The Laryngoscope C 2014 The American Laryngological, V
Rhinological and Otological Society, Inc.
Comparison of Voice Outcome After Vocal Fold Augmentation With Fat or Calcium Hydroxylapatite Wouter L. Lodder, MD, PhD; Frederik G. Dikkers, MD, PhD Objectives/Hypothesis: To evaluate the short-term voice outcomes of vocal fold augmentation using fat compared to calcium hydroxylapatite product Radiesse Voice (Merz Aesthetics). Study Design: Retrospective study design. Methods: Sixty-six consecutive patients with vocal fold insufficiency were recruited, including the final 33 patients treated with fat and all 33 patients treated with calcium hydroxylapatite product. Before April 2011, fat augmentation was the standard treatment; from April 2011, only calcium hydroxylapatite product was used. For all subjects, videolaryngostroboscopic evaluation, s/z ratios, and voice handicap index (VHI) were analyzed. Methods: Treatment outcomes were evaluated 3 months after the augmentation. Two patients augmented with fat (both after 6 months), versus four augmented with calcium hydroxylapatite product (mean after 7 months), needed reintervention. Mean VHI decreased from 18 points in the fat augmentation group compared to 17 points in the calcium hydroxylapatite group. Mean s/z ratio changed 20.33 in the fat augmentation group compared to 20.46 in the calcium hydroxylapatite group. Conclusion: This retrospective cohort demonstrates that there are no short-term differences in VHI outcome or number of reinterventions for augmentation with fat compared to calcium hydroxylapatite product Radiesse Voice (Merz Aesthetics). Key Words: Glottal insufficiency, outcome, fat augmentation, calcium hydroxylapatite, voice handicap index. Level of Evidence: Level 4. Laryngoscope, 125:1161–1165, 2015
INTRODUCTION Dysphonia due to glottal insufficiency may be caused by a variety of conditions. Lesion of the recurrent laryngeal nerve is one of the most common causes.1 Numerous techniques are available for correction of the insufficiency. Implantation of biomaterials in the vocal fold, fat augmentation, or medialization laryngoplasty are commonly used techniques.2–9 Various biomaterials are available for implantation. Autologous fat and Cymetra (LifeCell, Bridgewater, NY) are the most commonly used materials. The use of nonbiomaterials Gelfoam (Pharmacia and Upjohn, Pfizer, New York, NY), silicone, and various gels are also discussed in the literature.10 Complications of injection of both bio- and nonbiomaterials consist of airway obstruction due to mass effect, Additional Supporting Information may be found in the online version of this article. From the Department of Otorhinolaryngology/Head and Neck Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Editor’s Note: This Manuscript was accepted for publication November 27, 2014. Presented at the 10th Congress of the European Laryngological Society, Antalya, Turkey, April 9–12, 2014. The authors have no funding, financial relationships, or conflicts of interest to disclose. Send correspondence to Wouter L. Lodder, MD, PhD, Dept. of Otorhinolaryngology, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands. E-mail: [email protected] DOI: 10.1002/lary.25104
Laryngoscope 125: May 2015
inflammatory changes leading to increased tissue stiffness, and dissatisfying results of the intervention.11,12 Relatively new is the use of Radiesse (Merz Aesthetics, San Mateo, CA), developed primarily for facial plastic surgery.3,13 The present study is conducted to evaluate the short-term voice outcomes of vocal fold augmentation using fat compared to calcium hydroxylapatite (Radiesse Voice; Merz Aesthetics, San Mateo, CA).
MATERIALS AND METHODS Retrospective Study Design Patients. Patients charts of 66 consecutive patients with glottal insufficiency were reviewed, including all 33 patients treated with fat and all patients treated with Radiesse Voice (Merz Aesthetics) with a follow-up of at least 3 months. All patients were treated in our institution. Only patients with glottal insufficiency existing longer than 12 months were included. The etiology of glottal insufficiency is shown in Table I. Patients were evaluated by videolaryngostroboscopy before and 3 months after operation. Of the 66 patients, 32 were men and 34 were women. Three patients smoked at the time of the operation, eight smoked in the past, and 55 never smoked. In 77% of the patients, this was the primary therapy; 23% of the patients were initially treated elsewhere (6 with unknown surgery [no injections]; 9 with voice therapy). Operation Technique. Two different surgeons performed the intervention. Fifty-five patients were operated by the senior author; 11 patients were operated by a laryngology fellow. All patients underwent augmentation in general anesthesia with orotracheal intubation tube size 5 or 6. No complications occurred.
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TABLE I. Etiology of Glottal Insufficiency in a Cohort (N 5 66) Treated With Either Fat or Radiesse Voice Augmentation. Fat
Radiesse Voice
Total
Paralysis of unknown origin Postthyroidectomy
6 2
10 1
16 3
Intrathoracic surgery
5
5
10
Neck dissection Vocal fold atrophy (n 5 13)
1
1
2
Cause
Vocal fold paralysis (n 5 31)
voice outcome measurements, the s/z ratio was determined. As described in the literature, s/z ratios are significantly higher for dysphonic subjects with laryngeal pathology: patients with functional dysphonia free of laryngeal pathology demonstrated the same s/z ratios (approximately 1,0) as the normal-speaking control subjects.15 Patients were evaluated by videolaryngostroboscopy and VHI before and approximately 3 months after operation (mean 3.81 months; SD 3.6).
Statistics Statistical analysis was performed using SPSS (version 18.0; Statistical Package for Social Sciences, Inc, Chicago, IL). Chi-square test was performed to measure the difference in reoperation/no voice improvements.
Cerebrovascular accident
2
2
4
Parkinson’s disease Central incomplete closure due to presbylarynx
1 2
0 0
1 2
Central incomplete closure due to unknown origin
1
5
6
The internal review board of UMCG states that there is no need for explicit patient’s permission to conduct a retrospective study. This is based on the Dutch Medical Research Law (Wet Medisch Onderzoek).
2 1
4 0
6 1
RESULTS
Institutional Review Board Approval
Hypomobility vocal fold (n 5 7) Postradiotherapy Postintubation
Subjective Voice Outcome
Vocal fold scar/sulcus (n 5 15) Vocal fold vergeture Sulcus glottidis
2 5
0 1
2 6
Oncologic laryngeal surgery
3
4
7
Total
33
33
66
Before April 2011, fat augmentation was the standard treatment. Abdominal fat was harvested through a curved, small periumbilical-skin incision 3-cm in length. Fat was then harvested in three to five parts, with a cumulative volume of 15 to 20 ml. The wound was closed in two layers after placement of a drain, which was removed on the first postoperative day. Next, the fat was separated in three parts using a sterilized garlic press to separate the fat cells from connective tissue and fluid fat, yielding approximately 2 ml of injectable fat cells. The fat cells were then aspirated in a 1-ml syringe. The vocal folds were injected with a modified Br€ uning’s syringe during suspension microlaryngoscopy using a 1.3-mm outer diameter needle in the muscle of the vocal fold until a small glottis opening remained, which had to be palpable with comfortable resistance using a 3-mm suction tube. Fat was injected uni- or bilaterally in one to five locations (mean 3). Exact locations of injections were determined by the visual aspect of the vocal fold. Care was taken not to inject too superficially. The amount of injection was not recorded but rarely exceeded 1 ml. From April 2011, only Radiesse Voice (Merz Aesthetics) was used. It was injected during suspension microlaryngoscopy at one to eight locations (mean 3 standard deviation [SD] 1,9), in which 0.10 to 0.90 ml was injected per side (mean 0.36; SD 0.18). A standard rigid distally bent needle tip (needle tip diameter 0.6 mm) was used for injection. Similar rules concerning application were applied, as in fat augmentation. Assessment of Voice Outcome. The study was conducted in the voice clinic in our tertiary referral hospital, University of Groningen, University Medical Center Groningen (UMCG), Groningen, The Netherlands. As described earlier by Stuut et al.,14 all preoperative assessments of a patient’s voice were performed on the same day. After visiting the speech and language therapist and immediately before consulting the laryngologist, the patient filled out a validated Dutch version of the voice handicap index (VHI). During the study period, the same otolaryngologist performed all laryngoscopic assessments. For objective
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In total, 66 patients with dysphonia due to glottal insufficiency were included. Of three patients, no preoperative VHI was available; and of four patients, no postoperative VHI was available. In the final analysis, this yielded 60 cases with complete VHI data: 31 cases augmented with fat and 29 augmented with Radiesse Voice (Merz Aesthetics). Preoperative VHI ranged from 24 to 87 (mean 58; SD 16), and postoperative VHI ranged from 1 to 85 (mean 42; SD 19). The difference between the results of fat and Radiesse Voice (Merz Aesthetics) augmentation is displayed in Table II. Results of 60 individual patients (divided in subgroups analogous to Table I) are displayed in Table III, showing preoperative, postoperative, and delta VHI. Supporting Figures S1 and S2 (available online only) illustrate the gain in VHI.
Objective Voice Outcome s/z ratios were also compared. Preoperative s/z ratio ranged from 0 to 5.50 (mean 1.90; SD 1.1). Postoperative TABLE II. Differences Between Fat and Radiesse Voice Augmentation.* Fat Augmentation
Preoperative VHI
Radiesse Voice Augmentation
P Value
> 0.05
61
56
(range)
(24 to 87)
(31 to 87)
Postoperative VHI (range)
42 (1 to 76)
41 (4 to 85)
> 0.05
217
218
> 0.05
(range) s/z-ratio change
VHI change per patient
(259 to 125) 20.33
(280 to 19) 20.46
> 0.05
(mean values)
(1.81 to 1.48)
(1.99 to 1.53)
Number of reinterventions Follow-up in months (range)
2 10
4 7
(3 to 43)
(3 to 22)
> 0.05 > 0.05
*There is no statistically significant difference in any of the values. VHI 5 voice handicap index.
Lodder and Dikkers: Voice Outcome After Vocal Fold Augmentation
TABLE III. VHI Change per Patient and Subcategory, Divided by Means of Augmentation.
TABLE III. (Continued) B. Radiesse Voice Augmentation (n 5 31).
A. Abdominal Fat Augmentation (n 5 29).
Patient
Subgroup
VHI Preoperative
VHI Postoperative
VHI Change
Vocal Fold Paralysis
Patient
Subgroup
VHI VHI VHI Preoperative Postoperative Change
9 10
69 54
52 38
217 216
1
72
13
259
11
58
27
216
2
51
16
248
3 4
75 66
44 37
231 229
12 13
82 56
71 48
211 28
14
43
42
21
5
72
57
215
15
51
57
6
6 7
66 56
56 49
210 27
16
74
48
226
8
36
29
27
9 10
49 49
45 50
24 1
17 18
50 75
28 56
222 219
19
71
52
29
11
53
58
5
20 21
42 29
38 34
24 5
22
53
62
9
Vocal Fold Atrophy
Vocal Fold Atrophy 12
63
36
227
13
49
22
227
14 15
55 87
30 67
225 220
16
31
18
213
17
34
33
21
Hypomobility Vocal Fold 23
81
1
280
24 25
76 83
54 76
222 27
26
48
50
2
27
Hypomobility Vocal Fold 18 19
44 74
4 47
240 227
85
54
231
20
83
76
27
28 29
37 81
23 71
214 210
Vocal Fold Scar/Sulcus
Vocal Fold Scar/Sulcus 21
72
37
235
30
24
15
29
22
60
33
227
31
73
70
23
23 24
47 52
24 35
223 217
25
50
39
211
26 27
38 36
31 30
27 26
28
58
62
4
29
55
80
25
s/z ratio ranged from 0.58 to 3.0 (mean 1.50; SD 0.59). In the group treated with fat augmentation, the mean s/z ratio changed from 1.81 to 1.48 (20.33). In the Radiesse Voice (Merz Aesthetics) group, the mean s/z ratio changed from 1.99 to 1.53 (20.46).
Videolaryngostroboscopy
B. Radiesse Voice Augmentation (n 5 31).
Patient
Subgroup
VHI VHI VHI Preoperative Postoperative Change
Pre- and postoperative videolaryngostroboscopy were analyzed of all patients. Because we changed our videolaryngoscope during the study, we were unable to include these examinations.
Necessity of Reintervention
Vocal Fold Paralysis
Two patients with fat augmentation (both after 6 months) and four patients with Radiesse Voice (Merz Aesthetics) augmentation (mean after 7 months; range 4–12) needed reintervention. With P 5 0.392, this difference was not of statistical significance.
1 2
48 68
1 30
247 238
3
49
14
235
4 5
85 72
54 43
231 229
6
56
34
222
DISCUSSION
7 8
48 57
29 38
219 219
This study shows that there are no short-term differences in voice outcome after vocal fold augmentation with autologous fat or Radiesse Voice (Merz Aesthetics).
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Comparison With Other Studies In 2011, Sanderson described laryngeal complications of autologous fat injection in 98 patients treated between 1997 and 2008.11 Complications occurred in 4.5%. Over-injection–inducing dysphonia was seen in three patients. In patients treated with autologous fat, success rates after 1 year (measured with grade, roughness, breathiness, asthenia, and strain [GRBAS] scale; voice analyses; and number of reinterventions needed) range from 62 to 70%; after 4 years, the success rate is around 41%.11,16 Other complications reported in the literature include over-resorption of fat, infections, or subsequent bleeding at the harvest site.11,12,17 In the literature, only a few articles describe experiences with Radiesse Voice (Merz Aesthetics). Several compositions of it exist. The injectable implant contains synthetic calcium hydroxylapatite microspheres, with a diameter range of 25 to 45 mm, suspended in an aqueous gel carrier. These particles allow for a long-lasting augmentation shown to be effective up to from 12 to 24 months. Radiesse Voice (Merz Aesthetics) lasts longer than Radiesse Voice Gel (Merz Aesthetics). The voice gel has another carrier substance, carboxymethylcellulose,10 and is an injectable implant containing synthetically derived polymers. This material requires no preparation and has no biologic infection transmission risk. The substance typically lasts 2 to 3 months after injection. This has been utilized extensively for temporary vocal-fold paralysis and for trial vocal-fold injection augmentation for a variety of causes of glottic incompetence.18 In 2013, the effect of Radiesse Voice (Merz Aesthetics) was directly compared to thyreoplasty medialization. The effects of thyreoplasty and this injectable implant seem comparable after both 6 and 24 months follow-up.1 In the literature, there are no reports available that describe the long-term effect of Radiesse Voice (Merz Aesthetics) (3–5 years). A multiinstitutional clinical trial revealed results of 80% improvement at 12 month follow-up.13 Long-term clinical results show that persistent medialization after injection may be present up to 2 years and more, with an average duration of 18 months.10 The effect of injection was measured based on VHI and s/z ratios while a consensus assessment of perceptual voice evaluation was performed. Complications after injection can be granuloma formation, overinjection, and nonsatisfying voice results.10 In a study from 2011, the benefit of this injectable implant as a vocal-fold augmentation material was found to last an average of 18.6 months (8–36).19
Study Limitations Due to the retrospective order of our research, it was not possible to study glottic closure patterns. Preand postoperative videolaryngostroboscopy were analyzed for all patients. Unfortunately, we changed our videolaryngoscope in May 2011. Thus, we could not compare the videos in an unbiased way because retrieving old videos was impossible on the new system. Retrieving them on another system would induce bias, automatically implying that the videos were of an earlier group Laryngoscope 125: May 2015
1164
and thus increasing the chance that they would have been fat-injected patients. Therefore, this analysis was not included. A second limitation of our study is the difference in follow-up time between the fat augmentation and Radiesse Voice groups. The difference is induced by the nature of the study design for which an abrupt change of surgical technique was necessary due to new regulations concerning the sterility of reusable surgical instruments. However, in the group of patients treated with autologous fat, two reinterventions (both patients were treated 6 months after the first operation) were performed due to a dissatisfying voice result. In the Radiesse (Merz Aesthetics) group, four reinterventions were needed (the mean time between the first and second intervention was 7 months). Mean follow-up was 10 months in the fat augmentation group and 7 months in the Radiesse Voice (Merz Aesthetics) group. Although reinterventions were necessary more often in the Radiesse Voice (Merz Aesthetics) group, statistical analysis showed no significant difference in the number of reinterventions between both groups.
Future Prospective To our knowledge, this is the first report describing the differences in short-term voice outcomes after autologous fat augmentation compared to augmentation with Radiesse Voice (Merz Aesthetics). No statistically significant differences were seen between both treatments. However, no reports available of long-term voice outcomes are available, it would be interesting to update our results after a longer follow-up period within the Radiesse Voice group.
CONCLUSION This retrospective cohort demonstrated that there are no short-term differences in VHI outcome or reoperations for augmentation with fat compared to Radiesse Voice (Merz Aesthetics).
BIBLIOGRAPHY 1. Cantillo-Banos E, Jurado-Ramos A, Gutierrez-Jodas J, et al. Vocal fold insufficiency: medialization laryngoplasty vs calcium hydroxylapatite microspheres (Radiesse Voice(R)). Acta Otolaryngol 2013;133:270–275. 2. Reiter R, Brosch S. Laryngoplasty with hyaluronic acid in patients with unilateral vocal fold paralysis. J Voice 2012;26:785–791. 3. Rosen CA, Thekdi AA. Vocal fold augmentation with injectable calcium hydroxylapatite: short-term results. J Voice 2004;18:387–391. 4. Shen T, Damrose EJ, Morzaria S. A meta-analysis of voice outcome comparing calcium hydroxylapatite injection laryngoplasty to silicone thyroplasty. Otolaryngol Head Neck Surg 2013;148:197–208. 5. Hartl DM, Hans S, Crevier-Buchman L, et al. Long-term acoustic comparison of thyroplasty versus autologous fat injection. Ann Otol Rhinol Laryngol 2009;118:827–832. 6. Schneider-Stickler B, Gaechter J, Bigenzahn W. Long-term results after external vocal fold medialization thyroplasty with titanium vocal fold medialization implant (TVFMI). Eur Arch Otorhinolaryngol 2013;270: 1689–1694. 7. van Ardenne N, Van der wegen J, van Nuffelen G, et al. Medialization thyroplasty: vocal outcome of silicone and titanium implant. Eur Arch Otorhinolaryngol 2011;268:101–107. 8. Vinson KN, Zraick RI, Ragland FJ. Injection versus medialization laryngoplasty for the treatment of unilateral vocal fold paralysis: follow-up at six months. Laryngoscope 2010;120:1802–1807. 9. Yung KC, Likhterov I, Courey MS. Effect of temporary vocal fold injection medialization on the rate of permanent medialization laryngoplasty in
Lodder and Dikkers: Voice Outcome After Vocal Fold Augmentation
unilateral vocal fold paralysis patients. Laryngoscope 2011;121:2191– 2194. 10. Mallur PS, Rosen CA. Vocal fold injection: review of indications, techniques, and materials for augmentation. Clin Exp Otorhinolaryngol 2010; 3:177–182. 11. Sanderson JD, Simpson CB. Laryngeal complications after lipoinjection for vocal fold augmentation. Laryngoscope 2009;119:1652–1657. 12. Hsiung MW, Woo P, Minasian A, et al. Fat augmentation for glottic insufficiency. Laryngoscope 2000;110:1026–1033. 13. Rosen CA, Gartner-Schmidt J, Casiano R, et al. Vocal fold augmentation with calcium hydroxylapatite: twelve-month report. Laryngoscope 2009; 119:1033–1041.
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14. Stuut M, Tjon Pian Gi RE, Dikkers FG. Change of Voice Handicap Index after treatment of benign laryngeal disorders. Eur Arch Otorhinolaryngol 2014;271:1157–1162. 15. Eckel FC, Boone DR. The S/Z ratio as an indicator of laryngeal pathology. J Speech Hear Disord 1981;46:147–149. 16. McCulloch TM, Andrews BT, Hoffman HT, et al. Long-term follow-up of fat injection laryngoplasty for unilateral vocal cord paralysis. Laryngoscope 2002;112:1235–1238. 17. DeFatta RA, DeFatta RJ, Sataloff RT. Laryngeal lipotransfer: review of a 14-year experience. J Voice 2013;27:512–515. 18. Kwon TK, Rosen CA, Gartner-Schmidt J. Preliminary results of a new temporary vocal fold injection material. J Voice 2005;19:668–673. 19. Carroll TL, Rosen CA. Long-term results of calcium hydroxylapatite for vocal fold augmentation. Laryngoscope 2011;121:313–319.
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Rhinological and Otological Society, Inc.
Comparison of Voice Outcome After Vocal Fold Augmentation With Fat or Calcium Hydroxylapatite Wouter L. Lodder, MD, PhD; Frederik G. Dikkers, MD, PhD Objectives/Hypothesis: To evaluate the short-term voice outcomes of vocal fold augmentation using fat compared to calcium hydroxylapatite product Radiesse Voice (Merz Aesthetics). Study Design: Retrospective study design. Methods: Sixty-six consecutive patients with vocal fold insufficiency were recruited, including the final 33 patients treated with fat and all 33 patients treated with calcium hydroxylapatite product. Before April 2011, fat augmentation was the standard treatment; from April 2011, only calcium hydroxylapatite product was used. For all subjects, videolaryngostroboscopic evaluation, s/z ratios, and voice handicap index (VHI) were analyzed. Methods: Treatment outcomes were evaluated 3 months after the augmentation. Two patients augmented with fat (both after 6 months), versus four augmented with calcium hydroxylapatite product (mean after 7 months), needed reintervention. Mean VHI decreased from 18 points in the fat augmentation group compared to 17 points in the calcium hydroxylapatite group. Mean s/z ratio changed 20.33 in the fat augmentation group compared to 20.46 in the calcium hydroxylapatite group. Conclusion: This retrospective cohort demonstrates that there are no short-term differences in VHI outcome or number of reinterventions for augmentation with fat compared to calcium hydroxylapatite product Radiesse Voice (Merz Aesthetics). Key Words: Glottal insufficiency, outcome, fat augmentation, calcium hydroxylapatite, voice handicap index. Level of Evidence: Level 4. Laryngoscope, 125:1161–1165, 2015
INTRODUCTION Dysphonia due to glottal insufficiency may be caused by a variety of conditions. Lesion of the recurrent laryngeal nerve is one of the most common causes.1 Numerous techniques are available for correction of the insufficiency. Implantation of biomaterials in the vocal fold, fat augmentation, or medialization laryngoplasty are commonly used techniques.2–9 Various biomaterials are available for implantation. Autologous fat and Cymetra (LifeCell, Bridgewater, NY) are the most commonly used materials. The use of nonbiomaterials Gelfoam (Pharmacia and Upjohn, Pfizer, New York, NY), silicone, and various gels are also discussed in the literature.10 Complications of injection of both bio- and nonbiomaterials consist of airway obstruction due to mass effect, Additional Supporting Information may be found in the online version of this article. From the Department of Otorhinolaryngology/Head and Neck Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Editor’s Note: This Manuscript was accepted for publication November 27, 2014. Presented at the 10th Congress of the European Laryngological Society, Antalya, Turkey, April 9–12, 2014. The authors have no funding, financial relationships, or conflicts of interest to disclose. Send correspondence to Wouter L. Lodder, MD, PhD, Dept. of Otorhinolaryngology, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands. E-mail: [email protected] DOI: 10.1002/lary.25104
Laryngoscope 125: May 2015
inflammatory changes leading to increased tissue stiffness, and dissatisfying results of the intervention.11,12 Relatively new is the use of Radiesse (Merz Aesthetics, San Mateo, CA), developed primarily for facial plastic surgery.3,13 The present study is conducted to evaluate the short-term voice outcomes of vocal fold augmentation using fat compared to calcium hydroxylapatite (Radiesse Voice; Merz Aesthetics, San Mateo, CA).
MATERIALS AND METHODS Retrospective Study Design Patients. Patients charts of 66 consecutive patients with glottal insufficiency were reviewed, including all 33 patients treated with fat and all patients treated with Radiesse Voice (Merz Aesthetics) with a follow-up of at least 3 months. All patients were treated in our institution. Only patients with glottal insufficiency existing longer than 12 months were included. The etiology of glottal insufficiency is shown in Table I. Patients were evaluated by videolaryngostroboscopy before and 3 months after operation. Of the 66 patients, 32 were men and 34 were women. Three patients smoked at the time of the operation, eight smoked in the past, and 55 never smoked. In 77% of the patients, this was the primary therapy; 23% of the patients were initially treated elsewhere (6 with unknown surgery [no injections]; 9 with voice therapy). Operation Technique. Two different surgeons performed the intervention. Fifty-five patients were operated by the senior author; 11 patients were operated by a laryngology fellow. All patients underwent augmentation in general anesthesia with orotracheal intubation tube size 5 or 6. No complications occurred.
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TABLE I. Etiology of Glottal Insufficiency in a Cohort (N 5 66) Treated With Either Fat or Radiesse Voice Augmentation. Fat
Radiesse Voice
Total
Paralysis of unknown origin Postthyroidectomy
6 2
10 1
16 3
Intrathoracic surgery
5
5
10
Neck dissection Vocal fold atrophy (n 5 13)
1
1
2
Cause
Vocal fold paralysis (n 5 31)
voice outcome measurements, the s/z ratio was determined. As described in the literature, s/z ratios are significantly higher for dysphonic subjects with laryngeal pathology: patients with functional dysphonia free of laryngeal pathology demonstrated the same s/z ratios (approximately 1,0) as the normal-speaking control subjects.15 Patients were evaluated by videolaryngostroboscopy and VHI before and approximately 3 months after operation (mean 3.81 months; SD 3.6).
Statistics Statistical analysis was performed using SPSS (version 18.0; Statistical Package for Social Sciences, Inc, Chicago, IL). Chi-square test was performed to measure the difference in reoperation/no voice improvements.
Cerebrovascular accident
2
2
4
Parkinson’s disease Central incomplete closure due to presbylarynx
1 2
0 0
1 2
Central incomplete closure due to unknown origin
1
5
6
The internal review board of UMCG states that there is no need for explicit patient’s permission to conduct a retrospective study. This is based on the Dutch Medical Research Law (Wet Medisch Onderzoek).
2 1
4 0
6 1
RESULTS
Institutional Review Board Approval
Hypomobility vocal fold (n 5 7) Postradiotherapy Postintubation
Subjective Voice Outcome
Vocal fold scar/sulcus (n 5 15) Vocal fold vergeture Sulcus glottidis
2 5
0 1
2 6
Oncologic laryngeal surgery
3
4
7
Total
33
33
66
Before April 2011, fat augmentation was the standard treatment. Abdominal fat was harvested through a curved, small periumbilical-skin incision 3-cm in length. Fat was then harvested in three to five parts, with a cumulative volume of 15 to 20 ml. The wound was closed in two layers after placement of a drain, which was removed on the first postoperative day. Next, the fat was separated in three parts using a sterilized garlic press to separate the fat cells from connective tissue and fluid fat, yielding approximately 2 ml of injectable fat cells. The fat cells were then aspirated in a 1-ml syringe. The vocal folds were injected with a modified Br€ uning’s syringe during suspension microlaryngoscopy using a 1.3-mm outer diameter needle in the muscle of the vocal fold until a small glottis opening remained, which had to be palpable with comfortable resistance using a 3-mm suction tube. Fat was injected uni- or bilaterally in one to five locations (mean 3). Exact locations of injections were determined by the visual aspect of the vocal fold. Care was taken not to inject too superficially. The amount of injection was not recorded but rarely exceeded 1 ml. From April 2011, only Radiesse Voice (Merz Aesthetics) was used. It was injected during suspension microlaryngoscopy at one to eight locations (mean 3 standard deviation [SD] 1,9), in which 0.10 to 0.90 ml was injected per side (mean 0.36; SD 0.18). A standard rigid distally bent needle tip (needle tip diameter 0.6 mm) was used for injection. Similar rules concerning application were applied, as in fat augmentation. Assessment of Voice Outcome. The study was conducted in the voice clinic in our tertiary referral hospital, University of Groningen, University Medical Center Groningen (UMCG), Groningen, The Netherlands. As described earlier by Stuut et al.,14 all preoperative assessments of a patient’s voice were performed on the same day. After visiting the speech and language therapist and immediately before consulting the laryngologist, the patient filled out a validated Dutch version of the voice handicap index (VHI). During the study period, the same otolaryngologist performed all laryngoscopic assessments. For objective
Laryngoscope 125: May 2015
1162
In total, 66 patients with dysphonia due to glottal insufficiency were included. Of three patients, no preoperative VHI was available; and of four patients, no postoperative VHI was available. In the final analysis, this yielded 60 cases with complete VHI data: 31 cases augmented with fat and 29 augmented with Radiesse Voice (Merz Aesthetics). Preoperative VHI ranged from 24 to 87 (mean 58; SD 16), and postoperative VHI ranged from 1 to 85 (mean 42; SD 19). The difference between the results of fat and Radiesse Voice (Merz Aesthetics) augmentation is displayed in Table II. Results of 60 individual patients (divided in subgroups analogous to Table I) are displayed in Table III, showing preoperative, postoperative, and delta VHI. Supporting Figures S1 and S2 (available online only) illustrate the gain in VHI.
Objective Voice Outcome s/z ratios were also compared. Preoperative s/z ratio ranged from 0 to 5.50 (mean 1.90; SD 1.1). Postoperative TABLE II. Differences Between Fat and Radiesse Voice Augmentation.* Fat Augmentation
Preoperative VHI
Radiesse Voice Augmentation
P Value
> 0.05
61
56
(range)
(24 to 87)
(31 to 87)
Postoperative VHI (range)
42 (1 to 76)
41 (4 to 85)
> 0.05
217
218
> 0.05
(range) s/z-ratio change
VHI change per patient
(259 to 125) 20.33
(280 to 19) 20.46
> 0.05
(mean values)
(1.81 to 1.48)
(1.99 to 1.53)
Number of reinterventions Follow-up in months (range)
2 10
4 7
(3 to 43)
(3 to 22)
> 0.05 > 0.05
*There is no statistically significant difference in any of the values. VHI 5 voice handicap index.
Lodder and Dikkers: Voice Outcome After Vocal Fold Augmentation
TABLE III. VHI Change per Patient and Subcategory, Divided by Means of Augmentation.
TABLE III. (Continued) B. Radiesse Voice Augmentation (n 5 31).
A. Abdominal Fat Augmentation (n 5 29).
Patient
Subgroup
VHI Preoperative
VHI Postoperative
VHI Change
Vocal Fold Paralysis
Patient
Subgroup
VHI VHI VHI Preoperative Postoperative Change
9 10
69 54
52 38
217 216
1
72
13
259
11
58
27
216
2
51
16
248
3 4
75 66
44 37
231 229
12 13
82 56
71 48
211 28
14
43
42
21
5
72
57
215
15
51
57
6
6 7
66 56
56 49
210 27
16
74
48
226
8
36
29
27
9 10
49 49
45 50
24 1
17 18
50 75
28 56
222 219
19
71
52
29
11
53
58
5
20 21
42 29
38 34
24 5
22
53
62
9
Vocal Fold Atrophy
Vocal Fold Atrophy 12
63
36
227
13
49
22
227
14 15
55 87
30 67
225 220
16
31
18
213
17
34
33
21
Hypomobility Vocal Fold 23
81
1
280
24 25
76 83
54 76
222 27
26
48
50
2
27
Hypomobility Vocal Fold 18 19
44 74
4 47
240 227
85
54
231
20
83
76
27
28 29
37 81
23 71
214 210
Vocal Fold Scar/Sulcus
Vocal Fold Scar/Sulcus 21
72
37
235
30
24
15
29
22
60
33
227
31
73
70
23
23 24
47 52
24 35
223 217
25
50
39
211
26 27
38 36
31 30
27 26
28
58
62
4
29
55
80
25
s/z ratio ranged from 0.58 to 3.0 (mean 1.50; SD 0.59). In the group treated with fat augmentation, the mean s/z ratio changed from 1.81 to 1.48 (20.33). In the Radiesse Voice (Merz Aesthetics) group, the mean s/z ratio changed from 1.99 to 1.53 (20.46).
Videolaryngostroboscopy
B. Radiesse Voice Augmentation (n 5 31).
Patient
Subgroup
VHI VHI VHI Preoperative Postoperative Change
Pre- and postoperative videolaryngostroboscopy were analyzed of all patients. Because we changed our videolaryngoscope during the study, we were unable to include these examinations.
Necessity of Reintervention
Vocal Fold Paralysis
Two patients with fat augmentation (both after 6 months) and four patients with Radiesse Voice (Merz Aesthetics) augmentation (mean after 7 months; range 4–12) needed reintervention. With P 5 0.392, this difference was not of statistical significance.
1 2
48 68
1 30
247 238
3
49
14
235
4 5
85 72
54 43
231 229
6
56
34
222
DISCUSSION
7 8
48 57
29 38
219 219
This study shows that there are no short-term differences in voice outcome after vocal fold augmentation with autologous fat or Radiesse Voice (Merz Aesthetics).
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Comparison With Other Studies In 2011, Sanderson described laryngeal complications of autologous fat injection in 98 patients treated between 1997 and 2008.11 Complications occurred in 4.5%. Over-injection–inducing dysphonia was seen in three patients. In patients treated with autologous fat, success rates after 1 year (measured with grade, roughness, breathiness, asthenia, and strain [GRBAS] scale; voice analyses; and number of reinterventions needed) range from 62 to 70%; after 4 years, the success rate is around 41%.11,16 Other complications reported in the literature include over-resorption of fat, infections, or subsequent bleeding at the harvest site.11,12,17 In the literature, only a few articles describe experiences with Radiesse Voice (Merz Aesthetics). Several compositions of it exist. The injectable implant contains synthetic calcium hydroxylapatite microspheres, with a diameter range of 25 to 45 mm, suspended in an aqueous gel carrier. These particles allow for a long-lasting augmentation shown to be effective up to from 12 to 24 months. Radiesse Voice (Merz Aesthetics) lasts longer than Radiesse Voice Gel (Merz Aesthetics). The voice gel has another carrier substance, carboxymethylcellulose,10 and is an injectable implant containing synthetically derived polymers. This material requires no preparation and has no biologic infection transmission risk. The substance typically lasts 2 to 3 months after injection. This has been utilized extensively for temporary vocal-fold paralysis and for trial vocal-fold injection augmentation for a variety of causes of glottic incompetence.18 In 2013, the effect of Radiesse Voice (Merz Aesthetics) was directly compared to thyreoplasty medialization. The effects of thyreoplasty and this injectable implant seem comparable after both 6 and 24 months follow-up.1 In the literature, there are no reports available that describe the long-term effect of Radiesse Voice (Merz Aesthetics) (3–5 years). A multiinstitutional clinical trial revealed results of 80% improvement at 12 month follow-up.13 Long-term clinical results show that persistent medialization after injection may be present up to 2 years and more, with an average duration of 18 months.10 The effect of injection was measured based on VHI and s/z ratios while a consensus assessment of perceptual voice evaluation was performed. Complications after injection can be granuloma formation, overinjection, and nonsatisfying voice results.10 In a study from 2011, the benefit of this injectable implant as a vocal-fold augmentation material was found to last an average of 18.6 months (8–36).19
Study Limitations Due to the retrospective order of our research, it was not possible to study glottic closure patterns. Preand postoperative videolaryngostroboscopy were analyzed for all patients. Unfortunately, we changed our videolaryngoscope in May 2011. Thus, we could not compare the videos in an unbiased way because retrieving old videos was impossible on the new system. Retrieving them on another system would induce bias, automatically implying that the videos were of an earlier group Laryngoscope 125: May 2015
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and thus increasing the chance that they would have been fat-injected patients. Therefore, this analysis was not included. A second limitation of our study is the difference in follow-up time between the fat augmentation and Radiesse Voice groups. The difference is induced by the nature of the study design for which an abrupt change of surgical technique was necessary due to new regulations concerning the sterility of reusable surgical instruments. However, in the group of patients treated with autologous fat, two reinterventions (both patients were treated 6 months after the first operation) were performed due to a dissatisfying voice result. In the Radiesse (Merz Aesthetics) group, four reinterventions were needed (the mean time between the first and second intervention was 7 months). Mean follow-up was 10 months in the fat augmentation group and 7 months in the Radiesse Voice (Merz Aesthetics) group. Although reinterventions were necessary more often in the Radiesse Voice (Merz Aesthetics) group, statistical analysis showed no significant difference in the number of reinterventions between both groups.
Future Prospective To our knowledge, this is the first report describing the differences in short-term voice outcomes after autologous fat augmentation compared to augmentation with Radiesse Voice (Merz Aesthetics). No statistically significant differences were seen between both treatments. However, no reports available of long-term voice outcomes are available, it would be interesting to update our results after a longer follow-up period within the Radiesse Voice group.
CONCLUSION This retrospective cohort demonstrated that there are no short-term differences in VHI outcome or reoperations for augmentation with fat compared to Radiesse Voice (Merz Aesthetics).
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