Detection of Metastatic Lymph Nodes Using 5-Aminolevulinic Acid in Patients with Gastric Cancer

Abstract

Precise diagnosis of lymph node metastases is essential to select therapeutic strategy for patients with gastric cancer, and rapid intraoperative diagnosis is useful for performing less invasive surgery. In this study, we focused on a known photosensitizer, 5-aminolevulinic acid (5-ALA), and examined the feasibility of 5-ALA-induced protoporphyrin IX (PpIX) fluorescence to detect metastatic foci in excised lymph nodes of patients with gastric cancer. A total of 144 lymph nodes obtained from 14 gastric cancer patients were examined. The patients were administered 5-ALA orally before surgery. Excised lymph nodes were cut in half and observed by fluorescence microscopy. The diagnostic results were compared to those of the routine histopathological examination. Observed red fluorescence of PpIX was identical to the metastatic focus, with 84% accuracy. Twelve non-metastatic lymph nodes showed unexpected PpIX accumulation to lymphoid follicles, but these could be discriminated based on their characteristic fluorescence patterns. With incorporation of this morphological consideration, this method demonstrated good diagnostic power with 92.4% accuracy. On the quantitative analysis using the signal intensity ratio of red to the sum of red, green, and blue (R/(R+G+B) ratio) as an index corresponding to red fluorescence of PpIX, metastatic lymph nodes showed significantly higher value than non-metastatic lymph nodes (p<0.0001). The area under the curve was calculated as 0.832 throughout Receiver operating characteristic analysis. Our results demonstrated that 5-ALA-induced fluorescence diagnosis is a simple and safe method and is a potential candidate for a novel rapid intraoperative diagnostic method applicable to clinical practice.