperative to preoperative quality of life (QoL).Methods: Patients with ulcerative colitis who had undergone restorative proctocolectomy at least 5 years before and who had filled out a disease-specific validated questionnaire (Gastrointestinal Quality of Life Index, GIQLI) prior to surgery (n = 128) were included into this follow-up study. Factors potentially influencing QoL at the time of operation were investigated with regard to pre- and postoperative QoL in univariate and multivariate analysis.Results: A total of 105 patients responded (82%). QoL at least 5 years after colectomy was significantly improved compared to the preoperative situation (109 versus 75). This improvement was evident in all 5 dimensions (P < 0.0001). The Colitis Activity Index (CAI) (P < 0.00001), a shorter duration of the disease (P < 0.05), and a 3-staged procedure (<0.001) were negatively correlated with preoperative QoL, whereas neoplasia (P < 0.001) was positively correlated. Colectomy was the reason for most of the increase in QoL. Ileostomy closure resulted in a further improvement in 3 of 5 dimensions but not in overall QoL. Uni- and multivariate analysis of the difference in QoL before and 5 years after colectomy revealed CAI, the type of operation (both P < 0.001), and neoplasia as significant factors (P < 0.05).Conclusions: The patients in the worst clinical situation profit the most from restorative proctocolectomy.(Inflamm Bowel Dis 2007).

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Surg Clin North Am. 2007 Jun;87(3):633-41.
Elective and emergent operative management of ulcerative colitis.
Metcalf AM.
Department of Surgery, Roy J. and Lucille A. Carver College of Medicine, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242, USA. amanda-metcalf@uiowa.edu

Surgical therapy of ulcerative colitis is effective, safe, and provides an improved quality of life in those whose disease cannot be managed medically. In the elective setting, widespread acceptance of restorative proctocolectomy has made surgical therapy an attractive option in the overall management of ulcerative colitis. Enthusiasm for this procedure should be tempered by the acknowledgment of the significant incidence of pouchitis in the long term, however. Proctocolectomy with ileostomy remains a good surgical option for patients who are unsuitable for restorative procedures. The standard therapy for fulminant colitis or toxic megacolon remains subtotal colectomy with ileostomy. Patients undergoing subtotal colectomy are candidates for conversion to restorative procedures.

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J Gastroenterol Hepatol. 2007 Jun 7; [Epub ahead of print]
A single center experience of methotrexate in the treatment of Crohn's disease and ulcerative colitis: A case for subcutaneous administration.
Nathan DM, Iser JH, Gibson PR.
Department of Gastroenterology and Monash University Department of Medicine, Box Hill Hospital, Victoria, Australia.

Background and Aim: Methotrexate (MTX) is used as a second-line immunodulator in patients with inflammatory bowel disease when purine analogs are not tolerated or lack efficacy. High-level evidence indicates efficacy for intramuscular administration in Crohn's disease, but there are few reports of experience with subcutaneous delivery. This study aimed to evaluate the response to and tolerance of MTX where subcutaneous administration was the preferred option. Method: The records of all patients treated with MTX were evaluated with regard to the dose, duration, response, and tolerance to MTX. Remission was defined as improvement in symptoms with no corticosteroid requirement for 3 months or ability to wean off steroids. Results: MTX was initiated in 45 patients with Crohn's disease and 23 ulcerative colitis (median age, 46 years; range, 20-80 years; 54% men) because of intolerance (69%) or resistance (31%) to purine analogues. MTX was initiated in 74% of patients in doses of 25 mg (33) or 20 mg (17), administered by subcutaneous self-injection in 90% of subjects. Remission was achieved in 24 of 45 (53%) with Crohn's disease and 11 of 23 (48%) with ulcerative colitis. An additional four (9%) patients with Crohn's disease and three patients (13%) with ulcerative colitis demonstrated symptomatic improvement and/or ability to decrease corticosteroid dose. While nine patients ceased therapy and nine successfully reduced their doses due to intolerance, three of four patients had no adverse effects. Subcutaneous delivery was well accepted. Conclusions: Subcutaneously administered MTX exhibits apparent efficacy, acceptance, tolerance, and safety in patients with Crohn's disease or ulcerative colitis who are steroid-dependent and where purine analogs have been ineffective or intolerable.

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Tunis Med. 2007 May;85(5):417-20.
[Predictive factors of surgery in severe attacks of ulcerative colitis]
[Article in French]
Elloumi H, Ben Abdelaziz A, Arfaoui D, Lassoued Y, Letaief R, Jmaa A, Ghannem H, Ajmi S.
Service de Gastro-entdrologie, Hôpital universitaire Sahloul, Sousse, Tunisie.

AIM: The purpose of our study was to determine clinical, biological or endoscopic factors that predict surgery after a glucocortico steroid treatment failure in severe attacks of ulcerative colitis. METHODS: Sixty one patients were analyzed. A therapeutic response for glucocorticosteroid was defined as the absence of resort to surgery within the first 30 days after hospitalization. Predictive factors were assessed using univariate and multivariate analysis. RESULTS: Fifteen patients (24.6%) had a medical response. In univariate analysis, predictive factors of surgery were: male sex, tobacco, number of colitis attacks in case history, temperature over 38 degrees C, erythrocyte sedimentation rate over 30 mm, systolic blood pressure below 11, deep and wide ulcers. During the course, bowel movements/day over 7, pulse over 90/mn, temperature over 38 degrees C on day 3 after treatment initiation as well as passage of blood on day 5 were identified as predictors of surgery. In multivariate analysis, bowel movements over 7/day on day 3 of hospitalization was independently predicted a surgery. CONCLUSION: Bowel movements/day over 7 on day 3 of hospitalization was the only independently predictive factor of surgery after glucortico steroid treatment failure

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Clin Pharmacokinet. 2007;46(8):645-60.
Clinical pharmacokinetics and use of infliximab.
Klotz U, Teml A, Schwab M.
Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, and University of Tübingen, Tübingen, Germany.

Tumor necrosis factor-alpha (TNFalpha) is a key proinflammatory cytokine involved in chronic inflammatory diseases. Infliximab, a chimeric (human-murine) monoclonal IgG1 anti-TNFalpha antibody, is used in the treatment of Crohn's disease (including fistulising disease) and rheumatoid arthritis (in combination with methotrexate) if standard treatments have failed. The indications for infliximab have recently been expanded to include ankylosing spondylitis, psoriatic arthritis, psoriasis and ulcerative colitis. The biological agent infliximab is given by multiple intravenous infusions in a dosage of 3-5 mg/kg (initially at weeks 0, 2 and 6; subsequently in intervals of 4-8 weeks). In controlled trials, clinical response rates of 20-40% have been achieved with such regimens in Crohn's disease and rheumatoid arthritis. However, the therapeutic benefits must be balanced against the risks of a variety of severe adverse events (e.g. severe infections including tuberculosis, hepatotoxicity, infusion reactions, serum sickness-like disease and lymphoma).Following single and multiple infusions of infliximab, no relevant differences in median concentration-time profiles have been observed between patients with Crohn's disease, patients with rheumatoid arthritis and patients with psoriasis. The apparent volume of distribution of the high-molecular-weight infliximab (149.1 kDa) is low (3-6L) and represents the intravascular space. The long persistence in this compartment (elimination half-life 7-12 days, mean residence time 12-17 days) is due to the very low systemic clearance of about 11-15 mL/hour (0.18-0.25 mL/minute). Elimination of infliximab is most probably accomplished through degradation by unspecific proteases. During multiple infusions (every 4-8 weeks), no accumulation was observed, and serum concentrations and the area under the plasma concentration-time curve of infliximab increased in proportion to the infused dose, indicating linear pharmacokinetics. Co-medication with methotrexate delayed the decline in the serum concentrations of infliximab.When relating serum concentrations to the clinical response in patients with rheumatoid arthritis and patients with Crohn's disease, it can be assumed that trough concentrations above 1 microg/mL could be used as a kind of therapeutic target. In the future, identification of biomarkers for (non-)response and risk factors for adverse drug reactions would be very helpful. Furthermore, combined biological, pharmacokinetic, pharmacogenomic and clinical studies have not yet been performed and are needed to optimise the therapeutic potential of infliximab, which is currently established as a rescue treatment in refractory patients.

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Dig Liver Dis. 2007 May;39(5):430-4. Epub 2007 Mar 26.
Treatment of patients with acute ulcerative colitis: Conventional corticosteroid therapy (MP) versus granulocytapheresis (GMA): A pilot study.
Bresci G, Parisi G, Mazzoni A, Scatena F, Capria A.
Gastroenterology Department, Azienda Ospedaliera-Universitaria Pisana, Pisa, Italy.

AIM: The aim of our pilot study is to report the efficacy of granulocytapheresis in patients with acute ulcerative colitis with respect to the use of conventional corticosteroids such as methylprednisolone. METHODS: The activity of disease was evaluated by clinical activity index and endoscopic index. Forty patients with acute ulcerative colitis were randomly divided in two groups of 20 subjects each: one group was treated with five sessions of granulocytapheresis, the other one with methylprednisolone for 5 weeks. Complete response was defined as clinical activity index lower than 6 and endoscopic index lower than 4 after 6 weeks of follow-up. Partial response was defined as clinical activity index lower than 6 but endoscopic index more than 4 after 6 weeks of follow-up. All the conditions not included are classified as nonresponders. RESULTS: All the patients completed the trial. Complete clinical response was observed in 70% of patients treated with granulocytapheresis versus 60% of patients treated with methylprednisolone. A partial response was observed in 20% of patients treated with granulocytapheresis versus 15% of patients treated with methylprednisolone. During the sessions of granulocytapheresis only a transient mild headache was recorded in 10% of patients, while side effects were more common (50%) in the patients treated with methylprednisolone. CONCLUSION: Granulocytapheresis represents a new and promising approach to active ulcerative colitis. In fact, even if more expensive than conventional corticosteroids, it seems slightly more effective and, above all, with side effects much less frequent and serious. Thus, granulocytapheresis cycles could be prolonged or repeated, if necessary, in more severe diseases without significant risks for the patients.

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Dig Dis Sci. 2007 Apr 5; [Epub ahead of print]
Leukocytapheresis (LCAP) in the Management of Chronic Active Ulcerative Colitis-Results of a Randomized Pilot Trial.
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.

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Internist (Berl). 2007 Mar 29; [Epub ahead of print]
[Ileo pouch-anal anastomosis.]
[Article in German]
Stallmach A, Schmidt C.
Abteilung fur Gastroenterologie, Hepatologie und Infektiologie, Friedrich-Schiller-Universitat, Erlanger Allee 101, 07740, Jena, Deutschland, andreas.stallmach@med.uni-jena.de.

Restorative proctocolectomy with an ileal pouch-anal anastomosis is the treatment of choice in patients with ulcerative colitis (UC) and familial adenomatous polyposis requiring surgical therapy. Pouchitis is the most frequent complication, occurring in up to 50% of patients with underlying UC. Clinical symptoms of the disease are non-specific. Moreover, surgical complications must be differentiated from idiopathic pouchitis using pouchoscopy, endoscopic ultrasound or MRI of the pelvis in certain cases. The therapy for idiopathic pouchitis, its etiology and pathophysiology being unclear, is based on antibiotic treatment, usually with metronidazole or ciprofloxacin. Probiotics such as VSL#3(R) can be used to prevent relapse. In summary, the clinical and functional outcomes are excellent and stable for 20 years after surgery.

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BMC Gastroenterol. 2007 Mar 27;7(1):13 [Epub ahead of print]
Colectomy rate in steroid-refractory colitis initially responsive to cyclosporin: A long-term retrospective cohort study.
Actis GC, Fadda M, David E, Sapino A.

ABSTRACT: BACKGROUND: There is consistent evidence that 50% of patients with acute, steroid-resistant flare of ulcerative colitis (UC) may achieve remission and avoid colectomy if treated with cyclosporin (CsA). However, follow-up of the responders has shown that most of them relapse and need surgery shortly after the response. We compared the records of our CsA-treated patients with those of other groups in order to help clarify this matter. METHODS: All patients admitted consecutively to our Unit with an attack of UC and treated with CsA between January 1991 and December 1999 were studied. Patients were begun on continuously-infused CsA at 2 mg/kg/day (1991-1996), or on NEORAL at an initial dose of 5 mg/kg/day (1996-1999). The maintenance treatment included oral CsA for 3-6 months with or without azathioprine (AZA). CsA failure was defined as a relapse requiring steroids with or without progression to colectomy; the cumulative probability of relapse/colectomy was assessed by Fisher's exact tests and Kaplan-Meier analysis. RESULTS: Among the patients, 39/61 (63%) initially responded. These 39 included a fatality and 4 drop-outs (unrelated to the side-effects of CsA), leaving 34 patients for the study. Of these, 61% and 35% were colectomy-free at 1 and 7 years, respectively; the corresponding figures were 80 and 60% respectively in the subset treated with AZA, but 47% and 15% in the AZA-untreated subgroup (p= 0.0007 at 7 years). Among the 34 patients, 44% were relapse-free at 1 year, but all had relapsed at 7 years (p=0.0635). The overall resort to colectomy was 72%, while 19% of the patients remained colectomy-free. CONCLUSION: Sixty percent of a cohort of patients with steroid-refractory colitis responded to CsA and 60% of these responders retained the colon after 1 year. These figures fell to 35% at 7 years but improved to 60% on AZA. The overall need for colectomy remains high in these patients and toxicity must be monitored.

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Expert Opin Drug Saf. 2007 Mar;6(2):99-107.
The risks and the benefits of mesalazine as a treatment for ulcerative colitis.
Moss AC, Peppercorn MA.
Inflammatory Bowel Disease Fellow, Harvard Medical School, Center for Inflammatory Bowel Disease, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.

Mesalazine is a 5-aminosalicylic acid compound that is the primary treatment for mild-to-moderate ulcerative colitis. In both oral and topical formulations it has demonstrated efficacy in both induction of active colitis and maintenance of remission, regardless of the extent of inflammation. In addition, there is indirect evidence of a role in the chemoprophylaxis of colorectal cancer in these patients. Mesalazine is generally well tolerated by patients, although serious adverse effects have been reported. In particular, worsening of colitis, interstitial pneumonitis and nephritis are of concern to clinicians. Fortunately these reactions are mostly reversible with cessation of therapy.

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Ther Umsch. 2007 Mar;64(3):161-9.
[Pre- and probiotics.]
[Article in German]
Meier R, Lochs H.
Medizinische Universitatsklinik, Abteilung fur Gastroenterologie, Hepatologie und Ernahrung, Kantonsspital, Liestal.

Nowadays, the regular consumption of pre- and probiotics is recommended to provide various positive health benefits. The in vitro and in vivo demonstrated actions on the intestinal microflora, the mucosal barrier and the immunological system are very interesting to propose beneficial health effects, but the scientific proof in humans is not demonstrated yet. Pre- and probiotics are very active in the intestinal tract (mainly in the colon) by maintaining a healthy gut microflora and influencing metabolic, trophic and protective mechanism. Prebiotics stimulates the growth of apathogen bacteria and increase the short chain fatty acid concentration by fermentation. Short chain fatty acids are necessary substrates for a healthy gut. Probiotics inhibit the growth of pathogen bacteria, reduce the translocation of bacteria and toxins and modulate the intestinal immune system. For some specific clinical diseases (ulcerative colitis, pouchitis, diarrhoea) a therapeutic and prophylactic effect with pre- and probiotics was shown. In the near future more indications for pre- and probiotics (used as a single strain or as in a combination) will be added. Promising results are already shown in irritable bowel syndrome, prevention of antibiotic induced diarrhoea, in surgical and in intensive care patients. Future studies should focus to determine the characteristics of a healthy gut and the evaluation of specific health benefits by well-designed, controlled human studies of adequate duration.

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J Pediatr Gastroenterol Nutr. 2007 Mar;44(3):312-7.
Short- and long-term response to and weaning from infliximab therapy in pediatric ulcerative colitis.
Fanjiang G, Russell GH, Katz AJ.
Department of Pediatric Gastroenterology & Nutrition, Massachusetts General Hospital for Children, Boston 02114, USA. gfanjiang@partners.org

OBJECTIVES: We evaluated the response to infliximab in pediatric patients with ulcerative colitis (UC) and their long-term follow-up. We expanded our previous study of 14 patients and furthermore evaluated the success of weaning patients from infliximab. PATIENTS AND METHODS: We reviewed the charts of 27 pediatric patients with UC who were treated with infliximab instead of undergoing a colectomy. Patients with new-onset UC refractory to intravenous steroids for 5 to 10 days and patients with non-steroid-dependent UC with an acute exacerbation were classified as acutely ill (n = 16); patients with chronic steroid-dependent UC were classified as chronically ill (n = 11). The Lichtiger Colitis Activity Index (LCAI) was measured for all patients at baseline and at 1 and 2 months after treatment with infliximab was initiated. Patients were regarded as successfully treated if they remained off steroids and avoided colectomy. RESULTS: The acutely ill group had a mean LCAI score of 11.4 at induction and 0.3 after 2 months. The chronically ill group had a mean LCAI score of 11.2 at induction and 5.5 after 2 months. Treatment with infliximab was successful in 75% of acutely ill patients and in 27% of chronically ill patients. Infliximab was discontinued in 80% of successfully treated patients (83% of acutely ill, 67% of chronically ill). These patients had an average of 10 infusions and a mean follow-up time of 10 months from their last infliximab infusion. CONCLUSIONS: Our results suggest that infliximab is more effective in acutely ill UC patients than in patients with chronic steroid-dependent UC. In addition, some patients treated with infliximab can be weaned from infliximab and maintain remission.

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J Gastrointest Surg. 2007 Jan;11(1):3-7.
Laparoscopic restorative proctocolectomy for ulcerative colitis.
Boller AM, Larson DW.
Division of Colon and Rectal Surgery, Mayo Clinic, Gonda 9S, 200 First Street SW, Rochester, MN, 55905, USA, Larson.david2@mayo.edu.

Laparoscopic surgery of the colon has become an established method for the resection of both benign and malignant disease. Complex laparoscopic colon resections were once stigmatized due to their longer operating times and inherent technical difficulty. However, technological innovations and increased surgical experience with laparoscopy have advanced the field of complex laparoscopic surgery, including ileal pouch-anal anastomosis (IPAA) procedure, with safe feasible results. When these operations are broken down in a stepwise fashion, the complexity of the laparoscopic IPAA procedure becomes simplified, allowing one to effectively reproduce this operation. The systematic laparoscopic steps outlined establish a simple, reproducible approach to a laparoscopic IPAA procedure for ulcerative colitis patients. This approach to laparoscopic IPAA provides one with a viable approach to this complex operation.

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Int J Colorectal Dis. 2007 Jan 10; [Epub ahead of print]
Ten years experience of one-stage restorative proctocolectomy for ulcerative colitis.
Davies M, Hawley PR.
St. Mark's Hospital (Northwick Park), Watford Road, Harrow, HA1 3UJ, UK.

BACKGROUND: Ileal-pouch anal anastomosis has an established role in the treatment of ulcerative colitis. Controversy exists regarding the routine use of a diverting ileostomy. The aim of this study was to review the clinical and functional outcome of patients undergoing restorative proctocolectomy in the absence of a diverting ileostomy (one-stage). MATERIALS AND METHODS: Between 1990 and 1999, 87 patients with ulcerative colitis underwent a one-stage restorative proctocolectomy. The median age at the time of operation was 34 years (range 12-64 years) and median follow-up was 36 months (range 24-144 months). The clinical notes were reviewed retrospectively. RESULTS: The median in-patient stay was 15 days (range 9-36). There were no post-operative deaths. The complication rate within 30 days of surgery approximated to 40%. The median daytime pouch evacuation rate was 5. Only 13% of patients had to empty their pouch at night on a regular basis. Pelvic sepsis secondary to anastomotic leakage was the most commonly encountered problem, occurring in 15 patients. Small bowel obstruction was encountered in ten patients. One pouch required excision for a recurrent pouch-vaginal fistula. CONCLUSION: Despite refinements in the surgical technique, restorative proctocolectomy is associated with significant morbidity. For a selected group of patients undergoing an ileo-anal anastomosis, a defunctioning ileostomy may be avoided.

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J Pediatr Surg. 2007 Jan;42(1):31-4; discussion 34-5.
Pouch outcomes among children with ulcerative colitis treated with calcineurin inhibitors before ileal pouch anal anastomosis surgery.
Hait EJ, Bousvaros A, Schuman M, Shamberger RC, Lillehei CW.
The Center for Inflammatory Bowel Disease, Children's Hospital Boston, Harvard University, Boston, MA 02115, USA.

PURPOSE: The purpose of this article is to describe the outcomes of the pouches of 14 children with ulcerative colitis (UC) who were pretreated with calcineurin inhibitors before they underwent their ileal pouch anal anastomosis (IPAA) surgery. METHODS: An institutional review board-approved retrospective review of the charts of consecutive patients with UC treated with calcineurin inhibitors before undergoing IPAA surgery at a tertiary pediatric center between 1998 and 2003 was performed. The primary endpoint was pouch outcome after at least 2 years of follow-up (healthy pouch, acute pouchitis, chronic refractory pouchitis, or pouch failure); the secondary endpoints were early postoperative complications, number of stages, and time between stages. RESULTS: Fourteen of 53 consecutive patients who underwent IPAA for UC were treated with calcineurin inhibitors before their surgery (26%; 6 with cyclosporine and 8 with tacrolimus). All 14 patients were concomitantly treated with systemic steroids. Ten patients (71%) were also taking 6-mercaptopurine or azathioprine, and 9 (64%) were also taking mesalamine. Three patients (21%) had healthy pouches with no clinical evidence of pouchitis, 6 (43%) had at least one episode of acute pouchitis (average of 2 episodes per year), 3 (21%) had chronic relapsing pouchitis, and 2 (14%) were later determined to have Crohn's disease. There was no pouch failure. Two patients (14%) had an early postoperative complication (intraabdominal abscess, anastomotic stricture). Five patients (36%) had a 2-staged procedure, and 8 (64%) had a 3-staged procedure. For the 2-staged procedures, the mean time between the first and second stages was 3.14 months (range, 3-4 months). For the 3-staged procedures, the mean time between the first and second stages was 4.25 months (range, 2-6 months) and that between the second and third stages was 4 months (range, 2.5-6 months). CONCLUSIONS: In this series, chronic pouchitis was an infrequent complication among children who were pretreated with calcineurin inhibitors. Calcineurin inhibitor use did not lead to or portend increased early postoperative complications or affect the number or duration of surgical stages. Further studies are required to determine if preoperative calcineurin inhibitors improve pouch outcomes or facilitate the performance of 2-staged procedures.

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Am J Gastroenterol. 2006 Dec 11; [Epub ahead of print]
Continuous Infusion Versus Bolus Administration of Steroids in Severe Attacks of Ulcerative Colitis: A Randomized, Double-Blind Trial.
Bossa F, Fiorella S, Caruso N, Accadia L, Napolitano G, Valvano MR, Andriulli A, Annese V.
U.O. Gastroenterologia, Ospedale I.R.C.C.S. "Casa Sollievo della Sofferenza," S. Giovanni Rotondo, Italy.

BACKGROUND: In patients with severe attacks of ulcerative colitis (UC), IV steroids represent the first-line treatment, leading to clinical improvement in approximately 50-60% of patients. AIM: The aim of this study was to prospectively compare the efficacy and safety of different modalities of steroid administration, and to evaluate predictors of failure to therapy. MATERIALS In a single-center, double-blind trial, consecutive patients with a severe attack of UC received AND METHODS: 1 mg/kg/day of 6-methyl-prednisolone administered randomly by either a bolus injection (group A) or continuous infusion (group B). RESULTS: Sixty-six patients were enrolled (35 men, mean age 38 +/- 15, range 18-75 yr), 15 of them at their first attack of UC; in the remaining cases, the mean duration of disease was 4.5 +/- 5 yr. At inclusion, forty patients (60%) had pancolitis and the remainder had left-sided colitis. Overall, thirty-three patients (50%) underwent clinical remission after 7 days of treatment: 16 of 32 in group A and 17 of 34 in group B. Thirty-one patients eventually underwent total colectomy (12 in group A and 9 in group B), which was carried out by the first month in 10 patients (5 in each group). Twenty-eight patients (15 in group A and 13 in group B) experienced steroid-related adverse reactions. All differences between groups were not statistically significant. Previous use of steroids (OR 13.6, CI 2-86) and active smoking (OR 11.6, CI 1.4-107) were independent predictors of nonresponse. CONCLUSIONS: In severe attacks of UC, methyl-prednisolone given as a continuous infusion was no better than bolus administration in terms of efficacy and safety.

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Clin Gastroenterol Hepatol. 2006 Dec 1; [Epub ahead of print]
Response to Corticosteroids in Severe Ulcerative Colitis: A Systematic Review of the Literature and a Meta-Regression.
Turner D, Walsh CM, Steinhart AH, Griffiths AM.
Division of Gastroenterology, Hepatology and Nutrition, the Hospital for Sick Children, Toronto, Canada.

BACKGROUND & AIMS: Colectomy is a potentially life-saving procedure for patients with severe attacks of UC who fail medical therapy. We aimed to systematically review studies that reported the short-term colectomy rate in severe UC or reported variables that could predict treatment failure. METHODS: We conducted a systematic literature search for cohort studies and controlled trials published between 1974-2006. RESULTS: Thirty-two studies met the inclusion criteria; 16 reported short-term outcome and predictors of therapy failure, 13 only outcome, and 3 only predictors. In the pooled analysis, 581 of 1991 patients required colectomy (weighted mean 27; 95% confidence interval [CI], 26%-28%), and 22 died (1%; 95% CI, 0.7%-1.5%). In a heterogeneity-controlled meta-regression, colectomy rate did not change during the last 30 years (R(2) = 0.07, P = .8). Cyclosporine was used in only 100 patients, with a 51% (95% CI, 41%-60%) short-term success rate. A second meta-regression failed to demonstrate a dose-colectomy response of methylprednisolone therapy beyond 60 mg daily (R(2) < 0.01, P = .98). More than 20 variables were identified in 19 studies to predict medical therapy failure, but only a few were consistently reproduced: disease extent, stool frequency, temperature, heart rate, C-reactive protein, albumin, and radiologic assessment. CONCLUSIONS: The short-term colectomy rate in severe UC has remained stable during the last 30 years, despite the introduction of cyclosporine, which was not used frequently. We could not find any support for administering methylprednisolone at a higher dose than 60 mg/day. Variables that predict outcome of corticosteroid therapy could aid in the development of guidelines for introduction of rescue therapies in severe UC.

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Gastroenterol Clin North Am. 2006 Dec;35(4):821-36.
Infliximab in ulcerative colitis.
Aberra FN, Lichtenstein GR.
Division of Gastroenterology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA.

Infliximab is effective for treatment of moderate-to-severe UC and is recommended for patients who have had an inadequate response to medical therapy or who are intolerant of or do not desire to take the potential risk of using specific agents including immunomodulators (cyclosporine A, azathioprine, or 6-mercaptopurine), corticosteroids, and, potentially, mesalamine. Future trials are needed to assess the efficacy of infliximab with immunomodulators to see if additional benefit is achieved so that the risk-benefit ratio is positive. Based on the favorable efficacy of infliximab for UC therapy, the ground work has been established for evaluating infliximab and addressing some of the many unanswered questions and also for assessing other anti-TNF agents and streamlining the anti-TNG antibody to improve efficacy, reduce side effects, and ease administration.

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Inflamm Bowel Dis. 2006 Dec;12(12):1131-5.
Treatment of ulcerative colitis refractory to steroid therapy by oral microemulsion cyclosporine (Neoral).
Weber A, Fein F, Koch S, Dupont-Gossart AC, Mantion G, Heyd B, Carbonnel F.
Service de Gastroenterologie et Nutrition, Hopital Universitaire, F-25000 Besancon, France.

BACKGROUND: Intravenous cyclosporine is active in 60% to 80% of patients with ulcerative colitis (UC) who failed to respond to intravenous corticosteroids. Several studies have suggested that cyclosporine in microemulsion form (Neoral) has some efficacy in this setting, but the optimal dose, blood level, time to response, and remission need to be better defined. The aim of this study was to evaluate the response to Neoral and its toxicity in active corticosteroid-refractory UC. METHODS: Between March 2002 and August 2005, 20 courses of Neoral [initial dose, 2.3 mg/kg (range, 1.8 to 2.8 mg/kg) every 12 hours] were prescribed in 19 consecutive patients for a UC attack that did not respond to intravenous methylprednisolone. All patients received prophylaxis against Pneumocystis carinii. RESULTS: Response was obtained in 17 of 20 attacks (85%) after 3.5 days (range, 1 to 7). Remission was obtained in 15 of 20 attacks (75%) after 13 days (range, 2 to 30 days). Four responders relapsed and underwent colectomy 21 to 900 days after the start of Neoral. Overall, 14 of 19 patients (74%) were colectomy free after a median follow-up of 8 months (range, 1 to 41 months). Cyclosporine blood levels were measured at fasting (C0) and 2 hours after Neoral administration (C2) in a subgroup of 10 responders. The results were 103 ng/mL (range, 32 to 240 ng/mL) for C0 and 761 ng/mL (183 to 1390 ng/mL) for C2. One severe bedridden patient with neonatal encephalopathy died. Main side effects observed were mild transient renal impairment (n = 2), hypertension (n = 1), cytomegalovirus infection (n = 2), and esophageal candidiasis (n = 1). CONCLUSIONS: In active corticosteroid-refractory UC, Neoral seems to have the same efficacy and toxicity as the intravenous form. Trough target cyclosporine blood levels should not exceed 100 ng/mL for C0 and 700 ng/mL for C2.
  
Previous Ulcerative Colitis Research:
2002-2006   
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