Molecular diagnosis and translymphatic chemotherapy targeting sentinel lymph nodes of patients with early gastrointestinal cancers.
The sentinel lymph node (SLN) is defined as the lymph node(s) that first receives lymphatic drainage from the site of the primary tumor. Recent progress in molecular techniques has demonstrated the presence of micrometastatic tumor cells in SLNs. Quantitative real-time RT-PCR assay, which enables rapid analysis, is currently being undertaken for intraoperative molecular diagnosis of SLNs. We developed an intraoperative real-time RT-PCR assay to detect micrometastasis in SLNs for early gastric cancer. All SLNs and randomly selected non-SLNs in 96 cT1 or cT2 gastric cancer patients were biopsied intraoperatively and examined by routine hematoxylin and eosin staining, immunohistochemistry with anticytokeratin antibody (AE1/AE3), and multimarker real-time RT-PCR assay including cytokeratin (CK) 19, CK20, and carcinoembryonic antigen. All patients with histopathologically verified metastasis in their SLNs demonstrated positive results by RT-PCR assay. Forty percent of patients with histopathologically negative SLNs showed positive SLNs by RT-PCR assay. RT-PCR assay revealed that 4 patients (4%) with negative SLNs had positive non-SLNs; however, these positive non-SLNs were identified within each SLN basin. We recently developed a new drug delivery system targeting SLNs with a phospholipid polymer, using 2-methacryloyloxyethyl phosphorylcholine conjugated with paclitaxel. Our preliminary data suggest that this novel drug delivery system may be feasible for translymphatic chemotherapy targeting SLNs of patients with cN0 early gastrointestinal cancer, who have the potential for occult metastasis in SLNs. Endoscopic resection of the primary tumor followed by translymphatic chemotherapy targeting SLNs may become a promising minimally invasive multidisciplinary therapy.
Takeuchi
Hiroya
H
Department of Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan. htakeuch@sc.itc.keio.ac.jp
Ueda
Masakazu
M
Oyama
Takashi
T
Shimizu
Yoshimasa
Y
Kitagawa
Yuko
Y
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D004337:Drug Carriers; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008689:Methacrylates; D025202:Molecular Diagnostic Techniques; D017239:Paclitaxel / Q000008:administration & dosage*; D010767:Phosphorylcholine / Q000031:analogs & derivatives; D051381:Rats; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology*
D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D008689:Methacrylates; D010767:Phosphorylcholine; C079200:poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate); D017239:Paclitaxel