Bruno Rosa

European evidence based consensus for endoscopy in inflammatory bowel disease

Endoscopy plays an essential role in the diagnosis, management, prognosis, and surveillance of inflammatory bowel disease (IBD), but surprisingly there are few available guidelines.1,2 This prompted the ECCO Guidelines Committee (GuiCom) members to promote a Consensus on the appropriate indication and application of different endoscopic modalities in IBD. Since the development of guidelines is an expensive and time-consuming process, this Consensus may help to avoid duplication of effort in the future. It may also identify issues where the evidence is lacking and controlled studies are awaited. The strategy to reach the Consensus involved five steps: 1. Two members of the GuiCom (VA and RE) identified four main topics: a) Diagnosis and follow-up; b) Score of endoscopic activity; c) Small bowel endoscopy; and d) Surveillance. During 2012 a call for participants to the Guideline was made to ECCO members. In addition, expert endoscopists recognised for their active research in the field were invited. Participants were selected by the Guicom and four working groups were created. Each working group had a chair (VA, MD, MT, and RE), two ECCO members including young members (Y-ECCO) and one experienced endoscopist. For the development of the guideline, relevant questions on separate topics were devised by the chairmen and their working parties. The questions were focused on current practice and areas of controversy. Participants of the Consensus process were asked to answer the questions based on evidence from the literature as well as their experience (Delphi procedure)3; 2. The working parties working in parallel performed a systematic literature search of their topic with the appropriate key words using Medline/Pubmed and the Cochrane database, as well as other relevant sources; 3. Provisional guideline statements on their topic were then written by the chairmen. These were circulated and commented on first by working party members and …

Lewis Score: A useful clinical tool for patients with suspected Crohn's Disease submitted to capsule endoscopy

BACKGROUND/AIMS The Lewis Score (LS) can assess inflammatory activity on small bowel capsule endoscopy (SBCE). We aimed to evaluate the LS usefulness in the setting of suspected Crohns Disease (CD). METHODS Retrospective single-center study including 56 patients undergoing SBCE for suspected CD. Patients were divided into three groups, according to clinical presentation: Group 1 (28 patients): suspected CD not supported by the International Conference on Capsule Endoscopy (ICCE) criteria; Group 2 (19 patients): suspected CD based on two ICCE criteria; Group 3 (9 patients): patients fulfilling three or more criteria. Inflammatory activity was assessed with the LS. The diagnosis of CD required a minimum follow-up of 6 months after SBCE, basing on clinical evaluation, endoscopic, histological, radiological, and/or biochemical investigations. RESULTS SBCE detected significant inflammatory activity (LS≥135) in 23 patients (41.1%), being 5 patients from Group 1 (17.8%), 11 from Group 2 (57.9%) and 7 from Group 3 (77.8%) (p<0.05). CD was diagnosed in 23 patients (41.1%): six patients from Group 1 (21.4%), 10 from Group 2 (52.6%) and 7 from Group 3 (77.8%) (p<0.05). CD was diagnosed in 82.6% of patients with significant inflammatory activity on CE (LS≥135), but in only 12.1% of those having a LS<135 (p<0.05). The LS Positive Predictive Value, Negative Predictive Value, Sensitivity and Specificity were 82.6%, 87.9%, 82.6% and 87.9%, respectively. CONCLUSIONS The LS may be a valuable diagnostic tool in the setting of suspected CD. Patients not fulfilling the ICCE criteria have lower LS and fewer are diagnosed with CD during follow-up.

Validation of the Lewis score for the evaluation of small-bowel Crohn’s disease activity

BACKGROUND AND STUDY AIMS The Lewis score was developed to measure mucosal inflammatory activity as detected by small-bowel capsule endoscopy (SBCE). The aim of the current study was to validate the Lewis score by assessing interobserver correlation and level of agreement in a clinical setting. PATIENTS AND METHODS This was a retrospective, single-center, double-blind study including patients with isolated small-bowel Crohns disease who underwent SBCE. The Lewis score was calculated using a software application, based on the characteristics of villous edema, ulcers, and stenoses. The Lewis score was independently calculated by one of three investigators and by a central reader (gold standard). Interobserver agreement was assessed using intraclass correlation (ICC) coefficient and Bland - Altman plots. RESULTS A total of 70 patients were consecutively included (mean age 33.9 ± 11.7 years). The mean Lewis score was 1265 and 1320 for investigators and the central reader, respectively. There was a high correlation, both for scores obtained for each tertile (first tertile r = 0.659 - 0.950, second tertile r = 0.756 - 0.906, third tertile r = 0.750 - 0.939), and for the global score (r = 0.745 - 0.928) (P < 0.0001). Interobserver agreement was almost perfect between the investigators and the central reader (first tertile ICC = 0.788 - 0.971, second tertile ICC = 0.824 - 0.943, third tertile ICC = 0.857 - 0.968, global score ICC = 0.852 - 0.960; P < 0.0001). The inflammatory activity was classified as normal (score < 135) in 2.9 % vs. 2.9 %, mild (score ≥ 135 - < 790) in 51.4 % vs. 55.7 %, and moderate to severe (score ≥ 790) in 45.8 % vs. 41.4 % of patients, respectively (P < 0.001). CONCLUSION A strong interobserver agreement was demonstrated for the determination of the Lewis score in a practical clinical setting, validating this score for the reporting of small-bowel inflammatory activity. The Lewis score might be used for diagnosing, staging, follow-up, and therapeutic assessment of patients with isolated small-bowel Crohns disease.

Tailoring Crohn's disease treatment: The impact of small bowel capsule endoscopy

BACKGROUND AND AIMS Small bowel capsule endoscopy (SBCE) may detect proximal small bowel lesions that have been previously missed by ileocolonoscopy and small bowel imaging in patients with known ileal and/or colonic Crohns disease (CD). We aimed to evaluate whether the therapeutic management is influenced by SBCE findings. METHODS Retrospective single center study. Inclusion of consecutive patients with known non-stricturing and non-penetrating ileal and/or colonic CD, submitted to SBCE to evaluate disease extension and activity, with ≥ 1 year follow-up. Lesions were classified with the Lewis score (LS) as non-significant (LS<135), mild (135≤LS≤790), or moderate-to-severe (LS>790). Therapeutic changes were assessed three months after SBCE. RESULTS Fifty consecutive patients (35±13 years, 52% females) were included. At ileocolonoscopy, disease location was ileal (L1) in 60%, colonic (L2) in 10% and ileocolonic (L3) in 30% of the patients. In 33 patients (66%) SBCE detected significant proximal lesions previously missed by other modalities. The proportion of patients on thiopurines and/or biologics before SBCE was 2/50 (4%); this was significantly higher three months after SBCE, 15/50 (30%), p=0.023. Treatment with thiopurines and/or biologics was started more often in patients with proximal small bowel lesions [13/33 (39%) vs. 1/17 (6%), p=0.011, relative risk (RR) 6.5], particularly when severe (6%, 36% and 45% of patients with non-significant, mild and moderate-to-severe inflammation, respectively). CONCLUSIONS SBCE diagnoses previously undetected lesions and it influences therapeutic management of CD, triggering an earlier introduction of immunomodulators and/or biological therapy.

Oral purgative and simethicone before small bowel capsule endoscopy

AIM To evaluate small bowel cleansing quality, diagnostic yield and transit time, comparing three cleansing protocols prior to capsule endoscopy. METHODS Sixty patients were prospectively enrolled and randomized to one of the following cleansing protocols: patients in Group A underwent a 24 h liquid diet and overnight fasting; patients in Group B followed protocol A and subsequently were administered 2 L of polyethylene glycol (PEG) the evening before the procedure; patients in Group C followed protocol B and were additionally administered 100 mg of simethicone 30 min prior to capsule ingestion. Small bowel cleansing was independently assessed by two experienced endoscopists and classified as poor, fair, good or excellent according to the proportion of small bowel mucosa under perfect conditions for visualization. When there was no agreement between the two endoscopists, the images were reviewed and discussed until a consensus was reached. The preparation was considered acceptable if > 50% or adequate if > 75% of the mucosa was in perfect cleansing condition. The amount of bubbles was assessed independently and it was considered significant if it prevented a correct interpretation of the images. Positive endoscopic findings, gastric emptying time (GET) and small bowel transit time (SBTT) were recorded for each examination. RESULTS There was a trend favoring Group B in achieving an acceptable (including fair, good or excellent) level of cleansing (Group A: 65%; Group B: 83.3%; Group C: 68.4%) [P = not significant (NS)] and favoring Group C in attaining an excellent level of cleansing (Group A: 10%; Group B: 16.7%; Group C: 21.1%) (P = NS). The number of patients with an adequate cleansing of the small bowel, corresponding to an excellent or good classification, was 5 (25%) in Group A, 5 (27.8%) in Group B and 4 (21.1%) in Group C (P = 0.892). Conversely, 7 patients (35%) in Group A, 3 patients (16.7%) in Group B and 6 patients (31.6%) in Group C were considered to have poor small bowel cleansing (P = 0.417), with significant fluid or debris such that the examination was unreliable. The proportion of patients with a significant amount of bubbles was 50% in Group A, 27.8% in Group B and 15.8% in Group C (P = 0.065). This was significantly lower in Group C when compared to Group A (P = 0.026). The mean GET was 27.8 min for Group A, 27.2 min for Group B and 40.7 min for Group C (P = 0.381). The mean SBTT was 256.4 min for Group A, 256.1 min for Group B and 258.1 min for Group C (P = 0.998). Regarding to the rate of complete examinations, the capsule reached the cecum in 20 patients (100%) in Group A, 16 patients (88.9%) in Group B and 17 patients (89.5%) in Group C (P = 0.312). A definite diagnosis based on relevant small bowel endoscopic lesions was established in 60% of the patients in Group A (12 patients), 44.4% in Group B (8 patients) and 57.8% in Group C (11 patients) (P = 0.587). CONCLUSION Preparation with 2 L of PEG before small bowel capsule endoscopy (SBCE) may improve small bowel cleansing and the quality of visualization. Simethicone may further reduce intraluminal bubbles. No significant differences were found regarding GET, SBTT and the proportion of complete exploration or diagnostic yield among the three different cleansing protocols.

Finding the solution for incomplete small bowel capsule endoscopy

AIM To evaluate whether the use of real time viewer (RTV) and administration of domperidone to patients with delayed gastric passage of the capsule could reduce the rate of incomplete examinations (IE) and improve the diagnostic yield of small bowel capsule endoscopy (SBCE). METHODS Prospective single center interventional study, from June 2012 to February 2013. Capsule location was systematically checked one hour after ingestion using RTV. If it remained in the stomach, the patient received 10 mg domperidone per os and the location of the capsule was rechecked after 30 min. If the capsule remained in the stomach a second dose of 10 mg of domperidone was administered orally. After another 30 min the position was rechecked and if the capsule remained in the stomach, it was passed into the duodenum by upper gastrointestinal (GI) endoscopy. The rate of IE and diagnostic yield of SBCE were compared with those of examinations performed before the use of RTV or domperidone in our Department (control group, January 2009 - May 2012). RESULTS Both groups were similar regarding age, sex, indication, inpatient status and surgical history. The control group included 307 patients, with 48 (15.6%) IE. The RTV group included 82 patients, with 3 (3.7%) IE, P = 0.003. In the control group, average gastric time was significantly longer in patients with IE than in patients with complete examination of the small bowel (77 min vs 26 min, P = 0.003). In the RTV group, the capsule remained in the stomach one hour after ingestion in 14/82 patients (17.0%) vs 48/307 (15.6%) in the control group, P = 0.736. Domperidone did not significantly affect small bowel transit time (260 min vs 297 min, P = 0.229). The capsule detected positive findings in 39% of patients in the control group and 49% in the RTV group (P = 0.081). CONCLUSION The use of RTV and selective administration of domperidone to patients with delayed gastric passage of the capsule significantly reduces incomplete examinations, with no effect on small bowel transit time or diagnostic yield.

PillCam COLON 2 © in Crohn's disease: A new concept of pan-enteric mucosal healing assessment

AIM To evaluate mucosal healing in patients with small bowel plus colonic Crohns disease (CD) with a single non-invasive examination, by using PillCam COLON 2 (PCC2). METHODS Patients with non-stricturing nonpenetrating small bowel plus colonic CD in sustained corticosteroid-free remission were included. At diagnosis, patients had undergone ileocolonoscopy to identify active CD lesions, such as ulcers and erosions, and small bowel capsule endoscopy to assess the Lewis Score (LS). After ≥ 1 year of follow-up, patients underwent entire gastrointestinal tract evaluation with PCC2. The primary endpoint was assessment of CD mucosal healing, defined as no active colonic CD lesions and LS < 135. RESULTS Twelve patients were included (7 male; mean age: 32 years), and mean follow-up was 38 mo. The majority of patients (83.3%) received immunosuppressive therapy. Three patients (25%) achieved mucosal healing in both the small bowel and the colon, while disease activity was limited to either the small bowel or the colon in 5 patients (42%). It was possible to observe the entire gastrointestinal tract in 10 of the 12 patients (83%) who underwent PCC2. CONCLUSION Only three patients in sustained corticosteroid-free clinical remission achieved mucosal healing in both the small bowel and the colon, highlighting the limitations of clinical assessment when stratifying disease activity, and the need for pan-enteric endoscopy to guide therapeutic modification.

Virtual chromoendoscopy in small bowel capsule endoscopy: New light or a cast of shadow?

AIM To evaluate whether virtual chromoendoscopy can improve the delineation of small bowel lesions previously detected by conventional white light small bowel capsule endoscopy (SBCE). METHODS Retrospective single center study. One hundred lesions selected from forty-nine consecutive conventional white light SBCE (SBCE-WL) examinations were included. Lesions were reviewed at three Flexible Spectral Imaging Color Enhancement (FICE) settings and Blue Filter (BF) by two gastroenterologists with experience in SBCE, blinded to each others findings, who ranked the quality of delineation as better, equivalent or worse than conventional SBCE-WL. Inter-observer percentage of agreement was determined and analyzed with Fleiss Kappa (κ) coefficient. Lesions selected for the study included angioectasias (n = 39), ulcers/erosions (n = 49) and villous edema/atrophy (n = 12). RESULTS Overall, the delineation of lesions was improved in 77% of cases with FICE 1, 74% with FICE 2, 41% with FICE 3 and 39% with the BF, with a percentage of agreement between investigators of 89% (κ = 0.833), 85% (κ = 0.764), 66% (κ = 0.486) and 79% (κ = 0.593), respectively. FICE 1 improved the delineation of 97.4% of angioectasias, 63.3% of ulcers/erosions and 66.7% of villous edema/atrophy with a percentage of agreement of 97.4% (κ = 0.910), 81.6% (κ = 0.714) and 91.7% (κ = 0.815), respectively. FICE 2 improved the delineation of 97.4% of angioectasias, 57.1% of ulcers/erosions and 66.7% of villous edema/atrophy, with a percentage of agreement of 89.7% (κ = 0.802), 79,6% (κ = 0.703) and 91.7% (κ = 0.815), respectively. FICE 3 improved the delineation of 46.2% of angioectasias, 24.5% of ulcers/erosions and none of the cases of villous edema/atrophy, with a percentage of agreement of 53.8% [κ = not available (NA)], 75.5% (κ = NA) and 66.7% (κ = 0.304), respectively. The BF improved the delineation of 15.4% of angioectasias, 61.2% of ulcers/erosions and 25% of villous edema/atrophy, with a percentage of agreement of 76.9% (κ = 0.558), 81.6% (κ = 0.570) and 25.0% (κ = NA), respectively. CONCLUSION Virtual chromoendoscopy can improve the delineation of angioectasias, ulcers/erosions and villous edema/atrophy detected by SBCE, with almost perfect interobserver agreement for FICE 1.

Multicenter survey on the use of device-assisted enteroscopy in Portugal

Background Device-assisted enteroscopies (DAEs) are recent endoscopic techniques that enable direct endoscopic small-bowel evaluation. Objective The objective of this article is to evaluate the implementation of DAEs in Portugal and assess the main indications, diagnoses, diagnostic yield, therapeutic yield and complication rate. Methods We conducted a multicenter retrospective series using a national Web-based survey on behalf of the Portuguese Small-Bowel Study Group. Participants were asked to fill out two online databases regarding procedural data, indications, diagnoses, endoscopic therapy and complications using prospectively collected institutional data records. Results A total of eight centers were enrolled in the survey, corresponding to 1411 DAEs. The most frequent indications were obscure gastrointestinal bleeding (OGIB), inflammatory bowel disease and small-bowel tumors. The pooled diagnostic yield was 63%. A relation between the diagnostic yield and the indications was clear, with a diagnostic yield for OGIB of 69% (p = 0.02) with a 52% therapeutic yield. Complications occurred in 1.2%, with a major complication rate of 0.57%. Perforations occurred in four patients (0.28%). Conclusion DAEs are safe and effective procedures, with complication rates of 1.2%, the most serious of which is perforation. Most procedures are performed in the setting of OGIB. Diagnostic and therapeutic yields are dependent on the indication, hence appropriate patient selection is crucial.

Mucosal Healing in Ulcerative Colitis – When Zero is Better

BACKGROUND AND AIMS Extensive evidence has underlined the importance of mucosal healing as a treatment aim for ulcerative colitis (UC). We aimed to assess differences in the incidence of clinical relapse at 12 months between UC patients with Mayo endoscopic scores (MES) 0 and 1. METHODS This retrospective study included consecutive patients in corticosteroid-free remission between 2008 and 2013 and with follow-up of at least 1 year, with MES 0 or 1 in complete colonoscopy. Clinical relapse was defined as need for induction treatment, treatment escalation, hospitalization or surgery. A p value <0.05 was considered statistically significant. RESULTS The study included 138 patients, 72 (52.2%) female, with mean age of 49 (±14) years. Inflammatory activity was classified as MES 0 in 61 (44.2%) patients and MES 1 in 77 (55.8%) patients. Clinical relapse during follow-up was significantly more frequent in patients with MES 1 than MES 0 (27.3 vs 11.5%, p = 0.022), and in the multivariate analysis MES 1 was the only factor significantly associated with an increased risk of relapse (odds ratio 2.89, 95% confidence interval 1.14-7.36, p = 0.026). This association was encountered in the subgroup of patients with left-sided/extensive colitis (29.7 vs 11.1%, p = 0.049), but not proctitis (25.0 vs 12.0%, p = 0.202). CONCLUSIONS In patients with UC in corticosteroid-free remission, particularly those with left-sided colitis or extensive colitis, MES 1 was significantly associated with a 3-fold increased risk of relapse compared with endoscopic MES 0. Our results support the use of endoscopic MES 0 as the most suitable treatment endpoint to define mucosal healing in patients with UC.