Int. J. Mol. Sci. 2013, 14(11), 23140-23152; doi:10.3390/ijms141123140
Article

Detection of Lymph Node Metastases in Human Colorectal Cancer by Using 5-Aminolevulinic Acid-Induced Protoporphyrin IX Fluorescence with Spectral Unmixing

1 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 2 Division of Digestive Surgery, Department of Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho Hirokoji Kawaramachi, Kamigyo-ku, Kyoto 602-8566, Japan 3 Department of Surgical Pathology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho Hirokoji Kawaramachi, Kamigyo-ku, Kyoto 602-8566, Japan
* Author to whom correspondence should be addressed.
Received: 30 September 2013; in revised form: 8 November 2013 / Accepted: 12 November 2013 / Published: 21 November 2013
(This article belongs to the Special Issue Frontiers of Micro-Spectroscopy in Biological Applications)
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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.
Keywords: colorectal cancer; 5-aminolevulinic acid; lymph node metastasis; spectral unmixing; protoporphyrin IX

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MDPI and ACS Style

Harada, K.; Harada, Y.; Beika, M.; Koizumi, N.; Inoue, K.; Murayama, Y.; Kuriu, Y.; Nakanishi, M.; Minamikawa, T.; Yamaoka, Y.; Dai, P.; Yanagisawa, A.; Otsuji, E.; Takamatsu, T. Detection of Lymph Node Metastases in Human Colorectal Cancer by Using 5-Aminolevulinic Acid-Induced Protoporphyrin IX Fluorescence with Spectral Unmixing. Int. J. Mol. Sci. 2013, 14, 23140-23152.

AMA Style

Harada K, Harada Y, Beika M, Koizumi N, Inoue K, Murayama Y, Kuriu Y, Nakanishi M, Minamikawa T, Yamaoka Y, Dai P, Yanagisawa A, Otsuji E, Takamatsu T. Detection of Lymph Node Metastases in Human Colorectal Cancer by Using 5-Aminolevulinic Acid-Induced Protoporphyrin IX Fluorescence with Spectral Unmixing. International Journal of Molecular Sciences. 2013; 14(11):23140-23152.

Chicago/Turabian Style

Harada, Kenichi; Harada, Yoshinori; Beika, Masatomo; Koizumi, Noriaki; Inoue, Koji; Murayama, Yasutoshi; Kuriu, Yoshiaki; Nakanishi, Masayoshi; Minamikawa, Takeo; Yamaoka, Yoshihisa; Dai, Ping; Yanagisawa, Akio; Otsuji, Eigo; Takamatsu, Tetsuro. 2013. "Detection of Lymph Node Metastases in Human Colorectal Cancer by Using 5-Aminolevulinic Acid-Induced Protoporphyrin IX Fluorescence with Spectral Unmixing." Int. J. Mol. Sci. 14, no. 11: 23140-23152.

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