M. Ascolani

Endoscopic vs ultrasonographic findings related to Crohn's Disease recurrence: A prospective longitudinal study at 3 years

BACKGROUND AND AIMS Ileocolonoscopy (IC) is the gold standard for assessing Crohns Disease (CD) recurrence after ileo-colonic resection. In a prospective longitudinal study we compared findings related to CD recurrence when using techniques visualizing either the luminal or the extraluminal surface (IC and small bowel follow through, SBFT vs Small Intestine Contrast Ultrasonography, SICUS). METHODS From 2003 to 2008, 25 CD patients undergoing ileo-colonic resection were enrolled. Clinical assessment (CDAI) was performed at 1, 2 and 3 years. IC was performed at 1 (n=25) and 3 years (n=15), SBFT at 2 years (n=21) and SICUS at 1 (n=25), 2 (n=21) and 3 years (n=15). Recurrence was assessed by SBFT and SICUS (bowel wall thickness, BWT) when using IC as gold standard. RESULTS At 1 year, all patients were inactive and recurrence was detected by IC in 24/25 (96%) and by SICUS in 25/25 patients. At 2 years, 6/21 patients (29%) were active and recurrence was detected by SBFT in 12/21 (57%) and by SICUS in 21/21 patients. At 3 years, 5/15 patients (33%) were active, IC showed recurrence in 14/15 (93%), and SICUS in 15/15 patients. The endoscopic score at 1 year was higher in patients developing relapse at 2 years (n=5) than in patients maintaining remission (n=10) (median: 4, range 3-4 vs 2, range 0-3; p=0.003). The same finding was not observed by using SICUS (median BWT at 1 year: 5, range 4-7 vs 3.7, range 3.5-6; p=0.19). CONCLUSIONS Although IC and SICUS provide a different view of the bowel wall, in experienced hands SICUS provides findings compatible with endoscopic recurrence after ileo-colonic resection for CD. Discrepant findings may be observed in a low proportion of patients with minor lesions related to CD recurrence.

Anti-TNF-alpha treatments and obstructive symptoms in Crohn's Disease: A prospective study ☆

BACKGROUND The development of symptomatic strictures in Crohns Disease after anti-Tumour Necrosis Factor-α antibodies is undefined. AIM To assess, in a prospective longitudinal study, the frequency of sub/obstructions in Crohns Disease patients after treatment with Infliximab or Adalimumab. Changes of small bowel lesions after these biological therapies were searched by ultrasonography. MATERIALS AND METHODS From January 2007 to October 2008, 36 Crohns Disease patients with no previous sub/obstructions were treated with either Infliximab (n=13) or Adalimumab (n=23) for ≥12months (mean follow-up duration after the first treatment 23.2±6.8months). Small Intestine Contrast Ultrasonography was performed before and after treatment in 19/36 patients. Sonographic parameters included: bowel wall thickness, lumen diameter, bowel dilation and lesion extent. RESULTS Sub/obstructions developed in 3/36 patients treated with Infliximab (n=1) or Adalimumab (n=2), all with fibrostricturing Crohns Disease. Sonographic parameters did not significantly change after treatment. CONCLUSIONS Sub/obstructive symptoms may develop in one tenth of Crohns Disease patients treated with anti-Tumour Necrosis Factor-α antibodies, with no significant sonographic changes of the small bowel lesions.

Fistulizing pattern in Crohn's disease and pancolitis in ulcerative colitis are independent risk factors for cancer: A single-center cohort study

BACKGROUND & AIMS The combined role of immunomodulators (IMM) and clinical characteristics of Inflammatory Bowel Disease (IBD) in determining the cancer risk is undefined. The aim was to assess whether clinical characteristics of IBD are independent risk factors for cancer, when considering thiopurines and anti-TNFs use. METHODS In a single-center cohort study, clinical characteristics of IBD patients with IBD duration ≥1 year and ≥2 visits from 2000 to 2009 were considered. Tests for crude rates and survival analysis methods were used to assess differences of incidence of cancer between groups. The methods were adjusted for the time interval between diagnosis and immunomodulatory treatments. RESULTS IBD population included 1222 patients :615 Crohns disease (CD), 607 ulcerative colitis (UC). Cancer was diagnosed in 51 patients (34 CD,17 UC), with an incidence rate of 4.3/1000 pt/year. The incidence rate of cancer was comparable between CD and UC (4.6/1000 pt/year vs 2.9/1000 pt/year ;p=n.s.). Cancer most frequently involved the breast, the GI tract, the skin. Lymphoma was diagnosed in CD (1HL, 1NHL,0 HSTCL). Risk factors for cancer included older age at diagnosis of IBD (CD: HR 1.25;95%CI 1.08-1.45; UC:HR 1.33;95%CI 1.15-1.55 for an increase by 5 years; p=0.0023; p=0.0002), fistulizing pattern in CD (HR 2.55; 95%CI 1.11-5.86,p=0.0275), pancolitis in UC (HR 2.79;95%CI 1.05-7.40 p=0.0396 vs distal). IMM and anti-TNFs did not increase the cancer risk in CD, neither IMM in UC (anti-TNFs risk in UC not feasible as no cases observed). CONCLUSIONS Fistulizing pattern in CD, pancolitis in UC and older age at diagnosis of IBD are independent risk factors for cancer.

Small bowel capsule endoscopy vs conventional techniques in patients with symptoms highly compatible with Crohn's Disease

BACKGROUND & AIMS The diagnostic role of Small Bowel Capsule Endoscopy (SBCE) in Crohns Disease (CD) is under investigation. In a prospective study we investigated the diagnostic role of SBCE in patients with symptoms highly compatible with CD and undefined diagnosis after conventional techniques. METHODS From September 2005 to May 2009, all patients with clinically suspected CD and not conclusive diagnosis after Ileocolonoscopy (IC), Small Bowel Follow Through (SBFT) and Small Intestine Contrast Ultrasonography (SICUS) were enrolled. Findings compatible with CD included: bowel wall thickness (BWT) >3mm (for SICUS), ulcers, stenosis/strictures, fistulae (for SICUS, SBFT); >5 aphtoid ulcers, deep ulcers and/or strictures (for SBCE). RESULTS Conventional techniques did not lead to a conclusive diagnosis in 30 patients (19 F, median age 31 years, range 8-57), showing chronic diarrhoea (n=27), abdominal pain (n=23), weight loss (n=5), fever (n=5), Iron Deficiency Anaemia (IDA)(n=5) and/or perianal disease (n=4). Findings compatible but not diagnostic for small bowel CD were detected in 19 (63%) by IC in 12 (40%) by SICUS and in 15 (50%) by SBFT. SBCE showed ileal lesions in 15 (50%) patients, including findings compatible with CD in 12 (40%). SBCE retention requiring surgery was observed in 1 patient. A significant concordance was observed between SBCE and IC k=0.33 C(k)=[0.25;0.42], but not between SBCE and SICUS k=0.13 IC(k)=[0.045;0.22] and between SBCE and SBFT k=0 IC(k)=[-0.089;0.089]. CONCLUSIONS SBCE may detect lesions compatible with small bowel CD in almost one third of patients with symptoms highly compatible with CD and not conclusive diagnosis by using conventional techniques.

Psoriasis Phenotype in Inflammatory Bowel Disease: A Case-Control Prospective Study.

BACKGROUND AND AIMS Whether inflammatory bowel disease [IBD] is associated with specific psoriasis phenotypes is undefined. In a case-control prospective study, we aimed to assess the severity and phenotype of psoriasis in IBD vs matched non-IBD controls with psoriasis [non-IBD]. METHODS From 2011 to 2013, dermatological assessment was performed in all IBD patients showing lesions requiring characterisation. In patients with psoriasis, assessment included: presence, characteristics, and severity. Each IBD patient with psoriasis was matched [gender, ethnicity, age ± 5 years] with one non-IBD patient with psoriasis. STATISTICAL ANALYSIS data were expressed as median [range], chi-square, Students t test. RESULTS Dermatological assessment was performed in 251 IBD patients [115 females, age 47 [16-85]; IBD duration 9 years [1-46]]: 158 Crohns disease [CD] [63%], 93 ulcerative colitis [UC] [37%]. Psoriasis was detected in 62 [25%] IBD patients: 36 [58%] CD, 26 UC [42%; p = 0.44]. Clinical characteristics were comparable between IBD patients with or without psoriasis: age 50 [23-72] vs 47 [16-85]; IBD duration 9.5 [1-46] vs 9 [1-41]; p = non-significant]. The non-IBD group included 62 patients with psoriasis: 35 male; age 47 [18-75]. Mild psoriasis was more frequent in IBD vs non-IBD [87% vs 53%; p < 0.0001], whereas moderate and severe psoriasis were more frequent in non-IBD vs IBD [37% vs 13%, p = 0.004; 10% vs 0%; p = 0.036]. Plaque-type psoriasis was the most common phenotype in both IBD and non-IBD [p < 0.0001 vs others phenotypes].The frequency of plaque-type, nail psoriasis and psoriatic arthritis was lower in IBD vs non-IBD [p = 0.008; p < 0.0001; p = 0.006]. Psoriasis occurred after anti-tumour necrosis factor [TNF]α treatment in six CD patients [7%]. CONCLUSIONS Severity and phenotypes of psoriasis may differ between patients with IBD and their matched non-IBD controls.

High Expression of the “A Disintegrin And Metalloprotease” 19 (ADAM19), a Sheddase for TNF-α in the Mucosa of Patients with Inflammatory Bowel Diseases

Background:Tumor necrosis factor &agr; (TNF-&agr;) plays a major role in the tissue-damaging immune response in inflammatory bowel diseases (IBDs). The tissue concentration of TNF-&agr; is related to the activity of “A Disintegrin And Metalloprotease” (ADAMs), enzymes that process membrane-bound TNF-&agr; and liberate the TNF-&agr; trimer into the extracellular environment. Although IBD-related inflammation is associated with high ADAM17 levels, the contribution of other members of the ADAMs family is not known. In this study, we characterized the expression of other TNF-&agr; convertases (i.e., ADAM9, ADAM10, and ADAM19) in IBD. Methods:Normal and IBD biopsies were examined for the content of ADAMs by real-time polymerase chain reaction, Western blotting and immunohistochemistry. ADAM19 was also analyzed in intestinal epithelial cells and normal colonic explants stimulated with inflammatory cytokines and in ex vivo biopsies taken from IBD patients before and after a successful infliximab treatment. Results:ADAM19 RNA transcripts and protein were upregulated in patients with ulcerative colitis and, to a lesser extent, in patients with Crohns disease compared with normal controls. In contrast, ADAM9 and ADAM10 expression did not differ between patients with IBD and controls. Immunohistochemical analysis showed that epithelial cells were the major source of ADAM19 in IBD. ADAM19 expression was increased in colonic epithelial cell lines and normal colonic explants by TNF-&agr;, interleukin 21 and interleukin 6, and was downregulated in IBD tissue by infliximab. Conclusions:These findings suggest the existence of a positive feedback mechanism involving cytokines and ADAM19 that can amplify cytokine production in IBD.

Small intestine contrast ultrasonography vs computed tomography enteroclysis for assessing ileal Crohn's disease

AIM To compare computed tomography enteroclysis (CTE) vs small intestine contrast ultrasonography (SICUS) for assessing small bowel lesions in Crohns disease (CD), when using surgical pathology as gold standard. METHODS From January 2007 to July 2008, 15 eligible patients undergoing elective resection of the distal ileum and coecum (or right colon) were prospectively enrolled. All patients were under follow-up. The study population included 6 males and 9 females, with a median age of 44 years (range: 18-80 years). INCLUSION CRITERIA (1) certain diagnosis of small bowel requiring elective ileo-colonic resection; (2) age between 18-80 years; (3) elective surgery in our Surgical Unit; and (4) written informed consent. SICUS and CTE were performed ≤ 3 mo before surgery, followed by surgical pathology. The following small bowel lesions were blindly reported by one sonologist, radiologist, surgeon and histolopathologist: disease site, extent, strictures, abscesses, fistulae, small bowel dilation. Comparison between findings at SICUS, CTE, surgical specimens and histological examination was made by assessing the specificity, sensitivity and accuracy of each technique, when using surgical findings as gold standard. RESULTS Among the 15 patients enrolled, CTE was not feasible in 2 patients, due to urgent surgery in one patients and to low compliance in the second patient, refusing to perform CTE due to the discomfort related to the naso-jejunal tube. The analysis for comparing CTE vs SICUS findings was therefore performed in 13 out of the 15 CD patients enrolled. Differently from CTE, SICUS was feasible in all the 15 patients enrolled. No complications were observed when using SICUS or CTE. Surgical pathology findings in the tested population included: small bowel stricture in 13 patients, small bowel dilation above ileal stricture in 10 patients, abdominal abscesses in 2 patients, enteric fistulae in 5 patients, lymphnodes enlargement (> 1 cm) in 7 patients and mesenteric enlargement in 9 patients. In order to compare findings by using SICUS, CTE, histology and surgery, characteristics of the small bowel lesions observed in CD each patient were blindly reported in the same form by one gastroenterologist-sonologist, radiologist, surgeon and anatomopathologist. At surgery, lesions related to CD were detected in the distal ileum in all 13 patients, also visualized by both SICUS and CTE in all 13 patients. Ileal lesions > 10 cm length were detected at surgery in all the 13 CD patients, confirmed by SICUS and CTE in the same 12 out of the 13 patients. When using surgical findings as a gold standard, SICUS and CTE showed the exactly same sensitivity, specificity and accuracy for detecting the presence of small bowel fistulae (accuracy 77% for both) and abscesses (accuracy 85% for both). In the tested CD population, SICUS and CTE were also quite comparable in terms of accuracy for detecting the presence of small bowel strictures (92% vs 100%), small bowel fistulae (77% for both) and small bowel dilation (85% vs 82%). CONCLUSION In our study population, CTE and the non-invasive and radiation-free SICUS showed a comparable high accuracy for assessing small bowel lesions in CD.

Colonic phenotype of the ileum in Crohn's disease: a prospective study before and after ileocolonic resection.

Background:Colonic metaplasia has been described in pouchitis. In a prospective study, we investigated whether colonic phenotype may develop in Crohns disease (CD) ileum. The expression of sulfomucins (colonic mucin), sialomucins, and CD10 (small intestine mucin and phenotype) was evaluated before and after ileocolonic resection for CD. Methods:From February 2007 to March 2010, 22 patients with CD undergoing surgery were enrolled. Clinical (Crohns Disease Activity Index >150) and endoscopic recurrence (Rutgeerts score ≥1) rates were assessed at 6 and 12 months. Ileal samples were taken at surgery (T0), at 6 (T1), and 12 months (T2) for histology, histochemistry (High Iron Diamine-Alcian Blue), and immunohistochemistry (anti-CD10). Results:In 22 patients, recurrence was assessed at 6 and 12 months (clinical recurrence 9% and 18%; endoscopic recurrence 73% and 77%). In all 22 patients, ileal samples were taken at 6 and 12 months (involved area in patients with recurrence). In 19 of 22 (86.3%) patients, the involved ileum was also studied at surgery. At T0, T1, and T2, the expression of sialomucins and CD10 (small intestine mucin and phenotype) was comparable and higher (P < 0.0001) than the expression of sulfomucins (colonic mucin) (mean [range], T0:82 [35–100] versus 75 [0–100] versus 16 [0–50]; T1:96 [60–100] versus 94.7 [50–100] versus 3.89 [0–40]; T2:93.3 [60–100] versus 88.1 [25–100] versus 6.6 [0–40]). The expression of small-intestine mucin and phenotype was higher at T1 (P = 0.025) versus T0 (P = 0.026). Differently, the expression of colonic mucin was lower at T1 versus T0 (P = 0.027). Conclusions:In CD, the ileum involved by severe/established lesions develops a “metaplastic” colonic mucosa phenotype. Differently, CD ileum with no lesions or with early recurrence maintains the “native” small intestine type mucin secretion and phenotype.

FRI0222 Impact of a Multidisciplinary Approach in Enteropathic Spondiloarthritis: Usefulness of a Combined Assessment in Prevalence, Characteristics, Diagnostic Delay and Outcomes

Background Prevalence of Enteropathic-related Spondyloarthritis (SpAe) in inflammatory bowel disease (IBD) shows marked variations (18-45%) and may be underestimated by gastroenterologists. Objectives In a prospective study, in a combined GastroIntestinal and RHeumAtologic “GiRha” clinic of the University of Rome “Tor Vergata”, prevalence and characteristics of joint manifestations in inflammatory bowel disease (IBD) patients were evaluated. diagnostic delay and therapeutic modifications were also assessed. Methods The study prospectively enrolled patients affected by IBD who presented muscolo-skeletal pain between November 2012 and July 2014. Disease activity in SpA patients was assessed using the ASDAS-CRP, BASDAI, BASFI, DAS44-CRP and HAQ-S. Results SpAe was detected in 101 patients. In 65 cases this was a new diagnosis. Other rheumatologic diagnosis were: Osteoarthritis (30.3%), Fybromialgia (6.9%), Psoriatic Arthritis (4.3%), Rheumatoid Arthritis (3.2%) and Gout (1.6%). Prevalence of other extraintestinal manifestations (psoriasis, uveitis, primary sclerosing cholangitis and erythema nodosum) resulted higher in SpAe patients than that in IBD non-SpAe patients (p=0.04). 56.4% SpAe patients showed a high disease activity (ASDAS ≥2.1). 22.8% had axial involvement, peripheral involvement in 57.4% and a combination of peripheral and axial involvement in 19.8% of cases. Axial SpAe patients were preferentially male and showed increased ESR and CRP levels compared with peripheral SpAe patients. Peripheral SpAe patients showed higher DAS levels compared with that in both axial and axial+peripheral SpAe patients. The diagnostic delay (time between the onset of joint symptoms and first rheumatological encounter) was calculated for all SpAe patients. Patients with disease onset between 2000-2009 had a reduced diagnostic delay compared with those with joint onset in 1980-1989 and 1990-1999. The diagnostic delay was further reduced for those patients with joint onset after 2010 (Figure 1). A higher percentage of IBD patients were treated with disease-modifying anti-rheumatic drugs (p=0.04), anti-COX2 (p<0.0001) and anti-TNF drugs (p=0.001) after the rheumatological assessment. Clinical outcome demonstrate improuvement of disease activity after 6 months of combined aproach: ASDAS and DAS changed from 2.8±0.9 at baseline to 1.4±0.5 and 2.5±0.8 at baseline to 1.8±0.8 respectively. Conclusions Multidisciplinary care facilitates the diagnosis and the management of rheumatic disorders in IBD offering a comprehensive treatment approach. Disclosure of Interest None declared

P.04.5 SMALL BOWEL CAPSULE ENDOSCOPY FOR ASSESSING THE EARLY POSTOPERATIVE RECURRENCE OF CROHN'S DISEASE: CORRELATION WITH THE ENDOSCOPIC SCORE AT 6 AND 12 MONTHS IN A PROSPECTIVE STUDY

Background: Patients with Crohn’s disease (CD) are prone to sarcopenia and osteopenia. Sarcopenia represents the loss of muscle mass and strength, and is considered as well as osteopenia secondary to malnutrition. The aim of the study was to determine the prevalence of sarcopenia and osteopenia in CD patients and its relationship. Methods: We included 48 cases with CD (23 female/25 male; median age of 40 years ±15; body mass index (BMI) 20.36±3.6) and 20 healthy volunteers (10 female/10 male; median age 40 years ±15; BMI 23.2±2.7). Sarcopenia was assessed by grip strength (estimate muscle strength) and dual-energy x-ray absorptiometry (DXA) (estimate lean body mass) and defined as a skeletal muscle index (SMI) below 5.45 kg/m2 for women and 7.26 kg/m2 for men. Osteopenia was defined as a T-score for bone mineral density (BMD) below 1.0 measured by DXA. Results: We found sarcopenia in 56.2% of CD patients and osteopenia in 47.9% vs 15% and 5% of controls, respectively (P< 0.01). HGS, SMI as well as BMD was significantly lower in patients with CD than in controls (35 kg ±5 vs. 50 kg ±10; 5.9 kg/m2 ±1.2 vs. 6.4 kg/m2 ±1.5; 1.7 g/cm2 ±0.6 vs. 0.9 g/cm2 ±0.3; P< 0.01). Sarcopenic patients had significantly (P< 0.01) lower BMI (19.64 versus 21.9) than non-sarcopenic patients; 74% of sarcopenic patients were also osteopenic. Conclusions: The prevalence of sarcopenia and osteopenia is high in CD patients. These two phenomens may share similar mechanisms. Screening for sarcopenia and osteopenia may play an important role in the evaluation of CD patients.