Topical therapy is underused in patients with ulcerative colitis.

The availability of new topical preparations for the treatment of left sided ulcerative colitis offers a therapy optimization for many patients. Rectal application of steroids and 5-aminosalicylic acid (5-ASA) is associated with fewer side effects and has a higher therapeutic efficacy in left-sided colitis as compared to a systemic therapy. Therefore, we were interested in the use of topical therapy in patients with ulcerative colitis. The key question was whether topical treatment is more frequently used than oral therapy in patients with proctitis and left sided colitis. Data of 800 patients of the Swiss IBD cohort study were analyzed. Sixteen percent of patients of the cohort had proctitis, 21% proctosigmoiditis and 41% pancolitis. Topical therapy with 5-ASA or corticosteroids was given in 26% of patients with proctitis, a combined systemic and topical treatment was given in 13%, whereas systemic treatment with 5-ASA without topical treatment was given in 29%. Proportion of topical drug use decreased with respect to disease extension from 39% for proctitis to 13.1% for pancolitis (P=0.001). Patients with severe colitis received a significantly higher dose of topical 5-ASA than patients in remission. Side effects of topical or systemic 5-ASA or budesonide treatment were less frequently seen compared to other medications. Topical treatment was frequently stopped over time. The quality of life was the same in patients with limited disease compared to patients with pancolitis. Topical treatment in proctitis patients was underused in Switzerland. Since topical treatment is safe and effective it should be used to a larger extend.

Antineutrophil cytoplasmic antibodies in sera from colectomised ulcerative colitis patients and its relation to the presence of pouchitis.

BACKGROUND: Few studies have evaluated the influence of colectomy on antineutrophil cytoplasmic antibody (ANCA) positivity in ulcerative colitis (UC). In small series of patients it has been suggested that ANCA positivity in UC might be predictive for development of pouchitis after colectomy. AIMS: To assess the prevalence of ANCA in UC patients treated by colectomy and a Brooke's ileostomy (UC-BI) or ileal pouch anal anastomosis (UC-IPAA), and the relation between the presence of ANCA, the type of surgery, and the presence of pouchitis. SUBJECTS: 63 UC patients treated by colectomy (32 with UC-BI and 31 with UC-IPAA), 54 UC, and 24 controls. METHODS: Samples were obtained at least two years after colectomy. ANCA were detected by indirect immunofluorescent assay. RESULTS: There were no differences between patients with (36.3%) or without pouchitis (35.0%) and between patients with UC (55%), UC-BI (40.6%), and UC-IPAA (35.4%). However, ANCA prevalence significantly decreases in the whole group of operated patients (38.0%) compared with non-operated UC (p = 0.044). CONCLUSIONS: The prevalence of ANCA in operated patients was significantly lower than in non-operated UC, suggesting that it might be related either to the presence of inflamed or diseased tissue. ANCA persistence is not related to the surgical procedure and it should not be used as a marker for predicting the development of pouchitis.

Successive treatment with cyclosporine and infliximab in steroid-refractory ulcerative colitis.

OBJECTIVES: Rescue therapy with either cyclosporine (CYS) or infliximab (IFX) is an effective option in patients with intravenous steroid-refractory attacks of ulcerative colitis (UC). In patients who fail, colectomy is usually recommended, but a second-line rescue therapy with IFX or CYS is an alternative. The aims of this study were to investigate the efficacy and tolerance of IFX and CYS as a second-line rescue therapy in steroid-refractory UC or indeterminate colitis (IC) unsuccessfully treated with CYS or IFX.METHODS: This was a retrospective survey of patients seen during the period 2000-2008 in the GETAID centers. Inclusion criteria included a delay of <1 month between CYS withdrawal (when used first) and IFX, or a delay of <2 months between IFX (when used first) and CYS, and a follow-up of at least 3 months after inclusion. Time-to-colectomy, clinical response, and occurrence of serious adverse events were analyzed.RESULTS: A total of 86 patients (median age 34 years; 49 males; 71 UC and 15 IC) were successively treated with CYS and IFX. The median (+/-s.e.) follow-up time was 22.6 (7.0) months. During the study period, 49 patients failed to respond to the second-line rescue therapy and underwent a colectomy. The probability of colectomy-free survival (+/-s.e.) was 61.3 +/- 5.3% at 3 months and 41.3 +/- 5.6% at 12 months. A case of fatal pulmonary embolism occurred at 1 day after surgery in a 45-year-old man. Also, nine infectious complications were observed during the second-line rescue therapy.CONCLUSIONS: In patients with intravenous steroid-refractory UC and who fail to respond to CYS or IFX, a second-line rescue therapy may be effective in carefully selected patients, avoiding colectomy within 2 months in two-thirds of them. The risk/benefit ratio should still be considered individually.

First explicit criteria to decide on the appropriateness of therapy of ulcerative colitis: the European EPATUC panel

Background: Ulcerative colitis (UC) is a chronic disease with a wide variety of treatment options many of which are not evidence based. Supplementing available guidelines, which are often broadly defined, consensus-based and generally not tailored to specifically reflect the individual patient situation, we developed explicit appropriateness criteria to assist, and improve treatment decisions. Methods: We used the RAND appropriateness method which does not force consensus. An extensive literature review was compiled based on and supplementing, where necessary, the ECCO UC 2011 guidelines. EPATUC (endorsed by ECCO) was formed by 7 gastroenterologists, 2 surgeons and 2 general practitioners from throughout Europe. Clinical scenarios reflecting practice were rated on a 9-point scale from 1 (extremely inappropriate) to 9 (extremely appropriate), based on the expert's experience and the available literature. After extensive discussion, all scenarios were re-rated at a two-day panel meeting. Median and disagreement (D) were used to categorize ratings into 3 categories: appropriate (A), uncertain (U) and inappropriate (I). Results: 718 clinical scenarios were rated, structured in 13 main clinical presentations: not refractory (n = 64) or refractory (n = 33) proctitis, mild to moderate left-sided (n = 72) or extensive (n = 48) colitis, severe colitis (n = 36), steroid- dependant colitis (n = 36), steroid-refractory colitis (n = 55), acute pouchitis (n = 96), maintenance of remission (n = 248), colorectal cancer prevention (n = 9) and fulminant colitis (n = 9). Overall, 100 indications were judged appropriate (14%), 129 uncertain (18%) and 489 inappropriate (68%). Disagreement between experts was very low (6%). Conclusions: For the very first time, explicit appropriateness criteria for therapy of UC were developed that allow both specific and rapid therapeutic decision making and prospective assessment of treatment appropriateness. Comparison of these detailed scenarios with patient profiles encountered in the Swiss IBD cohort study indicates good concordance. EPATUC criteria will be freely accessible on the internet (epatuc.ch)

The positioning of colectomy in the treatment of ulcerative colitis in the era of biologic therapy.

The position of surgery in the treatment of ulcerative colitis (UC) has changed in the era of biologics. Several important questions arise in determining the optimal positioning of surgery in the treatment of UC, which has long been a challenge facing gastroenterologists and surgeons. Surgery is life-saving in some patients and leads to better bowel function and better quality of life in most patients. The benefits of surgery, however, must be weighed against the potential surgical morbidity and compromised functioning that clearly can occur. The introduction of biologic therapy has added further complexity to decisions about medical management, surgery, and the relative timing of these choices. Appropriate medical management of UC may induce and maintain remission and may prevent surgery. However, medical management also carries risks of adverse effects, and recent data suggest that delay of surgery during ineffective medical therapy can increase the chances of negative surgical outcomes. To make individualized timely treatment decisions, early collaboration between gastroenterologists and surgeons is important and more data on predictors of treatment response and positive outcomes are needed. Early identification of patients who would benefit from biologic therapy or surgery is challenging.

Fecal calprotectin more accurately reflects endoscopic activity of ulcerative colitis than the Lichtiger Index, CRP, and blood leukocytes

Background: Thus far, the correlation of noninvasive markers with endoscopic activity in ulcerative colitis (UC) according to the modified Baron Index is unknown. We aimed to evaluate the correlation between endoscopic activity and fecal calprotectin (FC), C-reactive protein (CRP), blood leukocytes, and the Lichtiger Index (clinical score). Methods: UC patients undergoing complete colonoscopy were prospectively enrolled and scored clinically and endoscopically in an independent fashion. Fecal and blood samples were analyzed in UC patients and controls. Results: We enrolled 228 UC patients and 52 controls. Endoscopic disease activity correlated best with FC (Spearman's rank correlation coefficient r = 0.821), followed by the Lichtiger Index (r = 0.682), CRP (r = 0.556), and leukocytes (r = 0.401). FC was the only marker discriminating between different grades of endoscopic activity (grade 0, 20}11 mg/g; grade 1, 44}34 mg/g; grade 2, 111}74 mg/g; grade 3, 330}332 mg/g; grade 4, 659}319 mg/g; P = 0.0018 for discriminating grade 0 vs. 1 and P < 0.001 for discriminating all other grades). FC had the highest overall accuracy (91%) to detect endoscopically active disease (modified Baron Index _2), followed by the Lichtiger Index of _4 (77%), CRP larger than 5 mg/L (69%) and blood leukocytosis (58%). Conclusions: FC better correlated with the endoscopic disease activity than clinical activity, CRP, and blood leukocytes. The strong correlation with endoscopic disease activity suggests that FC represents a useful biomarker for noninvasive monitoring of disease activity in UC patients.

Prevalence and risk factors for therapy escalation in ulcerative colitis in the Swiss IBD Cohort Study

BACKGROUND: Physicians traditionally treat ulcerative colitis (UC) using a step-up approach. Given the paucity of data, we aimed to assess the cumulative probability of UC-related need for step-up therapy and to identify escalation-associated risk factors. METHODS: Patients with UC enrolled into the Swiss IBD Cohort Study were analyzed. The following steps from the bottom to the top of the therapeutic pyramid were examined: (1) 5-aminosalicylic acid and/or rectal corticosteroids, (2) systemic corticosteroids, (3) immunomodulators (IM) (azathioprine, 6-mercaptopurine, methotrexate), (4) TNF antagonists, (5) calcineurin inhibitors, and (6) colectomy. RESULTS: Data on 996 patients with UC with a median disease duration of 9 years were examined. The point estimates of cumulative use of different treatments at years 1, 5, 10, and 20 after UC diagnosis were 91%, 96%, 96%, and 97%, respectively, for 5-ASA and/or rectal corticosteroids, 63%, 69%, 72%, and 79%, respectively, for systemic corticosteroids, 43%, 57%, 59%, and 64%, respectively, for IM, 15%, 28%, and 35% (up to year 10 only), respectively, for TNF antagonists, 5%, 9%, 11%, and 12%, respectively, for calcineurin inhibitors, 1%, 5%, 9%, and 18%, respectively, for colectomy. The presence of extraintestinal manifestations and extended disease location (at least left-sided colitis) were identified as risk factors for step-up in therapy with systemic corticosteroids, IM, TNF antagonists, calcineurin inhibitors, and surgery. Cigarette smoking at diagnosis was protective against surgery. CONCLUSIONS: The presence of extraintestinal manifestations, left-sided colitis, and extensive colitis/pancolitis at the time of diagnosis were associated with use of systemic corticosteroids, IM, TNF antagonists, calcineurin inhibitors, and colectomy during the disease course.

Systematic evaluation of clinical predictors of aggressive ulcerative colitis

Background: Studies evaluating risk factors associated with an "aggressive" disease course in ulcerative colitis (UC) are scarce. A recent definition of "aggressive" UC incorporated the following characteristics: 1) high relapse rate, 2) need for surgery, 3) development of colorectal cancer, and 4) presence of extraintestinal manifestations (EIM). The following factors for an aggressive / disabling disease course in UC have been identified so far: age < 40 years at S140 Poster presentations UC diagnosis, pancolitis, concomitant primary sclerosing cholangitis, and deep ulcerations of the colonic mucosa. We aimed to evaluate risk factors for an "aggressive" disease course in UC patients. Methods: Data from the Swiss IBD cohort study were analyzed. Patients were recruited from university centers (80%), regional hospitals (19%), and private practices (1%). We applied the following definition for "aggressive" UC: 1) patients ever treated with TNFantagonists or calcineurin inhibitors (tacrolimus / cyclosporine), and 2) need for (procto)-colectomy. Non-normal data are presented as median and interquartile range [IQR].

Buccodental health and oral mucositis. Clinical study in patients with hematological diseases

Objectives: The objective of the present study is to assess whether a good buccodental status (evaluated by means of dentogingival indices), is associated with a lower incidence and severity of oral mucositis in patients with hematological diseases who receive treatment with chemotherapy or bone marrow transplant. Study design: The study was carried out on 97 patients admitted to the Hematology Service of the Hospital Duran y Reynals in Barcelona during 2002-2003. These patients received treatment with chemotherapy or conditioning prior to bone marrow transplant. A descriptive study was made, analyzing oral hygiene, one dental index, and two gingivales indices, and evaluating their relationship with the appearance of mucositis. Results: The patients with high plaque (PI) and gingival (GI) indices during chemotherapy presented a higher percentage of mucositis (77.4% and 65.7% respectively) against those who had little or no visible plaque. In the case of the PI, the differences were statistically significant (p=0.015). Likewise, patients who brushed their teeth 3 times/day presented mucositis in only 26.7% of cases, against those who did not brush, or brushed only once a day (65.9% and 68.4%), these differences also being statistically significant (p=0.013). The CAO showed similar results in patients with or without mucositis (7.59 and 7.03 respectively). Conclusions: In our study, a good gingival status as well as good oral hygiene during chemoradiotherapy is associated with a lower incidence and severity of mucositis.

Systematic analysis of factors associated with progression and regression of ulcerative colitis in 918 patients.

BACKGROUND: Studies that systematically assess change in ulcerative colitis (UC) extent over time in adult patients are scarce. AIM: To assess changes in disease extent over time and to evaluate clinical parameters associated with this change. METHODS: Data from the Swiss IBD cohort study were analysed. We used logistic regression modelling to identify factors associated with a change in disease extent. RESULTS: A total of 918 UC patients (45.3% females) were included. At diagnosis, UC patients presented with the following disease extent: proctitis [199 patients (21.7%)], left-sided colitis [338 patients (36.8%)] and extensive colitis/pancolitis [381 (41.5%)]. During a median disease duration of 9 [4-16] years, progression and regression was documented in 145 patients (15.8%) and 149 patients (16.2%) respectively. In addition, 624 patients (68.0%) had a stable disease extent. The following factors were identified to be associated with disease progression: treatment with systemic glucocorticoids [odds ratio (OR) 1.704, P = 0.025] and calcineurin inhibitors (OR: 2.716, P = 0.005). No specific factors were found to be associated with disease regression. CONCLUSIONS: Over a median disease duration of 9 [4-16] years, about two-thirds of UC patients maintained the initial disease extent; the remaining one-third had experienced either progression or regression of the disease extent.

Editorial: Serial Fecal Calprotectin and Lactoferrin Measurements for Early Diagnosis of Pouchitis After Proctocolectomy for Ulcerative Colitis: Is Pouchoscopy No Longer Needed?

This editorial discusses the role of serial measurements of fecal calprotectin or fecal lactoferrin for the early detection of pouchitis in patients with ulcerative colitis having undergone procto-colectomy with ileo-pouch-anal anastomosis. Furthermore, the role of fecal calprotectin and fecal lactoferrin for the monitoring of pouchitis is highlighted.

Infrequent p53 gene alterations in ulcerative colitis

The purpose of this study was to determine whether point mutations and loss of the p53 gene take place in ulcerative colitis which is histologically negative for dysplasia. DNA was extracted from 13 frozen rectal or colon biopsies and blood samples. Ulcerative colitis was classified histologically as active (10 cases) and inactive (3 cases). Exons 5-8 were amplified by PCR, treated with exonuclease and shrimp alkaline phosphatase and sequenced by the dideoxy chain termination method with the Sequenase Version 2.0 DNA sequencing kit. PCR products of intron 6 and exon 4 were digested with MspI and AccII, respectively, for RFLP analysis. No p53 gene mutation was detected in these cases. The number of informative patients for loss of heterozygosity (LOH) at the p53 intron 6 was high, 11 out of 12 (92%), whereas no LOH was observed. LOH affecting p53 exon 4 was not detected in lesions from 5 of 12 patients (42%). In ulcerative colitis, tumor progression is similar to that in sporadic colon cancer, and other oncogenes and tumor suppressor genes are likely to be mutated before the p53 gene.