Clinical Trials Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 7, 2015; 21(21): 6706-6712
Published online Jun 7, 2015. doi: 10.3748/wjg.v21.i21.6706
Preliminary study of photodynamic diagnosis using 5-aminolevulinic acid in gastric and colorectal tumors
Munetaka Nakamura, Jun Nishikawa, Kouichi Hamabe, Atsushi Goto, Junichi Nishimura, Hiroaki Shibata, Misato Nagao, Sho Sasaki, Shinichi Hashimoto, Takeshi Okamoto, Isao Sakaida
Munetaka Nakamura, Jun Nishikawa, Kouichi Hamabe, Atsushi Goto, Junichi Nishimura, Hiroaki Shibata, Misato Nagao, Sho Sasaki, Shinichi Hashimoto, Takeshi Okamoto, Isao Sakaida, Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan
Author contributions: Nishikawa J, Hamabe K and Sakaida I designed research; Nakamura M, Nishikawa J, Goto A, Nishimura J, Shibata H, Nagao M, Sasaki S, Hashimoto S and Okamoto T performed research; Nakamura M analyzed data; Nakamura M and Nishikawa J wrote the paper.
Ethics approval: The study was reviewed and approved by the Yamaguchi University Hospital Institutional Review Board.
Clinical trial registration: This study is registered at UMIN-CTR: http://www.umin.ac.jp/ctr/. The registration identification number is 000010086.
Informed consent: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest: All authors disclosed no financial relationships relevant to this publication.
Data sharing: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Jun Nishikawa, MD, PhD, Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-kogushi, Ube, Yamaguchi 755-8505, Japan. junnis@yamaguchi-u.ac.jp
Telephone: +81-836-222241 Fax: +81-836-222240
Received: December 22, 2014
Peer-review started: December 23, 2014
First decision: January 27, 2015
Revised: February 3, 2015
Accepted: March 19, 2015
Article in press: March 19, 2015
Published online: June 7, 2015
Abstract

AIM: To investigate the utility of photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5-ALA) to detect gastric/colorectal tumors.

METHODS: This prospective single-center study investigated inter-subject variability in patients with early-stage gastric/colorectal tumor indicated for endoscopic resection. Subjects were patients with gastric or colorectal tumors who had undergone endoscopic resection between November 2012 and November 2013. Selection criteria included age 20-80 years, either sex, and provision of informed consent. Patients were orally administered 20 mg/kg of 5-ALA enteric-coated capsules (SBI ALApromo Co., Tokyo, Japan). Administration of 5-ALA was followed by endoscopic resection of gastric or colorectal tumors, and the resected specimens were examined using a video autofluorescence processor and a fluorescence endoscope (SAFE-3000 and EB-1970AK, respectively; Pentax, Tokyo, Japan). The primary endpoint was the presence of fluorescence in tumors. Endoscopic, macroscopic, and histopathologic findings of tumors were assessed. We also evaluated adverse events of the present procedure as a secondary endpoint and examined each patient for the presence of known adverse effects of 5-ALA, namely, hematocytopenia, liver dysfunction, hypotension, nausea, and photosensitivity.

RESULTS: We enrolled 10 patients (7 men, 3 women) (n = 13 lesions: 10 gastric/3 colorectal tumors). Fluorescence was detected in 7/13 (53.8%) lesions. No significant differences in sex (male: 55.6% vs female: 50.5%, P = 1.00), age (67.1 ± 1.9 years vs 65.0 ± 2.0 years, P = 0.45), tumor color (reddish: 60.0% vs discolored: 33.3%, P = 0.56), tumor diameter (15.0 ± 2.1 mm vs 14.2 ± 2.3 mm, P = 0.80), macroscopic type (protruded: 70.0% vs depressed 0%, P = 0.07), histologic type (differentiated type: 58.3% vs 0%, P = 0.46), invasion depth (mucosal layer: 55.6% vs submucosal layer: 33.3%, P = 1.00), lymphatic invasion (present: 33.3% vs absent: 50.0%, P = 1.00), venous invasion (present: 0% vs absent: 54.5%, P = 1.00) or procedure time of endoscopic resection (36.3 ± 8.3 min vs 36.7 ± 9.0 min, P = 0.98) were observed between the patients with and without fluorescence. Fluorescence detection rate tended to be high for elevated lesions. Liver dysfunction developed in 4/10 (40.0%) patients. The extent of the liver dysfunction was a slight increase in transaminases and total bilirubin levels, which spontaneously improved in the patients. None of the patients developed photosensitivity.

CONCLUSION: Results of this preliminary study suggest the utility of PDD using 5-ALA for screening of gastric and colorectal cancers.

Keywords: Photodynamic diagnosis, 5-aminolevulinic acid, Protoporphyrin IX, Gastric tumor, Colorectal tumor

Core tip: We took advantage of the high tumor specificity of fluorescent protoporphyrin IX to conduct this preliminary study to apply photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5-ALA) for gastrointestinal endoscopy. This study of PDD using 5-ALA showed the presence of fluorescence in early gastric cancers. This is the first study using enteric capsules for administration of 5-ALA. The findings in this study suggest that PDD with the oral administration of 5-ALA is useful and safe for the screening of early gastric and colorectal cancers.