Treatment Of Ulcerative Proctitis Research Articles

Experimental Study on the Treatment of Ulcerative Proctitis in Rats by Combining Baitouweng Decoction with Mesalamine Retention Enema

To study the effect and mechanism of Baitouweng decoction, mesalamine and its combination with an enema in the treatment of ulcerative proctitis in rats is the objective of the study. The rats were divided into seven groups: Control (Normal), model (ulcerative proctitis), mesalamine, Baitouweng decoction, lowdose Baitouweng decoction combined with mesalamine, medium-dose Baitouweng decoction combined with mesalamine, high-dose Baitouweng decoction combined with mesalamine group. Except for the control group, all rats were induced with a 5 % acetic acid solution for ulcerative proctitis. The severity of ulcerative proctitis was measured by the disease activity index score; morphological changes of rectal tissue were observed by hematoxylin and eosin staining; expression of cytokines tumor necrosis factor alpha, interleukin-1 beta, interleukin-6, interferon‐gamma, interleukin-10 messenger ribonucleic acid was detected by reverse transcription-polymerase chain reaction; Western blot analysis of signaling pathway proteins nuclear factor kappa B p65 and phosphorylated-nuclear factor kappa B p65 and the expression of tight junction proteins claudin-1, occludin and zonula occludens-1 was detected by Western blot and immunohistochemistry. The results revealed that the disease activity index scores of rats in each dosing group were significantly lower than those in the ulcerative proctitis group. After treatment, the expression of pro-inflammatory factors tumor necrosis factor alpha, interleukin-1 beta, interleukin-6 and interferon‐gamma was inhibited and the expression of the anti-inflammatory factor interleukin-10 was up-regulated. In conclusion, Baitouweng decoction combined with mesalamine had a synergistic effect on the treatment of ulcerative proctitis. The mechanism of action may be to regulate the synthesis and release of inflammatory factors by inhibiting the over-activation of nuclear factor kappa B p65, reducing the damage of pro-inflammatory factors to rectal mucosa and repairing the intercellular tight junction structure, thus improving the intestinal barrier and reducing the rectal inflammatory response.

P656 Is there a role for additional oral mesalamine therapy in the treatment of ulcerative proctitis with skip inflammation?

P656 Is there a role for additional oral mesalamine therapy in the treatment of ulcerative proctitis with skip inflammation?

Intractable Proctitis in a 46-Year-Old Man

46-year-old man was referred to the gastroenterAology clinic by the colorectal surgical team for medical management of presumed ulcerative proctitis. He had been investigated 1 year previously for bloody diarrhea when colonoscopy had revealed florid proctitis. Despite the initiation of oral and topical mesalamine, he continued to complain of the passage of blood per rectum associated with tenesmus and some recent weight loss. Repeat colonoscopy revealed a single, large ulcer in the rectum (Figures A and B) with a well-circumscribed, rolled edge that felt soft on biopsy. Examination was otherwise normal to the terminal ileum. The histology was atypical for inflammatory bowel disease but suggested a chronic ulcer without granulomata and with minimal crypt architectural distortion in the adjacent mucosa. Polymerase chain reaction of rectal biopsy confirmed infection with Chlamydia trachomatis and was consistent with lymphogranuloma venereum (LGV). On questioning, the patient reported a history of receptive anal intercourse. Human immunodeficiency virus (HIV) and syphilis serology were negative. The symptoms responded well to a 3-week course of doxycyline 100 mg twice daily, and repeat sigmoidosopy after 3 months confirmed ulcer healing (Figure C). Particularly in cases where the response to conventional treatment of ulcerative proctitis is poor, the possibility of infective proctitis should be considered and appropriate sexual history obtained. Several sexually transmitted infections including chlamydiosis, gonorrhea, syphilis, and herpesvirus can cause proctitis. Histology is usually nonspecific in the setting of LGV proctitis, and

Comparison of Xilei-san, a Chinese Herbal Medicine, and Dexamethasone in Mild/Moderate Ulcerative Proctitis: A Double-Blind Randomized Clinical Trial

Xilei-san is a traditional Chinese herbal medicine that has proven to be of possible use in the treatment of ulcerative proctitis (UP) in a pilot study. This study was intended to compare Xilei-san with dexamethasone enemas in subjects with mild-to-moderate active UP. A double-blind randomized study was performed in 35 subjects. During the initial 8 weeks, the subjects received an enema of Xilei-san or dexamethasone at bedtime, then discontinued the treatment and were followed for 12 weeks. All of the subjects received 3 g/day oral mesalazine during the entire study. The disease activity was assessed at inclusion and at weeks 4, 8, and 20. Both treatments showed significant improvement in clinical, endoscopic, and histological grades in comparison with the baseline. Xilei-san enemas are comparable to dexamethasone enemas in this study. This medicine is safe, well accepted, and may be an alternative drug in the treatment of mild-to-moderate active UP.

Treatment of Newly Diagnosed Ulcerative Proctitis in Community-Based Practice

Purpose: Treatment of ulcerative proctitis (UP) is aimed at controlling inflammation and reducing symptoms. While orally administered 5-aminosalicylates (“5-ASAs”) traditionally have been the mainstay of acute and maintenance therapy for UP, 5-ASA suppositories or enemas are generally considered to be first-line therapy, due to evidence that they are more effective at inducing and maintaining remission. Little is known, however, about how UP is typically treated in community-based practice. Methods: Using a large US healthcare claims database, we identified all persons with evidence of newly diagnosed UP (ICD-9-CM 556.2, 556.3) between 1/1/2005 and 12/31/2007, based on: (1) ≥2 encounters for UP ≤90 days apart; (2) evidence of sigmoidoscopy/colonoscopy within 60 days of first visit for UP (“index date”); and (3) no evidence of receipt of any medication used to treat UP (eg, 5-ASA, glucocorticoid, etc.) in the year preceding index date. All patients were followed for 365 days from their index date. We examined pharmacotherapy for UP over post-index periods of 30 days and 365 days alternatively. Results: We identified a total of 518 patients with newly diagnosed UP. Mean (SD) age was 48 (16) years, and there were equal numbers of men and women. Forty-five percent of patients were seen by a gastroenterologist at initial visit. In the 30-day post-index period, 37% of patients had evidence of receipt of mesalamine suppository; 23%, an oral 5-ASA; 12%, mesalamine enema; 12%, rectal hydrocortisone; and 6%, oral prednisone. Antidiarrheals, antimetabolites, and TNF inhibitors were rarely used. Over the entire 365-day post-index period, the number of patients ever-prescribed 5-ASA suppositories increased to 45%; oral 5-ASAs, 38%; 5-ASA enemas, 18%; and systemic glucocorticoids, 20%. Combination and sequential treatment was frequent. Over 365 days, 24% of patients had evidence of receipt of both oral and rectal 5-ASAs; 11%, rectal 5-ASAs and rectal steroids; 2%, rectal 5-ASAs and budesonide; and 11%, rectal 5-ASAs and systemic steroids. Conclusion: While local therapy is commonly prescribed in patients with newly diagnosed UP, approximately one in four patients receive an oral 5-ASA preparation. In the year following diagnosis, one in five patients receive systemic steroids—a marker of failure of conservative therapy and/or disease progression. Our findings suggest that treatment of newly diagnosed UP by community-based physicians largely conforms to guidelines and recommendations. Support: This research was funded by Axcan Pharma Inc., which manufactures and markets a 5-ASA suppository (Canasa®). Disclosure: This research was funded by Axcan Pharma Inc., which manufactures and markets a 5-ASA suppository (Canasa®).

Appendicectomy as a Therapy for Ulcerative Proctitis

Available data regarding whether appendicectomy performed after the onset of ulcerative colitis can modulate its clinical course are currently limited. This study aimed at addressing this issue. In this study, we report a prospective case series of 30 adult patients (median age 35 years, range 17-70 years; male/female: 11/19) with ulcerative proctitis (median duration of symptoms 5 years, range 8 months to 30 years; median Simple Clinical Colitis Activity Index score 9, range 7-12), who underwent appendicectomy in the absence of any history suggestive of previous appendicitis. Patients were subsequently followed up clinically with the assessment of the Simple Clinical Colitis Activity Index for a median of 14 months (range 9-32 months). After appendicectomy, the clinical activity index improved significantly to a median score of 2 (range 0-12) (P<0.0005). The improvement in the clinical activity index occurred in 27 of 30 (90%) patients, whereas the index remained unchanged in the remaining 3 of 30 (10%) patients. Furthermore, 12 of 30 (40%) patients experienced a complete resolution of symptoms (clinical activity index score of 0) by 12 months, such that all pharmacological treatments could be withdrawn, and have remained in remission off all previous treatments for a median 9 months (range 6-25 months). The time required for a complete resolution of symptoms post appendicectomy ranged from 1 to 12 months (median 3 months) (Kaplan-Meier analysis). None of the clinical or histological factors analyzed were significantly associated with post-appendicectomy outcome. This case series, the largest reported so far, provides rationale for controlled trials to properly evaluate the possible role of appendicectomy in the treatment of ulcerative proctitis.

Tripotassium dicitrato bismuthate enemas in the treatment of ulcerative proctitis

Eleven patients with active proctitis or proctosigmoiditis completed one month's treatment with tripotassium dicitrato bismuthate enemas administered at night. Symptoms, sigmoidoscopic appearances, and the histological grade of acute inflammation were assessed at the commencement of therapy and after one month. An overall score of these features showed improvement in 9 of 11 patients, which encourages further investigation of bismuth in controlled trials for patients with inflammatory bowel disease.

A Meta-Analysis of the Placebo Rates of Remission and Response in Clinical Trials of Active Ulcerative Colitis

Knowledge of the placebo outcomes and understanding specific study features that influence these outcomes is important for designing future clinical trials evaluating therapy of ulcerative colitis (UC). The aims of this study were to estimate the placebo rates of remission and response in placebo-controlled, randomized clinical trials for active UC and to identify factors influencing these rates. We performed a systematic review and meta-analysis of placebo-controlled, randomized clinical trials evaluating therapies for active UC identified from MEDLINE from 1966 through 2005. Forty studies met the inclusion criteria. The pooled estimates of the placebo rates of remission and response were 13% (95% confidence interval, 9%-18%; range, 0%-40%; median, 12%) and 28% (95% confidence interval, 23%-33%; range, 0%-67%; median, 30%), respectively, both with significant heterogeneity. Studies that used more stringent definitions of outcomes had lower placebo rates of remission and response. Study duration, number of study visits, disease duration, baseline composite and rectal bleeding scores of the disease activity index, and inclusion of endoscopic mucosal healing as the remission definition all were associated with the placebo remission rate. Rates of remission in the placebo arm of UC clinical trials ranges from 0% to 40%. The placebo remission rates are influenced by the trial length, number of study visits, use of stricter remission definitions, and design features that enroll patients with more active disease. These factors should be considered when designing future placebo-controlled clinical trials in patients with active UC.

Medical management of left-sided ulcerative colitis and ulcerative proctitis: Critical evaluation of therapeutic trials

The goal of this work was to critically evaluate the published studies on the treatment of ulcerative proctitis (UP) and left-sided ulcerative colitis (L-UC). The results of this review provided the content for the accompanying treatment guidelines, Clinical Guidelines for the Medical Management of Left-sided Ulcerative Colitis and Ulcerative Proctitis: Summary Statement. All English language articles published between 1995 and September 2005 were identified through a comprehensive literature search using OVID and PubMed. The quality of the data supporting or rejecting the use of specific therapies was categorized by a data quality grading scale. An "A+" grade was assigned to treatment supported by multiple high-quality randomized controlled trials with consistent results, whereas a "D" grade was given to therapy supported only by expert opinion. The therapeutic efficacy of a treatment was defined by its success in treating UP and L-UC compared with placebo. A medication was ranked as "excellent" if it was specifically studied for UP and L-UC and had consistently positive results compared with placebo or another agent. Quality and efficacy scores were agreed on by author consensus. For the acute treatment of UP or L-UC, the rectally administered corticosteroids and mesalazine (5-ASA), either alone or in combination with oral 5-ASAs, are the most effective therapy: evidence quality, A+; efficacy, excellent. Only rectally administered 5-ASA received an A+/excellent rating for maintenance of remission. Infliximab received an A+ grade for induction and maintenance of remission but only a "good" rating because the studies were performed in all UC, not specifically UP or L-UC. This critical evaluation of treatment provides a "report card" on medications available for the management of patients with UP and L-UC. The guidelines should provide a useful reference and supplement for physicians treating UC patients.

Diagnosis and treatment of ulcerative proctitis.

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.

Efficacy and Tolerance of 5-Aminosalicylic Acid Suppositories in the Treatment of Ulcerative Proctitis: A Review of Two Double-Blind, Placebo Controlled Trials

The efficacy and tolerance of 500 mg 5-aminosalicylic acid (mesalamine) suppositories in the treatment of ulcerative proctitis were assessed in two double-blind, placebo controlled studies of six weeks' duration, involving a total of 173 patients. In trial 1, patients used one 500 mg suppository tid. In trial 2, patients used one 500 mg suppository bid. Physician's global assessment and a disease activity index based upon patient symptoms and sigmoidoscopic appearance were used to assess efficacy. At the endpoint of trial l (tid), there was an 80.4% mean reduction in the disease activity index seen in patients treated with mesalamine compared to a 36.8% mean reduction in the placebo group (P&lt;0.05). Analysis of the physician's global assessment indicated that 84.2% of patients receiving mesalamine were considered to be 'much improved' compared to 41 % of patients on placebo (P&lt;0.01). At the endpoint of trial 2 (tid), there was a 74.7% mean reduction in disease activity index compared to 34.2% in the placebo group (P&lt;0.001). Analysis of the physician's global assessment indicated that 79.2% of the mesalamine group was considered to be 'much improved' compared to 26.2% on placebo (P&lt;0.001). There was no significant difference in efficacy seen in patients treated with 500 mg mesalamine suppositories bid or tid. Mesalamine suppositories are effective and well tolerated in the treatment of ulcerative proctitis.

Mesalazine (5-Aminosalicylic Acid) Suppositories in the Treatment of Ulcerative Proctitis or Distal Proctosigmoiditis: A Randomized Controlled Trial

A multicentre double-blind study was conducted to evaluate the efficacy and tolerability of 1 g or 1.5 g mesalazine daily compared with placebo in 94 patients with mild to moderate distal proctosigmoiditis (less than 20 cm). The study end point was the determination of clinical, endoscopic, and histologic remission rates at 4 weeks. Eleven patients, nine receiving placebo and two receiving 1.5 g mesalazine, withdrew during trial, mostly because of worsening of symptoms. At 4 weeks clinical remission was achieved in 7 of 31 (39%) patients with placebo, in 22 of 32 (69%) patients in the 1 g mesalazine group, and 23 of 31 (74%) patients in the 1.5 g mesalazine group. No serious clinical or biochemical side effect of treatment was reported. Mesalazine suppositories are safe, well tolerated, and very effective in patients with active distal proctosigmoiditis: 500 mg twice daily appears a suitable dose regimen.

Transit time in ulcerative proctitis.

Whole-gut transit time was measured by the time taken for an orally administered dose of brilliant blue dye to disappear from the stool in 20 patients with ulcerative proctitis and in 20 age- and sex-matched controls. Ten of the patients had active, and 10 inactive disease. The dye usually appeared in the stool with the next bowel movement after ingestion in both patients and controls; however, the time at which the dye disappeared from the stool (transit time) was prolonged to 76.1 h in the patients, compared with 50.2 h in the controls (p less than 0.01). This delay occurred both in patients with active disease at 70.5 h (p less than 0.05) and in those with inactive disease at 81.8 h (p less than 0.05). This prolongation of transit time may be relevant to both the pathogenesis and treatment of ulcerative proctitis.

II. Treatment of Ulcerative Proctitis

The incidence of ulcerative proctitis or proctosigmoiditis is 10 to 40% of whole ulcerative colitis patients in USA, British Kingdom and also in Japan. In our series, extent of involvement was limited to rectum or rectosigmoid in 10 out of 43 cases of ulcerative colitis. By the administration of salazopyrin, complete symptomatic relief was obtained in 75%, and endoscopic remission was observed in 69% of the cases. Patients in which the effects of solazopyrine were not complete, responed well to local steroid therapy. Medical management and prognosis of ulcerative proctitis were discussed.

The Treatment of Ulcerative Proctitis by Zinc Kataphoresis

The Treatment of Ulcerative Proctitis by Zinc Kataphoresis