Photodynamic diagnosis of pleural malignant lesions with a combination of 5-aminolevulinic acid and intrinsic fluorescence observation systems - PubMed (original) (raw)

Photodynamic diagnosis of pleural malignant lesions with a combination of 5-aminolevulinic acid and intrinsic fluorescence observation systems

Masahiro Kitada et al. BMC Cancer. 2015.

Abstract

Background: We have developed a new diagnostic method using the photosensitizer 5-aminolevulinic acid (5ALA) for diagnosing intrathoracic malignant lesions. When ingested exogenously, 5ALA is metabolized to a heme precursor, protoporphyrin IX, which stays in malignant cells and emits red to pink luminescence of about 630 nm.

Methods: We enrolled 40 patients who underwent respiratory surgery and consented to participate in this study. Twenty-eight patients had primary lung cancer, 8 metastatic lung tumors, 2 malignant pleural tumors, and 2 benign tumors. Localization of malignant lesions was attempted by observing such lesions with an autofluorescence imaging system and by comparing the color tone of the autofluorescence between malignant lesions and normal tissues after oral administration of 5ALA. Malignant lesions on the pleural surface emitted pink autofluorescence in contrast to the green autofluorescence of the surrounding normal tissues.

Results: When 28 patients with primary lung cancer were examined according to the degree of pleural infiltration (pl), red fluorescence was confirmed in 10 of 10 patients (100%) with p11-p13 and 5 of 18 patients (27.7%) with p10. The latter 5 patients had been diagnosed with PL1 preoperatively or intraoperatively.

Conclusion: This system achieved accurate localization of malignant lesions, suggesting that it may also be applicable to photodynamic therapy.

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Figures

Figure 1

Figure 1

The principle of autofluorescence observation. Normal tissue: In response to blue excitation rays of approximately 400–450 nm, green autofluorescence of approximately 520 nm is observed. Malignant Lesion: Autofluorescence is reduced due to thickening of the mucosal epithelium, decrease in autofluorescent substances, an increase in fluorescence absorbing substances, etc., causing the color spectrum of emitted fluorescence to shift.

Figure 2

Figure 2

The autofluorescence observation system. A small CCD camera is attached to the endoscopic color fluorescence system PDS-2000, to enable white light and autofluorescence to be observed via a filter. The color fluorescence camera is equipped with a thoracoscope using the Olympus endoscopic system attachment.

Figure 3

Figure 3

The metabolic pathway of 5ALA. Exogenous 5ALA is ingested and promptly metabolized to heme in normal cells. In contrast, the fluorescent substance protoporphyrin IX accumulates selectively in cancer cells, emitting red to pink fluorescence of about 630 nm, because cancer cells have high porphobilinogen deaminase activity and low ferrochelatase activity.

Figure 4

Figure 4

Lung cancer (a pl1 case). The tumor emits red light, whereas normal tissue shows green autofluorescence, providing clear borders demarcating the tumor from surrounding tissues.

Figure 5

Figure 5

Malignant Pleural Mesothelioma. Red light is seen on the parietal pleural surface, consistent with the tumor.

Figure 6

Figure 6

Metastatic pulmonary tumor from renal cell carcinoma. The tumor, although very small, emits red light, whereas normal tissue shows green autofluorescence.

Figure 7

Figure 7

Lung Cancer (a pleural dissemination case). Disseminated lesions were detected during surgery under the preoperative diagnosis of a clinical T2N0 lesion. Red light is present in the area of pleural dissemination, whereas no color change is seen in the area of fibrous pleural thickening.

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