Advancing parathyroid surgery: a critical examination of probe-based near-infrared autofluorescence technology

Intraoperative detection of parathyroid glands (PGs) can be challenging, even for experienced surgeons (1). This is even more pronounced among younger and less experienced surgeons who may lack the confidence needed for accurate PG identification. With the inherent difficulty in identifying PGs, coupled with the cost of frozen sections, near-infrared autofluorescence (NIRAF) detection emerges as a promising solution to address this challenge. In light of this, Kiernan and colleagues investigate the efficacy of probe-based NIRAF technology for parathyroid identification during parathyroidectomy (2). The recent study by Kiernan et al. is a single-center, randomized clinical trial encompassing 160 patients undergoing parathyroidectomy, who were randomly allocated to either the probe-based NIRAF or control group (visual identification).

The trial was conducted in a high-volume surgical center and involved two endocrine surgeons: a senior surgeon with >20-year experience and a junior surgeon with <5-year experience. The study enrolled adult patients undergoing parathyroid surgery for primary hyperparathyroidism (pHPT) or persistent/recurrent pHPT after a failed prior parathyroidectomy. Exclusion criteria comprised cases of secondary or tertiary hyperparathyroidism, or those undergoing concurrent thyroid procedures. Prior to surgery, patients underwent localization studies, including at least an ultrasound. While patients with radiologically localized disease were considered candidates for focused parathyroidectomy, at the discretion of the surgeon, cases deemed nonlocalized or discordant underwent bilateral neck exploration (BNE). Importantly, the senior surgeon in this study routinely performs BNE. Preoperative imaging studies varied among patients, with ultrasound being standard for all, and additional imaging studies performed based on the surgeons’ discretion. Intraoperative parathyroid hormone (ioPTH) monitoring was used in all cases, with cure defined according to the Miami criteria.

In their study, Kiernan et al. observe a significant improvement in parathyroid identification rates for both senior and junior surgeons, from 3.2 to 3.6 and 2.2 to 2.5 PGs, respectively. In the probe group, PG identification was even more pronounced for residents. Notably, the probe-based NIRAF approach also led to a significant reduction in the number of frozen sections used. The study concludes that probe-based NIRAF detection serves as a valuable intraoperative adjunct and educational tool, instilling confidence in PG identification and potentially reducing the dependence on frozen sections.

The study exhibits several strengths, including a well-defined methodology and a randomized clinical trial design that involves both experienced and junior surgeons. However, the study also has a number of limitations. These include the variability in surgical approaches, ranging from routine bilateral cervical explorations to focused approaches, and the potential underestimation of failure rates due to incomplete follow-up. It is worth noting that while Kiernan and colleagues assess the advantages of detecting more PGs, they do not explore the utility of discriminating between normal and diseased PGs, as noted by other authors (3-6).

Although this study aligns with prior research on NIRAF’s accuracy in PG identification (7-12), controversies arise when comparing the lower specificity observed in this trial to earlier studies (13). Understanding the reasons behind this specificity difference, such as variations in sample size and tissue types, is essential. The study prompts a critical examination of the technology’s limitations and areas for refinement. Yet in most clinical scenarios, experienced surgeons can easily distinguish parathyroid and nonparathyroid tissue, including colloid nodules and brown fat. An additional aspect to consider is that this study is conducted in a high-volume surgical center with experienced surgeons, potentially limiting the generalizability of findings to other settings. These aspects emphasize the need for further validation of the technology across both low- and high-volume centers (14).

In the broader context of parathyroid surgery, Kiernan and colleagues address a critical need for improved intraoperative tools. The findings of this study underscore the potential of probe-based NIRAF in this context, not only in enhancing surgeon confidence, but also in reducing the need for frozen section analyses, and potentially lowering costs associated with parathyroidectomy. Kiernan and colleagues address the practical implications of integrating advanced technologies into routine surgical practices. Notably, their study contributes significantly to the existing literature by being the first randomized controlled trial evaluating probe-based NIRAF during parathyroid surgery for pHPT. As highlighted in a recent population-based cohort study by Annebäck et al. (15), the risk of hypoparathyroidism after total thyroidectomy remains a significant concern, emphasizing the need for follow-up and improved tools to minimize such complications.

Although NIRAF technologies are frequently used to detect PGs and minimize postoperative hypoparathyroidism, there is a notable research gap regarding their impact in parathyroid surgery. Previous studies have shown NIRAF’s superiority over naked eye visualization during surgery (16). This study, consistent with recent research in other low-volume institutions (17,18), offers valuable insights into the impacts that autofluorescence guidance may have on surgical outcomes, particularly for less experienced surgeons.

Within the field of NIRAF imaging, there are currently two types of systems: probe-based and image-based modalities. The former includes the PTeye system (Medtronic, Minnesota, MN, USA) and provides quantitative and auditory feedback upon contact with parathyroid tissue. The latter utilizes a near-infrared light source with a filtered camera, enabling identification of autofluorescence signals on display monitors, and includes the Fluobeam-800/Fluobeam-LX (Fluoptics, France), EleVision^TM IR Platform (Medtronic, Minnesota, MN, USA), PDE Neo II (Hamamatsu, Shizuoka Pref. Japan), among others. Concerning parathyroid surgery, both systems offer distinct benefits and limitations. Image-based devices may be particularly advantageous in the hands of young, less experienced surgeons. This can be attributed to a broader simultaneous field of examination compared to probe-based devices, where the probe should be positioned on already visually suspicious parathyroid tissue as a confirmation. Image-based devices, which enable identification of fluorescent signals and thus help detect the heterogeneous fluorescent pattern of adenomas, may contribute to a more accurate prediction of the disease characteristics of a parathyroid adenoma (4-6). Yet both modalities can effectively detect and differentiate between normal and diseased PGs, as diseased PGs can be 30% less fluorescent than normal PGs. This may explain the presence of two false negatives in two parathyroid adenomas in this study. It is worth acknowledging that probe-based systems also hold a practical advantage over image-based modalities in this context, as the small size of the probe proves for surgical procedures conducted through (very) small neck incisions.

The ultimate goal of NIRAF technology is to reduce the incidence of postoperative complications, particularly persistent hyperparathyroidism, but also hypoparathyroidism in cases of multiglandular disease. Yet because experienced centers already have low complication rates (<5% and <1%, respectively), it is likely that no study will be sufficiently powered to address this question. In this context, the number of detected PGs serves as a surrogate marker, wherein detecting more PGs will lead to a reduction in complication rates. The authors should be congratulated for their effort in enhancing patient care.

Despite certain limitations, the integration of probe-based NIRAF in parathyroid surgery represents a promising avenue for improved PG identification. This study marks a pioneering effort in evaluating the utility of probe-based NIRAF in parathyroid surgery. And while it sheds light on the potential benefits of real-time identification, further research is essential to address limitations and establish the broader applicability of this technology in diverse clinical settings.

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Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.