Combined Use of Autofluorescence and Indocyanine Green Fluorescence Imaging in the Identification and Evaluation of Parathyroid Glands During Total Thyroidectomy: A Randomized Controlled Trial

Abstract

Background and objectivesAccurate identification and evaluation of the parathyroid glands (PGs) intraoperatively is critical to reduce the incidence of postoperative hypoparathyroidism after total thyroidectomy. Near-infrared fluorescence imaging (NIFI), including the autofluorescence (AF) and indocyanine green fluorescence (ICGF) imaging, is a promising technique to protect PGs. This study aimed to assess whether the combined use of AF and ICGF could reduce the incidence of postoperative hypoparathyroidism and improve the identification and evaluation of PGs during total thyroidectomy.MethodsThis randomized controlled trial enrolled 180 patients who were randomized into two groups and underwent total thyroidectomy with unilateral or bilateral central lymph node dissection. In the control group, the PGs were identified and evaluated by the naked eye. In the NIFI group, AF was used to identify the PGs and ICGF was applied to assess the blood perfusion of the PGs in situ. The primary outcome was the incidence of postoperative hypoparathyroidism. The secondary outcomes included the number of identified PGs, autotransplanted PGs, and known preserved PGs in situ.ResultsThe incidence of postoperative transient hypoparathyroidism was significantly lower in the NIFI group than in the control group (27.8% vs. 43.3%, P = 0.029). More PGs were identified in the NIFI group than in the control group (3.6 ± 0.5 vs. 3.2 ± 0.4, P < 0.001). No significant difference was observed in the number of autotransplanted PGs between the two groups (P = 0.134). Compared with the control group, a greater number of known PGs were preserved in situ in the NIFI group (1.3 ± 0.6 vs. 1.0 ± 0.5, P < 0.001). In the NIFI group, only 4.5% of the patients with at least one well-perfused PG (ICG score of 2) developed postoperative hypoparathyroidism, which was significantly lower than that of the control group (34.6%, P < 0.001).ConclusionCombined use of AF and ICGF during total thyroidectomy reduces the risk of transient postoperative hypoparathyroidism, enhances the ability to identify and preserve PGs, and improves the accuracy of evaluating the perfusion of PGs during surgery.Clinical Trial RegistrationChinese Clinical Trial Register (www.chictr.org.cn), identifier ChiCTR2100045320. Registered on April 12, 2021.

Factors in the occurrence and restoration of hypoparathyroidism after total thyroidectomy for thyroid cancer patients with intraoperative parathyroid autotransplantation

“…Parathyroid glands were routinely identified by the naked eye or ICG combined with autofluorescence if it was difficult to evaluate their location and blood supplies. Detailed methods of ICG combined with autofluorescence were described in our previous study (12). If the blood supply was deemed sufficient by the surgeon's verdict, the suspected parathyroid would be preserved in situ.…”

Use of fluorescence image-guided surgery and autofluorescence in thyroid and parathyroid surgery

“…In thyroid and parathyroid surgery, autofluorescence has been shown to reliably improve identification of the thyroid glands and differentiate between the parathyroid glands and surrounding tissues, including the thyroid gland, with randomized controlled trials demonstrating decreased rates of hypocalcemia following thyroidectomy [31,32] . Meanwhile, ICG FA may provide surgeons with information on the perfusion status of the parathyroid glands in addition to helping to identify them during parathyroidectomy.…”

“…These findings were supported by the PARAFLUO multicenter randomized trial comparing rates of hypocalcemia (corrected calcium < 8.0 mg/dL) on postoperative day (POD) 1 or 2. In that study, Benmiloud et al [32] randomized 241 patients to conventional thyroidectomy vs. NIRAF-assisted thyroidectomy and found that the rates of temporary hypocalcemia were 9.1% for the NIRAF group and 21.7% for the controls (P = 0.007), though they did not detect a significant difference in permanent hypocalcemia (0% vs. 1.6%, respectively). These findings persisted in multivariate analysis, with an odds ratio of 0.35 for hypocalcemia in the NIRAF group.…”

“…While other studies have had conflicting results regarding the ability of NIRAF imaging to reduce hypocalcemia, these three large randomized trials provide level II evidence that NIRAF can improve the identification and preservation of parathyroid glands during thyroid surgery [31,32,[34][35][36] . Additionally, a metaanalysis of eight studies by Lu et al [37] found that utilizing NIRAF during thyroidectomy compared to naked-eye assessment reduced the incidence of postoperative hypocalcemia from 22.40% to 7.11% (P < 0.001).…”

“…Based on early results, there has been a lot of excitement and numerous publications about the use of fluorescence image guidance in thyroid surgery. While the vast majority of studies are retrospective, singleinstitution case series or cohort studies, there are several large, randomized trials that seem to show the superiority of NIRAF visualization of the parathyroid glands compared to traditional surgery [31,32] . ICG FA may provide additional insight into the perfusion status of identified glands to help guide autotransplantation and the need for postoperative monitoring and supplementation.…”