Beginner coagulators, tumor in the antrum, and medicines were significant risk factors for post-ESD bleeding. Bleeding at the ulcer margin frequently occurred with beginner operators.

Our training system enabled novice operators to perform gastric ESD without a decline in clinical outcomes. Key features of this training are prior intensive learning and actual ESD during the learning period under expert supervision.

Aberrant DNA methylation plays an important role in genesis of colorectal cancer (CRC). Previously, we identified Group 1 and Group 2 methylation markers through genome-wide DNA methylation analysis, and classified CRC and protruded adenoma into three distinct clusters: high-, intermediate-and low-methylation epigenotypes. High-methylation epigenotype strongly correlated with BRAF mutations and these aberrations were involved in the serrated pathway, whereas intermediate-methylation epigenotype strongly correlated with KRAS mutations. Here, we investigated laterally spreading tumors (LSTs), which are flat, early CRC lesions, through quantitative methylation analysis of six Group 1 and 14 Group 2 methylation markers using pyrosequencing. Gene mutations in BRAF, KRAS and PIK3CA, and immunostaining of TP53 and CTNNB1 as well as other clinicopathological factors were also evaluated. By hierarchical clustering using methylation information, LSTs were classified into two subtypes; intermediate-methylation epigenotype correlating with KRAS mutations (p 5 9 3 10 24 ) and a granular morphology (LST-G) (p 5 1 3 10 27 ), and low-methylation epigenotype correlating with CTNNB1 activation (p 5 0.002) and a nongranular morphology (LST-NG) (p 5 1 3 10 27 ). Group 1 marker methylation and BRAF mutations were barely detected, suggesting that high-methylation epigenotype was unlikely to be involved in LST development. TP53 mutations correlated significantly with malignant transformation, regardless of epigenotype or morphology type. Together, this may suggest that two molecular pathways, intermediate methylation associated with KRAS mutations and LST-G morphology, and low methylation associated with CTNNB1 activation and LST-NG morphology, might be involved in LST development, and that involvement of TP53 mutations could be important in both subtypes in the development from adenoma to cancer.Colorectal cancer (CRC) arises through accumulation of multiple genetic and epigenetic alterations. 1-3 Somatic mutations in KRAS, APC and TP53 are well-known genetic alterations, which were demonstrated in the model of adenoma-carcinoma sequence. 4 Recent exome sequencing studies revealed the involvement of somatic mutations of other genes, e.g., SMAD4, PIK3CA, TCF7L2, ARID1A and TET family genes, or amplification of ERBB2 and IGF2. 5,6 In addition, aberrant DNA methylation of gene promoters has been reported to be a major epigenetic mechanism for silencing tumor-suppressor genes involved in colorectal carcinogenesis. 2,7 We previously performed DNA methylation analysis of CRC on genome-wide scale and identified Group 1 and Group 2 methylation markers to classify CRC into three distinct subsets, 8,9 which has also been reported by other groups. [10][11][12] Highmethylation epigenotype [or CpG island methylator phenotype (CIMP) 13 ] showed methylation of both Group 1 and Group 2 markers, while intermediate-methylation epigenotype showed methylation of Group 2 but not Group 1 markers, and lowmethylation epigenotype showed methylation of neithe...

Background and study aims  Colorectal cancer (CRC) is one of the most common neoplasms and endoscopic submucosal dissection (ESD) is an effective treatment for early-stage CRC. However, it has been observed that patients undergoing ESD often complain of pain, even if ESD has been successfully performed. Risk factors for such pain still remain unknown. The aim of this study was to explore the risk factors for post-colorectal ESD coagulation syndrome (PECS). Patients and methods  This was a prospective multicenter observational trial (UMIN000016781) conducted in 106 of 223 patients who underwent ESD between March 2015 and April 2016. We investigated age, sex, tumor location, ESD operation time, lesion size, duration of hospitalization, and frequency of PECS. We defined PECS as local abdominal pain (evaluated on a visual analogue scale) in the region corresponding to the site of the ESD that occurred within 4 days of the procedure. Results  PECS occurred in 15/106 (14.2 %), and 10 were women ( P  = 0.01, OR: 7.74 [1.6 – 36.4]), 7 had lesions in the cecum ( P  < 0.001, OR: 20.6 [3.7 – 115.2]), and 9 in whom ESD operation time was > 90 min ( P  = 0.002, OR: 10.3 [2.4 – 44.6]). Frequency of deviation from the prescribed clinical path was significantly higher (47 % [7/15] vs. 2 % [2/91], P  < 0.001, OR: 38.9 [6.9 – 219.6]), and hospital stay was significantly longer in the PECS group.  Conclusions  Female gender, location of lesion in the cecum, and ESD operation time > 90 minutes were significant risk factors independent of PECS. These findings are important to management of PECS.

Although colorectal endoscopic submucosal dissection (ESD) is superior to endoscopic mucosal resection (EMR) in en bloc resection rate, it is technically quite difficult because of the anatomical and histological characteristics of the colorectal wall. This difficulty prevents wide spread of the technique. Establishment of the training system for colorectal ESD is necessary to standardize training and to achieve wider acceptance of this technique. Herein, we describe our training system for colorectal ESD, and assess the validity of the training system for colorectal ESD, based on the clinical outcomes and learning curve of trainees. Our training system for colorectal ESD would help the spread of this procedure.