Langenbecks Arch Surg (2014) 399:199–207 DOI 10.1007/s00423-013-1141-y
REVIEW ARTICLE
Intraoperative neural monitoring in thyroid cancer surgery Gregory W. Randolph & Dipti Kamani
Received: 30 October 2013 / Accepted: 3 November 2013 / Published online: 27 November 2013 # Springer-Verlag Berlin Heidelberg 2013
Abstract Background Intraoperative neural monitoring (IONM) has increasingly garnered the attention of the surgeons performing thyroid and parathyroid surgery around the world. Current studies suggest a majority of general and head and neck surgeons utilize neural monitoring in their thyroid surgical case load in both the US and Germany. Purpose We aim to present an up-to-date review of the application of IONM specifically focusing on its utility in thyroid cancer surgery. Neural monitoring is discussed particularly as it relates to neural prognosis, the issues of staged thyroid surgery for thyroid cancer, and new horizons in the monitoring of the superior laryngeal nerve (SLN) and prevention of neural injury through continuous vagal neural monitoring. Conclusion IONM, as it relates to thyroid surgery, has obtained a widespread acceptance as an adjunct to the gold standard of visual nerve identification. The value of IONM in prognosticating neural function and in intraoperative decision making regarding proceeding to bilateral surgery is also well-known. Initial data on recent extensions of IONM in the form of SLN monitoring and continuous vagal nerve monitoring are promising. Continuous vagal nerve monitoring expands the utility of IONM by providing real-time electrophysiological information, allowing surgeons to take a corrective action in impending neural injury.
Keywords Recurrent laryngeal nerve . Electrophysiologic intraoperative neural monitoring . Continuous monitoring . Vocal cord paralysis . Voice . Thyroid surgery . Recurrent laryngeal nerve injury
Introduction Recurrent laryngeal nerve (RLN) visualization is currently considered the gold standard for RLN preservation. However, a key issue is that a visualized and structurally intact nerve not necessarily implies a normal postoperative nerve function. A recent analysis of 27 articles, which reviewed over 25,000 patients undergoing thyroidectomy found that the average postoperative vocal cord paralysis (VCP) rate was 9.8 % and ranged from 0–18.6 % [1]. Unilateral VCP can be associated with voice changes sufficient to alter vocation and can be commonly accompanied by dysphagia and aspiration [2]. Bilateral VCP may result in tracheotomy.
The application of IONM in thyroid cancer surgery—case reports To introduce how neural monitoring may be helpful to a thyroid cancer surgeon, we will review neural monitoring applications in several thyroid cancer cases.
G. W. Randolph : D. Kamani Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Division of Thyroid and Parathyroid Surgery, Harvard Medical School, 243, Charles St., Boston, MA 02114, USA D. Kamani e-mail: [email protected] G. W. Randolph (*) Massachusetts General Hospital, Division of Surgical Oncology, Endocrine Surgical Service, Harvard Medical School, Boston, MA 02114, USA e-mail: [email protected]
Case 1. Neural mapping: During revision right paratracheal dissection for recurrent papillary thyroid carcinoma (PTC) nodes, the intraoperative neural monitoring (IONM) technique of neural mapping may be used. A neural monitor probe set on 2 mA may be used to electrically map out the course of the nerve in the right paratracheal region, prior to its visualization. The entire course of the nerve through the paratracheal region can be mapped. The neural map provides significant advantage as a guide to subsequent dissection and visualization of the nerve in this region. Such a
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consider staging the right thyroid surgery to avoid potential bilateral cord paralysis. Case 4. Dynamic assessment through continuous vagal monitoring: During the delivery of group of matted malignant nodes in the left paratracheal region from the mediastinum to the neck base, EMG function of the vagal-RLN circuit can be assessed continually. Continuous real-time assessment of amplitude and latency measures may allow determination of incipient neural EMG changes evolving dynamically during such retraction maneuvers and may imply RLN stretch injury. Preliminary data suggest EMG changes associated with impending neural injury can be recognized and are largely reversible with modification of the associated surgical maneuver.
Standard IONM
Fig. 1 a Intraoperative view of the recurrent laryngeal nerve invaded by thyroid malignancy [19], b Microscopic view of the recurrent laryngeal nerve invaded by thyroid malignancy [19]
dissection can be limited and optimally focused to the region of the RLN. Case 2. Insight into pathologic states of the RLN: Preoperative examination of a patient with PTC reveals right VCP. Intraoperatively, the right RLN is found invaded by paratracheal lymphadenopathy (see Fig. 1a and b). Electrophysiologic stimulation of the nerve reveals significant residual electromyogaphic (EMG) activity. Despite malignant infiltration, the surgeon is now aware of the functional significance of neural resection, given the existing electrophysiologic activity of the nerve. Regardless of preoperative VCP, the resection of such a nerve will engender some degree of additional dysphagia and aspiration. Visual inspection of the nerve does not provide such functional information. Case 3. Neural function prognostication: During dissection of the left thyroid lobe in a patient with PTC, the initial EMG amplitude response decreases from 950 μV to approximately 75 μV. Loss of laryngeal twitch response is associated with this EMG change. The surgeon appreciates that postoperative function of the left RLN is likely to be abnormal and may
IONM has been increasingly employed in thyroid and parathyroid surgery as an adjunct to visual nerve identification, to aid in intraoperative nerve management and in prognostication of postoperative nerve function [3–6]. Several recent studies suggest that a majority of surgeons in the United States currently employ neural monitoring- 53 % of general surgeons and 65 % of otolaryngologists in the United States use IONM in some or all of their cases. A recent survey of surgical departments in Germany reported that more than 92 % of surgeons routinely utilize IONM during thyroidectomy [7–9]. IONM is more commonly used by surgeons with high volume surgeries of >100 cases per year than with lower volume thyroid surgeons [9]. Organizational support for neural monitoring is also accumulating. German Practice Guidelines and the International Neural Monitoring Study Group suggest that IONM should be considered for all cases of thyroid surgery [10, 11]. Recently published guidelines by the American Academy of Otolaryngology and Head and Neck Surgery (AAOHNS) propose IONM as an option for patients undergoing thyroid surgery, due to proven utility of IONM in three distinct areas: (1) reduction in RLN identification time, (2) decline in temporary VCP rates, and (3) avoidance of bilateral VCP (through prognostication of postoperative vocal cord function). These AAOHNS guidelines suggest significant utility of IONM in cases of (1) bilateral thyroid surgery, (2) revision thyroid surgery, and (3) surgery in the setting of an existing RLN paralysis [12]. Two recently published American Thyroid Association Surgical Affairs Committee consensus statements (on outpatient thyroid surgery and on optimal surgical management of goiters) note that neural monitoring can be helpful in confirming intact neural function at the end of surgery, and this may impact on discharge planning [13, 14]. Also, the American Head and Neck Society guidelines for the management of invasive thyroid cancer suggests that IONM provides important
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intraoperative and postoperative functional information that has an impact on timing of contralateral surgery, possible tracheotomy, and recommends IONM for all cases of thyroid cancer.
Laryngeal exam Routine preoperative and postoperative laryngeal exam at the time of thyroidectomy is currently recommended by the British Association of Endocrine and Thyroid Surgeons, the German Association of Endocrine Surgery [10], and by the International Neural Monitoring Study Group [11]. The NCCN recommend laryngeal exam in all patients with thyroid malignancy [16]. The American Thyroid Association Anaplastic Cancer Guidelines [15] and Goiter Surgery Guidelines both recommend preoperative laryngeal exam as do the American Thyroid Association Goiter Surgery Guidelines [14]. The American Head and Neck Society Invasive Thyroid Cancer Guidelines also recommend a preoperative laryngeal exam in all thyroid cancer patients.
American Academy of Otolaryngology Clinical Practice Guidelines 2013 A large multidisciplinary panel including otolaryngologists, laryngologists, anesthesiologists, general surgeons, medical endocrinologists, nursing representatives, patient advocacy representatives, and clinical practice guidelines experts representing the American Academy of Otolaryngology, the American Thyroid Association, the American Association of Endocrine Surgery, the American Head and Neck Society, and the American Medical Association was convened. Their effort over a nearly 2-year period included multiple face-to-face meetings, conference calls, and document drafts to open commentary. The product is an evidence-based clinical practice guidelines with12 key action statements reviewing laryngeal assessment pre- and post-surgery, intraoperative management, and other issues relating to voice optimization at the time of thyroidectomy [12]. The document reviews the healthcare burden of thyroid surgery, provides a comprehensive listing of all possible neural and non-neural causes of postthyroidectomy dysphonia, and reviews quality of life issues associated with VCP. This document describes that up to 80 % of patients undergoing thyroidectomy report temporary voice disturbance with up to 10 % experiencing temporary or permanent RLN injury. Incidence of RLN injury and impaired RLN function can be up to 30 % in patients undergoing revision thyroid surgery. Up to one third or more patients with unilateral VCP may be asymptomatic. The document recommends a baseline voice assessment for all patients undergoing thyroid surgery. This assessment includes voice observation by the physician and report of voice symptomatology by the
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patient. The AAOHNS recommends preoperative laryngeal exam in the setting of any undeserved or reported voice abnormality on preoperative assessment. Furthermore, preoperative laryngeal exam is recommended in the setting of normal voice in thyroid cancer patients with suspected or proven extrathyroidal extension or with history of neck surgery, that placed the vagus or RLN at risk, such as carotid endarterectomy or anterior approach to the cervical spine. The document further makes recommendations regarding management of the RLN and superior laryngeal nerve (SLN) during thyroid surgery. IONM is recommended as an option for thyroid surgery with proven utility (1) for reduction in RLN identification time, (2) for decline in rate of temporary VCP, and (3) for avoidance of bilateral VCP. The AAOHNS guidelines further suggest special utility for neural monitoring in cases of (1) bilateral thyroid surgery, (2) revision thyroid surgery, and (3) surgery in the setting of existing RLN paralysis. Postoperative voice evaluation is recommended in all patients between 2 to 8 weeks after surgery. Laryngeal exam is recommended for all patients with voice abnormality as determined through this postoperative voice assessment. Laryngeal exam is also recommended in all patients if documentation of VCP is desired, for example, in research studies investigating neural outcomes of thyroid surgery. This is because many patients with VCP may not be symptomatic, and so a post-operative laryngeal exam is warranted for accurate postoperative quality assessment of the true VCP rates in all postsurgical thyroid patients.
Neural monitoring standards The International Neural Monitoring Study Group has defined standards for both RLN and SLN neural monitoring (see Fig. 2 for IONM equipment setup) [12]. Accurate and uniform neural monitoring depends on adherence to these guidelines. Major domains reviewed in these guidelines include endotracheal tube placement and neural monitoring problem-solving. Conversion from neutral intubation position to the extended surgical position may move endotracheal tube positioning up to 6 cm, hence post-extension endotracheal tube position assessment is essential. Aggressive neural monitoring problem solving algorithm adherence improves positive predictive value in the setting of loss of signal (LOS) [11, 12, 18] (see Fig. 3 for LOS algorithm).
Neural monitoring in thyroid cancer We have recently reported on a series of over 1,100 consecutive neck surgeries performed with neural monitoring [19]. In this series, 2 % of patients had preoperative VCP, and 1.9 % had malignant invasion of the RLN at surgery. We found
202 Fig. 2 Basic monitoring equipment setup [11] ET =endotracheal tube, REC =recording electrodes, GND =ground electrodes
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Recording Side
ET
Stimulation Side
Patient
REC
GND
GND
Stimulator Probe
InterfaceConnector Box
nearly 50 % of patients with preoperative VCP had recognizable EMG activity at surgery. Furthermore, in nearly 60 % of cases with gross malignant RLN invasion identified intraoperatively, proximal stimulation of the RLN resulted in recognizable EMG activity. In the setting of the nerve invasion, if preoperative laryngeal exam was normal, intraoperative RLN EMG activity was within normal limits with amplitudes of over 400 μV. Such data provide insight into the pathologic states of RLN in the setting of thyroid cancer invasion. Given that invaded nerves frequently maintain significant EMG activity, further research is required to determine if such nerves may be preserved to optimize nerve function if postoperative adjunct radiotherapy is offered (see Figs. 4 and 5 for management algorithms). Our group has found that neural monitoring during revision thyroid cancer is associated with lower rates of neural complications and a gratifying thyroglobulin response in a series of 117 patients undergoing revision thyroid cancer nodal surgery [17]. In this series, nearly 30 % of the revision surgeries were second through seventh revision thyroid cancer surgery. Preoperatively, 14 % of patients in this series presented with VCP, but none developed new temporary or permanent VCP as a result of revision surgery performed in this series, which we consider is likely predominantly due to neural monitoring.
Neural monitoring and neural function prognosis Probably one of the most important applications of neural monitoring centers on the ability of electrical stimulation of
EMG Monitor
the nerve to sensitively evaluate neural function status. Without neural monitoring, visual examination of the nerve is the only modality available to determine nerve function. Limited data in the literature suggest approximately 10 % of traumatized nerves are visually identified as injured by the surgeon [20–22]. In contrast to such visual neural exam, several studies suggest EMG testing of the vagus-RLN circuit after lobectomy is a highly accurate neural function test and is associated with negative predictive value of over 95 % [23–29]. Positive predictive value is lower and more variable and is related to the degree to which troubleshooting equipment algorithm is applied in the setting of presumptive LOS. Accurate definition of LOS and a better understanding of normative parameters during neural monitoring is essential to optimize the prognostic function of post-lobectomy vagal stimulation [11, 17, 30]. Once definitive LOS is confirmed, retrograde testing of the affected RLN starting at the laryngeal entry point and extending proximally, may identify the segment of nerve injury. This has possible therapeutic and tremendous learning opportunities for the surgeon to appreciate the exact segment of nerve that has been injured. After such electrophysiologic testing of the nerve to identify the neuropraxic segment, the surgeon may consider whether staged surgery is appropriate with the potential goal of avoidance of bilateral nerve injury. LOS definition is an important parameter in maximizing neural prognostication applications of neural monitoring. The International Neural Monitoring Study Group has defined LOS as the reduction of EMG activity to 100 μV or less with concordant loss of laryngeal twitch or identifiable glottis
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Fig. 3 Intraoperative LOS evaluation standard [11]
twitch during laryngoscopy [11]. It is important to begin the surgery with an initial EMG value which suggests successful normative nerve function; we suggest an initial waveform of 500 μV or higher. Recent work has suggested that an important basic RLN EMG parameter at the conclusion of lobectomy is an amplitude of 250 μV or higher. Our recent series on the 125 neck surgeries performed with neural monitoring suggest that a 250 μV or higher amplitude at the conclusion of surgery is always associated with normal postoperative vocal cord function. The finding of the waveform of this magnitude in terms of amplitude should allow a safe performance of contralateral lobar surgery in all patients [31].
Fig. 4 Management algorithm for the recurrent laryngeal nerve with preoperative vocal cord paralysis [19]
Neural monitoring and staged thyroidectomy in thyroid cancer surgery—an emerging concept Staged surgery in surgical oncology of the head and neck has a long standing history. Frazzell in 1961, at Memorial Hospital New York, reported patients undergoing planned bilateral radical neck dissection as a staged procedure to reduce regional morbidity of bilateral jugular vein sacrifice [32]. Dunhill, in 1912 described staged thyroidectomy in patients with severe toxic goiter. Lahey, in 1936 also described staged thyroidectomy in patients with severe hyperthyroidism. Staged thyroidectomy can be first traced back to reports of Luigi Porta in 1811 [33, 34].
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Fig. 5 Management algorithm of the recurrent laryngeal nerve invaded by malignancy [19]
A small but emerging literature has investigated LOS and its influence on intraoperative decision to stage thyroid surgery. Incorporation of LOS in surgical decision-making regarding proceeding to bilateral thyroidectomy or staging the opposite side surgery has a great impact on bilateral postoperative VCP rate. When opposite side surgery is delayed and a staged thyroidectomy is performed, due to intraoperative LOS during initial side surgery, rate of bilateral VCP essentially reduces to zero as opposed to 9.5 to 17 %, when bilateral surgery is performed without incorporating LOS into surgical algorithm [35–37]. Melin has found no difference in patient satisfaction when surgery was offered in staged manner. Dionigi has discussed the importance of the preoperative consent process when offering possible staged thyroidectomy [38]. Dralle has recently found that 94 % of German surgeons, especially at hospitals with higher surgical volume, prefer to stage a planned bilateral thyroidectomy when they encounter a LOS during surgery on one side [7]. Staged surgery for advanced thyroid cancer is offered routinely in our unit. Recent reports from Japanese colleagues suggest thyroid cancer observation in a limited subset of
Fig. 6 APS electrode on vagus nerve [55]
patients resulted in no added morbidity or mortality in the patients with delayed surgery [39]. In our unit, cases with advanced nodal disease are typically offered initial unilateral surgery. This is done to avoid complications associated with bilateral nerve and bilateral parathyroid injury, to lessen morbidity from regional complications including chyle leak or bilateral jugular vein sacrifice, and to optimize the surgeon’s meticulousness which may decrease with single prolonged bilateral central neck extensive nodal surgery. In our unpublished series of patients presenting with advanced thyroid cancer who were offered planned staged surgery, overall 50 % had invasive disease, 13 % had RLN invasion, 10 % requiring RLN sacrifice, 96.7 % had nodal disease, and 33 % had five or more discreet cervical nodal compartments affected. The average first and second-stage surgery duration was approximately 3 hours each, and generally, the two surgeries were about 2 months apart. Despite this group of patients having advanced disease, permanent RLN paralysis rate was zero, and permanent hypoparathyroidism rate was 3.3 %. Postoperatively, thyroglobulin was undetectable in 90 % and averaged 0.8 ng/ml in 3-year follow-up.
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SLN monitoring Recent work by the International Neural Monitoring Study Group has clarified the role of neural monitoring as it applies to the extra branch of the SLN [18]. Neural stimulation is associated with discrete cricothyroid muscle twitch response which is an accurate measure of positive nerve localization. Neural monitoring is associated with higher rates of nerve identification than through visual identification alone, and recent work has shown the nerve localization is reliably associated with the laryngeal head of the sternothyroid muscle [40]. In addition to cricothyroid muscle twitch, two groups have reported that the EMG activity can be identified by endotracheal tube recording electrodes during external branch stimulation [40, 41]. Recent work has shown that, with appropriate endotracheal tube recording array, glottis EMG activity can be observed in 100 % of cases [42]; the reader is referred to the recent International Neural Monitoring Study Group’s summary of neural monitoring as it relates to the SLN [18].
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We have recently reported one of the largest prospective continuous vagal monitoring studies investigating unique EMG outcome parameters associated with imminent neuropraxic nerve injury and their relationship to intraoperative surgical maneuvers and postoperative VCP. Severe combined event (combined event was defined as concordant amplitude reduction and latency increase) and complete LOS both were strongly associated with postoperative VCP. Severe combined event represents an adverse but reversible EMG change when associated surgical maneuver is aborted; when allowed to continue, severe combined event may progress to LOS (which is significantly less recoverable) and to postoperative VCP. CIONM endows the surgeons to instigate corrective action to preserve nerve function by aborting maneuvers that lead to adverse EMG changes and thus may prevent VCP [55]. Conflicts of interest None. Author contribution GWR: Review conception, analysis and interpretation of literature, drafting of manuscript, critical revision of manuscript. DK: Analysis and interpretation of literature, drafting of manuscript, critical revision of manuscript.
Continuous vagal monitoring and neural injury prevention Existing IONM formats allow the surgeon to intermittently stimulate and evaluate RLN function. While this has significant utility, such intermittent stimulation monitoring format could potentially allows the RLN to be at risk for injury inbetween stimulations [28, 43]. This reality may underlie data signifying that present IONM formats are limited in their ability to prevent neural injury [5, 10, 28, 44–48]. An IONM format providing real-time electrophysiological information leading to detection of impending neural injury would address this issue. A continuous nerve monitor device (CIONM) has the potential to monitor the vagus and RLN functional integrity in real-time during entire surgery [49–51]. Initial studies on CIONM with a vagal nerve electrode (see Fig. 6) have suggested such monitoring is not associated with significant adverse neural, cardiac, pulmonary, or gastrointestinal vagal side effects [23, 43, 49, 52–54]. In order to establish utility, CIONM must provide accurate detection of EMG changes which are (a) considered adverse EMG events in that they are associated with impending VCP; (b) easily recognized by the surgeon intraoperatively; and (c) nascent so that they are completely reversible with modification of the associated surgical maneuver with a resolution of EMG changes. Furthermore, we must be able to segregate such EMG changes of impending neural injury from artifactual EMG changes associated with endotracheal tube malposition or other equipment problems.
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Langenbecks Arch Surg (2014) 399:199–207 observational trial for papillary thyroid microcarcinoma in Japanese patients. World J Surg 34(1):28–35. doi:10.1007/s00268-009-0303-0 40. Potenza AS, Phelan EA, Cernea CR, Slough CM, Kamani DV, Darr A, Zurakowski D, Randolph GW (2013) Normative intra-operative electrophysiologic waveform analysis of superior laryngeal nerve external branch and recurrent laryngeal nerve in patients undergoing thyroid surgery. World J Surg 37(10):2336–2342. doi:10.1007/ s00268-013-2148-9 41. Barczynski M, Nowak W, Sancho JJ, Sitges-Serra A (2010) The motor fibers of the recurrent laryngeal nerves are located in the anterior extralaryngeal branch. Ann Surg 251 (4):773–774; author reply 774–775. doi:10.1097/SLA.0b013e3181d57a59 42. Randolph G (2013) Surgical anatomy of recurrent laryngeal nerve. In: Randolph GW (ed) Surgery of the thyroid and parathyroid, glandsSecondth edn. Saunders, Philadelphia 43. Scott AR, Chong PS, Hartnick CJ, Randolph GW (2010) Spontaneous and evoked laryngeal electromyography of the thyroarytenoid muscles: a canine model for intraoperative recurrent laryngeal nerve monitoring. Ann Otol Rhinol Laryngol 119(1):54–63 44. Dralle H, Sekulla C, Haerting J, Timmermann W, Neumann HJ, Kruse E, Grond S, Muhlig HP, Richter C, Voss J, Thomusch O, Lippert H, Gastinger I, Brauckhoff M, Gimm O (2004) Risk factors of paralysis and functional outcome after recurrent laryngeal nerve monitoring in thyroid surgery. Surgery 136(6):1310–1322. doi:10.1016/j.surg.2004.07.018 45. Chiang FY, Lu IC, Kuo WR, Lee KW, Chang NC, Wu CW (2008) The mechanism of recurrent laryngeal nerve injury during thyroid surgery–the application of intraoperative neuromonitoring. Surgery 143(6):743–749. doi:10.1016/j.surg.2008.02.006 46. Dionigi G, Barczynski M, Chiang FY, Dralle H, Duran-Poveda M, Iacobone M, Lombardi CP, Materazzi G, Mihai R, Randolph GW, Sitges-Serra A (2010) Why monitor the recurrent laryngeal nerve in thyroid surgery? J Endocrinol Invest 33(11):819–822 47. Higgins TS, Gupta R, Ketcham AS, Sataloff RT, Wadsworth JT, Sinacori JT (2011) Recurrent laryngeal nerve monitoring versus identification alone on post-thyroidectomy true vocal
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REVIEW ARTICLE
Intraoperative neural monitoring in thyroid cancer surgery Gregory W. Randolph & Dipti Kamani
Received: 30 October 2013 / Accepted: 3 November 2013 / Published online: 27 November 2013 # Springer-Verlag Berlin Heidelberg 2013
Abstract Background Intraoperative neural monitoring (IONM) has increasingly garnered the attention of the surgeons performing thyroid and parathyroid surgery around the world. Current studies suggest a majority of general and head and neck surgeons utilize neural monitoring in their thyroid surgical case load in both the US and Germany. Purpose We aim to present an up-to-date review of the application of IONM specifically focusing on its utility in thyroid cancer surgery. Neural monitoring is discussed particularly as it relates to neural prognosis, the issues of staged thyroid surgery for thyroid cancer, and new horizons in the monitoring of the superior laryngeal nerve (SLN) and prevention of neural injury through continuous vagal neural monitoring. Conclusion IONM, as it relates to thyroid surgery, has obtained a widespread acceptance as an adjunct to the gold standard of visual nerve identification. The value of IONM in prognosticating neural function and in intraoperative decision making regarding proceeding to bilateral surgery is also well-known. Initial data on recent extensions of IONM in the form of SLN monitoring and continuous vagal nerve monitoring are promising. Continuous vagal nerve monitoring expands the utility of IONM by providing real-time electrophysiological information, allowing surgeons to take a corrective action in impending neural injury.
Keywords Recurrent laryngeal nerve . Electrophysiologic intraoperative neural monitoring . Continuous monitoring . Vocal cord paralysis . Voice . Thyroid surgery . Recurrent laryngeal nerve injury
Introduction Recurrent laryngeal nerve (RLN) visualization is currently considered the gold standard for RLN preservation. However, a key issue is that a visualized and structurally intact nerve not necessarily implies a normal postoperative nerve function. A recent analysis of 27 articles, which reviewed over 25,000 patients undergoing thyroidectomy found that the average postoperative vocal cord paralysis (VCP) rate was 9.8 % and ranged from 0–18.6 % [1]. Unilateral VCP can be associated with voice changes sufficient to alter vocation and can be commonly accompanied by dysphagia and aspiration [2]. Bilateral VCP may result in tracheotomy.
The application of IONM in thyroid cancer surgery—case reports To introduce how neural monitoring may be helpful to a thyroid cancer surgeon, we will review neural monitoring applications in several thyroid cancer cases.
G. W. Randolph : D. Kamani Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Division of Thyroid and Parathyroid Surgery, Harvard Medical School, 243, Charles St., Boston, MA 02114, USA D. Kamani e-mail: [email protected] G. W. Randolph (*) Massachusetts General Hospital, Division of Surgical Oncology, Endocrine Surgical Service, Harvard Medical School, Boston, MA 02114, USA e-mail: [email protected]
Case 1. Neural mapping: During revision right paratracheal dissection for recurrent papillary thyroid carcinoma (PTC) nodes, the intraoperative neural monitoring (IONM) technique of neural mapping may be used. A neural monitor probe set on 2 mA may be used to electrically map out the course of the nerve in the right paratracheal region, prior to its visualization. The entire course of the nerve through the paratracheal region can be mapped. The neural map provides significant advantage as a guide to subsequent dissection and visualization of the nerve in this region. Such a
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consider staging the right thyroid surgery to avoid potential bilateral cord paralysis. Case 4. Dynamic assessment through continuous vagal monitoring: During the delivery of group of matted malignant nodes in the left paratracheal region from the mediastinum to the neck base, EMG function of the vagal-RLN circuit can be assessed continually. Continuous real-time assessment of amplitude and latency measures may allow determination of incipient neural EMG changes evolving dynamically during such retraction maneuvers and may imply RLN stretch injury. Preliminary data suggest EMG changes associated with impending neural injury can be recognized and are largely reversible with modification of the associated surgical maneuver.
Standard IONM
Fig. 1 a Intraoperative view of the recurrent laryngeal nerve invaded by thyroid malignancy [19], b Microscopic view of the recurrent laryngeal nerve invaded by thyroid malignancy [19]
dissection can be limited and optimally focused to the region of the RLN. Case 2. Insight into pathologic states of the RLN: Preoperative examination of a patient with PTC reveals right VCP. Intraoperatively, the right RLN is found invaded by paratracheal lymphadenopathy (see Fig. 1a and b). Electrophysiologic stimulation of the nerve reveals significant residual electromyogaphic (EMG) activity. Despite malignant infiltration, the surgeon is now aware of the functional significance of neural resection, given the existing electrophysiologic activity of the nerve. Regardless of preoperative VCP, the resection of such a nerve will engender some degree of additional dysphagia and aspiration. Visual inspection of the nerve does not provide such functional information. Case 3. Neural function prognostication: During dissection of the left thyroid lobe in a patient with PTC, the initial EMG amplitude response decreases from 950 μV to approximately 75 μV. Loss of laryngeal twitch response is associated with this EMG change. The surgeon appreciates that postoperative function of the left RLN is likely to be abnormal and may
IONM has been increasingly employed in thyroid and parathyroid surgery as an adjunct to visual nerve identification, to aid in intraoperative nerve management and in prognostication of postoperative nerve function [3–6]. Several recent studies suggest that a majority of surgeons in the United States currently employ neural monitoring- 53 % of general surgeons and 65 % of otolaryngologists in the United States use IONM in some or all of their cases. A recent survey of surgical departments in Germany reported that more than 92 % of surgeons routinely utilize IONM during thyroidectomy [7–9]. IONM is more commonly used by surgeons with high volume surgeries of >100 cases per year than with lower volume thyroid surgeons [9]. Organizational support for neural monitoring is also accumulating. German Practice Guidelines and the International Neural Monitoring Study Group suggest that IONM should be considered for all cases of thyroid surgery [10, 11]. Recently published guidelines by the American Academy of Otolaryngology and Head and Neck Surgery (AAOHNS) propose IONM as an option for patients undergoing thyroid surgery, due to proven utility of IONM in three distinct areas: (1) reduction in RLN identification time, (2) decline in temporary VCP rates, and (3) avoidance of bilateral VCP (through prognostication of postoperative vocal cord function). These AAOHNS guidelines suggest significant utility of IONM in cases of (1) bilateral thyroid surgery, (2) revision thyroid surgery, and (3) surgery in the setting of an existing RLN paralysis [12]. Two recently published American Thyroid Association Surgical Affairs Committee consensus statements (on outpatient thyroid surgery and on optimal surgical management of goiters) note that neural monitoring can be helpful in confirming intact neural function at the end of surgery, and this may impact on discharge planning [13, 14]. Also, the American Head and Neck Society guidelines for the management of invasive thyroid cancer suggests that IONM provides important
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intraoperative and postoperative functional information that has an impact on timing of contralateral surgery, possible tracheotomy, and recommends IONM for all cases of thyroid cancer.
Laryngeal exam Routine preoperative and postoperative laryngeal exam at the time of thyroidectomy is currently recommended by the British Association of Endocrine and Thyroid Surgeons, the German Association of Endocrine Surgery [10], and by the International Neural Monitoring Study Group [11]. The NCCN recommend laryngeal exam in all patients with thyroid malignancy [16]. The American Thyroid Association Anaplastic Cancer Guidelines [15] and Goiter Surgery Guidelines both recommend preoperative laryngeal exam as do the American Thyroid Association Goiter Surgery Guidelines [14]. The American Head and Neck Society Invasive Thyroid Cancer Guidelines also recommend a preoperative laryngeal exam in all thyroid cancer patients.
American Academy of Otolaryngology Clinical Practice Guidelines 2013 A large multidisciplinary panel including otolaryngologists, laryngologists, anesthesiologists, general surgeons, medical endocrinologists, nursing representatives, patient advocacy representatives, and clinical practice guidelines experts representing the American Academy of Otolaryngology, the American Thyroid Association, the American Association of Endocrine Surgery, the American Head and Neck Society, and the American Medical Association was convened. Their effort over a nearly 2-year period included multiple face-to-face meetings, conference calls, and document drafts to open commentary. The product is an evidence-based clinical practice guidelines with12 key action statements reviewing laryngeal assessment pre- and post-surgery, intraoperative management, and other issues relating to voice optimization at the time of thyroidectomy [12]. The document reviews the healthcare burden of thyroid surgery, provides a comprehensive listing of all possible neural and non-neural causes of postthyroidectomy dysphonia, and reviews quality of life issues associated with VCP. This document describes that up to 80 % of patients undergoing thyroidectomy report temporary voice disturbance with up to 10 % experiencing temporary or permanent RLN injury. Incidence of RLN injury and impaired RLN function can be up to 30 % in patients undergoing revision thyroid surgery. Up to one third or more patients with unilateral VCP may be asymptomatic. The document recommends a baseline voice assessment for all patients undergoing thyroid surgery. This assessment includes voice observation by the physician and report of voice symptomatology by the
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patient. The AAOHNS recommends preoperative laryngeal exam in the setting of any undeserved or reported voice abnormality on preoperative assessment. Furthermore, preoperative laryngeal exam is recommended in the setting of normal voice in thyroid cancer patients with suspected or proven extrathyroidal extension or with history of neck surgery, that placed the vagus or RLN at risk, such as carotid endarterectomy or anterior approach to the cervical spine. The document further makes recommendations regarding management of the RLN and superior laryngeal nerve (SLN) during thyroid surgery. IONM is recommended as an option for thyroid surgery with proven utility (1) for reduction in RLN identification time, (2) for decline in rate of temporary VCP, and (3) for avoidance of bilateral VCP. The AAOHNS guidelines further suggest special utility for neural monitoring in cases of (1) bilateral thyroid surgery, (2) revision thyroid surgery, and (3) surgery in the setting of existing RLN paralysis. Postoperative voice evaluation is recommended in all patients between 2 to 8 weeks after surgery. Laryngeal exam is recommended for all patients with voice abnormality as determined through this postoperative voice assessment. Laryngeal exam is also recommended in all patients if documentation of VCP is desired, for example, in research studies investigating neural outcomes of thyroid surgery. This is because many patients with VCP may not be symptomatic, and so a post-operative laryngeal exam is warranted for accurate postoperative quality assessment of the true VCP rates in all postsurgical thyroid patients.
Neural monitoring standards The International Neural Monitoring Study Group has defined standards for both RLN and SLN neural monitoring (see Fig. 2 for IONM equipment setup) [12]. Accurate and uniform neural monitoring depends on adherence to these guidelines. Major domains reviewed in these guidelines include endotracheal tube placement and neural monitoring problem-solving. Conversion from neutral intubation position to the extended surgical position may move endotracheal tube positioning up to 6 cm, hence post-extension endotracheal tube position assessment is essential. Aggressive neural monitoring problem solving algorithm adherence improves positive predictive value in the setting of loss of signal (LOS) [11, 12, 18] (see Fig. 3 for LOS algorithm).
Neural monitoring in thyroid cancer We have recently reported on a series of over 1,100 consecutive neck surgeries performed with neural monitoring [19]. In this series, 2 % of patients had preoperative VCP, and 1.9 % had malignant invasion of the RLN at surgery. We found
202 Fig. 2 Basic monitoring equipment setup [11] ET =endotracheal tube, REC =recording electrodes, GND =ground electrodes
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Recording Side
ET
Stimulation Side
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nearly 50 % of patients with preoperative VCP had recognizable EMG activity at surgery. Furthermore, in nearly 60 % of cases with gross malignant RLN invasion identified intraoperatively, proximal stimulation of the RLN resulted in recognizable EMG activity. In the setting of the nerve invasion, if preoperative laryngeal exam was normal, intraoperative RLN EMG activity was within normal limits with amplitudes of over 400 μV. Such data provide insight into the pathologic states of RLN in the setting of thyroid cancer invasion. Given that invaded nerves frequently maintain significant EMG activity, further research is required to determine if such nerves may be preserved to optimize nerve function if postoperative adjunct radiotherapy is offered (see Figs. 4 and 5 for management algorithms). Our group has found that neural monitoring during revision thyroid cancer is associated with lower rates of neural complications and a gratifying thyroglobulin response in a series of 117 patients undergoing revision thyroid cancer nodal surgery [17]. In this series, nearly 30 % of the revision surgeries were second through seventh revision thyroid cancer surgery. Preoperatively, 14 % of patients in this series presented with VCP, but none developed new temporary or permanent VCP as a result of revision surgery performed in this series, which we consider is likely predominantly due to neural monitoring.
Neural monitoring and neural function prognosis Probably one of the most important applications of neural monitoring centers on the ability of electrical stimulation of
EMG Monitor
the nerve to sensitively evaluate neural function status. Without neural monitoring, visual examination of the nerve is the only modality available to determine nerve function. Limited data in the literature suggest approximately 10 % of traumatized nerves are visually identified as injured by the surgeon [20–22]. In contrast to such visual neural exam, several studies suggest EMG testing of the vagus-RLN circuit after lobectomy is a highly accurate neural function test and is associated with negative predictive value of over 95 % [23–29]. Positive predictive value is lower and more variable and is related to the degree to which troubleshooting equipment algorithm is applied in the setting of presumptive LOS. Accurate definition of LOS and a better understanding of normative parameters during neural monitoring is essential to optimize the prognostic function of post-lobectomy vagal stimulation [11, 17, 30]. Once definitive LOS is confirmed, retrograde testing of the affected RLN starting at the laryngeal entry point and extending proximally, may identify the segment of nerve injury. This has possible therapeutic and tremendous learning opportunities for the surgeon to appreciate the exact segment of nerve that has been injured. After such electrophysiologic testing of the nerve to identify the neuropraxic segment, the surgeon may consider whether staged surgery is appropriate with the potential goal of avoidance of bilateral nerve injury. LOS definition is an important parameter in maximizing neural prognostication applications of neural monitoring. The International Neural Monitoring Study Group has defined LOS as the reduction of EMG activity to 100 μV or less with concordant loss of laryngeal twitch or identifiable glottis
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Fig. 3 Intraoperative LOS evaluation standard [11]
twitch during laryngoscopy [11]. It is important to begin the surgery with an initial EMG value which suggests successful normative nerve function; we suggest an initial waveform of 500 μV or higher. Recent work has suggested that an important basic RLN EMG parameter at the conclusion of lobectomy is an amplitude of 250 μV or higher. Our recent series on the 125 neck surgeries performed with neural monitoring suggest that a 250 μV or higher amplitude at the conclusion of surgery is always associated with normal postoperative vocal cord function. The finding of the waveform of this magnitude in terms of amplitude should allow a safe performance of contralateral lobar surgery in all patients [31].
Fig. 4 Management algorithm for the recurrent laryngeal nerve with preoperative vocal cord paralysis [19]
Neural monitoring and staged thyroidectomy in thyroid cancer surgery—an emerging concept Staged surgery in surgical oncology of the head and neck has a long standing history. Frazzell in 1961, at Memorial Hospital New York, reported patients undergoing planned bilateral radical neck dissection as a staged procedure to reduce regional morbidity of bilateral jugular vein sacrifice [32]. Dunhill, in 1912 described staged thyroidectomy in patients with severe toxic goiter. Lahey, in 1936 also described staged thyroidectomy in patients with severe hyperthyroidism. Staged thyroidectomy can be first traced back to reports of Luigi Porta in 1811 [33, 34].
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Fig. 5 Management algorithm of the recurrent laryngeal nerve invaded by malignancy [19]
A small but emerging literature has investigated LOS and its influence on intraoperative decision to stage thyroid surgery. Incorporation of LOS in surgical decision-making regarding proceeding to bilateral thyroidectomy or staging the opposite side surgery has a great impact on bilateral postoperative VCP rate. When opposite side surgery is delayed and a staged thyroidectomy is performed, due to intraoperative LOS during initial side surgery, rate of bilateral VCP essentially reduces to zero as opposed to 9.5 to 17 %, when bilateral surgery is performed without incorporating LOS into surgical algorithm [35–37]. Melin has found no difference in patient satisfaction when surgery was offered in staged manner. Dionigi has discussed the importance of the preoperative consent process when offering possible staged thyroidectomy [38]. Dralle has recently found that 94 % of German surgeons, especially at hospitals with higher surgical volume, prefer to stage a planned bilateral thyroidectomy when they encounter a LOS during surgery on one side [7]. Staged surgery for advanced thyroid cancer is offered routinely in our unit. Recent reports from Japanese colleagues suggest thyroid cancer observation in a limited subset of
Fig. 6 APS electrode on vagus nerve [55]
patients resulted in no added morbidity or mortality in the patients with delayed surgery [39]. In our unit, cases with advanced nodal disease are typically offered initial unilateral surgery. This is done to avoid complications associated with bilateral nerve and bilateral parathyroid injury, to lessen morbidity from regional complications including chyle leak or bilateral jugular vein sacrifice, and to optimize the surgeon’s meticulousness which may decrease with single prolonged bilateral central neck extensive nodal surgery. In our unpublished series of patients presenting with advanced thyroid cancer who were offered planned staged surgery, overall 50 % had invasive disease, 13 % had RLN invasion, 10 % requiring RLN sacrifice, 96.7 % had nodal disease, and 33 % had five or more discreet cervical nodal compartments affected. The average first and second-stage surgery duration was approximately 3 hours each, and generally, the two surgeries were about 2 months apart. Despite this group of patients having advanced disease, permanent RLN paralysis rate was zero, and permanent hypoparathyroidism rate was 3.3 %. Postoperatively, thyroglobulin was undetectable in 90 % and averaged 0.8 ng/ml in 3-year follow-up.
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SLN monitoring Recent work by the International Neural Monitoring Study Group has clarified the role of neural monitoring as it applies to the extra branch of the SLN [18]. Neural stimulation is associated with discrete cricothyroid muscle twitch response which is an accurate measure of positive nerve localization. Neural monitoring is associated with higher rates of nerve identification than through visual identification alone, and recent work has shown the nerve localization is reliably associated with the laryngeal head of the sternothyroid muscle [40]. In addition to cricothyroid muscle twitch, two groups have reported that the EMG activity can be identified by endotracheal tube recording electrodes during external branch stimulation [40, 41]. Recent work has shown that, with appropriate endotracheal tube recording array, glottis EMG activity can be observed in 100 % of cases [42]; the reader is referred to the recent International Neural Monitoring Study Group’s summary of neural monitoring as it relates to the SLN [18].
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We have recently reported one of the largest prospective continuous vagal monitoring studies investigating unique EMG outcome parameters associated with imminent neuropraxic nerve injury and their relationship to intraoperative surgical maneuvers and postoperative VCP. Severe combined event (combined event was defined as concordant amplitude reduction and latency increase) and complete LOS both were strongly associated with postoperative VCP. Severe combined event represents an adverse but reversible EMG change when associated surgical maneuver is aborted; when allowed to continue, severe combined event may progress to LOS (which is significantly less recoverable) and to postoperative VCP. CIONM endows the surgeons to instigate corrective action to preserve nerve function by aborting maneuvers that lead to adverse EMG changes and thus may prevent VCP [55]. Conflicts of interest None. Author contribution GWR: Review conception, analysis and interpretation of literature, drafting of manuscript, critical revision of manuscript. DK: Analysis and interpretation of literature, drafting of manuscript, critical revision of manuscript.
Continuous vagal monitoring and neural injury prevention Existing IONM formats allow the surgeon to intermittently stimulate and evaluate RLN function. While this has significant utility, such intermittent stimulation monitoring format could potentially allows the RLN to be at risk for injury inbetween stimulations [28, 43]. This reality may underlie data signifying that present IONM formats are limited in their ability to prevent neural injury [5, 10, 28, 44–48]. An IONM format providing real-time electrophysiological information leading to detection of impending neural injury would address this issue. A continuous nerve monitor device (CIONM) has the potential to monitor the vagus and RLN functional integrity in real-time during entire surgery [49–51]. Initial studies on CIONM with a vagal nerve electrode (see Fig. 6) have suggested such monitoring is not associated with significant adverse neural, cardiac, pulmonary, or gastrointestinal vagal side effects [23, 43, 49, 52–54]. In order to establish utility, CIONM must provide accurate detection of EMG changes which are (a) considered adverse EMG events in that they are associated with impending VCP; (b) easily recognized by the surgeon intraoperatively; and (c) nascent so that they are completely reversible with modification of the associated surgical maneuver with a resolution of EMG changes. Furthermore, we must be able to segregate such EMG changes of impending neural injury from artifactual EMG changes associated with endotracheal tube malposition or other equipment problems.
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