title: Detection of lymph node metastases in human colorectal cancer by using 5-aminolevulinic acid-induced protoporphyrin IX fluorescence with spectral unmixing.
abstract: Accurate evaluation of metastatic lymph nodes (LNs) is indispensable for adequate treatment of colorectal cancer (CRC) patients. Here, we demonstrate detection of metastases of human CRC in removed fresh LNs using 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence. A spectral unmixing method was employed to reduce the overlap of collagen autofluorescence on PpIX fluorescence. A total of 17 surgery patients with advanced CRC were included in this study. After 5-ALA at a dose of 15 mg/kg of body weight was applied orally 2 h prior to surgery, 87 LNs were subjected to spectral fluorescence imaging and histopathological diagnosis, and statistical analysis was performed. No apparent side effect was observed to be associated with 5-ALA administration. The spectral unmixing fluorescence intensity of PpIX in metastatic LNs was 10.2-fold greater than that in nonmetastaic LNs. The receiver-operating-characteristic (ROC) analysis showed that the area under the curve (AUC) was calculated as 0.95. Our results show the potential of 5-ALA-induced PpIX fluorescence processed by spectral unmixing for detecting metastases in excised fresh LNs from patients with CRC, suggesting that this rapid and feasible method is applicable to gross evaluation of resected LN samples in pathology laboratories.
authors.affiliation: Department of Pathology and Cell Regulation, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho Hirokoji Kawaramachi, Kamigyo-ku, Kyoto 602-8566, Japan. yoharada@koto.kpu-m.ac.jp.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Harada
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Harada
authors.forename: Masatomo
authors.initials: M
authors.lastname: Beika
authors.forename: Noriaki
authors.initials: N
authors.lastname: Koizumi
authors.forename: Koji
authors.initials: K
authors.lastname: Inoue
authors.forename: Yasutoshi
authors.initials: Y
authors.lastname: Murayama
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kuriu
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Nakanishi
authors.forename: Takeo
authors.initials: T
authors.lastname: Minamikawa
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Yamaoka
authors.forename: Ping
authors.initials: P
authors.lastname: Dai
authors.forename: Akio
authors.initials: A
authors.lastname: Yanagisawa
authors.forename: Eigo
authors.initials: E
authors.lastname: Otsuji
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Takamatsu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000622:Aminolevulinic Acid / Q000737:chemistry / Q000494:pharmacology; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000473:pathology / Q000601:surgery*; D005260:Female; D005453:Fluorescence; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology / Q000601:surgery; D008207:Lymphatic Metastasis / Q000175:diagnosis* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011524:Protoporphyrins / Q000737:chemistry
chemical_list: D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX