Motoaki Kuriyama

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.

Methylation status of normal background mucosa is correlated with occurrence and development of neoplasia in the distal colon

The aim of this study is to evaluate the methylation status of normal colonic mucosa in relation to the stage of neoplasia arising from the mucosa. The methylation status of 2 age-related loci (ESR1 and MYOD1) and global methylation (the mean of Alu and Sat2) in the normal colonic mucosa of 156 patients with and without colorectal neoplasia were examined. The distal colon and proximal colon were analyzed separately because neoplasia is biologically and clinically different between these sites. The methylation status was determined by MethyLight using percentage of methylated reference (PMR). In the distal colon, methylation of the age-related loci decreased as the stage of neoplasia increased (patients with no neoplasia or with adenoma < or =9 mm versus patients with advanced adenoma or with invasive cancer: ESR1-PMR median, 21.0 versus 15.7; P = .015; MYOD1-PMR median, 5.35 versus 3.80; P = .0037, respectively). Interestingly, global methylation was inversely correlated with the stage of neoplasia (59.7 versus 61.5; P = .054). In contrast, the proximal colon showed no significant correlations. The methylation of MYOD1 in the normal mucosa was significantly correlated with K-ras mutation in neoplastic tissue arising from the mucosa. Specific epigenetic changes in normal colonic mucosa may be correlated with the occurrence and development of neoplasia in the distal colon.

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).

Risk Factors and Indications for Colectomy in Ulcerative Colitis Patients are Different According to Patient’s Clinical Background

PurposeDespite progress in medical treatment for ulcerative colitis, a considerable fraction of ulcerative colitis patients undergo colectomy. We analyzed the clinical variables of ulcerative colitis patients and determined the risk factors and indications for colectomy.MethodsThe clinical records of 981 consecutive Japanese patients with ulcerative colitis were reviewed both retrospectively and prospectively.ResultsOf 981 patients with ulcerative colitis, 85 patients underwent colectomy. Multivariate analysis indicated that male gender (risk ratio, 2.16; 95 percent confidence interval, 1.37–3.42), onset year during and after 2000 (risk ratio, 2.85; 95 percent confidence interval, 1.31–6.22), severe disease activity (risk ratio, 2; 95 percent confidence interval, 1.15–3.48), corticosteroid resistance (risk ratio, 7.05; 95 percent confidence interval, 4.29–11.59), and complications because of corticosteroid administration (risk ratio, 3.55; 95 percent confidence interval, 2.08–6.06) were significant risk factors for colectomy. In patients with disease duration of more than five years, only corticosteroid resistance and complications because of corticosteroid were significant risk factors for colectomy. When we stratified indications for colectomy for the 85 cases via patient disease duration, massive hemorrhage was a relatively frequent cause of colectomy in patients with a disease duration of less than five years (P = 0.091). On the other hand, colon dysplasia or cancer was a major cause for colectomy in patients with a disease duration of more than ten years (P = 0.0001).ConclusionsIn ulcerative colitis patients, the risk factors and indications for colectomy were different according to the patients clinical background. Our findings may help to predict patients with ulcerative colitis who have a high risk for colectomy.

Specific gastroduodenoscopic findings in Crohn's disease: Comparison with findings in patients with ulcerative colitis and gastroesophageal reflux disease.

BACKGROUND Crohns disease patients often carry gastroduodenal lesions. However, few reports have addressed specific gastroduodenoscopic findings in Crohns disease patients. METHODS The gastroduodenoscopic findings of 63 Crohns disease patients were examined. Those of 62 ulcerative colitis and 63 age- and gender-matched gastroesophageal reflux disease patients were also reviewed as controls. Findings of bamboo-joint-like appearance, gastric antral erosions, and duodenal lesions were the specific findings that were highlighted. RESULTS Of 63 Crohns disease patients, 47 (75%) had at least one of the specific gastroduodenoscopic findings, and the prevalence of these findings was significantly higher in Crohns disease patients than in ulcerative colitis and gastroesophageal reflux disease patients (ulcerative colitis, 24/62, 39%; gastroesophageal reflux disease, 15/63, 24%, P < 0.0001). In particular, bamboo-joint-like appearance was almost unique to Crohns disease patients (Crohns disease, 28/63, 44%; ulcerative colitis, 3/62, 5%; gastroesophageal reflux disease, 0/63, 0%, P < 0.0001). Analysis of the relationship between the Crohns disease patients background and gastrodunodenoscopic findings revealed that both patients with disease affecting the ileum and those with previous gut operations were more likely to exhibit the specific gastroduodenoscopic findings (P = 0.030 and P = 0.043, respectively). CONCLUSION Specific gastroduodenoscopic findings were observed in Crohns disease patients. In particular, bamboo-joint-like appearance could be a unique marker of Crohns disease.

Combination of Sigmoidoscopy and a Fecal Immunochemical Test to Detect Proximal Colon Neoplasia

BACKGROUND & AIMS The combination of sigmoidoscopy and a sensitive fecal occult blood test was recommended as one strategy for colorectal cancer screening by the US Preventive Services Task Force in 2008. However, there have been no studies to evaluate the sensitivity of a one-time screen that uses both flexible sigmoidoscopy and a fecal immunochemical test (FIT) to detect advanced colorectal neoplasia. METHODS We analyzed data from 21,794 asymptomatic persons who had undergone colonoscopy and a FIT. Analyses were performed with the following assumptions: colonoscopy would be performed for any positive FIT result; colonoscopy would be performed if the FIT result was negative and if advanced neoplasia was detected in the rectosigmoid (or plus descending) colon. The sensitivities and specificities of the combination of sigmoidoscopy and the FIT in detecting advanced neoplasia in the proximal colon were determined. RESULTS When colonoscopy was performed for a positive FIT result alone, for a positive sigmoidoscopy finding, and for a positive FIT result or sigmoidoscopy finding, the sensitivities in detection of advanced proximal neoplasia were 22.3%, 16.3%, and 31.7%, respectively. The sensitivities for detection of proximal invasive cancer were 58.3%, 8.3%, and 62.5%, respectively. CONCLUSIONS The combination of sigmoidoscopy and FIT can detect advanced proximal neoplasia better than either test alone. The incremental yield of advanced neoplasm detection by a screening program that uses both a FIT and sigmoidoscopy is approximately 10%. The FIT adds the most in terms of finding proximal cancers in a screening program that uses both tests. The combination of sigmoidoscopy and FIT is a viable and useful screening option.

Is sigmoidoscopy sufficient for evaluating inflammatory status of ulcerative colitis patients

Background and Aims:  An adequate range of colonic observations for precise evaluation of inflammation in ulcerative colitis (UC) patients has not been reported.

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.

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.

Ratio of Platelet Reduction is an Early Predictive Factor for the Effectiveness of Leukocytapheresis for Ulcerative Colitis Patients

Abstract:  Leukocytapheresis is effective for ulcerative colitis (UC), and both peripheral leukocyte and platelet counts decrease during apheresis. While leukocyte counts increase and overshoot after finishing the apheresis procedure, platelet reduction continues even after apheresis. The aim of this study is to elucidate the impact of the overshoot of leukocyte and continuous platelet reduction on the efficacy of leukocytapheresis for UC. Leukocyte and platelet counts before and one hour after each leukocytapheresis session of 43 UC cases were examined (31 entered remission, but 12 did not). The correlation between the efficacy of leukocytapheresis and leukocyte overshoot or platelet reduction was examined. The average increase ratio of leukocytes in the initial five sessions of the responders was not significantly different from that of the non‐responders (95% vs. 92%, P = 0.28). In contrast, the average decrease ratio of platelets in the initial five sessions of the responders was significantly higher than that of the non‐responders (34% vs. 27%, P = 0.0041). Moreover, the platelet reduction at the third and fourth apheresis sessions in the responders was remarkably greater than that in the non‐responders (33% vs. 20%, P = 0.0018). The efficiency of platelet reduction could be a predictive factor for the efficacy of leukocytapheresis.