Detecting tumour-positive resection margins after oral cancer surgery by spraying a fluorescent tracer activated by gamma-glutamyltranspeptidase

通过喷洒由 γ-谷氨酰转肽酶激活的荧光示踪剂检测口腔癌手术后肿瘤阳性切除边缘

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作者:Maxime D Slooter, Henricus J M Handgraaf, Martin C Boonstra, Lily-Ann van der Velden, Shadhvi S Bhairosingh, Ivo Que, Lorraine M de Haan, Stijn Keereweer, Pieter B A A van Driel, Alan Chan, Hisataka Kobayashi, Alexander L Vahrmeijer, Clemens W G M Löwik

Conclusion

This study demonstrates the feasibility to detect tumour-positive resection margins with gGlu-HMRG and a clinical fluorescence imaging system. Applying this technique would enable intraoperative screening of the entire resection margin and allow direct re-resection in case of tumour-positivity.

Methods

The preclinical Maestro and clinical Artemis imaging systems were compared in vitro and ex vivo with cultured human head and neck cancer cells (OSC19, GGT-positive; and FaDu, GGT negative) and tumour-bearing nude mice. Subsequently, frozen sections of normal and oral cancer tissues were ex vivo sprayed with gGlu-HMRG to determine the sensitivity and specificity. Finally, resection margins of patients with suspected oral cancer were ex vivo sprayed with gGlu-HMRG to detect tumour-positive resection margins.

Results

Both systems could be used to detect gGlu-HMRG activation in vitro and ex vivo in GGT positive cancer cells. Sensitivity and specificity of gGlu-HMRG and the Artemis on frozen tissue samples was 80% and 87%, respectively. Seven patients undergoing surgery for suspected oral cancer were included. In three patients fluorescence was observed at the resection margin. Those margins were either tumour-positive or within 1 mm of tumour. The margins of the other patients were clear (≥8 mm).

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