The Year in Surgical Thyroidology: Recent Technological Developments and Future Challenges

Abstract

Background:

The field of surgical and interventional thyroidology is rapidly evolving. In the past few years, we have seen the introduction and establishment of many novel surgical adjuncts, techniques, and disruptive ablative technologies that have impacted the field.

Methods:

We identified the most influential articles on technological developments in surgical and interventional thyroidology that were published from September 1, 2020, to August 1, 2021. We searched three electronic databases and consulted experts.

Results:

Major findings are summarized. Continuous intraoperative nerve monitoring (cIONM) lowered the risk of early postoperative vocal cord palsy 1.8-fold and permanent palsy 29 · 4-fold compared with intermittent intraoperative nerve monitoring. Parathyroid autofluorescence yielded a diagnostic odds ratio (OR) of 228.9 for detection of parathyroid glands over visualization, with 96% sensitivity and 92% specificity. There was no significant difference in the incidence of major complications between the transoral endoscopic thyroidectomy vestibular approach (TOETVA) and transcervical thyroidectomy (1.5% vs. 2.1%, p = 0.75), and a higher body mass index did not lead to a significant increase in the odds of cumulative complication with TOETVA for the overweight (OR = 0.52 [95% confidence interval {CI} 0.17–1.58]) and obese groups (OR = 1.69 [CI 0.74–3.88]). Radiofrequency ablation (RFA) for benign thyroid nodules typically resulted in a 50–85% volume reduction with faster recovery times, less pain levels, and higher social and psychological well-being compared with conventional thyroidectomy at 15 months post-treatment, although physical well-being levels were higher in the conventional thyroidectomy group at this time. RFA for papillary thyroid microcarcinoma showed no significant difference in local tumor progression (1.8% vs. 3.3%, p = 0.209), lymph node metastasis (0.6% vs. 0.6%, p = 1.000), recurrence (1.2% vs. 2.4%, p = 0.244), and 4-year recurrence-free survival rates (98.2% vs. 97.0%, p = 0.223) when compared with transcervical lobectomy.

Conclusions:

cIONM, parathyroid autofluorescence, transoral vestibular approach thyroid surgery, and RFA for benign and malignant thyroid nodules are some of the latest additions to the surgeon's and interventionalist's armamentarium to manage thyroid disease. These technological advancements demonstrate promise to improve outcomes, decrease complications, and enhance a patient's quality of life, but further rigorous studies are needed to define their utility and value.

Introduction

The COVID-19 pandemic has challenged the way we collaborate across the world for more than a year now, but that has not hindered the recent technological advancements in thyroid surgery and novel interventional techniques.

The main objectives of this review are to highlight some of these technological advancements that have occurred during this time:

- To discuss the new evidence on why continuous intraoperative nerve monitoring (cIONM) could decrease the rate of postoperative vocal fold palsy.

- To become familiar with the most contemporary data on parathyroid autofluorescence (AF).

- To understand transoral thyroid surgery outcomes, its current role, and its future outlook.

- To outline current data on radiofrequency ablation (RFA) for benign and differentiated thyroid cancer and how that compares with surgery.

Materials and Methods

We searched for studies in PubMed, Google Scholar, and SCOPUS, using the terms thyroid surgery, radiofrequency ablation, and thyroid interventions. We restricted our search to studies published from September 1, 2020, to August 1, 2021. We also queried surgical colleagues who were members of the American Thyroid Association to inform us of topic areas and articles that represented the most influential technological developments in surgical and interventional thyroidology.

Results

Preservation of recurrent laryngeal nerve function

Recurrent laryngeal nerve (RLN) injury is a common complication of thyroid surgery that surgeons are always trying to avoid. The introduction of intraoperative nerve monitoring (IONM) provided surgeons with a tool that could theoretically help minimize this risk, but no strong evidence exists that can support its routine use for this reason. Nonetheless, surgeons have still found value in this technology as evidenced by 83–93% of American head and neck surgeons and international endocrine surgeons use IONM (1). In May 2021, Schneider et al. (2) published a study that compared cIONM with intermittent IONM (iIONM).

While iIONM has helped surgeons in identifying RLN injury, its limitation is that it can only indicate that there is an injury after the nerve has already been damaged. cIONM may alert the surgeon of an impending injury that could result in vocal fold motion impairment. A decrease in the amplitude by 50% and/or an increase in latency by 10% of the electromyography (EMG) waveform signal an alarm that the nerve is being stressed, giving the surgeon an opportunity to modify the surgical technique to avoid an injury that would result in postoperative vocal fold motion impairment. The authors hypothesized cIONM should be better than iIONM in preventing intraoperative RLN injury. To prove that, the authors reviewed 10 years of data from 6029 patients of whom 3139 underwent cIONM and 2890 patients underwent iIONM.

They concluded that cIONM independently reduced the risk of early postoperative vocal cord palsy 1.8-fold (odds ratio [OR] = 0.56) and permanent palsy 29 · 4-fold (OR = 0.03) compared with iIONM, yielding greater sensitivity (88.5% vs. 52.4%), specificity (99.6% vs. 99.2%), positive predictive value (79.3% vs. 61.9%), negative predictive value (99.8% vs. 98.8%), and accuracy (99.5% vs. 98.0%). While this study was limited by the fact that visual nerve identification and IONM were used simultaneously, its main strength was the high level of standardization including documentation of nerve electrophysiological measurements coupled with assessment of preoperative and postoperative vocal cord function.

Parathyroid AF

Identification of parathyroid glands during surgery to preserve the healthy glands or remove the diseased glands depends mostly on the surgeon's experience and understanding of the embryologic derivation of the parathyroid glands and the relevant anatomy. Different methods such as optical coherence tomography, dynamic optical contrast imaging, and Raman spectroscopy have all been tried in the past to help in the noninvasive identification of the parathyroid glands during surgery but had limited utility because they were somewhat impractical and difficult to use along with being costly.

Unlike these other technologies, near-infrared AF detection technology for parathyroid gland identification during surgery seems to be gaining favor. Recently two near-infrared fluorescence detection devices were approved by the Food and Drug Administration (FDA) and more are being developed and studied to include the assessment of viability as well.

In July 2021, a systematic review and meta-analysis that focused on parathyroid AF detection was published by Kim et al. (3). The goal was to evaluate near-infrared AF-based accuracy in identifying the parathyroid glands during thyroidectomy or parathyroidectomy. Seventeen studies were reviewed that included 1198 patients in this analysis. Their finding was that near-infrared AF-based identification of parathyroid glands demonstrated a diagnostic OR for detection of 228.9 [95% confidence interval (CI) 134.1–390.6] over visualization.

The sensitivity, specificity, negative predictive value, and positive predictive values were 96%, 92%, 95%, and 94%, respectively. The study concluded that near-infrared AF detection technology is a valuable method and adjunct to visualization for identifying parathyroid glands during surgery. This meta-analysis was limited by the inability to perform regular biopsies to histologically confirm the presence of parathyroid tissue as it is not the standard of care to biopsy normal parathyroid glands.

Solórzano et al. (4) published a literature review on near-infrared fluorescence and it discussed the two commercially available devices that are image based and probe based, respectively. While both technologies have their own pros and cons, it appears from Kim's article that the diagnostic accuracy was higher for the probe-based detection than the image-based detection. Further studies are needed to assess these technologies and compare utility and outcomes. We should expect an abundance of original research and trials assessing these technologies in the years to come.

Remote access surgery

Transoral vestibular approach thyroid and parathyroid surgery has become the most common established remote access technique to avoid the traditional transcervical incision or any other cutaneous incision since its initial description in 2011 (5). In March 2021, a retrospective review of a prospective database by Russell et al. (6) compared 200 transoral endoscopic thyroidectomy vestibular approach (TOETVA) cases with 333 traditional transcervical approach thyroidectomy (TCA) cases.

“In this study TOETVA patients were found to be younger (median age 39 vs. 47, p = 0.001), thinner (median body mass index [BMI] 27.2 vs. 28.7, p = 0.001), and predominantly female (88.5% vs. 79.9%, p = 0.006). There was no difference in incidence of major complications between the TOETVA and TCA cohorts (1.5% vs. 2.1%, p = 0.75). No significant difference was found in the rate of temporary RLN injury (4.5% vs. 2.1%, p = 0.124) or temporary hypoparathyroidism (18.2% vs. 12.5%, p = 0.163) for TOETVA and TCA, respectively. The secondary outcome of this study found that higher BMI in TOETVA did not lead to a significantly greater odds of cumulative complication (0.52 (95% CI [0.17–1.58]) and 1.69 (95% CI [0.74–3.88]) for the overweight and obese groups, respectively),” demonstrating that this technique could be successfully applied to a North American patient demographic. This study was limited by selection bias as TOETVA patients were selected based on the surgeons' experience with this technique and inherent differences in the way they selected patients for surgery.

A retrospective chart review by Chen et al. (7) compared 150 patients who underwent 154 transoral thyroidectomies. Fifty-five of them had the transoral vestibular approach robotic thyroidectomy (TORT) and 99 had TOETVA. They found no significant differences in outcomes between the two techniques. The main difference though was a longer operative time with the use of the robot. The median operative times were 308 versus 228 minutes for TORT and TOETVA, respectively. The costs of the robot and operating room time cannot be overlooked when trying to determine applicability and value to any specific health care system and that is probably one of the main reasons why the TORT remains far less prevalent around the world compared with TOETVA.

Radiofrequency ablation

Finally, the most disruptive technology and intervention to be introduced now in a world-wide manner is RFA for carefully selected thyroid nodules. RFA is showing promising results in treating thyroid patients with benign thyroid nodules when compared with surgery. RFA also offers a minimally invasive alternative that fills the gap between surgery and active surveillance for some patients with papillary thyroid microcarcinoma (PTMC). RFA could also be a great option for older patients or patients with multiple comorbidities because it can be done safely under local anesthesia. RFA is done with ultrasound guidance so the surgeon is able to observe any hyperechoic changes in the targeted tissue, suggesting adequate treatment in real time.

In June 2021, Tufano et al. (8) published a literature review on RFA for benign thyroid nodules, and it found many reports that showed that RFA is safe and the volume reduction of benign nonfunctioning nodules ranged from 50% to 85%. When RFA was used to treat autonomously functioning thyroid nodules, euthyroidism was achieved in 86% of small nodules (<12 mL) versus 45% in medium size nodules (>12 mL). While surgery is still the standard of care for symptomatic benign thyroid nodules, RFA is a good alternative when surgery is not the ideal choice or if patients do not want to have surgery. Surgery has an increased risk for hypothyroidism over RFA that is a major concern for most patients beyond the specific risks of the surgery and general anesthesia necessary to perform it.

Jin et al. (9) examined the quality-of-life aspect of RFA versus traditional thyroidectomy by conducting a randomized clinical trial that was published in January 2021. It included 450 patients who were randomized 1:1 to either the RFA group or conventional thyroidectomy. At 15 months, all participants were asked to complete a thyroid-specific quality-of-life questionnaire and reported that more patients who underwent thyroid thermal ablation were satisfied with the treatment compared with those in the conventional thyroidectomy group (192 [97%] of 197 patients vs. 167 [86%] of 195 patients; percentage difference 11.8, [CI 5.0–14.3]; adjusted OR = 2.39; 1.81–3.42; p < 0.0001).

Moreover, patients who were treated with RFA reported faster recovery time, less pain levels, and higher social and psychological well-being, while patients in the conventional thyroidectomy reported higher physical well-being levels at 15-month follow-up. While this was a randomized clinical trial, the authors recognize that selection bias, misclassification, and inaccurate responses to questionnaires are all possible limitations.

Yan et al. (10) published a retrospective study in September 2021 that compared the outcomes between thyroid lobectomy and RFA in patients with low-risk PTMC. The study compared 884 patients with 332 patients undergoing thyroid lobectomy and 332 undergoing RFA. At 48 months, there was no significant difference in local tumor progression (1.8% vs. 3.3%, p = 0.209), development of lymph node metastasis (0.6% vs. 0.6%, p = 1.000), recurrent PTMC (1.2% vs. 2.4%, p = 0.244), persistent lesion (0% vs. 0.3%, p = 0.317) on imaging, and 4-year recurrence-free survival rates (98.2% vs. 97.0%, p = 0.223) between the 2 groups and no distant metastasis was detected.

Patients undergoing RFA had shorter procedure time (3.4 [2.5] vs. 86.0 [37.0] minutes, p < 0.001), lower estimated blood loss (0 vs. 20 [10.0] mL, p < 0.001), shorter hospitalization (0 vs. 7.0 [3.0] days, p < 0.001), lower cost ($2035.7 [254.0] vs. $2269.1 [943.4], p < 0.001), and lower complication rate (0% vs. 4.5%, p < 0.001) than those treated with conventional thyroid lobectomy. A strength of this study is that the authors set strict inclusion criteria and applied 1:1 propensity score matching to control for potential biases. A major limitation is that it had a relatively short follow-up duration leaving long-term efficacy as a question.

Discussion

Sometimes less is more but sometimes more is better. Whether this proves to be true over the long term for these new technologies and procedures requires continued rigorous study. It is incumbent upon us to get the best outcomes at the lowest costs. Our patients and societies demand value and we should do everything we can to provide it.

The promise of improved outcomes as it relates to voice and hypoparathyroidism is at the core of what we are trying to achieve in every thyroid intervention or surgery. Some challenges to adopting cIONM are cost and ease of use, given the trend toward smaller incisions and remote access surgery. Another future challenge is to make this technology compatible with directed ablation techniques such as RFA to help optimize preservation of nerve function in these procedures.

Parathyroid AF appears to be a promising technology to help identify and preserve parathyroid glands, but an easy and confident assessment of viability is lacking and sorely needed if this technology is truly to have an impact on reducing the rate of permanent hypoparathyroidism. Furthermore, the technology needs to be refined so that it can also be used in remote access surgery.

Quality-of-life impairment, a neck scar, or needing to take thyroid hormone is unacceptable to some patients. We must not be paternalistic; rather we should endeavor to understand our patients' fears and needs by seeking solutions or alternatives to what has been the standard especially when they may add value for that particular patient.

Transoral thyroid surgery seems to be safe and effective in select patients when performed endoscopically or robotically, but the time and cost that it takes to use the robot may make its use prohibitive for most health care systems. That does not mean that the robot should be discounted as future iterations may permit the inclusion of some patients with thyroid disease who are currently not candidates for the endoscopic technique.

There is no doubt that interventional ablative techniques such as RFA are disruptive to the field of thyroid surgery. The ability to reduce the size of a benign thyroid nodule to reduce symptoms or ablate a thyroid cancer in the office, without general anesthesia while reducing the risk of needing thyroid hormone supplementation, is appealing to almost all patients. One immediate future challenge that needs to be overcome is getting payors to cover this procedure. Newer ablative technologies will be developed that along with improvements in imaging and the introduction of automation will help to standardize the techniques and outcomes for a given disease process.

This will help make these ablative procedures more available to all patients and take the operator dependency out of the equation that is inherent in surgery. Our patients are searching for personalized treatments more and more. They will challenge us to learn about and refine these technologies and interventions so we may offer them as an option to all our patients.

Conclusions

cIONM and parathyroid AF detection technology seem to be the latest adjuncts that promise to improve thyroid surgical and interventional outcomes and require further study and refinement to see whether they become a standard. Transoral thyroid surgery eliminates the concern for a neck scar or any cutaneous scar for that matter when surgery is required and may be of value to some patients. Its future role with the advent of interventional ablative techniques such as RFA is questionable (Table 1).

Table 1.

Key Points

- Continuous intraoperative nerve monitoring is better at preventing intraoperative nerve injury, resulting in postoperative vocal fold motion impairment compared with intermittent intraoperative nerve monitoring.

- Near-infrared autofluorescence technology may prove to be an important surgical adjunct for the identification of parathyroid glands but further studies need to be performed to define utility.

- TOETVA can be done safely with comparable outcomes to open thyroidectomy by experienced surgeons for select patients in a North American demographic.

- Higher BMI did not have a significant effect on TOETVA outcomes in this study, which is important to demonstrate given the higher rate of obesity in the United States of America compared with other countries who have popularized this technique.

- Patients who underwent RFA for benign thyroid nodules had a better quality of life compared with patients who underwent traditional surgery early after the respective interventions. Further rigorous studies defining short- and long-term outcomes for RFA of benign nodules compared with observation and surgery are needed.

- RFA for PTMC appears to have a lower complication rate and lower cost compared with surgery with comparable oncologic outcomes over the short term. Long-term outcomes for RFA of PTMC need to be assessed and compared with active surveillance and surgery.

BMI, body mass index; PTMC, papillary thyroid microcarcinoma; RFA, radiofrequency ablation; TOETVA, transoral endoscopic thyroidectomy vestibular approach.

RFA of thyroid nodules is being refined and other interventional ablative technologies for these purposes are evolving. Considerations for automation with improved imaging may lead to standardized outcomes and safety profiles that may prove superior to the variability in outcomes seen with surgery. These new technologies together endeavor to disrupt the way we treat thyroid nodules both benign and malignant.

Footnotes

Author Disclosure Statement

R.P.T. discloses that he is a consultant for Medtronic, RGS Healthcare, and Pulse Biosciences. K.M.A. has nothing to disclose.

Funding Information

No funding was received for this study.

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