Mitsuhiro Akita

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

OBJECTIVES:Accumulating evidence has underlined the importance of mucosal healing as a treatment goal for ulcerative colitis (UC). Quantitative fecal immunochemical tests (FITs), which can rapidly quantify fecal blood with automated equipment, have been used recently to screen for colorectal neoplasia. The aim of this study is to determine whether an FIT can evaluate mucosal healing in UC.METHODS:Feces collected from UC patients who underwent colonoscopy were examined by FITs, and results were compared with colonoscopic findings. Mucosal status was assessed using the Mayo endoscopic subscore classification. Maximum score for the colorectum in each patient was recorded.RESULTS:Evaluated were FIT results in conjunction with 310 colonoscopies that were performed in 152 UC patients. A large majority of patients with a Mayo 0 endoscopic score had negative FIT (<100 ng/ml) results (92%), and the proportion of negative FIT results decreased with increases in the Mayo score (Mayo 1: 47%, Mayo 2: 13%, Mayo 3: 12%, P<0.0001, Cochran-Armitage trend test). When the negative FIT was defined as <100 ng/ml, the sensitivity and specificity of a negative FIT for mucosal healing (Mayo 0) were 0.92 and 0.71, respectively. When mucosal healing was defined as Mayo 0 or 1, those were 0.60 and 0.87, respectively. In addition, a positive FIT (≥100 ng/ml) predicted mucosal inflammation (Mayo 2 or 3) with sensitivity 0.87 and specificity 0.60, respectively.CONCLUSIONS:The FIT can effectively and noninvasively evaluate mucosal healing in UC. This easy, rapid method can help evaluate and control disease activity of UC.

ADVANTAGES OF USING THIN ENDOSCOPE‐ASSISTED ENDOSCOPIC SUBMUCOSAL DISSECTION TECHNIQUE FOR LARGE COLORECTAL TUMORS

Background:  Our purpose was to evaluate the effectiveness of a newly developed non‐invasive traction technique known as thin endoscope‐assisted endoscopic submucosal dissection (TEA‐ESD) procedure for the removal of colorectal laterally spreading tumors (LST).

Prognosis of ulcerative colitis differs between patients with complete and partial mucosal healing, which can be predicted from the platelet count.

AIM To determine the difference in clinical outcome between ulcerative colitis (UC) patients with Mayo endoscopic subscore (MES) 0 and those with MES 1. METHODS UC patients with sustained clinical remission of 6 mo or more at the time of colonoscopy were examined for clinical outcomes and the hazard ratios of clinical relapse according to MES. Parameters, including blood tests, to identify predictive factors for MES 0 and slight endoscopic recurrence in clinically stable patients were assessed. Moreover, a receiver operating characteristic curve was generated, and the area under the curve was calculated to indicate the utility of the parameters for the division between complete and partial mucosal healing. All P values were two-sided and considered significant when less than 0.05. RESULTS A total of 183 patients with clinical remission were examined. Patients with MES 0 (complete mucosal healing: n = 80, 44%) were much less likely to relapse than those with MES 1 (partial mucosal healing: n = 89, 48%) (P < 0.0001, log-rank test), and the hazard ratio of risk of relapse in patients with MES 1 vs MES 0 was 8.17 (95%CI: 4.19-17.96, P < 0.0001). The platelet count (PLT) < 26 × 10(4)/μL was an independent predictive factor for complete mucosal healing (OR = 4.1, 95%CI: 2.15-7.99). Among patients with MES 0 at the initial colonoscopy, patients of whom colonoscopy findings shifted to MES 1 showed significant increases in PLT compared to those who maintained MES 0 (3.8 × 10(4)/μL vs -0.6 × 10(4)/μL, P < 0.0001). CONCLUSION The relapse rate differed greatly between patients with complete and partial mucosal healing. A shift from complete to partial healing in clinically stable UC patients can be predicted by monitoring PLT.

Analysis of K-ras, BRAF, and PIK3CA mutations in laterally-spreading tumors of the colorectum.

Background and Aims:  Laterally‐spreading tumors (LST) are a newly‐recognized category of colorectal neoplasia, and are defined as lesions larger than 10 mm in diameter and extending circumferentially rather than vertically. However, genetic features of this new category of tumors are not fully elucidated. The aim of this study was to evaluate genetic alterations in LST.

Long-term follow-up of ulcerative colitis patients treated on the basis of their cytomegalovirus antigen status

AIM To clarify the impact of cytomegalovirus (CMV) activation and antiviral therapy based on CMV antigen status on the long-term clinical course of ulcerative colitis (UC) patients. METHODS UC patients with flare-up were divided into CMV-positive and -negative groups according to the CMV antigenemia assay. The main treatment strategy provided for the patients in the CMV-positive group comprised a dose reduction of corticosteroids and administration of ganciclovir. RESULTS The median number of days to initial remission was significantly greater for the patients in the CMV-positive group (21 d vs 16 d, P = 0.009). However, the relapse rate after remission and colectomy rate during more than 30 mo of observation did not differ between the two groups. Multivariate analysis revealed that administration of ganciclovir was the only independent factor for avoiding colectomy in patients of the CMV-positive group. CONCLUSION CMV antigen status did not significantly affect the long-term prognosis in UC patients under treatment with appropriate antiviral therapy.

TOLERABILITY AND USEFULNESS OF MERCAPTOPURINE IN AZATHIOPRINE-INTOLERANT JAPANESE PATIENTS WITH ULCERATIVE COLITIS

Background and Aim:  Azathioprine (AZA) and mercaptopurine (6‐MP) are established as effective therapeutic drugs for the induction and maintenance of remission in patients with ulcerative colitis (UC). However, AZA is often intolerable due to adverse effects. Evidence regarding the approach of switching from AZA to 6‐MP in patients of Asian ethnicity is lacking. We assessed the tolerability and usefulness of 6‐MP in Japanese UC patients who had shown intolerance to AZA.

Clinical Features of Intestinal Behçet's Disease Associated with Myelodysplastic Syndrome and Trisomy 8

Several studies have identified a relationship between myelodysplastic syndrome and Behçets disease (BD), especially intestinal BD, and trisomy 8 appears to play an important role in these disorders. Despite this, only few case reports or series have been reported in gastroenterology, meaning that endoscopic findings and characteristics of intestinal BD have not been clarified yet. In this report, we describe three cases of intestinal BD associated with myelodysplastic syndrome and trisomy 8, and discuss the clinical features and problems of these disorders from a gastroenterology perspective.

Tu1228 Disparity in Clinical Care for Patients With Inflammatory Bowel Disease Between Specialists and Non-Specialists

Background: Although inflammatory bowel disease (IBD) patients have been increasing and new therapeutic options for IBD have been developed, there are relatively few clinicians who specialize in IBD. Patients treated by a non-specialist of IBD may not receive appropriate treatment. This study aimed to compare disease and medication status between IBD patients treated by a specialist and those treated by a non-specialist. Methods: Medical charts of ambulating IBD patients in two hospitals were examined. All patients in one hospital were treated by one of the IBD specialists, while in the other hospital, patients were treated by one of the gastroenterologists who was a non-specialist of IBD. Results: The numbers of IBD patients were 255 (hospital with specialists) and 74 (hospital without specialists), respectively. Disease activity of the patients was not well-controlled in the hospital without specialists compared to in the hospital with specialists (ulcerative colitis (UC): p = 0.0006 and Crohn’s disease: p = 0.012, respectively). The proportion of UC patients who received an insufficient dose of mesalazine (Pentasa < 3 g/day or Asacol < 3.6 g/day) was higher in the hospital without specialists (47% vs. 15%, p < 0.0001). In the hospital without specialists, more patients received long-term corticosteroids (UC: 23% vs. 5%, p < 0.0001), while fewer patients received immunomodulators (UC: 8% vs. 46%, p < 0.0001). Conclusions: IBD patients of the hospital without specialists were not well-controlled and were not prescribed appropriately with therapeutic drugs. Fostering and placement of the specialist of IBD is an urgent problem.

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 physicians 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

Do Smoking and Drinking Habits and Obesity Affect Prevalence of Colorectal Neoplasia in Patients With Positive Immunochemical Fecal Occult Blood Test

G A A b st ra ct s tertiary center. Prolonged SBTT was defined as >6 hours. Regional and whole gut transit times were analyzed. For pts with slow SBTT, average amplitude (AUC) and frequency of contractions (Ct) 60 minutes before and after gastric emptying (GET) were analyzed and compared to the pressure profile of 66 healthy controls. Results: 77 pts underwent WMC test due to upper GI symptoms and suspected GI dysmotility. Of those, 10 pts (13%) had SB motility disorder with isolated prolonged SBTT, but normal gastric and colon transit times. Mean SBTT was 461 min (360-600), significantly longer than normal (p=0.001). The CTT in this group was not significantly different from healthy subjects. There was a tendency to have longer, although normal, mean GET 239 min (p=0.04), compared to healthy subjects. Pressure data: no significant differences were found between pts with isolated slow SBTT and healthy controls in Ct and AUC. The clinical presentation of the pts with isolated SBTT delay was analyzed. Upper GI symptoms were the most common: upper abdominal pain and discomfort -80%, bloating60%, nausea-50%, early satiation-50%, fullness sensation40%, vomiting30%, weight loss30%, abdominal distention-30%, loss of appetite20%, constipation50%. Two pts had DM. In all pts, extensive GI work up, including GES in 2 pts, was unrevealing prior to the WMC test. Following documenting of slow SBTT, in 50% of pts new treatment was initiated -3 pts were treated with lubiprostone, 2 pts were treated for SIBO. Conclusions: SB transit delay might be the underlining pathophysiology for GI symptoms in a subset of pts. Postprandial symptoms are the most common. Evaluation of SBTT by WMC might be considered for patients with upper GI symptoms resembling gastroparesis, in whom no other abnormality of GI tract was identified. An abnormal SBTT could serve as a target for treatment if found.