Taro Osada

Endoscopic submucosal dissection of large colorectal tumors by using a novel spring-action S-O clip for traction (with video)

BACKGROUND Endoscopic submucosal dissection (ESD) allows en bloc resection of large GI neoplasms, regardless of their size; however, technical difficulties associated with ESD in the colorectum make it less widely applied in the treatment of tumors in this region. To address this difficulty, we designed a rubber strip-based traction device, called the S-O clip (Sakamoto-Osada clip) and reported previously that ESD with this device was effective for complete resection of large, superficial colorectal neoplasms. In this report, we describe a novel spring-action version of the S-O clip (spring S-O clip) that improves the facility of clip use during ESD of colorectal tumors. OBJECTIVE To evaluate the efficacy and safety of the spring S-O clip for ESD of colorectal neoplasms. DESIGN Case series. SETTING Juntendo University Hospital. MAIN OUTCOME MEASUREMENTS The efficacy and safety of the spring S-O clip traction device during ESD of colorectal tumors. RESULTS In 3 cases, a large, superficial neoplasm in the right side of the colon was removed safely and successfully en bloc without complication. Procedure times for the 3 cases were 44, 27, and 49 minutes, with resected specimens measuring 40, 24, and 35 mm, respectively. LIMITATION Uncontrolled study. CONCLUSION This limited case series demonstrates that spring S-O clip-assisted ESD is safe and effective for en bloc resection of large superficial neoplasms in the right side of the colon.

Correlations among total colonoscopic findings, clinical symptoms, and laboratory markers in ulcerative colitis

Background and Aim:  Colonoscopy plays an integral role in the diagnosis, management and surveillance of ulcerative colitis (UC). In the present study we assessed the relationship between endoscopic and histological findings, clinical symptoms, and laboratory data.

Increased esophageal sensitivity to acid and saline in patients with nonerosive gastro-esophageal reflux disease

Goals To investigate the features of nonerosive reflux disease (NERD). Background NERD is not considered as a milder form of erosive gastro-esophageal reflux disease (eGERD). Although the prevalence of NERD was reported to be high in our country, there have been very few studies about NERD. Study We performed upper gastrointestinal endoscopy to confirm the diagnosis of GERD. The modified acid perfusion test and saline perfusion test were performed in 7 control subjects, 14 NERD, and 11 eGERD patients. The stimulus-response function to acid and saline was quantified by the duration of typical symptom perception (minutes), total sensory intensity rating (0 to 10), and the perfusion sensory score (SS), which was defined as the product of minutes and the sensory intensity rating. Results The mean value of SS by saline was 0 in control subjects, 12.0 in NERD patients, and 1.5 in eGERD patients (P<0.01 control vs. NERD, P<0.01 NERD vs. eGERD). The mean SS with acid was 0.9 in control subjects, 52.5 in NERD patients, and 23.0 in eGERD patients (P<0.01 control vs. NERD, control vs. eGERD, P<0.05 NERD vs. eGERD). A statistically significant association was shown between the acid and saline perfusion SSs with a correlation coefficient value of r=0.57 in the NERD group (P<0.05). Conclusions Both eGERD and NERD, but especially NERD, exhibited esophageal hypersensitivity not only to acid but also saline perfusion, suggesting that hyperalgesia to acid and other factors (eg, psychologic and/or autonomic nerve disturbance) may play some roles in symptom generation in NERD.

Comparison of several activity indices for the evaluation of endoscopic activity in UC: inter- and intraobserver consistency.

Background: This study evaluated inter‐ and intraobserver agreement in the assessment of ulcerative colitis (UC) activity using 4 established indices and a newly designed Modified 6‐point Activity Index. Method: In all, 279 endoscopic pictures of inflammatory lesions from 93 UC patients were displayed twice to 4 expert and 4 trainee endoscopists, at an interval of 1 month. Each picture was assessed for inflammatory changes using established indices (Matts, Schroeder [a.k.a. Mayo Score], Baron, and Blackstone) and our new Modified 6‐point Activity Index. Weighted kappa statistics were used to estimate intra‐ and interobserver variation. Results: The Matts and Schroeder indices gave a “good” degree of concordance for expert endoscopists in terms of inter‐ and intraobserver agreements (0.74–0.78); this was not so evident with the Baron and Blackstone indices (0.61–0.73). For trainee endoscopists, all scores for inter‐ and intraobserver weighted kappa values using established indices (0.41–0.51) were lower than for the experts. The degree of concordance using the Modified 6‐point Activity Index was rated as “good” for inter‐ and intraobserver agreements for expert endoscopists (0.65 and 0.79), and as “moderate” for trainee endoscopists (0.54 and 0.64). Conclusions: Accurate assessment of UC disease activity from endoscopic findings benefited from experience. For expert endoscopists, the Matts and Schroeder indices proved the most reliable of the 4 established indices. Current endoscopic technologies may be adequate for assessing UC activity, particularly if modified to permit a finer classification of disease severity based on 6 grades, as with our newly developed Modified 6‐point Activity Index. (Inflamm Bowel Dis 2009;)

Overexpression of a 60-kDa heat shock protein enhances cytoprotective function of small intestinal epithelial cells.

AIMS With the advancement of small intestinal (double balloon and capsule) endoscopy technology, incidence of small intestinal lesion caused by nonsteroidal anti-inflammatory drugs (NSAIDs) has been known to be high. However, therapy for small intestinal mucosal lesion has not yet been developed. Previous studies have shown that heat shock proteins (HSPs) are involved in cytoprotection mediated by their function as a molecular chaperone. In this study, we examined the effect of HSP60 or HSP70 overexpression on hydrogen peroxide-induced (H2O2) or indomethacin-induced cell damage in the small intestinal epithelial cells. MAIN METHODS cDNA of human HSP60 or HSP70 was transfected to rat small intestinal (IEC-6) cells, and HSP60- or HSP70-overexpressing cells were cloned. IEC-6 cells transfected with vector only were used as control cells. These cells were treated with H2O2 (0-0.14mM) or indomethacin (0-2.5mM). The cell viability was determined by MTT-assay. Cell necrosis was evaluated by LDH-release assay. Further, apoptosis was evaluated by caspases-3/7 activity and TUNEL assay. KEY FINDINGS Cell viability after H2O2 or indomethacin treatment was significantly higher in HSP60-overexpressing cells compared with that in control cells and HSP60-overexpressing cells. Apoptotic cells were also reduced in HSP60-overexpressing. CONCLUSION These results indicate that HSP60 plays an important role in protecting small intestinal mucosal cells from H2O2-induced or indomethacin-induced cell injury. HSP70-overexpressing cells did not show anti-apoptotic ability. SIGNIFICANCE These findings possibly suggest that function of each HSP is different in the small intestine. Therefore, for the therapy of small intestinal mucosal lesion, HSP60-induction therapy could be a new therapeutic strategy.

MAIT cells are activated and accumulated in the inflamed mucosa of ulcerative colitis

Ulcerative colitis (UC) is a chronic, relapsing and remitting, inflammatory disorder of the large intestine. Mucosal associated invariant T (MAIT) cells are a member of innate‐like lymphocytes found abundantly in the mucosal tissue. The contribution of MAIT cells in the pathogenesis of UC is still unclear; therefore, this study aimed at investigating the role of these cells in patients with UC.

Effect of a gastro-protective agent, rebamipide, on symptom improvement in patients with functional dyspepsia: a double-blind placebo-controlled study in Japan.

Background and Aim:  Although mucosal protective agents have been used frequently for treatment of symptomatic gastritis, there has been no well‐controlled study of functional dyspepsia. The aim of this study was to assess the efficacy of a 4‐week treatment with rebamipide for the relief of overall dyspeptic symptoms and the improvement in quality of life from an untreated baseline in Japanese patients with functional dyspepsia.

Phase I clinical trial of peptide vaccination with URLC10 and VEGFR1 epitope peptides in patients with advanced gastric cancer

Peptide vaccine treatment has attracted attention in recent years as a new therapy option for chemotherapy-resistant, advanced, unresectable cancer. The safety of peptide vaccination with HLA-A*2402-restricted URLC10-A24-177 and VEGFR1-A12-9 1084 epitope peptides (fixed 2-mg dose) was investigated in a phase I clinical trial of patients with advanced gastric cancer who were refractory to chemotherapy. We determined the HLA genotype of the subjects after enrollment, results of which were held by the evaluation committee and kept from both patients and investigators until completion of the study. The primary end-point was safety of the peptide vaccination. The secondary end-points were immunological responses and clinical outcome, which were compared between the HLA-A*2402-positive and HLA-A*2402-negative groups. The peptides were subcutaneously administered on day 1, 8, 15 and 22 within a 28-day treatment cycle. A total of 14 patients was enrolled in this study; 12 of the 14 patients received 4 or more vaccinations (at least 1 course). No patient had a severe treatment-related adverse event. Findings from evaluation of clinical responses after a single course showed that 4 cases had stable disease and 8 cases had progressive disease. The median overall survival time (MST) for the 12 patients was 3.9 months. The MSTs in the HLA-A*2402-positive and HLA-A*2402-negative groups were, 4.2 and 3.6 months (p= 0.9164), respectively. The results of this study showed that vaccination with URLC10 and VEGFR1 peptides was a safe treatment for advanced gastric cancer. This trial was registered with University Hospital Medical Information Network (UMIN, no. 000002409).

Factors associated with incomplete colonoscopy at a Japanese academic hospital

AIM To evaluate significant risk factors for incomplete colonoscopy at a Japanese academic hospital. METHODS A total of 11812 consecutive Japanese people were identified who underwent a colonoscopy at an academic hospital. A multiple logistic regression model was used to evaluate retrospectively the significant risk factors for incomplete colonoscopy. RESULTS The cecal intubation rate was 95.0%. By univariate analysis, age, female sex, poor bowel cleansing, and a history of abdominal or pelvic surgery were significant risk factors for incomplete colonoscopy (P < 0.001). Moreover, age- and sex-adjusted analysis showed that significant risk factors for incomplete colonoscopy were female sex (OR = 1.38, 95%CI: 1.17-1.64, P = 0.0002), age ≥ 60 years old (OR = 1.44, 95%CI: 1.22-1.71, P < 0.0001), a history of prior abdominal or pelvic surgery (OR = 1.55, 95%CI: 1.28-1.86, P < 0.0001), poor bowel cleansing (OR = 4.64, 95%CI: 3.69-5.84, P < 0.0001), and inflammatory bowel disease (IBD) (OR = 1.48, 95%CI: 1.13-1.95, P = 0.0048). In Japanese men, by age-adjusted analysis, IBD (OR = 1.69, 95%CI: 1.18-2.43, P = 0.005) was an independent risk factor for incomplete colonoscopy. CONCLUSION Several characteristics in the Japanese population were identified that could predict technical difficulty with colonoscopy.

Usefulness of flexible spectral imaging color enhancement for the detection and diagnosis of small intestinal lesions found by capsule endoscopy

Abstract Objective. Capsule endoscopy (CE) is an established technique for the detection and diagnosis of obscure gastrointestinal bleeding (OGIB). Flexible spectral imaging color enhancement (FICE) is a software feature of RAPID 6.5. This study assessed the value of FICE for accurate identification of red lesions during CE. Methods. We randomly selected 10 patients who underwent CE for OGIB at Juntendo University. The CE images were read by five endoscopists. Small bowel videos, which were recorded by regular CE devices (PillCam SB2, Given Imaging), were evaluated on RAPID 6.5. We standardized the reading condition to a dual view, at a speed of 20 frames/s in manual mode. This interpreted FICE-CE images obtained at settings 1–3. Both conventional and FICE images were read at random. We defined a conventional image as standard and investigated the potential of FICE in detecting small intestinal lesions by the Steel–Dwass test. Results. We considered that conventional images represented baseline (100). On this basis, detection rates for FICE images were as follows: FICE1 = 266.4 ± 33.1 (p < 0.0001); FICE2 = 255.4 ± 25.6 (p < 0.0001); and FICE3 = 117.0 ± 12.3 (p = 0.9447). Detection rates using FICE1 and FICE2 images were significantly higher than conventional CE images. FICE1 and FICE2 were more useful in detecting erosions than conventional CE (p < 0.0001) and FICE3 (p < 0.0001). Conclusions. FICE-CE has a high level of visibility by transparentizing bile or enhancing the color difference associated with reddish mucosa. We found that FICE-CE images were useful in the diagnosing of small intestinal lesions.