Kato Shigeru, Kawamura Junichiro, Kawada Kenji, Hasegawa Suguru, Sakai Yoshiharu
Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
J Surg Res. 2012 Aug;176(2):430-6. doi: 10.1016/j.jss.2011.10.031. Epub 2011 Nov 19.
Lymph node metastasis is one of the most critical prognostic factors in patients with colorectal cancer. Although regional lymph nodes should be surgically resected and pathologically examined, techniques for the intraoperative diagnosis of lymph node metastasis remain to be well established. Fluorescence diagnosis using 5-aminolevulinic acid (5-ALA) is a promising technique for evaluating various malignancies. After exogenous administration of 5-ALA, protoporphyrin IX (PPIX) accumulates in malignant cells and can be detected as red fluorescence. In this study, we investigated the usefulness of fluorescence diagnosis using 5-ALA for the detection of lymph node metastasis in a mouse model of colon cancer.
An orthotopic colon cancer model was prepared by inoculating the cecal wall of nude mice with HCA7, a human colon adenocarcinoma cell line. After 3 wk, 40 mg/kg of 5-ALA was administered intraperitoneally (IP) or orally (PO). Fluorescence diagnosis with a D-Light System (Karl Storz) was then performed after 3 or 6 h.
In the IP group, PPIX fluorescence was detected in metastatic lymph nodes as well as in other malignant lesions, including primary tumors and abdominal implantations, while non-metastatic nodes were fluorescence-negative. In contrast, no obvious fluorescence was detected in cancerous tissues in the PO group.
PPIX fluorescence induced by intraperitoneal injection of 5-ALA allows metastatic lymph nodes to be accurately diagnosed in this mouse model. This technique may facilitate the intraoperative diagnosis of lymph node metastases from colon cancer in a clinical setting.
淋巴结转移是结直肠癌患者最重要的预后因素之一。尽管区域淋巴结应进行手术切除并做病理检查,但术中诊断淋巴结转移的技术仍有待完善。使用5-氨基乙酰丙酸(5-ALA)进行荧光诊断是评估各种恶性肿瘤的一种有前景的技术。外源性给予5-ALA后,原卟啉IX(PPIX)在恶性细胞中蓄积,并可被检测为红色荧光。在本研究中,我们调查了使用5-ALA进行荧光诊断在结肠癌小鼠模型中检测淋巴结转移的有效性。
通过将人结肠腺癌细胞系HCA7接种到裸鼠盲肠壁制备原位结肠癌模型。3周后,腹腔内(IP)或口服(PO)给予40mg/kg的5-ALA。然后在3或6小时后使用D-Light系统(Karl Storz)进行荧光诊断。
在IP组中,在转移性淋巴结以及其他恶性病变(包括原发性肿瘤和腹部种植灶)中检测到PPIX荧光,而非转移性淋巴结荧光阴性。相比之下,PO组的癌组织中未检测到明显荧光。
腹腔注射5-ALA诱导的PPIX荧光可在该小鼠模型中准确诊断转移性淋巴结。该技术可能有助于在临床环境中对结肠癌淋巴结转移进行术中诊断。