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.
   

Ulcerative Colitis Research:
2002-2006
     
Cochrane Database Syst Rev. 2006 Jul 19;3:CD005112.
Tumour necrosis factor alpha blocking agents for induction of remission in ulcerative colitis.
Lawson M, Thomas A, Akobeng A.

BACKGROUND: Anti-TNF-alpha agents have been shown to be effective for the induction of remission in Crohn's disease. The role of TNF-alpha blocking agents in ulcerative colitis is, however, unclear and recent studies have yielded conflicting results. OBJECTIVES: To evaluate the efficacy of TNF-alpha antibody for induction of remission in ulcerative colitis, and to determine adverse events associated with TNF-alpha antibody treatment. SEARCH STRATEGY: We searched MEDLINE (1966 to 2005), EMBASE (1984 to 2005), the Cochrane Central Register of Controlled Trials (Issue 3, 2004) and the IBD/FBD Review Group Specialized Trials Register. We hand-searched the articles cited in each publication. SELECTION CRITERIA: Only randomised controlled trials in which patients with active ulcerative colitis (defined by a combination of clinical, radiographic, endoscopic and histologic criteria) were randomly allocated to receive a TNF-alpha blocking agent in the treatment arm, and to receive placebo or another treatment in the comparison arm were included. DATA COLLECTION AND ANALYSIS: Data extraction and assessment of methodological quality of each study were independently performed by two reviewers. Any disagreement among reviewers was resolved by consensus. The main outcome measure was the occurrence of remission as defined by the primary studies. Other endpoints were clinical, histological or endoscopic improvement as defined by the primary studies; improvement in quality of life as measured by a validated quality of life tool and the occurrence of adverse events. MAIN RESULTS: Seven randomised controlled trials were identified that satisfied the inclusion criteria. In patients with moderate to severe ulcerative colitis whose disease was refractory to conventional treatment using corticosteroids and/or immunosuppressive agents, infliximab (three intravenous infusions at 0, 2, and 6 weeks) was more effective than placebo in inducing clinical remission (Relative Risk (RR) 3.22, 95% CI 2.18 to 4.76); inducing endoscopic remission (RR 1.88, 95% CI 1.54 to 2.28); and in inducing clinical response (RR 1.99, 95% CI 1.65 to 2.41) at 8 weeks. A single infusion of infliximab was also more effective than placebo in reducing the need for colectomy within 90 days after infusion (RR 0.44, 95% CI 0.22 to 0.87). AUTHORS' CONCLUSIONS: In patients with moderate to severe ulcerative colitis whose disease is refractory to conventional treatment using corticosteroids and/or immunosuppressive agents, infliximab is effective in inducing clinical remission, inducing clinical response, promoting mucosal healing, and reducing the need for colectomy at least in the short term. Serious adverse events attributable to infliximab were not common in the included studies but physicians should be aware of and be prepared to deal with potential adverse events such as anaphylactic reactions and infections.

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Br Med Bull. 2006 Jul 17;75-76:131-44. Print 2006.
Management of acute severe colitis.
Jakobovits SL, Travis SP.
Senior Clinical Gastroenterology Fellow, Gastroenterology Unit, Level 2 John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK. Tel.: +44 01865 851072; fax: +44 01865 222614; sjakobovits@hotmail.com.

The management of acute severe ulcerative colitis depends on early recognition of the unwell patient with colitis, the prompt initiation of treatment and objective assessment of the likelihood of medical failure. This deters 'hopeful expectation' in an attempt to avoid surgery. Intravenous corticosteroids remain first-line therapy but are completely effective in only 40%, partially effective in 30% and around 30% come to colectomy. The decision to use ciclosporin or infliximab for those with a poor response to steroids should be made at an early stage, often 3 or 4 days after starting intensive therapy. Decision-making is becoming more difficult with agents such as visilizumab, tacrolimus and the technique of leucocytapheresis as further options. Nevertheless, intravenous corticosteroids and timely colectomy have reduced mortality from nearly 30% to <1% in specialist centres. Ciclosporin has delayed the need for urgent colectomy in many patients, but long-term follow-up suggests the majority come to colectomy within 7 years. Long-term outcome with newer agents, including infliximab, is not yet known.

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Curr Treat Options Gastroenterol. 2006 Jun;9(3):234-45.
Management of refractory ulcerative colitis.
Sohi S, Cohen RD.
Department of Medicine, Section of Gastroenterology, University of Chicago Medical Center, MC 4076, 5841 South Maryland Avenue, Chicago, IL 60637, USA. rcohen@medicine.bsd.uchicago.edu.

A physician's approach to patients with ulcerative colitis (UC) who are refractory to standard first-line therapies must be thoughtful and systematic and include the individual's physical and emotional state as the physician examines the various dietary, medical, and surgical options currently available. It is of foremost importance to confirm that the refractory patient's symptoms are not simply due to dietary indiscretion, concomitant bowel infection (especially with Clostridium difficile), an incorrect diagnosis (eg, colitis due to infection, NSAIDs, ischemia, diverticulitis, or Crohn's disease), or even a concomitant diagnosis (eg, celiac sprue, pancreatic insufficiency, functional bowel disorder, laxative or sorbitol intake). The ability to quickly assess the status of the colonic mucosa with flexible sigmoidoscopy aids in the ability to distinguish patients with refractory inflammation from those with other diagnoses. The initiation and optimization of the long-term purine analogues azathioprine (AZA) or 6-mercaptopurine (6-MP) remain the backbone of medical therapy for patients with refractory UC. For those unresponsive to corticosteroids, quicker induction of remission may necessitate infliximab, cyclosporine, or tacrolimus. Successful induction and maintenance with AZA, 6-MP, and/or infliximab should be followed by long-term therapy with these agents. Cessation of therapy often leads to relapse. Novel therapies under investigation hold the promise of offering more options for both the induction and maintenance of remission in refractory UC patients. Discussions of surgical intervention should not be put off as a last resort but rather included in the overall treatment plan offered to the patient.

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Hepatogastroenterology. 2006 May-Jun;53(69):317-21.
Efficacy and tolerability of olsalazine (dipentum) in the treatment of patients with ulcerative colitis—results of a field study.
Singer MV, Schmausser H, Schonfeld G.
Klinikum Mannheim der Universitat Heidelberg, Theodor-Kutzer-Ufer, Mannheim, Germany. manfred.v.singer@med.ma.uni-heidelberg.de

BACKGROUND/AIMS: In the treatment of ulcerative colitis, 5-aminosalicylic acid is the standard therapy for both acute exacerbations of the disease and the maintenance of remission. Clinical studies have shown that olsalazine (Dipentum)--a prodrug converted to two molecules of 5-ASA by colonic bacteria-induces and maintains remission. This study aimed to investigate the efficacy and tolerability of olsalazine in patients with ulcerative colitis who were being treated in daily practice by private physicians specializing in gastroenterology. METHODOLOGY: A total of 260 patients with ulcerative colitis (aged 17-77 years, 116 men) were studied. The doses of olsalazine and the clinical data (including acute disease symptoms and the occurrence of adverse events) were recorded over a 6-month period. RESULTS: Twenty per cent of patients had pancolitis, 48% had left-sided disease and 32% had proctitis or proctosigmoiditis. At study entry, 86% of patients had active disease; the percentages of these patients in remission after 6 weeks and 6 months were 42% and 91%, respectively. Patients with active disease received a mean dose of olsalazine - 2324mg per day initially and 1325mg per day at 6 months. The corresponding figures for patients in remission at study entry were 1386mg and 1162mg per day, respectively. Seventy-three per cent of patients took olsalazine with food, as recommended. The overall rate of adverse events was low; no serious adverse events occurred. CONCLUSIONS: Olsalazine therapy resulted in a rapid regression in the acute symptoms of ulcerative colitis. Olsalazine was also effective in maintaining remission. The drug was well tolerated.

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Aliment Pharmacol Ther. 2006 May 15;23(10):1443-53.
Low-molecular-weight heparin (enoxaparin) as adjuvant therapy in the treatment of active ulcerative colitis: a randomized, controlled, comparative study.
Zezos P, Papaioannou G, Nikolaidis N, Patsiaoura K, Papageorgiou A, Vassiliadis T, Giouleme O, Evgenidis N.
2nd Propaedeutic Department of Internal Medicine, Division of Gastroenterology, 'Hippokration' General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece. zezosp@hol.gr

BACKGROUND: Heparin could be beneficial to the treatment of active ulcerative colitis because of its anticoagulant, anti-inflammatory and immunomodulatory properties. AIM: To evaluate the tolerability, safety and efficacy of low-molecular-weight heparin as adjuvant therapy in patients with active ulcerative colitis. METHODS: Thirty-four adult patients with active ulcerative colitis were consecutively included in a prospective, randomized, comparative study, and were treated for 12 weeks. Eighteen patients in the 'standard therapy' group were treated with aminosalicylates and weekly tapered corticosteroids. Sixteen patients in the 'heparin therapy' group were treated with standard therapy plus enoxaparin 100 Anti-Xa IU/kg/day subcutaneously. RESULTS: Seventeen patients in the 'standard therapy' group and 15 patients in the 'heparin therapy' group completed the study. Tolerability and compliance to therapy were excellent and no withdrawals were noted because of complications. There was a significant improvement in the disease severity in both groups (P<0.001), without any difference between them (P=not significant). Both treatment groups showed similar proportions of disease improvement (65% and 73%, respectively; P=not significant). There were no significant differences in inflammation (fibrinogen, ESR, CRP) and coagulation (thrombin-antithrombin complex, F1+2, D-dimers) parameters during and at the end of the study between treatment groups. CONCLUSION: Adjuvant administration of low-molecular heparin in patients with active ulcerative colitis is safe and well tolerated, but no additive benefit over standard therapy for ulcerative colitis was noted.

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Aliment Pharmacol Ther. 2006 May 15;23(10):1435-42.
Basiliximab for the treatment of steroid-resistant ulcerative colitis: further experience in moderate and severe disease.
Creed TJ, Probert CS, Norman MN, Moorghen M, Shepherd NA, Hearing SD, Dayan CM; BASBUC INVESTIGATORS.
Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, Dorothy Hodgkin Building, Bristol, UK. t.j.creed@bristol.ac.uk

BACKGROUND: Preliminary data have suggested that interleukin-2 receptor blockade with basiliximab may increase steroid sensitivity. We have previously reported a small case series demonstrating the potential of basiliximab as a novel agent for the treatment of steroid-resistant ulcerative colitis. AIM: To report further experience of the efficacy and safety of treatment with the interleukin-2 receptor blocking monoclonal antibody basiliximab, in addition to steroids, for the treatment of severe and moderate steroid-resistant ulcerative colitis. METHODS: Twenty patients were enrolled - 13 patients with moderate steroid-resistant ulcerative colitis (Ulcerative Colitis Symptom Score: >or=6) and seven patients with severe steroid-resistant ulcerative colitis. All were given a single dose of 40 mg basiliximab plus standard steroid therapy in an open-label, uncontrolled trial. Primary end point was clinical remission within 8 weeks (Ulcerative Colitis Symptom Score: <or=2). RESULTS: Within 8 weeks, 10 of 20 (50%) patients achieved clinical remission (seven of 13 moderate, and three of seven severe). At 24 weeks, 13 of 20 (65%) patients were in clinical remission. Five patients required colectomy (four severe, one moderate ulcerative colitis) and one required rescue ciclosporin (moderate ulcerative colitis). Two patients developed herpes zoster, but treatment was generally well tolerated. CONCLUSIONS: Basiliximab appears to promote prolonged remission after a single treatment. Taken in combination with previously reported data, basiliximab shows particular promise in moderate steroid-resistant ulcerative colitis.

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Aliment Pharmacol Ther. 2006 May 15;23(10):1403-13.
Safety and efficacy of two dose formulations of alicaforsen enema compared with mesalazine enema for treatment of mild to moderate left-sided ulcerative colitis: a randomized, double-blind, active-controlled trial.
Miner PB Jr, Wedel MK, Xia S, Baker BF.
Oklahoma Foundation for Digestive Research, Health Sciences Center, University of Oklahoma, OK, USA. kay-springer@ouhsc.edu

BACKGROUND: Alicaforsen is an antisense oligonucleotide inhibitor of intercellular adhesion molecule 1 protein expression with activity in subjects with ulcerative colitis and pouchitis. AIM: To compare the effects of alicaforsen enema to standard of care mesalazine (mesalamine) enema in subjects with mild to moderate active left-sided ulcerative colitis. METHOD: A randomized, double-blind, active-controlled multicentre clinical trial. Subjects received a nightly enema of 120 mg alicaforsen (n=55), 240 mg alicaforsen (n=50), or 4 g mesalazine (n=54) for 6 weeks, followed by a 24-week monitoring period. The primary end point was Disease Activity Index at week 6. Clinical improvement, remission and relapse were secondary end points. RESULTS: No significant difference was observed between treatment arms in the primary end point. However, the median duration of response to alicaforsen enema treatment was two- to threefold longer (128 and 146 days) in comparison with mesalazine (54 days). Complete mucosal healing occurred in 24% of the 240 mg alicaforsen group, when compared with 17% in the mesalazine. CONCLUSIONS: Alicaforsen enema demonstrated an acute response and safety profile similar to mesalazine enema, but was differentiated by a more durable response. The extended length of remission suggests that alicaforsen enema treatment may have a disease modifying effect.

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Gastroenterol Clin Biol. 2006 Apr;30(4):594-7.
Colectomy with ileorectal anastomosis preserves female fertility in ulcerative colitis.
Mortier PE, Gambiez L, Karoui M, Cortot A, Paris JC, Quandalle P, Colombel JF.
Clinique des Maladies de l'Appareil Digestif, CHRU, 59037 Lille Cedex.

OBJECTIVES: Restorative proctocolectomy with ileoanal anastomosis (IPAA) is the surgical standard for patients with ulcerative colitis (UC). Significant reduction in female fertility and fecundity after IPAA has been shown in recent studies. In selected cases, colectomy with ileorectal anastomosis (IRA) is another surgical option. The aim of this study was to evaluate fertility in women with UC who underwent IRA. PATIENTS AND METHODS: This study included all women with UC who underwent IRA between 1962 and 1999 and who were 40 years old or younger at the time of surgery, and older than 18 years of age at the time of the interview. Data were collected using a structured telephone interview concerning reproductive behavior and waiting times to pregnancy. RESULTS: Among 40 eligible patients, 37 whose mean age at IRA was 28 years (range 11-39) answered the questionnaire. Twenty-two were unmarried, not wishful of pregnancy and/or already had children. Among 15 females wishing children after IRA, 10 (66%) became pregnant: one had therapeutic abortion, two had a miscarriage, four had 1 child, two had 2 children and one had 4 children. Five patients were sterile after IRA. CONCLUSION: These preliminary results suggest that IRA for UC preserves female fertility. If confirmed in other series this information should be provided to young women with UC before deciding surgical option.

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Rev Gastroenterol Disord. 2006 Spring;6(2):97-105.
Treatment of ulcerative colitis with oral mesalamine: advances in drug formulation, efficacy expectations and dose response, compliance, and chemoprevention.
Sandborn WJ.
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.

Sulfasalazine, olsalazine, balsalazide, delayed-release mesalamine, controlled-release mesalamine, mesalamine pellets, and Multi-Matrix System mesalamine are effective first-line therapies for the treatment of mildly to moderately active ulcerative colitis and for subsequent maintenance of remission. For induction therapy it is unclear if there is a dose response above 1.5 g, and for maintenance therapy existing data do not support a dose response above 1.5 g. Sulfasalazine has more frequent side effects than olsalazine, balsalazide, and mesalamine formulations. Once-daily dosing with multi-matrix system mesalamine 1.2 g tablets may lead to optimal compliance. Mesalamine >/= 1.2 g and sulfasalazine >/= 2 g reduce the risk of colorectal cancer in patients with ulcerative colitis. Drug formulations, efficacy expectations and dose response, toxicity expectations, compliance considerations, and chemoprevention considerations are reviewed.

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Gut. 2006 Apr;55(4):437-441.
Immunosuppressive drugs in ulcerative colitis: twisting facts to suit theories?
Sands BE.
MGH Crohn's and Colitis Center, Massachusetts General and Gastrointestinal Unit Hospital, 165 Cambridge St, 9th Floor, Boston, MA 02114, USA. bsands@partners.org.

Immunosuppressive drugs have become a mainstay of therapy for the inflammatory bowel diseases. Although robust evidence exists in support of the use of these drugs in Crohn's disease, a close evaluation of the available data in ulcerative colitis reveals a much weaker evidence base. In particular, randomised controlled trials of azathioprine, the most commonly used immunosuppressive agent, do not provide rich evidence of efficacy whereas observational cohorts suggest this agent is effective, particularly in patients with relapsing disease who require corticosteroids. Ciclosporin is also effective in the most refractory cases but its efficacy needs to be carefully weighed against the possibility of rare but life threatening complications. Although the evidence base in support of immunosuppressive drugs in ulcerative colitis is not as strong as in Crohn's disease, these agents clearly have a role in the treatment of this disease.

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Aliment Pharmacol Ther. 2006 Mar 1;23(5):577-85.
Systematic review: adherence issues in the treatment of ulcerative colitis.
Kane SV.
Section of Gastroenterology, Department of Medicine, The University of Chicago, Chicago, IL, USA. skane@medicine.bsd.uchicago.edu

Ulcerative colitis is a chronic inflammatory and debilitating disease requiring lifelong treatment. First-line therapy for ulcerative colitis is 5-aminosalicylic acid, which suffers from poor patient adherence outside the clinical trial setting. Formulations to deliver 5-aminosalicylic acid to the disease activity site, both orally and topically, are often inconvenient and require multiple daily dosing. Such regimens can interfere with normal life and reduce the overall quality of life, negatively impacting on treatment adherence and leading to poorer long-term outcomes. These include increased morbidity with an elevated risk of symptomatic relapse, possible greater risk of colorectal cancer and higher overall costs of care. Ulcerative colitis patients cite treatment regimen complexity, tablet quantity and dose frequency as key negative influencers of adherence. Solutions to these issues include addressing patient concerns, simplifying daily regimens and utilizing new formulations such as micropellet and multimatrix oral formulations, rectal gel and once-daily suppository formulations. This review examines the prevalence and impact of non-adherence to 5-aminosalicylic acid therapy among patients with ulcerative colitis, as well as drug delivery strategies that may enhance dosing regimens to improve patient acceptability, adherence and long-term clinical outcomes. It is a combination of understanding patient behaviour, recognizing signs of non-adherent behaviour and utilizing management strategies to change behaviour that will improve patient outcomes.

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Clin Gastroenterol Hepatol. 2006 Feb;4(2):203-11.
Safety of celecoxib in patients with ulcerative colitis in remission: a randomized, placebo-controlled, pilot study.
Sandborn WJ, Stenson WF, Brynskov J, Lorenz RG, Steidle GM, Robbins JL, Kent JD, Bloom BJ.
Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. sandborn.william@mayo.edu

BACKGROUND & AIMS: The safety of selective cyclooxygenase-2 inhibitors in patients with ulcerative colitis in remission is unknown. METHODS: We performed a placebo-controlled pilot trial to evaluate the safety of celecoxib in patients with ulcerative colitis in remission who had a present or past history of nonspecific arthritis, arthralgia, or other condition amenable to nonsteroidal anti-inflammatory drug therapy. A total of 222 patients with ulcerative colitis in remission were randomized to receive oral celecoxib 200 mg or placebo twice daily for 14 days. Remission was defined as a total Mayo Clinic score of 2 points or less and an endoscopic score of 1 point or less. Disease exacerbation was defined as a total Mayo Clinic score of 5 points or more and an increase in the endoscopic score of 1 point or more. The primary analysis was disease exacerbation through day 14 among patients who underwent randomization, had at least 1 dose of study drug, and had both endoscopy and Mayo Clinic disease activity index scores at the baseline and final assessments. RESULTS: Three percent of patients in the celecoxib group experienced disease exacerbation through day 14, as compared with 4% in the placebo group (P = .719). Eleven percent of patients in each group experienced a bowel-related adverse event (P > .20). CONCLUSIONS: Therapy with celecoxib for up to 14 days did not have a greater relapse rate than placebo in patients with ulcerative colitis in remission who had a present or past history of nonspecific arthritis, arthralgia, or other condition amenable to nonsteroidal anti-inflammatory drug therapy.

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Gut. 2006 Feb 16; [Epub ahead of print]
A randomised, dose-finding study of oral tacrolimus (FK506) therapy in refractory ulcerative colitis.
Ogata H, Matsui T, Nakamura M, Iida M, Takazoe M, Suzuki Y, Hibi T.
Keio University School of Medicine, Japan.

BACKGROUND AND AIMS: Immunosuppressive therapy with intravenous cyclosporin A is an alternative treatment option to total colectomy for patients with ulcerative colitis (UC), while the benefits of oral administration of tacrolimus are not well-defined and are based on reports of several uncontrolled studies. METHODS: Patients with refractory active UC were randomly assigned into a high trough concentration (10- 15ng/mL) group (HT group) (n=21), low trough concentration (5-10ng/mL) group (LT group) (n=22), or placebo group (n=20). Patients received an initial oral dose of 0.05 mg/kg tacrolimus or placebo bid. Efficacy was evaluated in 60 patients based on a disease activity index (DAI) score. Fifty-eight patients had additional treatment with tacrolimus and evaluated for efficacy in a 10 week open-label extension. RESULTS: An improvement rate in DAI score (>/=4 points, all categories improved) was observed for 68.4% in HT group compared with 10.0% in placebo group (p<0.001). In HT group, 20.0% of patients had clinical remission and 78.9% had mucosal healing. In the open- label extension, 55.2% of all patients improved in DAI score at week 10. The mean dose of prednisolone was reduced from 19.7 mg/day at study entry to 7.8mg/day at week 10. The incidence of side-effects in the HT group was significantly higher than that of placebo group (p=0.043). The most common event was mild finger tremor. CONCLUSIONS: Our findings demonstrate dose- dependent efficacy and safety of oral tacrolimus for remission-induction therapy of refractory UC. The optimal target range appears to be 10-15 ng/mL in terms of efficacy with 2-week therapy.

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Br J Surg. 2006 Feb;93(2):231-7.
Long-term results of abdominal salvage surgery following restorative proctocolectomy.
Tekkis PP, Heriot AG, Smith JJ, Das P, Canero A, Nicholls RJ.
Department of Surgery, St Mark's Hospital, Watford Road, Harrow HA1 3UJ, UK.

BACKGROUND: This study evaluated outcomes of patients who underwent abdominal salvage ileal pouch redo surgery and identified factors associated with pouch failure following restorative proctocolectomy. METHODS: Data on patients who underwent abdominal salvage surgery in a tertiary referral centre between 1985 and 2003 were collected. Outcomes studied included failure of salvage and bowel function of patients with an intact intestine. RESULTS: One hundred and twelve patients underwent 117 pouch salvage procedures for ulcerative colitis (86), indeterminate colitis/ulcerative colitis (eight), indeterminate colitis/Crohn's disease (three), familial adenomatous polyposis (ten) and other conditions (five). The most common indications for pouch salvage were intra-abdominal sepsis (45 patients), anastomotic stricture (13) and retained rectal stump (35). Median follow-up was 46 (range 1-147) months. Twenty-four patients (21.4 per cent) experienced pouch failure, the incidence of which increased with time. The pouch failed in all patients with Crohn's disease. Successful salvage at 5 years was significantly associated with non-septic (85 per cent) rather than septic (61 per cent) indications (P = 0.016). Frequency of night-time defaecation and faecal urgency improved after salvage surgery (P = 0.036 and P = 0.016 respectively at 5-year follow-up; n = 32). CONCLUSION: Abdominal salvage surgery was associated with a failure rate of 21.4 per cent. A successful outcome was less likely when the procedure was carried out for septic compared with non-septic indications. The rate of pouch failure increased with length of follow-up. Copyright (c) 2005 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

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Gut. 2006 Jan 19; [Epub ahead of print]
Sporadic adenoma in ulcerative colitis: endoscopic resection is an adequate treatment.
Vieth MW, Behrens H, Stolte M.
Klinikum Bayreuth, Germany.

BACKGROUND AND AIMS: In studies with small numbers of cases, it has been shown that endoscopic resection of adenomas in ulcerative colitis represents adequate treatment. In a larger study cohort and more prolonged follow-up, we checked the reliability of this finding. METHODS: Between 1988 and 2002, 148 consecutive patients mainly from private gastroenterologists' practices with ulcerative colitis were diagnosed as having an adenoma. In 60 patients, histological diagnosis was established in biopsies, in 87 patients in polypectomy specimens - one patient underwent proctocolectomy following the diagnosis. The outcome of these patients was analysed in a mean follow-up period of 6.0 + 3.63 years. RESULTS: Among 60 patients surprisingly without endoscopic treatment, 48.3% developed ulcerative colitis- associated neoplasia in the same colon segment (23.3% low grade intraepithelial neoplasia; 8.3% high grade intraepithelial neoplasia; 16.7% carcinoma). Among the 87 patients undergoing polypectomy of the adenoma, follow-up revealed in 4.6% colitis-associated neoplasia in other segments of colon. CONCLUSION: The development of adenocarcinomas in a total of 6.7% of the overall patient group, and in 2.3% of those undergoing polypectomy indicates that the biopsy- based diagnosis of an adenoma in ulcerative colitis must be considered to mandate endoscopic resection of the lesion. 40% of the affected patients did not receive any form of endoscopic removal of the lesion. This shows that most recent guidelines are not followed in a considerable number of patients with ulcerative colitis in private practice in Germany. Although polypectomy of the adenoma represents adequate therapy, further regular follow-up examinations are nevertheless necessary.

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World J Gastroenterol. 2006 Jan 28;12(4):520-5.
Safety and clinical efficacy of granulocyte and monocyte adsorptive apheresis therapy for ulcerative colitis.
Yamamoto T, Umegae S, Matsumoto K.

Active ulcerative colitis (UC) is frequently associated with infiltration of a large number of leukocytes into the bowel mucosa. Therefore, removal of activated circulating leukocytes by apheresis has the potential for improving UC. In Japan, since April 2000, leukocytapheresis using Adacolumn has been approved as the treatment for active UC by the Ministry of Health and Welfare. The Adacolumn is an extracorporeal leukocyte apheresis device filled with cellulose acetate beads, and selectively adsorbs granulocytes and monocytes/macrophages. To assess the safety and clinical efficacy of granulocyte and monocyte adsorptive apheresis (GMCAP) for UC, we reviewed 10 open trials of the use of GMCAP to treat UC. One apheresis session (session time, 60 min) per week for five consecutive weeks (a total of five apheresis sessions) has been a standard protocol. Several studies used modified protocols with two sessions per week, with 90-min session, or with a total of 10 apheresis sessions. Typical adverse reactions were dizziness, nausea, headache, flushing, and fever. No serious adverse effects were reported during and after GMCAP therapy, and almost all the patients could complete the treatment course. GMCAP is safe and well-tolerated. In the majority of patients, GMCAP therapy achieved clinical remission or improvement. GMCAP is a useful alternative therapy for patients with steroid-refractory or -dependent UC. GMCAP should have the potential to allow tapering the dose of steroids, and is useful for shortening the time to remission and avoiding re-administration of steroids at the time of relapse. Furthermore, GMCAP may have efficacy as the first-line therapy for steroid-naive patients or patients who have the first attack of UC. However, most of the previous studies were uncontrolled trials. To assess a definite efficacy of GMCAP, randomized, double-blind, sham-controlled trials are necessary. A serious problem with GMCAP is cost; a single session costs 145 000 ($1 300). However, if this treatment prevents hospital admission, re-administration of steroids and surgery, and improves a quality of life of the patients, GMCAP may prove to be cost-effective.

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Ned Tijdschr Geneeskd. 2006 Jan 7;150(1):12-7.
[Treatment of servere ulcerative colitis]
[Article in Dutch]
Weersma RK, van Dullemen HM, Kleibeuker JH, Ploeg RJ, Dijkstra G.
Universitair Medisch Centrum Groningen, Postbus 30.001, 9700 RB Groningen. r.k.weersma@int.umcg.nl

10-15% of patients with ulcerative colitis experience a severe episode of colonic inflammation that does not respond to mesalazine and oral corticosteroids. These patients require hospitalisation and treatment with intravenous corticosteroids. However, 25% of these patients do not respond to treatment. In these cases, intravenous cyclosporin is effective. Infliximab, an antibody against tumour necrosis factor alpha, is also beneficial. With these new treatment options, the colectomy rate in the acute phase has declined to about 35%. Other new therapies are under investigation in phase 2 and 3 trials. Surgery remains an important treatment option. Patients, gastroenterologists and surgeons should be involved in the clinical decision-making process.

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Surg Today. 2006;36(2):162-5.
Restorative proctocolectomy for pediatric patients with ulcerative colitis.
Sako M, Kimura H, Arai K, Koganei K, Kito F, Sugita A, Fukushima T.
Department of Surgery, Yokohama City Hospital, 56 Okazawa-cho, Hodogaya-ku, Yokohama, 240-8555, Japan.

PURPOSE: A restorative proctocolectomy has become an elective surgical treatment for patients with ulcerative colitis (UC). In children with UC, however, the role of this procedure has not yet been well evaluated. We investigated the postoperative status of pediatric patients with UC regarding the side effects of steroids, postoperative complications, and growth. METHODS: The medical records of 15 patients with UC who underwent a restorative proctocolectomy between August 1993 and October 2003 were retrospectively reviewed. RESULTS: Their mean age was 12.6 +/- 3.4 years (range 5.7-15.7; boys: 9, girls: 6). All patients had total colitis, except for one who had left-sided colitis. The mean cumulative dose of preoperative prednisolone was 6201 +/- 7980 mg (mean +/- SD). The operative indications were an unsuccessful response to medical treatments in 12 patients (80%) and severe colitis in 3 patients (20%). Surgery was performed in one stage in 6 patients and in two stages in 9 patients. Seven patients (47%) demonstrated growth retardation at the time of operation. Steroid-related complications were seen in 3 cases, i.e., steroid myopathy, glaucoma, and cataracts, respectively. As early postoperative complications, an intestinal obstruction was seen in 2 patients, peritonitis in 1, and pancreatitis in 1. As late complications, anastomotic stenosis was observed in 5 patients, pouchitis in 4, residual proctitis in 3, and anal or proctovaginal fistula in 2. An intestinal obstruction, peristomal pyoderma gangrenosum, and dehydration each was seen in 1 patient. A growth "catch-up" was obtained for all but one patient. All patients became free of corticosteroids. CONCLUSION: A restorative proctocolectomy was found to be an effective treatment alternative even in children with UC when conservative therapy proves to be ineffective.

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Gastroenterol Hepatol. 2005 Dec;28(10):607-14.
Cyclosporine in the treatment of severe attack of ulcerative colitis: a systematic review.
Garcia-Lopez S, Gomollon-Garcia F, Perez-Gisbert J.
Servicio de Aparato Digestivo, Hospital Universitario Miguel Servet, Zaragoza, Spain. sgarcial@meditex.es

INTRODUCTION: Intravenous steroid therapy is the standard treatment in severe attacks of ulcerative colitis (UC), but 20% to 60% of patients fail to respond and require colectomy. Cyclosporine (CyA) has shown efficacy in steroid failures and could avoid surgery, but controversy remains. AIM: The objective of this study was to conduct a systematic review to evaluate the effectiveness and safety of CyA in inducing remission in patients with a severe attack of UC. METHODS: We did a systematic review using Cochrane methodology, including data from published (in English, French, Spanish or German) clinical trials done in adults using intravenous or oral CyA in UC. Data on efficacy are obtained from controlled and observational clinical trials, and for safety issues case reports are also considered. RESULTS: 31 studies were identified which met the inclusion criteria, 22 (18 uncontrolled, 4 controlled) with intravenous CyA, and 9 (all uncontrolled) using oral CyA. Only 4 controlled trials (one in abstract form) are available, and only one compares CyA to placebo. However, efficacy results are very consistent in these 4 trials, and very similar to those in observational studies. CyA achieves remission in 91,4% and 71.4% of patients in controlled and uncontrolled studies using intravenous route, and in 71,2% using oral route. Two mg/kg/day seems so efficacious and safer as previous standard 4 mg/kg/day dose. Minor side effects are rather common but do not seriously limit therapy. Severe side effects, specially infections, are uncommon but clinically relevant with several deaths reported. CONCLUSION: CyA (intravenous, 2 mg/kg/day) constitutes an efficacious and relatively safe alternative in the treatment of severe, steroid-refractory, attack of UC. To optimize treatment, the correct selection of patients, a standardized protocol and clinical surveillance are recommended.

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Ther Apher Dial. 2005 Dec;9(6):459-68.
Therapeutic apheresis-state of the art in the year 2005.
Bosch T.
Nephrology Division, Department of Internal Medicine I, University Hospital Munich-Grosshadern, Munich, Germany.

Therapeutic apheresis is an extracorporeal blood purification method for the treatment of diseases in which pathological proteins or cells have to be eliminated. Selective plasma processing is more efficient in pathogen removal than unselective plasma exchange and does not require a substitution fluid like albumin. This overview presents the various selective devices for the treatment of plasma (plasmapheresis) and blood cells (leukocyte apheresis). Prospective randomized trials were performed for the treatment of age-related macular degeneration (Rheopheresis), sudden hearing loss (heparin-induced lipoprotein precipitation [HELP]), rheumatoid arthritis (Prosorba), dilative cardiomyopathy (Ig-Therasorb, Immunosorba), acute-on-chronic liver failure (molecular adsorbent recirculating system [MARS]), and ulcerative colitis (Cellsorba). Prospective non-randomized controlled trials were carried out treating hypercholesterolemia (Liposorber) and crossmatch-positive recipients before kidney transplantation (Immunosorba). Uncontrolled studies were done for ABO-incompatibility in living donor kidney transplantation (KT) (Glycosorb), acute humoral rejection after KT (Immunosorba) and acute liver failure (Prometheus). According to the 2002 International Apheresis Registry covering 11428 sessions in 811 patients, 79% of the patients showed an improvement of their condition by apheresis and only a few sessions were fraught with adverse effects (AE). The major AE were blood access difficulties (3.1%) and hypotension (1.6%). In summary, therapeutic apheresis is a safe and effective procedure for the treatment of diseases refractory to drug therapy.

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N Engl J Med. 2005 Dec 8;353(23):2462-76.
Infliximab for induction and maintenance therapy for ulcerative colitis.
Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, Travers S, Rachmilewitz D, Hanauer SB, Lichtenstein GR, de Villiers WJ, Present D, Sands BE, Colombel JF.
University Hospital Gasthuisberg, Leuven, Belgium. paul.rutgeerts@uz.kuleuven.ac.be

BACKGROUND: Infliximab, a chimeric monoclonal antibody directed against tumor necrosis factor alpha, is an established treatment for Crohn's disease but not ulcerative colitis. METHODS: Two randomized, double-blind, placebo-controlled studies--the Active Ulcerative Colitis Trials 1 and 2 (ACT 1 and ACT 2, respectively)--evaluated the efficacy of infliximab for induction and maintenance therapy in adults with ulcerative colitis. In each study, 364 patients with moderate-to-severe active ulcerative colitis despite treatment with concurrent medications received placebo or infliximab (5 mg or 10 mg per kilogram of body weight) intravenously at weeks 0, 2, and 6 and then every eight weeks through week 46 (in ACT 1) or week 22 (in ACT 2). Patients were followed for 54 weeks in ACT 1 and 30 weeks in ACT 2. RESULTS: In ACT 1, 69 percent of patients who received 5 mg of infliximab and 61 percent of those who received 10 mg had a clinical response at week 8, as compared with 37 percent of those who received placebo (P<0.001 for both comparisons with placebo). A response was defined as a decrease in the Mayo score of at least 3 points and at least 30 percent, with an accompanying decrease in the subscore for rectal bleeding of at least 1 point or an absolute rectal-bleeding subscore of 0 or 1. In ACT 2, 64 percent of patients who received 5 mg of infliximab and 69 percent of those who received 10 mg had a clinical response at week 8, as compared with 29 percent of those who received placebo (P<0.001 for both comparisons with placebo). In both studies, patients who received infliximab were more likely to have a clinical response at week 30 (P< or =0.002 for all comparisons). In ACT 1, more patients who received 5 mg or 10 mg of infliximab had a clinical response at week 54 (45 percent and 44 percent, respectively) than did those who received placebo (20 percent, P<0.001 for both comparisons). CONCLUSIONS: Patients with moderate-to-severe active ulcerative colitis treated with infliximab at weeks 0, 2, and 6 and every eight weeks thereafter were more likely to have a clinical response at weeks 8, 30, and 54 than were those receiving placebo. (ClinicalTrials.gov numbers, NCT00036439 and NCT00096655.) Copyright 2005 Massachusetts Medical Society.

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Tech Coloproctol. 2005 Dec;9(3):187-92. Epub 2005 Nov 21.
The ileoanal pouch procedure in the long-term perspective: a critical review.
Delaini GG, Scaglia M, Colucci G, Hulten L.
Department of Surgery and Gastroenterology, Ospedale Policlinico, University of Verona, Piazzale L.A. Scuro 1, I-37135, Verona, Italy, ggdelaini@virgilio.it.

An ileo-pouch anal anastomosis (IPAA) has become the gold standard procedure for ulcerative colitis and familial adenomatous polyposis. Clinical results on the pelvic pouch procedure have often been encouraging; when confronted with the different surgical options, the majority of patients select IPAA as the best operation. However, even if IPAA is a great innovation, it is by no means the first choice for all patients. For patients old enough to join in a responsible discussion, the pros and cons of the various operations must be carefully described; the choice of surgical procedure must meet the patient's wishes and appear soundly based to the surgeon. The young age of most patients has to be considered and a long follow-up time is required to establish whether and, if so, to what extent the operation may adversely impact the patient's continence, sex life, fertility, and quality of life. The risk of cancer transformation in the residual rectal mucosa in the muscular or columnar cuff is another important factor that may influence the eventual decision. This article critically reviews our experience and the literature.

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Dis Colon Rectum. 2005 Dec 2; [Epub ahead of print]
Maternal and Fetal Outcome After Colectomy for Fulminant Ulcerative Colitis During Pregnancy: Case Series and Literature Review.
Dozois EJ, Wolff BG, Tremaine WJ, Watson WJ, Drelichman ER, Carne PW, Bakken JL.
Division of Colon and Rectal Surgery, Mayo Clinic, 200 First Street SW, Rochester, Minnesota, 55905, USA, dozois.eric@mayo.edu.

PURPOSE: Previous studies have reported high morbidity and mortality in mothers and their offspring after colectomy for ulcerative colitis during pregnancy. This study was designed to assess the maternal and fetal outcomes of pregnant females undergoing colectomy for ulcerative colitis in the current era. METHODS: A retrospective analysis was performed at our institution of all pregnant females undergoing operation for ulcerative colitis between 1980 and 2004. To compare this data to that of past literature, a MEDLINE search from 1951 to 2004 reviewed all cases reported on this topic. RESULTS: Between 1980 and 2004, five females underwent an operation at our institution for fulminant ulcerative colitis while pregnant. All five patients underwent subtotal colectomy with Brooke ileostomy. Postoperative maternal morbidity included a superficial wound infection and a small asymptomatic intra-abdominal abscess. All females had successful pregnancies, and no maternal or fetal deaths occurred. Two patients went on to have an ileal pouch-anal anastomosis, one had a completion proctectomy and end ileostomy, oneis scheduled for an ileal pouch-anal anastomosis, andone patient is lost to follow-up. The literature review revealed 37 cases. The overall fetal and maternal mortality was 49 and 22 percent respectively. Postoperative maternal morbidity was reported in 24 percent. CONCLUSIONS: In contrast to historic data, the maternal and fetal mortality from our series was zero and maternal morbidity was low. Subtotal colectomy and Brooke ileostomy for ulcerative colitis during pregnancy is safe. A multidisciplinary team that includes a gastroenterologist, high-risk obstetrician, and experienced surgeon is necessary for an optimal outcome.

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Scand J Gastroenterol. 2005 Nov;40(11):1334-42.
Effectiveness of antibiotic combination therapy in patients with active ulcerative colitis: a randomized, controlled pilot trial with long-term follow-up.
Ohkusa T, Nomura T, Terai T, Miwa H, Kobayashi O, Hojo M, Takei Y, Ogihara T, Hirai S, Okayasu I, Sato N.
Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan. ohkusa@med.juntendo.ac.jp

OBJECTIVE: It is proposed that Fusobacterium varium might be one of the elusive pathogenic factors in ulcerative colitis (UC). Our goal was to assess whether an antibiotic combination therapy against F. varium is effective for induction and maintenance of remission of UC. MATERIAL AND METHODS: Twenty chronic, active UC patients with F. varium infection were enrolled consecutively and were randomly assigned to receive amoxicillin, tetracycline or metronidazole per os for 2 weeks (treatment group; n=10), or no antibiotics (control group; n=10). F. varium was sensitive to the antibiotics. Symptom assessment, endoscopic and histological evaluations were performed blind before enrollment at 3-5 months and 12-14 months after the treatment. Serum immunoglobulins to F. varium were measured using an enzyme-linked immunosorbent assay (ELISA). Immunohistochemical detection of F. varium in biopsy specimens was carried out using the avidin-biotin complex method. RESULTS: The clinical activity, endoscopic and histological scores in the treatment group decreased significantly at 3-5 and 12-14 months after the end of treatment compared with those in the control group (p=0.001-0.036). The remission rate in the treatment group was higher than that in the control group (p=0.037). In addition, the titers of antibody to F. varium and the F. varium density in the mucosa decreased at both the short- and long-term follow-ups in the treatment group (p=0.0002-0.049). No serious drug-related toxicity was observed during the trial. CONCLUSIONS: The 2-week antibiotic combination therapy against F. varium was effective and safe in patients with chronic, active ulcerative colitis in this long-term follow-up study.

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J Pediatr Surg. 2005 Nov;40(11):1773-9.
Stapled restorative proctocolectomy in children with refractory ulcerative colitis.
Mattioli G, Castagnetti M, Gandullia P, Torrente F, Jasonni V, Barabino AV.
Department of Paediatric Surgery, G. Gaslini Research Institute, University of Genoa, 16147-Genoa, Italy.

OBJECTIVE: The aim of this study was to review the results after stapled restorative proctocolectomy among children with refractory ulcerative colitis. PATIENTS AND METHODS: Clinical records of 16 consecutive children with refractory ulcerative pancolitis undergoing colectomy and stapled straight ileoanal anastomosis at a median age of 8.3 years (range, 3.1-14.9 years) were reviewed. Periodical clinical examinations and endoscopies with biopsies above (terminal ileum) and below (columnar cuff) the anastomosis were carried out during follow-up. Median follow-up after bowel restoration lasted 5.3 years (range, 1.2-9.6 years). RESULTS: Two major complications occurred (12.5%), 1 episode of sepsis treated conservatively and 1 bowel perforation proximal to the anastomosis treated with a temporary diverting ileostomy. All the anastomoses were functional at the end of the study. The columnar cuff averaged 2.6 cm in length and presented signs of persistent inflammation (cuffitis) in 94% of children. Inflammation responded poorly to any medical treatment but was symptomatic in 1 case only. Ileal inflammation was detected endoscopically in 31% of patients and histologically in 62.5%. No case of dysplasia or cancer was recorded. At final follow-up, children had an average of 7.1 +/- 3.1 bowel movements per day; full daytime and nighttime continence were achieved in 87.5% and 62.5% of cases, respectively. A severe inflammation of the columnar cuff was associated with an increased risk of nighttime incontinence. CONCLUSIONS: Stapled ileoanal anastomosis in children with pancolitis is associated with low morbidity. Refractory cuffitis persists in almost all patients but is mostly asymptomatic, although it could be associated with nighttime incontinence.

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Clin Gastroenterol Hepatol. 2005 Nov;3(11):1107-14.
A randomized trial of nicotine enemas for active ulcerative colitis.
Ingram JR, Thomas GA, Rhodes J, Green JT, Hawkes ND, Swift JL, Srivastava ED, Evans BK, Williams GT, Newcombe RG, Courtney E, Pillai S.
Department of Gastroenterology, Cardiff and Vale NHS Trust, Cardiff CF14 4XW, Wales, United Kingdom.

BACKGROUND & AIMS: Ulcerative colitis (UC) is largely a disease of nonsmokers in which transdermal nicotine improves the symptoms but often causes adverse events (AEs). Nicotine enemas cause fewer AEs and were used as supplemental treatment for active UC. METHODS: We treated 104 patients with active UC with either 6-mg nicotine enemas or placebo enemas for 6 weeks in a randomized double-blind study. Patients continued their oral therapy, if any, for UC: 68 patients were taking mesalamine, 15 patients were taking prednisolone, and 12 patients were taking thiopurines during the study. Clinical, sigmoidoscopic, and histologic assessments were made at baseline and at the end of the study and symptoms were recorded daily on a diary card. The primary end point was induction of clinical remission and clinical improvement also was measured by the UC disease activity index. After the study, patients then used nicotine enemas daily for 4 weeks and sigmoidoscopy with a biopsy examination was repeated. AEs and salivary cotinine levels were monitored throughout the study. RESULTS: Clinical remission was achieved in 14 of 52 (27%) patients on active treatment and 14 of 43 (33%) patients on placebo (P = .55). The UC disease activity index improved by 1.45 points in the active group and by 1.65 points for those on placebo (P = .88). Only 1 patient discontinued treatment because of an AE (abdominal pain). In the 47 patients taking mesalamine only, active treatment conferred benefit that was not statistically significant; disease remission occurred in 9 of 25 patients on active therapy and 4 of 21 patients on placebo (P = .20). CONCLUSIONS: Six-milligram nicotine enemas were well tolerated but were not found to be efficacious for active UC.

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Aliment Pharmacol Ther. 2005 Nov 15;22(10):907-16.
Review article: how and when to use ciclosporin in ulcerative colitis.
Durai D, Hawthorne AB.
Department of Medicine, University Hospital of Wales, Heath Park, Cardiff, UK.

Although colectomy for ulcerative colitis is curative, long-term quality of life is reduced. Intravenous ciclosporin 4 mg/kg/day has significant toxicity. There is now evidence that low-dose ciclosporin (2 mg/kg daily by intravenous infusion, or 5-6 mg/kg daily in a twice daily oral dosage) has an acceptable safety profile, even when used in combination with corticosteroids. Drug dosage should be adjusted to the levels of 150-250 ng/mL initially (random levels during intravenous infusion, or trough levels for oral use). Ciclosporin should be considered not only in those who have failed 7 days of corticosteroids, but also in fulminant colitis at day 3, if not responding to corticosteroids. The drug should be avoided in frail or elderly patients with significant comorbidity, and also where colectomy is likely to be necessary in the short to medium term. Ciclosporin should not be continued for more than 7 days, unless there is a definite response. A 70-80% initial response is likely, and responders are discharged on oral ciclosporin, adding thiopurines and tailing prednisolone rapidly. The drug should be continued for 3 months. The likelihood of avoiding colectomy over 2-3 years is 40-50%. More studies are needed to evaluate the use of oral ciclosporin in corticosteroid-refractory colitis in out-patients, and to assess whether monotherapy (without corticosteroids) is significantly safer, without loss of efficacy.

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Scand J Gastroenterol. 2005 Oct;40(10):1205-13.
A prospective, open-label trial of 6-thioguanine in patients with ulcerative or indeterminate colitis.
Teml A, Schwab M, Harrer M, Miehsler W, Schaeffeler E, Dejaco C, Mantl M, Schneider B, Vogelsang H, Reinisch W.
Universitatsklinik fur Innere Medizin IV, Abteilung fur Gastroenterologie und Hepatologie, Medizinische Universitat Wien, Vienna, Austria.

OBJECTIVE: 6-thioguanine (6-TG) has emerged as a promising therapeutic alternative in patients with Crohn's disease intolerant or resistant to azathioprine (AZA) and/or 6-mercaptopurine (6-MP). The aim of the present study was to evaluate the safety and efficacy of 6-TG in patients with ulcerative colitis (UC) or indeterminate colitis (IC) intolerant or resistant to AZA/6-MP. MATERIAL AND METHODS: Twenty patients with an acute flare, steroid-dependent or steroid-refractory disease attending our outpatient department were included in the study. Measurement of 6-TG nucleotide levels was done to check compliance. Complete, partial and non-response were defined by means of the clinical activity index and the daily steroid demand. Secondary outcome parameters included changes in cumulative steroid doses, C-reactive protein (CRP) levels, and an endoscopic score. RESULTS: Out of 20 patients 4 were excluded owing to noncompliance; 2/16 compliant patients (13%) had to be prematurely withdrawn because of adverse events, which ceased upon drug discontinuation. By per-protocol analysis, 5/14 patients (36%) were complete, 6/14 (43%) partial and 3/14 (21%) non-responders. In addition to the reduction of the cumulative steroid dose over 3 months, CRP decreased in the study population and the endoscopic score decreased in treatment responders. CONCLUSIONS: Treatment with 6-TG was effective in patients with UC or IC previously intolerant or resistant to AZA/6-MP. Future work is needed to define a subpopulation of patients at low risk for its potential hepatotoxicity, which we assume will benefit from 6-TG.

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Dig Dis Sci. 2005 Oct;50 Suppl 1:S119-23.
Rebamipide enemas-new effective treatment for patients with corticosteroid dependent or resistant ulcerative colitis.
Miyata M, Kasugai K, Ishikawa T, Kakumu S, Onishi M, Mori T.
Department of Gastroenterology, Aichi Medical University School of Medicine, 21 Yazako, Nagokute-cho, Aichi-Gun, Aichi, 480-1195, Japan, mmiyata@ aichi-med-u.ac.jp.

In this study we investigated the effect of rebamipide enema in patients with steroid-resistant and/or dependent ulcerative colitis. Rebamipide enemas were administered twice daily for a 12-week period; this treatment was further continued longer in patients who requested this. Disease activity index as reflecting the clinical condition and endoscopic index with histological grading were determined before and after the treatment period. Nine of 11 (81.8%) patients on 12-week treatment with rebamipide approved and were classified as colitis in remission. Moreover, seven of 11 patients requested long-term medication, the longest medication term being 80 weeks. These results medicated that rebamipide enemas may be effective in patients with steroid-resistant and/or dependent ulcerative colitis.

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J Gastroenterol Hepatol. 2005 Oct;20(10):1567-71.
Leukocytapheresis therapy for steroid-naive patients with active ulcerative colitis: Its clinical efficacy and adverse effects compared with those of conventional steroid therapy.
Nishioka C, Aoyama N, Maekawa S, Shirasaka D, Nakahara T, Tamura T, Fukagawa M, Umezu M, Abe T, Kasuga M.
Division of Diabetes, Digestive and Kidney Diseases, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.

Abstract Background: Steroid administration currently plays a central role in the medical management of ulcerative colitis (UC); however, long-term steroid usage causes adverse effects, which necessitates stoppage of drug intake, leading to worsening of the disease. A steroid-sparing, well-tolerated treatment is therefore required. As several investigators have reported the efficacy of leukocytapheresis (LCAP) combined with steroid therapy, we investigated the clinical usefulness and safety of LCAP for steroid-naive patients with active UC for comparison with those of conventional steroid therapy. Methods: Twenty-nine Japanese patients with active UC without a history of steroid usage were selected to be treated with LCAP (n = 9) or prednisolone (PSL) (n = 20). LCAP administration continued for 10 weekly cycles. In the PSL group, patients with moderately severe disease received 0.5 mg/kg per day of PSL and those with severe disease 1.0 mg/kg per day. The PSL dosage was gradually tapered in accordance with improvement. Results: Eight (88.9%) of the LCAP group and 16 (80.0%) of the PSL group showed clinical improvement and three (33.3%) of the LCAP group and seven (35.0%) of the PSL group achieved remission. As for the treatment complications, three major adverse effects were observed in the PSL group, but none were observed in the LCAP group. Conclusion: The results of this study suggest that the efficacy and safety of LCAP are equivalent, and in terms of severe adverse effects, superior to those of steroid therapy. LCAP therapy may thus be a promising candidate therapy for steroid-naive patients with active UC. (c) 2005 Blackwell Publishing Asia Pty Ltd.

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Curr Gastroenterol Rep. 2005 Oct;7(5):404-11.
Pouchitis: a spectrum of diseases.
Shen B, Lashner BA.
Department of Gastroenterology/Hepatology, Desk A30, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA. shenb@ccf.org.

Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgical treatment of choice for ulcerative colitis and familial adenomatous polyposis patients who require surgery. Pouchitis is the most common long-term complication after IPAA. Patients with pouchitis represent a heterogeneous group in terms of pathogenesis, clinical presentation, disease course, and prognosis, suggesting a wide range of disease mechanisms. Before the diagnosis of pouchitis is made, other inflammatory and non-inflammatory disease conditions, such as Crohn's disease, cuffitis, and irritable pouch syndrome, should be ruled out. Pouch endoscopy is the most important tool for diagnosis and differential diagnosis. Accurate diagnosis and classification are essential for appropriate management. Although the majority of patients with pouchitis respond to antibiotic therapy, a subset of these patients cannot achieve remission by means of antibiotics and thus require anti-inflammatory or immunosuppressive treatment.

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Dis Colon Rectum. 2005 Sep 7; [Epub ahead of print]
Laparoscopic-Assisted vs. Open Ileal Pouch-Anal Anastomosis: Functional Outcome in a Case-Matched Series.
Larson DW, Dozois EJ, Piotrowicz K, Cima RR, Wolff BG, Young-Fadok TM.
Division of Colon and Rectal Surgery, Mayo Clinic Rochester, Mayo Clinic College of Medicine, Rochester, Minnesota.

PURPOSE: Functional outcomes in laparoscopic-assisted ileal pouch-anal anastomosis have been incompletely studied. More than one-year follow-up has rarely been reported in these patients. This study was designed to assess operative, functional, and quality of life outcomes in patients with ulcerative colitis or familial adenomatous polyposis a minimum of one year after. METHODS: Thirty-three laparoscopic-assisted ileal pouch-anal anastomosis and 33 open ileal pouch-anal anastomosis patients, with a median of 13 months and minimum of 12 months follow-up, were identified from a prospective, laparoscopic database. Functional outcome was prospectively assessed by using a standardized survey. These cohorts were matched by individual patient for year of surgery, age, gender, body mass index, and indication. RESULTS: Median age was 27 years (open) and 28 years (laparoscopic). There were 27 females and 6 males in each group. All operations occurred between 1999 and 2001. Median body mass index was 22.3 (open) and 21.7 (laparoscopic) groups. There were no significant differences in diagnosis, use of diversion, and anastomotic technique. Postoperative morbidity occurred in 6 percent of the laparoscopic cases and 12 percent of the open cases. Functional outcome after a minimum of one year revealed equivalent median day and median nocturnal number of stools of six to seven and one to two respectively. Consistency of stool, medication usage, and continence were no different between groups. Daytime and nocturnal incontinence was similar. Quality of life in regard to social, home life, family, travel, sports, recreation, and sex life were equivalent. CONCLUSIONS: The function and quality of life outcomes for patients undergoing laparoscopic-assisted ileal pouch-anal anastomosis seem to be equivalent to our open experience. Laparoscopic-assisted ileal pouch-anal anastomosis offers selected patients a safe, feasible, and durable alternative.

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Dig Liver Dis. 2005 Sep 14; [Epub ahead of print]
Plasma fibrinogen in ulcerative colitis: The effect of disease activity and nicotine therapy in a randomised controlled trial.
Ingram JR, Rhodes J, Collins PW, Williams GT, Newcombe RG, Thomas GA.
Department of Gastroenterology, University Hospital of Wales, Heath Park, Cardiff and Vale NHS Trust, Cardiff CF14 4XW, UK.

BACKGROUND.: Smoking increases plasma fibrinogen and cardiovascular risk whereas transdermal nicotine may not. Fibrinogen is an acute phase protein and may reflect disease activity in ulcerative colitis. AIMS.: To examine the effect of topical nicotine on plasma fibrinogen and any relationship between fibrinogen and ulcerative colitis disease activity. PATIENTS.: Forty-eight non-smokers with moderately active ulcerative colitis. METHODS.: Patients were randomised to 6mg nicotine enema or placebo for 6 weeks, followed by open nicotine therapy for 4 weeks. Plasma fibrinogen was measured at baseline and after 6 and 10 weeks; at each assessment sigmoidoscopy with a rectal biopsy was performed. RESULTS.: At 6 weeks median plasma fibrinogen was 3.30g/l on nicotine compared to 3.05g/l on placebo, P=0.90 when adjusted for baseline values. There was a correlation between fibrinogen and the UC disease activity index (UCDAI) at weeks 0 and 10, P=0.036 and 0.033, respectively, and between fibrinogen and sigmoidoscopic grade at each assessment, P=0.014, 0.021 and 0.034. Changes in fibrinogen did not correlate with changes in disease severity. CONCLUSIONS.: There was no significant effect of nicotine enemas, in either direction, on plasma fibrinogen-this was raised in moderately active UC and correlated with the sigmoidoscopic grade of colitis and the UCDAI; however, fibrinogen was not sufficiently sensitive to be of practical clinical value.

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Aliment Pharmacol Ther. 2005 Sep 1;22(5):463-70.
Colonic spread and serum pharmacokinetics of budesonide foam in patients with mildly to moderately active ulcerative colitis.
Brunner M, Vogelsang H, Greinwald R, Kletter K, Kvaternik H, Schrolnberger C, Eichler HG, Brunner H, Dudczak R, Muller M.
Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, Medical University of Vienna, Vienna, Austria. martin.brunner@meduniwien.ac.at

BACKGROUND: Local treatment with foams in patients suffering from ulcerative proctitis or proctosigmoiditis is considered a rational treatment option. AIMS: To investigate colonic spread, safety, tolerability and acceptance of a newly developed budesonide foam formulation. METHODS: Twelve patients (four females, eight males) with acute proctosigmoiditis or left-sided ulcerative colitis were rectally administered a single dose of [99Tcm]-labelled budesonide foam (Budenofalk; Dr Falk Pharma GmbH, Freiburg, Germany) containing 2 mg budesonide in 20 mL foam after diagnostic colonoscopy. Thereafter, the colonic spread was assessed by means of gamma-scintigraphy for 6 h. Serum samples were taken simultaneously. RESULTS: Budesonide foam spread with a maximum between 11 and 40 cm, thus reaching the sigmoid colon in all patients. In some patients, the foam even extended into the distal third and the middle of the descending colon with maximum radioactivity at 4 h. Systemic budesonide absorption was rapid and pharmacokinetic data were comparable with published data on marketed budesonide enemas, with mean serum C(max) and AUC(0-8 h) values of 0.8 +/- 0.5 ng/mL and 3.7 +/- 1.9 ng h/mL, respectively. The new formulation was well accepted by all patients, who could retain the foam for at least 4 h. CONCLUSIONS: In the majority of patients, budesonide foam effectively spread up to the left-sided colon and thus qualifies for the local treatment of proctosigmoiditis.

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Aliment Pharmacol Ther. 2005 Aug 1;22(3):203-8.
Low-dose oral microemulsion ciclosporin for severe, refractory ulcerative colitis.
de Saussure P, Soravia C, Morel P, Hadengue A.
Department of Gastroenterology and Hepatology, Geneva University Hospital, Geneva, Switzerland. philippe.desaussure@hcuge.ch

BACKGROUND: The optimal modalities of treatment with oral microemulsion ciclosporin in patients with severe, steroid-refractory ulcerative colitis are uncertain. AIM: To assess the applicability, in terms of efficacy and tolerability, of a standard oral microemulsion ciclosporin treatment protocol targeting relatively low blood ciclosporin concentrations, in patients with severe, steroid-resistant ulcerative colitis. PATIENTS AND METHODS: Patients with a severe attack of ulcerative colitis and no satisfactory response to intravenous corticosteroids were started on oral microemulsion ciclosporin. Dosages were adapted according to a standard protocol, targeting a blood predose ciclosporin concentration (C0) of 100-200 ng/mL. Patients without a clinical response on day 8 were scheduled for colectomy. RESULTS: Sixteen patients were enrolled. A clinical response was observed in 14/16 (88%). The mean clinical activity index scores and concentrations of C-reactive protein on days 0, 4 and 8 were 11.8, 6.7 and 4.1, and 50.3, 19.3 and 9.7 mg/L respectively. The mean C0 (days 0-8) was 149 pg/mL. The mean creatinine clearance rates on days 0 and 8 were 88 and 96 mL/min. One patient had an acute elevation of transaminases that resulted in discontinuing ciclosporin. CONCLUSIONS: Even when dosed for a target C0 of 100-200 ng/mL, oral microemulsion ciclosporin for severe, steroid-refractory ulcerative colitis achieves an efficacy similar to that attained with higher, potentially more toxic levels. The oral route should replace intravenous treatment in this clinical setting.

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Surg Endosc. 2005 Jul 28; [Epub ahead of print]
Total laparoscopic proctocolectomy with Brooke ileostomy: a novel incisionless surgical treatment for patients with ulcerative colitis.
Larson DW, Dozois E, Sandborn WJ, Cima R.
Division of Colon and Rectal Surgery Mayo Clinic Rochester, Mayo Clinic, Gonda 9-S, 200 Fisrt Street SW, Rochester, MN 55905, USA, Larson.david2@mayo.edu.

BACKGROUND: This report describes the clinical benefits and safety of a novel (incisionless) laparoscopic operation for chronic ulcerative colitis. METHODS: The medical records for four patients with the diagnosis of chronic ulcerative colitis who underwent "incisionless" laparoscopic proctocolectomy with Brooke ileostomy were reviewed. A novel technique was used for successfully performance of four total proctocloectomies with end ileostomies that did not require abdominal incisions. The clinical outcomes measured included time to oral intake, time to ostomy output, operative time, postoperative and intraoperative complications, estimated blood loss, and length of stay. RESULTS: All the patients recovered without incident intraoperatively and postoperatively. The operative times ranged from 330 to 550 min. Postoperative findings included median time to oral intake (2 days), median time to ileostomy output (2 days), and median length of stay (4 days). CONCLUSION: This case series demonstrates that an incisionless approach to chronic ulocerative colitis for patients who desire an end ileostomy may be feasible and safe, offering patients short-term recovery and cosmetic benefits.

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Psychother Psychosom. 2005;74(5):277-87.
Effects of mind-body therapy on quality of life and neuroendocrine and cellular immune functions in patients with ulcerative colitis.
Elsenbruch S, Langhorst J, Popkirowa K, Muller T, Luedtke R, Franken U, Paul A, Spahn G, Michalsen A, Janssen OE, Schedlowski M, Dobos GJ.
Departement of Medical Psychology, University Clinic of Essen, Essen, Germany. sigrid.elsenbruch@uni-essen.de

BACKGROUND: The aim of this study was to investigate the effects of mind-body therapy on neuroendocrine and cellular immune measures, health-related quality of life and disease activity in patients with ulcerative colitis (UC) in remission. METHODS: Thirty UC patients in remission or with low disease activity were randomly assigned to an intervention group (n = 15) or a usual-care waiting control group (n = 15). Intervention consisted of a structured 60-hour training program over 10 weeks which included stress management training, moderate exercise, Mediterranean diet, behavioral techniques and self-care strategies. Quality of life, perceived stress and disease activity were assessed with standardized questionnaires (IBDQ, SF-36, PSS, CAI). In addition, the distribution of circulating lymphocytes and lymphocyte subsets as well as the beta-adrenergic modulation of TNF-alpha production in vitro were analyzed. Urine catecholamines and plasma cortisol, prolactin and growth hormone were measured pre- and postinterventionally, and were compared with a healthy control group (n = 10). RESULTS: In response to therapy, patients in the intervention group showed significantly greater improvement in the SF-36 scale Mental Health and the Psychological Health Sum score compared with changes observed in the usual-care waiting control group. Patients in the intervention group showed significantly greater improvement on the IBDQ scale Bowel Symptoms compared with the control group. However, no significant group differences in circulating lymphocyte subsets or endocrine parameters were observed in response to therapy. In addition, no significant effects of intervention on either the basal levels of TNF-alpha or the suppressive action of the beta-adrenergic agonist isoproterenol on TNF-alpha production were observed. CONCLUSION: Mind-body therapy may improve quality of life in patients with UC in remission, while no effects of therapy on clinical or physiological parameters were found, which may at least in part be related to selective patient recruitment. Copyright 2005 S. Karger AG, Basel.

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J Pediatr Surg. 2005 Jul;40(7):1216-7.
Surgery for ulcerative colitis in pediatric patients: Functional results of 10-year follow-up with straight endorectal pull-through.
Schmittenbecher P.

The incidence of inflammatory bowel disease is increasing in all developed countries. The annual incidence of ulcerative colitis is reported between 1.5 and 2.14 cases per 100.000. Many patients have a long period of complete remission, but less than 5% remain free from relapse after 10 years from diagnosis. The aim of the paper was to present a 10 year follow-up of endorectal pull-through (ERPT). In the 13 year interval from 1988 to 2001, 118 children affected by ulcerative colitis were treated in the authors division of gastroenterology and in 28 cases surgical treatment was necessary. The surgical procedure included total colectomy, rectal mucosectomy and straight ileo-anal anstomosis. In three cases, an ileal S-pouch was created. A telephone follow-up asked for stool patterns and urgency periods and calculated an incontinence score rating items for emission of gas, liquid stools, solid stools and use of diapers. The quality of life was evaluated in terms of school and physical activity, emotional status and social life. Twenty-eight children (23.7%) were operated with an age of 2 to 16 at time of operation. Mean time between diagnosis and surgery was 27.1 month. Urgent subtotal colectomy with delayed ileoanal anastomosis for severe rectal bleeding was done in four children, elective ERPT with temporary ileostomy in 24 patients, three of them with S-shaped pouch. Ileostomy closure took place about 4 month after surgery. Ten complications (47%) included 4 local recurrences and two anastomotic leaks. Two S-pouches were excised because of recurrent pouchitis. The follow-up of 24 children at 6(1/2) years after surgery demonstrated regular growth patterns, no bladder dysfunction and no male impotence. Half of the patients had more than six stools per day, seven reported loose or liquid stools, and incontinence was given in 11 children. The emotional status and the social life were reported to be normal in 72% and 66% respectively. Ninety percent of children with ulcerative colitis have moderate to severe disease activity. Ileal reservoir techniques are created to increase the rectal capacity and to reduce the frequency of bowel movements. According to that, median stool frequency is reported about four movements/day in pouches in contrast to seven movements/day in ERPT. Early and long-term functional results of pouches are superior to straight ERPT. Unfortunately, the authors do not comment on their unsatisfactory results in pouch creation. Independent from that, it is mentioned as important to assess the impact of chronic disease on quality of life. In adults, quality of life scores were low in inflammatory bowel disease before surgery and improved postoperatively. The authors conclude that these data justify aggressive surgical intervention in many patients. They pointed out that most of their patients experience a satisfactory lifestyle even if fecal incontinence and high frequency of defecation compromise quality of life. Finally the aspect of financial implications is discussed with the statement that early surgery prevents families and insurance companies from supporting health care expenditures in a long-term follow-up. ERPT is judged as good choice for treating severe ulcerative colitis, but new surgical techniques are desired to achieve better functional results and more acceptable quality of life.

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Gut. 2005 Jul;54(7):960-5.
Combined oral and enema treatment with Pentasa (mesalazine) is superior to oral therapy alone in patients with extensive mild/moderate active ulcerative colitis: a randomised, double blind, placebo controlled study.
Marteau P, Probert CS, Lindgren S, Gassul M, Tan TG, Dignass A, Befrits R, Midhagen G, Rademaker J, Foldager M.
Gastroenterology, Hopital Europeen Georges Pompidou, 20 rue Leblanc, 75908 Paris cedex 15, France. philippe.marteau@hop.egp.ap-hop-paris.fr.

BACKGROUND AND AIMS: Oral aminosalicylates are well established in the treatment of active mild/moderate ulcerative colitis (UC) when the disease is extensive (that is, beyond the splenic flexure). The majority of clinical symptoms relate to disease activity in the distal part of the colon and therefore this study was designed to investigate if adding a mesalazine enema to oral mesalazine has additional benefit for patients with extensive mild/moderate active UC. METHODS: A randomised double blind study was performed in 127 ambulatory patients. All received 4 g/day (twice daily dosing) oral mesalazine for eight weeks. During the initial four weeks, they additionally received an enema at bedtime containing 1 g of mesalazine or placebo. Disease activity was assessed using the ulcerative colitis disease activity index, with clinical and endoscopic signs at four and eight weeks. RESULTS: Remission was obtained in 44% (95% confidence interval (CI) 31%, 58%) of the mesalazine enema group (Me) and in 34% (95% CI 21%, 49%) of the placebo enema group (Pl) at four weeks (p = 0.31) and in 64% (95% CI 50%, 76%) of the Me group versus 43% (95% CI 28%, 58%) of the Pl group at eight weeks (p = 0.03). Improvement was obtained in 89% (95% CI 78%, 96%) of the Me group versus 62% (95% CI 46%, 75%) of the Pl group at four weeks (p = 0.0008) and in 86% (95% CI 75%, 94%) of the Me group versus 68% (95% CI 53%, 81%) of the Pl group at eight weeks (p = 0.026). CONCLUSION: In patients with extensive mild/moderate active UC, the combination therapy is superior to oral therapy. It is safe, well accepted, and may be regarded as firstline treatment.

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Gastroenterology. 2005 Jun;128(7):1805-11.
Infliximab as rescue therapy in severe to moderately severe ulcerative colitis: a randomized, placebo-controlled study.
Jarnerot G, Hertervig E, Friis-Liby I, Blomquist L, Karlen P, Granno C, Vilien M, Strom M, Danielsson A, Verbaan H, Hellstrom PM, Magnuson A, Curman B.

Background & Aims: Despite treatment with corticosteroids, severe to moderately severe attacks of ulcerative colitis have a high colectomy rate. We intended to find a rescue therapy other than cyclosporin A, which imposes a high risk of side effects and cyclosporine-related mortality. Methods: This was a randomized double-blind trial of infliximab or placebo in severe to moderately severe ulcerative colitis not responding to conventional treatment. Patients were randomized to infliximab/placebo either on day 4 after the initiation of corticosteroid treatment if they fulfilled the index criteria for fulminant ulcerative colitis on day 3 or on day 6-8 if they fulfilled index criteria on day 5-7 for a severe or moderately severe acute attack of ulcerative colitis. Results were analyzed according to the intention-to-treat principle. The primary end point was colectomy or death 3 months after randomization. Secondary end points were clinical and endoscopic remission at that time in patients who did not undergo operation. Results: Forty-five patients were included (24 infliximab and 21 placebo). No patient died. Seven patients in the infliximab group and 14 in the placebo group had a colectomy ( P = .017; odds ratio, 4.9; 95% confidence interval, 1.4-17) within 3 months after randomization. No serious side effects occurred. Three patients in the placebo group required operation for septic complications. Conclusions: Infliximab 4-5 mg/kg is an effective and safe rescue therapy in patients experiencing an acute severe or moderately severe attack of ulcerative colitis not responding to conventional treatment.

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Arch Surg. 2005 Jun;140(6):534-9; discussion 539-40.
Ileal pouch-anal anastomosis: does age at the time of surgery affect outcome?
Chapman JR, Larson DW, Wolff BG, Dozois EJ, Cima RR, Pemberton JH, Crownhart BS, Larson DR.
Division of Colorectal Surgery and the Department of Biostatistics, Mayo Clinic and Mayo Foundation, Mayo Clinic College of Medicine, Rochester, Minn, USA.

HYPOTHESIS: Functional outcome and quality of life in older patients (>55 years) undergoing ileal pouch-anal anastomosis (IPAA) for ulcerative colitis or familial adenomatous polyposis have been incompletely studied. Our aim was to update our understanding on how the age of the patient at the time of surgery influences functional outcome and quality of life after IPAA. METHODS: From January 1, 1981, to December 31, 2000, two thousand two patients who underwent IPAA were studied. Patients were grouped by age at operation: 45 years or younger (n = 1688), between 46 and 55 years (n = 249), and older than 55 years (n = 65). Mean age was 33.5 years. Postoperative complications, function, and quality of life were assessed with a questionnaire administered annually. RESULTS: Follow-up for patients older than 55 years was a mean +/- SD of 8.1 +/- 4.8 years. Overall, follow-up was a mean of 10.1 +/- 5.7 years. The pouch failure rate for patients older than 55 years was 1.6% at 10 years. No statistically significant difference in pouch failure between age groups was observed. Overall, frequent daytime and nighttime incontinence, respectively, occurred in 5.6% and 13.3% of the patients at 10 years. Incontinence was more common in older patients (P = .002 at 3 years). Quality of life as assessed by social activities, work, travel, sexual activity, family relationships, and sports and recreation was not significantly different among age groups. Most patients felt that their condition had improved or that they had no restrictions after IPAA. CONCLUSIONS: Postoperative complications after surgery seem to be unrelated to age at the time of surgery. Although incontinence may occur more frequently in older patients, IPAA does not adversely affect quality of life in patients older than 55 years.

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N Engl J Med. 2005 Jun 16;352(24):2499-507.
Treatment of ulcerative colitis with a humanized antibody to the alpha4beta7 integrin.
Feagan BG, Greenberg GR, Wild G, Fedorak RN, Pare P, McDonald JW, Dube R, Cohen A, Steinhart AH, Landau S, Aguzzi RA, Fox IH, Vandervoort MK.
Robarts Research Institute, London, ON N6A 5K8, Canada. bfeagan@robarts.ca

BACKGROUND: Selective blockade of interactions between leukocytes and vascular endothelium in the gut is a promising strategy for the treatment of inflammatory bowel diseases. METHODS: We conducted a multicenter, double-blind, placebo-controlled trial of MLN02, a humanized antibody to the alpha4beta7 integrin, in patients with active ulcerative colitis. We randomly assigned 181 patients to receive 0.5 mg of MLN02 per kilogram of body weight, 2.0 mg per kilogram, or an identical-appearing placebo intravenously on day 1 and day 29. Eligible patients also received concomitant mesalamine or no other treatment for colitis. Ulcerative colitis clinical scores and sigmoidoscopic assessments were evaluated six weeks after randomization. RESULTS: Clinical remission rates at week 6 were 33 percent, 32 percent, and 14 percent for the group receiving 0.5 mg of MLN02 per kilogram, the group receiving 2.0 mg per kilogram, and the placebo group, respectively (P=0.03). The corresponding proportions of patients who improved by at least 3 points on the ulcerative colitis clinical score were 66 percent, 53 percent, and 33 percent (P=0.002). Twenty-eight percent of patients receiving 0.5 mg per kilogram and 12 percent of those receiving 2.0 mg per kilogram had endoscopically evident remission, as compared with 8 percent of those receiving placebo (P=0.007). For the minority of patients in whom an MLN02 antibody titer greater than 1:125 developed, incomplete saturation of the alpha4beta7 receptor on circulating lymphocytes was observed and no benefit of treatment was identifiable. CONCLUSIONS: In this short-term study, MLN02 was more effective than placebo for the induction of clinical and endoscopic remission in patients with active ulcerative colitis.

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Clin Gastroenterol Hepatol. 2005 Jun;3(6):581-6.
Interferon-beta-1a for the Treatment of Steroid-Refractory Ulcerative Colitis: A Randomized, Double-Blind, Placebo-Controlled Trial.
Musch E, Andus T, Kruis W, Raedler A, Spehlmann M, Schreiber S, Krakamp B, Malek M, Malchow H, Zavada F, Engelberg Feurle G.

Background & Aims: We performed a randomized, double-blind, placebo-controlled, multicenter trial to investigate the efficacy and safety of recombinant interferon-beta-1a (rIFN-beta-1a) in outpatients with active steroid-refractory ulcerative colitis. Methods: Ninety-one randomized patients subcutaneously received 3 MIU rIFN-beta-1a (group A, n = 32), 1 MIU rIFN-beta-1a (group B, n = 30), or placebo (group C, n = 29) 3 times a week over a period of 8 weeks in addition to standard therapy. An intention-to-treat analysis was performed to evaluate the efficacy and safety of treatment. Results: In all 3 groups, the median prestudy clinical activity index (CAI) was 10. In 18 of 32 patients (56%) in group A, in 11 of 30 patients (36%) in group B, and in 10 of 29 patients (34%) in group C, a reduction of the CAI of 6 points or greater (response) was achieved (differences were not statistically significant). Complete response (reduction of CAI to </=4) was achieved in 56%, 30%, and 38% of patients in groups A, B, and C, respectively. Compared with baseline, the median endoscopic index had been reduced by 5, 3, and 4 points in groups A, B, and C, respectively. Steroid reduction was 12 mg in group A, 6 mg in group B, and 10 mg in group C. Identical side effects occurred in all 3 groups. Seven serious adverse events were reported (1 in group A and 6 in group C). All were unrelated to therapy as judged by the investigating physicians. Conclusions: rIFN-beta-1a was safe but not significant, at the dosage and/or duration of treatment used, in steroid-refractory ulcerative colitis. Further studies are indicated.

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Dis Colon Rectum. 2005 May 31; [Epub ahead of print]
Safety of One-Stage Restorative Proctocolectomy for Ulcerative Colitis.
Ikeuchi H, Nakano H, Uchino M, Nakamura M, Noda M, Yanagi H, Yamamura T.
Second Department of Surgery, Hyogo College of Medicine, Hyogo, Japan, ikeuci2s@hyo-med.ac.jp.

PURPOSE: The aim of this study was to compare clinical outcomes in patients with ulcerative colitis who underwent restorative proctocolectomy with and without diverting ileostomy. METHODS: A series of 245 consecutive patients who underwent ileal pouch anal anastomosis with mucosectomy with an ultrasonically activated scalpel (harmonic scalpel) was studied. Of these patients, 92 patients had a diverting ileostomy and 150 selected patients did not. The decision for or against an ileostomy was made at the end of the operation. RESULTS: Twelve patients (8 percent) in the group without ileostomy had pouch-related complications, which necessitated secondary ileostomy in five patients (3.3 percent). Intestinal obstruction developed in 17 patients (11.3 percent) who had no ileostomy and in 12 patients (13.0 percent) who underwent ileostomy. Two of 17 patients who had no ileostomy and 1 of 12 patients with ileostomy required laparotomy with division of adhesions, whereas the remaining patients responded to conservative measures. There were no significant differences in the incidence of postoperative complications after the initial operation between the two groups. In the group with ileostomy, the morbidity rate for ileostomy was 12.1 percent, and that for ileostomy closure was 18.7 percent. The total postoperative complication rate for the group with ileostomy was significant higher than that for the group without ileostomy. CONCLUSION: We conclude that restorative proctocolectomy with mucosectomy by use of an ultrasonically activated scalpel and without diversion is a superior therapeutic choice for selected patients.

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Nippon Rinsho. 2005 May;63(5):859-66.
[Surgical treatment for ulcerative colitis—recent advancement]
[Article in Japanese]
Sugita A, Kimura H, Arai K, Koganei K, Shimada H, Kitoh F, Fukushima T.
Department of Surgery, Yokohama Municipal Citizen's Hospital.

Surgical indication for ulcerative colitis is fulminant colitis, intractability, cancer or dysplasia. New surgical indication should be established because new medical treatment such as leucocytoapheresis or intravenous cyclosporine treatment developed. Standard surgical procedure is ileal pouch anal anastomosis with rectal mucosal stripping and stapled ileal pouch anal anastomosis. Postoperative bowel function and QOL are satisfactory in both of them. Surgical treatment should be performed without any delay for the patients who do not respond medical treatment.

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Nippon Rinsho. 2005 May;63(5):820-4.
[Drug therapy for ulcerative colitis: salazosulfapyridine and 5-ASA]
[Article in Japanese]
Jo Y, Matsumoto T, Iida M.
Department of Medicine and Clinical Sciences, Graduate School of Medical Sciences, Kyushu University.

Aminosalicylates have a wide range of anti-inflammatory and immunomodulatory effects. Oral salazosulfapyridine (SASP) and 5-aminosalicylic acid (5-ASA) are the 'first-line' therapy for induction of remission in mild to moderate active ulcerative colitis (UC). SASP, which is consisted of 5-ASA and sulfapyridine, has greater incidence of side effects. 5-ASA is a therapeutically active compound, while sulfapyridine is related to adverse effects. For this reason, 5-ASA formulas exclusive of sulfapyridine were developed and they enabled higher dose of 5-ASA administration without adverse effects. Topical treatment by 5-ASA enema or SASP suppository should be considered for the treatment of proctitis or distal type of UC. Oral aminosalicylate therapy is also effective for the maintenance of remission in UC. Therefore, aminosalicylates are key drugs for the treatment of UC.

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J Clin Gastroenterol. 2005 Apr;39(4):291-297.
Topical Treatment of Distal Active Ulcerative Colitis With Beclomethasone Dipropionate or Mesalamine: A Single-blind Randomized Controlled Trial.
Gionchetti P, D'arienzo A, Rizzello F, Manguso F, Maieron R, Lecis PE, Valpiani D, Iaquinto G, Annese V, Balzano A, Varoli G, Campieri M; and the Italian BDP Study Group.

GOALS:: Therapy for active ulcerative colitis (UC) usually involves rectal formulations of corticosteroids (CS), which are characterized by the risk of systemic steroid-related adverse effects. BACKGROUND:: To compare the efficacy and safety of the topically acting CS beclomethasone dipropionate (BDP) versus mesalamine (5-ASA) in the treatment of active UC. STUDY:: Patients with mild to moderate distal active UC were randomized to a 6-week treatment with BDP 3 mg enema o.d. or 5-ASA 1 g enema daily in a single-blind, multicenter, parallel-group, controlled study. The primary efficacy variable was the decrease in Disease Activity Index (DAI) score. Safety variables were adrenal function, monitoring of adverse events, vital signs, and laboratory parameters. RESULTS:: A total of 217 patients were enrolled and treated with BDP (n = 111) or 5-ASA (n = 106). A significant decrease in the DAI score (P < 0.05) was observed in both treatment groups, with a clinical remission rate of 36.7% in the BDP group and of 29.2% in the 5-ASA group. Both treatments were well tolerated. No changes from baseline in morning cortisol levels were observed in the BDP group. CONCLUSIONS:: BDP administered as a rectal enema over a 6-week treatment period was efficacious and safe in patients with active UC, without interference with pituitary adrenal axis.

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Inflamm Bowel Dis. 2005 Mar;11(3):213-8.
Infliximab efficacy in pediatric ulcerative colitis.
Eidelwein AP, Cuffari C, Abadom V, Oliva-Hemker M.
>From the Pediatric Gastroenterology and Nutrition, Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland.

BACKGROUND:: The effects of infliximab, a tumor necrosis factor-alpha (TNF-alpha) antibody, have been well established in adult patients with inflammatory and fistulizing Crohn's disease. This study evaluates short- and long-term efficacy of infliximab in children with ulcerative colitis. METHODS:: All pediatric patients with ulcerative colitis who received infliximab between July 2001 and November 2003 at the Johns Hopkins Children's Center were identified. Short- and long-term outcomes and adverse reactions were evaluated. RESULTS:: Twelve pediatric patients with ulcerative colitis received infliximab for treatment of fulminant colitis (3 patients), acute exacerbation of colitis (3), steroid-dependent colitis (5), and steroid-refractory colitis (1). Nine patients had a complete short-term response, and 3 had partial improvement. The mean per patient dose of corticosteroid after the first infliximab infusion decreased from 45 mg/day at the first infusion to 22.2 mg/day at 4 weeks (P = 0.02) and 7.8 mg/day at 8 weeks (P = 0.008). Eight patients were classified as long-term responders with a median follow-up time of 10.4 months. Of the 4 long-term nonresponders, 3 underwent colectomy, and the fourth has ongoing chronic symptoms. Three of 4 long-term nonresponders were steroid-refractory compared with 1 of 8 long-term responders. Patients receiving 6-mercaptopurine had a better response to infliximab. CONCLUSION:: Infliximab should be considered in the treatment of children with symptoms of acute moderate to severe ulcerative colitis.

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Dig Liver Dis. 2005 Feb;37(2):92-6.
Long-term oral plus topical mesalazine in frequently relapsing ulcerative colitis.
Frieri G, Pimpo M, Galletti B, Palumbo G, Corrao G, Latella G, Chiaramonte M, Caprilli R.
Gastroenterology, University of l'Aquila, L'Aquila, Italy. g.frieri@libero.it

BACKGROUND: In cross-sectional studies, it was demonstrated that the therapeutic effect of mesalazine is closely related to its mucosal concentration. AIM: This study was carried out to verify in a longitudinal study if it was possible to improve the clinical course of ulcerative colitis at high risk of recurrence by increasing mucosal mesalazine concentration. METHODS: Eighteen consecutive ulcerative colitis patients on continuous oral 5-ASA treatment (2.4-3.2 g/day) in clinical remission who had had at least four moderate to severe relapses in the preceding 2 years (referred period) were assigned to assume oral (3.2-4.8 g/day) and topical (4 g/day) mesalazine in order to increase mucosal drug concentration and were followed up for 2 years (study period). The localisation of disease was 12 pancolitis, six left colitis. The number and severity of recurrences, number of visits and endoscopies, courses of steroids and days of hospitalisation were compared with those of the previous 2 years. Rank signed test for paired data was used for statistical analysis. RESULTS: The total number of recurrences was significantly lower during the study period in comparison with that of referred period (8 versus 80, respectively, p < 0.0001). No courses of steroids or hospitalisation were necessary during study period in comparison with those of referred period (0 versus 33, p < 0.0001; 0 versus 93, p = 0.03, respectively). A total number of 249 visits were done during the referred period and 116 during the study period (p < 0.0001) with a total of 87 endoscopies during referred period and 44 during study period (p < 0.0001). CONCLUSIONS: The continuous use of topical mesalazine associated with a high oral dosage significantly improves the clinical course of ulcerative colitis patients at high risk of relapse.

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Aliment Pharmacol Ther. 2005 Feb 15;21(4):385-9.
Oral methotrexate in ulcerative colitis.
Cummings JR, Herrlinger KR, Travis SP, Gorard DA, McIntyre AS, Jewell DP.
Gastroenterology Unit, University of Oxford, Radcliffe Infirmary, Oxford, UK. fraserc@well.ox.ac.uk

BACKGROUND: We performed an audit of methotrexate for ulcerative colitis, because efficacy is unclear. Aim : To investigate the role of methotrexate in the management of ulcerative colitis. METHODS: Patients with ulcerative colitis treated with oral methotrexate at the inflammatory bowel disease clinics of Oxford and Wycombe General Hospital, UK, were evaluated. Efficacy was defined by remission (complete steroid withdrawal for >3 months) and response (good, partial or nil, proportionate reduction of steroids). RESULTS: There were 50 patients (42 ulcerative colitis alone; eight had rheumatoid arthritis associated with ulcerative colitis and were analysed separately). Indications for methotrexate in ulcerative colitis alone were azathioprine intolerance (31 of 42) and lack of benefit from azathioprine (11 of 42). The mean dose of methotrexate in ulcerative colitis alone was 19.9 mg/week for a median of 30 weeks (range: 7-395). Remission occurred in 42%. The response was good in 54% and partial in 18%. Side-effects occurred in 23%; 10% stopped treatment because of side-effects. Of those treated with methotrexate because of treatment failure with azathioprine, three of 11 achieved remission, but four came to colectomy within 90 days of starting methotrexate. The colitis remained in remission in seven of eight of those with RA treated with methotrexate and ulcerative colitis (mean dose 15.0 mg/week). CONCLUSION: Oral methotrexate (approximately 20 mg/week) is well-tolerated and moderately effective in steroid-dependent or steroid-refractory patients with ulcerative colitis.

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Aliment Pharmacol Ther. 2005 Jan 15;21(2):133-40.
A double-blind dose-escalating trial comparing novel mesalazine pellets with mesalazine tablets in active ulcerative colitis.
Marakhouski Y, Fixa B, Holoman J, Hulek P, Lukas M, Batovsky M, Rumyantsev VG, Grigoryeva G, Stolte M, Vieth M, Greinwald R; The International Salofalk Study Group.
Department of Gastroenterology and Nutrition, Byelorussian Medical Academy Postgraduate Education, Minsk, Republic of Belarus.

BACKGROUND: Mesalazine as the treatment standard for ulcerative colitis can be applied in different galenical preparations. AIM: A novel formulation of mesalazine pellets with delayed and prolonged release characteristics was compared with conventional Eudragit L-coated tablets. Furthermore, the effect of mesalazine dose escalation on nonresponders was evaluated in both treatment groups. METHODS: A total of 233 patients with mild to moderately active ulcerative colitis were randomized to receive either mesalazine (1.5 g/day in three doses) as pellets (n = 115) or tablets (n = 118) for 8 weeks. At insufficient response, the dose was increased to 3.0 g. RESULTS: The clinical remission rate (clinical activity index < or = 4) for pellets was 67% vs. 68% for tablets which statistically proved to be not inferior (significance level alpha = 2.5%). In patients without dose increase, the remission rate was 47% (pellets) vs. 42% (tablets). Endoscopic improvement was observed in 80% (pellets) vs. 83% (tablets), and histological improvement in 48% (pellets) vs. 52% (tablets) of patients. CONCLUSIONS: Mesalazine pellets are as effective as tablets in the treatment of mild to moderately active ulcerative colitis. Dose escalation to 3.0 g/day is a valid option for nonresponders to a starting dose of 1.5 g/day.

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Isr Med Assoc J. 2005 Jan;7(1):23-7.
Restorative proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis and familial adenomatous polyposis: twenty years follow-up in 174 patients.
Krausz MM, Duek SD.
Department of Surgery A, Rambam Medical Center, Haifa, Israel. m_krausz@rambam.health.gov.il

BACKGROUND: Restorative proctocolectomy with ileal pouch-anal anastomosis has become the surgical procedure of choice for patients with ulcerative colitis and familial adenomatous polyposis. OBJECTIVES: To evaluate the long-term functional outcome of patients who underwent this surgical procedure. METHODS: We performed this observational study in 174 consecutive patients: 146 with UC and 28 with FAP. The patients, 91 males and 83 females with a mean age of 34.1+/-10.6 years (range 6-67 years), underwent the procedure between January 1984 and January 2004 (mean follow-up 64.8 months, range 1-240 months). The indications for surgery were intractable disease in 124 patients (71%), dysplasia in 36 (21%), severe bleeding in 8 (5%), and perforation in 6 (3%). RESULTS: A protective ileostomy was performed in 140 patients (96%) with UC and 12 (43%) with FAP. An urgent three-stage procedure was necessary in 14 patients (8.4%). A mucosal proctectomy was performed in 94 (54%), and a double stapling technique in 80 (46%). Mean length of hospital stay was 9.4+/-6.6 days (range 5-34 days, median 8). Complications included pelvic sepsis in 7 patients (4.2%), anastomotic leakage in 8 (4.8%), bowel obstruction in 22 (13.2%), incisional hernia in 12 (7.2%), anastomotic stenosis that usually responded to manual dilatation in 46 (27.6%), pouchitis in 106 (61%), recto-vaginal fistula in 3 (1.8%), retrograde ejaculation in 3 (1.8%), and impotence in 2 (1.2%). There was no mortality in this group of patients. The median number of bowel movements per 24 hours was six in UC patients and five in FAP patients, with at least one bowel movement during the night. Complete daytime and night-time continence was documented in 124 patients (71%). Overall satisfaction was 95%. CONCLUSIONS: Restorative proctocolectomy with ileal pouch-anal anastomosis confers a long-term good quality of life to both UC and FAP patients, and the majority of patients are fully continent with five to six bowel movements per day.

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Acta Chir Iugosl. 2004;51(2):123-6.
Ulcerative colitis indications and timing for surgery.
Barisic G, Krivokapic Z, Markovic V, Saranovic D, Masulovic D.
Institute for Digestive Diseases, First Surgical Clinic, Clinical Center of Serbia, Belgrade, Serbia and Montenegro.

Surgery continues to have a major role in the management of ulcerative colitis because it may save the patient's life, eliminate the long-term risk of cancer, and most important, abolish the disease. Treatment of ulcerative colitis still remains the challenge despite growing knowledge about the disease, advances in medical treatment and surgical techniques. Indications and optimal timing for surgery are the mainstays of good outcome and are as important as the quality of medical therapy and surgery. Ulcerative colitis is a complex disease where medical and surgical treatment frequently overlap and clinical decision making should be in hands of well trained and experienced team consisting of surgeon, gastroenterologist, radiologist and pathologist. Recently developed drugs, with high potential in the treatment of severe attacks of ulcerative colitis brought some changes in therapy and indications for surgical treatment. Although as many as half of patients with inflammatory bowel disease require at least one surgical procedure to address complications derived from their disease, the decision in favor of a surgical approach and its timing is rarely an easy one.

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Aliment Pharmacol Ther. 2004 Dec;20(11-12):1353-63.
Mesalazine (5-aminosalicylic acid) micropellets show similar efficacy and tolerability to mesalazine tablets in patients with ulcerative colitis - results from a randomized-controlled trial.
Raedler A, Behrens C, Bias P.
Department of Internal Medicine II - Gastroenterology, Asklepios Westklinikum Hamburg, Teaching Hospital of the University of Hamburg, Hamburg.

Summary Background : Formulations containing 5-aminosalicylic acid, such as mesalazine, are the gold standard of treatment for mild-to-moderate ulcerative colitis. Current oral regimens require the use of large tablets and frequent dosing to reach the recommended treatment dose. Mesalazine micropellets were designed to allow less frequent dosing in an easier to swallow formulation. Aim : To compare the efficacy of mesalazine micropellets with the tablet formulation in patients with mild-to-moderate ulcerative colitis. Methods : This phase 2, double-blind, active-controlled, parallel-group, multiple dose clinical trial randomized 362 patients to either mesalazine micropellets or tablets, at a dosage of 3 g/day. The primary efficacy end-point was the incidence of clinical remission within 8 weeks, defined as the sum of clinical activity index components 1-4 (CAI(C1-4)) </= 2. Results : CAI(C1-4) decreased significantly in both treatment groups within 8 weeks. The micropellet formulation showed confirmatory non-inferiority with statistical significance compared with the tablet formulation, with regard to the incidence of clinical remission (odds ratio in according-to-protocol population 1.008; 95% CI: 0.623-1.632). There was no significant difference in the incidence of adverse events. Conclusions : The mesalazine micropellet formulation is as effective as tablets in patients with mild-to-moderate ulcerative colitis, enabling a larger dose to be taken comfortably and conveniently, thereby potentially improving patient compliance, treatment response and quality of life.

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Br J Surg. 2004 Dec 10; [Epub ahead of print]
Laparoscopic restorative proctocolectomy.
Kienle P, Z'graggen K, Schmidt J, Benner A, Weitz J, Buchler MW.
Department of Surgery, University of Heidelberg, Heidelberg, Germany.

BACKGROUND:: Restorative proctocolectomy is increasingly being performed using minimally invasive surgery. In published series laparoscopically assisted techniques have usually included a suprapubic incision to enable major parts of the operation to be done openly. METHODS:: Fifty consecutive patients with familial adenomatous polyposis or ulcerative colitis underwent laparoscopic restorative proctocolectomy using only a small perumbilical incision of 4 cm or less for vascular dissection and pouch formation; all other steps were performed entirely laparoscopically. Logistic regression was used for statistical analysis. RESULTS:: In four patients (8 per cent) the operation was converted to an open procedure. The diagnosis of ulcerative colitis was associated with a higher overall rate of complications (P = 0.011), and an increased body mass index (BMI) with a higher rate of major complications (P = 0.050). The occurrence of wound infection was related to the diagnosis of ulcerative colitis (P = 0.049). Conversion resulted in greater blood loss (P = 0.004), but not in a higher complication rate. No patient required a blood transfusion. Patients with an increased BMI and those taking immunosuppressive therapy had a longer hospital stay (P = 0.043). CONCLUSION:: Laparoscopic restorative proctocolectomy is technically feasible. Patients with ulcerative colitis and increased BMI have a higher risk of complications. This minimally invasive technique may reduce the need for perioperative blood transfusion. Copyright (c) 2004 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

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Ann Surg. 2004 Dec;240(6):984-91; discussion 991-2.
Hand-assisted laparoscopic versus open restorative proctocolectomy with ileal pouch anal anastomosis: a randomized trial.
Maartense S, Dunker MS, Slors JF, Cuesta MA, Gouma DJ, van Deventer SJ, van Bodegraven AA, Bemelman WA.
Department of Surgery, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.

OBJECTIVE: The aim of the study was to evaluate postoperative recovery after hand-assisted laparoscopic or open restorative proctocolectomy with ileal pouch anal anastomosis for ulcerative colitis and familial adenomatous polyposis in a randomized controlled trial. METHODS: Sixty patients were randomized for hand-assisted laparoscopic (n = 30) or open surgery (n = 30). Primary outcome parameter was postoperative recovery in the 3 months after surgery, measured by quality of life questionnaires (SF-36 and GIQLI). Secondary parameters were postoperative morphine requirement and surgical parameters, viz. operating time, morbidity, hospital stay, and costs. RESULTS: There was no difference between the 2 procedures in quality of life assessment in the 3 months after surgery. There was a significant decline in quality of life on all scales of the SF-36 (P < 0.001) and total GIQLI score (P < 0.001) in the first 2 weeks in both groups (no significant difference between the groups). Quality of life returned to baseline levels after 4 weeks. Operating times were longer in the laparoscopic group compared with the open group (210 and 133 minutes, respectively; P < 0.001). No significant differences were found in morphine requirement. Neither morbidity nor postoperative hospital stay differed between the laparoscopic and open group (20% versus 17%, in 10 versus 11 days, respectively). Median overall costs were 16.728 for the hand-assisted laparoscopic procedure and 13.406 for the open procedure (P = 0.095). CONCLUSIONS: Recovery measured using quality of life questionnaires is comparable for hand-assisted laparoscopic or open restorative proctocolectomy with ileal pouch anal anastomosis. The laparoscopic approach is as safe, but more costly than the open procedure.

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Gut. 2004 Nov;53(11):1646-51.
A randomised, controlled, double blind, escalating dose study of alicaforsen enema in active ulcerative colitis.
van Deventer SJ, Tami JA, Wedel MK.
Academisch Medisch Centrum, Room G2, 129, Poli Inglammatoire Darmzietkten, Meibergdreef 9, NL 1105 AZ, Amsterdam Ziodoost, the Netherlands. S.J.vanDeventer@amc.uva.nl.

OBJECTIVE: To evaluate the safety and efficacy of an enema formulation of alicaforsen, an antisense inhibitor of intercellular adhesion molecule, after 1, 3, and 6 months. METHODS: This was a randomised, placebo controlled, double blind, escalating dose multicentre study in 40 patients with mild to moderately active distal ulcerative colitis (disease activity index (DAI) 4-10). Patients were assigned to four dosing cohorts of 10 patients each (eight active, two placebo). Each patient received 60 ml of alicaforsen enema (0.1, 0.5, 2, or 4 mg/ml or placebo) once daily for 28 consecutive days. Safety and efficacy (DAI and clinical activity index) scores were evaluated up to six months after initiation of dosing. RESULTS: At day 29, alicaforsen enema resulted in dose dependent improvement in DAI (overall p = 0.003). Alicaforsen 4 mg/ml improved DAI by 70% compared with the placebo response of 28% (p = 0.004). Alicaforsen 2 and 4 mg/ml improved DAI status by 72% and 68% compared with a placebo response of 11.5% at month 3 (p = 0.016 and 0.021, respectively). Specifically, DAI improved from 5.6 to 1.6 and from 6.3 to 2.5 in the 2 and 4 mg/ml groups compared with placebo (7.5 to 6.1). None of the patients in the 4 mg/ml group compared with 4/8 placebo patients required additional medical or surgical intervention over baseline during the six month period after starting the enema treatment. The safety profile was favourable. CONCLUSIONS: Alicaforsen enema showed promising acute and long term benefit in patients with mild to moderate descending ulcerative colitis. Alicaforsen enemas had a favourable safety profile. These findings require verification in larger randomised controlled clinical trials.

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Aliment Pharmacol Ther. 2004 Nov 15;20(10):1133-41.
Randomized placebo-controlled trial assessing the effect of bifidobacteria-fermented milk on active ulcerative colitis.
Kato K, Mizuno S, Umesaki Y, Ishii Y, Sugitani M, Imaoka A, Otsuka M, Hasunuma O, Kurihara R, Iwasaki A, Arakawa Y.
Department of Gastroenterology and Hepatology, Nihon University School of Medicine, Tokyo, Japan. kimitosi@med.nihon-u.ac.jp

BACKGROUND: Probiotics are efficacious for treating and maintaining remission of ulcerative colitis. AIM: To conduct a randomized placebo-controlled trial of bifidobacteria-fermented milk supplementation as a dietary adjunct in treating active ulcerative colitis. METHODS: Twenty patients with mild to moderate, active, ulcerative colitis randomly received 100 mL/day of bifidobacteria-fermented milk or placebo for 12 weeks with conventional treatment. RESULTS: Clinical and endoscopic activity indices and histological scores were similar in the two groups before treatment. Although improvements were significant in both groups, the clinical activity index was significantly lower in the bifidobacteria-fermented milk than in the placebo group after treatment. The post-treatment endoscopic activity index and histological score were significantly reduced in the bifidobacteria-fermented milk, but not the placebo group. Increases in faecal butyrate, propionate and short-chain fatty acid concentrations were significant in the bifidobacteria-fermented milk, but not the placebo group. No adverse effects were observed in either group. CONCLUSION: Supplementation with this bifidobacteria-fermented milk product is safe and more effective than conventional treatment alone, suggesting possible beneficial effects in managing active ulcerative colitis. This is a pilot study and further larger studies are required to confirm the result these preliminary results.

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Aliment Pharmacol Ther. 2004 Oct;20 Suppl 4:97-101.
Review article: the long-term management of ulcerative colitis.
Hanauer SB.
Section of Gastroenterology, University of Chicago, IL 60637, USA. shanauer@medicine.bsd.uchicago.edu

After the induction of remission, the second priority of therapy for ulcerative colitis is sustained clinical remission, defined as the absence of inflammatory symptoms (diarrhoea, bleeding, rectal urgency) and the maintenance of an intact mucosa, with the absence of ulcers, friability or significant granularity at endoscopy. The 'optimal' maintenance strategy will depend on the therapy needed to induce remission. Thus, the transition from induction to maintenance therapy will be determined by the intensity of acute therapy necessary to induce remission and the duration of therapy required to complete the resolution of clinical symptoms. There are few controlled clinical trials pertaining to maintenance after each induction regimen. However, experience dictates that aminosalicylates are efficacious after aminosalicylate-induced remissions, that steroids should be tapered according to the time required to induce remission, that patients requiring ciclosporin will benefit from the addition of long-term immunomodulation with azathioprine or mercaptopurine, and that many patients with distal colitis who require topical mesalazine (mesalamine) will continue to need topical therapy to maintain remission, albeit at reduced frequency. The expectations for maintenance therapy require patient adherence to the prescribed treatment regimen. Patients require education with regard to the long-term goals of maintenance therapy (e.g. prevention of relapse, reduction of long-term complications of disease activity or risks of acute therapy with steroids), and should be warned against the use of nonsteroidal anti-inflammatory drugs and cautioned about the cessation of smoking, when applicable, due to potential risks of relapse or chronic activity.

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Aliment Pharmacol Ther. 2004 Oct;20 Suppl 4:88-92.
Review article: the management of mild to severe acute ulcerative colitis.
Travis SP.
John Radcliffe Hospital, Oxford, UK. Simon.Travis@orh.nhs.uk

The goals for the management of acute ulcerative colitis are the objective evaluation of disease activity, induction of remission, prevention of relapse and treatment of complications. Clinical practice should be guided by simple activity indices, as it is easy to underestimate severity. For the induction of remission, topical treatment with mesalazine (mesalamine) is appropriate initial therapy for distal disease but, if symptoms persist for over a fortnight, decisive treatment is usually appreciated by the patient. For mild to moderate disease, corticosteroids have been the mainstay in Europe, although high-dose aminosalicylates (such as Pentasa, 4 g orally daily and 1 g rectally) are an alternative for symptoms not interfering with daily activity. Novel therapeutic approaches in ulcerative colitis have lagged behind those used for Crohn's disease, but several (epidermal growth factor, RDP 58, basiliximab, leucocytapheresis) are on the horizon. Severe colitis, defined as a bloody stool frequency of more than six per day with any one of tachycardia (pulse > 90 beats/min), temperature (> 37.8 degrees C), anaemia (haemoglobin < 10.5 g/dL) or raised erythrocyte sedimentation rate (> 30 mm/h), is an indication for intensive intravenous treatment. National UK figures indicate that 30% of ulcerative colitis cases progress to colectomy, and objective criteria for predicting the need for colectomy have been validated. The timing of colectomy is the most important decision that a physician is called upon to make, in conjunction with the patient and surgical colleagues. For the maintenance of remission, aminosalicylates continue to be first-line therapy, although the choice of 5-aminosalicylate appears to be influenced as much by geography as by theoretical considerations. Steroids have no place in the maintenance of remission. Indications for azathioprine include patients after a severe relapse of ulcerative colitis, those with early relapse after steroids (dose of < 15 mg/day, or within 6 weeks of stopping) and those needing a second course of steroids within a year. Therapeutic decisions should have a strategy, aimed at navigating the patient around relapses and through to sustained remission. Good management depends on clinical skills, compassion and care of the individual, in addition to pharmaceuticals.

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Aliment Pharmacol Ther. 2004 Oct 15;20(8):859-65.
Nicotine enemas for treatment of ulcerative colitis: a study of the pharmacokinetics and adverse events associated with three doses of nicotine.
Ingram JR, Routledge P, Rhodes J, Marshall RW, Buss DC, Evans BK, Feyerabend C, Thomas GA.
Department of Gastroenterology, Cardiff and Vale NHS Trust, Cardiff.

Summary Background : Transdermal nicotine is of value in active ulcerative colitis but causes adverse events because of systemic absorption. Nicotine enemas may give rise to fewer adverse events. Aim : To assess the pharmacokinetics of nicotine enemas in three doses. Methods : Thirteen volunteers, all non-smokers but three ex-smokers, were given enemas on separate occasions containing 3, 6 and 9 mg of nicotine, in ascending dose order. Adverse events were recorded and blood samples taken over 8 h for measurement of serum nicotine and cotinine. Results : Enemas were retained by most subjects. Eleven of 14 adverse events were 'early'- 30-105 min after the enema, corresponding to maximum plasma nicotine concentrations; three events were later, 4-8 h after the enema and unrelated to the t(max). 'Early' adverse events occurred in eight subjects - six with 9 mg. The three highest plasma nicotine concentrations were with 9 mg and associated with headache, nausea and sweating. Only one had adverse events with 3 mg and withdrew from the study. Nicotine C(max) with 6 and 9 mg doses were respectively two and three times the value with 3 mg. Peak nicotine concentrations occurred 44-50 min after the enema. Conclusion : The 6 mg dose of nicotine probably represents the dose to use in clinical practice - for the highest therapeutic dose with a low risk of adverse events.

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J Clin Gastroenterol. 2004 Oct;38(9):741-745.
Current Therapeutic Recommendations: Infliximab for Ulcerative Colitis.
Shen EH, Das KM.
Crohn's and Colitis Center of New Jersey, Division of Gastroenterology and Hepatology, Robert Wood Johnson Medical School, New Brunswick, New Jersey.

Randomized, controlled studies have shown that infliximab, the chimeric anti-tumor necrosis factor alpha (TNF-alpha) antibody, is effective for the treatment of active and fistulizing Crohn's disease. Because infliximab is beneficial in patients with Crohn's disease, in whom other therapies have failed, it has been postulated that infliximab may also be helpful in patients with ulcerative colitis. Many investigators have studied the effectiveness of infliximab in ulcerative colitis, mainly in patients who are refractory to corticosteroids. Unfortunately, these studies have not yielded a conclusive answer to the efficacy of infliximab in inducing remission in patients with severe ulcerative colitis. However, some have reported excellent results and others less effective, with the overall data being inconclusive. The purpose of this review is to summarize the current literature on the use of infliximab in ulcerative colitis, as well as to provide insight into the possible mechanisms of why it may or may not work in these difficult-to-treat patients.

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J Clin Gastroenterol. 2004 Oct;38(9):733-40.
Diagnosis and treatment of ulcerative proctitis.
Regueiro MD.
Inflammatory Bowel Disease Center and Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh School of Medicine, Pennsylvania.

Proctitis refers to inflammation of the rectum, a diagnosis made by endoscopic evaluation. Symptoms of proctitis include rectal bleeding, urgency, tenesmus, diarrhea or constipation, and occasionally rectal pain. The causes of proctitis include infection, medication, ischemia, radiation, and ulcerative proctitis. Ulcerative proctitis is an important and increasingly common subcategory of ulcerative colitis (UC) in which inflammation is limited to the rectum. Historically, oral aminosalicylates have been the mainstay of acute and maintenance therapy. A growing body of data, however, indicates that topical aminosalicylates are effective first line agents in ulcerative proctitis and distal UC. Topical aminosalicylates act more effectively and rapidly to induce and maintain remission compared with their oral counterparts or topical steroids. Rarely ulcerative proctitis is refractory to topical therapy and in these instances systemic corticosteroids, antibiotics, immunomodulators, or surgery is required. This review highlights the pathogenesis, diagnosis, and treatment of ulcerative proctitis.

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Aliment Pharmacol Ther. 2004 Oct;20 Suppl 4:97-101.
The long-term management of ulcerative colitis.
Hanauer SB.
Section of Gastroenterology, University of Chicago, Chicago, IL, USA.

Summary After the induction of remission, the second priority of therapy for ulcerative colitis is sustained clinical remission, defined as the absence of inflammatory symptoms (diarrhoea, bleeding, rectal urgency) and the maintenance of an intact mucosa, with the absence of ulcers, friability or significant granularity at endoscopy. The 'optimal' maintenance strategy will depend on the therapy needed to induce remission. Thus, the transition from induction to maintenance therapy will be determined by the intensity of acute therapy necessary to induce remission and the duration of therapy required to complete the resolution of clinical symptoms. There are few controlled clinical trials pertaining to maintenance after each induction regimen. However, experience dictates that aminosalicylates are efficacious after aminosalicylate-induced remissions, that steroids should be tapered according to the time required to induce remission, that patients requiring ciclosporin will benefit from the addition of long-term immunomodulation with azathioprine or mercaptopurine, and that many patients with distal colitis who require topical mesalazine (mesalamine) will continue to need topical therapy to maintain remission, albeit at reduced frequency. The expectations for maintenance therapy require patient adherence to the prescribed treatment regimen. Patients require education with regard to the long-term goals of maintenance therapy (e.g. prevention of relapse, reduction of long-term complications of disease activity or risks of acute therapy with steroids), and should be warned against the use of nonsteroidal anti-inflammatory drugs and cautioned about the cessation of smoking, when applicable, due to potential risks of relapse or chronic activity.

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Aliment Pharmacol Ther. 2004 Oct;20 Suppl 4:88-92.
The management of mild to severe acute ulcerative colitis.
Travis SP.
John Radcliffe Hospital and Linacre College, Oxford, UK.

Summary The goals for the management of acute ulcerative colitis are the objective evaluation of disease activity, induction of remission, prevention of relapse and treatment of complications. Clinical practice should be guided by simple activity indices, as it is easy to underestimate severity. For the induction of remission, topical treatment with mesalazine (mesalamine) is appropriate initial therapy for distal disease but, if symptoms persist for over a fortnight, decisive treatment is usually appreciated by the patient. For mild to moderate disease, corticosteroids have been the mainstay in Europe, although high-dose aminosalicylates (such as Pentasa, 4 g orally daily and 1 g rectally) are an alternative for symptoms not interfering with daily activity. Novel therapeutic approaches in ulcerative colitis have lagged behind those used for Crohn's disease, but several (epidermal growth factor, RDP 58, basiliximab, leucocytapheresis) are on the horizon. Severe colitis, defined as a bloody stool frequency of more than six per day with any one of tachycardia (pulse > 90 beats/min), temperature (> 37.8 degrees C), anaemia (haemoglobin < 10.5 g/dL) or raised erythrocyte sedimentation rate (> 30 mm/h), is an indication for intensive intravenous treatment. National UK figures indicate that 30% of ulcerative colitis cases progress to colectomy, and objective criteria for predicting the need for colectomy have been validated. The timing of colectomy is the most important decision that a physician is called upon to make, in conjunction with the patient and surgical colleagues. For the maintenance of remission, aminosalicylates continue to be first-line therapy, although the choice of 5-aminosalicylate appears to be influenced as much by geography as by theoretical considerations. Steroids have no place in the maintenance of remission. Indications for azathioprine include patients after a severe relapse of ulcerative colitis, those with early relapse after steroids (dose of < 15 mg/day, or within 6 weeks of stopping) and those needing a second course of steroids within a year. Therapeutic decisions should have a strategy, aimed at navigating the patient around relapses and through to sustained remission. Good management depends on clinical skills, compassion and care of the individual, in addition to pharmaceuticals.

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Hepatogastroenterology. 2004 Sep-Oct;51(59):1345-9.
Controlled, open, randomized multicenter trial comparing the effects of treatment on quality of life, safety and efficacy of budesonide foam and betamethasone enemas in patients with active distal ulcerative colitis.
Hammond A, Andus T, Gierend M, Ecker KW, Scholmerich J, Herfarth H; German Budesonide Foam Study Group.
Department of Internal Medicine I, University of Regensburg, Regensburg, Germany.

BACKGROUND/AIMS: There is evidence of a higher quality of life with foams as compared with enemas. The purpose of this study was to assess the effect of treatment with budesonide foam or betamethasone enema on the quality of life and the clinical outcome in patients with distal ulcerative colitis. METHODOLOGY: In an open multicenter trial, patients with active distal ulcerative colitis were randomized to receive 2 mg/50 mL budesonide foam or 5 mg/100 mL betamethasone enema. Primary outcome variable was the change in the mean Life Quality Index. Therapeutic efficacy was determined by clinical activity, endoscopical and histological indices. RESULTS: 38 patients were included in the study. The decrease of the mean Life Quality Index was more pronounced in the budesonide group. No significant difference in the efficacy of treatment was observed for both groups. Betamethasone suppressed the plasma cortisol level in the majority of the patients (87%) compared to only 22% of the patients receiving budesonide. CONCLUSIONS: The quality of life is not significantly different in patients during treatment with budesonide foam or betamethasone enema for active distal ulcerative colitis. However, while having comparable clinical efficacy budesonide foam has less effect on the plasma cortisol level thus potentially minimizing steroid side effects.

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Postgrad Med J. 2004 Sep;80(947):516-26.
Probiotics and human health: a clinical perspective.
Gill HS, Guarner F.
Primary Industries Research Victoria, Department of Primary Industries, 600 Sneydes Road, Werribee, Victoria, Australia. harsharn.gill@dpi.vic.gov.au

There is unequivocal evidence that administration of probiotics could be effective in the treatment of acute infectious diarrhoea in children and the prevention of antibiotic associated diarrhoea and nosocomial/community acquired diarrhoea. Encouraging evidence is also emerging for the effectiveness of probiotics in the prevention and management of pouchitis and paediatric atopic diseases, and the prevention of postoperative infections. There is also strong evidence that certain probiotic strains are able to enhance immune function, especially in subjects with less than adequate immune function such as the elderly. Efficacy of probiotics in the prevention of traveller's diarrhoea, sepsis associated with severe acute pancreatitis, and cancers, the management of ulcerative colitis, and lowering of blood cholesterol remains unproven. In addition to firm evidence of efficacy (for a range of conditions), major gaps exist in our knowledge regarding the mechanisms by which probiotics modulate various physiological functions and the optimum dose, frequency, and duration of treatment for different probiotic strains.

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AORN J. 2004 Aug;80(2):243-58, 261-2; quiz 263-6.
Ulcerative colitis—diagnosis and surgical treatment.
Stein P.
Colon and Rectal Surgery Department, University of Minnesota Physicians, Minneapolis, USA.

ULCERATIVE COLITIS is a serious illness affecting the colon. Extracolonic manifestations include sclerosing cholangitis, arthritis, eye diseases, ankylosing spondylitis, and sacroiliitis. Ulcerative colitis may increase a patient's risk of cancer, depending on the duration and extent of the disease. SURGERY is the only definitive way to remove the disease in its entirety. It may be possible for patients who do not wish to have a permanent stoma to undergo a restorative proctocolectomy with ileal pouch-anal anastomosis. NORMAL BOWEL PHYSIOLOGY, pathophysiology of ulcerative colitis, medical and surgical treatments, and postoperative complications are discussed.

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Pediatr Surg Int. 2004 Aug 19 [Epub ahead of print]
Surgery for ulcerative colitis in pediatric patients: functional results of 10-year follow-up with straight endorectal pull-through.
Ceriati E, Deganello F, De Peppo F, Ciprandi G, Silveri M, Marchetti P, Rava L, Rivosecchi M.
Department of Paediatric Surgery, Paediatric Hospital "Bambino Gesu", Via Cassia, 569-00189, Rome, Italy.

Children and adolescents affected by ulcerative colitis (UC) frequently require colectomy because of refractory or chronic symptoms. The aim of this paper is to present our experience and 10-year follow-up results of 28 patients who underwent endorectal pull-through (ERPT) as surgical treatment for UC, with special regard to surgical complications, stooling patterns (frequency of defecation, stool consistency, urgency period), fecal incontinence, and quality of life. A retrospective chart review of these patients was performed to evaluate age at colectomy, indication for surgical treatment, operative procedures, technical details, and early or late complications. Frequency of defecation was less than twice per day in two patients, between three and five times per day in nine patients, and more than six times per day in 10 patients. Stool consistency was normal in 14 patients, loose in five, and liquid in only two cases. Urgency period was normal (minutes) in 14 patients, short (seconds) in four, and absent in three. Ten patients (47%) have perfect or good fecal continence, whereas 11 (52%) patients present moderate to total incontinence. The self-reported emotional health was good in most of the patients. A large number are progressing well at school and are coping with their operations. Studies of quality of life in UC patients who underwent surgical treatment in childhood or adolescence, comparing as well the results according to the surgical technique adopted, must be encouraged.

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Zhonghua Wai Ke Za Zhi. 2004 Jul 21;42(14):861-3.
[The prognosis of the total proctocolectomy and ileal-pouch anal anastomosis]
[Article in Chinese]
Lin JJ, Song ZF, Xu JH.
The Department of Anus, Rectum & Colon Surgery, the First Affiliated Hospital, Zhejiang University, Hangzhou 310003, China.

OBJECTIVE: To evaluate the prognosis of the total proctocolectomy and ileal-pouch anal anastomosis (IPAA) for ulcerative colitis (UC) and familial adenomatous polyposis (FAP). METHODS: Sixty-one patients with ulcer colitis or familial adenomatous polyposis were performed total proctocolectomy and ilealpouch-anal anastomosis during 1985 to 2002. There are S type pouch 25 cases, S-J type pouch 13 cases, J type pouch 17 cases and W type pouch 6 cases. The complication and function after the IPAA were also discussed. RESULTS: No patient died after operation. The total morbidity is 16% (10/61), the morbidity of group UC (6/25) is higher than FAP's (4/34). The W type pouch's morbidity is higher than other three types', the operation with stapled technique is associated with fewer complication than hand-sewn IPAA (2/20 vs 8/41), however, there is also no significant difference between them. The number of stools per 24 hours is 4.2, the percent of the normal continence of daytime and nighttime is 84% (43/51) and 75% (38/51) respectively. There's only about 6% (3/51) patient with fecal incontinence. The most patients are satisfied with IPAA. CONCLUSION: The proctocolectomy ileal pouch-anal anastomosis for FAP and UC has few complication with accepted frequence and preserve a good anal function, it is an ideal alternative approach.

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Scand J Gastroenterol. 2004 Feb;39(2):154-7.
Long-term intermittent treatment with low-dose 5-aminosalicylic enemas is efficacious for remission maintenance in ulcerative colitis.
Piodi LP, Ulivieri FM, Cermesoni L, Cesana BM.
U.O. di Gastroenterologia, Servizio di Medicina Nucleare, Milan, Italy.

BACKGROUND: The standard remission maintenance treatment for ulcerative colitis (UC) is 5-amino-salicylic acid (5-ASA), given orally and topically and in different doses, with various frequencies and duration of administration. Both the efficacy of long-term intermittent therapy with low-dose 5-ASA enemas in preventing UC relapses and its economic implications were evaluated. METHODS: In accordance with a prospective case control study, 42 adult UC outpatients (29 M and 13 F) were treated with 5-ASA tablets (1.6 g/day) and 5-ASA enemas (2 g/50 mL) twice weekly, and 42 concurrent UC outpatients, matched for sex, age, extension and duration of disease, received only the oral therapy; the median treatment period was 6 years. RESULTS: There was a significant reduction in the number (42%: P = 0.034) and incidence of relapses (43%: P = 0.022) in the patients receiving combined oral + topical 5-ASA, who also had a significantly higher cumulative probability of not experiencing a first relapse (P = 0.001). There were no dropouts or side effects. Local therapy increased drug costs, but decreased the costs of relapses by 48% and completely precluded hospitalization costs. CONCLUSIONS: The scheduled oral + topical 5-ASA treatment, at the lowest cumulative topical dosage tested over the longest known observation period, is efficacious in improving clinical outcome and decreasing overall costs in UC patients.

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Expert Opin Pharmacother. 2004 Feb;5(2):329-34.
Drug treatment of ulcerative colitis: unfractionated heparin, low molecular weight heparins and beyond.
Malhotra S, Bhasin D, Shafiq N, Pandhi P.
Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh, India. samirmalhotra345@yahoo.com

Ulcerative colitis (UC) is characterised by chronic inflammation of the colon of unknown aetiology. Medical treatment of UC is complex and sometimes unsatisfactory. A total of 75% of patients experience relapses during the course of their illness and 20 - 25% require a colostomy. Recent years have witnessed a paradigm shift in the way UC is medically treated. The focus has now shifted to newer forms of therapy along with the older established drugs such as sulfasalazine and corticosteroids. Unfractionated heparin and low molecular weight heparins have been tested for their efficacy in patients with UC with conflicting results in various studies. Immunosuppressive and immune-based therapies, drugs modifying biological responses, prebiotics, probiotics, symbiotics, melatonin and topical butyrate have all been tested with variable success. The current review delineates the recent therapeutic alternatives in UC with main emphasis on heparins.

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Gut. 2003 Jul;52(7):998-1002.
Infliximab in moderately severe glucocorticoid resistant ulcerative colitis: a randomised controlled trial.
Probert CS, Hearing SD, Schreiber S, Kuhbacher T, Ghosh S, Arnott ID, Forbes A.
University Division of Medicine, Bristol Royal Infirmary, Marlborough Street, Bristol BS2 8HW, UK. c.s.j.probert@bristol.ac.uk

BACKGROUND: Tumour necrosis factor production is increased in the mucosa of patients with active ulcerative colitis. The benefits of infliximab in Crohn's disease are established. We investigated its efficacy in ulcerative colitis. METHODS: We conducted a randomised placebo controlled trial of infliximab (5 mg/kg) in the treatment of glucocorticoid resistant ulcerative colitis. Infusions were given at weeks 0 and 2. Disease activity and quality of life were recorded over eight weeks of follow up. Remission was defined as an ulcerative colitis symptom score (UCSS) of < or =2 and/or Baron score of 0 at week 6. Patients not in remission were offered open label infliximab 10 mg/kg and reviewed two weeks later. RESULTS: After two weeks, there was no statistically significant difference between the infliximab and placebo groups in the proportion of patients with a Baron score of 0 (13% (3/23) v 5% (1/19) (95% confidence interval (CI) -9% to 24%); p=0.74). After six weeks, remission (UCSS < or =2) rates were 39% (9/23) versus 30% (6/20) (95% CI -19 to 34%; p=0.76). The median improvement in UCSS was 3 for the infliximab group and 2.5 for the placebo group (p=0.82, Mann-Whitney U test). A Baron score of 0 was likely in either group (26% (6/23) v 30% (6/20) (95% CI -30% to 23%); p=0.96). Improvement in the IBDQ and EuroQol was not significantly different between the groups (p=0.22 and 0.3, respectively, Mann-Whitney U test). Twenty eligible patients were given open labelled infusions. Remission was achieved in 3/11 (27%) patients initially treated with infliximab and in 1/9 (11%) patients treated with placebo. CONCLUSION: These data do not support the use of infliximab in the management of moderately active glucocorticoid resistant ulcerative colitis.

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Aliment Pharmacol Ther. 2003 Jun 1;17(11):1355-64.
Repifermin (keratinocyte growth factor-2) for the treatment of active ulcerative colitis: a randomized, double-blind, placebo-controlled, dose-escalation trial.
Sandborn WJ, Sands BE, Wolf DC, Valentine JF, Safdi M, Katz S, Isaacs KL, Wruble LD, Katz J, Present DH, Loftus EV Jr, Graeme-Cook F, Odenheimer DJ, Hanauer SB.
Mayo Clinic, Rochester, MN, USA. sandborn.william@mayo.edu

BACKGROUND: Repifermin (keratinocyte growth factor-2) has been shown to reduce inflammation in animal models of colitis. AIM: To evaluate repifermin for the treatment of active ulcerative colitis. METHODS: Eighty-eight patients with active ulcerative colitis were enrolled in a 6-week, double-blind trial. Patients were randomized to receive treatment for five consecutive days with intravenous repifermin at a dose of 1, 5, 10, 25 or 50 microg/kg, or placebo. The primary objective of the study was to evaluate the safety of repifermin. The primary efficacy outcome was clinical remission at week 4, defined as a score of zero on the endoscopic appearance and stool blood components of the Mayo score and a score of zero or unity on the stool frequency and physician's global assessment components. RESULTS: At week 4, the rates of clinical remission in the 1, 5, 10, 25 and 50 microg/kg repifermin groups were 19%, 9%, 0%, 0% and 0%, respectively, and 11% for the placebo group (P = 0.32 for repifermin vs. placebo). The frequencies of commonly occurring adverse events and severe adverse events were similar in both groups. CONCLUSIONS: Intravenous repifermin at a dose of 1-50 microg/kg was very well tolerated, but there was no evidence that repifermin was effective for the treatment of active ulcerative colitis at these doses. An additional study to determine the efficacy of repifermin at doses of > 50 microg/kg or for a longer treatment duration may be warranted, as the maximally tolerated dose was not reached in the present study.

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Ther Umsch. 2003 Mar;60(3):145-50.
[Management of ulcerative colitis]
[Article in German]
Rammert Ch, Kullak-Ublick GA.
Abteilung Gastroenterologie und Hepatologie, Departement Innere Medizin, Universitatsspital, Zurich.

Ulcerative colitis is a chronic inflammatory bowel disease. The disease is diagnosed on the basis of clinical parameters and endoscopic-histologic evaluation. 5-aminosalicylic acid (5-ASA, mesalamine) represents the first-line treatment of choice. For patients with distal and left-sided disease the use of rectal preparations is effective. Most patients respond to 5-ASA suppositories or to topic steroids such as budesonide suppositories or hydrocortisone foam. For patients with extended disease, oral medications are mandatory. In case of low- to moderate-grade inflammation, 5-ASA preparations should be implemented. In the case of severe disease treatment with steroids is required. Following induction of remission, prophylactic treatment with 5-ASA (1.5 g/d) should be maintained. For patients with frequent or severe relapses, immunosuppressive therapy with azathioprine or 6-mercaptopurine is indicated. In case of a fulminant course of disease, treatment with intravenous cyclosporine is required in patients who have not responded to high-dose intravenous steroids. When all conservative treatment options fail, proctocolectomy with construction of an ileoanal pouch should be performed. New therapeutic strategies such as infliximab and interferons are being evaluated in clinical trials. The long-term complications of ulcerative colitis include steroid-induced osteoporosis and anemia and should be treated adequately. Finally, the risk for development of colorectal cancer increases steadily with disease duration and dysplasia should be screened for by endoscopic surveillance programs.

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Rev Gastroenterol Disord. 2003 Spring;3(2):81-92.
The state of the art in the management of inflammatory bowel disease.
Hanauer SB, Present DH.
Section of Gastroenterology and Nutrition, University of Chicago, Pritzker School of Medicine, Chicago, IL, USA.

Ulcerative colitis (UC) and Crohn's disease (CD), collectively known as inflammatory bowel disease (IBD), afflict an estimated one million Americans and produce symptoms that impair quality of life and ability to function. Progress in IBD management strategies has led to optimized approaches for achieving the two primary clinical goals of therapy: induction and maintenance of remission. Although surgery is indicated to treat refractory disease or specific complications, pharmacotherapy is the cornerstone of IBD management. The efficacy of aminosalicylates for induction of remission in mild to moderate UC and CD is well established, as is their role for maintenance of remission in UC. The sulfa-free mesalamine formulation offers an adverse effect profile similar to that of placebo, enabling the administration of higher, more effective doses. Although corticosteroids provide potent anti-inflammatory effects, their benefits are countermanded by the risk of intolerable and serious adverse effects, and they are ineffective for maintenance therapy. Other agents effective in inducing or maintaining remission are azathioprine, 6-mercaptopurine, infliximab, cyclosporine, methotrexate, and antibiotics. Ongoing clinical trials of experimental therapies will generate new tools for IBD treatment. Currently, a broad range of options allows physicians to tailor treatment to each patient's needs and preferences. Such considerations are essential for maximizing adherence to therapy.

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Dig Dis Sci. 2003 May;48(5):1002-5.
Outpatient treatment of moderately severe active ulcerative colitis with pulsed steroid therapy and conventional steroid therapy.
Oshitani N, Kamata N, Ooiso R, Kawashima D, Inagawa M, Sogawa M, Iimuro M, Jinno Y, Watanabe K, Higuchi K, Matsumoto T, Arakawa T.
Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.

Pulsed steroid therapy may induce rapid remission in patients with moderately severe ulcerative colitis in outpatient clinics. A total of 19 patients with moderately severe active ulcerative colitis who refused hospitalization were treated between October 1999 and September 2001 in the outpatient clinic. Patients were treated with either conventional oral steroid therapy or intravenous pulsed steroid therapy followed by conventional oral steroid therapy. Eight patients received conventional steroid therapy and 11 patients received pulsed steroid therapy followed by conventional steroid therapy. The efficacies of the two types of steroid therapy were equal, but patients with active colitis responded more quickly to pulsed steroid therapy than to conventional steroid therapy. No serious adverse effects were observed. Moderately severe colitis can be safely treated with either conventional or pulsed steroid therapy in the outpatient clinic, but pulsed steroid therapy may induce clinical remission more quickly than conventional steroid therapy.

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Inflamm Bowel Dis. 2003 Mar;9(2):116-21.
Increasing fecal butyrate in ulcerative colitis patients by diet: controlled pilot study.
Hallert C, Bjorck I, Nyman M, Pousette A, Granno C, Svensson H.
Department of Internal Medicine, Vrinnevi Hospital, Norrkoping, Sweden. Claes.Hallert@lio.se

Topical butyrate has been shown to be effective in the treatment of ulcerative colitis (UC). Butyrate is derived from colonic fermentation of dietary fiber, and our aim was to study whether UC patients could safely increase the fecal butyrate level by dietary means. We enrolled 22 patients with quiescent UC (mean age, 44 years; 45% women; median time from last relapse, 1 year) in a controlled pilot trial lasting 3 months. The patients were instructed to add 60 g oat bran (corresponding to 20 g dietary fiber) to the daily diet, mainly as bread slices. Fecal short-chain fatty acids (SCFAs) including butyrate, disease activity, and gastrointestinal symptoms were recorded every 4 weeks. During the oat bran intervention the fecal butyrate concentration increased by 36% at 4 weeks (from 11 +/- 2 (mean +/- SEM) to 15 +/- 2 micromol/g feces) (p < 0.01). The mean butyrate concentration over the entire test period was 14 +/- 1 micromol/g feces (p < 0.05). Remaining fecal SCFA levels were unchanged. No patient showed signs of colitis relapse. Unlike controls, the patients showed no increase in gastrointestinal complaints during the trial. Yet patients reporting abdominal pain and reflux complaints at entry showed significant improvement at 12 weeks that returned to baseline 3 months later. This pilot study shows that patients with quiescent UC can safely take a diet rich in oat bran specifically to increase the fecal butyrate level. This may have clinical implications and warrants studies of the long-term benefits of using oat bran in the maintenance therapy in UC.

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Khirurgiia (Mosk). 2003;(4):24-6.
[Surgical policy in nonspecific ulcerative colitis]
[Article in Russian]
Navruzov SN, Iusupbekov AA, Khudaiarov AA, Rustamov AE, Sapaev DA, Turaev GKh, Rakfmonov ST.

Results of surgical treatment of 101 patients with nonspecific ulcerative colitis are analyzed. In 73 (72.3%) patients variants of abdomino-anal coloproctectomy were performed, 22 of them underwent total coloproctectomy with terminal ileo- or colostoma creation. In 21 (20.8%) patients who had no inflammatory-ulcerative process in the rectum resection of the affected part of the colon with ileo--or colorectal anastomosis was performed, in 8 cases suturing device AKA-2 was used. In 7 (6.9%) patients who had undergone total coloproctectomy S-type intestinal reservoir and reservoir-anal anastomosis were created. Rate of postoperative complications was 16.8%, lethality--3.0%. 6 months after creation of reservoir-anal anastomosis nearly complete recovery of anal sphincter function was seen that permits to regard this surgery as a method of choice in the treatment of patients with total ulcerative colitis.

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Gene Ther. 2003 May;10(10):854-60.
Gene transfer approaches for the treatment of inflammatory bowel disease.
Wirtz S, Neurath MF.
Laboratory of Immunology, I. Medical Clinic, University of Mainz, Germany.

The pathogenesis of Crohn's disease and ulcerative colitis, the two major forms of inflammatory bowel disease, involves a complex interplay between certain genetic, environmental and immunological factors. Considerable research progress in the last decade defined key inflammatory pathways in the inflamed gut and identified new potential therapeutic targets. Since the current medical treatment with corticosteroids and anti-inflammatory drugs is often associated with undesired side effects and cannot completely cure IBD, these current advances in our understanding of intestinal pathology may now allow the development of new biologic treatment strategies including gene therapy. In this review, we will give a brief overview of potential gene therapy target molecules related to chronic intestinal inflammation. Furthermore, we summarize the results of recent preclinical studies for intestinal gene transfer and discuss future perspectives.

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Nutr Hosp. 2003 Mar-Apr;18(2):57-64.
Pharmacological nutrition in inflammatory bowel diseases.
Campos FG, Waitzberg DL, Teixeira MG, Mucerino DR, Kiss DR, Habr-Gama A.
Department of Gastroenterology, Colorectal Surgery Unit, Hospital das Clinicas, University of Sao Paulo Medical School, Sao Paulo, Brasil. fgcampos@osite.com.br

Inflammatory Bowel Diseases--ulcerative colitis and Crohn's disease--are chronic gastrointestinal inflammatory diseases of unknown etiology. Decreased oral intake, malabsorption, accelerated nutrient losses, increased requirements, and drug-nutrient interactions cause nutritional and functional deficiencies that require proper correction by nutritional therapy. The goals of the different forms of nutritional therapy are to correct nutritional disturbances and to modulate inflammatory response, thus influencing disease activity. Nutritional intervention may improve outcome in certain individuals; however, because of the costs and complications of such therapy, careful selection is warranted. Total parenteral nutrition has been used to correct and prevent nutritional disturbances and to promote bowel rest during active disease, mainly in cases of digestive fistulae with a high output. Its use should be reserved for patients who cannot tolerate enteral nutrition. Enteral nutrition is effective in inducing clinical remission of disease in adults and promoting growth in children. Recent research has focused on the use of specific nutrients as primary treatment agents. Although some reports have indicated that glutamine, short-chain fatty acids, antioxidants and immunonutrition with omega-3 fatty acids are an important therapeutic alternative in the management of inflammatory bowel diseases, the beneficial reported effects have yet to be translated into the clinical practice. The real efficacy of these nutrients still need further evaluation through prospective and randomized trials.

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J Gastroenterol. 2003 Mar;38 Suppl 15:51-4.
Leukocytapheresis for treatment of IBD.
Kohgo Y, Ashida T, Maemoto A, Ayabe T.
Third Department of Internal Medicine, Asahikawa Medical College, 1-1 Midorigaoka, Higashi, Asahikawa 078-8510, Japan.

The recent development of effective and safe devices to remove leukocytes selectively from circulating blood has facilitated the application of leukocytapheresis for the treatment of inflammatory bowel disease (IBD). Successful results of preliminary trials of leukocytapheresis for IBD led to several nationwide multicenter clinical trials in Japan. As a result, five or six consecutive leukocytaphereses, which were undergone weekly, improved both symptoms and endoscopic findings in approximately 60%-80% of patients with ulcerative colitis (UC). In Japan, leukocytapheresis is now considered to be one of the standard treatments for UC patients with refractory disease to avoid surgery. Here, the current status of indications and mechanisms of action on UC are analyzed by reviewing the results of Japanese multicicenter trials, and the possible application for Crohn's disease is also discussed.

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Curr Issues Intest Microbiol. 2003 Mar;4(1):9-20.
Intestinal bacteria and ulcerative colitis.
Cummings JH, Macfarlane GT, Macfarlane S.
Department of Molecular and Cellular Pathology, University of Dundee, Ninewells Hospital Medical School, Dundee DD1 9SY, UK. h.cowper@dundee.ac.uk

Convincing evidence from both animal models and the study of patients with ulcerative colitis (UC) implicates the intestinal microflora in the initiation and maintenance of the inflammatory processes in this condition. Despite this, no specific pathogen has been identified as causal and the disease is widely believed to occur as the result of a genetically determined, but abnormal immune response to commensal bacteria. When compared with healthy people, UC patients have increased levels of mucosal IgG directed against the normal microflora. Studies of mucosal bacterial populations in UC indicate that there may be increased numbers of organisms, but reduced counts of "protective" bacteria such as lactobacilli and bifidobacteria. In animal models of colitis, antibiotics, particularly metronidazole, clindamycin, ciprofloxacin and the combination of vancomycin/impinemem protect against UC, especially if given before the onset of inflammation. These antibiotics target anaerobes and some Gram-positive organisms such as enterococci. However, antibiotic use in more than a dozen randomised control trials has been very disappointing, probably because we do not know which species to target, when to give the antibiotics, for how long and in what combinations. Surprisingly, therefore, there is a consistent benefit in the small number of studies reported of probiotics to manage UC and pouchitis. There is scope for more work in this area focussing on the mucosal microflora, its interactions with the gut immune system, its metabolic properties and the potential ways of modifying it.

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Eksp Klin Gastroenterol. 2003;(1):58-9, 183.
[Comparative efficacy of mezakol and sulfasalazine in treating chronic relapsing ulcerative colitis]
[Article in Russian]
Rogozina VA, Rumiantsev VG.
Central Scientific Research Institute of Gastroenterology, Moscow.

This research testifies to the fact that it is more preferable to use mesacol than sulfasalazine in treatment of common forms of ulcerative colitis of light and average severity. Mesacol acts faster in arresting inflammations in proximal parts of the larger intestine. One can assume that the pH-dependent release of 5-aminosalicylic acid in these forms of the disease suffers less than the destruction of the diazo link by the anaerobic microflora, due to which a higher concentration of the preparation is formed in the large intestine. Another alternative explanation can be the dose-dependent effect. Thus, 2.4. g of mesacol correspond to 6 g of sulfasalazine. The dose of sulfasalazine was smaller in our study. Mesacol had no advantages over sulfasalazine in treatment of distal colitis, which can and must be treated with rectal introduction of corticosteroids and 5-aminosalicylic acid preparations. Thus, mesacol must be reserved for treatment of patients with common ulcerative colitis of light and average severity in case of intolerance to sulfasalazine or impossibility to increase the preparation dose over 4 g/day. Its efficiency and price make the preparation available for most patients and patient care institutions.

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Am J Surg. 2003 Apr;185(4):333-8.
A longitudinal study of long-term quality of life after ileal pouch-anal anastomosis.
Weinryb RM, Liljeqvist L, Poppen B, Gustavsson JP.
Department of Clinical Neuroscience, Psychotherapy Section, Karolinska Institutet, Bjorngardsgatan 25, SE-118 52 Stockholm, Sweden. robert.weinryb@cns.ki.se

BACKGROUND: There is a lack of longitudinal long-term studies of quality of life (QOL) after surgery with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis, where cohorts of patients are used as their own controls. METHODS: Forty ulcerative colitis patients who had undergone IPAA were prospectively assessed while they had a temporary ileostomy, and at a median of 18 months and 7 years after ileostomy closure. QOL was measured with the Psychosocial Adjustment to Illness Scale and the Well-Being Profile. RESULTS: QOL was good at all three time points and, with some exceptions, did not change significantly between the assessments. There was a high degree of stability in the patients' evaluation of their QOL over time. CONCLUSIONS: QOL was already good when the patients had a temporary ileostomy and generally did neither improve nor deteriorate during 7 years after ileostomy closure. QOL was also quite stable in terms of individual differences.

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Hepatogastroenterology. 2003 Jan-Feb;50(49):91-4.
Efficacy of cyclosporin with corticotropin for refractory ulcerative colitis.
Okamura S, Aoki H, Ohashi S, Urano F, Shimodaira M, Kanamori S, Ishikawa H, Segawa K.
Division of Gastroenterology, Department of Internal Medicine Toyohashi, Municipal Hospital, Aotake-cho, Toyohashi, Aichi, 441-8570, Japan. s_okamura415@yahoo.co.jp

BACKGROUND/AIMS: Cyclosporin was reported to be useful for steroid-resistant severe ulcerative colitis in the short term, but limited data are available on the long-term follow-up of such patients. Our aim was to assess the short- and long-term efficacy of combination therapy with cyclosporin and corticotropin for steroid-resistant ulcerative colitis. METHODOLOGY: Twenty-one patients with ulcerative colitis who did not respond to corticosteroid therapy, were treated with corticotropin, and 9 patients (43%) of them achieved complete remission. Twelve patients (57%) who did not achieve complete remission by corticotropin alone were given combination therapy with cyclosporin and corticotropin. RESULTS: In 12 patients who received combined therapy with cyclosporin and corticotropin, clinical severity was distinctly improved in 11 patients (92%) by combination therapy within 2 weeks and 7 patients (58.3%) entered into complete remission with salicylazosulfapyridine or 5-aminosalicylic acid alone. Two patients (16.7%) demonstrated insufficient effect and continue to receive a lower dosage of cyclosporin or corticosteroid. Three patients (25%) failed to respond to the combination therapy and required colectomy. Three of 7 patients who entered into remission relapsed 0.5, 5 and 5.5 months (average: 3.7 months) after cyclosporin withdrawal, but the clinical severity at the time of relapse was milder than that at the beginning of the treatment, namely, moderate in 2 patients, and mild in 1 patient. There were no significant adverse effects in our series. CONCLUSIONS: We demonstrated that oral cyclosporin in combination with corticotropin was highly effective for ulcerative colitis refractory to corticosteroid or corticotropin therapy and severe relapse was uncommon during several years of follow-up.

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Best Pract Res Clin Gastroenterol. 2003 Feb;17(1):89-103.
Management of acute severe colitis.
Dunckley P, Jewell D.
Gastroenterology Unit, John Radcliffe Hospital, Oxford, United Kingdom.

Early identification of patients with acute severe colitis is essential so that prompt treatment can be instigated. Corticosteroids have remained the mainstay of treatment since 1955. The introduction of ciclosporin into the pharmacological armamentarium has reduced early colectomy rates but even with modern medical management up to 30% of patients will still undergo colectomy on the same admission. The overall mortality is now less than 1% in specialist centres compared to 30% in the pre-steroid era. The future promises further advances in treatment through medications that are targeted directly at the underlying inflammatory process.

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Eur J Gastroenterol Hepatol. 2003 Mar;15(3):239-44.
Ciclosporin and refractory colitis.
Hawthorne AB.
Department of Medicine, University Hospital of Wales, Heath Park, Cardiff, UK. Barney.Hawthorne@UHW-TR.wales.nhs.uk

Intravenous ciclosporin 4 mg/kg daily is rapidly effective as a salvage therapy for patients with refractory colitis, who would otherwise face colectomy, but its use is controversial because of risk of toxicity, and long-term failure rate. Opportunistic infections remain a serious concern, with a number of reports of death related to ciclosporin. Renal and neurotoxicity are also well-recognized. The drug should not be continued for more than 3-6 months and its main role is as a bridge to azathioprine or 6-mercaptopurine. Risks of toxicity can be reduced by using lower doses (2 mg/kg/day intravenously), by oral microemulsion ciclosporin, or by monotherapy without corticosteroids. Preliminary evidence shows good response rates, but further studies are needed to confirm optimal use of this potent, but hazardous, therapy.

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J Laparoendosc Adv Surg Tech A. 2002 Dec;12(6):403-6.
Laparoscopic restorative proctocolectomy for patients with ulcerative colitis.
Hasegawa H, Watanabe M, Baba H, Nishibori H, Kitajima M.
Department of Surgery, Keio University School of Medicine, Tokyo, Japan. hasegawa@sc.itc.keio.ac.jp

BACKGROUND: Significant concern continues about the feasibility of laparoscopic restorative proctocolectomy (RP) with an ileal J pouch anal anastomosis in the surgical treatment of patients with ulcerative colitis (UC). The aim of this study was to clarify the feasibility of laparoscopic RP at a single institution where the surgical routine of laparoscopic colorectal surgery has already been established. PATIENTS AND METHODS: Between July 1994 and December 2001, 18 patients with UC underwent laparoscopic RP. The median age was 30 (range, 18-51) years, and the median follow-up was 20 (range, 5-89) months. Five trocars were placed. After the entire colon and rectum were mobilized and the vessels were divided intracorporeally, the rectum was divided with use of a laparoscopic linear stapler. A pouch anal anastomosis was fashioned with use of a double stapling technique. A diverting loop ileostomy was fashioned. RESULTS: There were no conversions to the open procedure. The median operative time and median blood loss were 360 (range, 290-500) minutes and 105 (range, 10-586) mL, respectively. Six postoperative complications occurred (wound sepsis, 2; bowel obstruction, 1; anastomotic stricture, 2; pouchitis, 1). In one patient, a bowel obstruction developed 3 months after the operation, which was managed conservatively. The median length of the hospital stay was 9 (range, 7-21) days. CONCLUSIONS: The laparoscopic RP is safe and feasible in selected patients with UC. New laparoscopic instrumentation, such as a linear stapler, and a more reliable laparoscopic coagulating and dividing tool should be designed, which would make it possible to perform this procedure more frequently in the surgical treatment of UC.

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Rev Invest Clin. 2002 Sep-Oct;54(5):397-402.
[Quality of life after ileo-anal anastomosis]
[Article in Spanish]
Takahashi T, Ponce de Leon S, Cardenas S, Remes JM, Garcia-Osogobio S, Camilo Barreto J, Zarate Diaz X.
Departamento de Cirugia, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico, D.F. takahashit@infosel.net.mx

BACKGROUND: The ileo-anal pouch is the surgical procedure of choice for patients with Ulcerative Colitis or Familial Adenomatous Polyposis, but has functional limitations such as a higher frequency of bowel movements, anal leakage, and sometimes the necessity of a protective anal pad. OBJECTIVE: To analyze the functional results and quality of life after the pelvic pouch. MATERIAL AND METHODS: This is a descriptive, prolective, and cross-sectional study that analyzes the clinical variables, functional results and self-reported quality of life of patients after an ileo-anal pouch. A correlation between postoperative clinical variables and quality of life was searched. RESULTS: Twenty-seven patients were included. Mean age was 36 years. Surgical indications for the ileo-anal pouch were Ulcerative Colitis in 17 (63%), Familial Adenomatous Polyposis in 9 (33%) and a colo-rectostomy stricture in 1 (4%). Mean number of bowel movements was 4 at day and 1 at night. Eighteen percent of patients referred anal leakage, 11% had pouchitis, and 11% small bowel obstruction. Most of the patients reported high scores in all evaluated quality of life scales. There was a correlation between lower scores of quality of life and a higher number of bowel movements. CONCLUSIONS: The majority of patients reported an adequate quality of life after the ileo-anal pouch; there was a correlation between lower scores of quality of life and a higher number of bowel movements.

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Curr Pharm Des. 2003;9(4):307-21.
Multicenter randomized controlled trial for the treatment of ulcerative colitis with a
leukocytapheresis column.
Sawada K, Muto T, Shimoyama T, Satomi M, Sawada T, Nagawa H, Hiwatashi N, Asakura H, Hibi T.
Dept of Gastroenterology, Hyogo College of Medicine, Nishinomiya, Tokyo, Japan. sawadako@hyo-med.ac.jp

The administration of steroids is not always effective for the treatment of ulcerative colitis (UC). Their long-term use often causes adverse effects which sometimes result in their stoppage and acute exacerbation. Therefore, an alternative treatment is necessary in order to decrease steroid dosage and avoid the clinical problems associated with steroids. Methods The effectiveness and adverse effects of a leukocytapheresis (LCAP) were investigated in a controlled multicenter trial with randomized assignment of 76 active-stage UC patients in two groups. In the LCAP group (39 patients), LCAP weekly for 5 weeks as an intensive therapy was added to the on-going drug therapy, while steroids were maintained but not increased, and then LCAP was gradually reduced to once every 4 weeks as a maintenance therapy. In the high dose prednisolone (h-PSL) group (37 patients), PSL was added or increased 30 approximately 40 mg/day for moderately severe and 60 approximately 80 mg/day for severe patients and then gradually tapered. Findings The LCAP group showed a significantly higher effectiveness (74% vs. 38%; p=0.005) and lower incidence of adverse effects (24% vs. 68%; p<0.001). The patients were able to continue the trial for a longer period in the LCAP group than the h-PSL group (p=0.012). Clinical activity and endoscopic indexes showed the LCAP group had better improvements than the h-PSL group. Interpretation The results of the trial show that LCAP permits a reduction in total PSL dosage and is more effective and safer than high-dose PSL administration for intensive therapy, and LCAP may maintain remission longer than PSL.

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J Am Coll Nutr. 2003 Feb;22(1):56-63.
Randomized controlled trial of the effect of bifidobacteria-fermented milk on ulcerative colitis.
Ishikawa H, Akedo I, Umesaki Y, Tanaka R, Imaoka A, Otani T.
Department of Cancer Epidemiology, Research Institute, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan. cancer@gol.com

BACKGROUND: Alterations of intestinal flora, such as reduction in the concentration of bifidobacteria and increase in that of Bacteroides species, are apparently associated with the severity of ulcerative colitis. OBJECTIVE: We conducted a randomised clinical trial of the use of a bifidobacteria-fermented milk (BFM) supplement as a dietary adjunct in the treatment of ulcerative colitis. METHODS: The subjects were randomly divided into two groups: a group with BFM supplementation (BFM group, 11 subjects) and a control group (control group, 10 subjects). The BFM group was given 100 mL/day of BFM for one year. Colonoscopies, general blood markers and examinations of intestinal flora including the analysis of fecal organic acids were performed at the commencement of the study and after one year. RESULTS: Exacerbation of symptoms was seen in 3 out of 11 subjects in the BFM group and in 9 out of 10 in the control group. Log rank statistic analysis of the cumulative exacerbation rates showed a significant reduction in exacerbations for the BFM group (p = 0.0184). The analysis of microflora and the organic acids in the feces showed a significant reduction in the relative proportion of B. vulgatus in Bacteroidaceae and butyrate concentration, respectively, after supplementation with BFM, in comparison with before. CONCLUSION: Supplementation with the BFM product was successful in maintaining remission and had possible preventive effects on the relapse of ulcerative colitis.

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Aliment Pharmacol Ther. 2003 Feb;17(3):409-14.
Patients with refractory Crohn's disease or ulcerative colitis respond to dehydroepiandrosterone:
a pilot study.
Andus T, Klebl F, Rogler G, Bregenzer N, Scholmerich J, Straub RH.
Department of Internal Medicine I, University of Regensburg, Regensburg, Germany. TAndus@kbc-intern.de

BACKGROUND: Dehydroepiandrosterone is a steroid hormone used as an 'over-the-counter' drug in the USA. Treatment with dehydroepiandrosterone was effective in randomized controlled trials in patients with systemic lupus erythematosus. Dehydroepiandrosterone sulphate concentrations are decreased in patients with inflammatory bowel disease. Dehydroepiandrosterone inhibits nuclear factor-kappaB and the secretion of interleukin-6 and interleukin-12 via the peroxisome proliferator-activated receptor alpha. AIM: A phase II pilot trial was started to evaluate the effect of dehydroepiandrosterone in active inflammatory bowel disease. METHODS: Twenty patients with chronic active inflammatory bowel disease [seven Crohn's disease (Crohn's disease activity index, 242 +/- 51; mean +/- s.d.); 13 ulcerative colitis (clinical activity index, 7.8 +/- 2.1)] took 200 mg dehydroepiandrosterone per day orally for 56 days. RESULTS: Six of the seven patients with Crohn's disease and eight of the 13 patients with ulcerative colitis responded to treatment, with a decrease in the Crohn's disease activity index of > 70 points and a decrease in the clinical activity index of > 4 points, respectively. Six Crohn's disease patients and six ulcerative colitis patients went into remission (Crohn's disease activity index < 150; clinical activity index <or= 4). No patient withdrew from the study because of side-effects. CONCLUSIONS: In a pilot study, dehydroepiandrosterone was effective and safe in patients with refractory Crohn's disease or ulcerative colitis. Adjustment of the dehydroepiandrosterone dosage may further improve the treatment success.

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Kongressbd Dtsch Ges Chir Kongr. 2002;119:67-72.
[Surgical approach in toxic colitis]
[Article in German]
Vestweber KH.
Klinikum Leverkusen, Dhunnberg 60, 51375 Leverkusen.

Toxic colitis is still a major diagnostic and therapeutic challenge. Mortality rates depend on the severity of the disease and range from 2% to 30%. Interdisciplinary approaches are necessary and structured therapeutic steps from conservative to operative treatment seem to be most effective. The surgical option for toxic colitis usually is subtotal colectomy with closure of the rectal stump or mucus fistula and ileostomy. This procedure allows the reconstructive operation later on. In selected cases and suitable situations a primary colectomy with ilealpouch are also possible depending on local and general effects.

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Rev Gastroenterol Mex. 2002 Jul-Sep;67(3):179-85.
[Surgical treatment of unspecific chronic ulcerative colitis. A 5-year experience.]
[Article in Spanish]
Martinez-Hernandez-Magro P, Villanueva-Saenz E, Alvarez-Tostado-Fernandez F, Gutierrez-Roa A.
Servicio de Cirugia de Colon y Recto, Hospital de Especialidades Dr. Bernardo Sepulveda Centro Medico Nacional Siglo XXI, IMSS. paulinomhm@hotmail.com

BACKGROUND: Treatment of ulcerative colitis depends on clinical stage of disease and have precise surgical indications. The aim of this work was to review surgical indications and present data related to our experience. MATERIAL AND METHODS: Retrospective, descriptive, and transversal study. We reviewed records of all patients who underwent a surgical procedure for ulcerative colitis at our service from March 1996 to March 2001. RESULTS: Twenty two patients, 13 males and nine females, ages range 21 to 72 years. Main indication for surgery was no response to medical treatment (50%). Surgical procedures was subtotal colectomy with ileostomy in one patient, intersphincteric proctocolectomy with ileostomy in four intersphincteric proctectomy with ileostomy in three ileorectalanastomosis in three proctocolectomy with ileoanal "J" pouch in six and proctectomy with ileoanal J pouch in five. We had the following complications: oral candidiasis; phlebitis; eventration; pouchitis, and anal fissure in one patient, respectively, pouch-skin fistula in two patients (9%), and retrograde ejaculation in one of these. Follow-up was for 5 years. CONCLUSIONS: Surgical indications for ulcerative colitis are precise. We recommend early surgical evaluation. Ileoanal pouch is now considered the gold standard for surgical procedure because it eliminates disease, neoplasm development, and permanent extra-colonic manifestations, and restores continence.

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Acta Gastroenterol Belg. 2002 Oct-Dec;65(4):196-9.
The role of aminosalicylates in the treatment of ulcerative colitis.
Van Assche G, Baert F, De Reuck M, De Vos M, De Wit O, Hoang P, Louis E, Mana F, Pelckmans P, Rutgeerts P, Van Gossum A, D'Haens G.
Department of Internal Medicine-Gastroenterology, UZ Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium.

Aminosalicylates (5-ASA, sulfasalazine and mesalazine) play a central role in the treatment of ulcerative colitis (UC). For acute treatment of mild to moderate flares and in maintenance treatment, their efficacy has been established. Since ulcerative colitis is limited to the distal colon in two thirds of the patients, topical therapy also plays an important role. In mild/moderate active disease 5-ASA 4 g/d is as effective as oral corticosteroids. Ulcerative proctitis is treated with 2 x 500 mg or 1 x 1 g suppositories and proctosigmoiditis with 1 to 4 g enemas. Oral 5-ASA is also safe in maintenance treatment and is generally well tolerated. The risk of colorectal tumours is increased in patients with longstanding ulcerative colitis and epidemiological evidence indicates that chronic 5-ASA treatment reduces this risk. However, at present there is insufficient evidence to maintain patients on life-long 5-ASA maintenance treatment for this indication.

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Am J Gastroenterol. 2002 Dec;97(12):3078-86.
Balsalazide is superior to mesalamine in the time to improvement of signs and symptoms of acute mild-to-moderate ulcerative colitis.
Pruitt R, Hanson J, Safdi M, Wruble L, Hardi R, Johanson J, Koval G, Riff D, Winston B, Cross A, Doty P, Johnson LK.
Vanderbilt University School of Medicine, Nashville Medical Research Institute, Nashville, Tennessee, USA.

OBJECTIVE: Balsalazide is a novel azo-bonded 5-aminosalicylic acid treatment for mild-to-moderate ulcerative colitis. The study objective was to compare symptomatic remission rates with balsalazide and mesalamine while controlling for extent of disease and time since diagnosis in patients with active, mild-to-moderate ulcerative colitis. METHODS: A total of 173 patients with sigmoidoscopically verified ulcerative colitis were randomized to 8 wk of double-blind treatment with balsalazide 6.75 g/day or mesalamine 2.4 g/day. Both treatments provided 2.4 g/day of oral 5-aminosalicylic acid. Patients maintained symptom diaries throughout the treatment period. RESULTS: Overall, 46% of balsalazide- and 44% of mesalamine-treated patients achieved symptomatic remission. Higher response rates were noted in newly diagnosed patients with < or = 40 cm of disease (68% vs 61%) than in recently relapsed patients with >40 cm of disease (36% vs 25%). The median time to symptomatic remission was 12 days shorter with balsalazide (25 days) than with mesalamine (37 days). Significantly more balsalazide patients showed sigmoidoscopic (p = 0.002), stool frequency (p = 0.006), rectal bleeding (p = 0.006), and physician's global assessment score (p = 0.013) improvement by 14 days than did mesalamine patients. Similar proportions of patients reported adverse events (54% vs 64%), which were most commonly related to the gastrointestinal and central and peripheral nervous systems. CONCLUSIONS: Balsalazide is an effective and safe treatment for mild-to-moderate ulcerative colitis. Improvement of symptoms occurs considerably earlier with balsalazide than with mesalamine.

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Inflamm Bowel Dis. 2002 Sep;8(5):317-24.
Response of refractory colitis to intravenous or oral tacrolimus (FK506).
Fellermann K, Tanko Z, Herrlinger KR, Witthoeft T, Homann N, Bruening A, Ludwig D, Stange EF.
Department of Internal Medicine I, Robert-Bosch-Hospital, Stuttgart, Germany. klaus.fellermann@rbk.de

Intravenous cyclosporine has proven to be an alternative to emergency colectomy in steroid-refractory ulcerative colitis, whereas the experience with FK506 is limited. In this report we compare intravenous to oral FK506 treatment in 38 patients with refractory ulcerative (n = 33) or indeterminate (n = 5) colitis. FK506 was started intravenously in the first group (n = 18) at a dose of 0.01 to 0.02 mg/kg up to 14 days, followed by 0.1 to 0.2 mg/kg orally, or was started orally at this dose in a second group (n = 20). Additional azathioprine/6-mercaptopurine was given and steroids were tapered in responding patients, followed by a dose reduction of FK506. Clinical disease activity and laboratory parameters were assessed to evaluate efficacy and safety. Primary objectives were the induction of remission (Truelove index of mild) and colectomy-free survival. Treatment lasted for a mean of 7.6 months, and the mean observation period was 16.2 months. Eighteen of 38 patients improved within 14 days, and a complete remission was achieved in 13 patients after 1 month. A colectomy within 1 month was performed in 3 of 38 patients. The overall colectomy rate was 34%. One-half of the patients with a minimum follow-up of 2 years required a colectomy. Intravenous and per oral administration were equally safe and effective. The most frequent adverse events included tremor, hyperglycemia, hypertension, and infection, but none were severe. Renal impairment was rare and subsided upon drug withdrawal. In conclusion. FK506 is effective in the treatment of refractory colitis with per oral dosing being equivalent to intravenous administration.

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Inflamm Bowel Dis. 2002 Sep;8(5):311-6.
Azathioprine or 6-mercaptopurine before colectomy for ulcerative colitis is not associated with increased postoperative complications.
Mahadevan U, Loftus EV Jr, Tremaine WJ, Pemberton JH, Harmsen WS, Schleck CD, Zinsmeister AR, Sandborn WJ.
Division of Gastroenterology, University of California, San Francisco, USA.

AIM: To determine whether the use of azathioprine/6-mercaptopurine before colectomy is associated with an increased rate of postoperative complications. METHODS: All patients who underwent colectomy with ileal pouch-anal anastomosis for ulcerative colitis between 1997 and 1999 were identified. Medical records were abstracted for demographics, extent and duration of disease, dose and duration of corticosteroids and azathioprine/6-mercaptopurine, albumin, and Truelove/Witts score. Early (30-day) and late (6-month) complications were identified. Noncorticosteroid immunosuppressive use was coded as none, azathioprine/6-mercaptopurine within 1 week of surgery, or therapy with other immunosuppressive agents within 1 month of surgery. A logistic regression analysis assessed the association between these variables and complications. RESULTS: Early complications occurred in 49 of 151 (32%) patients not treated with immunosuppressive agents, 12 of 46 (26%) azathioprine/6-mercaptopurine-treated patients, and 4 of 12 (33%) patients treated with other immunosuppressive agents (p = 0.71). Late complications occurred in 72 of 148 (49%), 20 of 46 (43%), and 8 of 12 (67%) patients in these same groups, respectively. Intravenous or oral steroids at doses of 40 mg/d or greater (p < 0.01) and severe or fulminant disease (p = 0.0094) were associated with greater early complication rates. CONCLUSION: Early complications after restorative proctocolectomy for ulcerative colitis are associated with high dose steroids and severe disease but not use of azathioprine/6-mercaptopurine.

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Curr Gastroenterol Rep. 2002 Dec;4(6):497-505.
Evolving medical therapies for ulcerative colitis.
Cohen RD.
Department of Medicine, Section of Gastroenterology, University of Chicago Medical Center, MC 4076, 5841 South Maryland Avenue, Chicago, IL 60637, USA. rcohen@medicine.bsd.uchicago.edu

Therapies for patients with ulcerative colitis have, until recently, been limited in scope and efficacy. New formulations of mesalamine and corticosteroids have challenged the older therapies with respect to both efficacy and safety. The application of 6-mercaptopurine and azathioprine for steroid-refractory disease and maintenance of remission has resulted in studies of other candidate immunomodulatory agents. Biologic therapies targeting tumor necrosis factor, adhesion molecules, or other cytokines are under intense scrutiny as potential disease-altering agents that may even replace currently available products. Other approaches, including such wide-ranging products as heparin, nicotine, and probiotics, suggest that control of ulcerative colitis may require an individualized approach for each patient.

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Am J Gastroenterol. 2002 Nov;97(11):2834-8.
Appendectomy protects against the development of ulcerative colitis but does not affect its course.
Selby WS, Griffin S, Abraham N, Solomon MJ.
A. W. Morrow Gastroenterology and Liver Centre and Department of Colorectal Surgery, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.

OBJECTIVES: Appendectomy has been shown to protect against the development of ulcerative colitis. The objective of this study was to examine the effect of appendectomy on the clinical features and natural history of colitis. METHODS: A total of 259 consecutive adults patients with ulcerative colitis were studied. Of the patients, 20 had undergone appendectomy (12 before onset of colitis and eight after diagnosis). RESULTS: The frequency of appendectomy was significantly less than in a group of 280 controls, which comprised partners of the patients and a group from the community (OR = 0.25; 95% CI = 0.14-0.44). This was even more significant if only the 12 patients who underwent surgery before the onset of colitis were considered (OR = 0.15; 95% CI = 0.07-0.28). Patients with prior appendectomy developed symptoms of ulcerative colitis for the first time at a significantly later age than those without appendectomy (42.5 +/- 6.5 vs 32.1 +/- 0.8 yr; p < 0.01) or those who had appendectomy after the onset of colitis (24.6 +/- 3.4 yr; p < 0.05). Appendectomy did not influence disease extent, need for immunosuppressive treatment with azathioprine or 6-mercaptopurine (as a marker of resistant disease), or the likelihood of colectomy. Five patients in the appendectomy group had clinical evidence of primary sclerosing cholangitis (25%). This was more common than in those without appendectomy (8%; OR = 4.09; 95% CI = 1.04-13.60). CONCLUSIONS: These results indicate that although appendectomy may delay onset of colitis, it does not influence its course. However, it is associated with the development of primary sclerosing cholangitis. Appendectomy is unlikely to be of benefit in established ulcerative colitis.

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Scand J Gastroenterol Suppl. 2002;(236):42-7.
Role of mesalazine in acute and long-term treatment of ulcerative colitis and its complications.
Schroeder KW.
Inflammatory Bowel Disease Clinic, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minn, 55905, USA. schroeder.kenneth@mayo.edu

BACKGROUND: Sulfasalazine, consisting of 5-aminosalicylic acid bound to sulfapyridine by a diazo bond, was first used for treatment of ulcerative colitis in the early 1940s and later found effective in placebo-controlled trials for acute disease and for long-term maintenance of remission. Later studies found that the active moiety is 5-ASA (mesalazine, mesalamine) and the sulfapyridine moiety acts as a carrier molecule but causes many of the symptomatic adverse reactions. METHODS: Review of the literature. RESULTS: The finding that 5-ASA in the active motility led to the development of mesalazine prodrugs, olsalazine (Dipentum) and balsalazide (Colazide, Colazal), and targeted release mesalazine preparations, such as Asacol, Pentasa, and Salofalk, as well as enemas and suppository preparations for distal disease. Most patients with adverse effects from sulfasalazine will tolerate mesalazine. Mesalazine has been shown equivalent or superior to sulfasalazine, and superior to placebo, with a dose-response benefit, in inducing remission of acute disease. and comparable to sulfasalazine and superior to placebo for long-term maintenance of remission. Better tolerance of mesalazine and the ability to use higher doses favor its use in patients intolerant of sulfasalazine and in patients failing to respond to usual doses of sulfasalazine. Adverse effects from mesalazine are uncommon, but include idiosyncratic worsening of the colitis symptoms and renal toxicity. Mesalazine is safe to use during pregnancy and for nursing mothers. As maintenance therapy, mesalazine may reduce the risk of developing colorectal carcinoma. CONCLUSION: Mesalazine represents effective and well-tolerated first-line therapy for mildly to moderately acute disease as well as for the long-term maintenance treatment in the patient with ulcerative colitis.

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Dig Liver Dis. 2002 Sep;34(9):626-30.
Anti-tumour necrosis factor alpha (infliximab) in the treatment of severe ulcerative colitis: result of an open study on 13 patients.
Kohn A, Prantera C, Pera A, Cosintino R, Sostegni R, Daperno M.
Division of Gastroenterology, S. Camillo-Forlanini Hospital, Rome, Italy. annakohn@tiscalinet.it

BACKGROUND: Conventional treatment options for patients with severe steroid-refractory ulcerative colitis include intravenous cyclosporine, which is frequently burdened by toxicity, or colectomy. Preliminary data suggest a benefit from anti-tumour necrosis factor alpha (Infliximab) therapy in patients with steroid refractory ulcerative colitis. AIM: To evaluate the efficacy of Infliximab in the treatment of severe ulcerative colitis refractory to conventional therapy PATIENTS AND METHODS: A series of 13 patients with severe ulcerative colitis, refractory to therapy with methyl-prednisolone, 60 mg daily for seven or more days, were treated with a single intravenous infusion of Infliximab 5 mg/kg. RESULTS AND CONCLUSIONS: Of these 13 patients, 10 (77%) had a clinical response to therapy defined by a clinical activity index 10 on two consecutive days. In 2 patients (15%) total colectomy was necessary on account of clinical worsening whilst one patient refused surgery and was lost to follow-up. All patients who responded showed very rapid clinical improvement, within 2 to 3 days of infusion. Infusion with Infliximab produced no significant adverse events. The mean time of follow-up was 10.1 months (range 5-12; during this time, 9 out of 10 patients (90%) maintained clinical remission and were able to discontinue corticosteroid therapy. Infliximab appears to be an effective agent for inducing long-standing remission in refractory patients with severe ulcerative colitis.

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Ann Ital Chir. 2002 May-Jun;73(3):287-96; discussion 297.
[Clinical and functional results after restorative proctocolectomy with ileal J reservoir in the treatment of ulcerative colitis]
[Article in Italian]
Colombo PL, Tinozzi FP, Abelli M, Pini G, Benedetti M, Moglia P, Morone G, Albertario S, Forti P, Laera MR, Bianchi C, Tinozzi S.
Cattedra di Chirurgia dell'Apparato Digerente, Istituto di Chirurgia Generale Gastroenterologica e Mammaria, Universita degli Studi di Pavia.

PURPOSE: Restorative proctocolectomy is the procedure of choice in the treatment of ulcerative colitis. The operation is successful in removing all diseased mucosa while preserving a normal bowel function and a good quality of life for the patient. In this article are presented the clinical and functional results obtained in 28 patients, 19 males (68%) and 9 females (32%) after stapled restorative proctocolectomy with ileal J pouch-anal anastomosis. RESULTS: There were no perioperative deaths. The overall morbidity rate was 31%. Six patients (21%) presented pelvic abscess; 2 (7%) pelvic hematoma, 4 patients (14%) ileo-anal anastomotic stricture, 1 patient (3.6%) pouch-vagina fistula, three patients (11%) intestinal obstruction and 7 (25%) pouchitis. All patients were able to evacuate their pouches spontaneously. The mean bowel movements were 6-9/24 hours at the first postoperative month and 3-5/24 hours at the sixth month. Infrequent nocturnal seepage occurred in 6 patients (21%). Stool consistency returned to normal within 3-6 months. The mean pouch capacity was 210 cc. The mean resting pressure was diminished in 11 patients (39%), the men and maximal squeeze pressures were improved in 9 (32%); the ileo-rectal-anal inhibitory reflex was normal in 5 patients (18%), not defined in 12 (43%). Impotence or impaired bladder function was not present. CONCLUSION: The use of staplers in the surgical technique of restorative proctocolectomy with J shaped ileo-anal pouch is associated with low morbidity and better long-term results. The procedure requires a good selection of patients, a correct surgical timing, a very carefully technique and a low pre and postoperative treatment with steroids.

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