Intraoperative photodynamic diagnosis of lymph node metastasis in esophageal cancer patients using 5-aminolevulinic acid

Abstract

Abstract. Lymph node metastasis is the strongest prognostic factor in esophageal cancer patients who have undergone esophagectomy. The accurate diagnosis of lymph node metastasis is important, but the pre-operative diagnostic accuracy is poor. The intraoperative diagnosis based on histopathological examination of frozen tissue specimens is complicated and time-consuming. Therefore, the establishment of a simple and rapid intraoperative diagnostic method is essential. Exogenous application of 5-aminolevulinic acid (ALA) causes a selective accumulation of protoporphyrin IX, which is a fluorescent substrate, in cancer cells. The present study evaluated the feasibility of photodynamic diagnosis using ALA (ALA-PDD) for lymph node metastasis in esophageal cancer. A total of 292 lymph nodes were analyzed from 8 esophageal squamous cell cancer patients treated with esophagectomy. The patients were administered ALA orally prior to surgery. Excised lymph nodes were cut in half and examined by spectrometer. The diagnostic results of ALA-PDD were compared to those of the histopathological examination. Among the 292 lymph nodes, 19 nodes (6.5%) were histologically metastatic and 21 nodes (7.2%) were PDD-positive. The sensitivity and specificity of ALA-PDD were 84.2% (16/19) and 98.2% (268/273), respectively. The area of cancer nests of the PDD-negative lymph nodes was <2 mm 2 . Metastatic lymph nodes, including cancer nests >4 mm 2 , were correctly diagnosed by ALA-PDD. In conclusion, this study demonstrated that ALA-PDD of lymph node metastasis in patients with esophageal cancer is feasible. Further investigation would make this method a simple and rapid intraoperative diagnostic tool.

5-aminolevulinic acid (5-ALA) fluorescence-guided Mohs surgery resection of penile-scrotal extramammary Paget's disease

“…In contrast, the fluorescence of the tumor tissue is intense and sharply demarcated. When using 5-aminolevulinic acid (5-ALA)-mediated Photodynamic diagnosis (PDD), many studies have obtained better results (24)(25)(26)(27)(28).…”

Targeted Photodynamic Diagnosis and Therapy for Esophageal Cancer: Potential Role of Functionalized Nanomedicine

“…The application of PDD can allow easy visualization and identification of cancer cells, thereby facilitating prompt diagnosis and optimal prognosis [22]. The conventional photosensitizer used in PDD of esophageal cancer includes 5-aminolevulinic acid (5-ALA), indocyanine green, and methylene blue [23][24][25].…”

“…The classic photosensitizer used in PDD of esophageal cancer consists of 5-aminolevulinic acid (5-ALA), indocyanine green, and methylene blue [23][24][25]. Among these photosensitizers, 5-ALA has attracted much attention as a promising agent for PDD in identifying cancer sites.…”

“…5-ALA has been employed for PDD of various cancers such as bladder cancer [35], gastric cancer [36], and malignant glioma [37], as well as in esophageal cancer; this is due to its ability to fluorescence when activated within the visible blue and red light wavelength. It has minimal skin photosensitivity and absence of stricture [23,[38][39][40].…”

A next-generation bifunctional photosensitizer with improved water-solubility for photodynamic therapy and diagnosis

“…In recent years, Talaporfin sodium (TS), a second-generation photosensitizer in Japan, has been widely taken up for clinical use due to its improved water solubility and excretion [ 19 , 20 ]; however, TS has not yet replaced the ‘gold standard’ for PDT. Furthermore, in the field of PDD, almost all reports cite 5-ALA because it specifically visualizes some tumors and has few side effects [ 9 , 10 , 13 , 21 , 22 ].…”