Colorectal endoscopic submucosal dissection (ESD) has become common in recent years. Suitable lesions for endoscopic treatment include not only early colorectal carcinomas but also many types of precarcinomatous adenomas. It is important to establish practical guidelines in which the preoperative diagnosis of colorectal neoplasia and the selection of endoscopic treatment procedures are properly outlined, and to ensure that the actual endoscopic treatment is useful and safe in general hospitals when carried out in accordance with the guidelines. In cooperation with the Japanese Society for Cancer of the Colon and Rectum, the Japanese Society of Coloproctology, and the Japanese Society of Gastroenterology, the Japan Gastroenterological Endoscopy Society has recently compiled a set of colorectal ESD/endoscopic mucosal resection (EMR) guidelines using evidence-based methods. The guidelines focus on the diagnostic and therapeutic strategies and caveat before, during, and after ESD/EMR and, in this regard, exclude the specific procedures, types and proper use of instruments, devices, and drugs. Although eight areas, ranging from indication to pathology, were originally planned for inclusion in these guidelines, evidence was scarce in each area. Therefore, grades of recommendation were determined largely through expert consensus in these areas.

Suitable lesions for endoscopic treatment include not only early colorectal carcinomas but also several types of precarcinomatous adenomas. It is important to establish practical guidelines wherein preoperative diagnosis of colorectal neoplasia and selection of endoscopic treatment procedures are appropriately outlined and to ensure that actual endoscopic treatment is useful and safe in general hospitals when carried out in accordance with guidelines. In cooperation with the Japanese Society for Cancer of the Colon and Rectum, the Japanese Society of Coloproctology, and the Japanese Society of Gastroenterology, the Japan Gastroenterological Endoscopy Society compiled colorectal endoscopic submucosal dissection/endoscopic mucosal resection guidelines by using evidence‐based methods in 2014. The first edition of these guidelines was published 5 years ago. Accordingly, we have published the second edition of these guidelines based on recent new knowledge and evidence.

Only a few cases of gastric adenocarcinoma of fundic gland type have been reported. Gastric adenocarcinoma with chief cell differentiation (GA-CCD) has been recently reported as a new variant of gastric adenocarcinoma. However, its clinicopathologic features are uncertain. To elucidate them, GA-CCDs exhibiting pepsinogen-I expression (10 lesions: Group A) and randomly selected gastric adenocarcinomas of differentiated type (111 lesions: Group B) were evaluated in this study. Cell differentiation by MUC2, MUC5AC, MUC6, CD10, pepsinogen-I, H+/K+-ATPase and chromogranin A, cell proliferation by Ki-67, and overexpression of p53 protein were evaluated immunohistochemically. In Group A, all GA-CCDs were located in the upper third of the stomach. Tumors were small, with the average maximum diameter ranging from 4 to 20 (average, 8.6) mm. Histologically, GA-CCDs were well-differentiated adenocarcinomas composed of pale gray-blue, basophilic columnar cells with mild nuclear atypia, resembling chief cells. Immunohistochemically, scattered positivity for H+/K+-ATPase was observed in addition to expression of pepsinogen-I and MUC6, indicating focal differentiation toward parietal cells. In Group B, pepsinogen-I was very focally expressed in 2 cases. As these 2 cases exhibited different clinicopathological and histologic features, they cannot be categorized as GA-CCD. Mild atypism, no lymphovascular invasion, low proliferative activity, no overexpression of p53, and no recurrence indicated less aggressiveness of GA-CCD. GA-CCD is rare, but it has distinct clinicopathological characteristics, especially in terms of tumor location, histologic features, phenotypic expression, and low-grade malignancy. We propose gastric adenocarcinoma of fundic gland type (chief cell predominant type) as a new entity of gastric adenocarcinoma.

Extragastrointestinal stromal tumor (EGIST) is a unique tumor that occurs outside the gastrointestinal tract. EGIST shows a c-kit expression and histologic appearance similar to those of gastrointestinal stromal tumor (GIST). Most GISTs have gain-of-functional mutation of the c-kit gene, and some have mutation of the platelet-derived growth factor receptor-alpha (PDGFRA) gene. However, the frequency of mutation of those genes in EGISTs remains unclear. We examined the clinicopathologic features, prognostic factors, and c-kit and PDGFRA mutation in 39 cases of EGIST. Tumors with high mitotic counts (>or=5/50 high power fields) or a high Ki-67 labeling index (>or=10%) were significantly correlated with worse prognoses. The c-kit mutation was found in the juxtamembrane domain (exon 11) and the extracellular domain (exon 9) in 12 of 29 cases (41.4%) and 2 of 29 cases (6.9%), respectively. The PDGFRA gene mutation was found at the juxtamembrane domain (exon 12) and the tyrosine kinase domain (exon 18) in one case each. The pattern of kit and PDGFRA mutation in EGIST was essentially similar to that in GIST. Our results suggest that the c-kit and PDGFRA mutations play an important role in the tumorigenesis of EGIST. High mitotic counts and a high Ki-67 labeling index may be useful for predicting the aggressive biologic behavior in EGIST. Furthermore, STI-571, targeting c-kit and PDGFR tyrosine kinase, seems to be a possible therapeutic strategy for EGISTs, especially advanced cases.

Abstract. Histone deacetylase (HDAC) activity is one of the widely used and well-established mechanisms for regulation of various genes in cancer. To identify which subtype of class I HDACs are overexpressed in cancers, we analyzed the expression of class I HDAC isotypes composed of HDAC1, 2, 3 and 8 in several cell lines and human cancer tissues, including cancer of the stomach, esophagus, colon, prostate, breast, ovary, lung, pancreas and thyroid. The results showed that >75% of human cancer tissues and their corresponding non-cancerous epithelium showed high expression of these class I HDACs. However, the immunoreactivity of HDAC8 in both prostatic cancer tissue and non-cancerous prostate glands was lower than that in other cancer tissues. Furthermore, 5-40% of cancer tissues overexpressed class I HDACs, when compared with normal epithelium. The results suggest the potential usefulness of HDAC inhibitors for the treatment of a wide variety of human cancers.