Keiko Yamamoto1, Shunsuke Ohnishi2, Takeshi Mizushima3, Junichi Kodaira4, Masayoshi Ono5, Yutaka Hatanaka6, Kanako C Hatanaka6, Yugo Kuriki7, Mako Kamiya7, Nobuyuki Ehira3, Keisuke Shinada8, Hiroaki Takahashi4, Yuichi Shimizu1, Yasuteru Urano7,9, Naoya Sakamoto10. 1. Division of Endoscopy, Hokkaido University Hospital, N14, W5, Kita-ku, Sapporo, 060-8648, Japan. 2. Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, N15, W7, Kita-ku, Sapporo, 060-8638, Japan. sonishi@pop.med.hokudai.ac.jp. 3. Department of Gastroenterology, Japanese Red Cross Kitami Hospital, N6, E2, Kitami, 090-8666, Japan. 4. Department of Gastroenterology, Keiyukai Daini Hospital, N3-7-1, Hondori, Shiroishi-ku, Sapporo, 003-0027, Japan. 5. Department of Gastroenterology, Hakodate Municipal Hospital, 10-1, Minato-cho 1, Hakodate, 041-8680, Japan. 6. Department of Surgical Pathology, Hokkaido University Hospital, N14, W5, Kita-ku, Sapporo, 060-8648, Japan. 7. Laboratory of Chemical Biology and Molecular Imaging, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. 8. Department of Gastroenterology, Keiwakai Ebetsu Hospital, Ebetsu, 81-81-6, Yoyogi-cho, Ebetsu, 069-0817, Japan. 9. Japan Agency for Medical Research and Development (AMED)-CREST, 7-1 Ootemachi-1, Chiyoda-ku, Tokyo, 100-0004, Japan. 10. Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, N15, W7, Kita-ku, Sapporo, 060-8638, Japan.
Abstract
BACKGROUND: It is still difficult to detect and diagnose early adenocarcinoma of the esophagogastric junction (EGJ) using conventional endoscopy or image-enhanced endoscopy. A glutamylprolyl hydroxymethyl rhodamine green (EP-HMRG) fluorescent probe that can be enzymatically activated to become fluorescent after the cleavage of a dipeptidyl peptidase (DPP)-IV-specific sequence has been developed and is reported to be useful for the detection of squamous cell carcinoma of the head and neck, and esophagus; however, there is a lack of studies that focuses on detecting EGJ adenocarcinoma by fluorescence molecular imaging. Therefore, we investigated the visualization of early EGJ adenocarcinoma by applying EP-HMRG and using clinical samples resected by endoscopic submucosal dissection (ESD). METHODS: Fluorescence imaging with EP-HMRG was performed in 21 clinical samples resected by ESD, and the fluorescence intensity of the tumor and non-tumor regions of interest was prospectively measured. Immunohistochemistry was also performed to determine the expression of DPP-IV. RESULTS: Fluorescence imaging of the clinical samples showed that the tumor lesions were visualized within a few minutes after the application of EP-HMRG, with a sensitivity, specificity, and accuracy of 85.7, 85.7, and 85.7%, respectively. However, tumors with a background of intestinal metaplasia did not have a sufficient contrast-to-background ratio since complete intestinal metaplasia also expresses DPP-IV. Immunohistochemistry measurements revealed that all fluorescent tumor lesions expressed DPP-IV. CONCLUSIONS: Fluorescence imaging with EP-HMRG could be useful for the detection of early EGJ adenocarcinoma lesions that do not have a background of intestinal metaplasia.
BACKGROUND: It is still difficult to detect and diagnose early adenocarcinoma of the esophagogastric junction (EGJ) using conventional endoscopy or image-enhanced endoscopy. A glutamylprolyl hydroxymethyl rhodamine green (EP-HMRG) fluorescent probe that can be enzymatically activated to become fluorescent after the cleavage of a dipeptidyl peptidase (DPP)-IV-specific sequence has been developed and is reported to be useful for the detection of squamous cell carcinoma of the head and neck, and esophagus; however, there is a lack of studies that focuses on detecting EGJ adenocarcinoma by fluorescence molecular imaging. Therefore, we investigated the visualization of early EGJ adenocarcinoma by applying EP-HMRG and using clinical samples resected by endoscopic submucosal dissection (ESD). METHODS: Fluorescence imaging with EP-HMRG was performed in 21 clinical samples resected by ESD, and the fluorescence intensity of the tumor and non-tumor regions of interest was prospectively measured. Immunohistochemistry was also performed to determine the expression of DPP-IV. RESULTS: Fluorescence imaging of the clinical samples showed that the tumor lesions were visualized within a few minutes after the application of EP-HMRG, with a sensitivity, specificity, and accuracy of 85.7, 85.7, and 85.7%, respectively. However, tumors with a background of intestinal metaplasia did not have a sufficient contrast-to-background ratio since complete intestinal metaplasia also expresses DPP-IV. Immunohistochemistry measurements revealed that all fluorescent tumor lesions expressed DPP-IV. CONCLUSIONS: Fluorescence imaging with EP-HMRG could be useful for the detection of early EGJ adenocarcinoma lesions that do not have a background of intestinal metaplasia.
Entities:
Keywords:
Adenocarcinoma of the esophagogastric junction; Dipeptidyl peptidase-IV; Fluorescence imaging