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Intraoperative guidance in parathyroid surgery 99
INTRODUCTION
Primary hyperparathyroidism is a common endocrine disorder caused by parathyroid adenomas or hypertrophic parathyroid glands1. Complete surgical resection of these lesions is the only curative treatment. For diagnosis and surgical planning, preoperative imaging can be performed with several imaging modalities. Available imaging modalities currently consist of ultrasound (US), radionuclide scanning, magnetic resonance imaging, and both conventional and ā4 Dā computed tomography2. In daily practice, various combinations of these imaging options are used.
During surgery, adequate identi cation of parathyroid adenomas and parathyroid glands is of utmost importance for a curative treatment and to minimize the need for surgical exploration of the neck. However, few intraoperative imaging modalities are available. In 1971 Dudley et al. reported the use of intravenous administration of high dose Methylene Blue (MB) for the intraoperative identi cation of parathyroid adenomas3. Since then, this technique has been repeated by many groups4-6. However, administration of high dose MB (7.5 mg/kg) is associated with serious adverse events such as toxic metabolic encephalopathy7 and can lead to blue staining of the complete surgical eld due to leakage when surgical procedures takes longer.
Besides the use of high dose MB, several intraoperative imaging modalities are described, all with their own disadvantages. Radio-guided identi cation using 99mTc-sestamibi and hand-held gamma probes lacks real-time visual guidance5;8;9. Moreover, nuclear isotopes are scarce in large areas of the world. Aminolevulinic acid (ALA) was successfully tested in clinical studies, but can cause phototoxic reactions for which patients have to be protected from direct light exposure for 48 hours10-12. Moreover, ALA is mainly uorescent in the visual light spectrum, which leads to high absorption and scatter of visible light in living tissue.
One of the techniques that could overcome these issues is near-infrared (NIR) uorescence imaging. NIR uorescence imaging is an innovative technique to visualize tumors, vital structures and lymphatic channels and lymph nodes13. Recently, our research group showed feasibility of intraoperative identi cation of parathyroid adenomas using NIR uorescence imaging and low dose MB as uorescent tracer14. In this previous study, parathyroid adenomas were identi ed by surgical identi cation; whereafter 0.5 mg/kg MB (low-dose) was