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Livia Biancone

Publications and source records attributed to Livia Biancone.

13 recordsLinked to original sources
PubMed2006

Local injection of infliximab in the postoperative recurrence of Crohn's disease.

BACKGROUND: Local injection of infliximab in Crohn's disease (CD) lesions may reduce the risk of rare side effects, reduce the dose, and increase the efficacy of the drug. The objective was to prospectively assess the feasibility and the safety of local injection of infliximab for the postoperative recurrence of patients with CD who were followed for at least 1 year. METHODS: In a pilot, open-label study, 8 patients with CD (3 men; median age 48 years, range 35-82 years) undergoing ileocolonoscopy were prospectively enrolled. Inclusion criteria included the following: (1) localized (<5 cm) recurrence, (2) inflammatory pattern, and (3) clinically inactive CD. At the first endoscopy, lesions were injected with infliximab (median, 30 mg; range, 8-60 mg); a control endoscopy was performed at 2 weeks in 4 patients (3 received a second injection followed by a control endoscopy at 6 weeks) and at 4 weeks in 4 patients (2 received a second injection followed by a control endoscopy at 8 weeks). OBSERVATIONS: No patients showed side effects or clinical relapse in the short term and the long term (median follow-up, 20 months; range, 14-21 months). Endoscopic score improved in 3/8 patients. The histologic scores were reduced in 4 patients, worsened in 3, and were unchanged in one patient with CD. CONCLUSIONS: Local injection of infliximab into patients with CD recurrence is feasible and safe, requiring a low dose. Present findings suggest the need of placebo-controlled trials to assess the efficacy of this new and safe procedure in subgroups of patients with CD.

Adult↗
PubMed2006

A functional role of flip in conferring resistance of Crohn's disease lamina propria lymphocytes to FAS-mediated apoptosis.

BACKGROUND & AIMS: There is evidence that, in Crohn's disease (CD), lamina propria T lymphocytes (LPLs) are resistant to FAS-mediated apoptosis and that this defect contributes to the mucosal T-cell accumulation. In this study we examined the functional role of Flip, a Flice inhibitor protein, in the resistance of CD LPL to FAS-mediated apoptosis. METHODS: Biopsy specimens and LPLs were taken from CD and ulcerative colitis (UC) patients and normal controls and analyzed for Flip by Western blotting. We also examined whether inhibition of Flip by antisense oligonucleotide restored the susceptibility of CD LPLs to FAS-induced apoptosis. LPL apoptosis was assessed by flow cytometry. RESULTS: After FAS stimulation, the rate of apoptosis of CD3+ LPLs was higher in normal controls and patients with UC than in patients with CD. Enhanced expression of both long and short Flip isoforms was seen in biopsy specimens and purified CD3+ and CD45RO+ LPLs of CD patients in comparison with UC patients and normal controls. No increase in Flip was documented in untreated celiac disease mucosa, thus suggesting the possibility that induction of Flip in the gut does not simply rely on the ongoing inflammation. Finally, we showed that inhibition of Flip by antisense oligonucleotide reverted the resistance of CD LPLs to FAS-induced apoptosis. CONCLUSIONS: Data suggest a role for Flip in the resistance of CD LPLs to FAS-mediated apoptosis.

Annexin A5↗
PubMed2005

Interleukin-21 enhances T-helper cell type I signaling and interferon-gamma production in Crohn's disease.

BACKGROUND & AIMS: T-helper (Th)1 cells play a central role in the pathogenesis of tissue damage in Crohn's disease (CD). Interleukin (IL)-12/STAT4 signaling promotes Th1 cell commitment in CD, but other cytokines are needed to maintain activated Th1 cells in the mucosa. In this study, we examined the expression and role of IL-21, a T-cell-derived cytokine of the IL-2 family; in tissues and cells isolated from patients with inflammatory bowel disease. METHODS: IL-21 was examined by Western blotting in whole mucosa and lamina propria mononuclear cells (LPMCs) from patients with CD, ulcerative colitis (UC), and controls. We also examined the effects of exogenous IL-12 on IL-21 production, as well as the effects of blocking IL-21 with an IL-21-receptor Ig fusion protein. Interferon (IFN)-gamma was measured in the culture supernatants by enzyme-linked immunosorbent assay, and phosphorylated STAT4 and T-bet were examined by Western blotting. RESULTS: IL-21 was detected in all samples, but its expression was higher at the site of disease in CD in comparison with UC and controls. Enhanced IL-21 was seen in both ileal and colonic CD and in fibrostenosing and nonfibrostenosing disease. IL-12 enhanced IL-21 in normal lamina propria lymphocytes through an IFN-gamma-independent mechanism, and blocking IL-12 in CD LPMCs decreased anti-CD3-stimulated IL-21 expression. Neutralization of IL-21 in CD LPMC cultures decreased phosphorylated STAT4 and T-bet expression, thereby inhibiting IFN-gamma production. CONCLUSIONS: Our data suggest that IL-21 contributes to the ongoing Th1 mucosal response in CD.

Blotting, Western↗
PubMed2005

A new oral delivery system for 5-ASA: preliminary clinical findings for MMx.

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 < or =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.

Administration, Oral↗
PubMed2004

CARD15 mutation analysis in an Italian population: Leu1007fsinsC but neither Arg702Trp nor Gly908Arg mutations are associated with Crohn's disease.

BACKGROUND: CARD15 gene mutations have been demonstrated to confer a high risk of Crohn's disease (CD). Despite this, recent studies reported variable associations between CD and CARD15 mutations in distinct ethnic groups, thus raising the hypothesis that genetic and/or allelic heterogeneity may influence the relationship between CARD15 and CD. The purpose of this study was to evaluate the frequency of the main mutations of the CARD15 gene (Leu 1007fsinsC, Arg702Trp, and Gly908Arg) in Italian CD patients and to establish possible genotype-phenotype correlations. METHODS: One hundred sixty-five CD patients and 125 healthy subjects were consecutively enrolled from January to November 2001. The Leu1007fsinsC mutation was assessed by denaturing high-performance liquid chromatography and Arg702Trp and Gly908Arg mutations by Pyrosequencing technology. RESULTS: Among the CARD15 gene mutations tested, only the Leu1007fsinsC was associated with CD (30/165 CD patients, 18%, versus 3/125 healthy subjects, 2.4%; p < 0.001). In particular, 23 CD patients were heterozygotes and 7 were homozygotes. No healthy subject exhibited the mutant homozygous genotype. Odds ratios for CD were 6.9 for heterozygotes and 41.0 for homozygotes. The genotype-phenotype analysis revealed that a fibrostenosing CD of the distal ileum was more frequent in patients carrying the Leu1007fsinsC mutation. CONCLUSIONS: This study confirms the association between CARD15 gene mutations and CD and shows that only the Leu1007fsinsC mutation is a risk factor of CD in an Italian population.

Adolescent↗
PubMed2003

99mTc-interleukin-2 and (99m)Tc-HMPAO granulocyte scintigraphy in patients with inactive Crohn's disease.

Crohn's disease (CD) is a chronic inflammatory bowel disease that may involve the whole gut. Marked intestinal T cell and macrophage activation is a key feature of the disease. Polymorphonuclear cell infiltration is also observed in the diseased gut, mainly during active inflammation. Scintigraphic detection of granulocytes and activated lymphocytes infiltrating the gut wall may be useful in identifying a subgroup of patients with clinically inactive CD who are undergoing early clinical relapse. The aims of the present study were (a) to compare the effectiveness of scintigraphy with (99m)Tc-labelled interleukin-2 ((99m)Tc-IL2) and with (99m)Tc-HMPAO labelled granulocytes ((99m)Tc-WBC) in detecting the presence and extent of bowel inflammation in patients with long-term inactive CD (>12 months) and (b) to assess the accuracy of these techniques in predicting future disease relapse. We studied 29 patients with ileal and/or colonic CD in stable clinical remission (Crohn's Disease Activity Index <150 for at least 12 months) using both (99m)Tc-IL2 and (99m)Tc-WBC scintigraphy in order to evaluate the extent of acute and chronic inflammation in the bowel. Planar and single-photon emission tomography images were acquired in each patient at 1 h p.i. For quantitative analysis of (99m)Tc-IL2 uptake, the abdomen was divided into 32 regions of interest. Despite the absence of symptoms, 18 patients (62%) showed a positive (99m)Tc-IL2 and 18 (62%) a positive (99m)Tc-WBC scan. Only 12 patients (41.4% of the total group) were positive on both scans, and the sites of IL2 and granulocyte bowel uptake were usually located in different segments, indicating that in CD, acute and chronic inflammation can be present in different sites. As far as the prognostic role of the two scans in predicting future disease relapse is concerned, both (99m)Tc-IL2 and (99m)Tc-WBC scintigraphy showed a high negative predictive value (1.00 and 0.91, respectively) but a weak positive predictive value (0.44 and 0.39, respectively). Nevertheless, Kaplan-Meier curves generated between scintigraphic findings and time free from disease relapse were statistically different only for (99m)Tc-IL2 scintigraphy (log-rank test, P=0.013). These results indicate that (99m)Tc-IL2 scintigraphy can be useful in selecting CD patients in clinical remission who could benefit from preventive therapy to avoid disease relapse.

Crohn Disease↗
PubMed2003

Fecal alpha 1-antitrypsin clearance as a marker of clinical relapse in patients with Crohn's disease of the distal ileum.

BACKGROUND: Crohn's disease (CD) shows a chronic relapsing course but no marker of relapse is currently available. However, fecal alpha 1-antitrypsin (alpha 1-AT) clearance (alpha 1-ATCl) is an indicator of protein loss and increases during active inflammation. We assessed the usefulness of fecal alpha 1-ATCl in predicting clinical relapse in patients with inactive ileal CD. DESIGN: In a prospective longitudinal study, 26 patients with inactive ileal CD (Crohn's disease activity index (CDAI) < 150) (18 males, mean age 43 +/- 10, range 23-58) were enrolled. Fecal alpha 1-ATCl and concentration, daily stool weight and serum alpha 1-AT were measured at baseline (visit 1), after 1 week (visit 2) and 3 weeks (visit 3) in 24/26 patients (two drop-outs) (short-term study). In six of these 26 patients, fecal alpha 1-ATCl was also measured every 3 months for 1 year (long-term study). All patients were clinically assessed every 3 months for 1 year and every 6 months for 2 years. Ten healthy volunteers were tested as controls. METHODS: Serum and fecal alpha 1-AT concentration was quantified by radial immunodiffusion. RESULTS: The median fecal alpha 1-ATCl value at baseline was higher in inactive patients undergoing clinical relapse (CDAI > 200) in the next 6 months than in those remaining in remission at 6 months (P = 0.03). Fecal alpha 1-ATCl showed a 75% sensitivity, 85% specificity, 50% positive predictive value and 94% negative predictive value in predicting CD relapse in the next 6 months. In the long-term follow-up, fecal alpha 1-ATCl values increased at 12 months compared with both baseline and 6 month values (P = 0.005; P = 0.009). Fecal alpha 1-ATCl was higher in patients with raised C-reactive protein (P = 0.039). CONCLUSIONS: Results from our study suggest that fecal alpha 1-ATCl is an indicator of clinical relapse in patients with CD of the distal ileum under regular surveillance.

Adult↗
PubMed2003

Virtual colonoscopy compared with conventional colonoscopy for stricturing postoperative recurrence in Crohn's disease.

BACKGROUND: The place of virtual colonoscopy (VC) in patients with Crohn's disease (CD) requiring endoscopic follow-up after surgery is unknown. The authors compared findings from VC versus conventional colonoscopy (CC) for assessing the postoperative recurrence of CD. METHODS: Sixteen patients with ileocolonic anastomosis for CD were prospectively enrolled from January 2001 to January 2002. Recurrence was assessed by CC according to Rutgeerts et al. VC was performed with a computed tomography scanner, with images examined by three radiologists who were unaware of the endoscopic findings. RESULTS: CC showed perianastomotic recurrence in 15 of 16 patients. Perianastomotic narrowing or stenosis was detected by VC in 11 of these 15 patients. There were 11 true positive, 1 true negative, 0 false-positive, and 4 false-negative findings (73% sensitivity, 100% specificity, 100% positive predictive value, 20% negative predictive value, 75% accuracy). Among the eight patients showing a rigid stenosis of the anastomosis not allowing passage of the colonoscope, VC detected narrowing or stenosis in seven patients. CONCLUSIONS: The current findings suggest that although the widespread use of VC in CD is currently not indicated because of possible false-negative findings, this technique may represent an alternative to CC in noncompliant postsurgical patients with a rigid stenosis not allowing passage of the endoscope.

Adult↗
PubMed2003

Tropomyosin expression in the ileal pouch: a relationship with the development of pouchitis in ulcerative colitis.

OBJECTIVE: Human tropomyosin isoform 5 (hTM5) is a cytoskeletal protein expressed in normal epithelial cells, predominantly in the colon. An autoimmune response toward hTM5 has been reported in ulcerative colitis (UC). Whether hTM5 expression in the ileum is involved in pouchitis is unknown. We assessed hTM5 expression on ileal epithelial cells at surgery and subsequently on development of pouchitis in UC. METHODS: In a prospective longitudinal study, 28 UC patients undergoing ileal pouch procedures were included. Biopsy samples were taken from the rectum at surgery, as well as from the ileal pouch at surgery and at 6 months. The specimens were stained by immunoperoxidase using the anti-hTM5 monoclonal antibody CG3. Pouchitis was assessed by the Pouchitis Disease Activity Index and hTM5 expression on a scale of 0-3. RESULTS: At surgery, in rectal samples, hTM5 expression was strong in all epithelial cells including the luminal surface, whereas in ileal samples hTM5 was not expressed or focally expressed only in the goblet cells. At 6 months, the ileum was found to have undergone morphological changes, becoming similar to the colon and showing shortening or reduced number of villi. These changes were associated with a diffuse hTM5 staining in the goblet cells and in the nongoblet epithelial cells lining the crypts and the lumen. The hTM5 score was related to the Pouchitis Disease Activity Index at 6 months (r = 0.82; p = 0.01). CONCLUSIONS: Expression of hTM5 shows a different pattern in the ileal pouch in UC after surgery. This event is associated with morphological changes of the ileum toward colonic epithelium, related to the development of pouchitis.

Antibodies, Monoclonal↗
PubMed2002

Metastatic Crohn's disease of the forehead.

BACKGROUND: Metastatic Crohn's disease (CD) involves the presence of cutaneous granuloma distant from the intestinal lesions related to the disease, usually observed in colonic CD. CASE HISTORY: A 35-year-old female with a permanent ileostomy following proctocolectomy for CD presented in 1999 with a 2-month history of an unusual skin lesion of the forehead. A diagnosis of CD of the ileum, colon, and rectum had been made in 1994. In 1997, a proctocolectomy with ileostomy was performed due to fistulizing severe refractory disease. Microscopic aspects of the intestinal lesions showed deep and fissuring ulcers. After surgery, she went into remission, and a small bowel follow-up in 1999 showed no recurrence, when she presented with the skin lesion of the forehead. MICROSCOPIC DATA: Histological analysis of endoscopical and surgical intestinal specimens showed chronic granulomatous inflammation of the ileum, colon, and rectum, confirming the diagnosis of CD. The forehead skin biopsy was examined by three independent histopathologists. The lesion was composed of numerous small granulomas (Ziehl-Nielsen negative), with no foreign bodies, mainly composed of CD68-positive and periodic acid Schiff-negative monocytes. Despite the low number of lymphocytes, the macroscopical and microscopical aspect of the forehead lesion, together with the clinical history, led to a diagnosis of rare metastatic CD of the forehead. CONCLUSIONS: This case report describes the development of an unusual granulomatous skin lesion of the forehead in a patient with established CD showing no postoperative recurrence.

Adult↗