Squires Malcolm H, Shirley Lawrence A, Shen Chengli, Jarvis Rachel, Phay John E
Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus.
JAMA Otolaryngol Head Neck Surg. 2019 Oct 1;145(10):897-902. doi: 10.1001/jamaoto.2019.1987.
Intrinsic near-infrared (NIR) autofluorescence of the parathyroid gland enables intraoperative gland identification without the need for contrast agent injection. However, whether real-time autofluorescence imaging is useful in patients with multiple endocrine neoplasia type 1 (MEN1) and primary hyperparathyroidism is unknown.
To compare quantified intraoperative parathyroid autofluorescence imaging results for patients with MEN1-associated vs those with non-MEN1 sporadic primary hyperparathyroidism.
DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis of prospectively collected data on a cohort of 71 consecutive patients undergoing surgery for primary hyperparathyroidism by 2 experienced endocrine surgeons between June 1, 2017, and July 31, 2018, was conducted. Intraoperative imaging was performed with a handheld NIR autofluorescence device and images were captured for analysis. Post hoc blinded imaging analysis was conducted with Image J software to quantify representative areas of greatest autofluorescence from the parathyroid, thyroid, and adjacent soft tissue.
Primary end points were parathyroid autofluorescence and background thyroid and soft tissue autofluorescence, reported as median values with interquartile ranges. Rates of false-negative (lack of significant parathyroid gland autofluorescence compared with background autofluorescence, defined as parathyroid autofluorescence-background autofluorescence ratio <1.10) and false-positive autofluorescence (aberrant autofluorescence of nonparathyroid tissue confirmed by pathologic testing) were analyzed.
Of the 71 consecutive patients with primary hyperparathyroidism who underwent parathyroidectomy during the study period, 6 patients had genetically or clinically diagnosed MEN1 and 65 had sporadic non-MEN1 hyperparathyroidism. Most patients were women (MEN1: 4 [67%]; non-MEN1: 51 [78%]). Median (interquartile range) age was 49.0 (38.0-53.8) years in the MEN1 cohort and 61.0 (54.0-67.0) years in the non-MEN1 cohort. No clinically significant differences in serum preoperative parathyroid hormone level or parathyroid gland size or weight on pathologic examination were observed between the 2 cohorts. The median absolute value of in situ parathyroid autofluorescence was significantly lower in the MEN1 cohort than the non-MEN1 cohort (54.4 vs 74.3; Hedges g = -1.03; 95% CI, -1.89 to -0.17), as was the ratio of parathyroid to background autofluorescence (1.08 vs 1.59; g = -1.59; 95% CI, -2.23 to -0.96). Three patients (50%) with MEN1 had false-negative nonfluorescent parathyroid adenomas vs 6 patients (9%) without MEN1. Nonparathyroid fibroadipose tissue of patients with MEN1 exhibited greater background autofluorescence, leading to high false-positive rates (5 of 6 patients [83%]) vs only 3 of 65 (5%) false-positive autofluorescence nonparathyroid specimens among patients without MEN1.
Intraoperative identification of parathyroid glands using their autofluorescence by real-time NIR imaging appears to have utility in patients with primary hyperparathyroidism. In this initial cohort of patients with MEN1, decreased parathyroid autofluorescence and increased background autofluorescence of nonparathyroid tissue may be associated with high rates of false-negative and false-positive fluorescence, potentially limiting the utility of this adjunct in this specific subset of patients.
甲状旁腺的固有近红外(NIR)自发荧光能够在术中识别腺体,而无需注射造影剂。然而,实时自发荧光成像在1型多发性内分泌腺瘤(MEN1)合并原发性甲状旁腺功能亢进患者中是否有用尚不清楚。
比较MEN1相关性原发性甲状旁腺功能亢进患者与非MEN1散发性原发性甲状旁腺功能亢进患者术中甲状旁腺自发荧光成像的量化结果。
设计、设置和参与者:对2017年6月1日至2018年7月31日期间2名经验丰富的内分泌外科医生为71例连续接受原发性甲状旁腺功能亢进手术的患者前瞻性收集的数据进行回顾性分析。术中使用手持式NIR自发荧光设备进行成像,并采集图像进行分析。使用Image J软件进行事后盲法成像分析,以量化甲状旁腺、甲状腺和相邻软组织中自发荧光最强的代表性区域。
主要终点是甲状旁腺自发荧光以及甲状腺和软组织背景自发荧光,以中位数及四分位间距报告。分析假阴性(与背景自发荧光相比,甲状旁腺无明显自发荧光,定义为甲状旁腺自发荧光与背景自发荧光比值<1.10)和假阳性自发荧光(经病理检查证实的非甲状旁腺组织异常自发荧光)的发生率。
在研究期间接受甲状旁腺切除术的71例连续原发性甲状旁腺功能亢进患者中,6例经基因或临床诊断为MEN1,65例为散发性非MEN1甲状旁腺功能亢进。大多数患者为女性(MEN1组:4例[67%];非MEN1组:51例[78%])。MEN1队列的中位(四分位间距)年龄为49.0(38.0 - 53.8)岁,非MEN1队列的中位年龄为61.0(54.0 - 67.0)岁。两个队列在术前血清甲状旁腺激素水平、甲状旁腺大小或病理检查时的重量方面未观察到临床显著差异。MEN1队列中原位甲状旁腺自发荧光的中位绝对值显著低于非MEN1队列(54.4对74.3;Hedges g = -1.03;95%CI,-1.89至-0.17),甲状旁腺与背景自发荧光的比值也是如此(1.08对1.59;g = -1.59;95%CI,-2.23至-0.96)。3例(50%)MEN1患者有假阴性的无荧光甲状旁腺腺瘤,而非MEN1患者中有6例(9%)。MEN1患者的非甲状旁腺纤维脂肪组织表现出更强的背景自发荧光,导致假阳性率较高(6例患者中有5例[83%]),而非MEN1患者中65例只有3例(5%)非甲状旁腺标本出现假阳性自发荧光。
通过实时NIR成像利用甲状旁腺的自发荧光在术中识别甲状旁腺似乎对原发性甲状旁腺功能亢进患者有用。在这个初始的MEN1患者队列中,甲状旁腺自发荧光降低和非甲状旁腺组织背景自发荧光增加可能与高假阴性和假阳性荧光率相关,这可能限制了这种辅助手段在这一特定患者亚组中的应用。