Role of small-bowel endoscopy in the management of patients with inflammatory bowel disease: an international OMED-ECCO consensus.

Crohn's disease and ulcerative colitis are lifelong diseases seen predominantly in the developed countries of the world. Whereas ulcerative colitis is a chronic inflammatory condition causing diffuse and continuous mucosal inflammation of the colon, Crohn's disease is a heterogeneous entity comprised of several different phenotypes, but can affect the entire gastrointestinal tract. A change in diagnosis from Crohn's disease to ulcerative colitis during the first year of illness occurs in about 10 % - 15 % of cases. Inflammatory bowel disease (IBD) restricted to the colon that cannot be characterized as either ulcerative colitis or Crohn's disease is termed IBD-unclassified (IBDU). The advent of capsule and both single- and double-balloon-assisted enteroscopy is revolutionizing small-bowel imaging and has major implications for diagnosis, classification, therapeutic decision making and outcomes in the management of IBD. The role of these investigations in the diagnosis and management of IBD, however, is unclear. This document sets out the current Consensus reached by a group of international experts in the fields of endoscopy and IBD at a meeting held in Brussels, 12-13th December 2008, organised jointly by the European Crohn's and Colitis Organisation (ECCO) and the Organisation Mondiale d'Endoscopie Digestive (OMED). The Consensus is grouped into seven sections: definitions and diagnosis; suspected Crohn's disease; established Crohn's disease; IBDU; ulcerative colitis (including ileal pouch-anal anastomosis [IPAA]); paediatric practice; and complications and unresolved questions. Consensus guideline statements are followed by comments on the evidence and opinion. Statements are intended to be read in context with qualifying comments and not read in isolation.

Bowel ultrasound and mucosal healing in ulcerative colitis.

BACKGROUND AND AIM: Mucosal healing (MH) after short-term medical treatment is being considered as an important step in the therapeutic work-up of inflammatory bowel disorder (IBD) patients due to the potential prognostic role of MH in predicting disease outcome. However, IBD patients are reluctant to be re-endoscoped during follow-up; therefore, there is a need for non-invasive alternative index of MH which can replace endoscopy in clinical practice. We evaluated bowel ultrasound (US) as a surrogate of colonoscopy in a series of consecutive patients with active ulcerative colitis (UC). PATIENTS AND METHODS: 83 patients with moderate to severe UC requiring high-dose steroids were initially recruited; endoscopic severity of UC was graded 0-3 according to Baron score, and US severity was also graded 0-3 according to the colonic wall thickening and the presence of vascular signal at power Doppler. 74 patients responsive to steroids and then maintained on 5-ASA compounds were followed up with repeated colonoscopy and bowel US at 3, 9 and 15 months from entry. Concordance between clinical, endoscopic and US scores at various visits was determined by kappa statistics. Multiple unconditional logistic regression models were used to assess the predictivity of Truelove, Baron and US scores measured at 3 and 9 months on the development of a UC relapse (Baron score 2-3) at 15 months. RESULTS: An inconsistent concordance was found over time between 0 and I Baron scores and Truelove score (weighted kappa between 0.38 and 0.94), with high and consistent concordance between 0 and I Baron scores and US scores (weighted kappa between 0.76 and 0.90). On logistic regression analysis, a moderate/severe Baron score, regardless of their Truelove score, at 3 months was associated with a high risk of endoscopic activity at 15 months (OR 5.2; 95% CI: 1.6-17.6); similarly, patients with severe US scores (2-3) at 3 months had a high risk of severe endoscopic activity at 15 months (OR 9.1; 95% CI: 2.5-33.5). DISCUSSION: In expert hands bowel US may be used as a surrogate of colonoscopy in evaluating the response to high-dose steroids in severe forms of UC. US score after 3 months of steroid therapy accurately predicts clinical outcome of disease at 15 months.

Immunomodulatory effects of 1,25-dihydroxyvitamin D3 on TH1/TH2 cytokines in inflammatory bowel disease: an in vitro study.

Crohn's disease (CD) is associated with a higher type-1-helper T cell (Th1) cytokine expression, whereas ulcerative colitis (UC) appears to express a modified Th2 response. In addition to its classic role in calcium homeostasis, calcitriol, the hormonal active form of vitamin D, exerts immunoregulatory effects such as modulation of Th1/Th2 cytokines. Therefore, calcitriol administration could modify immune dysfunction in CD and UC. Nine patients with UC (M/F: 5/4; mean age 47 years, remission(R)/active(A) disease: 7/2), 8 patients with CD (M/F: 2/6; mean age 36, R/A 5/3) and 6 healthy controls (HC) (M/F: 3/3, mean age 4) were enrolled. Peripheral blood was collected after a drug-washout of 15 days and peripheral blood mononuclear cells were stimulated with mitogens alone or in the presence of physiological concentrations of calcitriol (100 pg/ml). Type 1 (IL-2, TNF-alpha, IFN-gamma) and type 2 (IL-10) cytokine production was assayed on supernatants by ELISA. Compared to HC, TNF-alpha production was significantly higher both in UC (p=0.0002) and CD (p=0.0001) patients, at baseline and after incubation with calcitriol (UC p=0.0003, CD p=0.0009). The effects of calcitriol incubation were: 1) reduced IFN-gamma (p=0.024) and increased IL-10 (p=0.06) production in UC patients; 2) reduced TNF-alpha production in CD (p=0.032); 3) no significant effects in HC. Calcitriol increased, albeit not significantly, IL-10 production in UC compared to CD patients (p=0.09). These results suggest an important modulatory role of vitamin D in the Th1/Th2 immune response. The observation that the effect of this modulation was different in CD compared to UC patients provides an interesting area of research into the pathogenesis and treatment of these inflammatory conditions.

Autologous haematopoietic stem cell transplantation without CD34+ cell selection in refractory Crohn's disease.

OBJECTIVES: Autologous haematopoietic stem cell transplantation (HSCT) with CD34(+) cell selection has recently been used in the treatment of refractory Crohn's disease, showing good safety and promising efficacy. We investigated the safety and efficacy of HSCT with unselected peripheral blood stem cells (PBSCs) in moderate-severe refractory Crohn's disease. PATIENTS: Four patients (three male, one female; age range 26-45 years) with active moderate-severe Crohn's disease (median Crohn's Disease Activity Index (CDAI) 319, range 272-345), refractory or intolerant to multiple drugs including infliximab, were enrolled. INTERVENTIONS: Unselected PBSCs were collected after mobilisation with cyclophosphamide (CTX) 1.5 g/m2 and granulocyte-colony stimulating factor (G-CSF) 10 microg/kg. The conditioning regimen included CTX 50 mg/kg on days -5 to -2 and rabbit anti-thymocyte globulin (ATG) 2.5 mg/kg on days -4 to -2. MAIN OUTCOME MEASURES: Primary endpoints were toxicity and clinical remission (CDAI<150) at 3 months. Secondary endpoints were clinical and endoscopic response at 3 months and toxicity, clinical and endoscopic remission at 12 months. RESULTS: No improvement or slight deterioration was observed following mobilisation (median CDAI 339, range 258-404). At the third month, the primary endpoint of clinical remission was achieved in all patients, with a median CDAI of 91 (range 56-102), and complete endoscopic remission was achieved in 2/3 patients. After a median follow-up of 16.5 months, 3/4 patients maintained both clinical and endoscopic remission, despite withdrawal of all drugs, and complete fistula closure was observed in all affected patients. No deaths or life-threatening infection occurred. Unexpected adverse events included a perianal abscess after mobilisation in one patient, pleural and pericardial effusions in another and BK virus-related macrohaematuria in another, all rapidly resolved with conservative treatment. CONCLUSION: Autologous HSCT with unselected PBSC appears to be safe and can induce and maintain remission in previously refractory Crohn's disease patients.

Multidrug resistance 1 gene polymorphism and susceptibility to inflammatory bowel disease.

BACKGROUND: Several studies have evaluated the role of the multidrug resistance 1 gene (MDR1) polymorphism, which encodes the membrane-bound efflux transporter P-glycoprotein 170, in determining susceptibility to and disease behavior in inflammatory bowel disease (IBD), but with conflicting results. METHODS: A total of 211 patients with Crohn's disease (CD), 97 patients with ulcerative colitis (UC), and 212 control subjects were investigated for the presence of MDR1 G2677T/A and C3435T polymorphisms. Genotype frequencies of CD and UC patients were compared to those observed in a control population. Genotype-phenotype correlations with major clinical features were also established and estimated risks (odds ratio [OR] with 95% confidence interval [CI]) for the mutations were calculated by a logistic regression analysis and multiple correspondent analysis. RESULTS: No significant difference was observed for genotype frequencies for both MDR1 G2677T/A and C3435T polymorphisms on overall disease susceptibility for either CD or UC patients compared with control subjects. A significant association was found between the MDR1 C3435T polymorphism and patients with ileo-colonic CD (OR = 3.34; 95% CI: 1.34-8.27). Interestingly, a negative association was found between MDR1 C3435T polymorphism in patients with a positive family history for IBD (OR = 0.44; 95% CI: 0.20-0.95) and articular manifestations (OR = 0.29; 95% CI: 0.13-0.68). Both susceptible and protective effects were identified. No significant association between G2677T/A polymorphism and any specific subphenotypes was found, nor was there any association with subphenotypic categories of UC and both single nucleotide polymorphisms. CONCLUSIONS: The results of our study suggest that MDR1 gene polymorphism could have a role in determining susceptibility to IBD. The variability of this possible effect in the several studies reported so far may be the indirect expression of the complex role played by the MDR1 gene and its product, P-glycoprotein 170, in the regulation of host-bacteria interactions and in the pathogenesis of IBD.

Review article: the management of steroid dependency in ulcerative colitis.

BACKGROUND: Approximately 20% of patients with ulcerative colitis have a chronic active disease often requiring several courses of systemic steroids in order to achieve remission, but followed by relapse of symptoms during steroid tapering or soon after their discontinuation. Although short term control of symptoms can be achieved with steroid treatment, this pattern of drug response, known as steroid-dependency, leads to important complications of the treatment, while a significant proportion of patients requires colectomy. AIM: To review the studies currently available specifically evaluating the management of steroid-dependent ulcerative colitis. RESULTS: The clinical and biological mechanisms of steroid-dependency are not well understood compared with those determining steroid-refractoriness. Very few evidence-based data are available concerning the management of patients with steroid-dependent ulcerative colitis. The therapeutic role of aminosalicylates, thiopurines, methotrexate, infliximab, leukocyte apheresis and other drugs in the treatment of steroid-dependent ulcerative colitis are evaluated. CONCLUSIONS: Outcomes of studies in steroid-refractory patients may not be applicable to steroid-dependency. Trials are needed to define the correct approaches and new strategies to ameliorate the therapy of steroid-dependent ulcerative colitis.

Imaging of perianal Crohn's disease.

Perianal fistulas and abscesses are common complications of Crohn's disease, affecting up to 50% of patients during their disease course. Accurate diagnosis and classification of perianal disease is crucial before and during treatment to plan an adequate approach for each patient and to avoid irreversible functional consequences. Although examination under anaesthesia has been considered the gold standard for diagnosis and classification of Crohn's disease perianal fistulas, taken alone it does not have perfect accuracy, stressing the need for concomitant or alternative, non-invasive, methods of evaluation. In this context, imaging modalities assessed for diagnosis, classification and monitoring of Crohn's disease perianal fistulas include pelvic magnetic resonance imaging, anorectal endoscopic ultrasonography, transcutaneous perianal ultrasound, fistulography and computed tomography. In particular, magnetic resonance imaging and endoscopic ultrasonography findings have shown the best accuracy, and the ability to influence therapeutic management of these patients. For transcutaneous perianal ultrasound too, good preliminary data have been reported. This paper reviews the available data on imaging methods for the management of perianal Crohn's disease.

Anorectal ultrasound for neoplastic and inflammatory lesions.

Accurate staging of rectal and anal carcinoma is crucial for planning surgery and indicating adjuvant therapy. Although, computed tomography and magnetic resonance imaging are very sensitive in detecting metastatic disease, the local staging of rectal cancer with these techniques has been disappointing. Endorectal ultrasound (ERUS) and anal endosonography (AE) remain the most accurate methods for staging rectal and anal cancer. Anal endosonography is also of value in evaluating perianal sepsis: it can assist the surgeon in planning the surgical strategy by delineating the anatomy of fistula tracts, and can aid in puncturing abscesses in the operating room. Continued research and development has made the instrumentation for ERUS and AE more accurate and user-friendly. New techniques that have contributed significantly to the evolution of ERUS include three-dimensional ERUS, high-frequency miniprobes, transrectal ultrasound-guided biopsy techniques and hydrogen peroxide-enhanced endosonography. Further improvements can be expected from contrast enhancement with microbubbles and colour Doppler imaging. In this new millennium, new developments in ERUS and anal endosonography, such as tri-dimensional ERUS and anal endosonography and radial electronic probing, widen the role of ERUS in the staging of rectal and anal carcinoma, as well as for perianal inflammatory conditions.

Impact of patient characteristics on the clinical efficacy of mongersen (GED-0301), an oral Smad7 antisense oligonucleotide, in active Crohn's disease.

BACKGROUND: In a phase 2 study, mongersen, an oral antisense oligonucleotide targeting Smad7, was effective in inducing clinical remission in approximately 60% of patients with active Crohn's disease (CD). AIM: In a post hoc analysis to evaluate those patient disease characteristics that may have influenced the efficacy and safety of mongersen therapy. METHODS: Patients with steroid-dependent/resistant, active CD were randomised to mongersen 10, 40 or 160 mg/day or placebo for 2 weeks; patients were followed for 10 weeks. Clinical remission [Crohn's Disease Activity Index (CDAI) score <150] and clinical response (CDAI score reduction ≥100 points) were assessed at weeks 2, 4 and 12 for these subgroups: disease duration <5/≥5 years, human serum C-reactive protein (hsCRP) <3/≥3 mg/L, and CDAI at baseline ≤260/>260. Additional patient baseline and disease characteristics were explored. RESULTS: Clinical remission and response rates were significantly higher in patients receiving mongersen 40 and 160 mg/day but not 10 mg/day vs. placebo and independent of disease duration and hsCRP. Patients with baseline CDAI ≤260 had significantly higher remission rates with 40 and 160 mg/day. In patients with baseline CDAI >260, remission rates were statistically greater with 160 mg/day and numerically better with 40 mg/day vs. placebo. Adverse event rates were similar across treatment groups. Mongersen was safe and well tolerated. CONCLUSIONS: Patients with higher CDAI scores achieved clinical remission most frequently with the highest mongersen dose. Disease duration and baseline human serum C-reactive protein did not appear to significantly impact efficacy of mongersen in this study (EudraCT Number: 2011-002640-27.).

Is interferon-alpha therapy safe and effective for patients with chronic hepatitis C and inflammatory bowel disease? A case-control study.

BACKGROUND: Hepatitis C virus infection is more common in patients with inflammatory bowel disease than in general population. Limited data are available as to the safety and efficacy of alpha-interferon therapy for chronic active hepatitis C in patients with concomitant inflammatory bowel disease. AIM: To evaluate the efficacy and safety of alpha-interferon monotherapy in patients with chronic active hepatitis C and inactive or mildly active inflammatory bowel disease. METHODS: A total of 513 consecutive inflammatory bowel disease patients at a single centre were tested for antibodies to hepatitis C virus (anti-hepatitis C virus) between 1995 and 2000. Twenty-one patients had detectable anti-hepatitis C virus Ab and were hepatitis C virus-RNA positive with histologically proved chronic active hepatitis. Each of these patients, whose inflammatory bowel disease was in clinical remission or mildly active, was sex- and age-matched to three controls with similar histological grade and stage of chronic hepatitis C virus but without inflammatory bowel disease; and all were treated with human leucocyte alpha-interferon 6 million units given thrice weekly for 12 months. Responses to treatment were classified as follows: complete response--persistently normal alanine aminotransferase and viral clearance (hepatitis C virus-RNA-ve) at the end-of-treatment, incomplete response--alanine aminotransferase normalization without viral clearance (hepatitis C virus-RNA+ve), and sustained response--alanine aminotransferase normalization and hepatitis C virus clearance 12 months after the end-of-treatment. RESULTS: Twenty-one patients with chronic active hepatitis C and inflammatory bowel disease (10 with Crohn's disease and 11 with ulcerative colitis) and 63 sex- and age-matched controls with chronic hepatitis C virus alone received alpha-interferon monotherapy. Response rates to interferon were similar for inflammatory bowel disease patients compared with controls [CR 42% vs. 35% and SR 24% vs. 18% (P, not significant), respectively]. None of the 21 inflammatory bowel disease patients had severe adverse effects and the mild ones observed were comparable with those seen in the control group. No patients developed an inflammatory bowel disease relapse during the interferon treatment period or in the 12 months thereafter. CONCLUSIONS: The biochemical and virological response to a 12-month human leucocyte alpha-interferon treatment in patients with chronic active hepatitis C are similar to that observed in matched controls with chronic hepatitis C virus without inflammatory bowel disease. Adverse effects are similar in both groups of patients and unrelated to the underlying inflammatory bowel condition. This provides hepatologists with evidence that alpha-interferon can be safely administered to patients with chronic hepatitis C virus and inflammatory bowel disease provided that the inflammatory bowel condition is in clinical remission.

Autoantibody profile during short-term infliximab treatment for Crohn's disease: a prospective cohort study.

BACKGROUND: The potential clinical implications of autoimmunity during treatment with infliximab are unclear. AIM: To determine the frequency and correlation of autoantibody formation in patients with Crohn's disease treated with infliximab in a routine clinical setting. METHODS: Sixty-three patients with refractory/inflammatory (31) and/or fistulising Crohn's disease (32), received an infliximab infusion at a dose 5 mg/kg in weeks 0, 2 and 6, and were evaluated for the development of antinuclear, anti-double-stranded DNA, anti-Sm, anti-RNP, anti-SSA, anti-SSB and antihistone antibodies. The correlates with pharmacological treatments, the response to infliximab and adverse events were evaluated. RESULTS: Antinuclear antibodies were found in five of the 63 patients (8%) at baseline and in 26 (42%) after 10 weeks (P < 0.001). Of the 26 antinuclear antibody-positive patients who were further subtyped, nine of 63 (17%) had anti-double-stranded DNA (P = 0.003), and 1.5% were extractable nuclear antigen (ENA) and antihistone-positive. Five patients were initially positive for anticardiolipin antibodies and two more patients became positive during infliximab treatment. New autoantibody formation was more frequent in the patients with inflammatory/refractory disease than in those with fistulising disease (17 vs. 7; P = 0.02). One patient developed drug-induced lupus without major organ damage. CONCLUSIONS: Autoantibody formation occurs in 42% of patients (8% of these patients were positive before infliximab treatment) with Crohn's disease receiving induction treatment with infliximab, but the clinical significance of this remains to be determined.

Prevalence, detection rate and outcome of cytomegalovirus infection in ulcerative colitis patients requiring colonic resection.

OBJECTIVE: To determine the prevalence of cytomegalovirus infection in patients with steroid-refractory ulcerative colitis who required colonic resection, and to assess its possible association with the use of immunosuppressive and steroid treatment and outcome after colectomy. PATIENTS AND METHODS: The study included surgical specimens and related pre-operative endoscopic biopsy specimens of 77 consecutive ulcerative colitis patients (34 females) who underwent colectomy because of intractable steroid-refractory ulcerative colitis (55 patients), toxic megacolon (6 patients), dysplasia or cancer (7 patients) or loss of function of the colon (9 patients). Clinical features and current and past treatments were analysed. Haematoxylin and eosin and specific immunohistochemical staining for cytomegalovirus were used to detect inclusion bodies in all specimens. RESULTS: Cytomegalovirus infection was found in 15 of 55 steroid-refractory ulcerative colitis patients (27.3%) and in 2 of 22 non-refractory patients (9.1%) (p=0.123). Only six patients had positive staining for cytomegalovirus in pre-operative endoscopic biopsy specimens. Detection of cytomegalovirus inclusion in biopsy specimens was not related to the number of biopsies or to time that had elapsed since colonoscopy and index surgery. Cytomegalovirus-positive patients were more likely to be on systemic corticosteroids (p=0.03). In contrast, current use and duration of immunosuppressive treatment, number of steroid cycles since diagnosis and in the last year, as well as chronic use of steroid in the last year were not significantly related to cytomegalovirus infection. Cytomegalovirus-positive patients did not receive antiviral therapy following proctocolectomy but did not show endoscopic or histological cytomegalovirus reactivation in the ileo-anal pouch and in the remaining bowel. CONCLUSIONS: Cytomegalovirus infection is frequently found in surgical specimens of patients with steroid-refractory ulcerative colitis and is more likely in patients on corticosteroid treatment. Cytomegalovirus infection is frequently unrecognised in pre-operative biopsy specimens, thus raising concerns about the accuracy of the available diagnostic tools. Unrecognised and untreated cytomegalovirus infection does not affect the outcome of ulcerative colitis patients following proctocolectomy.

Appropriateness of immunosuppressive drugs in inflammatory bowel diseases assessed by RAND method: Italian Group for IBD (IG-IBD) position statement.

INTRODUCTION: Despite the explosion of biological therapies, the old immunosuppressants continue to play a pivotal role in the management of inflammatory bowel diseases. AIM: To assess the appropriateness of immunosuppressants-azathioprine, 6-mercaptopurine, methotrexate, cyclosporine A, tacrolimus (FK506), mycophenolate mofetil and thalidomide-in the treatment of inflammatory bowel disease by using RAND/University of California Appropriateness Method. METHODS: The RAND method consists of a combination of evidence from the literature and experts' opinions. Appropriateness has been defined to mean that the expected health benefit exceeds the expected negative consequences by a sufficiently wide margin. A panel of 10 experts from the Italian Group for Inflammatory Bowel Disease has rated, in two rounds, on a scale from 1 to 9, the appropriateness of each indication selected by the Promoter Centre, on the basis of their own clinical experience. An indication was considered appropriate if the median of the panelists' ratings fell within the area 7-9, inappropriate in the area 1-3 and uncertain in the area 4-6. A total of 2781 indications were grouped into 13 categories (mild to moderate Crohn's disease; severe Crohn's disease; fistulizing Crohn's disease; steroid-dependant and -resistant Crohn's disease; maintenance of remission induced by medical treatment in Crohn's disease; maintenance of remission induced by surgery in Crohn's disease; mild to moderate ulcerative colitis; severe ulcerative colitis; steroid-dependant and -resistant ulcerative colitis; maintenance of remission induced by medical treatment in ulcerative colitis; extra-intestinal manifestations in inflammatory bowel disease; pregnancy and inflammatory bowel disease; azathioprine-resistant or -intolerant inflammatory bowel disease patients). RESULTS: Of the 2781 scenarios, 212 (7.6%) were rated appropriate, 645 (23.2%) uncertain and 1924 (69.2%) inappropriate. The most relevant results were: in steroid-dependant or -resistant Crohn's disease, azathioprine, 6-mercaptopurine and methotrexate were defined as appropriate in 25 (86.2%) and 14 (48.3%) of the 29 scenarios respectively; in Crohn's disease, azathioprine and 6-mercaptopurine were defined as appropriate combined with Infliximab (bridge therapy); in steroid-dependant or -resistant ulcerative colitis, azathioprine and 6-mercaptopurine were defined as appropriate in 45 (77.6%) out of 58 scenarios, while methotrexate was defined appropriate only after previous azathioprine failure; in severe ulcerative colitis, cyclosporine A was defined as appropriate only after previous failure with steroids; in azathioprine-intolerant or -resistant inflammatory bowel disease patients, methotrexate was appropriate in 20 (66.7%) out of 30 scenarios; it is inappropriate to stop azathioprine treatment before conception in the presence of active disease. The use of FK506, mycophenolate mofetil and Thalidomide resulted as inappropriate or uncertain. CONCLUSIONS: Results of this study show that only azathioprine, 6-mercaptopurine and methotrexate are appropriate in the treatment of inflammatory bowel diseases. Cyclosporine A was found to be appropriate only in severe ulcerative colitis after the failure of steroids. FK506, mycophenolate mofetil and Thalidomide resulted as inappropriate but experience with these agents is somewhat limited.

Patterning of polymer brushes made easy using titanium dioxide: direct and remote photocatalytic lithography.

Photocatalytic lithography is proved for the realization of micropatterned polymer brushes. Initiator-functionalized titanium dioxide or silicon surfaces are respectively exposed directly to near-UV light through a photomask (direct approach) or through a transparent photoactive TiO2 film (remote approach). Initiator patterns are then amplified as polymer brushes with SI-ATRP. Features down to 10 µm could be obtained using simple equipment. The process is intrinsically parallel, has high throughput and scalable to wafer size, making it powerful for microfabrication purposes.

Hazardous o-toluidine mineralization by photocatalytic bismuth doped ZnO slurries.

Photocatalytic mineralization of o-toluidine in aqueous media under UV/solar irradiation was achieved by bare and bismuth doped zinc oxide nanoparticles. By adopting different analytical approaches a reaction mechanism is proposed, explaining the differences in photodetoxification performances.

The second European evidenced-based consensus on reproduction and pregnancy in inflammatory bowel disease.

Trying to conceive and being pregnant is an emotional period for those involved. In the majority of patients suffering from inflammatory bowel disease, maintenance therapy is required during pregnancy to control the disease, and disease control might necessitate introduction of new drugs during a vulnerable period. In this updated consensus on the reproduction and pregnancy in inflammatory bowel disease reproductive issues including fertility, the safety of drugs during pregnancy and lactation are discussed.

A practical guide to the management of distal ulcerative colitis.

This article reviews the role of corticosteroids, sulfasalazine and mesalazine (5-aminosalicylic acid, mesalamine), immunosuppressive agents and alternative novel drugs for the treatment of distal ulcerative colitis. Short cycles of traditional, rectally administered corticosteroids (methylprednisolone, betamethasone, hydrocortisone) are effective for the treatment of mild to moderately active distal ulcerative colitis. In this context, their systemic administration is limited to patients who are refractory to either oral 5-amino-salicylates, topical mesalazine or topical corticosteroids. Of no value in maintaining remission, the long term use of either or topical corticosteroids may be hazardous. A new class of topically acting corticosteroids [budesonide, fluticasone, beclomethasone dipropionate, prednisolone-21-methasulphobenzoate, tixocortol (tixocortol pivalate)] represents a valid alternative for the treatment of active ulcerative colitis, and may be useful in the treatment of refractory distal ulcerative colitis. Although there is controversy concerning dosage or duration of therapy, oral and topical mesalazine is effective in the treatment of mild to moderately active distal ulcerative colitis. Sulfasalazine and mesalazine remain the first-choice drugs for the maintenance therapy of distal ulcerative colitis. Evidence exists showing a trend to a higher remission rate with higher doses of oral mesalazine. Topical mesalazine (suppositories or enemas) also is effective in maintenance treatment. For patients with chronically active or corticosteroid-dependent disease, azathioprine and mercaptopurine are effective in reducing either the need for corticosteroids or clinical relapses. Moreover, they are effective for long term maintenance remission. Cyclosporin may be useful in inducing remission in patients with acutely severe disease who do not achieve remission with an intensive intravenous regimen. Existing data suggest that azathioprine and mercaptopurine may be effective in prolonging remission in these patients. The role of alternative drugs for the treatment of distal ulcerative colitis and its different forms is reviewed. In particular data are reported concerning the effectiveness of 5-lipoxygenase inhibitors, topical use of short chain fatty acids, nicotine, local anaesthetics, bismuth subsalicylate enema, sucralfate, clonidine, free radical scavengers, heparin and hydroxychloroquine.

Sucralfate and hydrocortisone enemas in the treatment of active ulcerative proctitis--a randomized single-blind comparative study.

BACKGROUND: Sucralfate is a non-absorbable aluminium salt of sucrose octasulphate which in recent studies has proved to be of possible use in the treatment of active distal ulcerative colitis. AIM: The aim of this randomized, single-blind, study was to compare 10 g sucralfate with 100 mg hydrocortisone enemas in the treatment of 40 patients (26 male and 14 female; mean age 36.5 years, range 18-65 years) with active ulcerative proctitis, twice daily for 4 weeks. METHODS: A clinical, sigmoidoscopic and histological assessment was performed before and 4 weeks after the start of the therapy. RESULTS: Both treatments showed significant within-treatment improvement in clinical, endoscopic and histological grades (Wilcoxon's matched pair test, P < 0.05). Between-treatment comparisons, using the Mann-Whitney test, showed that hydrocortisone is more effective than sucralfate in improving the clinical score (P < 0.05). CONCLUSIONS: Sucralfate enema treatment, which was significantly less effective than hydrocortisone enemas in this study, has very limited use in the treatment of active ulcerative proctitis.

Is maintenance therapy always necessary for patients with ulcerative colitis in remission?

BACKGROUND: The efficacy of sulphasalazine and mesalazine in preventing relapse in patients with ulcerative colitis is well known. It is less clear how long such maintenance should be continued, and if the duration of disease remission is a factor that affects the risk of recurrence. AIM: To determine whether the duration of disease remission affects the relapse rate, by comparing the efficacy of a delayed-release mesalazine (Asacol, Bracco S.p.A., Milan, Italy) against placebo in patients with ulcerative colitis with short- and long-duration of disease remission. METHODS: 112 patients (66 male, 46 female, mean age 35 years), with intermittent chronic ulcerative colitis in clinical, endoscopic and histological remission with sulphasalazine or mesalazine for at least 1 year, were included in the study. Assuming that a lower duration of remission might be associated with a higher relapse rate, the patients were stratified according to the length of their disease remission, prior to randomization into Group A (Asacol 26, placebo 35) in remission from 1 to 2 years, or Group B (Asacol 28, placebo 23) in remission for over 2 years, median 4 years. Patients were treated daily with oral Asacol 1.2 g vs. placebo, for a follow-up period of 1 year. RESULTS: We employed an intention-to-treat analysis. In Group A, whilst no difference was found between the two treatments after 6 months, mesalazine was significantly more effective than placebo in preventing relapse at 12 months [Asacol 6/26 (23%), placebo 17/35 (49%), P = 0.035, 95% Cl: 48-2.3%]. In contrast, in Group B no statistically significant difference was observed between the two treatments, either at 6 or 12 months [Asacol 5/28 (18%), placebo 6/23 (26%), P = 0.35, 95% Cl: 31-14%] of follow-up. Patients in group B were older, and had the disease and remission duration for longer, than those in Group A. CONCLUSIONS: Mesalazine prophylaxis is necessary for the prevention of relapse by patients with ulcerative colitis in remission for less than 2 years, but this study casts doubt over whether continuous maintenance treatment is necessary in patients with prolonged clinical, endoscopic and histological remission, who are at very low risk of relapse.