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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aliment Pharmacol Ther 2011; 34: 982-993 Summary 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. [ABSTRACT FROM AUTHOR]

Background: Endometriosis is a common estrogen-dependent disease. The aim of this study was to assess whether controlled ovarian hyperstimulation (COH) for assisted reproductive technology (ART) was associated with an increased incidence in endometriosis recurrence as documented by transvaginal ultrasound (TV-US). Methods: In a retrospective cohort study of 592 patients submitted to laparoscopy for endometriosis, 177 with infertility-related endometriosis who underwent a periodic ultrasound follow-up after laparoscopy were selected. Women who started ART after laparoscopy ( n = 90) were compared with the control group, who did not undergo ART ( n = 87). Recurrence of endometriosis was defined as the presence of endometriotic lesions observed through TV-US. Results: During a long-term TV-US follow-up (1-15 years), 40 (22.6%) recurrences were observed. Patients submitted to ART showed a cumulative recurrence rate similar to that of the control group (28.6% and 37.9% respectively, p = 0.471). Recurrent lesions were ovarian cysts (47.5%), ovarian nodules (37.5%), and rectovaginal disease (15%). The stratified analysis based on stages of endometriosis and pelvic pain did not show differences. Conclusions: Gonadotropin treatments do not seem to affect the natural history of endometriotic lesions. The most important prognostic factors in recurrent disease observed by TV-US seem to be the stage of endometriosis and the presence of pelvic pain at the time of the first laparoscopic treatment. [ABSTRACT FROM AUTHOR]

The article presents a study that assesses the effect of tissue harmonic imaging (THI) on the measurement of fetal nuchal translucency thickness (NT). It notes that the first trimester NT measurement of the 103 pregnant women were assessed using conventional ultrasanography (CUS) and THI without changing any other ultrasound parameter. The study concludes that THI causes a small yet significant reduction of the NT measurement which could lessen the sensitivity of screening for Down syndrome.

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. [ABSTRACT FROM AUTHOR]

Aliment Pharmacol Ther 2010; 32: 603–611 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 CB1 receptors has been investigated in the human gastrointestinal mucosa, as expression of inflammatory process. Aim To evaluate the CB1 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/CB1 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 CB1mRNA/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 CB1/GUSB were 0.38 and 0.17, respectively, with highly significant differences between the NERD vs. ERD groups. Semi-quantitative analysis of CB1 expression, performed with WB, shows in NERD patients a higher CB1 receptor expression than ERD patients. Conclusions With this study, we showed for the first time the presence of CB1 receptors in the human oesophageal epithelium. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 ≤2, endoscopic score of ≤1 and total Pouchitis Disease Activity Index score of ≤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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background 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. Methods 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. Results 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. Conclusions 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and aims: The widespread use of anti-tumour necrosis factor α antibody (Infliximab) in Crohn's disease (CD) raises concerns about a possible cancer risk in the long term. In a matched pair study, we assessed whether Infliximab is associated with an increased risk of neoplasia. Methods: In a multicentre matched pair study, 404 CD patients treated with Infliximab (CD-IFX) were matched with 404 CD patients who had never received Infliximab (CD-C). Cases and controls were matched for sex, age (± 5 years), site of CD, age at diagnosis (± 5 years), immunosuppressant use, and follow up. New diagnoses of neoplasia from April 1999 to October 2004 were recorded. Results: Among the 404 CD-IFX, neoplasia was diagnosed in nine patients (2.22%) while among the 404 CD-C, seven patients developed neoplasia (1.73%) (odds ratio 1.33 (95% confidence interval 0.46–3.84); p = 0.40). The survival curve adjusted far patient year of fallow up showed no differences between CD-IFX and CD-C (p=0.90; log rank test). In the CD-IFX group, there was one cholangiocarcinoma, three breast cancers, one skin cancer, one leukaemia, one laryngeal cancer, and two anal carcinomas. Among the 7/404 (1.73%) CD-C, there were three intestinal adenocarcinomas (two caecum, one rectum), one basalioma, one spinalioma, one non-Hodgkin's lymphoma, and one breast cancer. Age at diagnosis of neaplasla did not differ between groups (CD-IFX v CD-C: median 50 (range 40–70 years) v 45 [27–72); p=0.50). Conclusion: In our multicentre matched pair study, the frequency of a new diagnosis of neoplasia in CD patients treated with Infliximab was comparable with CD patients who had never received Infliximab. [ABSTRACT FROM AUTHOR]

PURPOSE: 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 inflixinlab 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. METHODS: 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 influx- imab 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 inflixiniab, 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. RESULTS: No major adverse effects were reported. Ten of 15 patients healed after 3 to 12 infusions. CONCLUSIONS: Local injection of inflixiniab 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. [ABSTRACT FROM AUTHOR]

With the increasing demand for assisted reproductive techniques (ARTs), it is important to consider how to manage infection. Three main positive factors that contribute to successful in vitro fertilization (IVF) cycles are maternal age, the ovarian hyperstimulation protocol used, and the number and quality of transferred embryos. Negative factors include contamination and infection. This paper describes the issues relating to infection during IVF and proposes guidelines to control infection and to increase laboratory safety. [ABSTRACT FROM AUTHOR]

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-c 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. [ABSTRACT FROM AUTHOR]

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, allowing the delivery of the active drug directly to the site of inflammation and limiting systemic absorption and potential side-effects. Topical aminosalicylate therapy is the most effective approach, and most patients will benefit hugely, provided that the formulation reaches the upper extent of the disease. Therefore, the choice of topical preparation should be based on the proximal extent of the disease and on patient preference. Oral aminosalicylates are less effective than topical therapies; however, a combination of oral and topical aminosalicylates can be successful in refractory patients. Alternatives to aminosalicylates are the new glucocorticoids, budesonide and beclometasone dipropionate, either as enemas or oral formulations (only beclometasone dipropionate). A combination of oral or rectal new glucocorticoids with rectal aminosalicylates should be considered in patients refractory to either approach. When these measures fail, treatment with oral glucocorticoids is necessary. An intensive intravenous steroid regimen is also helpful for patients refractory to oral steroids. Alternative treatments include short-chain fatty acid enemas, nicotine enemas and patches, acetarsol suppositories, ciclosporin enemas and epidermal growth factor enemas. Several factors potentially having a negative impact on therapeutic response include concurrent enteric pathogens, coexistent irritable bowel syndrome, patient nonadherence to therapy, inadequate dosing and duration of therapy, and proximal progression of the disease. Surgical colectomy may be required in those rare patients refractory or intolerant to pharmacotherapy. [ABSTRACT FROM AUTHOR]

BACKGROUND: Ten to 15% of patients with pouchitis experience refractory or recurrent disease. The aim of this study was to evaluate the effectiveness of a single daily high dose probiotic preparation (VSL#3) in maintaining antibiotic induced remission, and quality of life (QOL), for one year in such patients. METHODS: Patients with pouchitis at least twice in the previous year or requiring continuous antibiotics, associated with a pouchitis disease activity index (PDAI) > or =7 (0 = perfect; 18 = worst), in whom remission was induced by four weeks of combined metronidazole and ciprofloxacin, were randomised to receive VSL#3 6 g or placebo once daily for one year or until relapse. Symptomatic, endoscopic, and histological evaluations were made before, and two and 12 months after randomisation or at the time of relapse. Remission was defined as a clinical PDAI < or =2 and endoscopic PDAI < or =1. Relapse was defined as an increased clinical PDAI score > or =2 and increased endoscopic PDAI score > or =3. QOL was assessed using the inflammatory bowel disease questionnaire (IBDQ). RESULTS: Thirty six patients were randomised: 20 to VSL#3 and 16 to placebo. Remission was maintained at one year in 17 patients (85%) on VSL#3 and in one patient (6%) on placebo (p<0.0001). The IBDQ score remained high in the VSL#3 group (p = 0.3) but deteriorated in the placebo group (p = 0.0005). CONCLUSION: The once daily high dose probiotic VSL#3 is effective in maintaining antibiotic introduced remission for at least a year in patients with recurrent or refractory pouchitis. This is associated with a high level of quality of life. [ABSTRACT FROM AUTHOR]

Summary Aim: To explore the efficacy and safety of the topically acting steroid beclometasone dipropionate (BDP) in an oral controlled release formulation in the treatment of extensive or left-sided ulcerative colitis. Methods: In a multicentre, randomised, parallel-group, single-blind study, patients with active mild to moderate ulcerative colitis were randomised to a 4-week treatment with BDP 5 mg/day o.d. vs. 5-ASA 0.8 g t.d.s. The primary efficacy variable was the decrease of Disease Activity Index (DAI) (clinical symptoms and endoscopic appearance of mucosa). Safety was evaluated by monitoring adverse events, vital signs, haematochemical parameters and adrenal function. Results: One hundred and seventy-seven patients were enrolled and randomly treated with BDP (n = 90) or 5-ASA (n = 87). Mean DAI score decreased in both treatments groups (P < 0.0001 vs. baseline for both groups). Clinical remission was achieved in 63.0% of patients in the BDP group vs. 62.5% in the 5-ASA group. A significant DAI score improvement (P < 0.05) in favour of BDP was observed in patients with extensive disease. Both treatments were well tolerated. Mean plasma cortisol levels were significantly reduced vs. baseline in BDP recipients, but without signs of pituitary–adrenal function depletion. Conclusion: Oral BDP gave an overall treatment result in patients with active ulcerative colitis without signs of systemic side-effects. [ABSTRACT FROM AUTHOR]

Summary 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 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 cyclosporin or to refer the patient to the surgeon. This decision requires a careful evaluation of the patient and a medical /surgical team. Infliximab seems to be a promising drug but more controlled trial are needed. [ABSTRACT FROM AUTHOR]

Background and aims. To determine the early biological changes occurring in intestinal ischemia in vivo. Patients and methods. We studied the effects of acute transient intestinal ischemia in 15 patients undergoing elective open surgery for the treatment of abdominal subrenal aortic aneurysm induced by clamping of the aorta at subrenal level and above the branching of the inferior mesenteric artery. Blocking the blood flow results in hypoperfusion of the inferior mesenteric artery and then to rectal mucosal ischemia. Results. With the introduction of a mucosal ischemic period the basal intestinal mucosal pH decreased during ischemia, and showed a rapid increase during reperfusion to the level preceding ischemia. Parameters were evaluated in blood taken from inferior mesenteric vein. A rectal dialysis was put into the rectum to evaluate eicosanoid concentrations in rectal fluid collected before and during clamping and after declamping. Significant enhancement in plasma level of xanthine, a marker for tissue damage, was observed during reperfusion. Interleukin-6 levels were significantly elevated from 11.28±3.4 pg/ml (preischemic) to 109±85.9 pg/ml (ischemic) and to 189.33±120.24 pg/ml (reperfusion); and tromboxane B2 levels from 141.57±51.20 pg/ml preoperation to 473.01±319.01 pg/ml during the surgical procedure. Conclusion. These observations indicate that even transient ischemia modifies the inflammatory pattern. [ABSTRACT FROM AUTHOR]

Summary The meta-analyses of published trials have shown topical therapy with 5-aminosalicylic acid (5-ASA) to be the treatment of choice in active distal ulcerative colitis. Oral aminosalicylates are effective for both distal and extensive ulcerative colitis, but in distal colitis the rates of improvement and remission are usually lower than those reported for rectal 5-ASA therapy. An alternative to 5-ASA therapy is represented by the new steroids; budesonide and beclometasone dipropionate (BDP) enemas, the most extensively studied, have been shown to be as effective as conventional steroids but with a significantly lower inhibition of plasma cortisol. Patients who do not respond to 5-ASA or new steroids should be treated with oral steroids. Azathioprine or 6-mercaptopurine may be effective in patients who do not respond or cannot be weaned off steroids. Treatment of pouchitis is largely empirical and few controlled studies have been carried-out. Antibiotics are the treatment of choice and most patients make a good response to metronidazole or ciprofloxacin. Chronic refractory pouchitis may benefit from a prolonged course of a combination of antibiotics. Highly concentrated probiotics (VSL#3) are effective both for the prevention of pouchitis onset and the prevention of relapses. [ABSTRACT FROM AUTHOR]

Summary Refractoriness to conventional therapy is a common and intriguing problem in Crohn's disease patients. At the present time there is no agreement on its definition and several mechanisms are involved in its determination. Immunosuppressors, such as azathioprine (AZA), 6-mercaptopurine (6MP) and methotrexate (MTX) are effective drugs for controlling the inflammatory process and avoid chronic glucocorticosteroid treatment and its related related side-effects. Recently, the introduction of tumour necrosis factor antibodies (infliximab) has dramatically changed the natural history of Crohn's disease and its therapeutic approach. Several studies have determined the efficacy, mechanisms and safety of infliximab. However, this molecular approach has also left several questions unanswered about the mechanisms of refractoriness, possible concomitant treatments and long-term safety and efficacy. [ABSTRACT FROM AUTHOR]

Summary The monitoring of patients with ulcerative colitis is easier than in patients with Crohn's disease for several reasons: the severity of symptoms and activity of inflammation tend to run parallel in ulcerative colitis when involvement of the large bowel is more extensive. The easy accessibility of the colonic mucosa by endoscopic and histologic examination provides further information concerning the degree of inflammation. In severe attacks, the patient must be admitted to hospital and monitored carefully. Clinical and laboratory parameters (such as daily stools, CRP, fever, haemoglobin, albumin, etc.) and plain abdominal X-ray are useful in monitoring the activity of the disease and to predict the outcome. In mild to moderate attacks, endoscopic and histologic evaluation are the best methods for choosing the appropriate treatment and for assessing response. [ABSTRACT FROM AUTHOR]

Summary Aim : To evaluate efficacy and safety of oral beclometasone dipropionate (BDP) when added to 5-ASA in the treatment of patients with active ulcerative colitis. Methods : In a 4-week, placebo-controlled, double-blind study, patients with extensive or left-sided mild to moderate active ulcerative colitis were randomized to receive oral 5-ASA (3.2 g/day) plus BDP (5 mg/day) or placebo. Clinical, endoscopic and histologic features, and haematochemical parameters were recorded at baseline and at the end of the study. Results : One hundred and nineteen patients were enrolled and randomly treated with BDP plus 5-ASA (n = 58) or placebo plus 5-ASA (n = 61). Both treatment groups showed a statistically significant decrease of disease activity index (DAI) and histology score at the end of treatment (P = 0.001, each). DAI score was lower in the BDP group than in the placebo group (P = 0.014), with more patients in clinical remission in the BDP group (58.6% vs. 34.4%, P = 0.008). Serum cortisol levels significantly decreased in BDP group vs. baseline (P = 0.002), but without signs of pituitary-adrenal function depletion. A low incidence of adverse events was observed in both groups. Conclusions : Oral BDP in combination with oral 5-ASA is significantly more effective than 5-ASA alone in the treatment of patients with extensive or left-sided active ulcerative colitis. [ABSTRACT FROM AUTHOR]

Background: Preliminary data suggest that short-term antibiotic therapy with a single drug is effective for the treatment of patients with pouchitis. However, some patients are resistant to treatment. Aim: To evaluate the therapeutic efficacy of a prolonged course of a combination of two antibiotics in patients with refractory or recurrent pouchitis, as well as its impact on their quality of life. Methods: Patients with active refractory or recurrent pouchitis were recruited. This was defined as both: (i) a history of pouchitis at least twice in the last 12 months or persistent pouchitis requiring continual intake of antibiotics; and (ii) a Pouchitis Disease Activity Index score 3 7 (best to worst pouchitis=0–18) at the beginning of therapy. Treatment consisted of a combination of metronidazole, 400 or 500 mg twice daily, and ciprofloxacin, 500 mg twice daily, for 28 days. Symptomatic, endoscopic and histological evaluations were undertaken before and after antibiotic therapy using the Pouchitis Disease Activity Index score. Remission was defined as a combination of a Pouchitis Disease Activity Index clinical score of <= 2, endoscopic score of <= 1 and total score of <= 4. The quality of life was assessed with the Inflammatory Bowel Disease Questionnaire, which encompasses bowel, systemic and emotional symptoms as well as social function (worst to best=32–224). Results: Forty-four patients (24 male, 20 female; median age, 37.5 years) entered the trial and completed treatment. Thirty-six (82%) went into remission. The median Pouchitis Disease Activity Index scores before and after therapy were 12 (range, 8–17) and 3 (range, 1–10), respectively (P < 0.0001). The median Inflammatory Bowel Disease Questionnaire score also significantly improved from 96.5 (range, 74–183) to 175 (range, 76–215) with this therapy (P < 0.0001). The eight patients (five male, three female) who did not go into remission were... [ABSTRACT FROM AUTHOR]

OBJECTIVES:Promising results from clinical studies on the effect of probiotics as maintenance therapy in inflammatory bowel disease and in the prevention of onset of pouchitis ask for studies to unravel the still poorly understood mechanism of action of probiotics.METHODS:To evaluate whether the probiotic bacteria that were used in the clinical studies (VSL#3, Escherichia coli Nissle 1917, and Lactobacillus GG) are able to induce chemokine production in epithelial cells, HT29/19A monolayers were incubated with cell debris and cell extract fractions of single strains of the probiotic bacteria in doses ranging from 103 to 109 colony-forming units/ml for 32 h. Supernatants were measured for interleukin 8 by ELISA.RESULTS:Lactobacilli and bifidobacteria strains from VSL#3 and Lactobacillus GG did not induce interleukin 8, whereas both cell debris and cell extracts from E. coli Nissle 1917 induced interleukin 8 production in a dose-dependent way. Cell extracts from streptococcal strains induced interleukin 8 when applied at high concentrations.CONCLUSIONS:Probiotic Gram-positive bacteria did not induce interleukin 8, whereas the nonpathogenic, Gram-negative E. coli Nissle 1917 strain induced interleukin 8 in a dose-dependent way in this culture model. These results suggest that probiotic Gram-positive bacteria and E. coli Nissle 1917 may exert their beneficial effects on the host by a different mechanism of action. [Copyright &y& Elsevier]

Systemic glucocorticosteroids have demonstrated efficacy in ulcerative colitis (UC) but cause undesired systemic side effects. Beclomethasone dipropionate (BDP) has potent topical activity and is extensively metabolized. This randomized double-blind study investigated an oral gastroresistant controlled-release preparation of BDP in 57 patients with mild to moderately severe extensive or left-sided UC. Patients were assigned to receive BDP 5 or 10 mg/d; a third group took a clinically inactive dose (1.6 g/d) of 5-aminosalicylic acid (5-ASA). Both BDP doses displayed excellent efficacy confirmed by results of endoscopy, biopsy, and clinical evaluation. Significant improvement from baseline occurred in most signs and symptoms of UC, particularly stool frequency, rectal bleeding, and mucus in the stool (P<.01). Tolerability was good in both BDP groups. Morning plasma cortisol levels decreased significantly from baseline with BDP 10 mg, but no significant changes in vital signs were observed at the end of treatment. Despite a small sample size and the open comparison with 5-ASA, this multicenter study showed the therapeutic equivalence of BDP 5 and 10 mg/d in alleviating clinical symptoms and improving endoscopic and biopsy scores in patients with mild to moderate UC. BDP 5 mg/d displayed better general tolerability and less reduction of plasma cortisol levels, however, and may be preferable to the higher dose in this indication. [ABSTRACT FROM AUTHOR]

Background : 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. Aims : To evaluate the efficacy of an antibiotic combination for chronic active, treatment-resistant pouchitis. Patients and Methods : 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. Results : 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 (P < 0.002). 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. Conclusions : 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. [ABSTRACT FROM AUTHOR]

Nitric oxide is thought to play an important role in modulating the inflammatory process. Recently an increase in the inducible form of nitric oxide synthase (iNOS) has been found in the rat trinitrobenzene sulfonic acid model of experimental colitis, and inhibition of nitric oxide synthase activity resulted in an amelioration of tissue injury. The aim of our study was to evaluate in vivo intracolonic release of nitric oxide in this model of colitis. Experimental colitis was induced in male Sprague-Dawley rats by a single intracolonic administration of trinitrobenzene sulfonic acid. Nitrite levels were determined in rectal dialysates by HPLC. The tissue myeloperoxidase and iNOS and the luminal leukotriene B4 were also measured. Nitrite levels were significantly increased in rectal dialysates during colitis and correlated significantly with tissue myeloperoxidase and iNOS activity. The correlation between nitrite dialysate levels and wall iNOS activity confirms that nitrite in dialysates is produced by inflammatory cells and not by colonic bacterial flora. Determination of nitrite levels in rectal dialysates seems a valuable method to monitor colonic inflammation in rat trinitrobenzene sulfonic acid colitis. [ABSTRACT FROM AUTHOR]

The aim of our study was to compare the efficacy and safety of oral mesalazine with mesalazine suppositories in patients with active ulcerative proctitis.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.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.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. [ABSTRACT FROM AUTHOR]

The article discusses probiotics and barrier function in colitis. There is strong evidence of a role for the indigenous flora in driving inflammatory response in inflammatory bowel disease in genetically predisposed individuals. The exact mechanisms by which probiotics can influence barrier function remain to be elucidated. It is known that certain lactobacilli adhere to mucosal surfaces, inhibit attachment of pathogenic bacteria and enhance secretion of mucins. These properties may be instrumental in improving mucosal barrier function remain to be elucidated.

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 immunofluorescence 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-. 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. [ABSTRACT FROM PUBLISHER]