The Year in Thyroidology: Surgical Science

Introduction

This past year, there were many outstanding publications in field of surgical thyroidology. As the invited speaker for the “Year in Surgical Thyroidology” plenary session, at the 2022 Annual Meeting of the American Thyroid Association (ATA), I had the honor of selecting and reviewing what I believe are the most insightful and influential studies published between September 2021 and August 2022. The main objectives of this review are to highlight some of these surgical and technological advancements (Table 1). A comprehensive PubMed review was performed and surgical colleagues who are members of the ATA were queried for topic areas and articles they felt were the most impactful.

Parathyroid Detection

Injury to the parathyroid glands during thyroid surgery is a devastating complication. Proper identification of the parathyroid glands is critical to potentially help decrease this concern. Parathyroid near-infrared autofluorescence (NIRAF) is a technology that has been shown to help identify parathyroid glands intraoperatively, but whether that decreases the incidence of postoperative hypoparathyroidism is still unclear.

In February 2020, the results of the PARAFLUO multicenter randomized clinical trial were published. ¹ The study was performed at three referral hospitals, with a 6-month follow-up. The primary outcome was the rate of postoperative hypocalcemia after total thyroidectomy (TT). ¹ All surgeons performed >25 total thyroidectomies per year. Two hundred forty-one patients were analyzed for the primary outcome: 121 had NIRAF-assisted thyroidectomy and 120 had conventional thyroidectomy (control group). The respective rates of temporary hypocalcemia were 9.1% in the NIRAF arm and 21.7% in the control arm (p = 0.007), whereas the rates of permanent hypocalcemia rates were not significantly different.

In a multivariable analysis, NIRAF use was associated with a reduced the risk of temporary hypocalcemia. In secondary analyses, fewer patients experienced parathyroid autotransplantation in the NIRAF group than in the control group, 3.3% versus 13.3% (p = 0.009) and the inadvertently resected parathyroid glands was significantly lower in the NIRAF group compared with controls, 2.5% versus 11.7%, respectively (p = 0.006).

Kim et al reported a retrospective study on the use of NIRAF during TT and central neck dissection. ² This study included 261 patients in the NIRAF group and 281 controls. The incidence of postoperative hypoparathyroidism 1 month after surgery was significantly lower in the NIRAF group; however, there was no difference between the NIRAF group and the control group in the permanent hypoparathyroidism rate (6 months after surgery) (4.2% vs. 4.6%; p = 0.816). The number of inadvertently resected parathyroid glands was significantly lower in the NIRAF group (16.9% vs. 12.8%; p = 0.021), but there was no difference in the incidence of hypocalcemia between the two groups.

Although NIRAF helps identify parathyroid glands, it does not provide information on the perfusion and viability of the parathyroid gland. The use of indocyanine green fluorescence imaging (ICGF) has been proposed in evaluating blood perfusion and predicting the function of parathyroid glands in situ. In June 2022, Yin et al published their results of a randomized controlled trial combining the use of ICGF and NIRAF in identifying and evaluating parathyroid glands during TT. ³ The study enrolled 180 patients. These authors reported that the combined use of NIRAF and ICGF during TT reduced the risk of transient postoperative hypoparathyroidism (43.3%–27.8%), and enhanced the ability to identify and preserve parathyroid glands, with no difference in the rate of permanent hypoparathyroidism.

One of the criticisms of studies utilizing NIRAF for parathyroid detection is that the surgeons involved in the trials have been high-volume surgeons where this technology may not augment their experience. To help address this, Thomas et al published a surgeon-blinded multicenter study comparing intraoperative parathyroid identification, stratified by surgeon experience, versus NIRAF detection. ⁴ The six endocrine surgeons were categorized according to years of experience.

All surgeons were blinded to output of NIRAF when identifying tissues. The surgeons' ability to identify parathyroid glands was then compared with NIRAF. Junior surgeons (<5 years of experience) were reported to have lower confidence in identifying parathyroid glands and a higher tissue misclassification rate per specimen as compared with NIRAF or senior surgeons (>10 years of experience). NIRAF achieved 92.7% accuracy, which was similar to that of the senior surgeons. The authors concluded these technologies should be studied in the context of low-volume surgeons or surgeons who are not specialized in thyroid surgery.

NIRAF appears to be a promising tool to enable more accurate identification and preservation of parathyroid glands. The data show an improvement in temporary postoperative hypoparathyroidism when NIRAF is used during TT, but there seems to be no significant improvement in rates of permanent postoperative hypoparathyroidism. An important limitation is the lack of accurate technology for the evaluation of parathyroid gland viability. The use of ICGF did not seem to improve upon NIRAF use alone. Surgeon experience and volume may be a factor in determining the value of parathyroid autofluorescence technology. Further advances in this technology may yield promising results.

Thermal Ablation

The role of thermal ablation (TA), specifically radiofrequency ablation (RFA), for symptomatic benign thyroid nodules has been well described. Recently, TA has been proposed as a potential therapeutic option for patients with papillary thyroid microcarcinoma (PTMC). However, the clinical outcomes of TA versus surgery remains controversial because of a lack of sufficient data. In November 2021, Yan et al published a propensity-matched cohort study comparing the clinical outcomes between RFA and thyroid lobectomy (TL) for low-risk PTMC. ⁵ After propensity score matching (PSM), a total of 332 patients underwent TL and 332 underwent RFA. No significant differences were observed in any of the measured clinical outcomes. Limitations of the study included its retrospective nature, short follow-up duration, and variable cost utility analysis depending on practices in different countries. Further studies comparing RFA, TL, and active surveillance for low-risk PTMC are needed.

Extent of Surgery

Laryngeal Nerve Monitoring

Recurrent laryngeal nerve (RLN) injury during thyroid surgery is a dreaded complication that should be avoided. Intraoperative nerve monitoring (IONM) provides surgeons with a tool that could theoretically help identify and minimize risk of RLN injury. The International Neural Monitoring Study Group established a large international registry and reported descriptive data on surgical anatomy and variability of the RLN course in 574 patients (with 1000 nerves at risk) who underwent thyroid surgery in 17 centers from 12 countries. ¹⁰

The authors reported a higher than expected percentage of nerves followed an abnormal trajectory (23%). Loss of signal was identified in 3.5% of nerves, with 34% of these followed an abnormal intraoperative trajectory. Loss of signal was most commonly encountered when the nerve was fixed, splayed, or entrapped, with extensive neural dissection, cancer invasion, or when lateral lymph node dissection was needed. Traction injury was the most common form of RLN injury and recovery was lower than expected (only 62% recovery). ¹⁰ Some intrinsic limitations to this large database study include selection bias and data entry accuracy.

Memeh et al reported on the largest published retrospective study to use a national surgical outcomes registry and the first to use a doubly robust approach, to specifically evaluate the effect of IONM on RLN injury. ¹¹ The authors included 24,370 patients undergoing thyroid surgery, 15,836 (70%) of whom underwent IONM. RLN injury occurred in 1498 (6.2%) cases. The authors reported that variables associated with RLN included older age, larger body mass index, a cancer diagnosis, previous neck operation, TT, and nodal dissection.

Their doubly robust model suggested that the use of IONM was associated with a significant reduction in overall rate of RLN injury (risk ratio 0.77, p < 0.001) and postoperative length of stay. This study was limited by its retrospective design and a 30-day time horizon. Furthermore, some of the reported hoarseness may have been attributed to causes other than RLN injury. This study did not account for surgeon volume, nonetheless, surgeons need to be familiar with IONM and appreciate its utility in their practice.

Conclusions

Novel surgical adjuncts and interventions are transforming the delivery of care to our patients. As we adopt these procedures and technologies, it is incumbent upon us to study them in the context of improved outcomes, cost, and quality of life for our patients. Parathyroid autofluorescence and IONM technology promise the potential to improve surgical outcomes by decreasing the risk of the complications of hypoparathyroidism and RLN injury. Advances in interventional thyroidology along with optimal extent of surgery will guide outcomes in the future. Patient quality of life is a critical component and must be incorporated in our surgical and interventional decision-making process at all levels.