Fat implantation into Reinke's space: a histologic and stroboscopic study in the canine.

The scarred vocal fold is a cause of persistent dysphonia after laryngeal trauma, microsurgery, and tumor resection. The loss of Reinke's space with scar and stiffness is the primary cause. This study explores the technical aspects of endoscopic implantation of fat as an autologous implant for restoring the bulk and pliability of the vocal folds. Fat from the buccal area was harvested and prepared in 6 dogs. A mucosal flap submucosal pocket was prepared by means of microlaryngoscopy instrumentation. The fat implant was placed into the submucosal pocket. The mucosal flap was sutured endoscopically. Six weeks later, the larynx was harvested and mounted, and vocal fold oscillation was studied while driven by a humidified flow source. The vibratory patterns were studied by stroboscopy. Histologic sections of the vocal folds were made in the coronal plane. All 6 specimens had histologic evidence of viable implanted fat and/or fibrous tissue at the implant site. The site of implantation was in the superior aspect of the vocal fold, but contributed to mass in vocal fold bulk. This increase in bulk histologically corresponded to stroboscopic evidence of increased mass. On stroboscopy, the implant side continued to demonstrate good vibratory function. The study shows that fat implantation can be carried out as an endoscopic procedure. Fat implantation may be useful as a surgical procedure for restoration of Reinke's space. It may be applicable in patients with scars, sulcus vocalis, or vocal fold atrophy.     

喉良性增生性病变的嗓音学特点及治疗转归

目的 :探讨喉良性增生性病变对发声功能的影响及CO2 激光显微外科术后的转归特点。方法 :对2 92例喉良性增生性病变患者 (声带息肉、任克水肿、声带小结、囊肿、慢性肥厚性喉炎 )的流行病学、嗓音声学、形态及CO2 激光显微外科术后转归进行分析。结果 :声带小结患者均为青年女性 ,2 3.0 8%与职业有关 ;任克水肿为中老年患者。声带息肉及小结病变局限 ,手术仅涉及声带局部 ,术后改善明显 ,术后 1个月达正常状态 ;任克水肿患者术后 1个月改善明显 ,术后 3个月恢复最佳稳定 ;声带囊肿患者术后 1个月声音达最佳状态 ,但由于病变切除术后局部存在缺损 ,一定程度上影响预后 ;慢性肥厚性喉炎患者术后改善不满意。术后声门上代偿纠正均不明显。结论 :喉良性增生性病变主要累及声带被覆层 ,嗓音声障碍的程度及疗效与受累范围有关 ,激光显微外科手术可以保留良好结构及功能。除外科治疗外 ,还应及时矫正不良发声习惯等因素 ,以期获得最佳疗效。     

Expression and distribution of CD44 and hyaluronic acid in human vocal fold mucosa

OBJECTIVES: Expression of CD44 (a cell surface receptor for hyaluronic acid) and the distribution of hyaluronic acid were examined in the human vocal fold mucosa. METHODS: Light microscopic investigation was carried out on 10 normal larynges of newborn, infant, younger adult, and older adults with Alcian blue staining, a hyaluronidase digestion study, and immunohistochemistry for CD44. RESULTS: Before the appearance of hyaluronic acid in the newborn vocal fold mucosa, CD44 was expressed on the stellate cells in the macula flava and on the fibroblasts in Reinke's space. During infancy, hyaluronic acid appeared and was distributed in the vocal fold mucosa. Many more stellate cells in the macula flava showed CD44 expression, and a large amount of hyaluronic acid was present around the infant stellate cells; however, the fibroblasts in Reinke's space expressed little CD44. During adulthood, hyaluronic acid was distributed in the vocal fold mucosa. Almost all of the stellate cells in the macula flava showed CD44 expression, and much hyaluronic acid existed around the stellate cells in the adult macula flava. However, fibroblasts in the adult Reinke's space expressed little CD44, and hyaluronic acid density in that space was lower than that in the macula flava. CONCLUSIONS: Stellate cells in the macula flava and CD44 cooperatively play important roles in maintaining hyaluronic acid in the human vocal fold mucosa as a vibrating tissue.     

Phonomicrosurgical management of the disease of vocal fold]

OBJECTIVE: To find a way of reserving normal high quality phonatory function after vocal cord surgery. METHODS: Various benign lesions (vocal nodules, polyp of vocal cord, cyst of vocal cord, etc) as well as premalignant lesion and early glottic cancer were treated with minimally excision, lateral microflap, medial microflap, submucosal infusion, mucosal stripping or epithelium stripping of phonomicrosurgical techniques to achieve minimally invasion. RESULTS: The 1,044 (99.8%) patients suffering from vocal nodules, polyp or cyst and 12 Reinke's edema achieved a normal phonation within a week. The recovery of normal phonation in 20 Reinke's edema, 31 vocal cases needed 1-3 months, by mucosal stripping. The restoration of phonation on 5 papilloma, 36 early malignancy were better than trans-cervical operation. After 5 year follow-up, 3 cases of vocal cord premalignant lesions received the re-stripping operation. 32 cases of early glottic cancer remained tumor free, 5 cases relapsed and 2 cases received the re-stripping operation, and 2 cases received laryngectomy operation. CONCLUSION: The phonomicrosurgery may cure vocal disease and reserves good voice function.     

Granuloma of the membranous vocal fold: an unusual complication of microlaryngoscopic surgery

OBJECTIVES: We describe the clinical features of granuloma of the membranous vocal fold (as opposed to granuloma of the vocal process, or "contact granuloma"), a poorly recognized sequela of microlaryngoscopic surgery. Membranous vocal fold granuloma may mimic the initial lesion in appearance, and thus be mistaken for recurrence. METHODS: We performed a retrospective review of cases from 2 institutions. RESULTS: Fifteen cases of membranous vocal fold granuloma from 2 institutions were identified. In all but 1 case, granuloma developed in the early postoperative period, within 8 weeks. Of the 15 cases, 10 followed laser resection of carcinoma. Five were noted following cold steel resection of benign lesions (2 papillomas, 2 cysts, 1 Reinke's edema). Technical aspects of these cases suggest that membranous vocal fold granulomas result from surgical violation of deep tissue planes and/or epithelial defects. All patients were treated with proton pump inhibitors. In 12 cases, the granulomas proved self-limited, resolving over weeks to months following surgery. Three patients underwent surgical removal of the lesion, which confirmed the diagnosis. One of these cases recurred and was treated nonsurgically. CONCLUSIONS: Granuloma should be suspected when a mass lesion appears at the surgical site early in the postoperative course. Surgical excision is generally not necessary and may provoke further growth of granulation tissue.     

Unilateral arytenoid adduction improves voice in a patient with bilateral vocal fold immobility

Bilateral vocal fold immobility (BVFI) due to prolonged endotracheal intubation resulted in aphonia without any airway morbidity and was treated by several reconstructive procedures. Laryngeal reinnervation and silicone implantation failed to medialize one of those two fixed cords. Arytenoid adduction (AA) eventually achieved this goal. To select an optimal reconstructive procedure, a careful perusal of the history and head and neck examination including laryngeal electromyography, are necessary to determine the causes. AA procedure played an essential clinical indication in this study, not just an adjunct to the medialization laryngoplasty as usual. Since both the vocal cords positions were ranked as lateral positions subjectively, the full adduction for one of those two fixed vocal cords was performed without significant airway obstruction. The practice in this study provided an experience in correcting the voice in patients with BVFI. We need further experience to medialize the vocal cord in an appropriate magnitude since its counterpart may position variously and compromise the airway.     

DiHA (dextranomers in hyaluronan) injections for treatment of insufficient closure of the vocal folds: early clinical experiences

OBJECTIVE: To determine the clinical effects of injecting DiHA (a mixture of dextranomer molecules and 1% hyaluronan solution in equal proportions) as a "space filler" into the vocal folds of patients experiencing insufficient closure of the vocal folds resulting from either unilateral vocal fold paralysis or bowed vocal folds. STUDY DESIGN: A consecutive series of patients with insufficient closure of the vocal folds treated with DiHA injections and prospectively followed up with videostroboscopy and voice recordings that were evaluated by expert panels. METHODS: During a 21/2-year period, 14 patients with insufficient closure of the vocal folds were included. Six had a unilateral vocal fold palsy and 8 patients had "bowed" vocal folds. DiHA was injected into one vocal fold. Laryngoscopic examination and voice recordings were performed pre- and postoperatively. Expert panels did the evaluation of the stroboscopy examination and the perceptual voice analysis. RESULTS: Three patients were operated on with local and 11 under general anesthesia. All patients with unilateral palsy improved their stroboscopic status regarding both the wave and the closure after injection. Also, their voice parameters were significantly improved. Among the patients with bowed vocal folds, all except 2 showed an improvement in the glottic wave, 5 of 8 improved in glottic closure, and 3 improved their voice parameters significantly. CONCLUSION: This early clinical experience indicates that DiHA fulfills most of the requirements of an ideal "space-filling" substance for voice restoration in patients experiencing insufficient vocal fold closure.     

声带息肉和Reinke水肿细胞外基质蛋白mRNA表达

目的探讨声带息肉和Reinke水肿中，声带固有层细胞外基质主要成分mRNA表达的变化，为阐明疾病发病机制提供依据。方法应用逆转录-聚合酶链反应检测手术切除标本（声带息肉12例，Reinke水肿2例，5例行全喉切除而声带未受肿瘤侵犯的声带作为正常对照），细胞外基质中与胶原纤维、弹性纤维和透明质酸有关的9种蛋白的mRNA表达。结果声带息肉与对照声带比较，胶原酶mRNA表达下降，纤连蛋白mRNA表达升高，而纤调蛋白mRNA表达下降，差异均有统计学意义（P值均〈0．05）；赖氨酰氧化酶、透明质酸合成酶在病变和对照组织mRNA表达量差异无统计学意义（P值均〉0．05）；前弹性蛋白原、透明质酸酶、弹性蛋白酶在病变组织mRNA阳性表达率低于对照组织；前胶原Ⅰ在所有组织中均无表达。声带Reinke水肿组纤连蛋白表达量接近息肉组，纤调蛋白表达量接近对照组，因样本量小未做统计学分析。结论纤连蛋白和纤调蛋白是参与声带息肉病理过程的两种细胞外基质成分。反复用声造成损伤以及声带对损伤的修复过程可能在声带息肉发病机制起重要作用。     

Anterior and posterior medialization (APM) thyroplasty

OBJECTIVE: In unilateral vocal fold paralysis with dysphonia, most of the paralyzed vocal folds may be medialized effectively by medialization laryngoplasty. However, if the posterior glottal gap is wide, these procedures may sometimes have a limit to medialize the posterior glottis and cannot be effective for acceptable voice quality. The objective of this study is to introduce a new surgical technique for medializing the membranous and cartilaginous portions of the paralyzed vocal fold: anterior and posterior medialization (APM) thyroplasty. METHOD: Six patients underwent APM thyroplasty. They completed preoperative and postoperative evaluation with acoustic analysis and video laryngoscopy. RESULTS: All patients satisfied their voice subjectively after surgery. The paralyzed vocal folds, membranous and cartilaginous parts, were medialized well, and the paralyzed arytenoid showed less anterior tipping postoperatively. On voice analysis all patients showed prolonged phonation times and decreased perturbations after surgery. CONCLUSION: The advantages of this procedure are to medialize the membranous and cartilaginous portions of the paralyzed vocal fold directly and to correct vertical mismatch between two vocal folds. This procedure might be especially indicated in the lateralized position of the paralyzed vocal fold but not in the higher paralyzed vocal fold compared with the normal vocal fold.     

Laterofixation of the vocal fold using an endo-extralaryngeal needle carrier for bilateral vocal fold paralysis

Objectives

Laterofixation of the vocal fold is a simple and reliable surgical intervention for laryngeal obstruction due to bilateral vocal fold fixation to obtain sufficient glottal space. Nevertheless, it has some technical disadvantages. This report summarizes the surgical outcomes in patients who underwent laterofixation of the vocal fold with or without the use of an endo-extralaryngeal needle carrier (EENC).

Methods

A prospective study of 11 consecutive patients with bilateral vocal fold paralysis. All of the patients underwent unilateral vocal fold laterofixation. Six patients were assigned to the non-EENC group and five to the EENC group. The surgical outcomes were evaluated, including the operating time and respiratory and phonatory functions.

Results

The operating time was 44% shorter in the EENC group and less skin incisions were required. Postoperatively, the dyspnea was eliminated in all of the patients in both groups, and the six patients who required a tracheotomy were successfully decannulated. Spirometry confirmed the improvements in %FEV₁ and %PEF in the two groups. Postoperative voice function was socially acceptable in all patients, and it tended to be better in the non-EENC group. In the EENC group, one patient developed a minor submucosal hematoma and another patient had a recurrence of dyspnea 2 months postoperatively, probably due to thread disruption.

Conclusion

The present study confirms that laterofixation of the vocal fold with or without EENC relieves laryngeal obstruction. Surgery with the EENC is simpler and quicker than the conventional procedure. However, the surgery with the EENC has some disadvantages, including likely problems with the thread and downward traction on the vocal fold. Surgeons should be aware of these possible shortcomings.     

The first case of osteoma in the false vocal fold

Objectives

This article reports the first evidence of a larynx osteoma of the false vocal fold.

Study design

Case report and literature review.

Methods

Case report and review of previously published cases of larynx osteomas.

Results

A 79-year-old patient was referred to our institution for dysphagia and hoarseness. Fibrolaryngoscopy showed a regular surface tumefaction of the false fold and the left ventricle, with preserved cordal motility. Patient underwent direct laryngoscopy with CO₂ laser excision of the lesion. Pathologic examination of the lesion (1.6 cm × 1 cm) showed features consistent with an osteoma. Complete regression of symptoms was observed after surgery, with no lesions found on routine 1-year follow-up.

Conclusions

Osteomas are benign, slow growing tumors of the craniofacial bone area, very rarely located in the larynx. Although the etiology is unknown, accepted theories point to embryologic, post-traumatic and infectious causes. Surgical excision is indicated only in symptomatic cases. This case report is the fourth evidence of laryngeal osteoma and, to our knowledge, the first finding of a false vocal fold osteoma.     

Quantitative Evaluation of the Effects of Thyroarytenoid Muscle Activity upon Pliability of Vocal Fold Mucosa in an In Vivo Canine Model

Stiffness of the vocal fold is a significant factor in determining mucosal wave propagation and in the control of the fundamental frequency of phonation. We measured pliability of the vocal fold mucosa in an in vivo canine model as an index of stiffness while the histological layer-by-layer structure of the vocal fold was not disrupted. The point 1 mm below the free edge showed a maximal pliability that gradually diminished toward the tracheal side and reached a minimum. When the thyroarytenoid (TA) muscle contracted, pliability of the mucosa was significantly increased (P < 0.001). Mucosal pliability of the excised larynx was significantly increased compared with that in vivo (P < 0.001). The point of minimal pliability in the absence of TA muscle contraction did not shift after excision of the larynx, while TA muscle contraction caused a downward shift of the point of minimal pliability. Mucosal pliability can thus be used to quantitatively assess the effects of TA muscle contraction on stiffness of the vocal fold mucosa.     

Bipedicled strap muscle transposition for vocal fold deficit after laser cordectomy in early glottic cancer patients

OBJECTIVE: In treating early glottic carcinomas, the outcomes of endoscopic laser cordectomy have been proven to be valuable in local control, survival, and vocal function preservation. In some extended cases, however, laser cordectomy may leave patients with poor vocal function because of vocal fold deficit. This work assesses the vocal outcome of medialization laryngoplasty with bipedicled strap muscle transposition for vocal fold deficit resulting from laser cordectomy in early glottic cancer patients. STUDY DESIGN: A prospective clinical series. METHODS: Thirteen early glottic cancer patients who had vocal fold deficit caused by previous laser cordectomy underwent medialization laryngoplasty with bipedicled strap muscle transposition. The thyroid lamina on the cordectomy side was paramedially separated. The inner perichondrium was circumspectly raised from the overlying thyroid cartilage. After separating the thyrohyoid and cricothyroid membranes, the lamina was retracted laterally. A bipedicled strap muscle flap was then transposed into the area between the lamina and the paraglottic soft tissue. The thyroid cartilages were carefully sutured back in position. All patients received pre- and postoperative voice assessments comprising laryngostroboscopy and vocal function studies. RESULTS: Vocal enhancement was present in 92% (12/13) of patients after medialization laryngoplasty with strap muscle transposition. The glottal closure and maximal phonation time were noticeably improved by surgery. No dyspnea or other significant complications were observed in any patients. CONCLUSION: The outcomes show that bipedicled strap muscle transposition is a prosthesis-free, safe, and valuable laryngoplastic technique for correcting glottal incompetence caused by endoscopic laser cordectomy in early glottic cancer patients.     

Microendoscopy of Reinke's space

OBJECTIVES: Contemporary surgical treatment of the superficial layer of the lamina propria or Reinke's space is most commonly performed through an incision in the overlying vocal fold epithelium. This approach may disrupt normal tissue, induce scarring, and allow extrusion of implanted materials. Previously reported external approaches to Reinke's space required either a laryngofissure or a "minithyrotomy" for access. These surgical approaches were performed without direct imaging of Reinke's space. Instruments placed below the vocal fold epithelium via this external approach were visualized through the translucent vocal fold epithelium. We designed this study to identify the feasibility of limited-access surgery of the lamina propria using microendoscopes placed into Reinke's space through an external approach. METHODS: A cadaveric human larynx was dissected, and microendoscopes were directly advanced into Reinke's space through a subepithelial puncture of the cricothyroid membrane, as well as lateral fenestration through the thyroid cartilage. RESULTS: Photodocumentation of the undersurface of vocal fold epithelium, the opposing surface of the vocal ligament, and the intervening Reinke's space was successfully accomplished. CONCLUSIONS: Advances in both microendoscopes and accompanying instrumentation permit access to the superficial layer of the lamina propria without disrupting the overlying epithelium. This approach to microendoscopy of Reinke's space may allow for more effective surgical treatment of cysts, chronic edema, vascular abnormalities, atrophy, scarring, and sulcus vocalis.     

Prevention of vocal fold scarring by topical injection of hepatocyte growth factor in a rabbit model

OBJECTIVES/HYPOTHESIS: Vocal fold scarring disrupts the layer structure of the vocal fold lamina propria that is essential for optimal mucosal vibration. Prevention of vocal fold scarring remains challenging. Hepatocyte growth factor (HGF) has strong antifibrotic activity. The authors' previous studies have found that HGF stimulates hyaluronic acid production and suppresses collagen production from vocal fold fibroblasts, suggesting that HGF has therapeutic potential in prevention of vocal fold scarring. The present study aimed to demonstrate the effects of HGF on vocal fold scarring in an in vivo rabbit model. STUDY DESIGN: Animal experiment. METHODS: The vocal fold mucosa was stripped unilaterally in 20 rabbits, then HGF or saline (sham-treated group) was immediately injected into the injured site. At 6 months after the procedure, histological, rheological, and physiological examinations of vibratory behavior were completed. RESULTS: Histological examination revealed excessive collagen deposition and disorganized elastin in the sham-treated group, whereas the HGF-treated group presented with better wound healing exhibiting less collagen deposition. Contraction of the injured vocal folds observed in the sham-treated group did not occur in the HGF-treated group. Rheological data indicated that the HGF-treated vocal folds were less stiff and viscous compared with the sham-treated group. Mucosal vibration of HGF-treated vocal folds appeared much better than the sham-treated group in terms of phonation threshold pressure, vocal efficiency, mucosal wave amplitude, and glottal closure. CONCLUSION: Hepatocyte growth factor proved to be useful in preventing vocal fold scarring and maintaining viscoelastic shear properties of the vocal fold.     

Laser-assisted voice adjustment (LAVA) in transsexuals

OBJECTIVE: The objective of this study was to evaluate results of laser-assisted voice adjustment (LAVA) surgery in male-to-female (MTF) transsexual patients with androphonia. METHODS: The authors conducted a prospective case-control study of MTFs who underwent CO2 laser vocal fold vaporization between 1997 and 2003. Thirty-one patients were self-referred for voice feminization. Pre- and postoperative evaluations were completed. Patients' voices were recorded to obtain Fo before and after surgery. Voice Handicap Index (VHI) questionnaires were completed by post-LAVA patients. A panel of blinded listeners identified patients as male or female based on samples of connected speech recorded over the telephone. RESULTS: Mean follow-up (23 weeks) revealed pitch increases averaging 26 Hz. Self-evaluations revealed increases in voice femininity, congruity with self-image, and satisfaction. However, the evaluations also showed decreased vocal quality, loudness, and vocal range. Mean VHI was consistent with VHI scores associated with Reinke's edema. Six of 10 patients were consistently perceived as female. CONCLUSION: LAVA provides a conservative treatment for androphonia. Postoperative voice therapy may optimize outcomes.     

Homologous collagen substances for vocal fold augmentation

OBJECTIVES/HYPOTHESIS: Dysphonia resulting from failure of glottic closure during voicing is a difficult clinical problem. Recently developed homologous collagen compounds may be beneficial in treating this problem. The objectives of this thesis are to: 1) evaluate the potential site(s) of collagen graft placement in the human vocal fold, quantify the amount of graft material that can be injected into these sites, and determine how these sites are accessed by the currently available surgical tools for injection; 2) determine the effects of the superficial vocal fold implant on laryngeal vibratory patterns and characterize how the implant affects the forces required to bring vocal folds into an adducted position for vibration; and 3) evaluate the host response to two different forms of cadaveric collagen. STUDY DESIGN: Prospective laboratory. METHODS: Three separate experiments were undertaken: 1) Eight cadaver larynges were injected with collagen compounds through a 27-gauge needle. The amount of substance required to medialize the vocal fold and potential positions for graft placement were evaluated. 2) Six cadaver larynges were mounted on a stabilizing stand while airflow, vocal fold length, adduction forces, and abduction forces on the vocal folds were manipulated. Vibratory patterns before and after the injection of the vocal folds with solubilized collagen were assessed. 3) A nude mouse model was used to study the host response to two different exogenous collagen compounds. RESULTS: Solubilized collagen compounds could be injected reliably into the superficial layer of the lamina propria (SLLP), medial portion of the thyroarytenoid muscle, or lateral portion of the thyroarytenoid muscle. When injected superficially, significantly less material was required to displace the medial edge of the vocal fold to midline (P =.0001). When graft material was placed into the medial portion of the thyroarytenoid (TA) muscle, the forces required to bring the vocal fold into a position suitable for vibration were significantly reduced (P =.0106) and the vibratory patterns of the vocal folds were not impaired. Both AlloDerm(R) and Dermalogen(R) solubilized preparations of human dermal tissue were well tolerated in the nude-mouse model. Minimal inflammatory reaction occurred. Small amounts of graft material were identified histologically at the end of the 6-month study period. The graft material appeared organized and had been infiltrated with fibroblasts of host origin. CONCLUSIONS: Homologous collagen compounds can be reliably injected into the cadaveric human larynx. When the substances are injected into the medial portion of the TA muscle, immediately deep to the vocal ligament, they decrease the force of contraction needed to bring the vocal folds into a position adequate for phonation and have minimal affect on the vibratory patterns. These forms of homologous collagen are well tolerated. A small amount persists over a 6-month interval. These materials warrant further clinical trials in human subjects.     

Vocal function after vertical partial laryngectomy with glottic reconstruction by false vocal fold flap: durational and frequency measures.

OBJECTIVE: Compare vocal function following vertical partial laryngectomy (VPL) with or without glottic reconstruction by false vocal fold (FVF) mucosal flap. STUDY DESIGN: Twenty-seven patients with Tla squamous cell carcinoma (SCC) of the glottis were included in a prospective randomized clinical study. All patients were treated by frontolateral partial laryngectomy (FLPL). Glottic reconstruction with FVF mucosal flap was performed in 14 patients at the time of the FLPL, whereas 13 patients had standard FLPL. METHODS: Objective voice assessment was based on computerized acoustic recordings performed before and 1 year after surgery. When possible, additional recordings were performed at 3 months, 6 months, and 2 years postoperatively. Incidence of postoperative granuloma and anterior neoglottic web were noted. Repeated analysis of variance (ANOVA) was used to compare the durational (maximum phonation time, speech rate) and frequency measurements (average fundamental frequency [Fo], standard deviation of Fo, jitter, shimmer, noise-to-harmonics ratio, degree of voice breaks) between patients with or without glottic reconstruction, postoperative granuloma, and anterior neoglottic web. Linear regression was used to study the evolution over time of the durational and frequency measurements. RESULTS: Frequency measurements improved with time and were significantly better in patients treated with glottic reconstruction. In addition, glottic reconstruction decreased incidence of postoperative granuloma and anterior neoglottic web. CONCLUSIONS: The FVF mucosal flap technique can improve vocal results in selected cases of Tla SCC of the glottis when FLPL is the adequate surgical treatment. false vocal folds; glottic reconstruction; vertical partial laryngectomy; vocal function.     

Gender-related differences of hyaluronic acid distribution in the human vocal fold

OBJECTIVE: To quantify the distribution of hyaluronic acid (HA) within the normal human vocal fold and evaluate gender- and age-related differences. STUDY DESIGN: Prospective, cross-sectional study by age and gender groups using cadaveric vocal folds to study hyaluronic acid differences. METHODS: Twenty-five vocal fold halves obtained at autopsy were evaluated from nine adult male (age range, 34-52 y), seven adult female (age range, 21-41 y), four geriatric male (age range, 65-77 y), and five geriatric female (age range 65-82 y) subjects. Midmembranous vocal fold sections were stained for HA using the Muller-Mowry colloidal iron (acid mucopolysaccharide) stain with and without hyaluronidase. Digital imaging software was used to quantify the distribution of HA across the lamina propria at the vocal fold edge from superficial (subepithelial) to deep (vocalis muscle). RESULTS: A significant gender difference (P =.03) was noted in distribution when controlled for age. Combined, male subjects had a relatively constant distribution pattern throughout the depth of lamina propria. Female subjects showed relatively less HA in the first 15% of depth (most superficial) but showed more HA in the deeper 40% to 100% (toward vocalis muscle) than in male subjects. CONCLUSIONS: Important clinical implications may be extrapolated from our findings. First, relatively less HA in the most superficial area implies less protection from vibratory trauma and overuse and may explain in part why more female than male patients have phonotrauma to phonotraumatic lesions. Second, evaluating the distribution of HA in the normal human vocal fold allows more direction in our application of HA as a therapeutic lamina propria substitute in patients with voice disorders.