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

Kitada M, Ohsaki Y, Matsuda Y, Hayashi S, Ishibashi K - BMC Cancer (2015)

Bottom Line: Malignant lesions on the pleural surface emitted pink autofluorescence in contrast to the green autofluorescence of the surrounding normal tissues.The latter 5 patients had been diagnosed with PL1 preoperatively or intraoperatively.This system achieved accurate localization of malignant lesions, suggesting that it may also be applicable to photodynamic therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory Center, Asahikawa Medical University, Midorigaoka-Higashi 2-1-1-1, Asahikawa, Hokkaido, 078-8510, Japan. k1111@asahikawa-med.ac.jp.

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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Related in: MedlinePlus

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.
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Fig1: 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.

Mentions: Autofluorescence is spontaneous emission of fluorescence that occurs when biological structures such as mitochondria and lysosomes absorb light. The sources of autofluorescence in human tissues are collagen and fibronectin, in addition to nicotinamide-adenine dinucleotide phosphate and flavin-adenine dinucleotide [6,7]. In normal tissues, green autofluorescence of about 520 nm can be observed in response to blue excitation rays of 400–450 nm. In contrast, in cancer lesions, green autofluorescence is reduced, or the color tone of the emitted fluorescence is changed, due to thickening of the mucosal epithelium, a decrease in autofluorescent substances, or an increase in fluorescence-absorbing substances (Figure 1). The autofluorescence observation system allows autofluorescence to be observed by visualizing decreases or changes in the wavelengths of the fluorescence, and this system has already been applied clinically in the field of bronchoscopy. In this study, we endeavored to establish a method for the diagnosis of intrathoracic malignant lesions using a thoracoscope (rigid scope) equipped with the autofluorescence imaging system. The autofluorescence imaging system used in this study was shown to be an improved color fluorescence system, the PDS-2000 (Hamamatsu Photonics, Shizuoka, Japan) equipped with a small charge-coupled device (CCD) camera, allowing the observation of white light and autofluorescence via a filter [8,9]. A thoracoscope was attached to the color fluorescence camera, using an Olympus endoscopic system attachment. In addition, the LED light source, which can emit an excitation wavelength of light with a peak at 420 nm, was used (Figure 2).Figure 1


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

Kitada M, Ohsaki Y, Matsuda Y, Hayashi S, Ishibashi K - BMC Cancer (2015)

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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4374504&req=5

Fig1: 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.
Mentions: Autofluorescence is spontaneous emission of fluorescence that occurs when biological structures such as mitochondria and lysosomes absorb light. The sources of autofluorescence in human tissues are collagen and fibronectin, in addition to nicotinamide-adenine dinucleotide phosphate and flavin-adenine dinucleotide [6,7]. In normal tissues, green autofluorescence of about 520 nm can be observed in response to blue excitation rays of 400–450 nm. In contrast, in cancer lesions, green autofluorescence is reduced, or the color tone of the emitted fluorescence is changed, due to thickening of the mucosal epithelium, a decrease in autofluorescent substances, or an increase in fluorescence-absorbing substances (Figure 1). The autofluorescence observation system allows autofluorescence to be observed by visualizing decreases or changes in the wavelengths of the fluorescence, and this system has already been applied clinically in the field of bronchoscopy. In this study, we endeavored to establish a method for the diagnosis of intrathoracic malignant lesions using a thoracoscope (rigid scope) equipped with the autofluorescence imaging system. The autofluorescence imaging system used in this study was shown to be an improved color fluorescence system, the PDS-2000 (Hamamatsu Photonics, Shizuoka, Japan) equipped with a small charge-coupled device (CCD) camera, allowing the observation of white light and autofluorescence via a filter [8,9]. A thoracoscope was attached to the color fluorescence camera, using an Olympus endoscopic system attachment. In addition, the LED light source, which can emit an excitation wavelength of light with a peak at 420 nm, was used (Figure 2).Figure 1

Bottom Line: Malignant lesions on the pleural surface emitted pink autofluorescence in contrast to the green autofluorescence of the surrounding normal tissues.The latter 5 patients had been diagnosed with PL1 preoperatively or intraoperatively.This system achieved accurate localization of malignant lesions, suggesting that it may also be applicable to photodynamic therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory Center, Asahikawa Medical University, Midorigaoka-Higashi 2-1-1-1, Asahikawa, Hokkaido, 078-8510, Japan. k1111@asahikawa-med.ac.jp.

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.

Show MeSH
Related in: MedlinePlus