Acta Oto-Laryngologica. 2014; 134: 1179–1184
ORIGINAL ARTICLE
Long-term efficacy of primary intraoperative recurrent laryngeal nerve reinnervation in the management of thyroidectomy-related unilateral vocal fold paralysis
SEUNG WON LEE1, KI NAM PARK1, SOL KIL OH1, CHAN-HEE JUNG2, JI-OH MOK2 & CHUL-HEE KIM2 1
Department of Otolaryngology - Head and Neck Surgery, Soonchunhyang University College of Medicine, Bucheon, Korea and 2Department of Internal Medicine, Division of Endocrinology, Soonchunhyang University College of Medicine, Bucheon, Korea
Abstract Conclusion: Primary intraoperative recurrent laryngeal nerve (RLN) reinnervation techniques demonstrated significant voice improvement at 24 months postoperatively and could be an effective alternative treatment for thyroidectomy-related permanent unilateral vocal fold paralysis (VFP). Objectives: To assess the long-term efficacy of intraoperative RLN reinnervation techniques in the management of thyroidectomy-related unilateral VFP. Methods: A prospective study was conducted from January 2008 to June 2012 at Soonchunhyang University Bucheon Hospital. Nineteen patients who underwent RLN reinnervation with either direct reinnervation (neurorrhaphy) or ansa cervicalis to RLN (ansa-RLN) anastomosis and completed subjective and objective voice measurement over a 1-year follow-up period were included in this study. Results: The causes of VFP were cancer involving the RLN (68.4%, 13/19) and iatrogenic nerve transection (31.5%, 6/19). Reinnervation techniques were direct neurorrhaphy (63.2%, 12/19) and ansa-RLN anastomosis (36.8%, 7/19). Subjective parameters such as the Voice Handicap Index (VHI), posterior glottic closure, and mucosal wave demonstrated significant improvement 6 months postoperatively, and the majority of parameters remained stable up to 24 months (p < 0.05). Objective parameters, such as maximum phonation time (MPT), jitter, shimmer, and the harmonics-to-noise ration (HNR), demonstrated significant improvement at 12 months and most remained stable at 24 months (p < 0.05).
Keywords: voice improvement, neurorrhaphy, anastomosis
Introduction The recurrent laryngeal nerve (RLN) can be injured if it is invaded directly by thyroid cancer or iatrogenically during thyroid surgery. Although unilateral RLN injury is often well tolerated, it can be life-threatening in some patients, especially when it leads to aspiration pneumonia in older patients or those with impaired pulmonary function. In addition, postoperative dysphonia can cause serious problems, especially for patients who use their voice professionally [1]. Currently, medialization thyroplasty with or without arytenoid adduction is the standard treatment for
thyroidectomy-related permanent vocal fold paralysis (VFP) [2]. However, medialization thyroplasty is an open surgery that requires an external skin incision and may require future revisions [3]. And this additional procedures are likely stressful for patients. Recently, injection laryngoplasty techniques have regained popularity in the management of thyroidectomy-related VFP, since they are easier and less invasive than conventional medialization thyroplasty and may be equally effective [4]. However, injection laryngoplasty is less suitable for patients with large posterior glottic gaps, and long-term results have not been verified [5].
Correspondence: Seung Won Lee MD PhD, Department of Otolaryngology - Head and Neck Surgery, Soonchunhyang University College of Medicine, Bucheon, Korea. Tel: +82 32 621 5450. Fax: +82 32 621 5016. E-mail: [email protected] and [email protected]
(Received 30 April 2014; accepted 16 June 2014) ISSN 0001-6489 print/ISSN 1651-2251 online 2014 Informa Healthcare DOI: 10.3109/00016489.2014.939301
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In comparison, intraoperative RLN reinnervation is theoretically an ideal approach, because it may prevent the progressive loss of thyroarytenoid (TA) muscle tension and bulk and does not require implantation of a foreign body. Intraoperative RLN reinnervation has the potential to restore a normal or near-normal voice, while preserving the laryngeal anatomy [6]. Primary intraoperative RLN reinnervation has additional advantages over conventional procedures. It can be performed safely without compromising the airway, without an additional incision [7]. However, no prospective long-term studies of the efficacy of intraoperative RLN reinnervation in the management of thyroidectomy-related VFP have been conducted. Therefore, this prospective study examined the efficacy of primary intraoperative RLN reinnervation in the management of thyroidectomy-related permanent unilateral VFP.
Material and methods Patients Intraoperative RLN reinnervation was performed in 19 consecutive patients between January 2008 and June 2012 at the Department of OtolaryngologyHead and Neck Surgery, Soonchunhyang University Bucheon Hospital by a single surgeon (S.W.L.). All patients that underwent RLN reinnervation due to RLN tumor invasion or iatrogenic RLN transection were followed for at least 1 year. Patients with insufficient follow-up, bilateral or temporary vocal fold paralysis, or abnormal vocal fold mucosa were excluded from this study. Patients did not receive any postoperative voice therapy during the follow-up period. The mean patient age was 48.4 ± 10.5 (range 30–68) years and the mean follow-up period was 25.1 ± 9.0 months. The main cause of RLN injury was direct invasion by thyroid cancer in 13 patients (68.4%) and iatrogenic RLN transection during surgery in 6 patients (31.6%, Table I). Among the 19 patients, only 2 (10.5%) had preoperative VFP and 17 (89.5%) had normal vocal fold movement before surgery. Twelve patients (63.2%) underwent direct reinnervation of the injured RLN and seven (36.8%) underwent ansa cervicalis to RLN (ansa-RLN) anastomosis. The study design was approved by the Institutional Review Board of Soonchunhyang University Bucheon Hospital (SCHBC_IRB_ 2012_142). Informed consent for thyroid surgery and the RLN reinnervation procedure was obtained from each patient.
Table I. Patient demographics and summary (n = 19). Characteristic Mean age (years)
Value 48.4 ± 10.5 (range 30–68)
Causes of vocal fold paralysis Thyroid cancer invasion
13/19 (68.4%)
Iatrogenic transection
6/19 (31.6%)
Time to voice improvement following reinnervation
4.3 ± 2.6 months
Objective voice evaluation Acoustic and aerodynamic voice data were collected at baseline, and 6, 12, and 24 months postoperatively by a single speech–language pathologist. If the patient had VFP preoperatively then preoperative voice data were used as a baseline. If the patient’s RLN was iatrogenically transected during the surgery, day 7 voice data were used as a baseline, because vocal fold edema from endotracheal intubation had mostly subsided and nerve regeneration following RLN reinnervation would not be a factor at 7 days postoperatively. Jitter, shimmer, and harmonics-to-noise ratio (HNR) data were collected using the MultiDimensional Voice Program (MDVP model 4500; Kay Pentax, Lincoln Park, NJ, USA). Maximum phonation time (MPT) data were collected using the Computerized Speech Lab (CSL model 4500; Kay Pentax, NJ, USA). Subjective voice evaluation Psychosocial data were collected using the Korean language version of the Voice Handicap Index (VHI-30). Endoscopic and videostroboscopic data were collected using the Rhino-Laryngeal Stroboscope (RLS model 9100; Kay Pentax). The posterior glottal gap was rated on a four-point equal-appearing interval scale (0 = severe posterior glottic gap exceeding 3 mm during phonation, 1 = moderate posterior glottic gap between 2 and 3 mm during phonation, 2 = mild posterior glottic gap within 2 mm during phonation, and 3 = absent posterior glottic gap). Glottic mucosal wave was rated on a four-point equal-appearing interval scale (0 = absent, 1 = severely reduced, 2 = mildly reduced, and 3 = intact) [8]. Operative technique The reinnervation technique (direct reinnervation (neurorrhaphy) or ansa-RLN reinnervation) was determined based on the length of the defect in the
Recurrent laryngeal nerve reinnervation transected RLN with considerations for the tension of the anastomosis. For the majority of cases when the length of the defect in the transected RLN was less than 5 mm, direct RLN reinnervation was performed, and when the defect was over 10 mm, an ansa-RLN anastomosis was performed. Direct reinnervation was performed when the length of the defect in the transected RLN was small enough to allow for a tension-free anastomosis. Before the neural anastomosis the entire length of the RLN was mobilized to relieve tension. For neurorrhaphy four to five interrupted 9-0 nylon epineural sutures were placed under an operating microscope after nerve-end trimming [9]. The ansa-RLN reinnervation technique was used when the defect in the transected RLN was large and a direct reinnervation would result in excess tension. For the ansa-RLN reinnervation the ipsilateral sternocleidomastoid muscle was retracted laterally, and the ansa cervicalis was identified overlying the internal jugular vein. After identifying the branches of the ansa cervicalis leading to the sternohyoid and sternothyroid muscles, it was transected at the lateral aspect of the strap muscle. After mobilizing the ansa cervicalis, four to five interrupted 9-0 nylon epineural sutures were placed to complete the anastomosis with the RLN (Figure 1). Statistical analyses
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Table II. Objective analysis of recurrent laryngeal nerve (RLN) reinnervation (n = 19).
Characteristic
Baseline
6 months after RLN reinnervation
12 months after RLN reinnervation
MPT (s)
6.69 ± 3.01
8.46 ± 3.64
10.40 ± 2.55*
Jitter (%)
4.86 ± 5.82
2.93 ± 2.74
1.73 ± 1.07*
Shimmer (%)
8.05 ± 5.33
5.74 ± 4.58
5.11 ± 4.03*
HNR (dB)
16.8 ± 5.3
22.3 ± 9.2
34.9 ± 1.2*
Baseline: baseline voice data; HNR: harmonics-to-noise ratio; MPT: maximum phonation time. *Significantly improved between baseline and 12 months postoperatively.
Results Objective parameters Table II presents objective voice data following RLN reinnervation. The MPT and HNR were increased, while the percentages of jitter and shimmer were decreased, although not significantly (p > 0.05), at 6 months postoperatively. At 12 months, the MPT and HNR were increased significantly (p < 0.05), and the percentage of shimmer was decreased significantly (p < 0.05). Subjective parameters
Statistical analyses were performed using the Wilcoxon signed-rank test and Mann–Whitney test (Korean version of SPSS 17.0 for Windows). p values < 0.05 were considered to indicate statistical significance.
Med
RLN
Table III presents subjective voice data following RLN reinnervation. VHI scores improved significantly at 6 months postoperatively and remained stable at 12 months. Stroboscopic analyses revealed that the average mucosal wave and posterior glottic gap grades were significantly improved (p < 0.05) at both 6 and 12 months postoperatively.
Table III. Subjective analysis of recurrent laryngeal nerve (RLN) reinnervation (n = 19).
Baseline
6 months after RLN reinnervation
12 months after RLN reinnervation
VHI
84. 8 ± 17.0
38.2 ± 24.1*
44.1 ± 2.93†
Mucosal wave
0.47 ± 0.71
2.42 ± 0.69*
2.33 ± 0.48†
Glottic gap
0.59 ± 0.79
2.84 ± 0.96*
2.60 ± 0.57†
Sup Ansa cervicalis
Figure 1. In the ansa cervicalis to recurrent laryngeal nerve reinnervation procedure, the branches of the ansa cervicalis were identifiedand mobilized. The ansa cervicalis was anastomosed directly to the recurrent laryngeal nerve using interrupted 9-0 nylon epineural sutures. Med, medial side; Sup, superior side.
Characteristic
Baseline:baseline voice data; Glottic gap: grades of posterior glottic gap; Mucosal wave: grades of glottic mucosal wave; VHI: Voice Handicap Index – 30. *Significantly improved between baseline and 6 months postoperatively. † Significantly improved between baseline and 12 months postoperatively.
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Table IV. Voice analysis of long-term follow-up patients (n = 8).
Baseline
12 months after RLN reinnervation
24 months after RLN reinnervation
MPT (s)
6.69 ± 3.01
10.40 ± 2.55*
10.18 ± 2.71†
Jitter (%)
4.86 ± 5.82
1.73 ± 1.07*
3.00 ± 2.09
Shimmer (%)
8.05 ± 5.33
5.11 ± 4.03*
5.14 ± 1.98†
HNR (dB)
16. 8 ± 5.3
34.9 ± 12.3*
32.3 ± 6.0†
VHI
84.8 ± 1.70
44.1 ± 29.3*
38.0 ± 1.42†
Mucosal wave
0.47 ± 0.71
2.33 ± 0.48*
2.57 ± 1.13†
Glottic gap
0.59 ± 0.79
2.60 ± 0.57*
2.43 ± 1.13†
Characteristic
Baseline: baseline voice data; Glottic gap: grades of posterior glottic gap; HNR: harmonics-to-noise ratio; MPT: maximum phonation time; Mucosal wave: grades of glottic mucosal wave; VHI: Voice Handicap Index – 30. *Significantly improved between baseline and 12 months postoperatively. † Significantly improved between baseline and 24 months postoperatively.
Voice analyses for long-term follow-up patients Table IV presents the voice analysis data for the eight patients followed for 2 years postoperatively. In these long-term follow-up patients, the MPT, percentage of shimmer, VHI, grade of mucosal wave, and posterior glottic gap were improved significantly 12 months postoperatively and remained stable at 24 months (p < 0.05). In contrast, the percentage of jitter was improved significantly at 12 months (p < 0.05), but not at 24 months (p > 0.05) postoperatively. Comparative voice results between direct RLN and ansa-RLN reinnervation techniques Table V presents the voice analysis data for direct RLN and ansa-RLN reinnervation techniques. There
were no significant different voice parameters between direct RLN reinnervation and ansa-RLN reinnervation techniques at baseline and 12 months after reinnervation, respectively.
Postoperative complications No serious adverse events related to RLN reinnervation were observed during the follow-up period, including airway obstruction or laryngeal hematoma.
Discussion Permanent unilateral VFP is a well-known complication of thyroid surgery. Even experienced surgeons can damage the RLN, especially during revisional operations or when extensive or paratracheal lymph node metastasis are present [10]. When cancer infiltrates the RLN, resection of the infiltrated nerve is inevitable and patients may suffer from breathy voice and aspiration problems as a result. These complications negatively affect the patient’s quality of life and can also have a negative effect on the doctor–patient relationship, especially in patients who suffer from severe aspiration following thyroidectomy or those who use their voice professionally [11]. Several surgical techniques have been developed with the aim of improving the patient’s voice quality, improving quality of life, and eliminating aspiration. These techniques include medialization thyroplasty with or without arytenoid adduction, reinnervation procedures, and injection laryngoplasty. Although considerable improvements in voice quality have been observed after medialization thyroplasty or injection laryngoplasty, both procedures have specific limitations and complications [12].
Table V. Comparative voice analysis between direct recurrent laryngeal nerve (RLN) reinnervation (n = 12) and ansa RLN reinnervation techniques (n = 7). Baseline
12 months after reinnervation
Characteristic
Direct group
Ansa-RLN group
Direct group
Ansa-RLN group
MPT (s)
7.77 ± 3.17
6.01 ± 1.86
10.57 ± 2.33
10.23 ± 2.51
Jitter (%)
4.61 ± 6.79
5.25 ± 4.36
1.72 ± 1.14
1.73 ± 1.04
Shimmer (%)
7.64 ± 5.14
8.72 ± 5.96
5.88 ± 4.75
3.96 ± 2.62
HNR (dB)
17.5 ± 5.6
15.5 ± 4.7
33.6 ± 3.5
36.8 ± 2.4
VHI
85.2 ± 17.4
84.4 ± 17.7
40.7 ± 22.9
49.1 ± 26.6
Mucosal wave
0.50 ± 0.70
0.43 ± 0.78
2.31 ± 0.50
2.37 ± 0.52
Glottic gap
0.70 ± 0.82
0.43 ± 0.78
2.56 ± 0.52
2.67 ± 0.51
Ansa-RLN group: patients underwent ansa cervicalis to RLN anastomosis; Baseline: baseline voice data; Direct group: patients underwent direct RLN anastomosis; Glottic gap: grades of posterior glottic gap; HNR: harmonics-to-noise ratio; MPT: maximum phonation time; Mucosal wave: grades of glottic mucosal wave; VHI: Voice Handicap Index – 30.
Recurrent laryngeal nerve reinnervation Currently, medialization thyroplasty with or without arytenoid adduction is the gold standard for treating permanent unilateral VFP. However, medialization thyroplasty is an additional open surgical procedure that requires another external skin incision. Additional procedures are stressful for patients who have already undergone a thyroidectomy. Also, medialization thyroplasty cannot prevent the atrophy of denervated vocal fold muscles over time, and further surgical revision may be needed. Compared with medialization thyroplasty, injection laryngoplasty can be performed under local anesthesia in an office setting. However, it also has some drawbacks. Injection laryngoplasty cannot correct a large posterior glottic gap, and it involves absorption of injected materials. In addition, the long-term efficacy of injection thyroplasty has not been verified [2]. While some may prefer primary intraoperative medialization thyroplasty or intraoperative injection laryngoplasty after thyroidectomy, it is difficult to check the voice during these procedures, and there is a risk of airway obstruction. Compared to medialization thyroplasty and injection laryngoplasty, primary intraoperative RLN reinnervation during thyroid surgery is theoretically an ideal approach, because it can prevent the progressive loss of thyroarytenoid muscle tension and bulk [6], does not involve the implantation of foreign material, and has the potential to restore a normal or near-normal voice while preserving the laryngeal anatomy. Yumato et al. reported that their primary intraoperative RLN reinnervation group showed excellent postoperative voice results, which were better than those in the group that did not undergo RLN reconstruction [13]. One of the great advantages of an intraoperative reinnervation procedure is that reoperation and further surgical incisions are avoided by performing the procedure at the time of thyroid surgery. Additionally, primary intraoperative reinnervation can be done safely without airway compromise. However, it also has disadvantages. Nerve regeneration takes 3–6 months and the voice can initially worsen following the procedure due to denervation [14,15]. Miyauchi et al. reported that the MPT started to increase rapidly 2–5 months after immediate ansa-RLN reinnervation in operations for thyroid cancer [16]. In the present study, patients began to notice improvement in their voice 4.3 ± 2.6 months after reinnervation. The objective parameters improved at 6 months postoperatively, and although not statistically significant at 6 months the improvements were significant at 12 months. The subjective parameters showed significant improvement at 6 months
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postoperatively and remained stable at 12 months (Tables II and III). Patients suffering from aspiration problems or those with a large voice demand may benefit from the addition of injection laryngoplasty with absorbable material to RLN reinnervation, which could alleviate symptoms before nerve regeneration [17,18]. The present study revealed that intraoperative RLN reinnervation confers significant improvements in voice and voice-related quality of life as demonstrated by the aerodynamic, stroboscopic, and VHI results, and these therapeutic effects are present for at least 12 months. The vibratory activity of the vocal fold and the posterior glottic gap were also improved during follow-up stroboscopic examination. The majority of the subjective and objective improvements persisted for 2 years postoperatively (Table IV). Regarding the limitations of this study, although this was a prospective clinical trial it included only a small number of patients who were not randomized, and did not include a control group. Based on this study, primary intraoperative RLN reinnervation is a valid treatment option for thyroidectomy-related permanent unilateral VFP when RLN resection is inevitable due to cancer invasion or in cases of iatrogenic RLN transection.
Conclusion Primary intraoperative RLN reinnervation demonstrated significant voice improvement up to 24 months postoperatively and may be an effective treatment for thyroidectomy-related permanent unilateral VFP.
Acknowledgment This work was supported by the Soonchunhyang University Research Fund. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
References [1] Crumley RL. Unilateral recurrent laryngeal nerve paralysis. J Voice 1994;8:79–83. [2] Mallur PS, Rosen CA. Vocal fold injection: review of indications, techniques, and materials for augmentation. Clin Exp Otorhinolaryngol 2010;3:177–82. [3] Isshiki N, Okamura H, Ishikawa T. Thyroplasty type I (lateral compression) for dysphonia due to vocal cord paralysis or atrophy. Acta Otolaryngol 1975;80:465–73.
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[4] Lee SW, Kim JW, Chung CH, Mok JO, Shim SS, Koh YW, et al. Utility of injection laryngoplasty in the management of post-thyroidectomy vocal cord paralysis. Thyroid 2010;20:513–17. [5] McCulloch TM, Andrews BT, Hoffman HT, Graham SM, Karnell MP, Minnick C. Long-term follow-up of fat injection laryngoplasty for unilateral vocal cord paralysis. Laryngoscope 2002;112:1235–8. [6] Aynehchi BB, McCoul ED, Sundaram K. Systematic review of laryngeal reinnervation techniques. Otolaryngol Head Neck Surg 2010;143:749–59. [7] Lee WT, Milstein C, Hicks D, Akst LM, Esclamado RM. Results of ansa to recurrent laryngeal nerve reinnervation. Otolaryngol Head Neck Surg 2007;136:450–4. [8] Lee SW, Kim JW, Koh YW, Shim SS, Son YI. Comparative analysis of efficiency of injection laryngoplasty technique for with or without neck treatment patients: a transcartilaginous approach versus the cricothyroid approach. Clin Exp Otorhinolaryngol 2010;3:37–41. [9] Wang W, Chen D, Chen S, Li D, Li M, Xia S, et al. Laryngeal reinnervation using ansa cervicalis for thyroid surgery-related unilateral vocal fold paralysis: a long-term outcome analysis of 237 cases. PLoS One 2011;6:e19128. [10] Affleck BD, Swartz K, Brennan J. Surgical considerations and controversies in thyroid and parathyroid surgery. Otolaryngol Clin North Am 2003;36:159–87; x.
[11] Kwon TK, Buckmire R. Injection laryngoplasty for management of unilateral vocal fold paralysis. Curr Opin Otolaryngol Head Neck Surg 2004;12:538–42. [12] Rubin AD, Sataloff RT. Vocal fold paresis and paralysis: what the thyroid surgeon should know. Surg Oncol Clin N Am 2008;17:175–96. [13] Yumoto E, Sanuki T, Kumai Y. Immediate recurrent laryngeal nerve reconstruction and vocal outcome. Laryngoscope 2006;116:1657–61. [14] Smith ME, Roy N, Stoddard K. Ansa-RLN reinnervation for unilateral vocal fold paralysis in adolescents and young adults. Int J Pediatr Otorhinolaryngol 2008;72:1311–16. [15] Crumley RL. Update: ansa cervicalis to recurrent laryngeal nerve anastomosis for unilateral laryngeal paralysis. Laryngoscope 1991;101:384–7; discussion 8. [16] Miyauchi A, Matsusaka K, Kihara M, Matsuzuka F, Hirai K, Yokozawa T, et al. The role of ansa-to-recurrent-laryngeal nerve anastomosis in operations for thyroid cancer. Eur J Surg 1998;164:927–33. [17] Graboyes EM, Bradley JP, Meyers BF, Nussenbaum B. Efficacy and safety of acute injection laryngoplasty for vocal cord paralysis following thoracic surgery. Laryngoscope 2011;121:2406–10. [18] Sato K, Umeno H, Nakashima T. Autologous fat injection laryngohypopharyngoplasty for aspiration after vocal fold paralysis. Ann Otol Rhinol Laryngol 2004;113:87–92.
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ORIGINAL ARTICLE
Long-term efficacy of primary intraoperative recurrent laryngeal nerve reinnervation in the management of thyroidectomy-related unilateral vocal fold paralysis
SEUNG WON LEE1, KI NAM PARK1, SOL KIL OH1, CHAN-HEE JUNG2, JI-OH MOK2 & CHUL-HEE KIM2 1
Department of Otolaryngology - Head and Neck Surgery, Soonchunhyang University College of Medicine, Bucheon, Korea and 2Department of Internal Medicine, Division of Endocrinology, Soonchunhyang University College of Medicine, Bucheon, Korea
Abstract Conclusion: Primary intraoperative recurrent laryngeal nerve (RLN) reinnervation techniques demonstrated significant voice improvement at 24 months postoperatively and could be an effective alternative treatment for thyroidectomy-related permanent unilateral vocal fold paralysis (VFP). Objectives: To assess the long-term efficacy of intraoperative RLN reinnervation techniques in the management of thyroidectomy-related unilateral VFP. Methods: A prospective study was conducted from January 2008 to June 2012 at Soonchunhyang University Bucheon Hospital. Nineteen patients who underwent RLN reinnervation with either direct reinnervation (neurorrhaphy) or ansa cervicalis to RLN (ansa-RLN) anastomosis and completed subjective and objective voice measurement over a 1-year follow-up period were included in this study. Results: The causes of VFP were cancer involving the RLN (68.4%, 13/19) and iatrogenic nerve transection (31.5%, 6/19). Reinnervation techniques were direct neurorrhaphy (63.2%, 12/19) and ansa-RLN anastomosis (36.8%, 7/19). Subjective parameters such as the Voice Handicap Index (VHI), posterior glottic closure, and mucosal wave demonstrated significant improvement 6 months postoperatively, and the majority of parameters remained stable up to 24 months (p < 0.05). Objective parameters, such as maximum phonation time (MPT), jitter, shimmer, and the harmonics-to-noise ration (HNR), demonstrated significant improvement at 12 months and most remained stable at 24 months (p < 0.05).
Keywords: voice improvement, neurorrhaphy, anastomosis
Introduction The recurrent laryngeal nerve (RLN) can be injured if it is invaded directly by thyroid cancer or iatrogenically during thyroid surgery. Although unilateral RLN injury is often well tolerated, it can be life-threatening in some patients, especially when it leads to aspiration pneumonia in older patients or those with impaired pulmonary function. In addition, postoperative dysphonia can cause serious problems, especially for patients who use their voice professionally [1]. Currently, medialization thyroplasty with or without arytenoid adduction is the standard treatment for
thyroidectomy-related permanent vocal fold paralysis (VFP) [2]. However, medialization thyroplasty is an open surgery that requires an external skin incision and may require future revisions [3]. And this additional procedures are likely stressful for patients. Recently, injection laryngoplasty techniques have regained popularity in the management of thyroidectomy-related VFP, since they are easier and less invasive than conventional medialization thyroplasty and may be equally effective [4]. However, injection laryngoplasty is less suitable for patients with large posterior glottic gaps, and long-term results have not been verified [5].
Correspondence: Seung Won Lee MD PhD, Department of Otolaryngology - Head and Neck Surgery, Soonchunhyang University College of Medicine, Bucheon, Korea. Tel: +82 32 621 5450. Fax: +82 32 621 5016. E-mail: [email protected] and [email protected]
(Received 30 April 2014; accepted 16 June 2014) ISSN 0001-6489 print/ISSN 1651-2251 online 2014 Informa Healthcare DOI: 10.3109/00016489.2014.939301
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In comparison, intraoperative RLN reinnervation is theoretically an ideal approach, because it may prevent the progressive loss of thyroarytenoid (TA) muscle tension and bulk and does not require implantation of a foreign body. Intraoperative RLN reinnervation has the potential to restore a normal or near-normal voice, while preserving the laryngeal anatomy [6]. Primary intraoperative RLN reinnervation has additional advantages over conventional procedures. It can be performed safely without compromising the airway, without an additional incision [7]. However, no prospective long-term studies of the efficacy of intraoperative RLN reinnervation in the management of thyroidectomy-related VFP have been conducted. Therefore, this prospective study examined the efficacy of primary intraoperative RLN reinnervation in the management of thyroidectomy-related permanent unilateral VFP.
Material and methods Patients Intraoperative RLN reinnervation was performed in 19 consecutive patients between January 2008 and June 2012 at the Department of OtolaryngologyHead and Neck Surgery, Soonchunhyang University Bucheon Hospital by a single surgeon (S.W.L.). All patients that underwent RLN reinnervation due to RLN tumor invasion or iatrogenic RLN transection were followed for at least 1 year. Patients with insufficient follow-up, bilateral or temporary vocal fold paralysis, or abnormal vocal fold mucosa were excluded from this study. Patients did not receive any postoperative voice therapy during the follow-up period. The mean patient age was 48.4 ± 10.5 (range 30–68) years and the mean follow-up period was 25.1 ± 9.0 months. The main cause of RLN injury was direct invasion by thyroid cancer in 13 patients (68.4%) and iatrogenic RLN transection during surgery in 6 patients (31.6%, Table I). Among the 19 patients, only 2 (10.5%) had preoperative VFP and 17 (89.5%) had normal vocal fold movement before surgery. Twelve patients (63.2%) underwent direct reinnervation of the injured RLN and seven (36.8%) underwent ansa cervicalis to RLN (ansa-RLN) anastomosis. The study design was approved by the Institutional Review Board of Soonchunhyang University Bucheon Hospital (SCHBC_IRB_ 2012_142). Informed consent for thyroid surgery and the RLN reinnervation procedure was obtained from each patient.
Table I. Patient demographics and summary (n = 19). Characteristic Mean age (years)
Value 48.4 ± 10.5 (range 30–68)
Causes of vocal fold paralysis Thyroid cancer invasion
13/19 (68.4%)
Iatrogenic transection
6/19 (31.6%)
Time to voice improvement following reinnervation
4.3 ± 2.6 months
Objective voice evaluation Acoustic and aerodynamic voice data were collected at baseline, and 6, 12, and 24 months postoperatively by a single speech–language pathologist. If the patient had VFP preoperatively then preoperative voice data were used as a baseline. If the patient’s RLN was iatrogenically transected during the surgery, day 7 voice data were used as a baseline, because vocal fold edema from endotracheal intubation had mostly subsided and nerve regeneration following RLN reinnervation would not be a factor at 7 days postoperatively. Jitter, shimmer, and harmonics-to-noise ratio (HNR) data were collected using the MultiDimensional Voice Program (MDVP model 4500; Kay Pentax, Lincoln Park, NJ, USA). Maximum phonation time (MPT) data were collected using the Computerized Speech Lab (CSL model 4500; Kay Pentax, NJ, USA). Subjective voice evaluation Psychosocial data were collected using the Korean language version of the Voice Handicap Index (VHI-30). Endoscopic and videostroboscopic data were collected using the Rhino-Laryngeal Stroboscope (RLS model 9100; Kay Pentax). The posterior glottal gap was rated on a four-point equal-appearing interval scale (0 = severe posterior glottic gap exceeding 3 mm during phonation, 1 = moderate posterior glottic gap between 2 and 3 mm during phonation, 2 = mild posterior glottic gap within 2 mm during phonation, and 3 = absent posterior glottic gap). Glottic mucosal wave was rated on a four-point equal-appearing interval scale (0 = absent, 1 = severely reduced, 2 = mildly reduced, and 3 = intact) [8]. Operative technique The reinnervation technique (direct reinnervation (neurorrhaphy) or ansa-RLN reinnervation) was determined based on the length of the defect in the
Recurrent laryngeal nerve reinnervation transected RLN with considerations for the tension of the anastomosis. For the majority of cases when the length of the defect in the transected RLN was less than 5 mm, direct RLN reinnervation was performed, and when the defect was over 10 mm, an ansa-RLN anastomosis was performed. Direct reinnervation was performed when the length of the defect in the transected RLN was small enough to allow for a tension-free anastomosis. Before the neural anastomosis the entire length of the RLN was mobilized to relieve tension. For neurorrhaphy four to five interrupted 9-0 nylon epineural sutures were placed under an operating microscope after nerve-end trimming [9]. The ansa-RLN reinnervation technique was used when the defect in the transected RLN was large and a direct reinnervation would result in excess tension. For the ansa-RLN reinnervation the ipsilateral sternocleidomastoid muscle was retracted laterally, and the ansa cervicalis was identified overlying the internal jugular vein. After identifying the branches of the ansa cervicalis leading to the sternohyoid and sternothyroid muscles, it was transected at the lateral aspect of the strap muscle. After mobilizing the ansa cervicalis, four to five interrupted 9-0 nylon epineural sutures were placed to complete the anastomosis with the RLN (Figure 1). Statistical analyses
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Table II. Objective analysis of recurrent laryngeal nerve (RLN) reinnervation (n = 19).
Characteristic
Baseline
6 months after RLN reinnervation
12 months after RLN reinnervation
MPT (s)
6.69 ± 3.01
8.46 ± 3.64
10.40 ± 2.55*
Jitter (%)
4.86 ± 5.82
2.93 ± 2.74
1.73 ± 1.07*
Shimmer (%)
8.05 ± 5.33
5.74 ± 4.58
5.11 ± 4.03*
HNR (dB)
16.8 ± 5.3
22.3 ± 9.2
34.9 ± 1.2*
Baseline: baseline voice data; HNR: harmonics-to-noise ratio; MPT: maximum phonation time. *Significantly improved between baseline and 12 months postoperatively.
Results Objective parameters Table II presents objective voice data following RLN reinnervation. The MPT and HNR were increased, while the percentages of jitter and shimmer were decreased, although not significantly (p > 0.05), at 6 months postoperatively. At 12 months, the MPT and HNR were increased significantly (p < 0.05), and the percentage of shimmer was decreased significantly (p < 0.05). Subjective parameters
Statistical analyses were performed using the Wilcoxon signed-rank test and Mann–Whitney test (Korean version of SPSS 17.0 for Windows). p values < 0.05 were considered to indicate statistical significance.
Med
RLN
Table III presents subjective voice data following RLN reinnervation. VHI scores improved significantly at 6 months postoperatively and remained stable at 12 months. Stroboscopic analyses revealed that the average mucosal wave and posterior glottic gap grades were significantly improved (p < 0.05) at both 6 and 12 months postoperatively.
Table III. Subjective analysis of recurrent laryngeal nerve (RLN) reinnervation (n = 19).
Baseline
6 months after RLN reinnervation
12 months after RLN reinnervation
VHI
84. 8 ± 17.0
38.2 ± 24.1*
44.1 ± 2.93†
Mucosal wave
0.47 ± 0.71
2.42 ± 0.69*
2.33 ± 0.48†
Glottic gap
0.59 ± 0.79
2.84 ± 0.96*
2.60 ± 0.57†
Sup Ansa cervicalis
Figure 1. In the ansa cervicalis to recurrent laryngeal nerve reinnervation procedure, the branches of the ansa cervicalis were identifiedand mobilized. The ansa cervicalis was anastomosed directly to the recurrent laryngeal nerve using interrupted 9-0 nylon epineural sutures. Med, medial side; Sup, superior side.
Characteristic
Baseline:baseline voice data; Glottic gap: grades of posterior glottic gap; Mucosal wave: grades of glottic mucosal wave; VHI: Voice Handicap Index – 30. *Significantly improved between baseline and 6 months postoperatively. † Significantly improved between baseline and 12 months postoperatively.
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Table IV. Voice analysis of long-term follow-up patients (n = 8).
Baseline
12 months after RLN reinnervation
24 months after RLN reinnervation
MPT (s)
6.69 ± 3.01
10.40 ± 2.55*
10.18 ± 2.71†
Jitter (%)
4.86 ± 5.82
1.73 ± 1.07*
3.00 ± 2.09
Shimmer (%)
8.05 ± 5.33
5.11 ± 4.03*
5.14 ± 1.98†
HNR (dB)
16. 8 ± 5.3
34.9 ± 12.3*
32.3 ± 6.0†
VHI
84.8 ± 1.70
44.1 ± 29.3*
38.0 ± 1.42†
Mucosal wave
0.47 ± 0.71
2.33 ± 0.48*
2.57 ± 1.13†
Glottic gap
0.59 ± 0.79
2.60 ± 0.57*
2.43 ± 1.13†
Characteristic
Baseline: baseline voice data; Glottic gap: grades of posterior glottic gap; HNR: harmonics-to-noise ratio; MPT: maximum phonation time; Mucosal wave: grades of glottic mucosal wave; VHI: Voice Handicap Index – 30. *Significantly improved between baseline and 12 months postoperatively. † Significantly improved between baseline and 24 months postoperatively.
Voice analyses for long-term follow-up patients Table IV presents the voice analysis data for the eight patients followed for 2 years postoperatively. In these long-term follow-up patients, the MPT, percentage of shimmer, VHI, grade of mucosal wave, and posterior glottic gap were improved significantly 12 months postoperatively and remained stable at 24 months (p < 0.05). In contrast, the percentage of jitter was improved significantly at 12 months (p < 0.05), but not at 24 months (p > 0.05) postoperatively. Comparative voice results between direct RLN and ansa-RLN reinnervation techniques Table V presents the voice analysis data for direct RLN and ansa-RLN reinnervation techniques. There
were no significant different voice parameters between direct RLN reinnervation and ansa-RLN reinnervation techniques at baseline and 12 months after reinnervation, respectively.
Postoperative complications No serious adverse events related to RLN reinnervation were observed during the follow-up period, including airway obstruction or laryngeal hematoma.
Discussion Permanent unilateral VFP is a well-known complication of thyroid surgery. Even experienced surgeons can damage the RLN, especially during revisional operations or when extensive or paratracheal lymph node metastasis are present [10]. When cancer infiltrates the RLN, resection of the infiltrated nerve is inevitable and patients may suffer from breathy voice and aspiration problems as a result. These complications negatively affect the patient’s quality of life and can also have a negative effect on the doctor–patient relationship, especially in patients who suffer from severe aspiration following thyroidectomy or those who use their voice professionally [11]. Several surgical techniques have been developed with the aim of improving the patient’s voice quality, improving quality of life, and eliminating aspiration. These techniques include medialization thyroplasty with or without arytenoid adduction, reinnervation procedures, and injection laryngoplasty. Although considerable improvements in voice quality have been observed after medialization thyroplasty or injection laryngoplasty, both procedures have specific limitations and complications [12].
Table V. Comparative voice analysis between direct recurrent laryngeal nerve (RLN) reinnervation (n = 12) and ansa RLN reinnervation techniques (n = 7). Baseline
12 months after reinnervation
Characteristic
Direct group
Ansa-RLN group
Direct group
Ansa-RLN group
MPT (s)
7.77 ± 3.17
6.01 ± 1.86
10.57 ± 2.33
10.23 ± 2.51
Jitter (%)
4.61 ± 6.79
5.25 ± 4.36
1.72 ± 1.14
1.73 ± 1.04
Shimmer (%)
7.64 ± 5.14
8.72 ± 5.96
5.88 ± 4.75
3.96 ± 2.62
HNR (dB)
17.5 ± 5.6
15.5 ± 4.7
33.6 ± 3.5
36.8 ± 2.4
VHI
85.2 ± 17.4
84.4 ± 17.7
40.7 ± 22.9
49.1 ± 26.6
Mucosal wave
0.50 ± 0.70
0.43 ± 0.78
2.31 ± 0.50
2.37 ± 0.52
Glottic gap
0.70 ± 0.82
0.43 ± 0.78
2.56 ± 0.52
2.67 ± 0.51
Ansa-RLN group: patients underwent ansa cervicalis to RLN anastomosis; Baseline: baseline voice data; Direct group: patients underwent direct RLN anastomosis; Glottic gap: grades of posterior glottic gap; HNR: harmonics-to-noise ratio; MPT: maximum phonation time; Mucosal wave: grades of glottic mucosal wave; VHI: Voice Handicap Index – 30.
Recurrent laryngeal nerve reinnervation Currently, medialization thyroplasty with or without arytenoid adduction is the gold standard for treating permanent unilateral VFP. However, medialization thyroplasty is an additional open surgical procedure that requires another external skin incision. Additional procedures are stressful for patients who have already undergone a thyroidectomy. Also, medialization thyroplasty cannot prevent the atrophy of denervated vocal fold muscles over time, and further surgical revision may be needed. Compared with medialization thyroplasty, injection laryngoplasty can be performed under local anesthesia in an office setting. However, it also has some drawbacks. Injection laryngoplasty cannot correct a large posterior glottic gap, and it involves absorption of injected materials. In addition, the long-term efficacy of injection thyroplasty has not been verified [2]. While some may prefer primary intraoperative medialization thyroplasty or intraoperative injection laryngoplasty after thyroidectomy, it is difficult to check the voice during these procedures, and there is a risk of airway obstruction. Compared to medialization thyroplasty and injection laryngoplasty, primary intraoperative RLN reinnervation during thyroid surgery is theoretically an ideal approach, because it can prevent the progressive loss of thyroarytenoid muscle tension and bulk [6], does not involve the implantation of foreign material, and has the potential to restore a normal or near-normal voice while preserving the laryngeal anatomy. Yumato et al. reported that their primary intraoperative RLN reinnervation group showed excellent postoperative voice results, which were better than those in the group that did not undergo RLN reconstruction [13]. One of the great advantages of an intraoperative reinnervation procedure is that reoperation and further surgical incisions are avoided by performing the procedure at the time of thyroid surgery. Additionally, primary intraoperative reinnervation can be done safely without airway compromise. However, it also has disadvantages. Nerve regeneration takes 3–6 months and the voice can initially worsen following the procedure due to denervation [14,15]. Miyauchi et al. reported that the MPT started to increase rapidly 2–5 months after immediate ansa-RLN reinnervation in operations for thyroid cancer [16]. In the present study, patients began to notice improvement in their voice 4.3 ± 2.6 months after reinnervation. The objective parameters improved at 6 months postoperatively, and although not statistically significant at 6 months the improvements were significant at 12 months. The subjective parameters showed significant improvement at 6 months
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postoperatively and remained stable at 12 months (Tables II and III). Patients suffering from aspiration problems or those with a large voice demand may benefit from the addition of injection laryngoplasty with absorbable material to RLN reinnervation, which could alleviate symptoms before nerve regeneration [17,18]. The present study revealed that intraoperative RLN reinnervation confers significant improvements in voice and voice-related quality of life as demonstrated by the aerodynamic, stroboscopic, and VHI results, and these therapeutic effects are present for at least 12 months. The vibratory activity of the vocal fold and the posterior glottic gap were also improved during follow-up stroboscopic examination. The majority of the subjective and objective improvements persisted for 2 years postoperatively (Table IV). Regarding the limitations of this study, although this was a prospective clinical trial it included only a small number of patients who were not randomized, and did not include a control group. Based on this study, primary intraoperative RLN reinnervation is a valid treatment option for thyroidectomy-related permanent unilateral VFP when RLN resection is inevitable due to cancer invasion or in cases of iatrogenic RLN transection.
Conclusion Primary intraoperative RLN reinnervation demonstrated significant voice improvement up to 24 months postoperatively and may be an effective treatment for thyroidectomy-related permanent unilateral VFP.
Acknowledgment This work was supported by the Soonchunhyang University Research Fund. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
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