Feasibility and safety of self-expandable metal stent in nonmalignant disease of the lower gastrointestinal tract.

In recent years, self-expandable metal stents (SEMSs) have been employed to treat benign gastrointestinal strictures secondary to several conditions: Acute diverticulitis, radiation colitis, inflammatory bowel disease (IBD), and postanastomotic leakages and stenosis. Other applications include endometriosis and fistulas of the lower gastrointestinal tract. Although it may be technically feasible to proceed to stenting in the aforementioned benign diseases of the lower gastrointestinal tract, the outcome has been reported to be poor. In fact, in some settings (such as complicated diverticulitis and postsurgical anastomotic strictures), stenting seems to have a limited evidence-based benefit as a bridge to surgery, while in other settings (such as endometriosis, IBD, radiation colitis, etc.), even society guidelines are not able to guide the endoscopist through decisional algorithms for SEMS placement. The aim of this narrative paper is to review the scientific evidence regarding the use of SEMSs in nonmalignant diseases of the lower gastrointestinal tract, both in adult and pediatric settings.

[Evolving therapeutic targets in inflammatory Bowel Disease: mucosal healing as an emerging end point]. / Il trattamento delle malattie infiammatorie croniche dell'intestino oltre il controllo dei sintomi: la guarigione mucosa come obiettivo terapeutico emergente.

In the last years the therapeutic goals of inflammatory bowel disease have changed from control of symptoms only towards long term strategies aimed at modifying the natural history of the disease. In this setting mucosal healing has emerged as an important therapeutic goal both in clinical trials and in clinical practice. Growing evidence suggests that mucosal healing may be associated with lower relapse rates, reduced hospitalizations and reduced need of surgery both in ulcerative colitis and in Crohn's disease. However, a validated definition of mucosal healing is lacking: as a consequence, although several drugs are capable of inducing and maintaining mucosal healing in different clinical settings, the effect size of different treatments is difficult to assess. One of the most important question for clinical practice is if we should systematically assess mucosal healing in all patients and target our treatment strategies to achieve mucosal healing. This review focuses on the definition of mucosal healing and on the ability of different medications to induce and maintain mucosal healing in inflammatory bowel disease. The significance of mucosal healing as a surrogate end point of disease outcome is also discussed.

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 Crohn's 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 (Crohn's 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.

A family study of asymptomatic small bowel Crohn's disease.

BACKGROUND: Discrepancies between severity of lesions and symptoms may be observed in Crohn's disease. We prospectively assessed whether Crohn's disease may be diagnosed among asymptomatic relatives of patients, using Small Bowel Contrast Ultrasonography. METHODS: Diagnosis of asymptomatic Crohn's disease relatives was defined ultrasonographically as: bowel wall thickness >3mm, bowel dilation/stricture, lumen diameter >2.5 cm. Diagnosis was confirmed by ileocolonoscopy. Subjects were also screened for the Leu3020insC mutation. RESULTS: Consent was given by 35 asymptomatic first-degree relatives of 18 Crohn's disease patients. Ultrasonography indicated increased bowel wall thickness (5mm) compatible with ileal Crohn's disease in 1 relative (2.8%), a 42 year-old male. Ileocolonoscopy, histology, and radiology confirmed the diagnosis of stricturing ileal Crohn's disease. Gallbladder stones were detected in 7/35 (20%) relatives and Leu3020insC mutation in 3/35 (8.5%). CONCLUSIONS: Small Bowel Contrast Ultrasonography may be a useful tool to diagnose asymptomatic small bowel Crohn's disease among first-degree relatives of patients.

Accuracy of small-intestine contrast ultrasonography, compared with computed tomography enteroclysis, in characterizing lesions in patients with Crohn's disease.

BACKGROUND & AIMS: Small-intestine contrast ultrasonography (SICUS) is a radiation-free technique that can detect intestinal damage in patients with Crohn's disease (CD). We evaluated the diagnostic accuracy of SICUS in determining the site, extent, and complications of CD, compared with computed tomography (CT) enteroclysis as the standard. METHODS: We performed a retrospective analysis of data from 59 patients with CD evaluated by SICUS and CT enteroclysis 3 months apart, between January 2007 and April 2012. We evaluated disease site (based on bowel wall thickness), extent of lesions, and presence of complications (stenosis, prestenotic dilation, abscess, or fistulas) using CT enteroclysis as the standard. Sensitivity, specificity, and diagnostic accuracy were calculated. We determined the correlations in maximum wall thickness and disease extent in the small bowel between results from SICUS and CT enteroclysis. RESULTS: SICUS identified the site of small bowel CD with 98% sensitivity, 67% specificity, and 95% diagnostic accuracy; it identified the site of colon CD with 83% sensitivity, 97.5% specificity, and 93% diagnostic accuracy. Results from SICUS and CT enteroclysis correlated in determination of bowel wall thickness (rho, 0.79) and disease extent (rho, 0.89; P < .0001 for both). SICUS detected ileal stenosis with 95.5% sensitivity, 80% specificity, and 91.5% diagnostic accuracy, and prestenotic dilation with 87% sensitivity, 67% specificity, and 75% diagnostic accuracy. SICUS detected abscesses with 78% sensitivity, 100% specificity, and 97% diagnostic accuracy, and fistulas with 78.5% sensitivity, 95.5% specificity, and 91.5% diagnostic accuracy. CONCLUSIONS: SICUS identified lesions and complications in patients with CD with high levels of sensitivity, specificity, and accuracy compared with CT enteroclysis. SICUS might be used as an imaging tool as part of a focused diagnostic examination of patients with CD.

TRAF3IP2 gene is associated with cutaneous extraintestinal manifestations in inflammatory bowel disease.

BACKGROUND AND AIMS: Genome-wide association (GWA) studies recently identified a novel gene, TRAF3IP2, involved in the susceptibility to psoriasis. Common immune-mediated mechanisms involving the skin or the gut have been suggested. We therefore aimed to assess the role of TRAF3IP2 gene in IBD, with particular regard to the development of cutaneous extraintestinal manifestations (pyoderma gangrenosum, erythema nodosum). The association with psoriasis was also assessed in a secondary analysis. METHODS: The analysis included 267 Crohn's disease (CD), 200 ulcerative colitis (UC) patients and 278 healthy controls. Three TRAF3IP2 SNPs were genotyped by allelic discrimination assays. A case/control association study and a genotype/phenotype correlation analysis have been performed. RESULTS: All three SNPs conferred a high risk to develop cutaneous manifestations in IBD. A higher risk of pyoderma gangrenosum and erythema nodosum was observed in CD patients carrying the Rs33980500 variant (OR 3.03; P=0.026). In UC, a significantly increased risk was observed for both the Rs13190932 and the Rs13196377 SNPs (OR 5.05; P=0.02 and OR 4.1; P=0.049). Moreover, association of TRAF3IP2 variants with ileal (OR=1.92), fibrostricturing (OR=1.91) and perianal CD (OR=2.03) was observed. CONCLUSIONS: This is the first preliminary report indicating that TRAF3IP2 variants increase the risk of cutaneous extraintestinal manifestations in IBD suggesting that the analysis of the TRAF3IP2 variants may be useful for identifying IBD patients at risk to develop these manifestations.

Anti-TNF-alpha treatments and obstructive symptoms in Crohn's disease: a prospective study.

BACKGROUND: The development of symptomatic strictures in Crohn's Disease after anti-Tumour Necrosis Factor-α antibodies is undefined. AIM: To assess, in a prospective longitudinal study, the frequency of sub/obstructions in Crohn's 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 Crohn's 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 Crohn's Disease. Sonographic parameters did not significantly change after treatment. CONCLUSIONS: Sub/obstructive symptoms may develop in one tenth of Crohn's Disease patients treated with anti-Tumour Necrosis Factor-α antibodies, with no significant sonographic changes of the small bowel lesions.

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 Crohn's 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.

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 Crohn's 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 Crohn's 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.

Wireless capsule endoscopy and proximal small bowel lesions in Crohn's disease.

AIM: To investigate the prevalence of proximal small bowel (SB) lesions detected by wireless capsule endoscopy (WCE) in Crohn's disease (CD). METHODS: WCE was performed in 64 patients: 32 with CD of the distal ileum, and 32 controls with iron-deficiency anemia (IDA) or diarrhea. WCE was performed using the Given SB-WCE, followed by small intestine contrast ultrasonography (SICUS). Findings compatible with CD by using WCE included erosions, aphthoid or deep ulcers, and strictures/stenosis. RESULTS: WCE detected proximal SB lesions in 16/32 (50%) patients (14 aphthoid ulcers, 2 deep ulcers, one stricture), which appeared not to be related to clinical parameters [epigastric pain, age, smoking, non-steroidal anti-inflammatory drugs (NSAIDs), IDA]. Among patients with proximal SB lesions, 6 (37%) were smokers, 3 (19%) NSAID users, 3 (19%) had epigastric pain and 4 (25%) had IDA. SICUS detected proximal SB lesions in 3/32 patients (19%) also showing lesions with WCE. No correlations were observed between proximal SB lesions assessed by WCE or by SICUS (chi(2) = 1.5, P = 0.2). CONCLUSION: The use of WCE allows the detection of previously unknown upper SB lesions in a high proportion of patients with a previous diagnosis of CD involving the distal ileum.

Severity of postoperative recurrence in Crohn's disease: correlation between endoscopic and sonographic findings.

BACKGROUND: Crohn's disease (CD) recurrence is currently assessed by ileocolonoscopy. Small intestine contrast ultrasonography (SICUS) visualizes the small bowel lesions in CD, although its role after curative resection is undefined. We aimed to investigate the accuracy of SICUS in assessing CD recurrence after ileocolonic resection when using ileocolonoscopy as a gold standard. The correlation between the bowel wall thickness (BWT) measured by SICUS and the endoscopic score of recurrence was also assessed. METHODS: The analysis included 72 CD patients with ileocolonic resection requiring ileocolonoscopy, undergoing SICUS within 6 months. Recurrence was assessed by ileocolonoscopy using the Rutgeerts' score. SICUS was performed after PEG ingestion and findings compatible with recurrence included: increased BWT (>3 mm), bowel dilation (>25 mm) or stricture (<10 mm). RESULTS: Ileocolonoscopy detected recurrence in 67/72 (93%) patients. SICUS detected findings compatible with recurrence in 62/72 (86%) patients (5 false negative (FN), 4 false positive (FP), 1 true negative (TN), 62 true positive (TP)), showing a 92.5% sensitivity, 20% specificity, and 87.5% accuracy for detecting CD recurrence. The BWT detected by SICUS was correlated with the Rutgeerts' score (P = 0.0001; r = 0.67). The median BWT, the extent of the ileal lesions, and the prestenotic dilation were higher in patients with an endoscopic degree of recurrence >or=3 versus or=3 versus

Frequency, pattern, and risk factors of postoperative recurrence of Crohn's disease after resection different from ileo-colonic.

BACKGROUND: The frequency of recurrence in Crohn's disease (CD) patients after curative resection different from the ileo-colonic is undefined. We aimed to assess the frequency, pattern, outcome, and risk factors of postoperative recurrence in CD patients under regular follow-up after anastomosis different from ileo-colonic. MATERIALS AND METHODS: In a retrospective study, clinical records of 537 CD patients under regular follow-up from January 2001 to August 2007 were reviewed. The outcome after surgery was assessed on the basis of clinical records prospectively recorded. RESULTS: Previous resection was observed in 183 of 537 (34%) patients, including the ileo-colon in 145 (79%) and other gastrointestinal (GI) segments in 38 (21%). Recurrence was detected in 16 of 38 (42%) patients (all symptomatic) including five of 14 (35%) with ileostomy, five of five (100%) with ileo-rectal, three of 11 (27%) with ileo-ileal, one or four (25%) with colorectal, and two of three (33%) with duodenum-jejunal anastomosis. Ileo-colonic resection was reported in 145 of 183 (79%) patients, showing recurrence in 128 (88.3%) and symptomatic in 47 (36.7%) patients. The frequency of recurrence was higher in patients with ileo-colonic resection than in patients with other types of resection (128/145, 88% vs 16/38, 42%, p < 0.001). The frequency of symptomatic recurrence was lower in patients with ileo-colonic resection than in those with other resections (47/128, 37% vs 16/16, 100%; p < 0.001). Risk factors for recurrence were comparable in the two subgroups (smoke, odds ratio, OR 1.5 vs 1.4; appendectomy, OR 0.32 vs 0.33; familial inflammatory bowel disease, OR 0.43 vs 1.26). CONCLUSIONS: Postoperative recurrence is observed in a high proportion of CD patients after resection different from ileo-colon (including ileostomy), although at a lower frequency than observed after ileo-colonic resection.

Ileal lesions in patients with ulcerative colitis after ileo-rectal anastomosis: relationship with colonic metaplasia.

AIM: To assess whether in ulcerative colitis (UC) patients with ileo-rectal anastomosis (IRA), ileal lesions may develop in the neo-terminal-ileum and their possible relation with phenotypic changes towards colonic epithelium. METHODS: A total of 19 patients with IRA under regular follow up were enrolled, including 11 UC and 8 controls (6 Crohn's disease, CD; 1 familial adenomatous polyposis, FAP; 1 colon cancer, colon K). Ileal lesions were identified by ileoscopy with biopsies taken from the ileum (involved and uninvolved) and from the rectal stump. Staining included HE and immunohistochemistry using monoclonal antibodies against colonic epithelial protein CEP (Das-1) and human tropomyosin isoform 5, hTM5 (CG3). Possible relation between development of colonic metaplasia and ileal lesions was investigated. RESULTS: Stenosing adenocarcinoma of the rectal stump was detected in 1 UC patient. The neo-terminal ileum was therefore investigated in 10/11 UC patients. Ileal ulcers were detected in 7/10 UC, associated with colonic metaplasia in 4/7 (57.1%) and Das-1 and CG3 reactivity in 3/4 UC. In controls, recurrence occurred in 4/6 CD, associated with colonic metaplasia in 3/4 and reactivity with Das-1 and CG3 in 2/3. CONCLUSION: Present findings suggest that in UC, ileal lesions associated with changes towards colonic epithelium may develop also after IRA. Changes of the ileal content after colectomy may contribute to the development of colonic metaplasia, leading to ileal lesions both in the pouch and in the neo-terminal ileum after IRA.