Francisca Dias de Castro

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.

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.

Utilisation of pulp and paper industry wastes as raw materials in cement clinker production

The present work assesses the incorporation of grits and dregs, both wastes from cellulose and paper making industry, in cement clinker production. Industrial trials were developed with conventional raw clinker, used as a reference material and with the addition of grits and dregs, 0.25% and 0.13%, respectively. All raw meals were fired at 1400?1500°C. Chemical composition of the final mixtures, gaseous emissions quality during clinker production and leaching behaviour of the final products were evaluated. The results show that such incorporation could be an effective process for waste management from both the environmental and economic points of view.

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.

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.

Improving diagnostic yield in obscure gastrointestinal bleeding--how virtual chromoendoscopy may be the answer.

Background and aim A significant proportion of patients presenting with obscure gastrointestinal bleeding (OGIB) have negative small bowel capsule endoscopy (SBCE) examinations, and yet remain at risk of rebleeding. We aimed to evaluate whether a second-look review of SBCE images using flexible spectral color enhancement (FICE) may improve the detection of potentially bleeding lesions. Materials and methods This was a retrospective, single-center study including consecutive patients with OGIB subjected to SBCE, whose standard white light examination was nondiagnostic. Each SBCE was reviewed using FICE 1. New findings were labeled as either P1 or P2 lesions according to bleeding potential. Patients were followed up to assess the incidence of rebleeding. Results A total of 42 consecutive patients were included. Sixteen patients (38%) experienced rebleeding after a mean follow-up of 26 months. Review of SBCE images using FICE 1 enabled the identification of previously unrecognized P2 lesions, mainly angioectasias, in nine patients (21%) and P1 lesions, mainly erosions, in 26 patients (62%). Among patients who experienced rebleeding, 13/16 (81%) were diagnosed with P1 lesions with FICE 1 (P=0.043), whereas 3/16 (19%) had confirmed nondiagnostic SBCE and only 1/16 (6%) had newly diagnosed P2 (plus P1) lesions. An alternative source of bleeding outside the small bowel was found in only 3/16 (19%) patients with rebleeding during the follow-up. Conclusion In a significant proportion of patients with OGIB, FICE 1 may detect potentially bleeding lesions previously missed under conventional white light SBCE. Review of nondiagnostic SBCE with FICE 1 may be a valuable strategy to obviate the need for further investigations in patients with OGIB, particularly for those who experience rebleeding.

LOWER LEVELS OF VITAMIN D CORRELATE WITH CLINICAL DISEASE ACTIVITY AND QUALITY OF LIFE IN INFLAMMATORY BOWEL DISEASE

BACKGROUND Inflammatory bowel disease, comprising Crohns disease and ulcerative colitis, is a group of debilitating conditions associated with deregulated mucosal immune response. Vitamin D has been implicated in immune response and gastrointestinal function. OBJECTIVES To investigate the correlation between serum vitamin D levels and disease activity and quality of life in patients with inflammatory bowel disease. METHODS This cross-sectional study enrolled ambulatory patients with inflammatory bowel disease and assessed clinical disease activity and quality of life (Short Inflammatory Bowel Disease Questionnaire [SIBDQ]). Vitamin D levels were determined via serum 25-hydroxyvitamin D measurement; deficiency was defined as values <20 ng/mL. Statistical analysis was performed with SPSS vs 20.0. RESULTS A total of 76 patients were enrolled, 19 with ulcerative colitis (25%) and 57 with Crohns disease (75%). Overall, mean serum 25-hydroxyvitamin D levels were low (26.0±10.0 ng/mL), while those in patients with Crohns disease were significantly lower than ulcerative colitis (24.6±8.0 vs 30.0±12.5 ng/mL; P=0.032). Vitamin D deficiency was found in 30% of patients. Patients who were in clinical remission were found to have higher levels of vitamin D than those who were not in remission (28.0±10.3 vs 21.6±6.0 ng/mL, P=0.001). Inflammatory bowel disease patients with SIBDQ scores <50 were found to have significantly lower mean vitamin D levels compared with patients who had SIBDQ scores ≥50 (23.4±6.9 vs 27.9±10.8 ng/mL, P=0.041). CONCLUSIONS A high proportion of patients with inflammatory bowel disease were vitamin D deficient, particularly patients with Crohns disease. Both clinical disease activity and quality of life correlated significantly with lower levels of vitamin D, illustrating a clear need for supplementation in patients with inflammatory bowel disease.

Small bowel capsule endoscopy in obscure gastrointestinal bleeding: normalcy is not reassuring.

Background/Aim Small bowel capsule endoscopy (SBCE) is currently a fundamental tool in the etiological study of obscure gastrointestinal bleeding (OGIB). However, the impact of a negative exam and the risk of rebleeding are not entirely known. The aim of this study was to evaluate the outcomes of patients with OGIB and a negative SBCE examination in terms of follow-up duration, additional diagnostic studies, and achievement of a diagnosis as well as to assess the incidence of rebleeding and possible associated factors. Materials and methods We retrospectively analyzed 256 patients who consecutively underwent an SBCE examination for the study of OGIB between April 2006 and December 2011, and then selected the 79 whose results excluded potentially bleeding lesions. Eleven patients were lost to follow-up and the remaining 68 were eligible for a nested case–control analysis. Pre-SBCE and post-SBCE information was collected, including follow-up interval and incidence of rebleeding, defined as admission to the hospital for symptomatic anemia, need for blood transfusion, decrease in hemoglobin value of greater than 2 g/dl, or evidence of melena or hematochezia. Univariate analysis included age, sex, OGIB presentation (occult or visible), hemoglobin levels at presentation, and comorbidities. Results In the 68 patients analyzed, the mean age was 52±18 years and 61.8% were women. The OGIB was occult in 54 patients (79.4%) and overt in 14 patients (20.6%). Patients were followed up for an average of 32 months. Thirty-nine patients (57.4%) underwent further diagnostic investigations during the period of follow-up and a cause for the gastrointestinal bleeding was found in five of them. Rebleeding was documented in 16 (23.5%) patients, occurring on average 15±13.8 months after the SBCE. Male sex was associated significantly with higher incidence of rebleeding (P=0.004). Conclusion Approximately one quarter of patients with OGIB and negative SBCE examination will experience rebleeding, with higher incidence among men; thus, a negative SBCE in this setting is not reassuring. As the vast majority of rebleeding episodes seem to occur within the following 2 years after SBCE, the maintenance of regular medical surveillance during the above-mentioned period of time after a negative SBCE seems advisable.