Department of Pathology and Cell Regulation, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Ann Surg Oncol. 2013 Oct;20(11):3541-8. doi: 10.1245/s10434-013-3017-3. Epub 2013 Jul 12.
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.
准确诊断淋巴结转移对于胃癌患者的治疗策略选择至关重要，术中快速诊断有助于实施微创性手术。本研究聚焦于一种已知的光敏剂——5-氨基酮戊酸（5-ALA），并研究了 5-ALA 诱导的原卟啉 IX（PpIX）荧光在检测胃癌患者切除淋巴结中转移灶的可行性。
本研究共纳入 14 例胃癌患者的 144 枚淋巴结。患者术前口服 5-ALA。切除的淋巴结被对半切开，并通过荧光显微镜进行观察。将诊断结果与常规组织病理学检查进行比较。
PpIX 的红色荧光与转移灶完全一致，准确率为 84%。12 枚无转移的淋巴结出现了意外的 PpIX 向淋巴滤泡聚集，但可以根据其特征性荧光模式进行区分。将这种形态学考虑纳入其中，该方法的准确率高达 92.4%。利用红色与红、绿、蓝（R/(R+G+B) 比值）信号强度比值作为 PpIX 红色荧光的指标进行定量分析，转移性淋巴结的比值明显高于非转移性淋巴结（p<0.0001）。整个受试者工作特征分析的曲线下面积为 0.832。
我们的研究结果表明，5-ALA 诱导的荧光诊断是一种简单、安全的方法，有望成为一种新的适用于临床实践的快速术中诊断方法。
