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Pouchitis is the most common complication of Proctocolectomy with ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC). The diagnosis of pouchitis requires the presence of symptoms, together with characteristic endoscopic and histological abnormalities. The exact cause of pouchitis is not known. Whereas ‘acute’ pouchitis can be treated rapidly and successfully in the majority of patients, “refractory” and ‘chronic pouchitis’ remain therapeutic challenges to patients and physicians. Metronidazole and Ciprofloxacin budesonide enemas and oral probiotic therapy with VSL#3 all appear to be effective therapies for acute and/or chronic pouchitis. The medical therapy of pouchitis remains largely empiric, and additional multicenter, randomized, double-blind, placebo-con- trolled, dose-ranging trials are needed. In future trials, treatment indications such as active acute or chronic pouchitis and maintenance of remission for acute or chronic pouchitis should be clearly defined.

Although new salicylates are now available for the treatment of ulcerative colitis, sulphasazaline still has an important therapeutic role. The role of salicylates in Crohn's disease is limited to the mild activity phase; further data are required to clarify its role in maintenance on remission. New steroids are a real alternative to traditional steroids in active ulcerative colitis and Crohn's disease.

Although new salicylates are now available for the treatment of ulcerative colitis, sulphasazaline still has an important therapeutic role. The role of salicylates in Crohn's disease is limited to the mild activity phase; further data are required to clarify its role in maintenance on remission. New steroids are a real alternative to traditional steroids in active ulcerative colitis and Crohn's disease.

Bacteria are present throughout the GI tract but their pattern and concentrations vary greatly. Probiotics are living microorganisms that belong to the normal intestinal flora and are important to the health and well-being of the host. The concept of probiotic therapy is still controversial; there are many data from in vitro and animal studies, however, to date the beneficial effects of probiotics in humans have mostly been demonstrated under poorly defined experimental conditions. Several experimental and clinical observations suggest a role for the intestinal microflora in inflammatory bowel disease (IBD) pathogenesis and there is increasing evidence supporting the potential therapeutic role for probiotics in the treatment of IBD. The use of probiotics to treat GI infections has produced contrasting results; their efficacy in the prevention or treatment of infective diarrhoea was evaluated in a large number of studies; however, the most convincing evidence of their benefit concerns rotavirus infection in children. Future research needs to focus on obtaining more precise information on the composition of the enteric microflora and the mechanisms of action of probiotics.

Thirty-nine patients with documented active distal proctitis (<20 cm) received either 5-aminosalicylic acid (5-ASA) enemas (2 g in 100 ml) or suppositories 1 g b.i.d., in a controlled study. Twenty patients received enemas, while 19 patients received suppositories, for 30 days. No difference could be observed in terms of efficacy; however, it was the patients' opinion that treatment with suppositories was easier than that with enemas (p < 0.01).

In Crohn's disease, prednisone is believed to be ineffective for relapse prevention. Because all patients with Crohn's Disease Activity Index lower than 150 and with some altered lab tests (erythrocyte sedimentation rate, C-reactive protein, alpha-1 -acid gly coprotein, alpha-1 -acid antitrypsin, and white blood cell count) had a clinical relapse in 18 months of follow-up, we tried to ascertain whether methylprednisolone could reduce the risk of clinical relapse in such patients. Eighteen patients were included in a controlled study against placebo. Nine patients were treated with methylprednisolone at a dosage of 0.25 mg/kg daily for a period of 6 months; treatment was discontinued if disease relapsed or if lab tests were normalized. During the steroid treatment, 1 of 9 patients showed a clinical relapse; in 7, the normalization of lab tests was obtained; in 5 of these 7 patients a relapse occurred within 1 month after the suspension of the treatment; in 1 patient, lab tests remained altered. In those 9 patients on placebo, relapses occurred in 7. We conclude that methylprednisolone was effective in the prevention of relapses for patients in clinical remission but with altered lab tests.

A multicentre double-blind study was conducted to evaluate the efficacy and toler-ability of 1 g or 1.5 g mesalazine daily compared with placebo in 94 patients with mild to moderate distal proctosigmoiditis (<20cm). 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.

Background: Rectal treatment with mesalazine enemas is the first-line therapy for distal ulcerative colitis. In order to improve the benefits of rectal therapy, a new 60 mL 5-ASA rectal gel enema preparation has been developed using a device which excludes direct contact of the inert propellant gas with the active drug. The purpose of the present study was to assess by scintigraphy the colonic distribution of this new mesalazine rectal gel enema.

Mesalazine suppositories at 500 mg b.d. are a safe and effective treatment for patients with ulcerative proctitis or distal proctosigmoiditis. Recently a mesalazine 1 g suppository (Pentasa) has been developed.

Background: Mucosal inflammation of the ileal pouch (pouchitis) is the major long-term complication after ileal pouch-anal anastomosis for ulcerative colitis. Broad-spectrum antibiotics are the mainstay of treatment, however, 15% of patients with pouchitis have a chronic, treatment-resistant disease.

We report two cases of pulmonary involvement in ulcerative colitis. The first patient, a 37-year-old woman, had bilateral basal bronchiectasis full of mucopurulent secretion, with a marked improvement of pulmonary function and roentgenographic appearance after a conservative approach. The second patient had severe pulmonary fibrosis of autoimmune nature and died owing to a pulmonary infection. In the second patient, a sulfasalazine reaction as an etiologic factor was excluded, while in the first this possibility seemed unlikely. Therefore, we take these two cases as examples of the extraintestinal manifestations of ulcerative colitis.

A controlled trial has been carried out in order to compare the efficacy of enemas containing a high dosage of 5-ASA (4g) versus enemas containing hydrocortisone 100 mg. The trial was conducted on 86 patients, 44 of whom received 5-ASA and 42 received hydrocortisone. The results were favorable in terms of clinical, sigmoidoscopic, and histologic criteria for 5-ASA treatment. Other aspects have been investigated, such as retrograde spread of enemas which have been shown to reach the left colon. No nephrotoxicity was detected. The long term experience confirmed the preliminary positive results.

Concentrations of interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) were determined by solid-phase ELISA in tissue homogenates of mucosal biopsy specimens obtained from pelvic ileal pouches in 13 patients with pouchitis (reservoir ileitis) and 17 with pouches without pouchitis. Normal ileal mucosa was used as a control. IL-1β was detected in all tissue homogenates from patients with pouchitis compared with only 29% from pouches without pouchitis and none from controls. IL-6 and IL-8 were present in all pouchitis specimens, in 70% of the specimens from nonpouchitis and only 30% of specimens from controls. TNF-α was undetectable in all specimens examined. The concentrations of IL-1β, IL-6, and IL-8 were significantly greater (P<0.001) in biopsy specimens from pouchitis compared to those from pouches without pouchitis or normal ileal mucosa and in patients with pouchitis tissue levels of IL-1β significantly correlated with IL-6 (P<0.05) and IL-8 (P<0.01). Furthermore IL-1 and IL-8 levels were significantly higher in tissue specimens from nonpouchitis pouches than in those from normal ileal mucosa (P<0.02). These results suggest that an enhanced cellular immunity operatesin vivo at the mucosal level in pouchitis as in the case of ulcerative colitis.

PURPOSE: The aim of our study was to compare the efficacy and safety of oral mesalazine with mesalazine suppositories in patients with active ulcerative proctitis. PATIENTS AND METHODS: A four-week, randomized, single-blind trial was performed in 58 patients with active, histologically confirmed ulcerative proctitis (≤15 cm) to evaluate the efficacy and safety of oral 800-mg mesalazine tablets taken three times per day (n=29) compared with 400 mg of mesalazine suppositories administered three times per day (n=29). Patients were evaluated at study entry and after two and four weeks. Efficacy evaluations included a disease activity index, which represents a score with four variables: stools frequency, rectal bleeding, mucosal appearance, and physician's assessment of disease severity. Histologic activity was also assessed at study entry and after two and four weeks in accordance with the criteria by Truelove and Richard. Safety assessment included clinical laboratory parameters and adverse event reports. RESULTS: There were no significant differences with regard to baseline comparisons of demographics and severity between the two treatment groups. Improvement in mean disease activity index score was significantly greater with suppositories compared with oral mesalazine, both at two-week and four-week visits (mean disease activity index scores at baseline, two, and four weeks: suppositories = 7.7, 2.59, and 1.48; tablets = 7.42, 5.72, and 3.48, respectively (P<0.001)). The rate of histologic remission was significantly greater with suppositories compared with tablets both at two and four weeks (P<0.01). There were no significant differences in adverse events or clinical laboratory results between treatment groups. CONCLUSIONS: Results of this study indicate that treatment with mesalazine suppositories produces earlier and significantly better results than oral mesalazine in the treatment of active ulcerative proctitis.

Medical treatment of ulcerative colitis and Crohn's disease is based on the results of clinical trials. For treatment of ulcerative colitis, in addition to the use of corticosteroids at different dosages and routes according to severity of attacks, there is now a place for high dosage of oral mesalamines or, even better, for topical treatment using suppositories or rectal enemas; the use of mesalamine colonic foams seems promising. Enemas with corticosteroids, which are topically active and have no systemic effects, are providing good results. Long-term treatment has been done with sulfasalazine; now new oral mesalamine or diazoderivative compounds are available and rectal mesalamine preparations have shown a prophylactic effect. Treatment of pouchitis, usually with metronidazole, might benefit also by a topical approach—either with mesalamine or steroids. Crohn's disease patients might be more safely treated using new corticosteroids along with traditional steroids, which can avoid systemic side effects, but high dosages of oral mesalamines are also useful to induce remission. The antibacterial agent metronidazole appears to be beneficial, whereas the role of antimycobacterial agents needs further clinical investigation. For prevention of relapse, low or intermittent dosage of steroids seems to offer some benefit and possibly oral mesalamine. In refractory or steroid-dependent Crohn's disease, patients on azathioprine or 6-mercaptopurine usually have a better outcome, whereas cyclosporine is effective in a short, but not long-term, period. Methotrexate should be cautiously used in patients in whom immunosuppressive agents have failed. New selectively acting agents, such as lipoxygenase inhibitors, eicosapentanoic acid, free-radical scavengers, and interleukin-1 receptor antagonists, are now under clinical investigation.

The medical management of patients with inflammatory bowel disease derives from attempts and errors. Historical studies have shown the utility of corticosteroids for inducing remission of attacks of ulcerative colitis and for active Crohn's disease; sulfasalazine has been mainly used for preventing relapses in ulcerative colitis patients. Immunosuppressive agents such as azathioprine or 6-mercaptopurine have been used either in steroid-resistant patients or those with refractory disease, and now cyclosporine is under clinical investigation. Antibiotics, above all metronidazole, have shown efficacy in patients with Crohn's disease, mainly with perianal involvement, and now tobramycin seems to have a role in active colitis. The oral aminosalicylate derivatives, a second generation of sulfasalazine, have been shown to be effective in preventing relapses in ulcerative colitis and Crohn's disease patients. When administered at high dosages, they have also controlled mild attacks of active ulcerative colitis and of Crohn's disease as well. Their primary indication, however, is for patients who cannot take sulfasalazine. Topical administration of mesalamine has been used with excellent results. This agent is given either in enema or suppository form in patients with distal colitis. Nutritional support seems to have a role as a primary therapeutic step in active Crohn's disease and also as long-term treatment. A new exciting area of investigation is the possibility of selective inhibition at different levels of the inflammatory cascade.

Abstract: The clinical course of Crohn's disease in 131 patients was studied for a mean period of 4.2±3.2 years. The clinical activity of the disease, expressed as percentage of patients per year in an active phase, is high in the first year (70.2 percent) and progressively decreases during subsequent years (25 percent after seven years). The percentage of patients who needed steroid treatment is high during the first year (68 percent) and falls to 19 percent after seven years. An operative risk rate of 54 percent was registered, with a probability of reoperation equal to 34 percent. Clinical relapse after the first surgery occurred in 70 percent of cases. The registered mortality was 6.9 percent, with a ratio of 6 to 1 between observed and expected mortality. In conclusion, the disease, while showing a tendency to reduce its activity over the years, is burdened by a risk of surgery and mortality which progressively increases with time

Background: Mucosal inflammation of the ileal pouch (pouchitis) is the major long‐term complication after ileal pouch‐anal anastomosis for ulcerative colitis. Broad‐spectrum antibiotics are the mainstay of treatment, however, 15% of patients with pouchitis have a chronic, treatment‐resistant disease.

Background: Rectal treatment with mesalazine enemas is the first‐line therapy for distal ulcerative colitis. In order to improve the benefits of rectal therapy, a new 60 mL 5‐ASA rectal gel enema preparation has been developed using a device which excludes direct contact of the inert propellant gas with the active drug. The purpose of the present study was to assess by scintigraphy the colonic distribution of this new mesalazine rectal gel enema.

The effect of domperidone, a peripheral antidopaminergic drug, on sigmoid motor activity in the irritable bowel syndrome, has been evaluated by measuring pressures in 3 opentipped tubes perfused with distilled water at a constant flow rate of 0.636 ml/min and inserted into the sigmoid colon. Domperidone 20 mg i.v. in 10 patients, did not induce any significant change in basal motility, but prevented the increase in motor activity produced by the infusion of dopamine 5 µg/kg/min for 10 min. It appears that domperidone had no effect on sigmoid motor activity, although the inhibition of dopamine-induced motility confirms the presence of specific dopaminergic receptors in the colon and the antidopaminergic action of domperidone.

Sulpiride, a benzamide derivative, selectively antagonizes dopaminergic receptors within and outside the central nervous system. Dopamine has previously been shown to increase colonic motility. In the present investigation the motor response of the pelvic colon to a standard 1000 calorie meal was studied in 12 patients with the irritable bowel syndrome. The meal induced a significant increase in motor activity, lasting for 1 h and greatest in the first 30 min. In 6 cases the administration of sulpiride 100 mg i.m. significantly reduced the postprandial increase in colonic motor activity. Thus dopaminergic receptors may be involved in the colonic motor response to food.

Thein vitro antioxidant capacity of sulfasalazine (SASP), its metabolites (SP, 5-SSA), and olsalazine (OAZ), was studied by evaluating their effects on superoxide (O2-•) production. Assay systems were the xanthine-xanthine oxidase (X/XOD) reaction and phorbol myristate acetate (PMA)-activated polymorphonuclear leukocytes (PMNs), using the cytochromec (cyt-c) reduction assay and a luminol-dependent chemiluminescence method. 5-ASA, SASP, and OAZ showed a dose-dependent scavenger effect in both O2-• generating systems, 5-ASA being the most powerful (>50% of inhibition in the PMNs system and >70% in the X/XOD system at 10 µM concentration). SP had an inhibitory effect only in the PMNs system but did not modify the activity of xanthine oxidase, thus excluding a scavenger action. These data suggest that the scavenger effect of 5-ASA, SASP, and OAZ may be an important mechanism of action.

Fish oil has been recently proposed as a possible effective treatment in inflammatory bowel disease (IBD); however, a lot of annoying side effects (ie, belching, halitosis, diarrhea, etc) affect patient compliance. We carried out a study of patient tolerance in a group of Crohn's disease (CD) patients with a new fish oil derivative consisting of 500-mg capsules of eicosapentaenoic-docosahexaenoic (EPA 40%-DHA 20%), a free fatty acid mixture (Purepa), and we also evaluated its incorporation into phospholipids, both in plasma and in red cell membranes. Five groups of 10 CD patients in remission received nine Purepa capsules daily in four different preparations (A: uncoated, B: coated, pH 5.5; C: coated, pH 5.5, 60 min time release; D: coated, pH 6.9) and 12 × 1-g capsules daily of a triglyceride preparation (Max-EPA, EPA 18%-DHA 10%), respectively. We coated three of the four Purepa preparations in order to delay the release of contents in an attempt to minimize the side effects. After six weeks of treatment, the group taking Purepa capsules, coated, pH 5.5, 60 min time release (group C) showed the best incorporation of EPA and DHA in red blood cell phospholipid membranes (EPA from 0.2 to 4.4%, DHA from 3.7 to 6.3%), and no side effects were registered, whereas in all other groups side effects were experienced in 50% or more of subjects. This new preparation will make it possible to treat patients for long periods.

Cimetropium bromide is an antimuscarinic compound with antispasmodic properties. Its effect on meal-stimulated sigmoid motor activity in 30 patients with the irritable bowel syndrome, mainly with pain and constipation, has been evaluated.

An increase in splanchnic blood flow in both arterial and venous beds has been demonstrated in inflammatory bowel disease (IBD) by means of angiographic and scintigraphic studies. Doppler ultrasound (US) enables a non-invasive evaluation of splanchnic arterial inflow in the superior mesenteric artery (SMA) and of venous outflow in the portal vein. The aim of this study was to assess the role of Doppler US in detecting changes in the hemodynamic variables measured in patients with IBD. Forty-five patients with IBD were studied, including 22 with Crohn's disease (CD) and 23 with ulcerative colitis (UC), and compared with 45 matched normal subjects. The mean velocity of portal flow (Vmean) and the resistance index (RI) of the SMA were evaluated by Doppler US. In CD the Vmean of portal flow was significantly higher in patients with active disease than in controls (p < 0.001) and patients with inactive disease (p < 0.001). The RI of the SMA was significantly lower in active disease than in controls (p < 0.005), but no significant difference was noted between active and inactive CD. Also in UC, the Vmean of portal flow was significantly higher in patients with active disease than in controls (p < 0.01) and patients with inactive disease (p < 0.05). The RI of the SMA was significantly lower in active disease than in controls (p < 0.005) and in patients with inactive disease (p < 0.005). Doppler follow-up studies were carried out in 10 patients after initiation of treatment. A normalization of hemodynamic variables occurred in 7 of 10 patients in whom clinical and laboratory remission was noted (p < 0.01 for Vmean and p < 0.05 for RI). This preliminary study suggests the utility of Doppler US in the non-invasive evaluation of hemodynamic changes in IBD. Whether this can translate into a helpful tool for the assessment of disease activity and patient management requires further investigation.

Abstract: In an attempt to know the exact retrograde spread of high-dosage 5-aminosalicylic acid enemas, we have studied eight patients with active left-sided colitis, by adding a small amount of barium sulfate to the enemas and by checking the spread radiologically after 15 minutes, 1 hour, and 6 hours. Four grams of 5-aminosalicylic acid in 100-ml enemas and 4 gm in 200-ml enemas were used. The same experiment was repeated in a subsequent attack, with enemas labeled with technetium-99m and checked by scintiscans in five of these patients. We always have observed a volume-dependent spread of enemas but, interestingly, in the patients studied with technetium-99m there was always a wider spread than that which was detected with barium enemas. In all five patients, 100-ml enemas reached the splenic flexure. In two patients with total colitis, a progression of 100-ml technetium-99m enemas was performed in the transverse colon, but the maximum opacity remained in the left side. We can conclude that 4 gm of 5-aminosalicylic acid in 100-ml enemas can be suitable for treating patients with left-sided colitis, and will represent a valid addition for patients with more extensive colitis.

Interleukin-1, a cytokine produced by macrophages and other tissue cells, has a major role in inflammatory and immunological responses. Increased levels of IL-1 activity have been reported in experimental colitis and in patients with active Crohn's disease (CD) and ulcerative colitis (UC). IL-1β release from fresh and cultured colonic biopsies and IL-1β plasma concentrations was determined in 15 patients with active UC, 16 with UC in remission and 10 normal control subjects. Biopsies, taken at colonoscopy were weighed, washed in 1 ml of 0.9% sodium chloride solution and then cultured for 24 h in 10% fetal calf serum/RPMI. IL-1β activity was determined by ELISA KIT (Cystron Biotechnology) in plasma samples, washing solution and the incubation medium. Very low levels of IL-1β were detected only in 3 plasma samples, all from active patients. Significantly more IL-1β was released from fresh and cultured colonic mucosa obtained from patients with UC in remission compared to normal mucosa (p<0.01). Furthermore, specimens from active UC released significantly more IL-1β than those from patients in remission (p<0.01). In conclusion, IL-1 may play an important role in mediating the inflammatory response in UC.

Steroids are very useful drugs in the treatment of active Crohn's disease (CD), but clinical relapses after steroid withdrawal may be very high.

Clinical experience with mesalazine enemas in the treatment of ulcerative colitis is reviewed. After rectal administration, plasma mesalazine levels remain low, and 15% of the administered dose is recovered in the urine. Enemas containing 2 and 4g of mesalazine have been shown to be effective, safe, and well tolerated by patients with mild and moderate ulcerative colitis. Patients who cannot tolerate sulfasalazine and patients who do not respond to other treatments have been successfully treated with mesalazine enemas. Suppositories of mesalazine are more suitable for patients with disease confined to the distal region of the colon, whereas mesalazine enemas should be used in patients with more extensive disease. Mesalazine enemas have also been used for maintenance therapy in ulcerative colitis.

Steroids are very useful drugs in the treatment of active Crohn's disease (CD), but clinical relapses after steroid withdrawal may be very high.

Interleukin-1, a cytokine produced by macrophages and other tissue cells, has a major role in inflammatory and immunological responses. Increased levels of IL-1 activity have been reported in experimental colitis and in patients with active Crohn's disease (CD) and ulcerative colitis (UC). IL-1β release from fresh and cultured colonic biopsies and IL-1β plasma concentrations was determined in 15 patients with active UC, 16 with UC in remission and 10 normal control subjects. Biopsies, taken at colonoscopy were weighed, washed in 1 ml of 0.9% sodium chloride solution and then cultured for 24 h in 10% fetal calf serum/RPMI. IL-1β activity was determined by ELISA KIT (Cystron Biotechnology) in plasma samples, washing solution and the incubation medium. Very low levels of IL-1β were detected only in 3 plasma samples, all from active patients. Significantly more IL-1β was released from fresh and cultured colonic mucosa obtained from patients with UC in remission compared to normal mucosa (p<0.01). Furthermore, specimens from active UC released significantly more IL-1β than those from patients in remission (p<0.01). In conclusion, IL-1 may play an important role in mediating the inflammatory response in UC.

Sixty-two patients with ulcerative colitis localised to the distal sigmoid colon and rectum (<20 cm) entered the trial. Thirty-two were treated with 5-ASA 500 mg suppositories (Asacol) 3 times a day for 1 month while 30 received a placebo given in the same regime. Clinical, sigmoidoscopic and histological assessment was carried out before, after 15 days and after 1 month of treatment. At the end of the study 5-ASA suppositories showed significantly better results in all the parameters recorded than placebo (p<0.01). There were no unwanted effects related to the use of suppositories. This treatment should therefore be offered as a first choice for patients with distal rectosigmoiditis.