Annamaria Pronio

Probiotic administration in patients with ileal pouch–anal anastomosis for ulcerative colitis is associated with expansion of mucosal regulatory cells

Background: Probiotics have anti‐inflammatory effects in patients with inflammatory bowel disease and appear to regulate mucosal immune response through reductions in proinflammatory cytokines. The probiotic VSL#3 prevents pouchitis if started within a week of ileostomy closure and maintains remission following antibacterial treatment in patients with refractory or recurrent pouchitis. However, the efficacy of probiotics and their effects on regulatory cells if started at a greater time after surgery in patients undergoing ileal pouch anal anastomosis (IPAA) for ulcerative colitis are unknown. Methods: We conducted an open‐label study in which 31 patients at different periods from surgery without signs and symptoms of pouchitis were randomized to 2 sachets of VSL#3 once daily or no treatment for 12 months. Pouchitis disease activity index (PDAI) was evaluated at baseline and after 3, 6, and 12 months. The percentage of CD4+ T lymphocytes expressing CD25 and the inactive form of transforming growth factor‐&bgr; [latency‐associated peptide (LAP)] were evaluated at baseline and after 3 and 6 months in peripheral‐blood mononuclear cells and mucosal biopsies. Variation in tissue interleukin‐1&bgr; and Foxp3 mRNA expression was also evaluated. Results: During the study period, VSL#3‐treated patients showed a significant reduction in PDAI score and a significant increase in the percentage of mucosal CD4+CD25high and CD4+ LAP‐positive cells compared with baseline values. Tissue samples at different points showed a significant reduction in IL‐1&bgr; mRNA expression, and a significant increase in Foxp3 mRNA expression. Conclusions: We conclude that VSL#3 administration in patients with IPAA modulates the PDAI and expands the number of mucosal regulatory T cells.

Small intestine contrast ultrasonography (SICUS) for the detection of small bowel complications in crohn's disease: A prospective comparative study versus intraoperative findings

Background: In Crohns disease (CD) patients, small intestine contrast ultrasonography (SICUS) accurately assesses small bowel lesions. Its diagnostic role is not known in the assessment of intraabdominal CD complications. The aim was to assess the value of SICUS to detect intestinal complications in patients with CD. Methods: Forty‐nine CD patients (21 female, mean age 37.7 years; range 12–78 years) underwent resective bowel surgery and were included in this study. The accuracy of SICUS to preoperatively detect number, site, and length of strictures, fistulas, and abscesses was compared with surgical and pathological findings by kappa statistics. Results: SICUS identified at least one stricture in 39/40 and excluded it in 9/9 (97.5% sensitivity, 100% specificity, k = 0.93); two or more strictures in 9/12 (75% sensitivity, 100% specificity, k = 0.78). The agreement by k‐statistics between SICUS and surgery in identifying proximal and distal small intestine site of stricture was 1 and 0.92, respectively. The extension of strictures was 6.8 ± 5.4 cm at surgery, 6.6 ± 5.4 cm at SICUS (NS). Fistulas were correctly identified in 27/28 patients and excluded in 19/21 patients (96% sensitivity, 90.5% specificity, k = 0.88). Intraabdominal abscesses were correctly detected in 10/10 patients and excluded in 37/39 patients (100% sensitivity, 95% specificity, k = 0.89). Conclusions: SICUS is an accurate method for the detection of small intestinal complications in CD. Noninvasive SICUS is valuable as a primary investigative method for evaluating and planning proper treatment in patients with severe CD of the small bowel. (Inflamm Bowel Dis 2011;)

The challenge of imaging dense breast parenchyma is magnetic resonance mammography the technique of choice? a comparative study with x-ray mammography and whole-breast ultrasound

Purpose:To establish the value of magnetic resonance imaging (MRI) of the breast in comparison to x-ray mammography and ultrasound for breast cancer evaluation in women with dense breast parenchyma. Materials and Methods:Two hundred thirty-eight women with dense breast parenchyma who were suspicious for breast cancer or inconclusive for the presence of breast lesions based on clinical examination, ultrasound or x-ray mammography, and who underwent breast MRI at 1.5 T before and after administration of 0.1 mmol/kg gadobenate dimeglumine were evaluated. Lesions considered malignant (Breast Imaging Reporting and Data System (BI-RADS) 4 or 5) on x-ray mammography and/or ultrasound and as BI-RADS 3, 4, or 5 on MRI were evaluated histologically. Other lesions were followed up at 6 and/or 18 months. The diagnostic performance (sensitivity, specificity, accuracy, and positive and negative predictive values) of each technique was determined and compared using a general linear mixed model with appropriate correction for multiplicity. Results:At final diagnosis 121 of 238 (50.8%) women had one or more confirmed malignant lesions, whereas 117 (49.2%) had benign lesions or no lesions. Among 97 women who underwent all 3 techniques more lesions (malignant and benign) were detected with breast MRI (n = 135) than with x-ray mammography (n = 85) or ultrasound (n = 107) and diagnostic confidence was greater. In terms of patient-based diagnostic accuracy breast MRI was significantly (P[r] < 0.0001) superior to both x-ray mammography and ultrasound (96.9% accuracy for MRI vs. 60.8% for mammography and 66.0% for US). Malignant lesions were histologically confirmed in 55 of 97 women who underwent all 3 techniques. Breast MRI detected more cases of multifocal, multicentric, and contralateral disease and fewer misdiagnoses occurred. Overall, breast MRI led to a modification of the surgical approach for 28 (23.1%) of the 121 women with diagnosed malignant disease. Conclusion:Breast MRI should be considered for routine breast cancer evaluation in women with dense breast parenchyma.

Lamina Propria CD4+LAP+ Regulatory T Cells Are Increased in Active Ulcerative Colitis but Show Increased IL-17 Expression and Reduced Suppressor Activity

BACKGROUND A CD4+CD25- regulatory T cell population expressing the surface TGF-β in its latent form LAP+ [latency associated peptide] cells was proved to be protective in experimental colitis and to be suppressive of human peripheral blood [PB] T proliferation. We investigated the frequency and function of lamina propria [LP] CD4+LAP+ T cells in inflammatory bowel disease [IBD] patients. METHODS Specimens from patients undergoing colonoscopy or bowel resection for IBD and colonic cancer were used as source of lamina propria mononuclear cells [LPMC]. The ulcerative colitis [UC] group was divided according to endoscopic activity evaluated with modified Baron Score. IL-17, IFN-γ, IL-10, LAP, and Foxp3 expression in CD3+CD8- [CD4] or CD3+/CD4+ gated cell population was assessed by immunofluorescence. The ability of FACS-sorted LP CD3+CD8-[CD4] LAP+CD25- to inhibit stimulated autologous PB CD3+CD8-[CD4] LAP- CD25- cells proliferation was assessed. RESULTS LP CD4LAP+ cells were significantly increased, when compared with controls, in active UC patients and not in Crohns disease patients. The majority of LP CD4+LAP+ cells were Foxp3-. The percentage of IL-17+ cells in LP CD3+CD8-[CD4] LAP+ cells was significantly higher in active UC patients when compared with controls. LP CD3+CD8-[CD4]LAP+CD25- isolated from UC patients showed reduced or no ability to inhibit autologous PB CD3+CD8-[CD4]LAP-CD25- cell proliferation when compared with controls. Removal of IL-17+ cells from LP CD3+CD8-[CD4] LAP+ cells increases their suppressive ability. CONCLUSIONS The percentage of LP CD4LAP+ cells is increased in active UC, showing reduced suppressor activity due to their increased proportion of intracellular IL-17 expression.

Restorative proctocolectomy : morphological and functional study with coronal CT

Abstract.Background: Restorative proctocolectomy with ileal pouch has become the surgical treatment of choice for patients with ulcerative colitis (UC) and familial polyposis of the colon. Defecography is the radiological technique commonly employed to obtain detailed information on function and morphology of the ileal pouch; it allows the direct visualization of the ileal pouch and the anal canal, but it does not provide the visualization of the pelvis. Methods: In all patients, computed tomography (CT) on coronal planes was performed to determine its possibilities as an alternative to defecography; 10 patients with UC submitted to restorative proctocolectomy and were examined. Results: Coronal CT images provided a panoramic vision of the pelvis and demonstrated the morphology of the ileal pouch, the thickness of its walls, and its correlation with the surrounding tissues. Coronal CT also allowed the evaluation of the continence of ileo-anal and ileo-ileal anastomosis and the functional changes of the perineal muscles at rest and during squeezing. Conclusion: CT images acquired on coronal planes allows an easy and clear detection of the major postoperative complications, such as stenosis or dehiscences of the anastomosis, pelvic phlogosis, and fistulae.

Genetic diversity, phylogroup distribution and virulence gene profile of pks positive Escherichia coli colonizing human intestinal polyps

Some Escherichia coli strains of phylogroup B2 harbor a (pks) pathogenicity island that encodes a polyketide-peptide genotoxin called colibactin. It causes DNA double-strand breaks and megalocytosis in eukaryotic cells and it may contribute to cancer development. Study of bacterial community that colonizes the adenomatous polyp lesion, defined as precancerous lesions, could be helpful to assess if such pathogenic bacteria possess a role in the polyp progression to cancer. In this cross-sectional study, a total of 1500 E. coli isolates were obtained from biopsies of patients presenting adenomatous colon polyps, the normal tissues adjacent to the polyp lesion and patients presenting normal mucosa. pks island frequency, phylogenetic grouping, fingerprint genotyping, and virulence gene features of pks positive (pks+) E. coli isolates were performed. We found pks+E. coli strongly colonize two patients presenting polypoid lesions and none were identified in patients presenting normal mucosa. Predominant phylogroups among pks+E. coli isolates were B2, followed by D. Clustering based on fragment profiles of composite analysis, typed the pks+ isolates into 5 major clusters (I-V) and 17 sub-clusters, demonstrating a high level of genetic diversity among them. The most prevalent virulence genes were fimH and fyuA (100%), followed by vat (92%), hra and papA (69%), ibeA (28%), and hlyA (25%). Our results revealed that pks+E. coli can colonize the precancerous lesions, with a high distribution in both the polyp lesions and in normal tissues adjacent to the lesion. The high differences in fingerprinting patterns obtained indicate that pks+E. coli strains were genetically diverse, possibly allowing them to more easily adapt to environmental variations.

Adenocarcinoma of the ileal pouch mucosa: a new diagnostic challenge

Dear editor, We read with interest the manuscript recently published by O’Mahoney et al. entitled “Adenocarcinoma of the ileal pouch mucosa: case report and literature review” [1]. The authors well presented a case of adenocarcinoma of ileal pouch mucosa diagnosed after 13 years of pouch creation. They reviewed literature for true pouch adenocarcinoma, and a total of 27 patients have been described around the world. Of these, 63 % (17/27) had neoplasia in their original proctocolectomy specimen. Mean time of adenocarcinoma development was 8.9 years. Five-year survival after excision of the pouch was 70 %. In our experience of 112 ileal pouch anastomosis, we had one case of true pouch adenocarcinoma. A 71-year-old man was diagnosed of ulcerative colitis for 30 years; he underwent a total colectomy 26 years ago (on 1985). Patient course was complicated by chronic pouchitis medically treated. After 11 years of follow-up, primary sclerosing cholangitis diagnosis was done. During annual endoscopic control, a polypectomy was performed. At pathology, a wide area of high-grade dysplasia with a minute focus of adenocarcinoma polyp was observed. A magnetic resonance imaging was performed, and a mucosal thickening was observed. Considering oncological indication to remove the pouch, patient age, and technical difficulty to restore intestinal continuity, the patient underwent ileal pouch excision with end ileostomy. After 34 months of follow-up, the patient is alive with no local or systemic recurrence. In our experience, mean age at surgery was 37 years old with a mean follow-up of 123 months. For a 6-month endoscopical follow-up for the first 4 years after surgery and if no complication is observed, a 12-month control is performed. We agree with O’Mahoney et al. highlighting the need for long-term follow-up and attention to these patients. Through the absence of consensus in the surveillance of pouch, many authors may suggest there own clinical practice [2–4]. However, we suggest to perform a closed follow-up with random biopsy in all patients, with or without previous neoplasia. In patients with ileal pouch anastomosis, no limits of time should be considered to be out of risk.