Strictureplasty for Crohn's disease of the small bowel in the biologic era: long-term outcomes and risk factors for recurrence.

BACKGROUND: The number of indications for strictureplasty for Crohn's disease has been greatly reduced since the widespread use of biologics, although the risk of intestinal failure remains. The aim of the study was to analyze the outcomes of strictureplasty and to identify risk factors for site-specific recurrence in the era of biologics. METHODS: Consecutive patients treated with strictureplasty for Crohn's disease between 2002 and 2018 were retrospectively included. Univariate analysis was carried out. Risk factors for recurrence were identified through a multilevel logistic regression analysis. RESULTS: Two hundred sixty-six patients were included in the study ( 171 males, median age 39.5 years, range 18-76 years). The majority of the 718 strictures requiring surgery in these patients were located in the ileum (61%), treated with conventional strictureplasty (89.6%) and required an additional resection (73.7%). Median follow-up time and time to recurrence were 96 months and 62.5 months respectively. The site-specific recurrence rate was 12.2% at 5 years and 25.7% at 10 years. Smoking was associated with a higher risk of recurrence in patients with milder disease. The 10-year recurrence rate was significantly higher for strictureplasties performed in the terminal ileum (30.9%, p = 0.0019) as compared to the ileum (21.8%) and the jejunum (8.4%). Multilevel logistic regression analysis showed that postoperative exposure to biologics (OR 4.74, p 0.001), nonconventional strictureplasty (OR 3.57, p 0.008) and a strictureplasty performed on a previous anastomosis (OR 13.58, p 0.002) were associated with site-specific recurrence. CONCLUSIONS: Strictureplasty is associated with optimal long-term outcomes in the biologic era and should be performed when feasible, to reduce the risk of intestinal failure in Crohn's disease patients.

Influence of male human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection on the reproductive outcomes in serodiscordant couples: a case-control study.

BACKGROUND: Nowadays, serodiscordant couples (SDCs) with human immunodeficiency virus (HIV) or hepatitis C virus (HCV)-infected men have the chance to conceive safely, giving birth with a minimum risk of cross-infection. OBJECTIVE: To assess the impact of male HIV and HCV infection on the assisted reproductive technologies (ART) outcomes in SDCs, with HIV or HCV seropositive men and negative partners. MATERIALS AND METHODS: Of 153 couples: 24 in Group 1 (HIV-seropositive men), 60 in Group 2 (HCV-seropositive men) and 69 in Group 3 (controls). Sperm-washing procedure was performed using a three-step system. Fresh ICSI cycles were carried out in HIV SDCs, HCV SDCs and controls. Seminal parameters, fertilization rate (FR), cleavage rate (CR), pregnancy rate per cycle (PR/C), miscarriage rate, implantation rate (IR) and live birth rate were evaluated. RESULTS: All the seropositive men have undetectable viral loads at the time of insemination, and both partners were free from co-morbid infections. The median number of embryos transferred was 2.0 (IQR 1.0-3.0), with no differences among groups. FR was significantly reduced in HIV and HCV SDCs compared to the controls (66%, 61% and 75%, respectively; p < 0.01). CR was similar between groups (p = 0.3). IR was 12.1%, 11.1% and 14.1%, respectively, in the three groups (p = 0.30). PR/C was 21.7%, 17.6% and 20.2% in HIV, HCV and controls, respectively. Live birth rate per cycle was 17.4%, 15.7% and 15.9%, respectively. There were no significant differences in clinical pregnancies per cycle, as well as miscarriages and live births (p = 0.30; 0.30; 0.60, respectively). CONCLUSIONS: The sperm-washing technique with ICSI may generate a promising way to improve pregnancy outcomes and to reduce the risk of viral transmission in these couples. In this setting, we can correctly counsel HIV- and HCV-infected men of SDCs with regard to the likelihood of father their own biological child.

Risk of permanent stoma in extensive Crohn's colitis: the impact of biological drugs.

AIM: The overall risk of permanent stoma was determined in patients with extensive Crohn's colitis. An attempt was made to analyse whether biological drugs have modified the surgical approach in patients with anorectal involvement. METHOD: In all, 233 patients with Crohn's disease colitis operated on between 1995 and 2010 were reviewed retrospectively. Fifty-one were treated before 2002 (prebiological era) and 182 after 2002 (biological era). The relationship was determined between the use of immunosuppressors, biological drugs, the presence of perianal disease and anorectal stenosis and the rate of permanent stoma formation. RESULTS: In the prebiological era 23 (45.1%) patients without anorectal involvement underwent colectomy and ileorectal anastomosis, 17 (33.3%) with severe anorectal disease had proctocolectomy and 11 (21.6%) with anorectal involvement had abdominal colectomy with permanent ileostomy. In the biological era 73 (40.1%) patients without anorectal involvement underwent colectomy and ileorectal anastomosis, nine (5%) with severe anorectal involvement had proctocolectomy and 100 (54.9%) with anorectal involvement had colectomy with terminal ileostomy. Of these 100, 75 have subsequently been treated with biological drugs with full regression of anorectal lesions in 81.3%. Rates of permanent stoma in the prebiological and biological era were 60.8% and 19.2% (P < 0.001). Univariate and multivariate analysis showed that only the use of biological drugs was significantly associated with an increased rate of rectal preservation (P < 0.05). CONCLUSION: The risk of a permanent stoma in patients with Crohn's colitis and anorectal involvement is significantly reduced with combined surgical and biological treatment.

New insights into the brain involvement in patients with Crohn's disease: a voxel-based morphometry study.

BACKGROUND: Crohn's disease (CD) is a chronic intestinal disorder characterized by overproduction of inflammatory cytokines and recurrent abdominal pain. Recently, brain morphological abnormalities in the pain matrix were found in patients with chronic pain disorders including irritable bowel syndrome. To investigate potential structural brain changes associated with CD, we used magnetic resonance imaging (MRI). Furthermore, we tested whether in patients gray matter (GM) volumes correlated with disease duration. METHODS: Eighteen CD patients in remission and 18 healthy controls underwent structural MRI. Voxel-based morphometry (VBM) is a fully automated technique allowing identification of regional differences in the amount of GM enabling an objective analysis of the whole brain between groups of subjects. VBM was used for comparisons and correlation analysis. KEY RESULTS: With respect to controls, CD patients exhibited decreased GM volumes in portion of the frontal cortex and in the anterior midcingulate cortex. Disease duration was negatively correlated with GM volumes of several brain regions including neocortical and limbic areas. CONCLUSIONS & INFERENCES: Crohn's disease is associated with brain morphological changes in cortical and subcortical structures involved in nociception, emotional, and cognitive processes. Our findings provide new insight into the brain involvement in chronic inflammatory bowel disorders.

Randomized controlled trials in pouchitis.

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.

Distinct proteomic profiles characterise non-erosive from erosive reflux disease.

BACKGROUND: Erosive reflux disease (ERD) and non-erosive reflux disease (NERD) are often regarded as part of the spectrum of the same disease. AIM: To elucidate molecular features that characterise NERD and ERD at the protein level. METHODS: A total of 56 consecutive subjects were enrolled: 10 healthy subjects, 24 with NERD and 22 with ERD. Eight specimens were taken from macroscopically normal mucosa at 5 cm of gastro-oesophageal junction. Four were processed for the proteins extraction and four for evaluation using haematoxylin-eosin and immunohistochemistry. We used shotgun proteomics to identify tentative disease molecular features for ERD or NERD. Candidate distinctive proteins were verified using immunohistochemistry. RESULTS: Shotgun proteomics analysis revealed 33 differentially expressed proteins in NERD vs. ERD samples, involved in cellular proliferation, keratinisation, stress responses and sugar metabolism. Based on a gene ontology meta-analysis, seven of them were further analysed using Western blotting (WB) and four also using immunohistochemistry. We identified novel candidate disease molecular features for GERD and few distinctive proteins to discriminate NERD and ERD. In particular, Transitional Endoplasmic Reticulum ATPase (TER ATPase), GAPDH, Alpha 1 Acid Glycoprotein 1, Annexin A1, Calmodulin and 14-3-3 proteins were confirmed at WB analysis. CONCLUSIONS: Non-erosive reflux disease and ERD are distinct disease entities at the protein level. This study proposes an array of candidate biomarkers possibly useful to discriminate between NERD and ERD.

Selective cyclooxygenase-2 silencing mediated by engineered E. coli and RNA interference induces anti-tumour effects in human colon cancer cells.

BACKGROUND: Cyclooxygenase-2 (COX-2) overexpression is strongly associated with colorectal tumourigenesis. It has been demonstrated that the chronic use of non-steroidal anti-inflammatory drugs (COX inhibitors) partially protects patients from colorectal cancer (CRC) development and progression but induces severe cardiovascular side effects. New strategies for selective COX-2 blockade are required. METHODS: We developed an improved technique, based on RNA interference (RNAi), to gain a selective COX-2 silencing in CRC cells by a tumour-dependent expression of anti-COX-2 short-hairpin RNA (shCOX-2). Anti-COX-2 shRNA-expressing vectors were delivered in CRC cells (in vitro) and in colon tissues (ex vivo) using engineered Escherichia coli strains, capable of invading tumour cells (InvColi). RESULTS: A highly tumour-dependent shCOX-2 expression and a significant COX-2 silencing were observed in CRC cells following InvColi strain infection. Cyclooxygenase-2 silencing was associated with a strong reduction in both proliferative and invasive behaviour of tumour cells. We also demonstrated a pivotal role of COX-2 overexpression for the survival of CRC cells after bacterial infection. Moreover, COX-2 silencing was achieved ex vivo by infecting colon tissue samples with InvColi strains, leading to anti-inflammatory and anti-tumour effects. CONCLUSION: Our RNAi/InvColi-mediated approach offers a promising tool for a highly selective COX-2 blockade in vitro and in vivo.

Potential role of the cannabinoid receptor CB in the pathogenesis of erosive and non-erosive gastro-oesophageal reflux disease.

BACKGROUND: Cannabinoid (CB) receptors have been located in brain areas involved in the triggering of TLESRs as well as in the nodose ganglion from which vagal afferents emanate. The distribution of CB(1) receptors has been investigated in the human gastrointestinal mucosa, as expression of inflammatory process. AIM: To evaluate the CB(1) expression in oesophageal mucosa. METHODS: A total of 87 consecutive subjects were enrolled: 10 controls, 39 NERD and 38 erosive oesophagitis. Eight specimens were taken from macroscopically normal mucosa. Five were processed by haematoxylin-eosin, MIB1/CB(1) evaluation and three for the RNA and proteins extraction. RESULTS: The mean MIB1-LI value was 31% and 22% in NERD and ERD patients, respectively, compared to 68% in the healthy subjects. Mean CB(1)mRNA/GUSB mRNA value of the controls was 0.66, while in GERD patients, it was 0.28. In NERD and ERD, the mean values of CB(1)/GUSB were 0.38 and 0.17, respectively, with highly significant differences between the NERD vs. ERD groups. Semi-quantitative analysis of CB(1) expression, performed with WB, shows in NERD patients a higher CB(1) receptor expression than ERD patients. CONCLUSIONS: With this study, we showed for the first time the presence of CB(1) receptors in the human oesophageal epithelium.

Impact of tissue harmonic imaging on measurement of nuchal translucency thickness.

OBJECTIVES: To evaluate the effect of tissue harmonic imaging (THI) on the measurement of fetal nuchal translucency thickness (NT). METHODS: One-hundred and three pregnant women underwent first-trimester NT measurement according to The Fetal Medicine Foundation criteria. NT was evaluated using conventional ultrasonography (CUS) and THI without modifying any other ultrasound parameter (e.g. gain). For each patient three images with CUS and three images with THI were stored and then measured independently on the ultrasound system by two different operators. The maximum measurements using CUS and THI were compared. Differences between the values of CUS and THI NT measurements were tested using the Wilcoxon signed-rank test. Bland-Altman plots were constructed, and intraobserver and interobserver variabilities were assessed by calculation of the intraclass correlation coefficient. Probability values of < 0.05 were considered significant. RESULTS: Mean maternal age was 32.8 (range, 20-42) years, mean gestational age at examination was 12 + 1 (11 + 0 to 13 + 6) weeks and mean crown-rump length (CRL) was 55.8 (SD, 7.2) mm. Median fetal NT was 1.4 (0.8-3.5) mm using CUS and 1.2 (0.6-3.3) mm using THI (P < 0.001) for the first operator. A second operator remeasured the first 51 cases: median fetal NT was 1.4 (0.8-3.8) mm using CUS and 1.1 (0.6-3.1) mm using THI (P < 0.001). Fetal NT measurements were above the expected median value according to CRL in 49 cases (47.6%) using CUS and in only 24 cases (23.3%) using THI. CONCLUSIONS: THI leads to a small, but significant, reduction of the NT measurement and this could reduce the sensitivity of screening for Down syndrome.

Implications of antioxidant enzymes in human gastric neoplasms.

The present study is the first to evaluate the expression and activity of MnSOD, Cu/ZnSOD and catalase in human gastric samples, since ROS play a significant role in the pathogenesis of different forms of malignancy inducing mutations and various diseases such as gastric cancer. Biopsies and surgical samples from 53 patients (male/female 22/31, mean age 56.5+/-15.8 years) consisted of 15 healthy, 12 autoimmune atrophic gastritis, 10 Helicobacter pylori (HP) infection, 8 HP-negative chronic gastritis (CG) and 8 adenocarcinoma cases. Enzyme activity and expression were evaluated by spectrophotometry and immunoblotting after specific extraction in phosphate buffer. We found that MnSOD activity was increased in adenocarcinoma, CG and HP tissues (p<0.05-0.001), while Cu/ZnSOD was significantly lower in adenocarcinoma and HP tissues (p<0.001) when compared to the healthy control. MnSOD and Cu/ZnSOD were expressed to a significantly higher degree in adenocarcinoma and HP tissues (p<0.05 and <0.001 respectively) and to a significantly lower degree in CG tissues with respect to the healthy patients (p<0.05 and <0.001). A significant decrease in CAT activity in adenocarcinoma and HP tissues was observed (p<0.01 and <0.05). Gastric human neoplasms showed significant changes in antioxidant enzymes, that represent the first line in antioxidant protection against radical attack. The difficulties in correlating the antioxidant enzyme with the neoplasms was related to the complexity of the biochemical pathways that regulate the cellular redox balance. Our results are important in enhancing the understanding of the role that these enzymes play in the promotion/suppression of the carcinogenesis cascade in human gastric mucosa.

Medical treatment and management of severe ulcerative colitis.

Severe colitis is a life-threatening complication of ulcerative colitis. Early recognition of the severity of the colitis and intensive treatment and monitoring have all contributed to improved outcome. Since their introduction in the 1950s, corticosteroids are the first line therapy for severe active ulcerative colitis (UC). Several prognostic parameters (such as stools movement per day, C-reactive protein, increased amount of intestinal gas or small bowel dilation, hypoalbuminemia, fever, etc.) help the physician to quickly introduce infliximab or cyclosporine or to refer the patient to the surgeon. This decision requires a careful evaluation of the patient and a medical/surgical team.

Interaction of probiotic Lactobacillus and Bifidobacterium strains with human intestinal epithelial cells: adhesion properties, competition against enteropathogens and modulation of IL-8 production.

The human intestinal microbiota plays a pivotal role in human nutrition and health by promoting the supply of nutrients, preventing pathogen colonization and shaping and maintaining normal mucosal immunity. The depletion of the individual microbiota can result in a higher susceptibility to enteropathogenic bacteria infection. In order to reduce this risk, the use of food supplements containing probiotic bacteria has been recently addressed. In this paper, we investigate the protective role toward enteropathogen infection of probiotic strains belonging to Lactobacillus and Bifidobacterium. According to our experimental data, Lactobacillus acidophilus Bar13, L. plantarum Bar10, Bifidobacterium longum Bar33 and B. lactis Bar30 were effective in displacing the enteropathogens Salmonella typhimurium and Escherichia coli H10407 from a Caco-2 cell layer. Moreover, L. acidophilus Bar13 and B. longum Bar33 have been assessed for their immunomodulatory activity on IL-8 production by HT29 cells. Both strains showed the potential to protect enterocytes from an acute inflammatory response. These probiotic strains are potential candidates for the development of new functional foods helpful in counteracting enteropathogen infections.

Ninety-six-hour wireless oesophageal pH monitoring following proton pump inhibitor administration in NERD patients.

BACKGROUND: Comparative studies of proton pump inhibitors (PPIs) have revealed that acid reflux is influenced by PPI treatment, formulations and dosing regimens. Wireless pH capsules have circumvented some of the limitations of conventional catheter-based pH testing with the additional advantage of 96-h recording periods. AIM: To clarify the effectiveness of intra-oesophageal acid suppression by omeprazole, pantoprazole and lansoprazole in non-erosive reflux disease patients through a 4-day monitoring of oesophageal pH and related symptoms. METHODS: Twenty-four patients with typical symptoms of gastro-oesophageal reflux disease were enrolled and administered upper endoscopy and placement of a wireless pH capsule. Patients randomly received omeprazole, pantoprazole or lansoprazole for 3 days after the first 24 h. Symptom-reflux associations were expressed using the symptom index (SI). RESULTS: All patients completed the study. Significant decrease in acid exposure occurred on day 2 and in each successive day in all groups. Pantoprazole and omeprazole are more effective than lansoprazole at inducing a normalization of intra-oesophageal acid exposure at days 2 and 3. Significant reduction in SI at day 2 was observed. CONCLUSIONS: Four-day ambulatory oesophageal pH monitoring is feasible and safe. Omeprazole, pantoprazole and lansoprazole have an equivalent potency for normalizing intra-oesophageal acid exposure after 3 days of treatment in non-erosive reflux disease patients.

Short-term treatment with infliximab in chronic refractory pouchitis and ileitis.

BACKGROUND: Chronic refractory pouchitis is a long-term complication after ileal pouch-anal anastomosis and it may be associated with ileal inflammation. AIM: To determine the efficacy of infliximab in treatment of chronic refractory pouchitis complicated by ileitis, using a wireless capsule endoscopy. METHODS: Sixteen patients with chronic refractory pouchitis complicated by ileitis were enrolled. Pouchitis was diagnosed by clinical, endoscopic and histological criteria. Ileitis was documented using wireless capsule endoscopy. Duodenum-jejunum and proximal-middle ileum were evaluated and the presence of small lesions and large lesions were noted. Crohn's disease, intestinal infections were excluded in all patients. Patients were treated with infliximab and clinical response was recorded. Wireless capsule endoscopy was repeated at week 10 and Pouchitis Disease Activity Index score was determined. RESULTS: Ten patients were enrolled and completed the study. Clinical remission was achieved in nine patients. At wireless capsule endoscopy and pouch endoscopy, a complete recovery of lesions was observed in eight patients. One patient presented four small lesions of the ileum at the 6 weeks of treatment and one patient did not show any modification. Clinical and endoscopic remission was maintained in these eight patients at least 6 months. CONCLUSION: These preliminary results indicate that infliximab may be recommended for the treatment of chronic refractory pouchitis complicated by ileitis.

Controlled study using wireless capsule endoscopy for the evaluation of the small intestine in chronic refractory pouchitis.

BACKGROUND: Pouchitis is a common long-term complication after ileal pouch anal anastomosis for ulcerative colitis. Chronic refractory pouchitis is a treatment-resistant condition that affects 5-15% of patients. AIM: To test the hypothesis of a small bowel involvement using wireless capsule endoscopy. MATERIAL AND METHODS: This is a single-blind, prospective, cohort study. Twenty-four patients: 16 were patients with chronic refractory pouchitis and eight, with a macroscopically and histologically normal ileal pouch, were considered as control subjects. Diagnosis of pouchitis was confirmed using the pouchitis disease activity index. All subjects were submitted to wireless capsule endoscopy procedure. Within 2 weeks before wireless capsule endoscopy, patients underwent a pouch endoscopy and a small bowel follow-through. Re-examination of the colonic surgical and histological specimens was also performed. RESULTS: One patient with chronic pouchitis was excluded because of incomplete bowel cleaning. At small bowel follow-through of 16 patients, two subjects (13%) showed only a focal ectasia of the middle ileum and a substenosis of the pouch. At wireless capsule endoscopy all the 15 evaluable patients with chronic pouchitis (100%) showed diffuse lesions from duodenum to ileum consisting of aphthae, erosions, erythema, atrophy, cobblestone, deep/fissural ulcers. CONCLUSIONS: This enteropathy needs further research, and wireless capsule endoscopy could be useful to show involvement of small bowel in patients with chronic pouchitis.

Oral budesonide in the treatment of chronic refractory pouchitis.

BACKGROUND: Pouchitis is the major long-term complication after ileal-pouch nal anastomosis for ulcerative colitis. Ten to 15% of patients develop a chronic pouchitis, either treatment responsive or treatment refractory. AIM: To evaluate the efficacy of oral budesonide in inducing remission and improving quality of life in patients with chronic refractory pouchitis. METHODS: Twenty consecutive patients with active pouchitis, not responding after 1 month of antibiotic treatment were treated with budesonide controlled ileal release 9 mg/day for 8 weeks. Symptomatic, endoscopic and histological evaluations were undertaken before and after treatment according to Pouchitis Disease Activity Index. Remission was defined as a combination of Pouchitis Disease Activity Index clinical score of < or = 2, endoscopic score of < or = 1 and total Pouchitis Disease Activity Index score of < or = 4. The quality of life was assessed with the Inflammatory Bowel Disease Questionnaire. RESULTS: Fifteen of 20 patients (75%) achieved remission. The median total Pouchitis Disease Activity Index scores before and after therapy were, respectively, 14 (range 9-16) and 3 (range 2-10) (P < 0.001). The median Inflammatory Bowel Disease Questionnaire score also significantly improved from 105 (range 77-175) to 180 (range 85-220) (P < 0.001). CONCLUSION: Eight-week treatment with oral budesonide appears effective in inducing remission in patients with active pouchitis refractory to antibiotic treatment in this open-label study.

In vivo association to human colon of Lactobacillus paracasei B21060: map from biopsies.

BACKGROUND: Adhesion to the intestinal mucosa is one of the main suitable properties for probiotic bacteria. Several in vitro studies have been published, but a very few data are available about the in vivo adhesion to intestinal surfaces of probiotics. Moreover, there are no data regarding the distribution of a probiotic strain along the entire intestine. AIM: The present study aimed to preliminary evaluate the intestinal recovery of a new synbiotic formulation containing Lactobacillus paracasei B21060. METHODS: Seven volunteers participated in the study. Subjects assumed three times a day for 15 days a sachet with a synbiotic preparation containing 5 x 10(9)CFUs of Lactobacillus paracasei strain B21060. Samples were recovered from the faeces and from the cecum, transverse, descending and sigmoid colon. RESULTS: Identification at strain level showed that following administration, strain B21060 could be recovered from all sampled sites (except in one subject), representing 66.6% of the total vancomycin insensitive CFUs isolated from faecal samples, and 74.7% isolated from colonic samples. CONCLUSIONS: Our results demonstrate that Lactobacillus paracasei B21060 probiotic strain is able to temporarily associate throughout the different sites of the entire intestinal tract.

Review article: aminosalicylates for distal colitis.

About two-thirds of patients with ulcerative colitis have an inflammatory involvement distal to the splenic flexure and therefore may be effectively treated with topical treatment. This allows the delivery of the active drug directly to the site of inflammation, limiting the systemic absorption and the potential side effects. Topical aminosalicylate therapy is the most effective approach, provided that the formulation reaches the upper extent of the disease. Suppositories should be considered the treatment of choice for proctitis and distal sigmoiditis. A 1 g Pentasa-suppository once daily induces a quicker clinical and endoscopic remission and was better tolerated than a 500-mg suppository twice daily. Enemas, foams and gel, thanks to their proximal spread, should be the treatment of choice for proctosigmoiditis and left-sided colitis. Oral aminosalicylates are less effective than topical therapies for patients with active disease; however, a combination of oral and topical aminosalicylates can be successfully tried in refractory patients. Topical aminosalicylates also play an important role in the maintenance of remission, and the combination of oral plus rectal 5-aminosalicylate is superior to the single agent. Patients who prefer not to continue on long-term rectal therapy can be treated with oral aminosalicylates.