Appearance Of Mucosa Research Articles

PTU-058 One Year Likelihood of Relapse in Ulcerative Colitis (UC) is Predicted by Mucosal Appearance but not by Faecal Calprotectin: Data from the Coda Study of once Daily Versus Three Times Daily Asacol

IntroductionFaecal calprotectin (FC) has become a useful marker of mucosal healing, with studies showing raised levels predictive of relapse1,2,3. These studies did not assess mucosal healing however, so did not...

Cone‐beam computed tomographic analysis of sinus membrane thickness, ostium patency, and residual ridge heights in the posterior maxilla: implications for sinus floor elevation

To determine, using cone-beam computed tomography (CBCT), the residual ridge height (RRH), sinus floor membrane thickness (MT), and ostium patency (OP) in patients being evaluated for implant placement in the posterior maxilla. CBCT scans of 128 patients (199 sinuses) with ≥1 missing teeth in the posterior maxilla were examined. RRH and MT corresponding to each edentulous site were measured. MT >2 mm was considered pathological and categorized by degree of thickening (2-5, 5-10 mm, and >10 mm). Mucosal appearance was classified as "normal", "flat thickening", or "polypoid thickening", and OP was classified as "patent" or "obstructed". Descriptive and bivariate statistical analyses were performed. MT >2 mm was observed in 60.6% patients and 53.6% sinuses. Flat and polypoid mucosal thickening had a prevalence of 38.1% and 15.5%, respectively. RRH ≤4 mm was observed in 46.9% and 48.9% of edentulous first and second molar sites, respectively. Ostium obstruction was observed in 13.1% sinuses and was associated with MT of 2-5 mm (6.7%), 5-10 mm (24%), and >10 mm (35.3%, P < 0.001). Polypoid mucosal lesions were more frequently associated with ostium obstruction than flat thickenings (26.7% vs. 17.6%, P < 0.001). Thickened sinus membranes (>2 mm) and reduced residual ridge heights (≤4 mm) were highly prevalent in this sample of patients with missing posterior maxillary teeth. Membrane thickening >5 mm, especially of a polypoid type, is associated with an increased risk for ostium obstruction. In the presence of these findings, an ENT referral may be beneficial prior to implant-related sinus floor elevation.

Evaluation of colonoscopy in the diagnosis and treatment of rectal carcinoid tumors with diameter less than 1 cm in 21 patients

The aim of this study was to evaluate colonoscopy in the diagnosis and treatment of rectal carcinoid tumors with diameter <1 cm. Elevated lesions with normal mucosal appearance under colonoscopy were identified. Endoscopic ultrasound (EUS) was performed in 16 patients. Lesions diagnosed as rectal carcinoid tumors were resected by endoscopic mucosal resection (EMR). The diagnosis of specimens by EMR was confirmed by pathological examination. Immunohistochemical staining was undertaken and follow-up data were collected. Twenty-two lesions were found among the 21 cases. The majority of these were located within 10 cm of the anal opening. Twenty two cases with rectal carcinoids were diagnosed by EUS under colonoscopy and all cases were verified by pathological examination. The resection rate was 95.5% (21/22). Of the lesions, six were mucosal and 10 were submucosal. Immunohistochemistry was undertaken for carcinoid tumors. Histological patterns of rectal carcinoids revealed solid nests or trabecular patterns. Eleven cases were synaptophysin (SYN)-positive, 8 cases were neurone-specific enolase (NSE)-positive and 5 cases were chromogranin A (CgA)-positive. Colonoscopy combined with EUS is effective in the diagnosis and determination of small rectal carcinoids. Endoscopic treatment is effective for small-sized tumors. Pathology and immunohistochemistry remain the diagnostic gold standard.

Clinical outcomes and predictive factors in oral corticosteroid-refractory active ulcerative colitis

To evaluate the clinical outcomes and prognostic factors after intravenous corticosteroids following oral corticosteroid failure in active ulcerative colitis patients. Consecutive patients with moderate to severe ulcerative colitis who had been treated with a course of intravenous corticosteroids after oral corticosteroid therapy failure between January 1996 and July 2010 were recruited at Severance Hospital, Seoul, South Korea. The disease activity was measured by the Mayo score, which consists of stool frequency, rectal bleeding, mucosal appearance at flexible sigmoidoscopy, and Physician Global Assessment. We retrospectively evaluated clinical outcomes at two weeks, one month, three months, and one year after the initiation of intravenous corticosteroid therapy. Two weeks outcomes were classified as responders or non-responders. One month, three month and one year outcomes were classified into prolonged response, steroid dependency, and refractoriness. Our study included a total of 67 eligible patients. At two weeks, 56 (83.6%) patients responded to intravenous corticosteroids. At one month, complete remission was documented in 18 (32.1%) patients and partial remission in 26 (46.4%). Eleven patients (19.7%) were refractory to the treatment. At three months and one year, we found 37 (67.3%) and 25 (46.3%) patients in prolonged response, ten (18.2%) and 23 (42.6%) patients in corticosteroid dependency, 8 (14.5%) and 6 (11.1%) patients with no response, respectively. Total 9 patients were underwent elective proctocolectomy within 1 year. The duration of oral corticosteroid therapy (> 14 d vs ≤ 14 d, P = 0.049) and lower hemoglobin level (≤ 11.0 mg/dL vs >11.0 mg/dL, P = 0.02) were found to be poor prognostic factors for response at two weeks. For one year outcome, univariate analysis revealed that only a partial Mayo score (≥ 6 vs <6, P = 0.057) was found to be associated with a poor response. The duration of oral corticosteroid therapy and lower hemoglobin level were strongly associated with poor outcome.

Periovulatory changes in the endoscopic appearance of the reproductive tract and teasing behavior in the bitch

A variety of diagnostic techniques have been applied to address the problem of determining optimal mating time in the bitch, although some have not been objectively investigated. Nine healthy bitches were examined daily using routine clinical methods as part of their normal breeding management with the aim of establishing which method was most useful. Accordingly, measurement of the degree of vulval swelling, endoscopic measurement of the vaginal mucosal color and appearance, and objective evaluation of behavior of the bitch were related to the time of ovulation (calculated when progesterone reached 5 ng/mL; Day 0) and the duration of the fertilization period (Day 2 to Day 5) determined by measurement of plasma progesterone concentration and assessment of vaginal cytology. There was a surprisingly large individual variation in measurements of vulval swelling, such that although trends were apparent this technique was not precise enough to establish the optimal mating time. However, measuring color saturation and vaginal mucosal fold width was successful. A consistent change in the mucosal color saturation was observed that related to the beginning (Day −5) and duration of the fertile period although there was no difference in measurement of color saturation between Day −5 and Day 2 (P = 0.31), and Day 2 and Day 5 (P = 0.43). The vaginal mucosal folds were smaller in width at the beginning of the fertilization period (Day 2) than at the beginning of the fertile period (Day −5) (P = 0.008), and all bitches had a consistent appearance of mucosal contours on Day 3. Assessment of sexual behavior was not considered precise enough to enable determination of the optimal time for mating because of the large amount of individual variation in behavioral scores. There was no difference in female behavior scores between Day −5 and Day 2 (P = 0.29), or between Day 2 and Day 5 (P = 0.06). Using objective techniques this study has quantified changes in the color and fold width of the vaginal mucosa that have previously only been subjectively reported. These changes can be used to identify the fertilization period and it is possible, with future refining of the technique, that endoscopic examination could replace vaginal cytology to be used in conjunction with plasma progesterone concentration when examining bitches to determine the optimal time to breed.

Candidiasis of the Small Bowel Causing Gastrointestinal Bleed

Purpose: Recognize small bowel Candidiasis as a rare cause of gastrointestinal bleed. Case Report: A 31-year-old woman with a history of juvenile idiopathic arthritis, not on chronic immunosuppression, was initially admitted to an outside hospital with acute malaise, arthralgias and rash complicated by the development of ARDS, requiring transfer to our hospital for further workup and management. Upon presentation, she was diagnosed with Adult-onset Still's disease and was treated with high doses of IV methylprednisolone. On hospital day #7, she developed hemoccult negative watery diarrhea of unclear etiology. The infectious workup, including cultures, was negative. Despite aggressive ICU management including multiple broad spectrum antibiotics, she remained critically ill with multi-organ dysfunction and was eventually initiated on Anakinra for treatment of her rheumatologic condition. She did experience overall clinical improvement, but her loose stools persisted. On hospital day #20, she developed melena and, subsequently, transfusion-dependent anemia. An esophagogastroduodenoscopy revealed a diffusely edematous and erythematous small bowel with active oozing of blood from the duodenum extending into the mid-jejunum. This mucosal appearance was also noted in the terminal ileum on colonoscopy. Biopsies from throughout the small bowel were positive for fungus, suggestive of Candida. Gastric and colonic biopsies were negative for fungus. IV fluconazole was initiated with subsequent improvement in her melena and anemia. Discussion: Small bowel Candidiasis has been recognized as a rare cause of watery diarrhea in immunocompromised patients. Rare case reports have documented small bowel fungal infections leading to gastrointestinal bleeding. In a 1992 autopsy study of 890 patients with malignant disease, Prescott et al. described 14 cases of small bowel fungal infections (Candida or Aspergillus spp), with only three Candidal infections associated with melena. Only one case of fungal infection was confined solely to the small intestine. Unlike previously described cases of melena caused by small bowel Candidiasis, our case demonstrates that small bowel Candidiasis can occur in the absence of underlying malignancy or extraintestinal Candidal infection. Though rare, small bowel Candidiasis should be considered in severely immunocompromised, acutely ill, hospitalized patients who develop clinically significant gastrointestinal bleeding even in the absence of underlying malignancy. Prompt recognition of this uncommon disease along with initiation of anti-fungal therapy is necessary to limit further bleeding and prevent potential complications such as small bowel perforation.

Fecal Microbiota Transplantation in Ulcerative Colitis: Review of 24 Years Experience

Purpose: Fecal Microbiota Transplantation (FMT) has traditionally been employed in Clostridium difficile infection (CDI), achieving near 100% cure rates1. However, preliminary reports are emerging of FMT's reversal of idiopathic Ulcerative Colitis (UC)2. To date, analysis of remission rates and treatment response to FMT in UC have not been available. At CDD, FMT has been offered as a treatment option for patients with UC since 1988. We provide an analysis of this cohort of patients aimed at documenting the success rate of this therapy. Methods: A review of all UC patients who underwent FMT at our centre was conducted. UC diagnosis was confirmed clinically, endoscopically, and histologically. Patients with indeterminate colitis or Crohn's Disease were excluded from the analysis. Sixty-two patients (40M; m 42.3 +/- 11.5y: 22F m 48.45 +/- 16.49y) with active UC and follow-up results were included in the analysis. Clinical remission was defined as a 0-1 modified Powell-Tuck index and partial remission as a ≥2 point decrease. Non-response was defined as ≤2 point decrease, unchanged score, increase in score over two consecutive visits, surgical intervention, or FMT-related adverse event requiring treatment cessation. Results: Overall, 91.9% of patients responded to FMT. Of these, 67.7% of patients (42/62) achieved complete clinical remission, and 24.2% of patients (15/62) achieved partial response. The remaining 8% (5/62) were treatment failures. Improvement in CRP and ESR correlated with clinical response observed in FMT patients. Twenty-one patients underwent repeat colonoscopy with a mean time to follow-up of 33 mths (range 1-198 mths). Of these 12/21 (57.1%) were found to have profound mucosal healing with a normal mucosal appearance, return of vascular pattern and no histological inflammation, but in one patient scarring was seen in areas of previously severe inflammation. A further eight patients (8/21, 38.1%) achieved normalisation of mucosa but had some isolated areas of patchy, mild inflammation. One patient (1/21, 4.8%) had remaining active colitis. FMT was well tolerated and produced no significant adverse events. Conclusion: FMT achieves high response rates in UC, and can cure UC in a subset of patients. This should be followed with blinded trials and metagenomic analyses to establish protocols for successful remission in UC. This is the first analysis of UC response rates in relation to FMT.

Novel STAT3 Selective Inhibitor Natura-α Shows Great Promises in Treating Moderate-to-severe Ulcerative Colitis in a Randomized, Double-blind, Placebo-controlled Phase II Clinical Trial

Purpose: Increases in Th1/Th17 cells, and decreases in Treg cells, have been observed in patients with various autoimmune/inflammatory diseases including ulcerative colitis (UC). Natura-α, a synthetic small molecule, which selectively inhibits STAT3 dimerization by its direct binding to the SH2 domain of STAT3. This skews T cell differentiation from the Th1/Th17 lineages toward the Treg lineage. The final outcome is an aberrant immune system returned to normal homeostasis, with minimal side effects. We conducted a Phase 2 study to assess the safety and efficacy of two oral dose levels of Natura-α in patients with moderate to severe UC treated for 28 days, the results of which have been presented previously. Our trial used somewhat unusual, stringent efficacy criteria. In order to gain comparability, we re-evaluated the data using published efficacy criteria from the Tofacitinib UC trial. Methods: This was a randomized, double-blind, placebo-controlled study at 10 US clinical centers in 70 patients with moderate to severe UC defined as: Disease Activity Index (DAI) score of 6 to 10 (inclusive); endoscopic evidence of active UC (mucosal appearance score of ≥2) by flexible sigmoidoscopy; rectal bleeding (DAI sub score of ≥1); and Physician's Global Assessment (PGA score ≥2). Patients were randomized to placebo, 10 mg or 20 mg Natura-α administered orally twice daily for 28 days. Assessments were made at baseline and after 7, 14 and 28 days of treatment with off-treatment follow up at days 35 and 56. Results: Clinical response was 86.4%, 95.0%, and 36.4%, clinical remission 81.8%, 45.0% and 9.1% in 10 mg, 20 mg Natura-α and placebo group, respectively, all statistically significantly different. No difference between treatment groups and placebo was observed on AEs, which were mild to moderate and no SAEs related to Natura-α treatment were reported. Conclusion: This phase 2 clinical trial provides strong evidence that Natura-α shows great promise for the treatment of moderate to severe UC. All categories of clinical response were improved and the drug was well tolerated. This novel STAT3 inhibitor, rebalancing Th17/Treg axis is an effective therapeutic strategy for UC. Disclosure: Dr. Long G. Wang, employee; Simon Mencher, employee; Allen Tsao, employee; Dr. Balfour Sartor, consultant.

Diagnostic Value of Fundic Red Spots in Helicobacter pylori (Hp) Infection

Purpose: Hp-related endoscopic features are under-emphasised in clinical practice, with their use as supportive diagnostic criteria contentious1,2. Numerous studies associate gastric nodularity with Hp infection, however, other mucosal features are yet to be fully investigated. We report the predictive nature of fundic red spots (FRS) in Hp infection and discuss their potential role as an additional diagnostic tool during endoscopic mucosal inspection. Methods: A retrospective analysis of patients displaying FRS on gastroscopy was conducted. FRS appeared as areas of focal hyperemia with mosaic mucosal patterning (Figure A). A total of 73 patients (37F, m: 56.1±13.7yrs; 36M, m: 54.6±13.1yrs) were included. Hp infection was confirmed by positive culture, or positive results for 2 of the following: urease biopsy test, urease breath test, histology.Figure A: Characteristic fundic red spots.Results: Of 73 FRS patients, 78% (57/73) were Hp-positive. Of these, only 10 patients displayed gastric nodularity. FRS did not appear influenced by current or recent proton-pump inhibitor (PPI) or antibiotic use, with 16 such patients displaying FRS. Conclusion: Our analysis reveals a strong positive correlation between FRS and Hp infection. In our experience, FRS can indicate the presence of Hp even with PPI or antibiotic use, a clinically important observation as such agents can compromise even gold standard tests. Despite some investigation of other Hp-related mucosal appearances, the majority of published work has focused on gastric nodularity. While such nodularity is highly specific for Hp infection, sensitivity can be low1,3. Önal et al (2009) reported that only 65.4% (121/185) of nodular gastritis cases were positive for Hp, notably less than the 78% positivity seen here. As such, the observation of FRS with or without nodularity during endoscopy may enhance our diagnostic ability. This study highlights the importance of endoscopic observations in Hp detection and supports the use of such observations as additional diagnostic tools, particularly in cases of concurrent PPI use. 1. Khan et al (1999) Saudi J Gastroenterol 5:9-14 2. Yan et al (2010) World J Gastroenterol 16:496-500 3. Chen et al (2008) Dig Dis Sci 52:2662-6 4. Önal et al (2009) Turk J Med Sci 39:719-23. Disclosure: Professor Borody has a pecuniary interest in the Centre for Digestive Diseases.

Mucosal Healing in Crohn’s Disease: Relevance for Clinical Outcomes

The clinical management of Crohn's disease (CD) has evolved in recent years from symptom control to healing of mucosal lesions. Mucosal healing, induced and maintained by immunomodulators and/or biologicals, has been shown to alter the disease course in patients with CD. As a consequence, long-term disease outcomes have been dramatically improved, in particular since the introduction of anti-tumor necrosis factor (TNF) agents. CD patients with active inflammation (ileocolonic ulcers and/or increased C-reactive protein levels) benefit most from treatment with TNF antagonists. Since healing of the inflamed mucosa is now considered an important treatment goal, endoscopic monitoring is gradually entering routine practice. Therefore, the mucosal appearance will more and more influence the therapeutic decision making process. Mucosal healing has also become an end-point in therapeutic trials. We will summarize some of the fundamental issues regarding mucosal healing and discuss data to support its clinical relevance in the management of CD.

Duodenal Endoscopic Findings and Histopathologic Confirmation of Intestinal Lymphangiectasia in Dogs

The diagnosis of intestinal lymphangiectasia (IL) has been associated with characteristic duodenal mucosal changes. However, the sensitivity and specificity of the endoscopic duodenal mucosal appearance for the diagnosis of IL are not reported. To evaluate the utility of endoscopic images of the duodenum for diagnosis of IL. Endoscopic appearance of the duodenal mucosal might predict histopathologic diagnosis of IL with a high degree of sensitivity and specificity. 51 dogs that underwent upper gastrointestinal (GI) endoscopy and endoscopic biopsies. Retrospective review of images acquired during endoscopy. Dogs were included if adequate biopsies were obtained during upper GI endoscopy and digital images were saved during the procedure. Images were assessed for the presence and severity of IL. Using histopathology as the gold standard, the sensitivity and specificity of endoscopy for diagnosing IL were calculated. Intestinal lymphangiectasia (IL) was diagnosed in 25/51 dogs. Gross endoscopic appearance of the duodenal mucosa had a sensitivity and specificity (95% confidence interval) of 68% (46%, 84%) and 42% (24%, 63%), respectively for diagnosis of IL. Endoscopic images in cases with lymphopenia, hypocholesterolemia, and hypoalbuminemia had a sensitivity of 80%. Endoscopic duodenal mucosa appearance alone lacks specificity and has only a moderate sensitivity for diagnosis of IL. Evaluation of biomarkers associated with PLE improved the sensitivity; however, poor specificity for diagnosis of IL supports the need for histopathologic confirmation.

The use of Pillcam Colon in assessing mucosal inflammation in ulcerative colitis: a multicenter study

Treatment of ulcerative colitis should be tailored to the severity of colonic inflammation, which in the past has been gauged mainly by clinical features and biochemical parameters. Recently, mucosal healing has been proposed as a standard to guide therapy. The aim of this multicenter study was to test whether mucosal appearance, as reported by colon capsule endoscopy (CCE), can be used to differentiate active from inactive ulcerative colitis. Adult patients from Hong Kong, Singapore, and Taiwan who were suspected or known to have ulcerative colitis were included in this prospective study. CCE and conventional optical colonoscopy were offered to these patients on the same day after receiving standard bowel preparation. The primary endpoint was the accuracy of CCE in assessing colonic inflammation (defined as the presence of ulcers, erythema, erosions, edema, exudates in mucosa), using optical colonoscopy as the gold standard. At total of 100 patients (42 females; median age 50 years; range 22 - 68 years) were enrolled. Four cases were excluded from the analysis due to technical failure or slow transit of the capsule. In nine patients, the capsule was not excreted within 8.5 hours and required retrieval during colonoscopy. The sensitivity of CCE to detect active colonic inflammation was 89 % (95 % confidence interval [CI] 80 - 95) and specificity was 75 % (95 %CI 51 - 90). The positive and negative predictive values of CCE for colonic inflammation were 93 % (95 %CI 84 - 97) and 65 % (95 %CI 43 - 83), respectively. No serious adverse event related to the CCE procedure or preparation was reported. CCE is a safe procedure to monitor mucosal healing in ulcerative colitis. However, at this stage, CCE cannot be recommended to replace conventional colonoscopy in the management of this condition.

PMO-047 Diversion colitis treatment with rapidly fermentable fibre-suppositories

IntroductionDiversion colitis, a nutritional deficiency disease of short chain fatty acids (SCFAs) in the defunctioned rectum, responds to butyrate enemas but these are impracticable due to unpleasant malodour. Treatment with...

Mesalazine granules 1.5 g once‐daily maintain remission in patients with ulcerative colitis who switch from other 5‐ASA formulations: a pooled analysis from two randomised controlled trials

Mesalazine (mesalamine) granules (MG) were shown to be effective for the maintenance of remission of ulcerative colitis (UC) in two double-blind placebo-controlled trials. To evaluate the efficacy of once-daily MG for maintenance of remission in patients with UC who switched from other 5-aminosalicylic acid (5-ASA) formulations. Data from two independent multicenter, randomised, double-blind, placebo-controlled, 6-month trials evaluating patients with UC in remission were combined for analysis of a subpopulation of patients who switched from other 5-ASA formulations to MG 1.5 g or placebo upon randomisation. The primary endpoint was the percentage of patients who remained relapse-free at Month 6 or end of treatment. Relapse was defined as a Sutherland Disease Activity Index (SDAI) rectal bleeding score ≥1 and mucosal appearance score ≥2, a UC flare or medication used to treat a UC flare. Of the 487 patients who received 5-ASA maintenance therapy at enrolment, 322 were in the MG group and 165 were in the placebo group. The percentage of patients who remained relapse-free (based on Sutherland Disease Activity Index scores) after 6 months was significantly higher with MG than placebo (78.3% vs. 58.8%, P < 0.001). Rectal bleeding, stool frequency and the physician's rating of disease activity remained unchanged after 6 months in a higher percentage of patients using MG compared with those on placebo (P < 0.004 for each endpoint). Mesalazine granules 1.5 g once-daily is effective for maintenance of remission in UC patients who switch from other 5-ASA formulations. ClinicalTrials.gov identifiers NCT00744016, NCT00767728.

Mo1673 Evaluation of Mucosal Healing of Ulcerative Colitis by Using a Quantitative Fecal Immunochemical Test

Background and Aim: Evidence has been accumulated to show that achievement of mucosal healing (MH) is associated with sustained clinical remission, and reduced rates of hospitalization and surgical resection. The combination of oral and topical mesalazine is thought to be more effective than alone in patients with mild-to-moderate disatal colitis and mild-tomoderate extensive colitis. However, endoscopic evaluation of the combined treatment on colonic mucosa is scarce. We conducted conventional endoscopic evaluation as well as segmental endoscopic evaluation in mild-to-moderate ulcerative colitis (UC) patients treated with oral Pentasa® and Pentasa® enema. Materials and Methods: Patients with active mildto-moderate UC were included and treated with 4 g/day of mesalazine combined with 1 g/ day mesalazine enema for 8 wks. At both baseline and 8 wks patients were endoscopically asseseed using Mayo Endoscopic Score and using Segmental Endoscopic Score. Segmental endoscopic evaluation was performed for each of 8 contiguous anatomic segments (rectum below/above the peritoneal reflection, rectosigmoid, sigmoid, left colon, transverse, right colon, cecum). The criteria of segmental endoscopy included erythema, vascular pattern, friability and erosion/ulcer (score range per segment: 0 10). MH was defined as Mayo Endoscopic Score = 0, 1. Disease activity was also assessed at baseline and 8 wks using the UC Disease Activity Index (UCDAI), with clinical and endoscopic signs. Remission and improvement were defined as a UCDAI score < 2 and as a decrease of UCDAI score by ≥ 2 points from baseline, respectively. Abbreviated UCDAI score (aUCDAI) obtained from stool frequency, rectal bleeding and physician's global assessment was assessed at baseline, 4 and 8 wks. Result: Of the 31 patients included, 29 completed endoscopic evaluations at both baseline and 8 wks. Median disease duration was 72.7 months and mean baseline UCDAI score was 6.72. The extents of disease were 10.3% in proctitis, 34.5% in left-sided colitis and 55.2% in extensive colitis. Mayo endscopic score significantly decreased from 2.14 to 1.45 (p < 0.001) and MH rate was 51.7%. The segmental endscopic scores of every assessed area at 8 wks decreased significantly compared to that at baseline (Table). UCDAI significantly decreased from 6.72 to 3.00 (p < 0.001). Remission and improvement rates were 31.0% and 79.3%, respectively. aUCDAI significantly decreased from 4.59 at baseline to 1.76 at 4 wks and 1.55 at 8 wks (p < 0.001). Conclusion: These results demonstrate that the combination of oral and topical mesalazine ameliorates mucosal appearances of the whole colon with fast clinical improvement. Therefore, combined mesalazine therapy is thought to be the optimum first line therapy for mild-to-moderate UC patients independent of the extent of disease. Segmental Endoscopic Score

Mo1670 Segmental Endoscopic Evaluation of Combined Oral and Topical Mesalazine (Pentasa(r)) in Patients With Mild-to-Moderate Ulcerative Colitis

Background and Aim: Evidence has been accumulated to show that achievement of mucosal healing (MH) is associated with sustained clinical remission, and reduced rates of hospitalization and surgical resection. The combination of oral and topical mesalazine is thought to be more effective than alone in patients with mild-to-moderate disatal colitis and mild-tomoderate extensive colitis. However, endoscopic evaluation of the combined treatment on colonic mucosa is scarce. We conducted conventional endoscopic evaluation as well as segmental endoscopic evaluation in mild-to-moderate ulcerative colitis (UC) patients treated with oral Pentasa® and Pentasa® enema. Materials and Methods: Patients with active mildto-moderate UC were included and treated with 4 g/day of mesalazine combined with 1 g/ day mesalazine enema for 8 wks. At both baseline and 8 wks patients were endoscopically asseseed using Mayo Endoscopic Score and using Segmental Endoscopic Score. Segmental endoscopic evaluation was performed for each of 8 contiguous anatomic segments (rectum below/above the peritoneal reflection, rectosigmoid, sigmoid, left colon, transverse, right colon, cecum). The criteria of segmental endoscopy included erythema, vascular pattern, friability and erosion/ulcer (score range per segment: 0 10). MH was defined as Mayo Endoscopic Score = 0, 1. Disease activity was also assessed at baseline and 8 wks using the UC Disease Activity Index (UCDAI), with clinical and endoscopic signs. Remission and improvement were defined as a UCDAI score < 2 and as a decrease of UCDAI score by ≥ 2 points from baseline, respectively. Abbreviated UCDAI score (aUCDAI) obtained from stool frequency, rectal bleeding and physician's global assessment was assessed at baseline, 4 and 8 wks. Result: Of the 31 patients included, 29 completed endoscopic evaluations at both baseline and 8 wks. Median disease duration was 72.7 months and mean baseline UCDAI score was 6.72. The extents of disease were 10.3% in proctitis, 34.5% in left-sided colitis and 55.2% in extensive colitis. Mayo endscopic score significantly decreased from 2.14 to 1.45 (p < 0.001) and MH rate was 51.7%. The segmental endscopic scores of every assessed area at 8 wks decreased significantly compared to that at baseline (Table). UCDAI significantly decreased from 6.72 to 3.00 (p < 0.001). Remission and improvement rates were 31.0% and 79.3%, respectively. aUCDAI significantly decreased from 4.59 at baseline to 1.76 at 4 wks and 1.55 at 8 wks (p < 0.001). Conclusion: These results demonstrate that the combination of oral and topical mesalazine ameliorates mucosal appearances of the whole colon with fast clinical improvement. Therefore, combined mesalazine therapy is thought to be the optimum first line therapy for mild-to-moderate UC patients independent of the extent of disease. Segmental Endoscopic Score

Recognition of Microscopic Colitis at Colonoscopy

Microscopic colitis is a common condition in Canada and is characterized by watery diarrhea with normal endoscopic mucosal appearance using conventional white-light endoscopy. Two types of microscopic colitis are recognized by histological appearance: lymphocytic colitis and collagenous colitis. Recent studies suggest that 10% to 30% of older patients who present with diarrhea and demonstrate normal mucosal appearance at endoscopy have microscopic colitis (1). Increasingly, however, with high-definition endoscopy assisted by postprocessing of images by filter techniques in combination with chromoendoscopy, subtle abnormalities of the mucosa are apparent in patients with microscopic colitis. iScan (Pentax, Japan) is a newly developed postprocessing light filter that enhances details of the mucosal surface, mucosal patterns (i-Scan p designated iScan 1) and vessel architecture (i-Scan v designated iScan 2). i-Scan is a technique designed for differentiating neoplastic from non-neoplastic lesions in the colon. This new digital modality can characterize mucosal patterns of the gastrointestinal mucosa in detail. Subtle abnormalities can, therefore, be recognized as either neoplastic or inflammatory. Hoffman et al (2) have tested the efficacy of high-definition endoscopy alone in comparison with i-Scan or chromoendoscopy with methylene blue (0.1%) in screening for colorectal cancer. They demonstrated that both i-Scan and chromoendoscopy identified more lesions compared with high-definition endoscopy alone. i-Scan was also able to predict neoplasia as precisely as chromoendoscopy, with an accuracy of 89% to 97%. Case Presentation A 50-year-old woman with persistent undiagnosed chronic watery diarrhea underwent colonoscopy, with random biopsies that were negative. Another colonoscopy was performed with iScan + chromoendoscopy with 0.2% indigo carmine to enhance mucosal surfaces and patterns, and to target biopsies in the colon. iScan 1 and iScan 2 showed irregularity of the colonic mucosal pattern, although the mucosa appeared normal with white-light endoscopy. iScan + chromoendoscopy with indigo carmine characterized, in detail, the mucosal pattern as nodularmosaic with a small honeycomb pit-pattern appearance (Figure 1). Such an appearance is characteristic of microscopic colitis. Targeted

Faecal S100A12 Concentrations Correlate with Mucosal Inflammation More Strongly Than Clinical Symptom Scores in Crohn and #8217;s Disease Patients and #8211; Results of the Novel Biomarkers in Inflammatory Bowel Disease (NBIBD) Project

Background Inflammatory bowel disease (IBD) lead to significant morbidity amongst the New Zealand population. The gold standard for assessing inflammation is colonoscopy but this is invasive and costly. Clinical assessment is subjective and may not reflect mucosal inflammation. The faecal biomarker, S100A12 has been shown to correlate with inflammation in paediatric patients. We aimed to correlate S100A12 concentration and symptom scores with mucosal appearances in IBD patients. Methods Patients with known/possible IBD provided faecal samples prior to colonoscopy. Concentrations of S100A12 and calprotectin were measured using validated ELISA methods. The endoscopic appearances were scored using the Simple Endoscopic Score for CD (SES) and the Rachmilewitz score for UC. Clinical symptom scores were calculated using the Harvey Bradshaw Index (HBI) for CD and the Simple Clinical Colitis Activity Index (SCCAI) for UC. Results 44 CD, 39 UC and 19 controls have currently been assessed. Using mucosal scores 10 CD and 9 UC patients had inactive disease. For CD, the HBI did not significantly correlate with SES (r=0.178, p=0.247). For UC, the SCCAI did correlate with the Rachmilewitz Index (r=0.529, p=0.001). S100A12 concentrations correlated significantly with SES (r=0.56, p=0.001) for CD, and the Rachmilewitz index (r=0.439, p=0.007) for UC. Concentrations of S100A12 were significantly correlated with calprotectin (r=0.798, p

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Induction of Clinical and Endoscopic Remission of Mild to Moderately Active Ulcerative Colitis With Budesonide MMX® 9 mg: Analysis of Pooled Data from Two Phase 3 Studies

Purpose: To evaluate the efficacy and safety of budesonide MMX® (B-MMX) 6 mg and 9 mg oral tablets in patients (pts) with active mild to moderate ulcerative colitis (UC), when administered for 8 weeks, compared to placebo (PBO). Methods: Pooled data from two Phase 3 studies evaluating patients achieving clinical and endoscopic remission with B-MMX 9 mg or 6 mg tablets once daily compared with PBO over an 8 week period were analyzed. The primary endpoint was induction of clinical and endoscopic remission; defined by strict criteria with a UCDAI score ≤1 after 8 weeks with scores of 0 for rectal bleeding and stool frequency, no mucosal friability after full colonoscopy, and a ≥1-point reduction from baseline in the endoscopic index score. Clinical improvement (≥3 point reduction in UCDAI), endoscopic improvement (≥1 point reduction in the UCDAI mucosal appearance subscore), and symptom resolution (score of 0 for rectal bleeding and stool frequency from UCDAI) were also evaluated at week 8. Results: 672 patients from the pooled modified intent-to-treat (mITT) population, which included randomized patients who received ≥1 dose of study drug, were treated with PBO, B-MMX 9 mg, or B-MMX 6 mg. The mITT population excluded patients without histological evidence of active disease at baseline or with major eligibility or GCP violations according to ICH E9 Guidelines. Clinical and endoscopic remission for B-MMX 9 mg vs. PBO was 17.7% vs. 6.2% (p=0.0002). Symptom resolution was 26.3% vs. 14.3%, respectively (p=0.0018). Clinical improvement and endoscopic improvement were both numerically greater for B-MMX 9 mg than PBO but not statistically different (Table). Treatment related adverse events, including potential glucocorticoid effects, occurred with similar frequencies across study groups.Table: No Caption available.Conclusion: Pooled data showed that B-MMX 9 mg given once daily is safe and effective for inducing clinical and endoscopic remission and symptom resolution in patients with mild to moderately active UC. Disclosure: Dr. Sandborn- Consultant: Cosmo Pharmaceuticals, Santarus Dr. Travis- Consultant: Cosmo Pharmaceuticals, Santarus Dr. Moro- Employee: Cosmo Pharmaceuticals, Dr. Bala- Investigator: Santarus Dr. Danese- Investigator: Cosmo Pharmaceuticals, Dr. Ballard- Employee: Santarus Dr. Bagin-Employee: Santarus Ms. Gautille- Employee: Santarus Dr. Huang- Employee: Santarus. This research was supported by an industry grant from Cosmo Pharmaceuticals and Santarus.