Diagnostic yield of small bowel capsule endoscopy in obscure gastrointestinal bleeding: a real-world prospective study.

Small bowel capsule endoscopy (SBCE) visualizes the small bowel (SB) mucosa. Gastrointestinal (GI) bleeding from SB accounts for the majority of SBCE indications. We aimed to assess, in a "real-world" prospective study, the diagnostic yield of SBCE in a cohort of consecutive patients with obscure gastrointestinal bleeding (OGIB). Secondary end point was to assess the frequency of adverse events and the role of SBCE in determining the diagnostic work-up and clinical outcome. From 2016 to 2018, all patients referred for SBCE examination were enrolled. Indication for SBCE was re-assessed by 2 dedicated gastroenterologists. Inclusion criteria: (1) age ≥ 18 and ≤ 85 years; (2) diagnosis of OGIB; 3) non-diagnostic standard bidirectional endoscopy; (4) informed consent. Exclusion criteria: (1) deglutition impairment; (2) SBCE contraindications; (3) pregnancy. The cohort included 50 patients [males 18 (36%), age 68 (27-83)]. SBCE indication: patients with ongoing overt OGIB (Group A) (n = 11; 22%), previous overt OGIB (Group B) (n = 14; 28%), occult bleeding (with Iron Deficiency Anaemia) (Group C) (n = 25; 50%). SBCE detected clinically relevant lesions in 46 (92%) cases. Clinically relevant lesions were more frequent in Group C (24/25; 96%), followed by Group A (10/11; 91%) and Group B (12/14; 85.5%). After SBCE, treatment was medical (60%); endoscopic (14%), surgical (36%) or conservative (18%). Clinical follow-up showed complete resolution in 63.2%, partial/absent resolution in 18.4% of cases. In a prospective study, the high diagnostic yield of SBCE supports its role as first-line investigation in patients with OGIB. However, this achievement requires an accurate and timely assessment by dedicated gastroenterologists.

Super selective arterial embolization to treat radiation-induced hemorrhagic gastritis: a case report and review of the literature.

Radiation-induced hemorrhagic gastritis (RIHG) is a rare but potentially fatal event following radiotherapy for locally advanced gastric cancer; the treatment of this condition is not standardized. Only few cases of RIHG have been reported, treated with different therapeutic approaches. Here we report the case of a 79-year-old patient who underwent subtotal gastrectomy for gastric cancer, followed by adjuvant chemo-radiotherapy. Approximately 3 months after the end of the treatment, she developed recurrent diffuse bleeding originating from the entire mucosa of the gastric pouch and from a marginal ulcer. As the bleeding was refractory to several endoscopic treatments and surgery was not indicated, the patient underwent two sessions of transcatheter selective arterial embolization, with resolution of bleeding. Arterial embolization has already been reported for the treatment of hemorrhagic cystitis, developing after irradiation of the pelvis for prostate, bladder, rectum, and cervix cancer. However, to our knowledge, it has never been reported as a treatment for hemorrhagic gastritis. Based on this case, we suggest arterial embolization as an option in the management of RIHG, when standard endoscopic treatment fails.

Cancer Risk in Inflammatory Bowel Disease: A 6-Year Prospective Multicenter Nested Case-Control IG-IBD Study.

BACKGROUND: In a 6-year, multicenter, prospective nested case-control study, we aimed to evaluate risk factors for incident cancer in inflammatory bowel disease (IBD), when considering clinical characteristics of IBD and immunomodulator use. The secondary end point was to provide characterization of incident cancer types. METHODS: All incident cases of cancer occurring in IBD patients from December 2011-2017 were prospectively recorded in 16 Italian Group for the Study of Inflammatory Bowel Disease units. Each of the IBD patients with a new diagnosis of cancer was matched with 2 IBD patients without cancer, according to IBD phenotype (ulcerative colitis [UC] vs Crohn's disease [CD]), age (±5 years), sex. Risk factors were assessed by multivariate logistic regression analysis. RESULTS: Cancer occurred in 403 IBD patients: 204 CD (CD cases), 199 UC (UC cases). The study population included 1209 patients (403 IBD cases, 806 IBD controls). Cancer (n = 403) more frequently involved the digestive system (DS; 32%), followed by skin (14.9%), urinary tract (9.7%), lung (6.9%), genital tract (6.5%), breast (5.5%), thyroid (1.9%), lymphoma (2.7%, only in CD), adenocarcinoma of the small bowel (SBA; 3.9%, 15 CD, 1 pouch in UC), other cancers (15.9%). Among cancers of the DS, colorectal cancer (CRC) more frequently occurred in UC (29% vs 17%; P < 0.005), whereas SBA more frequently occurred in CD (13% vs 6.3% P = 0.039). In CD, perforating (B3) vs non-stricturing non-perforating (B1) behavior represented the only risk factor for any cancer (odds ratio [OR], 2.33; 95% confidence interval [CI], 1.33-4.11). In CD, risk factors for extracolonic cancer (ECC) were a B3 vs B1 and a stricturing (B2) vs B1 behavior (OR, 2.95; 95% CI, 1.62-5.43; OR, 1.79; 95% CI, 1.09-2.98). In UC, risk factors for ECC and for overall cancer were abdominal surgery for UC (OR, 4.63; 95% CI, 2.62-8.42; OR, 3.34; 95% CI, 1.88-5.92) and extensive vs distal UC (OR, 1.73; 95% CI, 1.10-2.75; OR, 1.99; 95% CI, 1.16-3.47). Another risk factor for ECC was left-sided vs distal UC (OR, 1.68; 95% CI, 1.00-2.86). Inflammatory bowel disease duration was a risk factor for skin and urinary tract cancers. CONCLUSIONS: Perforating CD, extensive UC, and abdominal surgery for UC were identified as risk factors for overall incident cancer and for ECC. The clinical characteristics associated with severe IBD may increase cancer risk.

Safety of treatments for inflammatory bowel disease: Clinical practice guidelines of the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD).

Inflammatory bowel diseases are chronic conditions of unknown etiology, showing a growing incidence and prevalence in several countries, including Italy. Although the etiology of Crohn's disease and ulcerative colitis is unknown, due to the current knowledge regarding their pathogenesis, effective treatment strategies have been developed. Several guidelines are available regarding the efficacy and safety of available drug treatments for inflammatory bowel diseases. Nevertheless, national guidelines provide additional information adapted to local feasibility, costs and legal issues related to the use of the same drugs. These observations prompted the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD) to establish Italian guidelines on the safety of currently available treatments for Crohn's disease and ulcerative colitis. These guidelines discuss the use of aminosalicylates, systemic and low bioavailability corticosteroids, antibiotics (metronidazole, ciprofloxacin, rifaximin), thiopurines, methotrexate, cyclosporine A, TNFα antagonists, vedolizumab, and combination therapies. These guidelines are based on current knowledge derived from evidence-based medicine coupled with clinical experience of a national working group.

Inflammatory Bowel Disease Phenotype as Risk Factor for Cancer in a Prospective Multicentre Nested Case-Control IG-IBD Study.

BACKGROUND AND AIMS: Cancer risk in inflammatory bowel disease [IBD] is still debated. In a prospective, multicentre, nested case-control study, we aimed to characterise incident cases of cancer in IBD. The role of immunomodulators vs clinical characteristics of IBD as risk factors for cancer was also investigated. MATERIALS AND METHODS: From January 2012 to December 2014, each IBD patient with incident cancer was matched with two IBD patients without cancer for: IBD type, gender, and age. Risk factors were assessed by multivariate regression analysis. RESULTS: IBD patients considered numbered 44619: 21953 Crohn's disease [CD], 22666 ulcerative colitis [UC]. Cancer occurred in 174 patients: 99 CD [CD-K], 75 UC [UC-K]. Controls included 198 CD [CD-C], 150 UC [UC-C]. Cancer incidence in IBD was 3.9/1000, higher in CD (4.5/1000 [99/21,953]) than in UC (3.3/1000 [75/22,666]; p = 0.042). Cancers involved: digestive system [36.8%], skin [13.2%], urinary tract [12.1%], lung [8.6%], breast [8%], genital tract [6.9%], thyroid [4.6%], lymphoma [3.5%], others [6.3%]. In CD, penetrating behaviour and combined thiopurines and tumour necrosis factor alpha [TNFα] antagonists were risk factors for cancer overall: odds ratio [OR] (95% confidence interval [CI] 2.33 [1.01-5.47]); 1.97 [1.1-3.5]; and for extracolonic cancers 3.9 [1.56-10.1]; 2.15 [1.17-4.1], respectively. In UC, risk factors were pancolitis and disease-related surgery for cancer overall (OR: 2.52 [1.26-5.1]; 5.09 [1.73-17.1]); disease-related surgery for colorectal cancer [CRC] (OR 3.6 [1.0-12]); and extensive and left-sided vs distal UC for extracolonic cancers (OR: 2.55 [1.15-5.9]; 2.6 [1.04-6.6]), respectively. CONCLUSIONS: In a multicentre study, penetrating CD and extensive UC were risk factors for cancer overall. Cancer incidence was higher in CD than in UC.

Post-operative recurrence of Crohn's disease: A prospective study at 5 years.

BACKGROUND: We aimed to prospectively assess whether endoscopic recurrence severity at 1 year in Crohn's disease is predictive of clinical recurrence within 5 years. METHODS: Clinical recurrence (Crohn's Disease Activity Index>150) was assessed yearly for 5 years in Crohn's disease patients undergoing ileo-colonic resection. At 1 year, recurrence was assessed by colonoscopy (Rutgeerts' score ≥i1 or ≥2i) and small intestine contrast ultrasonography. RESULTS: 40 patients were included (23 males, median age 39 [16-69] years). Clinical recurrence occurred within 5 years in 16 (40%) patients (years 1, 2, 3, 4, 5: 2 [5%]; 10 [25%]; 4 [10%]; 2 [5%]; 4 [10%], respectively). At 1 year, endoscopic recurrence (score≥i1) occurred in 39 (97.5%) patients (score≥i2: 33 [82.5%]). Ultrasound detected lesions compatible with recurrence in 39/40 (97.5%) patients. Endoscopic score at 1 year was correlated with clinical score at 2 years (p=0.007; r=0.41). Endoscopic score at 1 year was higher in patients with (n=10) vs without (n=30) clinical recurrence at 2 years (3 [2-4] vs 2 [0-4]; p=0.003). Higher endoscopic score (>i2) at 1 year was a risk factor for clinical recurrence within 5 years (OR=0.18; 95% CI 0.04-0.71; p=0.008). CONCLUSIONS: In Crohn's disease, severity of endoscopic recurrence at 1 year remains a predictive marker of clinical recurrence within 5 years. Small intestine contrast ultrasonography is useful for assessing 1-year recurrence.

Impact of a multidisciplinary approach in enteropathic spondyloarthritis patients.

Spondyloarthritis (SpA) and inflammatory bowel disease (IBD) are chronic autoinflammatory diseases that partially share the genetic predisposition and the unchecked inflammatory response linking the gut to the joints. The coexistence of both conditions in patients and the increased cross-risk ratios between SpA and IBD strongly suggest a shared pathophysiology. The prevalence of Enteropathic-related Spondyloarthritis (ESpA) in IBD patients shows a wide variation and may be underestimated. It is well accepted that the management of joint pain requires rheumatological expertise in conjunction with gastroenterologist assessment. In this view, we aimed at assessing, in a prospective study performed in a combined Gastro-Intestinal and Rheumatologic "GI-Rhe" clinic: (1) the prevalence of ESpA and other rheumatologic diseases in IBD patients with joint pain; (2) the features of the ESpA population; and (3) the diagnostic delay and the potential impact of the combined assessment. From November 2012 to December 2014, IBD patients with joint pain referring to a dedicated rheumatologist by the IBD-dedicated gastroenterologist were enrolled. Clinical and biochemical evaluations, joint involvement and disease activity assessment, diagnostic delay, and treatment were recorded. IBD patients (n=269) with joint pain were jointly assessed in the "GI-Rhe" Unit. A diagnosis of ESpA was made in 50.5% of IBD patients with joint pain. ESpA patients showed a peripheral involvement in 53% of cases, axial in 20.6% and peripheral and axial in 26.4% of cases. ESpA patients had a higher prevalence of other autoimmune extra-intestinal manifestations and received more anti-TNF treatment compared with IBD patients. A mean diagnostic delay of 5.2 years was revealed in ESpA patients. Patients with joint disease onset in the 2002-2012 decade had reduced diagnostic delay compared with those with onset in the 1980-1990 and 1991-2001 decades. Diagnostic delay was further reduced for patients with joint onset in the last two years in conjunction with the establishment of the GI-Rhe clinic. Multidisciplinary approach improved management of rheumatic disorders in IBD patients allowing a more comprehensive care.

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, Student's t test. RESULTS: Dermatological assessment was performed in 251 IBD patients [115 females, age 47 [16-85]; IBD duration 9 years [1-46]]: 158 Crohn's 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.

Cancer and immunomodulators in inflammatory bowel diseases.

The widespread use of thiopurines and anti-tumor necrosis factors (TNFs) in inflammatory bowel disease (IBD) is a rising concern regarding their potential cancer risk. MEDLINE, EMBASE, and the Cochrane Library database were searched for articles regarding immunomodulators anti-TNF agents in IBD, hematologic malignancies, and solid tumors. Current evidences support that thiopurines and anti-TNFs used alone or in combination do not increase the overall cancer risk in IBD. Thiopurines use, with or without anti-TNFs, is associated with an increased risk of lymphoma, particularly non-Hodgkin lymphoma, in Crohn's disease. Combined treatment significantly increases the risk of a rare hepatosplenic T-cell lymphoma, particularly in young male patients with Crohn's disease. An increased risk of nonmelanotic skin cancer is also observed when using thiopurines in IBD, whereas a slightly increased risk of melanoma is observed when using anti-TNFs. The role played by immunomodulators in the development of other cancer types (i.e., urinary) as also by the severity of IBD is under investigation. Although the incidence of specific malignancies (lymphoma, skin cancers) seems to be increased by immunomodulators, their absolute number is low. As thiopurines and anti-TNFs are highly effective in IBD, current evidences support that in appropriate hands, their benefits overwhelm the cancer risk. However, a careful selection of both patients and timing of treatment is mandatory, particularly in young male patients with Crohn's disease. Immunomodulators should therefore be handled by experienced and dedicated gastroenterologists who aware of the potential, although low, cancer risk associated with their use in patients with IBD.

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.

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.

Development of a numerical index quantitating small bowel damage as detected by ultrasonography in Crohn's disease.

Small intestine contrast ultrasonography (SICUS) has emerged as a valuable tool in the detection of intestinal damage in Crohn's disease (CD). Our aim was to develop a numerical index quantitating small bowel damage as detected by SICUS in patients with an established diagnosis of CD. One hundred and ten patients with ileal or ileocolonic CD were prospectively enrolled and followed up for one year. Disease activity was assessed by CDAI and CRP levels. Study variables included bowel wall thickness, lumen diameter, lesion length and number of lesion site. Fistula, mesenteric adipose tissue alteration, abscess and lymphnodes were also considered. Bowel segments were considered as a hollow cylinder. Standardized variations of variables were combined into a statistical and mathematical model to create an algorithm scoring an index value ranging from 0 to 200. Index was subdivided into a severity scale with 5 classes from the lower (A) to the higher score (E). Median lesion index value was significantly higher (p<0.005) in patients with a CDAI>150 and in patients with CRP>5 mg/l (p=0.003). Patients classified in class E and D at SICUS underwent surgery within one year follow up more frequently than those in class C, B and A (p<0.0001). We propose a new index for assessment of small bowel lesions in CD (SLIC: sonographic lesion index for CD) developed by using SICUS. This index may turn ultrasonography in CD from a descriptive qualitative assessment to a quantitative numerical index suitable for comparison studies.

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.

Cancer in Crohn's Disease patients treated with infliximab: a long-term multicenter matched pair study.

BACKGROUND: The long-term risk of neoplasia in Crohn's disease (CD) patients treated with infliximab is undefined. The aim was to assess, in a multicenter, matched-pair study, whether infliximab use in CD is associated with an increased frequency of neoplasia in the long term. METHODS: A multicenter, long-term, matched-pair study was conducted in 12 referral inflammatory bowel disease (IBD) centers. An initial cohort of 808 CD patients, including 404 infliximab-treated (CD-IFX) and 404 matched CD controls never treated with infliximab (CD-C) studied from 1999 to 2004, was followed up for an additional 4 years (2004-2008). Cases and controls were matched for: sex, age (±5 years), CD site, follow-up (±5 years), immunosuppressant use, and CD duration (±5 years). From 1999 to 2008 the frequency and characteristics of neoplasia were compared between CD-IFX and CD-C. RESULTS: In 2008, 591 patients (304 CD-IFX, 287 CD-C) were in follow-up. Matched couples included 442 patients: 221 CD-IFX and 221 CD-C (median follow-up, months: 72, range 48-114 versus 75, range 44-114). From 1999 to 2008 the frequency of neoplasia among the 591 patients did not differ between CD-IFX (12/304; 3.94%) and CD-C (12/287; 4.19%; P = 0.95). A comparable frequency of neoplasia was also observed between the 221 matched couples (CD-IFX: 8/221; 3.61% versus CD-C: 9/221; 4.07%; P = 1). No specific histotype of cancer appeared associated with infliximab use. CONCLUSIONS: The frequency of neoplasia was comparable in an adult population of CD patients treated or not with infliximab, matched for clinical variables and followed up for a median of 6 years.

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.