Exploratory analyses of factors related to 5-aminolevulinic acid-induced intraoperative hypotension during malignant glioma surgery via literature review

Background: Photodynamic diagnosis using 5-aminolevulinic acid (5ALA) improves glioma resection but has been associated with intraoperative hypotension (IOH), particularly in Japan. Although nitric oxide (NO) production has been suggested as a mechanism, the pathophysiology remains unclear. Methods:...

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Main Authors: Kyoichi Tomoto, Akihiko Teshigawara, Tomohiro Aoki, Masahiko Itani, Yuzuru Hasegawa, Yuichi Murayama, Toshihide Tanaka
Format: Article
Language:English
Published: Elsevier 2025-10-01
Series:Photodiagnosis and Photodynamic Therapy
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Online Access:http://www.sciencedirect.com/science/article/pii/S1572100025002078
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author Kyoichi Tomoto
Akihiko Teshigawara
Tomohiro Aoki
Masahiko Itani
Yuzuru Hasegawa
Yuichi Murayama
Toshihide Tanaka
author_facet Kyoichi Tomoto
Akihiko Teshigawara
Tomohiro Aoki
Masahiko Itani
Yuzuru Hasegawa
Yuichi Murayama
Toshihide Tanaka
author_sort Kyoichi Tomoto
collection DOAJ
description Background: Photodynamic diagnosis using 5-aminolevulinic acid (5ALA) improves glioma resection but has been associated with intraoperative hypotension (IOH), particularly in Japan. Although nitric oxide (NO) production has been suggested as a mechanism, the pathophysiology remains unclear. Methods: We retrospectively analyzed 148 glioma patients who underwent surgery between 2015 and 2024, comparing 5ALA(+) and 5ALA(-) groups in terms of IOH incidence and potential contributing factors, including age, body mass index, antihypertensive drug use, anesthesia duration, and extent of resection. IOH was defined as a mean arterial pressure <60 mmHg after induction. We also assessed phosphorylation of endothelial NO synthase (eNOS) in surgical specimens using immunofluorescence. Results: IOH occurred in 88.9 % of the 5ALA(+) group and 82.9 % of the 5ALA(-) group (p = 0.296). Elderly patients (>60 years old) and those using angiotensin II receptor blockers (ARBs) showed significantly higher IOH incidence in the 5ALA(+) group. Immunofluorescence revealed no detectable phospho-eNOS expression in tumor tissues, regardless of IOH presence. Conclusions: Our findings confirm previously reported risk factors for 5ALA-induced IOH, including older age and ARB use. The lack of eNOS expression in glioma tissues suggests that systemic, rather than tumoral, endothelial responses may mediate IOH via heme-dependent NO synthesis. Further studies using non-tumor tissues or experimental models are needed to elucidate the precise mechanisms and potential interactions between ARBs and 5ALA metabolism.
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spelling doaj-art-8ff496c4bf6b4b8a93f2b357c145ff7b2025-08-20T03:41:43ZengElsevierPhotodiagnosis and Photodynamic Therapy1572-10002025-10-015510467510.1016/j.pdpdt.2025.104675Exploratory analyses of factors related to 5-aminolevulinic acid-induced intraoperative hypotension during malignant glioma surgery via literature reviewKyoichi Tomoto0Akihiko Teshigawara1Tomohiro Aoki2Masahiko Itani3Yuzuru Hasegawa4Yuichi Murayama5Toshihide Tanaka6Department of Neurosurgery, Kameda Medical Center, 929, Higashi-cho, Kamogawa, Chiba, Japan; Department of Neurosurgery, The Jikei University Kashiwa Hospital, 163-1, Kashiwashita, Kashiwa, Chiba, JapanDepartment of Neurosurgery, The Jikei University Kashiwa Hospital, 163-1, Kashiwashita, Kashiwa, Chiba, JapanDepartment of Pharmacology, The Jikei University School of Medicine, 3-25-8, Nishi-shimbashi, Minato-ku, Tokyo, JapanDepartment of Pharmacology, The Jikei University School of Medicine, 3-25-8, Nishi-shimbashi, Minato-ku, Tokyo, JapanDepartment of Neurosurgery, The Jikei University Kashiwa Hospital, 163-1, Kashiwashita, Kashiwa, Chiba, JapanDepartment of Neurosurgery, The Jikei University School of Medicine, 3-25-8, Nishi-shimbashi, Minato-ku, Tokyo, JapanDepartment of Neurosurgery, The Jikei University Kashiwa Hospital, 163-1, Kashiwashita, Kashiwa, Chiba, Japan; Department of Neurosurgery, The Jikei University School of Medicine, 3-25-8, Nishi-shimbashi, Minato-ku, Tokyo, Japan; Corresponding author at: The Jikei University School of Medicine, 3-25-8, Nishi-shimbashi, Minato-ku, Tokyo 105-8461, Japan.Background: Photodynamic diagnosis using 5-aminolevulinic acid (5ALA) improves glioma resection but has been associated with intraoperative hypotension (IOH), particularly in Japan. Although nitric oxide (NO) production has been suggested as a mechanism, the pathophysiology remains unclear. Methods: We retrospectively analyzed 148 glioma patients who underwent surgery between 2015 and 2024, comparing 5ALA(+) and 5ALA(-) groups in terms of IOH incidence and potential contributing factors, including age, body mass index, antihypertensive drug use, anesthesia duration, and extent of resection. IOH was defined as a mean arterial pressure <60 mmHg after induction. We also assessed phosphorylation of endothelial NO synthase (eNOS) in surgical specimens using immunofluorescence. Results: IOH occurred in 88.9 % of the 5ALA(+) group and 82.9 % of the 5ALA(-) group (p = 0.296). Elderly patients (>60 years old) and those using angiotensin II receptor blockers (ARBs) showed significantly higher IOH incidence in the 5ALA(+) group. Immunofluorescence revealed no detectable phospho-eNOS expression in tumor tissues, regardless of IOH presence. Conclusions: Our findings confirm previously reported risk factors for 5ALA-induced IOH, including older age and ARB use. The lack of eNOS expression in glioma tissues suggests that systemic, rather than tumoral, endothelial responses may mediate IOH via heme-dependent NO synthesis. Further studies using non-tumor tissues or experimental models are needed to elucidate the precise mechanisms and potential interactions between ARBs and 5ALA metabolism.http://www.sciencedirect.com/science/article/pii/S15721000250020785-aminolevulinic acidIntraoperative hypotensionGlioma surgeryNitric oxidePhotodynamic Diagnosis
spellingShingle Kyoichi Tomoto
Akihiko Teshigawara
Tomohiro Aoki
Masahiko Itani
Yuzuru Hasegawa
Yuichi Murayama
Toshihide Tanaka
Exploratory analyses of factors related to 5-aminolevulinic acid-induced intraoperative hypotension during malignant glioma surgery via literature review
Photodiagnosis and Photodynamic Therapy
5-aminolevulinic acid
Intraoperative hypotension
Glioma surgery
Nitric oxide
Photodynamic Diagnosis
title Exploratory analyses of factors related to 5-aminolevulinic acid-induced intraoperative hypotension during malignant glioma surgery via literature review
title_full Exploratory analyses of factors related to 5-aminolevulinic acid-induced intraoperative hypotension during malignant glioma surgery via literature review
title_fullStr Exploratory analyses of factors related to 5-aminolevulinic acid-induced intraoperative hypotension during malignant glioma surgery via literature review
title_full_unstemmed Exploratory analyses of factors related to 5-aminolevulinic acid-induced intraoperative hypotension during malignant glioma surgery via literature review
title_short Exploratory analyses of factors related to 5-aminolevulinic acid-induced intraoperative hypotension during malignant glioma surgery via literature review
title_sort exploratory analyses of factors related to 5 aminolevulinic acid induced intraoperative hypotension during malignant glioma surgery via literature review
topic 5-aminolevulinic acid
Intraoperative hypotension
Glioma surgery
Nitric oxide
Photodynamic Diagnosis
url http://www.sciencedirect.com/science/article/pii/S1572100025002078
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