Katrin Brauckhoff

Thyroid cancer is the most common endocrine malignancy and consists of a diverse group of histological entities¹. Although ranging from indolent and well differentiated to aggressive and rapidly developing carcinomas, advanced disease may present in each histological subtype. Even though the characteristics of advanced thyroid cancer are recognized intuitively by experienced surgeons in the field, a common definition among scientific societies is yet to be reached². General definitions of advanced disease are included in the broader management guidelines for each cancer subtype, such as the American Thyroid Association (ATA) guidelines for differentiated thyroid cancer (DTC)³, medullary thyroid cancer (MTC)⁴, and anaplastic thyroid cancer (ATC)⁵. In the European setting, the 2019 European Society of Medical Oncology (ESMO) guideline⁶ on thyroid cancer includes a subsection on the management of advanced disease for each thyroid cancer type. Given the recent progress and new developments in targeted therapy, depending on the genetic alterations of the tumour, new interest has emerged in better defining advanced thyroid disease and selecting candidates for tailored therapy, either in an adjuvant systemic or neoadjuvant setting. This is reflected in the most recent published position statement by the American Head and Neck Society (AHNS) and International Thyroid Oncology Group⁷, as well as the clinical practice guidelines update by ESMO for the use of systemic therapy in advanced thyroid cancer⁸. Nevertheless, existing efforts to define advanced thyroid cancer and to produce management guidelines have been burdened by a common denominator, the lack of high-quality evidence, especially regarding definitions and surgical management.

Techniques for autofluorescence have been introduced to visualize the parathyroid glands during surgery and to reduce hypoparathyroidism after thyroidectomy. This parallel multicentre RCT investigated the use of Fluobeam^® LX to visualize the parathyroid glands by autofluorescence during total thyroidectomy compared with no use. There was no restriction on the indication for surgery. Patients were randomized 1 : 1 and were blinded to the group allocation. The hypothesis was that autofluorescence enables identification and protection of the parathyroid glands during thyroidectomy. The primary endpoint was the rate of low parathyroid hormone (PTH) levels the day after surgery. Some 535 patients were randomized, and 486 patients received an intervention according to the study protocol, 246 in the Fluobeam^® LX group and 240 in the control group. Some 64 patients (26.0 per cent) in the Fluobeam^® LX group and 77 (32.1 per cent) in the control group had low levels of PTH after thyroidectomy (P = 0.141; relative risk (RR) 0.81, 95 per cent c.i. 0.61 to 1.07). Subanalysis of 174 patients undergoing central lymph node clearance showed that 15 of 82 (18 per cent) in the Fluobeam^® LX group and 31 of 92 (33 per cent) in the control group had low levels of PTH on postoperative day 1 (P = 0.021; RR 0.54, 0.31 to 0.93). More parathyroid glands were identified during operation in patients who had surgery with Fluobeam^® LX, and fewer parathyroid glands in the surgical specimen on definitive histopathology. No specific harm related to the use of Fluobeam^® LX was reported. The use of autofluorescence during thyroidectomy did not reduce the rate of low PTH levels on postoperative day 1 in the whole group of patients. It did, however, reduce the rate in a subgroup of patients. Registration number: NCT04509011 (http://www.clinicaltrials.gov).

Objective: Vocal cord (VC) movement has been demonstrated by the use of accelerometry (ACC) to decrease in parallel with the electromyographic amplitude (EMG) during ongoing traction injury to the recurrent laryngeal nerve (RLN). When RLN function recovers, discrepancies between EMG and VC movement have been reported in clinical and experimental studies. The present study was conducted to clarify the actual relationship between EMG and VC movement measured by ACC during nerve recovery. Methods: EMG obtained by continuous nerve monitoring (C-IONM) was compared with ACC during traction injury to the RLN, and throughout 40-min nerve recovery. A three-axis linear accelerometer probe was attached to the VC, and ACC data were registered as described. Traction damage was applied to the RLN until there was a 70% amplitude decrease from base-line EMG, or until loss of signal (LOS), that is, EMG values <= 100 mu V. Results: Thirty-two RLN from 16 immature pigs were studied. Correlation between EMG and ACC were calculated during nerve injury and nerve recovery. The mean correlations were for the 70% and LOS group from start to end of traction: 0.82 (+/- 0.17) and 0.87 (+/- 0.17), respectively. Corresponding correlation coefficients during 40-min recovery was 0.50 (+/- 0.48) in the 70% group and 0.53 (+/- 0.33) in the LOS group. Conclusion: There is a high correlation between EMG and VC movement during nerve injury, and a moderate correlation during early nerve recovery. EMG recovery after RLN injury ensures sufficient VC function as assessed by ACC.

Objective If bilateral thyroid surgery is planned and staged thyroidectomy considered in case of loss of neuromonitoring signal (LOS), a waiting time of 20 minutes is suggested for evaluation of early nerve recovery. This recommendation is based on clinical observations and has not been thoroughly validated experimentally. Methods Sixteen pigs were randomly studied, and electromyogram (EMG) was continuously recorded during traction injury until an amplitude decrease of 70% from baseline (BL) (16 nerves) or LOS (16 nerves), and further during 40‐minute recovery time. At the end of the experiments, vocal cord twitch was evaluated by video‐laryngoscopy. Results In the 70% group, 8 of 16 nerves recovered to or above an amplitude of 50% of baseline after 20 minutes and finally one more after 40 minutes. In the LOS group, only one nerve showed recovery after 20 minutes and one more after 40 minutes. Video‐laryngoscopy revealed good or strong vocal cord twitches, in 10 of 14 nerves in the 70% group and in only 2 of 14 nerves in the LOS group. Conclusions The overall intraoperative recovery was low after LOS. Even after 70% amplitude depression, only half of the nerves showed recovery to amplitudes ≥50% of BL. Nerve recovery is dynamic, and a waiting time of 20 minutes seems appropriate for the identification of early nerve recovery before decisions are taken to continue or terminate surgery. The final EMG amplitude was not always well correlated with estimated vocal cord twitch, evaluated by video‐laryngoscopy. This observation needs further investigation.

Objective: Gradual impairment of nerve conduction is expected to be tightly associated with simultaneous gradual loss of vocal cord contractility, related to the fact that injured axons are connected to a defined number of muscle cells. In clinical studies, there is a time gap between observed adverse electromyographic (EMG) changes and examination of vocal cord function. This study evaluates the impact of intraoperative EMG changes on synchronous vocal cord contractility by simultaneous use of continuous intraoperative neuromonitoring (C‐IONM) and accelerometry for registration of actual vocal cord function at a given change of EMG amplitude.Methods: EMG was obtained following vagus nerve stimulation by use of C‐IONM. A vocal cord accelerometer probe that could be attached to the vocal cords was developed based on a LIS3DH ultra low‐power high performance three axis linear accelerometer (STMicroelectronics, Geneva, Switzerland). Accelerometer data were registered continuously together with EMG data during traction injury of the recurrent laryngeal nerve (RLN) until an amplitude depression ≤100 μV.Results: Six RLN from four immature domestic pigs were studied. Vocal cord contractility assessed by vocal cord accelerometry decreased in parallel with EMG amplitude, with significant correlations ranging from 0.707 to 0.968.Conclusion: Decrease of EMG amplitude during traction injury to the RLN injury is closely associated with a parallel drop in vocal cord contractility.Level of Evidence: NA Laryngoscope, 130:1090–1096, 2020

The purpose of this publication was to inform surgeons as to the modern state‐of‐the‐art evidence‐based guidelines for management of the recurrent laryngeal nerve invaded by malignancy through blending the domains of 1) surgical intraoperative information, 2) preoperative glottic function, and 3) intraoperative real‐time electrophysiologic information. These guidelines generated by the International Neural Monitoring Study Group (INMSG) are envisioned to assist the clinical decision‐making process involved in recurrent laryngeal nerve management during thyroid surgery by incorporating the important information domains of not only gross surgical findings but also intraoperative recurrent laryngeal nerve functional status and preoperative laryngoscopy findings. These guidelines are presented mainly through algorithmic workflow diagrams for convenience and the ease of application. These guidelines are published in conjunction with the INMSG Guidelines Part I: Staging Bilateral Thyroid Surgery With Monitoring Loss of Signal.Level of Evidence: 5Laryngoscope, 128:S18–S27, 2018

This publication offers modern, state‐of‐the‐art International Neural Monitoring Study Group (INMSG) guidelines based on a detailed review of the recent monitoring literature. The guidelines outline evidence‐based definitions of adverse electrophysiologic events, especially loss of signal, and their incorporation in surgical strategy. These recommendations are designed to reduce technique variations, enhance the quality of neural monitoring, and assist surgeons in the clinical decision‐making process involved in surgical management of recurrent laryngeal nerve. The guidelines are published in conjunction with the INMSG Guidelines Part II, Optimal Recurrent Laryngeal Nerve Management for Invasive Thyroid Cancer–Incorporation of Surgical, Laryngeal, and Neural Electrophysiologic Data. Laryngoscope , 128:S1–S17, 2018

Background: Recurrent laryngeal nerve (RLN) injury during surgery may reveal differences in electromyographic (EMG) changes after sustained compression or traction.Methods: In 20 pigs with the NIM‐FLEX EMG‐endotracheal tube, EMG was recorded at baseline, during sustained RLN compression, or traction until 70% amplitude decrease and during 30 minutes of recovery.Results: Seventy percent amplitude decrease from baseline was reached after 110 ± 98 seconds (compression group) and 2034 ± 2108 seconds (traction group). Traction induced a pronounced latency increase, peaking at 122 ± 8% in contrast to compression with 106 ± 5% (P < .001). The EMG amplitude recovery to ≥50% of baseline failed in 7 nerves after compression and 8 nerves after traction.Conclusion: Compression caused a fast decrease of EMG amplitude with minor effects on latency. In contrast, RLN traction showed early and significant latency increase preceding a delayed amplitude decrease. Recovery rate of the EMG signals were similar in both groups.

Purpose Traction is the most common cause of injury to the recurrent laryngeal nerve (RLN) in endocrine neck surgery. The purpose of this study was to evaluate specific alterations to the electromyogram (EMG) and verify safe alarm limits in a porcine model of sustained traction of the RLN using continuous intraoperative neuromonitoring (C-IONM). Methods Sixteen Norwegian Landrace pigs were anesthetized and intubated with a tracheal tube with a stick-on laryngeal electrode. EMG was recorded at baseline (BL) and during sustained traction applied to each RLN until 70 % amplitude decrease from BL, and during 30-min recovery. Results In 29 nerves at risk (NAR), BL amplitude and latency values were 1098 ± 418 (586–2255) μV (mean ± SD (range)) (right vagus) and 845 ± 289 (522–1634) μV (left vagus), and 4.7 ± 0.5 (4.1–5.9) ms and 7.9 ± 0.8 (6.7–9.6) ms, respectively. At 50 % amplitude decrease, latency increased by 14.0 ± 5.7 % (right side) and 14.5 ± 9.1 % (left side) compared with BL. Corresponding values for 70 % amplitude depression were 17.9 ± 6.1 % and 17.3 ± 12.8 %. Traction time to 50 and 70 % amplitude decrease ranged from 3 to 133 min and 3.9–141 min, respectively. In 16 NAR (55 %), time from 50 to 70 % reduction in amplitude was ≤5 min, but in six NAR (21 %) ≤1 min. In only 11 (38 %) of 29 nerves, the amplitude recovered to more than 50 % of BL. Conclusions Latency increase may be the first warning of RLN stretch injury. Given the short interval between 50 and 70 % amplitude reduction of the EMG, amplitude reduction by 50 % can be taken as an appropriate alert limit.

Background: Continuous vagal intraoperative neuromonitoring (CIONM) of the recurrent laryngeal nerve (RLN) may reduce the risk of RLN lesions during high‐risk endocrine neck surgery such as operation for large goiter potentially requiring transsternal surgery, advanced thyroid cancer, and recurrence.Methods: Fifty‐five consecutive patients (41 female, median age 61 years, 87 nerves at risk) underwent high‐risk endocrine neck surgery. CIONM was performed using the commercially available NIM‐Response 3.0 nerve monitoring system with automatic periodic stimulation (APS) and matching endotracheal tube electrodes (Medtronic Inc.). All CIONM events (decreased amplitude/increased latency) were recorded.Results: APS malfunction occurred on three sides (3 %). A total of 138 CIONM events were registered on 61 sides. Of 138, 47 (34 %) events were assessed as imminent (13 events) or potentially imminent (34 events) lesions, whereas 91 (66 %) were classified as artifacts. Loss of signal was observed in seven patients. Actions to restore the CIONM baseline were undertaken in 58/138 (42 %) events with a median 60 s required per action. Four RLN palsies (3 transient, 1 permanent) occurred: one in case of CIONM malfunction, two sudden without any significant previous CIONM event, and one without any CIONM event. The APS vagus electrode led to temporary damage to the vagus nerve in two patients.Conclusions: CIONM may prevent RLN palsies by timely recognition of imminent nerve lesions. In high‐risk endocrine neck surgery, CIONM may, however, be limited in its utility by system malfunction, direct harm to the vagus nerve, and particularly, inability to indicate RLN lesions ahead in time.