5-aminosalicylic acid enema (Pentasa) versus hydrocortisone acetate foam (Proctocort) for the treatment of outbreaks of proctitis and cryptogenetic proctosigmoiditis. A comparative randomized multicenter trial]

The therapeutic efficacy of 1 g 5-aminosalicylic acid enema was compared with that of 90 mg hydrocortisone acetate foam following daily rectal administration to patients with idiopathic proctitis or proctosigmoiditis during two weeks. A total of 199 patients (103 5-aminosalicylic acid, 96 hydrocortisone acetate) were included in a randomized, multicenter trial. Endoscopic and clinical remission was seen in 67 and 69 percent of the 5-aminosalicylic acid-treated and in 50 and 45 percent of the hydrocortisone acetate-treated patients (P less than 0.05), respectively. Mild side effects were seen in 10.7 percent of the 5-aminosalicylic acid-treated patients and in 3.1 percent of the hydrocortisone acetate-treated patients (P = 0.05). After 2 weeks, 5-aminosalicylic acid enemas are more effective than hydrocortisone foam for topical treatment of patients with idiopathic proctitis or proctosigmoiditis.     

Low Pentasa Dosage Versus Hydrocortisone in the Topical Treatment of Active Ulcerative Colitis: A Randomized, Double-Blind Study

Objectives : To compare a low dosage (1 g/day) rectal preparation of 5-aminosalicylic acid in slightly acidic, buffered suspension (Pentasa) with a hydrocortisone 100 mg/day enema (Cortenema). Methods : Fifty-two patients with mild to moderate distal ulcerative colitis were randomized under double-blind conditions to receive a rectal preparation of either Pentasa (1 g/day) or Cortenema (100 mg/day) for 3 wk. Results : After 3 wk, both types of treatment resulted in statistically significant improvements in clinical and endoscopic activity. No significant difference was observed between the two drugs in any of the parameters considered, although a statistical trend in favor of Pentasa was evident when analysis was limited to clinical activity ( p = 0.07). No side effects were reported in either group. Conclusions : Our experience confirms that short term topical treatment with a low dosage 5-aminosalicylic acid is at least as effective as 100-mg hydrocortisone enemas in treating mild to moderate distal ulcerative colitis and is generally well tolerated.     

Effects of topical 5-aminosalicylic acid and prednisolone on prostaglandin E2 and leukotriene B4 levels determined by equilibrium in vivo dialysis of rectum in relapsing ulcerative colitis

To determine the influence of inflammation and topical treatment with 5-aminosalicylic acid or prednisolone on arachidonic acid metabolism in vivo, we carried out a double-blind controlled study on the release of prostaglandin E2 and leukotriene B4 to the rectal lumen in 24 consecutive patients with proven distally located ulcerative colitis. Before and at days 15 and 29 a dialysis bag was placed in the emptied rectum for 4 h prior to assessing clinical, endoscopic, and histologic disease activity. A single enema was given daily at bedtime (1 g 5-aminosalicylic acid or 25 mg prednisolone) until complete remission or for a maximum of 4 wk. Clinical and endoscopic remission was obtained in 16 (7 on 5-aminosalicylic acid) and 11 (3 on 5-aminosalicylic acid) patients, respectively. Luminal concentrations of prostaglandin E2 and leukotriene B4 were positively correlated to disease activity and significantly decreased among the prednisolone-treated patients. In both treatment groups a decrease toward normal levels occurred in patients responding to therapy. In retrospect, the pretreatment prostaglandin E2 and leukotriene B4 levels were significantly higher in patients not responding to therapy than in those improving during treatment. In conclusion, luminal prostaglandin E2 and leukotriene B4 levels may prove more useful predictors of the outcome of treatment in relapsing ulcerative colitis than clinical indices of disease activity.     

Randomised controlled trial of azathioprine and 5-aminosalicylic acid for treatment of steroid dependent ulcerative colitis

BACKGROUND AND AIMS: There are limited evidence based data concerning the use of azathioprine in ulcerative colitis. We aimed to compare the efficacy of azathioprine and oral 5-aminosalicylic acid in inducing remission of steroid dependent ulcerative colitis. METHODS: Seventy two patients with steroid dependent ulcerative colitis were admitted to this investigator-blind study. Steroid dependence was defined as a requirement for steroid therapy > or =10 mg/day during the preceding six months, with at least two attempts to discontinue the medication. The disease had to be clinically and endoscopically active at study entry, and all patients were taking systemic prednisolone (40 mg/day). Patients were randomised to receive azathioprine 2 mg/kg/day or oral 5-aminosalicylic acid 3.2 g/day, for a six month follow up period. The outcome of the treatment was defined as (1) success, indicating induction of clinical and endoscopic remission and steroid discontinuation, or (2) failure, indicating the absence of clinical and endoscopic remission and therefore the need for at least one further cycle of systemic steroids to control symptoms, apart from the initial one, or colectomy. RESULTS: Significantly more patients in the azathioprine than in the 5-aminosalicylic acid group had clinical and endoscopic remission, and discontinued steroid therapy, both in the intention to treat (azathioprine v 5-aminosalicylic acid: 19/36 patients (53%) v 7/36 (21%); odds ratio (OR) 4.78 (95% confidence interval (CI) 1.57-14.5)) and per protocol (azathioprine v 5-aminosalicylic acid: 19/33 patients (58%) v 7/34 (21%); OR 5.26 (95% CI 1.59-18.1)) analysis. CONCLUSIONS: Azathioprine is significantly more effective than 5-aminosalicylic acid in inducing clinical and endoscopic remission and avoiding steroid requirement in the treatment of steroid dependent ulcerative colitis.     

Comparison of 5-aminosalicylic acid (3 g) and prednisolone phosphate sodium enemas (30 mg) in the treatment of distal ulcerative colitis. A prospective, randomized, double-blind trial

Twenty-nine patients with attacks of distal ulcerative colitis were treated randomly with 3 g 5-aminosalicylic acid (5-ASA) or 30 mg of prednisolone phosphate sodium (PP) enemas (40 ml). Endoscopic, clinical, and histologic improvement were comparable in the two treatment groups. Our study showed that topical treatment with 5-ASA is as efficacious as PP in improving distal ulcerative colitis.     

Budesonide in inflammatory bowel disease

Due to its immunomodulatory and anti-inflammatory properties glucocorticosteroids have proved to be highly efficacious in patients with inflammatory bowel disease. However, because of the risk of side-effects, the dose and duration of therapy with systemically acting glucocorticosteroids have to be restricted. Recently the use of topically acting glucocorticosteroids has attracted great interest. Among the various topically acting glucocorticosteroids budesonide has emerged as the most promising. Budesonide is highly potent, is readily water-soluble and has low systemic bioavailability, thus reducing the risk of corticosteroid-related side-effects. When given as enema to patients with proctitis or proctosigmoiditis, the efficacy of budesonide is greater than that of placebo and equal to that of prednisolone or 5-aminosalicylic acid enemas. In an enteric-coated formulation budesonide is more effective than placebo in achieving and maintaining remission in patients with ileocecal Crohn's disease. Although corticosteroidrelated side-effects are rare, some suppression of the hypothalamic-pituitary-adrenal axis may occur.     

Drug therapy for ulcerative colitis

Ulcerative colitis (UC) is an inflammatory destructive disease of the large intestine occurred usually in the rectum and lower part of the colon as well as the entire colon. Drug therapy is not the only choice for UC treatment and medical management should be as a comprehensive whole.Azulfidine, Asacol, Pentasa, Dipentum, and Rowasa all contain 5-aminosalicylic acid (5-ASA), which is the topical anti-inflammatory ingredient. Pentasa is more commonly used in treating Crohn‘s ileitis because Pentasa capsules release more 5-ASA into the small intestine than Asacol tablets. Pentasa can also be used for treating mild to moderate UC. Rowasa enemas are safe and effective in treating ulcerative proctitis and proctosigmoiditis. The sulfafree 5-ASA agents (Asacol, Pentasa, Dipentum and Rowasa) have fewer side effects than sulfa-containing Azulfidine. In UC patients with moderate to severe disease and in patients who failed to respond to 5-ASA compounds,systemic (oral) corticosteroids should be used. Systemic corticosteroids (prednisone, prednisolone, cortisone, etc.)are potent and fast-acting drugs for treating UC, Crohn‘s ileitis and ileocolitis. Systemic corticosteroids are not effective in maintaining remission in patients with UC.Serious side effects can result from prolonged corticosteroid treatment. To minimize side effects, corticosteroids should be gradually reduced as soon as the disease remission is achieved. In patients with corticosteroid-dependent or unresponsive to corticosteroid treatment, surgery or immunomodulator is considered. Immunomodulators used for treating severe UC include azathioprine/6-MP,methotrexate, and cyclosporine. Integrated traditional Chinese and Western medicine is safe and effective in maintaining remission in patients with UC.     

Double blind, controlled trial of 4-aminosalicylic acid and prednisolone enemas in distal ulcerative colitis.

Corticosteroid or 5-aminosalicylic acid enemas are the treatment of choice for distal ulcerative colitis but up to one third of patients may be unresponsive. As an alternative therapy might be advantageous, the efficacy of six weeks' treatment with 2 g 4-aminosalicylic acid (4-ASA) (n = 24) and 20 mg prednisolone enemas (n = 21) were compared in a double blind, randomised trial in patients with acute distal (less than 30 cm from the anus) ulcerative colitis. Baseline demography and clinical severity were similar in both groups. Five of 24 patients receiving 4-ASA and 4 of 21 receiving prednisolone did not complete the trial because of deteriorating symptoms, failure to improve, or side effects. At the time of leaving the trial, 24 hour stool frequency, the presence of blood in the stools, and histological and sigmoidoscopic appearances were similar in both groups. Symptomatic improvement occurred in 17 of 24 patients receiving 4-ASA compared with 11 of 21 receiving prednisolone (chi 2 = 1.62, NS). Complete symptomatic improvement occurred in 9 of 24 patients receiving 4-ASA compared with 5 of 21 receiving prednisolone (chi 2 = 0.98, NS). Histological improvement was seen in 9 of 24 patients on 4-ASA compared with 7 of 21 on prednisolone (chi 2 = 0.08, NS). One patient receiving 4-ASA was considered to have an idiosyncratic reaction to the drug but other side effects were not considered to be drug related. Thus, 4-ASA, previously used in the treatment of tuberculosis (para-aminosalicyclic acid), is as good as prednisolone in the treatment of distal ulcerative colitis and should be considered in patients unresponsive to steroids or in whom steroid treatment is undesirable.     

Maintenance Oral Sulfasalazine Prolongs Remission in Ulcerative Proctitis and Proctosigmoiditis

We have retrospectively compared the effectiveness of five different regimens for inducing and maintaining clinical remission in 206 patients with idiopathic proctitis (n = 115) and proctosigmoiditis (n = 91). The five therapeutic regimens were: corticosteroid enemas, 5-aminosalicylic acid (5-ASA) enemas, oral 5-ASA (sulfasalazine or mesalamine), corticosteroid enemas plus oral 5-ASA, or 5-ASA enemas plus oral 5-ASA. Clinical remission was achieved within 28 days of therapy in 47%, and eventually in 94% of these patients. No significant differences in efficacy were found among the five regimens. Most patients ultimately experienced a recurrence of symptoms, but the duration of remission was significantly longer with maintenance oral sulfasalazine or mesalamine (17.2 months) than with no therapy (11.8 months), P less than 0.01. We conclude that several regimens are equally effective in inducing remission of proctitis and proctosigmoiditis, although prolonged therapy may be needed to accomplish this goal. Maintenance oral 5-ASA significantly prolongs symptomatic remission in proctitis and proctosigmoiditis.     

Superoxide inhibition following different stimuli of respiratory burst and metabolism of aminosalicylates in neutrophils

Reactive oxygen species such as superoxide radicals have been proposed to play an important role in the pathogenesis of inflammatory bowel disease. Some of the antiinflammatory actions of aminosalicylates have been ascribed to their capability to scavenge superoxide radicals directly or to inhibit its production in stimulated neutrophils. However, as a controversy still exists with regard to the precise mechanisms of inhibition and the metabolism within inflammatory cells, we compared scavenger properties of 5-aminosalicylic acid, 4-aminosalicylic acid,N-acetyl aminosalicylic acid, olsalazine, and benzalazine in systems with defined superoxide radical generation such as the dimethyl sulfoxide-NaOH and the potassium superoxide system. We also studied possible inhibition of the superoxide production following different stimuli of the respiratory burst in neutrophils and investigated the uptake and potential metabolism (N-acetylation) of 5-aminosalicylic acid in lipopolysaccharide-primed and resting neutrophils. We found that 5-aminosalicylic acid and 4-aminosalicylic acid had defined scavenger properties in the dimethyl sulfoxide-NaOH or potassium superoxide systems, respectively, whereas compounds with a modified aminophenolic structure had no effects. At the cellular level, 5-aminosalicylic acid inhibited phorbol myristate acetate (100 ng/ml)-activated superoxide generation to 82.3±9.3%, the formylmethionyl leucyl peptide (10^–5 M) to 61.0±6.8%, and the NaF (20 mM) -stimulated production to 32.3±3.2% (X±sd,P<0.01). the=" actions=" of=" the=" other=" drugs=" were=" less=" pronounced.=" almost=" identical=" retention=" times=">R _t=11.2 min) of³H-labeled phorbol myristate acetate in the presence and absence of 5-aminosalicylic acid revealed noin vitro interactions. 5-Aminosalicylic acid permeates cells in a dose- and time-dependent manner; there was, however, no acetylation of 5-aminosalicylic acid regardless whether the cells had been stimulated or not with lipopolysaccharide. From our results we suggest that (1) the extra- (scavenger) and intracellular inhibition of superoxide radicals by 5-aminosalicylic acid may be an important mechanism of action, (2) an intact aminophenolic structure may be necessary for such actions, and (3) the inability of inflammatory neutrophils to acetylate and, therefore, inactivate 5-aminosalicylic acid could be an important determinant for its local actions.This work was supported by a grant from Kabi-Pharmacia GmbH, Erlangen, Germany.     

5-Aminosalicylic Acid Suppositories in the Maintenance of Remission in Idiopathic Proctitis or Proctosigmoiditis: A Double-Blind Placebo-Controlled Clinical Trial

Thirty patients with distal ulcerative colitis in remission (17 proctitis, 13 proctosigmoiditis) were randomly given either 5-aminosalicylic acid (5-ASA) or placebo suppositories, 400 mg bid. During the 1-yr follow-up, patients were assessed clinically every month, and flexible sigmoidoscopy with a rectal pinch biopsy specimen and laboratory data were carried out every 3 months. Two patients in the 5-ASA group chose to withdraw from the study, one relapsed, and 12 remained in remission. In the placebo group, one patient chose to withdraw, 11 relapsed, and three remained in remission. The cumulative remission rate at the 12th month was 92% in the 5-ASA group and 21% in the placebo group. Log rank test showed a significant difference in the relapse rate between the two groups (chi 2 = 14.26, p less than 0.001). No side effects were observed. We conclude that 5-ASA in suppository form (800 mg/day), administered for 1 yr, is safe and effective in maintaining remission of distal ulcerative colitis.     

Intermittent therapy with high-dose 5-aminosalicylic acid enemas for maintaining remission in ulcerative proctosigmoiditis

Sixty patients who had presented recently with a relapse of mild to moderate ulcerative colitis with rectosigmoid involvement were randomly assigned to treatment with either 5-aminosalicylic acid enemas (N=29) or oral sulfasalazine (N=31). All patients were in remission, which was documented by clinical, histologic, and endoscopic criteria. Five-aminosalicylic acid treatment was administered on an intermittent schedule, consisting of 4 gm daily for the first seven days of each month; sulfasalazine was given as continuous therapy (2 gm daily as oral tablets). The study period was 2 years. Overall, 9 relapses occurred in the 5-aminosalicylic acid group and 12 occurred in the sulfasalazine group. The actuarial relapse rate at 12 months was 20 percent in the 5-aminosalicylic acid group and 24 percent in the sulfasalazine group; at 24 months, these rates were 37 and 43 percent, respectively. The actuarial relapse curves of the two groups were very similar. The relapse severity was also similar between the two groups. These results show that the authors proposed schedule of maintenance treatment with high-dose 5-aminosalicylic acid enemas is effective in subjects with rectosigmoiditis. This form of intermittent therapy may therefore be proposed for maintaining remission in patients who are refractory to oral and/or rectal treatment with sulfasalazine and steroids or who are intolerant or allergic to sulfasalazine. Treatment with 5-aminosalicylic acid enemas for seven days each month can also constitute an alternative for patients who favor the intermittent schedule over the classic continuous regimen of oral administrations.Presented in part at the International Meeting, Clinical Controversies in Inflammatory Bowel Disease, September 9 to 11, 1987, Bologna, Italy.     

Bioavailability of 5-aminosalicylic acid from slow release 5-aminosalicylic acid drug and sulfasalazine in normal children

The bioavailability of a controlled release 5-aminosalicylic acid preparation (Pentasa) was investigated in nine healthy children after a medication period of six days (1000 mg/day) and compared with sulfasalazine (Salazopyrin) (2000 mg/day). The local bioavailability in the distal gut lumen, reflected by the 5-aminosalicylic acid concentration in the fecal water, showed comparable values after Pentasa (4.44 mmol/liter) and Salazopyrin (6.25 mmol/liter). The concentration ofN-acetyl-5-ASA was significantly higher after Pentasa, reflecting the more proximal release of 5-aminosalicylic acid compared with Salazopyrin. No relation was found between the 5-aminosalicylic acid fecal water concentration and the 5-aminosalicylic acid dose per kilogram of body weight. The urinary excretion of 5-aminosalicylic acid andN-acetyl-5-aminosalicylic acid was higher after Pentasa than after Salazopyrin (32% vs 25%). Dose interval plasma concentration curves showed low values after both preparations. Based on the concept that the fecal water concentration is decisive for the efficacy of 5-aminosalicylic acid in distal inflammatory bowel disease, Pentasa treatment offers a relevant alternative in cases of Salazopyrin intolerance or allergy in children. The higher systemic bioavailability from Pentasa warrants monitoring of the renal function.     

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.     

A case of eosinophilic pneumonia possibly associated with 5-aminosalicylic acid (5-ASA)]

A 30-year-old man was diagnosed as having ulcerative colitis and was treated with 2,250 mg/day of 5-aminosalicylic acid (5-ASA). After 4 weeks of the administration, the patient complained of cough and fever and was admitted to our hospital. His chest radiograph showed infiltrative shadows bilaterally in the lung fields. Peripheral blood analysis indicated eosinophilia. We confirmed eosinophilic pneumonia by bronchoalveolar lavage and transbronchial lung biopsy. Improvement in clinical symptoms and radiological findings was obtained after the cessation of 5-ASA and initiation of prednisolone. Finally, mesalazine-induced eosinophilic pneumonia was diagnosed on the basis of his clinical course. The literature contains a few reports on patients with mesalazine-induced eosinophilic pneumonia.     

Prevention by Intrarectal 5-Aminosalicylic Acid of <Emphasis Type="Italic">N</Emphasis>-Methylnitrosourea–Induced Colon Cancer in F344 Rats

PURPOSE: The protective effect of 5-aminosalicylic acid against colon carcinogenesis was investigated. METHODS: Eighty female F344 rats aged seven weeks received an intrarectal dose of 2 mg N-methylnitrosourea dissolved in 0.5 ml of water three times weekly for five weeks to induce colon cancer. Beginning at 6 weeks after the last dose of N-methylnitrosourea, the rats were treated with an intrarectal dose of 1 mg 5-aminosalicylic acid suspended in 0.5 ml of vehicle solution (0.3 percent water solution of methylcellulose) three times weekly for 15 weeks. RESULTS: Colon cancer incidence and mean number of tumors per rat at the end of the 15-week treatment period were significantly lower and smaller in the 5-aminosalicylic acid–treated group (10 percent and 0.2) than in the vehicle-treated (80 percent and 1.6) and untreated (68 percent and 1.1) control groups. However, the mean numbers of tumors per tumor-bearing rat were comparable: 1.5, 2, and 1.6. No distinct differences among the groups were observed in the tumor pathology with respect to their location (within 0–10 cm proximal to the anus), shape (plaque shaped or polypoid), size (<10 mm in diameter), invasion (restricted to the mucosa or submucosa), or histologic type (differentiated adenocarcinoma). CONCLUSION: Our results indicate that 5-aminosalicylic acid administered directly into the colonic lumen strongly suppresses the promotion stage of colon carcinogenesis.     

Double-blind,placebo-controlled evaluation of 5-ASA suppositories in active distal proctitis and measurement of extent of spread using<Superscript>99m</Superscript>Tc-labeled 5-ASA suppositories

Patients with active distal proctitis received either 5-aminosalicylic (5-ASA) acid or identical placebo suppositories, 500mg t.i.d. for 6 weeks. Activity at 3 and 6 wks was assessed using a Disease Activity Index (DAI), derived from four categories: number of daily evacuations more than usual, evacuations containing blood, sigmoidoscopy appearance, and physician's overall assessment. Each category was graded 0–3. There was thus 0–12 points scored ranging from complete remission to severe disease. A minimum score of 3 from two categories was necessary for study entry. Of 27 patients randomized, 14 received active medication and 13 placebo. Of the 14 patients, with initial mean DAI 7.1 ±1.8, 11 were in complete remission at 6 wks (78.6%). Whereas, there was no significant change in the placebo group, with initial mean DAI 7.1±1.8. An additional 6 patients with inflammatory bowel disease and 6 healthy volunteers were given^99mTc-labelled 5-aminosalicylic acid suppositories. The extent of spread was limited to the rectum, and the suppositories were retained for 3 hours. There was no absorbed radioactivity. 5-ASA suppositories are safe, well-tolerated, and effective treatment for active distal proctitis.     

L-glutamine enemas attenuate mucosal injury in experimental colitis

PURPOSE: The aim of this study was to investigate the role of I-glutamine, short chain fatty acid, prednisolone, and mesalazine (5-aminosalicylic acid) enemas on mucosal damage and inflammation in experimental colitis. METHODS: Colitis was induced in rats with trinitrobenzene sulfonic acid in ethanol. Saline (n=14), prednisolone (n=13), 5-aminosalicylic acid (n=14), I-glutamine (n=14), and short chain fatty acid (n=13) enemas were applied twice daily to the rats for seven days after the induction of colitis. The sham group (n=9) received only saline enemas. Rats were killed at the seventh day and their colonic macroscopic inflammatory scores were determined. Colonic mucosal gamma glutamyl transpeptidase activity and colonic mucosal malondialdehyde levels were measured. The same measurements but no enemas were done in the control group (n=7). RESULTS: There were significant differences in macroscopic inflammatory scores between sham and colitis groups (P<0.001). The macroscopic inflammatory scores of the colitis group were higher than the short chain fatty acid and glutamine groups (P<0.05). Whereas the mucosal gamma glutamyl transpeptidase activity was diminished in prednisolone, 5-aminosalicylic acid, and short chain fatty acid groups when compared with the control group; in the colitis, sham, and glutamine groups the activity of this enzyme did not change. The mucosal malondialdehyde levels were significantly lower in the prednisolone and glutamine groups than in the colitis group. CONCLUSION: Only one of four agents tested, namely, I-glutamine enemas, could decrease the severity of colitis both morphologically and biochemically. Moreover, L-glutamine prevented the colitis-induced oxidant injury in the colonic mucosa. On the other hand, prednisolone and short chain fatty acids seemed to improve only the physiologic changes of colitis.Supported by The Scientific and Technical Research Council of Turkey.Presented in part at the 8th European Congress of Surgery, Budapest, Hungary, 17 to 20 June, 1998.     

The role of aminosalicylates in the treatment of ulcerative colitis

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.     

Is argon plasma coagulation an efficient treatment for digestive system vascular malformation and radiation proctitis?

BACKGROUND AND AIMS: Argon beam coagulation is an innovative no-touch electrocoagulation technique in which high-frequency monopolar alternating current is delivered to the tissue through ionized argon gas. The aim of this prospective study was to evaluate the efficacy and safety of argon plasma coagulation (APC) for the treatment of hemorrhagic digestive vascular malformations and hemorrhagic radiation proctosigmoiditis. METHODS AND PATIENTS: From March 1998 through April 1999, we used endoscopic APC (ERBE, Lyon, France, argon gas source ICC 300, high-frequency electrosurgical generator ICC 200, gas flow 1 L/min, power setting 50 W) to treat 39 consecutive patients (mean age 70.3 +/- 10 years). The indications for treatment were anemia (n =10), active or oozing haemorrhage (n =15) from digestive angiodysplastic lesions (n =25), hemorrhagic antral telangiectatic vascular lesions (n =2), and hemorrhagic radiation proctosigmoiditis (n =12) after failure of medical treatments (5-aminosalicylic acid, corticosteroids, or sucralfate enemas). The efficacy of APC treatment was evaluated on symptoms, transfusion requirement, bleeding recurrence, hemoglobin value before and 6 months after APC therapy. RESULTS: On the average, 1 +/- 0.5 sessions per patient was required to treat digestive vascular malformations. Definitive haemostasis of digestive angiodysplastic lesions with active or oozing haemorrhage was achieved in one session in all patients. No bleeding recurrence was observed during the follow-up period of 6 months. Anemia recurrence was observed in 2 patients (7%). Average hemoglobin levels recorded before and 6 months after APC therapy were 78.8 +/- 21.2 g/L and 108 +/- 13.7 g/L, respectively (P<0.05). On the average, 2.8 +/- 0.8 sessions per patient were required to treat hemorrhagic radiation proctosigmoiditis. Ten patients (83%) reported improvement or cessation of rectal bleeding, most of them immediately after APC therapy. Endoscopic control was performed one month after APC therapy and showed complete disappearance of lesions in 8 patients (66%). Average hemoglobin levels recorded before and 6 months after APC therapy were of 102.7 +/- 21 g/L and 120 +/- 19.5 g/L, respectively (P <0.05). Complications were observed in 5 cases (13%): pneumoperitoneum in 2 cases, chronic rectal ulcerations in 2 cases, and nonsymptomatic rectal stenosis in 1 case. CONCLUSION: APC appears to be a simple, safe, and effective technique in the management of hemorrhagic radiation-induced proctosigmoiditis and hemorrhagic lesions.