Preliminary Report: Rapid Intraoperative Detection of Residual Glioma Cell in Resection Cavity Walls Using a Compact Fluorescence Microscope.

Jiro Akimoto,Michihiro Kohno,Kenta Nagai,Megumi Ichikawa,Shinjiro Fukami

doi:10.3390/jcm10225375

Abstract

Objective: The surgical eradication of malignant glioma cells is theoretically impossible. Therefore, reducing the number of remaining tumor cells around the brain–tumor interface (BTI) is crucial for achieving satisfactory clinical results. The usefulness of fluorescence–guided resection for the treatment of malignant glioma was recently reported, but the detection of infiltrating tumor cells in the BTI using a surgical microscope is not realistic. Therefore, we have developed an intraoperative rapid fluorescence cytology system, and exploratorily evaluated its clinical feasibility for the management of malignant glioma. Materials and methods: A total of 25 selected patients with malignant glioma (newly diagnosed: 17; recurrent: 8) underwent surgical resection under photodiagnosis using photosensitizer Talaporfin sodium and a semiconductor laser. Intraoperatively, a crush smear preparation was made from a tiny amount of tumor tissue, and the fluorescence emitted upon 620/660 nm excitation was evaluated rapidly using a compact fluorescence microscope in the operating theater. Results: Fluorescence intensities of tumor tissues measured using a surgical microscope correlated with the tumor cell densities of tissues evaluated by measuring the red fluorescence emitted from the cytoplasm of tumor cells using a fluorescence microscope. A “weak fluorescence” indicated a reduction in the tumor cell density, whereas “no fluorescence” did not indicate the complete eradication of the tumor cells, but indicated that few tumor cells were emitting fluorescence. Conclusion: The rapid intraoperative detection of fluorescence from glioma cells using a compact fluorescence microscope was probably useful to evaluate the presence of tumor cells in the resection cavity walls, and could provide surgical implications for the more complete resection of malignant gliomas.

Highlights

In the management of the malignant gliomas, the extent of the surgical resection is the most important prognostic factor [1,2,3,4,5]
We investigated the possibilities of performing the fluorescence–guided resection (FGR) method using another photosensitizer, talaporfin sodium (TPS), for malignant gliomas, and reported the selective accumulation of TPS in glioma cells in both in vitro and in vivo studies, as well as having developed an intraoperative photodiagnosis method using TPS with semiconductor laser systems [16,17,18,19,20]
We reported that additional intraoperative photodynamic therapy (PDT) applied to the wall of the resection cavity of malignant gliomas using TPS with a semiconductor laser improves the median of progression-free survival and overall survival of patients, and PDT was subsequently approved for use under insurance by the Japanese Government in 2013 [21,22,23]

Summary

Introduction

In the management of the malignant gliomas, the extent of the surgical resection is the most important prognostic factor [1,2,3,4,5]. With the spread of the FGR method, its problems and limitations have become clear, such as the problem of specificity of 5-ALA accumulation in tumor cells, and the problem of the subjective assessment of the intensity of fluorescence by the surgeon’s naked eye under the surgical microscope [9,10] To overcome these problems, several authors performed basic and clinical studies on the quantification of the 5-ALA metabolite protoporphyrin IX (PPIX) in the brain and tumor tissues using optical spectroscopy, and an intraoperative augmentation method of these optical information using artificial intelligence [11,12,13,14,15]

Methods

Results

Conclusion