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Review article
peer-reviewed
2 Place Winner

Intraoperative Photodynamic Surgery (iPDS) with Acridine Orange for Musculoskeletal Sarcomas



Abstract

We recently established the new limb salvage modality of acridine orange (AO) therapy (AOT), in an attempt to develop minimally invasive limb salvage surgery with minimal damage of normal tissues and a low risk of local recurrence. The treatment modality consists of intraoperative photodynamic surgery (iPDS) and photodynamic therapy (iPDT), followed by postoperative radiodynamic therapy (RDT) using AO for patients with high-grade malignant musculoskeletal sarcomas. Clinical results have shown that the treatment is associated with a low risk of local recurrence, the risk being almost the same as that following conventional wide resection, and yields superior limb function as compared to that obtained after wide resection.

In this review, we present the detailed mechanism of selective accumulation of AO in sarcomas, which is related to the acidic environment and lysosomal acidity of the tumor cells induced by cancer-specific glycolysis not involving the define tricarboxylic acid (TCA) cycle (Warburg’s effect). We also describe the clinical uses of AOT and the procedure for intraoperative photodynamic surgery (iPDS) using local administration of AO. 



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Review article
peer-reviewed

Intraoperative Photodynamic Surgery (iPDS) with Acridine Orange for Musculoskeletal Sarcomas


Author Information

Katsuyuki Kusuzaki Corresponding Author

Department of Orthopaedic Surgery, Kyoto Kujo Hospital

Takao Matsubara

Department of Orthopaedic Surgery, Mie University Graduate School of Medicine

Haruhiko Satonaka

Department of Orthopaedic Surgery, Mie University Graduate School of Medicine

Akihiko Matsumine

Department of Orthopaedic Surgery, Mie University Graduate School of Medicine

Tomoki Nakamura

Department of Orthopaedic Surgery, Mie University Graduate School of Medicine

Akihiro Sudo

Department of Orthopaedic Surgery, Mie University Graduate School of Medicine

Hiroaki Murata

Department of Orthopaedic Surgery, Matsushita Memorial Hospital

Shigekuni Hosogi

Department of Biomedical and Neuromotor Sciences, University of Bologna

Nicola Baldini

Department of Biomedical and Neuromotor Sciences, University of Bologna


Ethics Statement and Conflict of Interest Disclosures

Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: Animal studies were supported and verified by Grants-in-Aid 08877235, 12470312, 11877256 for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.


Review article
peer-reviewed

Intraoperative Photodynamic Surgery (iPDS) with Acridine Orange for Musculoskeletal Sarcomas


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Review article
peer-reviewed
2 Place Winner

Intraoperative Fluorescence Research

Intraoperative Photodynamic Surgery (iPDS) with Acridine Orange for Musculoskeletal Sarcomas

Katsuyuki Kusuzaki">Katsuyuki Kusuzaki , Takao Matsubara">Takao Matsubara, Haruhiko Satonaka">Haruhiko Satonaka, Akihiko Matsumine">Akihiko Matsumine, Tomoki Nakamura">Tomoki Nakamura, Akihiro Sudo">Akihiro Sudo, Hiroaki Murata">Hiroaki Murata, Shigekuni Hosogi">Shigekuni Hosogi, Nicola Baldini">Nicola Baldini

  • Author Information
    Katsuyuki Kusuzaki Corresponding Author

    Department of Orthopaedic Surgery, Kyoto Kujo Hospital

    Takao Matsubara

    Department of Orthopaedic Surgery, Mie University Graduate School of Medicine

    Haruhiko Satonaka

    Department of Orthopaedic Surgery, Mie University Graduate School of Medicine

    Akihiko Matsumine

    Department of Orthopaedic Surgery, Mie University Graduate School of Medicine

    Tomoki Nakamura

    Department of Orthopaedic Surgery, Mie University Graduate School of Medicine

    Akihiro Sudo

    Department of Orthopaedic Surgery, Mie University Graduate School of Medicine

    Hiroaki Murata

    Department of Orthopaedic Surgery, Matsushita Memorial Hospital

    Shigekuni Hosogi

    Department of Biomedical and Neuromotor Sciences, University of Bologna

    Nicola Baldini

    Department of Biomedical and Neuromotor Sciences, University of Bologna


    Ethics Statement and Conflict of Interest Disclosures

    Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: Animal studies were supported and verified by Grants-in-Aid 08877235, 12470312, 11877256 for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

    Acknowledgements


    Article Information

    Published: September 15, 2014

    DOI

    10.7759/cureus.204

    Cite this article as:

    Kusuzaki K, Matsubara T, Satonaka H, et al. (September 15, 2014) Intraoperative Photodynamic Surgery (iPDS) with Acridine Orange for Musculoskeletal Sarcomas . Cureus 6(9): e204. doi:10.7759/cureus.204

    Publication history

    Received by Cureus: July 13, 2014
    Peer review began: July 14, 2014
    Peer review concluded: September 10, 2014
    Published: September 15, 2014

    Copyright

    © Copyright 2014
    Kusuzaki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License CC-BY 3.0., which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

    License

    This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

We recently established the new limb salvage modality of acridine orange (AO) therapy (AOT), in an attempt to develop minimally invasive limb salvage surgery with minimal damage of normal tissues and a low risk of local recurrence. The treatment modality consists of intraoperative photodynamic surgery (iPDS) and photodynamic therapy (iPDT), followed by postoperative radiodynamic therapy (RDT) using AO for patients with high-grade malignant musculoskeletal sarcomas. Clinical results have shown that the treatment is associated with a low risk of local recurrence, the risk being almost the same as that following conventional wide resection, and yields superior limb function as compared to that obtained after wide resection.

In this review, we present the detailed mechanism of selective accumulation of AO in sarcomas, which is related to the acidic environment and lysosomal acidity of the tumor cells induced by cancer-specific glycolysis not involving the define tricarboxylic acid (TCA) cycle (Warburg’s effect). We also describe the clinical uses of AOT and the procedure for intraoperative photodynamic surgery (iPDS) using local administration of AO. 



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Katsuyuki Kusuzaki, M.D., Ph.D.

Department of Orthopaedic Surgery, Kyoto Kujo Hospital

For correspondence:
18kusu43@gmail.com

Takao Matsubara

Department of Orthopaedic Surgery, Mie University Graduate School of Medicine

Haruhiko Satonaka

Department of Orthopaedic Surgery, Mie University Graduate School of Medicine

Akihiko Matsumine

Department of Orthopaedic Surgery, Mie University Graduate School of Medicine

Tomoki Nakamura

Department of Orthopaedic Surgery, Mie University Graduate School of Medicine

Akihiro Sudo

Department of Orthopaedic Surgery, Mie University Graduate School of Medicine

Hiroaki Murata, M.D., Ph.D.

Department of Orthopaedic Surgery, Matsushita Memorial Hospital

Shigekuni Hosogi

Department of Biomedical and Neuromotor Sciences, University of Bologna

Nicola Baldini

Department of Biomedical and Neuromotor Sciences, University of Bologna

Katsuyuki Kusuzaki, M.D., Ph.D.

Department of Orthopaedic Surgery, Kyoto Kujo Hospital

For correspondence:
18kusu43@gmail.com

Takao Matsubara

Department of Orthopaedic Surgery, Mie University Graduate School of Medicine

Haruhiko Satonaka

Department of Orthopaedic Surgery, Mie University Graduate School of Medicine

Akihiko Matsumine

Department of Orthopaedic Surgery, Mie University Graduate School of Medicine

Tomoki Nakamura

Department of Orthopaedic Surgery, Mie University Graduate School of Medicine

Akihiro Sudo

Department of Orthopaedic Surgery, Mie University Graduate School of Medicine

Hiroaki Murata, M.D., Ph.D.

Department of Orthopaedic Surgery, Matsushita Memorial Hospital

Shigekuni Hosogi

Department of Biomedical and Neuromotor Sciences, University of Bologna

Nicola Baldini

Department of Biomedical and Neuromotor Sciences, University of Bologna