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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.

Gram-positive anaerobic cocci (GPAC) are responsible for 30% of anaerobic infections. Parvimonas micra is an emergent pathogen that is part of the oral and gastrointestinal commensal flora, and its role in several infection processes has recently emerged thanks to the improvement of diagnostic techniques. P. micra bacteraemia is reported in immunocompromised patients and is often complicated by abscesses. Here, we present a case study of multiple hepatic and brain abscesses caused by P. micra bacteraemia in a patient with complicated diverticulitis.

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.

We report a 60-year-old woman with a previous history of an endoscopically treated walled-off necrosis that developed 12 months after an 80-mm recurrent symptomatic pancreatic body pseudocyst. Drainage was attempted using a 16 × 20-mm biflanged metal stent (Nagi), but the stent was mistakenly released inside the collection. A rescue attempt was made to retrieve the stent and avoid surgical intervention.

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.

Background Enteropathic spondyloarthritis (eSpA) is a chronic autoimmune disease associated with inflammatory bowel disease (IBD) that is poorly diagnosed and managed. Objectives To assess the diagnostic and therapeutic effect of a combined gastro-rheumatological approach in eSpA patients. Methods IBD-patients with joint pain referred to a dedicated rheumatologist by gastroenterologist were enrolled. Clinical and biochemical variables, SpA and intestinal disease activity measures, and treatment (biologic; bDMARDs and conventional synthetic; csDMARDs) were recorded at baseline, 3, 6, 12 and 24 months. The association between treatment on demographic and clinical characteristics was evaluated by logistic regression. Results From a total of 229 IBD patients, 147 (64.2%) were diagnosed with eSpA; 96 (65.3%) showing peripheral involvement and 51 (34.7%) with axial involvement. The majority (67.3%) of eSpA patients were female (n=99), median age and disease duration of 46 and 14.6 years. bDMARD treatment increased over the follow-up period (baseline-24 months: 32.6%>60%; AOR:3.45, 95% CI: 1.93–6.2, p Conclusions A multidisciplinary approach can improve in the therapeutic management and outcome (e.g. disease activity measures) of eSpA patients. bDMARD use paralleled an improvement in disease measures and confirmed a good safety profile. Disclosure of Interest None declared

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. * Abbreviations: CD : Crohn's Disease UC : ulcerative colitis IBD : inflammatory bowel disease IMM : immunomodulators AZA : azathioprine 6-MP : 6-mercaptopurine MTX : methotrexate Anti-TNFs : anti-tumor necrosis factor alpha EIM : extraintestinal manifestations GI : gastrointestinal OR : odds ratio HR : hazard ratio HSTCL : hepatosplenic T cell lymphoma

Infliximab and adalimumab are highly effective in Crohn's Disease (CD). This is supported by clinical trials and open-label studies using either infliximab or adalimumab, thus not allowing a proper comparison between these anti-TNFs in CD.To evaluate the efficacy and safety of infliximab and adalimumab in active CD.In a longitudinal study, CD patients with indication for anti-TNFs were treated with infliximab or adalimumab.Ninety-three patients were treated with infliximab (n = 44) or adalimumab (n = 49). In the infliximab group, the induction was completed by 77.3% of patients, due to no response (n = 2), delayed hypersensitivity reactions (DHR) or infusion reactions (n = 8). Maintenance with infliximab was completed by 60% of patients, due to clinical worsening or loss of efficacy (n = 5), DHR or infusion reactions (n = 5). In the adalimumab group, all patients completed the induction, while maintenance was completed by 67% of patients, due to clinical worsening or loss of efficacy (n = 8), DHR (n = 1), other causes (n = 7). In both groups, the CDAI significantly reduced at baseline vs. each visit (P0.04). The Kaplan-Meier survival analysis performed to evaluate the risk of steroid-free remission in patients treated with infliximab vs. adalimumab detected no differences (log-rank test P = 0.4). Cox proportional-hazards regression identified two predictors of steroid-free remission using anti-TNFs: no smokers [HR = 2.94 (1.52-5.70), P = 0.001] and non stricturing non penetrating behaviour [HR = 3.116 (1.06-9.13), P = 0.03826].Infliximab and adalimumab showed a similar efficacy. No smoking and non-stricturing non-penetrating behaviour were predictors of steroid-free remission.

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 31years, 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.

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. 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. 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

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.

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.

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.

BACKGROUND AND AIMS: The widespread use of anti-tumour necrosis factor alpha antibody (Infliximab) in Crohn's disease (CD) raises concerns about a possible cancer risk in the long term. In a matched pair study, we assessed whether Infliximab is associated with an increased risk of neoplasia. METHODS: In a multicentre matched pair study, 404 CD patients treated with Infliximab (CD-IFX) were matched with 404 CD patients who had never received Infliximab (CD-C). Cases and controls were matched for sex, age (+/-5 years), site of CD, age at diagnosis (+/-5 years), immunosuppressant use, and follow up. New diagnoses of neoplasia from April 1999 to October 2004 were recorded. RESULTS: Among the 404 CD-IFX, neoplasia was diagnosed in nine patients (2.22%) while among the 404 CD-C, seven patients developed neoplasia (1.73%) (odds ratio 1.33 (95% confidence interval 0.46-3.84); p=0.40). The survival curve adjusted for patient year of follow up showed no differences between CD-IFX and CD-C (p=0.90; log rank test). In the CD-IFX group, there was one cholangiocarcinoma, three breast cancers, one skin cancer, one leukaemia, one laryngeal cancer, and two anal carcinomas. Among the 7/404 (1.73%) CD-C, there were three intestinal adenocarcinomas (two caecum, one rectum), one basalioma, one spinalioma, one non-Hodgkin's lymphoma, and one breast cancer. Age at diagnosis of neoplasia did not differ between groups (CD-IFX v CD-C: median 50 (range 40-70 years) v 45 (27-72); p=0.50). CONCLUSION: In our multicentre matched pair study, the frequency of a new diagnosis of neoplasia in CD patients treated with Infliximab was comparable with CD patients who had never received Infliximab.

Summary Background : The safety and efficacy of selective cyclo-oxygenase-2 inhibitors in inflammatory bowel disease are under investigation. Aim : To assess, in a prospective, open-label trial, the efficacy and safety of rofecoxib (12.5 mg/day) in inflammatory bowel disease patients and controls. Methods : The inflammatory bowel disease group included 45 inactive patients (25 Crohn's disease; 20 ulcerative colitis) with associated arthralgia. The control group included 30 dyspeptic patients. The efficacy and safety of rofecoxib were assessed in inflammatory bowel disease patients and controls before and after treatment (range, 3 days to 3 months). Results : In inflammatory bowel disease, nine of the 45 patients (20%) required rofecoxib withdrawal due to gastrointestinal symptoms inducing clinical relapse, which subsided on drug discontinuation. The percentage of patients requiring rofecoxib discontinuation was comparable in patients with Crohn's disease and ulcerative colitis (20% vs. 20%), but was higher in inflammatory bowel disease patients than in controls (20% vs. 3%; P

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.

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.

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 >3 mm, 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 (5 mm) 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.

1880 www.thelancet.com Vol 380 November 24, 2012 In November, 2010, a 75-year-old woman presented to us with persistent diarrhoea, anorexia, and weight loss. She did not respond to empiric antibiotics or loperamide. She had a history of hypertension, and was being treated with perindopril, autoimmune hypo thyroidism treated with thyroxine, and widespread arthrosis. On physical examination, she was in a stable condition, with dry mucous membranes and skin. Stool tests suggested watery diarrhoea. The faecal volume exceeded 1 L per day, and persisted despite fasting. Stool para sitological examination and culture were negative. Upper gastrointestinal endoscopy and colonoscopy were done immediately and were normal so a biopsy sample was not taken. Laboratory tests showed mild normo chromic, microcytic, anaemia (haemoglobin 110 g/L), hyponatraemia, and persistent hypokalaemia. C-reactive protein was 47 mg/L, total protein 50 g/L, and albumin was 27 g/L. Serum protein electrophoresis showed an irregular gamma profi le. Serum iron and ferritin were normal, and transferrin was low 1·03 g/L, (normal range 2–3·6). Total cholesterol and HDL choles terol concen trations were low (2·28 mmol/L and 0·44 mmol/L). Tryglicerides were normal. An HIV test was negative. Serological investigation for coeliac disease was negative, and total IgA was normal. Tumour markers were negative. Normal values of gastrin, chromogranin, and 5-hydroxyindoleacetic acid excluded the possibility of endocrine syndrome. Vasoactive intestinal polypeptide and somatostatin assays were not available. A total body CT scan was normal. After admission our patient was put on a fast and total parenteral nutrition was initiated. Within a few days, she had progressive reduction of consciousness leading to a comatose state. No focal signs or symptoms preceded or followed the loss of consciousness. An MRI of the brain showed a diff usion-weighted imaging abnormality in the thalamus bilaterally, which was consistent with Wernicke syndrome triggered by the infusion of glucose. Clinical resolution of the coma and radiological remission of bilateral thalamus abnormalities after treatment with Persistent watery diarrhoea and coma in an elderly woman

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.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.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.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 (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 (p0.005) in patients with a CDAI150 and in patients with CRP5 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 (p0.0001). 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.

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. (Inflamm Bowel Dis 2011)

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 (χ2 = 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.

Background and aims Ileocolonoscopy (IC) is the gold standard for assessing Crohn's 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.

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 (

Postoperative recurrence after ileo-colonic resection is a feature of Crohn's Disease (CD), almost 73% of patients show endoscopic recurrence at 1 year and 90% at 3 years. After surgical resection for CD, symptoms may be related to the surgical resection itself. Moreover, the development of an early severe endoscopic recurrence within 1 year represents a risk factor for early clinical recurrence. On the basis of these observations, the early detection and assessment of asymptomatic endoscopic recurrence may allow a timely and appropriate treatment of CD patients after ileo-colonic resection. At this purpose, conventional colonoscopy with ileoscopy currently represents the gold standard for assessing CD recurrence, graded according to the Rutgeerts' score. Lesions compatible with CD recurrence can be also detected by conventional radiology, including small bowel follow through and enema, both associated with a high radiation exposure. Due to the ineluctable course of CD after resection, and to the need of a proper follow up for assessing CD recurrence, several alternative, non invasive techniques have been searched in order to assess the post-operative recurrence, including: faecal alpha 1-antitrypsin clearance, faecal calprotectin, 99Tc-HMPAO scintigraphy, virtual colonoscopy, ultrasonography and, more recently, wireless capsule endoscopy (WCE) and Small Intestine Contrast Ultrasonography (SICUS). Among these, current evidences suggest that in experienced hands, ultrasound examination by SICUS represents a non-invasive technique useful for assessing recurrence in CD patients under regular follow up after surgery. The same findings are suggested for WCE, although the impact risk related to the recurrence or to the surgical anastomosis itself limits the use of this non-invasive technique for assessing CD recurrence after surgery.

Frequency and Pattern of Endoscopic Recurrence in Crohn's Disease Patients With Ileocolonic Resection Using a Laparoscopic Versus Laparotomic Approach: A Prospective Longitudinal Study

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.

Background: The best available tool to assess recurrence of Crohn’s disease (CD) is ileocolonoscopy (CC). Small intestine contrast ultrasonography (SICUS) and wireless capsule endoscopy (WCE) are noninvasive techniques able to detect small bowel lesions. In a prospective longitudinal study, we aimed to investigate the usefulness of SICUS and WCE for assessing postoperative recurrence of CD 1 year after surgery, using CC as the gold standard. Methods: Twenty-two patients (11 men, median age 33 years, range 22– 67 years) undergoing ileocolonic resection for CD were prospectively followed from July 2003 to May 2006, with the Crohn’s Disease Activity Index (CDAI) used for clinical assessment every 3 months for 1 year. At 1 year, recurrence was assessed by SICUS and CC, followed by WCE. CD recurrence was assessed by CC (Rutgeerts score). SICUS was performed after ingestion of polyethylene glycol, and WCE was performed with Given M2A equipment. Results: At 1 year, all 22 patients had inactive CD (CDAI 150). In 5 patients, WCE was not performed because of luminal narrowing or stenosis. Seventeen of the 22 patients had all 3 techniques performed. CC detected recurrence in 21 of 22 patients. Lesions compatible with recurrence were detected by SICUS in all 22 patients (1 false positive). When considering only the 17 patients studied by all 3 techniques, recurrence was detected by CC in 16 of 17 patients, whereas lesions compatible with recurrence were detected by SICUS in all 17 patients (16 true positives [TPs], 1 FP) and by WCE in 16 of 17 patients (16 TPs, 1 true negative). Conclusions: The present findings suggest that SICUS and WCE may be used as noninvasive techniques for the assessment of recurrence of CD in patients being regularly followed up after ileocolonic resection. (Inflamm Bowel Dis 2007;13:1256 –1265)

The proven involvement of cytokines in the pathophysiology of IBD has led to the development of powerful, selective, anticytokine drugs--so-called biologics--as a therapy for IBD. Although the efficacy of infliximab, a chimeric monoclonal IgG1 antibody directed against tumor necrosis factor, is proven and the use of biologic agents is growing worldwide, there is concern about their long-term safety, which includes the risk of developing cancer. An increased risk of malignancies, particularly lymphoma, has been reported in some studies of infliximab-treated patients with IBD; however, the increased risk could be caused by the underlying chronic disease, severity of the disease, concomitant medications (e.g. conventional immunomodulators), infliximab itself, or all of these variables. At present, the data do not provide clear evidence for a causal association between infliximab and the increased cancer risk. In appropriately selected patients with severe, refractory Crohn's disease, the benefits of biologic therapy seem to outweigh the cancer risk. Multicenter, case-control studies in large populations, with a long-term follow-up are needed to define the outcome of patients with IBD treated with biologic therapies.

Background. Topical beclomethasone diproprionate has shown efficacy in ulcerative colitis. Aim. To assess, in a multicenter, randomized, double-blind study, the tolerability and safety of topical beclomethasone diproprionate (3 mg) enema and foam versus mesalazine (2 g) enema and foam in mild–moderate distal ulcerative colitis. Patients. In 15 referral gastrointestinal units, 99 patients with distal ulcerative colitis were enrolled. This number was lower than planned according to the statistical analysis, due to a low recruitment rate. Methods. Patients were randomly assigned to random preparations (beclomethasone diproprionate enema, beclomethasone diproprionate foam, mesalazine enema, mesalazine foam) once nightly for 8 weeks, with clinical and endoscopical assessment (Disease Activity Index score) at baseline (T0 ), 4( T4) and 8 weeks (T8). Results were expressed as median and range (95% confidence interval). The efficacy was assessed by comparing the Disease Activity Index value at T4 and T8 by using the Student’s t-test or the Wilcoxon–Mann–Whitney test. Results. Efficacy was comparable in the beclomethasone diproprionate or mesalazine groups at both T4 and T8 (response at T4: beclomethasone diproprionate 78% [95% confidence interval 0.6–0.8] versus mesalazine 79% [95% confidence interval 0.6–0.8]; T8: beclomethasone diproprionate 84% [95% confidence interval 0.7–0.9] versus mesalazine 90% [95% confidence interval 0.7–1.0]; p = n.s.; remission at T4: beclomethasone diproprionate 24% [95% confidence interval 0.1–0.3] versus mesalazine 28% [95% confidence interval 0.1–0.3]; remission at T8: beclomethasone diproprionate 36% [95% confidence interval 0.2–0.5] versus mesalazine 52% [95% confidence interval 0.3–0.6]; p = n.s.).The Disease Activity Index lowered at T4 and T8 versus T0 in the four groups (T4 versus T0: beclomethasone diproprionate foam Disease Activity Index 2 versus 6 p < 0.0001; beclomethasone diproprionate enema 4 versus 6, mesalazine enema 3 versus 6, mesalazine foam 3.5 versus 7, p < 0.001 for all three groups; T8 versus T0: p < 0.01). The Disease Activity Index lowered at T8 versus T4 in the beclomethasone diproprionate enema and foam (Disease Activity Index: 2 versus 4 and 1 versus 4, respectively; p < 0.05) and in the mesalazine enema (Disease Activity Index: 1.5, range 0–4 versus 3, range 0–12; p < 0.01), but not in the mesalazine foam group (Disease Activity Index: 1, range 0–9 versus 3.5, range 0–8; p = n.s.). The safety profile was favourable for all groups. Conclusions. Beclomethasone diproprionate and mesalazine enema and foam show a comparable tolerability and efficacy in mild active distal ulcerative colitis.

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 Conclusions Multidisciplinary care facilitates the diagnosis and the management of rheumatic disorders in IBD offering a comprehensive treatment approach. Disclosure of Interest None declared