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Therapy for active ulcerative colitis (UC) usually involves rectal formulations of corticosteroids (CS), which are characterized by the risk of systemic steroid-related adverse effects.To compare the efficacy and safety of the topically acting CS beclomethasone dipropionate (BDP) versus mesalamine (5-ASA) in the treatment of active UC.Patients with mild to moderate distal active UC were randomized to a 6-week treatment with BDP 3 mg enema o.d. or 5-ASA 1 g enema daily in a single-blind, multicenter, parallel-group, controlled study. The primary efficacy variable was the decrease in Disease Activity Index (DAI) score. Safety variables were adrenal function, monitoring of adverse events, vital signs, and laboratory parameters.A total of 217 patients were enrolled and treated with BDP (n = 111) or 5-ASA (n = 106). A significant decrease in the DAI score (P0.05) was observed in both treatment groups, with a clinical remission rate of 36.7% in the BDP group and of 29.2% in the 5-ASA group. Both treatments were well tolerated. No changes from baseline in morning cortisol levels were observed in the BDP group.BDP administered as a rectal enema over a 6-week treatment period was efficacious and safe in patients with active UC, without interference with pituitary adrenal axis.

Previous studies have reported genetic anticipation, genomic imprinting, and phenotypic concordance of some clinical features in familial cases of Crohn's disease (CD) and ulcerative colitis (UC). The aim of our study was to investigate the phenotypic features of affected members in a large sample of CD and UC Italian families.In a multicenter study, CD and UC families were recruited. Affected members were questioned about date of birth, gender, age at onset of symptoms and at diagnosis, location and extension of disease, occurrence of extraintestinal manifestations, use of steroids and/or of immunosuppressive drugs, need for resective surgery, and number of relapses per year (1 yr oror = 1 yr). Statistical analysis was performed with chi2, Fisher's, Mann-Whitney U, and binomial probability tests, when appropriate.A total of 128 families with 270 affected members were studied: 35 were CD, 64 UC, and 29 mixed families (when UC and CD affected different members). In 99 of 128 families (77%), the diagnosis was concordant. In CD families, a high concordance for localization (46%), extraintestinal manifestations (67%), need for steroids (77%), need for immunosuppressive drugs (100%), need for surgery (29%), and relapse rate (36%) was found. In UC families, a high concordance for disease extension (33%), need for steroids (47%), and relapse rate (34%) was disclosed. A higher than expected concordance for ileal localization (p0.4) in CD families and extensive colitis (p0.05) in UC families was demonstrated. A generation difference of 15-20 yr in mean ages at onset of symptoms and at diagnosis was recorded. No features of more aggressive disease in subsequent generations and no differences in gender of transmitting parents and relatives were found.Our study shows a high rate of concordance for diagnosis and clinical features in UC and, especially, CD families. The disease occurred 15-20 yr earlier than in previous generations without features of increased severity.

To compare beclomethasone dipropionate 3 mg/60 mL enema (BDP) and prednisolone sodium phosphate 30 mg/60 mL enema (PP) once daily in patients with active distal ulcerative colitis.One hundred and fifty-seven patients were enrolled in a multicentre, 4-week, randomized, double-blind trial. Patients were assessed at baseline, 2 and 4 weeks.Both treatment groups showed statistically significant improvement of clinical activity after 2 and 4 weeks. Endoscopy and biopsy showed a reduction in the activity score at the end of the treatment period in both groups. No statistically significant difference was observed between the two treatment groups. After 4 weeks, 29% of patients in the BDP group and 25% in the PP group were considered to be in clinical remission; an improvement was observed in 40% of patients on BDP and in 47% on PP. Mean morning plasma cortisol levels showed a slight but significant reduction in the PP group, while the ACTH test showed that neither drug interfered with the hypothalamic-pituitary-adrenal (HPA) axis function. No significant changes were observed in the laboratory tests. Finally, there was a low incidence of adverse events in both groups.It is concluded that, in the topical treatment of active distal ulcerative colitis, BDP 3 mg enemas are as efficacious as PP 30 mg enemas, without interference with the HPA axis.

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-1 beta release from fresh and cultured colonic biopsies and IL-1 beta 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-1 beta activity was determined by ELISA KIT (Cystron Biotechnology) in plasma samples, washing solution and the incubation medium. Very low levels of IL-1 beta were detected only in 3 plasma samples, all from active patients. Significantly more IL-1 beta was released from fresh and cultured colonic mucosa obtained from patients with UC in remission compared to normal mucosa (p less than 0.01). Furthermore, specimens from active UC released significantly more IL-1 beta than those from patients in remission (p less than 0.01). In conclusion, IL-1 may play an important role in mediating the inflammatory response in UC.

Pouchitis is the major long-term complication after ileal pouch-anal anastomosis for ulcerative colitis. About 15% of patients have a chronic, treatment-resistant disease.To evaluate the efficacy of an antibiotic combination for chronic active, treatment-resistant pouchitis.Eighteen patients were treated orally with rifaximin 1 g b.d. + ciprofloxacin 500 mg b.d. for 15 days. Symptoms assessment, endoscopic and histological evaluations were performed at screening and after 15 days using the Pouchitis Disease Activity Index (PDAI). Improvement was defined as a decrease of at least 3 points in PDAI score, and remission as a PDAI score of 0. Systemic absorption of rifaximin was determined by high performance liquid chromatography. Faecal samples were collected before and after antibiotic treatment for stool culture.Sixteen out of 18 patients (88.8%) either improved (n=10) or went into remission (n=6); the median PDAI scores before and after therapy were 11 (range 9-17) and 4 (range 0-16), respectively (P0.002). No side-effects were reported. Rifaximin plasma levels and urinary excretion were negligible, confirming its mainly topical activity. A significant decrease in total anaerobes and aerobes, enterococci, lactobacilli, bifidobacteria and bacteroides in faecal samples was observed, while the reduction in number of coliforms and Clostridium perfringens did not reach a statistical significance.A combination of rifaximin and ciprofloxacin was effective in patients with active chronic, treatment-resistant pouchitis, suggesting the need, in these patients, for treatment using antibiotic agents with wide antibacterial spectrum of activity.

Background—The use of corticosteroids in active Crohn’s disease often becomes limited by side effects. Budesonide is a potent corticosteroid with low systemic bioavailability due to an extensive first pass liver metabolism.Aims—To compare the efficacy and safety of two dosage regimens of budesonide and prednisolone in patients with active Crohn’s disease affecting the ileum and/or the ascending colon.Patients and methods—One hundred and seventy eight patients were randomised to receive budesonide controlled ileal release (CIR) capsules 9 mg once daily or 4.5 mg twice daily, or prednisolone tablets 40 mg once daily. The treatment period was 12 weeks. The primary efficacy variable was clinical remission, defined as a Crohn’s Disease Activity Index (CDAI) of 150 or less.Results—After eight weeks of treatment, remission occurred in 60% of patients receiving budesonide once daily or prednisolone and in 42% of those receiving budesonide twice daily (p=0.062). The presence of glucocorticoid associated side effects was similar in all groups; however, moon face was more common in the prednisolone group (p=0.0005). The highest frequency of impaired adrenal function, as measured by a short ACTH test, was found in the prednisolone group (p=0.0023).Conclusions—Budesonide CIR, administered at 9 mg once daily or 4.5 mg twice daily, is comparable to prednisolone in inducing remission in active Crohn’s disease. The single dose administration is as promptly effective as prednisolone and represents a simpler and safer therapeutic approach, with a considerable reduction in side effects.

The exact role of 111In leukocyte scanning in the assessment of clinical activity of Crohn's disease (CD) is still a matter of controversy. In our center we studied 22 patients with CD (8 with active disease) with standard 111In labelled mixed leukocyte scans. We determined the extent of the lesion measured as lesion-occupied cells on scanned area and the degree of inflammatory activity assessed as count ratio between the involved region and the iliac crest. Particularly in delayed scans, these scintigraphic parameters showed good correlation with clinical and laboratory indices of disease activity. In our series, only 6 patients had completely negative scans. They were in clinical and laboratory remission, and 5 of them had undergone surgery for CD during the previous year, with no radiological and/or endoscopic findings of recurrence. Among the other 8 patients in clinical remission, 5 had positive early scans, while the rest showed persistent delayed images. Moreover both early and delayed leukocyte scans were positive in 8 cases in which disease was undoubtedly active. A 1-year follow-up was available for 14 patients in clinical remission when 111In-scan was performed. During this period, 3 patients, all of whom had had early and delayed positive 111In-scan, suffered from clinical relapse; no clinical relapses were documented in patients with only 4th hour positive scans. In conclusion, in our series, 111In-scan was also frequently positive in patients in clinical remission; in this patient subset persistent images on delayed scans might suggest the risk of clinical relapse.

The causes of ulcerative colitis are still unknown and above all the circumstances which can lead to inflammatory episodes are unclear. Antibiotic therapy has not provided encouraging results so far but it is possible that the pathogenesis of this disease may involve bacterial species which have not yet been identified. The use of an antibiotic with specific colic activity therefore seems to be justified.

1. Aliment Pharmacol Ther. 2006 Apr 15;23(8):1117-25. Antibiotic treatment of Crohn's disease: results of a multicentre, double blind, randomized, placebo-controlled trial with rifaximin. Prantera C, Lochs H, Campieri M, Scribano ML, Sturniolo GC, Castiglione F, Cottone M. Operative Unit of Gastroenterology, St Camillo-Forlanini Hospital, Rome, Italy. prantera@tin.it BACKGROUND: Clinicians often employ antibiotics in Crohn's disease. Rifaximin is active against bacteria frequently found in the intestinal mucosa of Crohn's disease patients. AIM: To evaluate the difference in efficacy between once and twice/daily oral administration of rifaximin and placebo in the treatment of active Crohn's disease. METHODS: We enrolled 83 patients with mild-to-moderate Crohn's disease and randomized to three treatments for 12 weeks: Group A (rifaximin 800 mg o.d. + placebo), Group B (rifaximin 800 mg b.d.) and Group C (placebo b.d.). RESULTS: Clinical remission was achieved by 52% of Group B, 32% (A) and 33% (C). Clinical response was seen in 67% (B), 48% (A) and 41% (C), without reaching a statistically significant difference. Treatment failures were: 4% (B), 12% (A) and 33% (C), (P = 0.010). Remission and response rates of rifaximin 800 mg b.d. were significantly higher than those of placebo and rifaximin 800 mg o.d. in patients with elevated C reactive protein values (P < 0.05). CONCLUSIONS: Rifaximin 800 mg b.d. was superior to placebo in inducing clinical remission of active Crohn's disease. Although this difference was not statistically significant, the number of the failures in the placebo group was significantly higher than those who received rifaximin 800 mg b.d. PMID: 16611272 [PubMed - indexed for MEDLINE]

Background - Antineutrophil cytoplasmic antibodies (ANCAs) from patients with vasculitidis can induce neutrophils to release oxygen radicals in vitro. ANCAs with a perinuclear pattern of immunofluorescence are found in most patients with ulcerative colitis, but several findings are against ANCAs having a pathogenetic role in this disease. Aims - To evaluate the influence of ANCAs associated with ulcerative colitis on the respiratory burst activity of neutrophils. Patients - Serum samples were obtained from 14 patients with ulcerative colitis, seven of whom showed positivity for p-ANCAs, three patients with vasculitidis, two with positivity for p-ANCAs, and one for c-ANCAs, and seven healthy volunteers. Methods - A positive ANCA serology was determined with a standard indirect immunofluroescence assay. Purified immunoglobulins (IgGs) were prepared from serum samples by DEAE-Affigel blue chromatography. Human neutrophils were prepared by dextran-Ficoll-Hypaque separation. Superoxide anion (O2-. generation was measured by following the superoxide dismutase inhibitable reduction of ferricytochrome. Results - There were no significant differences among samples from ulcerative colitis IgG p-ANCA positive, ulcerative colitis IgG p-ANCA negative patients, and controls on O2-6. production, whereas ANCA positive IgG from vasculitidis significantly enhanced O2-. release (p < 0.001). Conclusions - p-ANCAs associated with ulcerative colitis have no effect on the respiratory burst activity of normal human neutrophils in vitro. These results reinforce the hypotheses that ANCAs are unlikely to contribute to the pathogenesis of ulcerative colitis.

The study exploited autologous microfragmented fat to treat refractory complex Crohn’s perianal fistula, obtaining 66.7% of combined remission at 6 months in patients already treated without success using combined biosurgical approaches and multiple repair surgeries following the failure of biological therapy., Background Complex perianal fistulas represent one of the most challenging manifestations of Crohn’s disease. Combined surgical and medical therapy with biologic drugs today represent the first-line treatment option, but its efficacy does not exceed 60%. Recently, new therapeutic approaches, such as the use of mesenchymal stromal cells, have shown promising results. The adipose tissue is an abundant and easy to access source. The effectiveness, safety, and feasibility of local injections of microfragmented adipose tissue in patients with refractory complex fistulizing perianal Crohn’s disease (PCD) were evaluated. Methods Fifteen patients with persistent complex fistulizing PCD after biosurgical approach and subsequent surgical “rescue” repair were treated in S. Orsola-Malpighi Hospital with a single-local administration of microfragmented adipose tissue prepared using a minimal manipulation technique (Lipogems) in a closed system. Clinical outcomes were determined at 24-week follow-ups assessing success rate, defined as combined clinical and radiological remission. Results Upon clinical examination at 24 weeks, 10 patients had combined remission (clinical and radiographic), 4 patients showed improvements, and 1 patient failed. The results were confirmed in all patients by pelvic MRI. No relevant postoperative complications nor adverse events were reported. Conclusion These results suggest that the local injection of autologous microfragmented adipose tissue is a safe and promising “rescue therapy” for patients with multiresistant complex fistulizing PCD. This approach might be proposed as routine because it is affordable, is minimally invasive, has no risk of sphincteric damage, and can be carried out in a day-surgery setting.

Essential oils (EOs) are a complex mixture of hydrophobic and volatile compounds synthesized from aromatic plants, most of them commonly used in the human diet. In recent years, many studies have analyzed their antimicrobial, antioxidant, anti-inflammatory, immunomodulatory and anticancer properties in vitro and on experimentally induced animal models of colitis and colorectal cancer. However, there are still few clinical studies aimed to understand their role in the modulation of the intestinal pathophysiology. Many EOs and some of their molecules have demonstrated their efficacy in inhibiting bacterial, fungi and virus replication and in modulating the inflammatory and oxidative processes that take place in experimental colitis. In addition to this, their antitumor activity against colorectal cancer models makes them extremely interesting compounds for the modulation of the pathophysiology of the large bowel. The characterization of these EOs is made difficult by their complexity and by the different compositions present in the same oil having different geographical origins. This review tries to shift the focus from the EOs to their individual compounds, to expand their possible applications in modulating colon pathophysiology.

Background (Trans)-3,7-Dimethyl-2,6-octadien-1-ol, commonly called geraniol (Ge-OH), is an acyclic monoterpene alcohol with well-known anti-inflammatory and antimicrobial properties. Ge-OH is a non-toxic compound classified as Generally Recognized As Safe (GRAS) by the US Food and Drug Administration and the European Food Security Agency. Methods Ge-OH was orally administered at a maximum daily dose of 8 mg kg(− 1) body weight for four weeks in a delayed release formulation capable of reaching the colon. Fecal microbiota and blood cytokines were analyzed before and after Ge-OH treatment, as well as IBS symptomatology by using Visual Analogue Scale (VAS-IBS). Results The results show that orally administered Ge-OH is a powerful modulator of the intestinal microbial ecosystem, capable of leading to increased relative abundances of Collinsella and especially Faecalibacterium, a well-known health-promoting butyrate producer consistently found to be decreased in IBS patients. Moreover, Ge-OH strongly improved the clinical symptoms of colitis by significantly reducing the score recorded by the VAS-IBS questionnaire. Clinical improvement was associated with a significant reduction in the circulating MIP-1β, a chemokine found to be increased in several IBS patients. Conclusion Ge-OH could be a powerful component for food supplement targeted to the treatment of IBS patients. Trial registration ISRCTN47041881, retrospectively registered on 19th July 2018.

International audience; Gut microbiota dysbiosis has been associated with inflammatory bowel diseases (IBD). In colorectal cancer, the gut microbiota has also been recognized as potentially involved in aggravating or favoring the tumor development. However, very little is known on the structure and role of the microbiota in colitis associated cancer (CAC), an important complication of IBD in human. Here we analyzed the bacterial and fungal composition of the mucosa associated microbiota of patients suffering CAC, sporadic cancer (SC) and of healthy subjects (HS) by barcode sequences analysis on the following cohort: 7 CAC patients, 10 SC patients and 10 HS using 16S (MiSeq) and ITS2 (pyrosequencing) sequencing, for bacteria and fungi respectively. Mucosa-associated bacterial microbiota in CAC was significantly different from the ones in SC or in HS, while the fungal showed no differences. Comparison between mucosa-associated microbiota on the tumor site or in normal mucosa near the tumor showed very similar patterns. The global mucosa-associated bacterial microbiota in cancer patients was characterized by a restriction in biodiversity but no change for the fungal community. Compared to SC, CAC was characterized by an increase of Enterobacteriacae family and Sphingomonas genus and a decrease of Fusobacterium and Ruminococcus genus. Our study confirms the alteration of the mucosa-associated bacterial microbiota in IBD and SC. Although the cohort is limited in number, this is the first evidence of the existence of an altered bacterial microbiota in CAC clearly different from the one in SC patients.

Intestinal tumors represent less than 6 % of digestive tumors, and, because of the limitations of intestinal investigations, these tumors are difficult to diagnose. In this context, capsule endoscopy has proven effective, especially in patients with obscure digestive bleeding. In a large series of patients undergoing capsule endoscopy, small bowel tumors are found in 2.4–8.9 % of cases. The aim of this retrospective, single-center study, based on prospective database, is to evaluate the frequency of small bowel tumors detected by capsule endoscopy in patients with occult gastrointestinal bleeding. During 2004–2014, 849 consecutive patients underwent CE at our Department for occult gastrointestinal bleeding. Following capsule endoscopy, the medical records of the study population were reviewed. Results of double-balloon enteroscopy or surgery performed after capsule endoscopy were retrieved. Capsule endoscopy identified 55 small bowel tumors (6.5 %), of which 28 malignancies (51 %) and 27 benign neoplasms (49 %) underwent surgery or endoscopic treatment. Malignancies included adenocarcinoma (18.7 %), gastrointestinal stromal tumors (GIST) (12 %) and lymphoma (6.7 %). Benign neoplasms included dysplastic adenomatous polyps (36 %) and hyperplastic polyps (25.3 %). Non-neoplastic masses included one inflammatory polyp. Capsule retention occurred in four patients (5.3 %) and the retained capsule was retrieved during surgery. In our experience neoplasms of small bowel are found in 6.5 % of patients with occult gastrointestinal bleeding. Of these malignancies, small bowel neoplasms are found in 3.3 % of cases. Capsule endoscopy is an effective and sensitive diagnostic tool, and plays an important role in the algorithm for the diagnostic workup of suspected small bowel tumors.

Traditional corticosteroids represent a well-established and effective treatment for active ulcerative colitis (UC). However, the severity of their systemic side effects, led in recent years to look for new steroid molecules that could reduce them, maximizing the anti-inflammatory activity. Budesonide has been one of the most studied steroid compounds and it has been approved for the treatment of mild to moderate active Crohn's disease (CD). In order to extend the release until the distally located inflammation, budesonide has been coupled with a controlled delivery system, called Multi-Matrix system (MMX), already successfully tested with oral mesalazine for the treatment of distal UC. After in vitro and in vivo models, the efficacy of Budesonide-MMX has been investigated in active UC with a first small phase II study, and partially encouraging results. This article will review the evidences on the use of budesonide in inflammatory bowel diseases and will discuss the role of Budesonide-MMX in active UC nowadays.

Colitis is the term used for chronic inflammatory bowel diseases at substantially increased risk of developing a form of colorectal cancer (CRC) known as colitis-associated cancer. In our study we synthesized core-shell polymeric micelles obtained by self-assembly of block copolymers for high efficiency delivery of anti-inflammatory and anti-cancer compounds to colonocytes and colon mucosa. We achieved an efficient intracellular delivery of these hydrophobic compounds (prednisone, retinoic acid and doxorubicin) to cultured colonocytes without cellular toxicity. The efficacy of retinoic acid and doxorubicin administration was significantly increased using these nanosized carriers. Moreover, these polymeric micelles have been shown to overcome the multidrug resistance efflux mechanism effectively delivering doxorubicin to multidrug-resistant colon cancer cells. These nanocarriers are also suitable for selective in vivo delivery of lipophilic drugs by enema administration to the inflamed colon tissue, specifically targeting the inflamed mucosa. From the Clinical Editor This team of investigators studied polymeric micelles as highly efficient drug delivery systems enabling intracellular delivery of hydrophobic compounds (prednisone, retinoic acid, and doxorubicin) to cultured colonocytes without cellular toxicity, also demonstrating beneficial in vivo effects.

Background In Crohn's disease (CD) patients, stress is believed to influence symptoms generation. Stress may act via central nervous system pathways to affect visceral sensitivity and motility thus exacerbating gastrointestinal symptoms. The neural substrate underpinning these mechanisms needs to be investigated in CD. We conducted an explorative functional magnetic resonance imaging (fMRI) study in order to investigate potential differences in the brain stress response in CD patients compared to controls. Methods 17 CD patients and 17 healthy controls underwent a fMRI scan while performing a stressful task consisting in a Stroop color-word interference task designed to induce mental stress in the fMRI environment. Key Results Compared to controls, in CD patients the stress task elicited greater blood oxygen level dependent (BOLD) signals in the midcingulate cortex (MCC). Conclusions & Inferences The MCC integrate “high” emotional processes with afferent sensory information ascending from the gut. In light of these integrative functions, the stress-evoked MCC hyperactivity in CD patients might represent a plausible neural substrate for the association between stress and symptomatic disease. The MCC dysfunction might be involved in mechanisms of central disinhibition of nociceptive inputs leading to amplify the visceral sensitivity. Finally, the stress-evoked MCC hyperactivity might affect the regulation of intestinal motility resulting in exacerbation of disease symptoms and the autonomic and neuroendocrine regulation of inflammation resulting in enhanced inflammatory activity.

Ulcerative colitis (UC) is associated with psychological stress and poor emotional functioning. The neural emotional processing involves the complex integration of several cortical and subcortical brain structures. The amygdala plays a fundamental role in the neural processing of emotional stimuli and is a core structure of the brain-gut axis (BGA) that represents the anatomo-functional substrate for the bidirectional influences between emotions and gastrointestinal functions. The aim of this study was to investigate the brain emotional processing in UC patients compared to healthy people. METHODS: Ten UC patients in remission and 10 matched healthy controls underwent a functional magnetic resonance imaging (fMRI) scan while performing a task involving emotional visual stimuli. A set of negative, positive, and neutral pictures were used to study brain-related emotional responses. RESULTS: A significantly reduced blood oxygen level-dependent (BOLD) signal in UC patients relative to controls was found in the amygdala, thalamic regions, and cerebellar areas (P < 0.05 corrected for multiple comparisons). The group-related differences were detected in the brain activity in response to positive emotional stimuli. CONCLUSIONS: UC is associated with an emotional dysfunction characterized by decreased sensitivity to emotions with a positive content. The previous intestinal inflammatory activity in UC patients might have contributed to determine the functional changes of the amygdala that we found. On the other hand, the dysfunction of the amygdala may influence the course of the disease.

Background: Steroids are highly effective in active Crohn's disease; clinical relapse following steroid withdrawal, however, is frequent. We used two steroid regimens of different duration in order to compare their efficacy in inducing and maintaining clinical remission. Methods: Seventy patients with active Crohn's disease were treated with methylprednisolone 40 mg/day i.m. for 3 weeks and then with two different regimens of tapering dosage: one for a further 4 weeks and another for a further 12 weeks. Results: Steroid therapy induced remission within 3 weeks in 91 % of the whole group of patients: at the end of each protocol remission rates were 85% of patients in the group treated for the shorter period and 87% of those treated for the longer period (difference 2%. CI = ‐ 14 to 18, P = NS); remission rates within 6 months after stopping steroids were 53% and 37% respectively (difference 16%, CI = ‐9 to 41, P = NS). Conclusions: No significant differences were found between the two regimens. Multiple courses of steroid treatment in the previous 3 years and a short time interval following previous steroid treatment seem to be risk factors for relapse. Copyright © 1994, Wiley Blackwell. All rights reserved

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.

To evaluate the efficacy and safety of oral budesonide for maintenance of remission in patients with mild to moderately active Crohn's disease (CD) of the ileum and/or ascending colon.Four double-blind, placebo-controlled trials with identical protocols were combined according to a predetermined analysis plan. Three hundred eighty patients with CD in medically induced remission (CD activity index [CDAI]or =150) were randomized to receive oral budesonide 3 mg, 6 mg, or placebo daily for 12 months. The primary outcome measure was time to relapse (increase in CDAI of 60 points above baseline and150).The median time to relapse was 268, 170, and 154 days for budesonide 6 mg, budesonide 3 mg, and placebo groups, respectively (p= 0.0072). The frequency of adverse events and glucocorticosteroid side effects were similar in all groups.Budesonide 6 mg/day is effective for prolonging time to relapse and for significantly reducing rates of relapse at 3 and 6 months but not 12 months in patients with CD in medically induced remission.

Background: Probiotic therapy has been shown to prevent the onset of pouchitis and to improve the quality of life in ulcerative colitis patients who required ileal pouch anal anastomosis. Pouchitis has been associated with elevated levels of proinflammatory cytokines and chemokines. Methods: In this retrospective analysis of archived endoscopic samples from responding patients enrolled in the above-mentioned trial, we were interested in studying mucosal gene expression of the pleiotropic proinflammatory cytokines (interleukin-1β, interleukin-6), TH1 cytokines (interferon-γ, tumor necrosis factor-α, interleukin-12), regulatory cytokines (interleukin-10, transforming growth factor-β), and the chemokine interleukin-8. In addition to assessment of cytokine gene expression, the presence of polymorphonuclear cells in the mucosal tissue was evaluated. Results: Data show that patients who were treated with probiotics had significant lower mucosal mRNA expression levels of interleukin-1β, interleukin-8, and interferon-γ compared with placebo-treated patients. Conclusions: In addition, a lower number of polymorphonuclear cells was present in the tissue of patients within the probiotic group compared with the number of polymorphonuclear cells in the tissue of patients receiving placebo and patients having an episode of pouchitis. Conclusions: These data suggest that probiotic treatment regulates the mucosal immune response by reducing mucosal levels of neutrophil-chemoattractant IL-8 and tissue influx of polymorphonuclear cells, and may further act by inhibition of T-cell activation, by reinforcement of barrier function and by a tight control of the potent pro-inflammatory cytokine IL-1β.

Perianal disease is a serious complication of Crohn’s disease and its surgical management is still controversial. It has been suggested that the local injection of infliximab has resulted in some potential benefit. This pilot study analyzed the feasibility and safety of such therapy in selected patients with severe perianal Crohn’s disease. The study included 15 patients with complex perianal Crohn’s disease in which sepsis was not controllable using surgical and medical therapy. Among them, four had previously undergone intravenous infusion of infliximab with no significant response, nine had contraindications for intravenous infusion, and two had associated stenosing ileitis and severe coloproctitis. The injection of 15 to 21 mg of infliximab, associated with surgical treatment, was performed at the internal and external orifices and along the fistula tract. Efficacy was measured by a complete morphologic evaluation using a personal score. No major adverse effects were reported. Ten of 15 patients healed after 3 to 12 infusions. Local injection of infliximab adjacent to the fistula tract of perianal Crohn’s disease is safe and may help in fistula healing. A controlled, randomized trial is required to prove the value.

PURPOSE: The anti-tumor necrosis factor (TNF) agents infliximab (IFX) and adalimumab (ADA) have been recently introduced to treat severe inflammatory bowel disease (IBD) that is unresponsive to other drugs. Several studies have confirmed the safety and efficacy of these agents for adult IBD patients, whereas there is less data on pediatric IBD. Mucosal healing, associated with fewer complications and surgeries, is considered the goal of treatment by some authors. The objective of this study was to evaluate the safety and efficacy (in terms of endoscopic, clinical, and laboratoristic response) of IFX and ADA in a cohort of pediatric patients with Crohn's disease (CD). METHODS: We conducted a retrospective analysis of prospectively collected data; we studied 33 patients (20 male, 13 female) with a diagnosis of CD established before 18 years of age: 29/33 were treated with IFX and 19/33 received ADA (four of them were naive to IFX). We evaluated clinical, endoscopic, and laboratoristic response to IFX and ADA for each patient and recorded the adverse effects of these drugs. RESULTS: With regard to IFX treatment, 22.2% of patients achieved mucosal healing and 44.4% showed an endoscopic response. With regard to ADA therapy, 25% of patients achieved mucosal healing and 50% showed an endoscopic response. Overall clinical response rates for IFX and ADA were 84 and 92.3%, respectively. Both drugs were well tolerated. CONCLUSION: To our knowledge, this is the first study reporting mucosal healing after ADA therapy in pediatric CD. We found significant mucosal healing and response rates in our group of patients. Compared with other pediatric studies, we reported similar clinical response rates and longer follow-up of patients.

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.

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. Aim: To determine the safety and efficacy of bismuth carbomer enemas in achieving and maintaining remission in treatment-resistant chronic pouchitis. Methods: Twelve patients with treatment-resistant chronic pouchitis were treated nightly for 45 days with enemas containing elemental bismuth complexed with carbomer. Diagnosis of pouchitis and response to treatment were evaluated with the Pouchitis Disease Activity Index (PDAI), which includes clinical, sigmoidoscopic and histological criteria. Serum bismuth concentrations were determined by atomic absorption. Results: Ten of 12 patients (83%) went into remission, with a significant decrease of mean total PDAI score from 12 (range 9–15) to 6 (4–15) (P

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. Methods: Twelve patients with active ulcerative colitis were administered 4 g of the mesalazine rectal enema labelled with 100 MBq technetium sulphur colloid (99mTc-SC). Anterior scans of the abdomen were acquired at intervals for 4 h. Scans were analysed to evaluate the extent of retrograde flow and homogeneity of distribution of the radiolabelled enema in the rectum, sigmoid, descending and transverse colon. In addition, plasma levels of 5-ASA and Ac-5-ASA were measured for 6 h. Results: All patients retained the entire rectal gel throughout the course of the study without reporting adverse events. In 11 out of 12 patients (92%) the gel had spread homogeneously beyond the sigmoid colon and had reached the upper limit of disease in all cases. The maximum spread (splenic flexure) was observed in 6 out of 12 patients (50%) within the first 2 h. The systemic absorption of mesalazine and its metabolite Ac-5-ASA was low. Conclusions: The new mesalazine enema represents an adequate alternative and a further technological improvement in the topical treatment of distal ulcerative colitis.

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

The advent of capsule endoscopy (CE) has resulted in a paradigm shift in the approach to the diagnosis and management of patients with obscure gastrointestinal bleeding (OGIB). With increasing global availability of this diagnostic tool, it has now become an integral part of the diagnostic algorithm for OGIB in most parts of the world. However, there is scant data on optimum timing of CE for maximizing diagnostic yield. OGIB continues to be a challenge because of delay in diagnosis and consequent morbidity and mortality. We evaluated the diagnostic yield of CE in identifying the source of bleeding in patients with OGIB. We identified patients who underwent CE at our institution from May 2006 to May 2011. The patients’ medical records were reviewed to determine the type of OGIB (occult, overt), CE results and complications, and timing of CE with respect to onset of bleeding. Out of 346 patients investigated for OGIB, 246 (71.1%) had some lesion detected by CE. In 206 patients (59.5%), definite lesions were detected that could unequivocally explain the OGIB. Small bowel angiodysplasia, ulcer/erosions secondary to Crohn’s disease, non-steroidal anti-inflammatory agent use, and neoplasms were the commonest lesions detected. Visualization of the entire small bowel was achieved in 311 (89.9%) of cases. Capsule retention was noted in five patients (1.4%). In this study, CE was proven to be a safe, comfortable, and effective, with a high rate of accuracy for diagnosing OGIB.

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

Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in Western countries. Although the aberrant expression of several microRNAs (oncomiRs) is associated with CRC progression, the molecular mechanisms of this phenomenon are still under investigation. Here we show that miR-101 expression is differentially impaired in CRC specimens, depending on tumour grade. miR-101 re-expression suppresses cell growth in 3D, hypoxic survival and invasive potential in CRC cells showing low levels of miR-101. Additionally, we provide molecular evidence of a bidirectional regulatory mechanism between miR-101 expression and important CRC pro-malignant features, such as inflammation, activation of the Wnt/β-catenin signalling pathway and epithelial–mesenchymal transition (EMT). We then propose that up-regulated miR-101 may function as a tumour suppressor in CRC and that its pharmacological restoration might hamper the aggressive ehaviour of CRC in vivo. MiR-101 expression may also represent a cancer biomarker for CRC diagnosis and prognosis.

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. © 1994 Plenum Publishing Corporation.

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

In patients with Crohn's disease (CD) stress is believed to increase the incidence of disease relapse. The brain processes stressful stimuli and triggers the stress-evoked responses. Habituation to stress is an adaptive process that allows minimizing these responses. We hypothesized inadequate habituation to stress in CD patients. The aim of this study was to compare the neural habituation between CD patients and controls. Twenty CD patients and eighteen controls underwent a functional magnetic resonance imaging while performing two repeated runs of a stress-evoking task. The task elicited different neural activity between the groups across runs in (1) amygdala, hippocampus, (2) insula, putamen (3) cerebellar regions, suggesting altered habituation to stress in patients. These structures regulate the neuroendocrine and autonomic stress-evoked responses that control the proinflammatory responses. The inadequate habituation to stress that we found in patients could play a role in the relationship between stress and inflammatory exacerbations in CD.

Outstanding progress regarding the pathophysiology of Crohn’s disease (CD) has led to the development of innovative therapeutic concepts. Numerous controlled trials have been performed in CD. This review concentrates on the results of randomized, placebo-controlled trials, and meta-analyses when available, that provide the highest degree of evidence. Current guidelines on the management of CD recommend a step-up approach to treatment involving the addition of more powerful therapies as the severity of disease and refractoriness to therapy increase. The advent of biological drugs has opened new therapeutic horizons for treating CD, modifying the treatment goals. However, the large majority of patients with CD will be managed through conventional therapy, even if they are a prelude to biological therapy.

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.

Background and aims The long-term natural history of collagenous (CC) and lymphocytic colitis (LC) is not well known. The aims of this study were to evaluate the clinical course of microscopic colitis (MC) and to describe the morbidity evolution of the disease. Material and methods This study is based on a cohort of 54 patients (35 LC/19 CC), previously included in a randomized trial treated with mesalazine with or without cholestyramine. Patients were followed-up closely during the subsequent 5years, undergoing clinical, endoscopic and histologic evaluation at least yearly. After this period, they were encouraged to undergo periodical clinical evaluations. Results In a mean follow-up time of 104.9±14.1months (range 81–138months) at the end of the therapy, 12 patients (7 LC and 5 CC) relapsed. Of these patients, 4 reported a mild clinical relapse self-treated with antidiarrheal medication. In total 49 patients are clinically free from diarrhea, to date. At multivariate analysis the only predictive factor of relapse seems to be a slow response to treatment. Conclusions Only a minority of patients with MC had diarrhea more than once a week in a long-term follow-up and the symptom pattern was similar between CC and LC patients.

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.

The in 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 cytochrome c (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. © 1991 Plenum Publishing Corporation.

Hypo and hyperactivity of the autonomic nervous system have been associated with chronic bowel inflammation diseases. We investigated the autonomic function in 11 patients with chronic ulcerative colitis (UC) and 17 healthy controls by means of cardiovascular autonomic tests and heart rate variability. Autonomic responses were normal in patients and controls. At rest, LF/HF ratios were significantly (P < 0.05) higher in chronic UC patients (2.4 +/- 1.6) compared to controls (1.2 +/- 1.0). Our results suggest a higher sympathetic tone at rest in patients with chronic UC.

Pouchitis is the major long-term complication after ileal-pouch anal anastomosis for ulcerative colitis. Broad-spectrum antibiotics are the mainstay of treatment in this condition. Recently, we have shown the efficacy of a highly concentrated probiotic preparation (VSL#3, 900 billions/sachet lyophilized viable bacteria) in preventing relapses of chronic pouchitis and in preventing pouchitis onset. This study was designed to evaluate the efficacy of high-dose VSL#3 in the treatment of mildly active pouchitis. Twenty-three consecutive patients with mild pouchitis, defined as a score of between 7 and 12 in the Pouchitis Disease Activity Index, which includes clinical, endoscopic, and histological criteria, were treated with VSL#3, 2 sachets b.i.d. (3600 billion bacteria/day) for four weeks. Symptomatic, endoscopic, and histologic evaluations were undertaken before and after treatment according to Pouchitis Disease Activity Index. Remission was defined as a combination of a Pouchitis Disease Activity Index clinical score of ≤2, endoscopic score of ≤1, and total Pouchitis Disease Activity Index score of ≤4. Patients in remission after treatment were treated with VSL#3, 1 sachet b.i.d. (1800 billion bacteria), as maintenance treatment for six months. The quality of life was assessed with the Inflammatory Bowel Disease Questionnaire. Sixteen of 23 patients (69 percent) were in remission after treatment. The median total Pouchitis Disease Activity Index scores before and after therapy were 10 (range, 9–12) and 4 (range, 2–11), respectively (P

Many experimental and clinical observations suggest a potential role for intestinal microflora in the pathogenesis of inflammatory bowel disease (IBD). Manipulation of the luminal content using antibiotics may therefore represent a potentially effective therapeutic option. However, the available studies do not support the use of antimicrobials in ulcerative colitis and larger studies are required. These drugs are however effective in treating septic complications of Crohn’s disease (CD). The use of antibacterial agents as primary therapy for CD is more controversial, although this approach is frequently and successfully adopted in clinical practice. Despite the fact that properly controlled trials have been not carried out, antimicrobials are the mainstay of the treatment of pouchitis. Rifaximin is a poorly absorbed, broad-spectrum antibiotic that, thanks to its efficacy and long-term safety, could represent the preferred tool of manipulating enteric flora in patients with IBD. Preliminary data suggest that rifaximin may be beneficial in the treatment of active ulcerative colitis (and pouchitis), mild to moderate CD as well as prevention of post-operative recurrence of CD.

Background: The intestinal microbiota plays a critical role in the pathophysiology of pouchitis, a major complication after ileal pouch anal anastomosis in patients with ulcerative colitis. Recently, controlled trials have demonstrated that probiotics are effective in maintenance of remission in pouchitis patients. However, the mechanism by which therapy with probiotics works remains elusive. This study explores the role of the bacterial and fungal flora in a controlled trial for maintenance of remission in pouchitis patients with the probiotic VSL#3 compound. Methods: The mucosa associated pouch microbiota was investigated before and after therapy with VSL#3 by analysis of endoscopic biopsies using ribosomal DNA/RNA based community fingerprint analysis, clone libraries, real time polymerase chain reaction (PCR), and fluorescence in situ hybridisation. Patients were recruited from a placebo controlled remission maintenance trial with VSL#3. Results: Patients who developed pouchitis while treated with placebo had low bacterial and high fungal diversity. Bacterial diversity was increased and fungal diversity was reduced in patients in remission maintained with VSL#3 (p = 0.001). Real time PCR experiments demonstrated that VSL#3 increased the total number of bacterial cells (p = 0.002) and modified the spectrum of bacteria towards anaerobic species. Taxa specific clone libraries for Lactobacilli and Bifidobacteria showed that the richness and spectrum of these bacteria were altered under probiotic therapy. Conclusions: Probiotic therapy with VSL#3 increases the total number of intestinal bacterial cells as well as the richness and diversity of the bacterial microbiota, especially the anaerobic flora. The diversity of the fungal flora is repressed. Restoration of the integrity of a “protective” intestinal mucosa related microbiota could therefore be a potential mechanism of probiotic bacteria in inflammatory barrier diseases of the lower gastrointestinal tract.

Percutaneous abscess drainage (PAD) is the current therapy for abdominal or pelvic collections. PAD has poorer curative rate for abscesses in Crohn’s disease (CD), commonly complicated by wide fistulas and multiloculations. We retrospectively evaluated abscess cure rate, complications and final outcome in 87 CD patients, 70 with spontaneous and 17 with postoperative pelvic abscesses, all treated with CT-guided PAD during the last 7 years. A 77% primary success rate and an 84.3% secondary success rate were obtained without major complications. The higher success rate for PAD was for postoperative (88.2%) rather than spontaneous abscesses (74.2%). Seventy-two percent of treated patients did not develop recurrent abscesses and underwent elective surgery up to 40 months later. PAD in pelvic abscess complicating CD is an effective alternative to early surgery with satisfactory curative success rates. In unsuccessful cases, due to wide fistulas or postoperative anastomotic dehiscence, PAD helped in planning elective surgery, reducing surgical complications.

Background: Multi-matrix (MMx), a new delivery system for mesalazine, seems to release 5-aminosalicyclic acid (5-ASA) preferentially in the sigmoid colon. This study had 2 objectives: (1) to evaluate the therapeutic response to MMx in patients with active left-sided disease and (2) to gain additional insights as to how the therapy would compare with topical 5-ASA. Methods: Patients received either 1.2 g of 5-ASA MMx three times per day plus placebo enema or 4 g of 5-ASA enema plus placebo tablets for 8 weeks. The primary endpoint was clinical remission (clinical activity index ≤4) at 8 weeks. Secondary endpoints were endoscopic and histologic remissions. Results: Seventy-nine patients were enrolled. Clinical remission rates at 4 and 8 weeks were 57.5% and 60.0% for patients treated with MMx and 68.4% and 50.0% for patients randomized to 5-ASA enemas, respectively (95% confidence interval for the difference at 8 weeks, −12 to +32). Endoscopic remission was achieved by 45.0% of patients on 5-ASA MMx and by 36.8% of those on enema, whereas 15.0% and 8% of patients, respectively, showed histologic remission. Compliance was 97.0% for oral and 87.5% for topical therapy. In the enema group, compliance was 88.0% for the patients in remission and 65.5% for those with active disease. Conclusions: Preliminary studies suggest that similar rates for induction of remission can be expected from 5-ASA enemas and MMx for patients with left-sided ulcerative colitis.

An increasing number of both clinical and laboratory-derived observations support the importance of luminal components in driving the inflammatory response in ulcerative colitis and Crohn’s disease. Although its role is unclear, antibiotic therapy is commonly used in clinical practice for the treatment of moderately to severely active ulcerative colitis. Metronidazole and/or ciprofloxacin are currently employed in active Crohn’s disease, particularly in patients with colonic involvement and with perianal disease. Rifaximin, a rifamycin-derived antibiotic, is characterized by a wide range of antibacterial activity and a very low systemic absorption. Some preliminary data show its efficacy in severe active ulcerative colitis, pouchitis and prevention of postoperative recurrence in Crohn’s disease.

Microflora represent a heterogeneous mixture of microorganisms that are distributed throughout the gastrointestinal (GI) tract, but the highest concentrations of bacteria are present in the large intestine. Circa 400 bacterial species constitute the colonic flora. Compared with the huge concentration of bacteria in the GI tract, the stomach contains a relatively small number of bacteria (

Intestinal bacteria have been implicated in the initiation and perpetuation of IBD; in contrast, "probiotic bacteria" have properties possibly effective in treating and preventing relapse of IBD. We evaluated the safety and efficacy of VSL#3 and the components, and the composition of the biopsy-associated microbiota in patients with active mild to moderate ulcerative colitis (UC).Thirty-four ambulatory patients with active UC received open label VSL#3, 3,600 billion bacteria daily in two divided doses for 6 wk. The presence of biopsy-associated bacteria was detected using a nucleic acid-based method and the presence of VSL#3 species confirmed by DNA sequencing of 16S rRNA.Thirty-two patients completed 6 wk of VSL#3 treatment and 2 patients did not have the final endoscopic assessment. Intent to treat analysis demonstrated remission (UCDAIor = 2) in 53% (n = 18); response (decrease in UCDAIor = 3, but final scoreor =3) in 24% (n = 8); no response in 9% (n = 3); worsening in 9% (n = 3); and failure to complete the final sigmoidoscopy assessment in 5% (n = 2). There were no biochemical or clinical adverse events related to VSL#3. Two of the components of VSL#3 were detected by PCR/DGGE in biopsies collected from 3 patients in remission.Treatment of patients with mild to moderate UC, not responding to conventional therapy, with VSL#3 resulted in a combined induction of remission/response rate of 77% with no adverse events. At least some of the bacterial species incorporated in the probiotic product reached the target site in amounts that could be detected.

Background: “Probiotic” bacteria are effective in treating some inflammatory bowel diseases. However which bacteria confer benefit and mechanisms of action remain poorly defined. Dendritic cells, which are pivotal in early bacterial recognition, tolerance induction, and shaping of T cell responses, may be central in mediating the effects of these bacteria. Aims: To assess effects of different probiotic bacteria on dendritic cell function. Methods: Human intestinal lamina propria mononuclear cells, whole blood, or an enriched blood dendritic cell population were cultured with cell wall components of the eight bacterial strains in the probiotic preparation VSL#3 (four lactobacilli, three bifidobacteria, and one streptococcal strains). Dendritic cells were identified and changes in dendritic cell maturation/costimulatory markers and cytokine production in response to probiotic bacteria were analysed by multicolour flow cytometry, in addition to subsequent effects on T cell polarisation. Results: VSL#3 was a potent inducer of IL-10 by dendritic cells from blood and intestinal tissue, and inhibited generation of Th1 cells. Individual strains within VSL#3 displayed distinct immunomodulatory effects on dendritic cells; the most marked anti-inflammatory effects were produced by bifidobacteria strains which upregulated IL-10 production by dendritic cells, decreased expression of the costimulatory molecule CD80, and decreased interferon-γ production by T cells. VSL#3 diminished proinflammatory effects of LPS by decreasing LPS induced production of IL-12 while maintaining IL-10 production. Conclusions: Probiotic bacteria differ in their immunomodulatory activity and influence polarisation of immune responses at the earliest stage of antigen presentation by dendritic cells.