Vocal Fold Reconstruction Research Articles

Role of Peri- and Postoperative Antibiotics in Microscopic Laryngeal Surgery

There are no widely accepted guidelines for the use of peri- and postoperative antibiotics for microdirect laryngoscopy (MDL) to prevent postoperative surgical site infection (SSI). This study examines the incidence of not only SSI, but also respiratory and oropharyngeal infections among patients who underwent MDL. Retrospective cohort. Medical records from a quaternary laryngology practice were reviewed retrospectively for patients who underwent MDL between October 2015 and December 2018. Adults who underwent MDL with excision of nonmalignant masses, vocal fold (VF) reconstruction with buccal graft, superficial VF injection, VF injection augmentation, use of carbon dioxide (CO2) or potassium titanyl phosphate (KTP) laser, and laryngeal dilation were included. Subjects were divided into three groups based on the use of antibiotics during the peri- or postoperative period. Group 1 did not receive peri- or postoperative antibiotics. Group 2 received perioperative antibiotics without postoperative antibiotics. Group 3 received both peri- and postoperative antibiotics. Antibiotic use was determined by surgeon policy, which changed over time, not by patient risk factors. Other data collected include demographics, medical comorbidities, surgical procedure, operative time, American Society of Anesthesiology class, incidence of SSI, respiratory or oropharyngeal infection, and postoperative antibiotic and steroid prescriptions for complications. 190 surgeries met inclusion criteria. Groups 1, 2, and 3 consisted of 113, 57, and 20 subjects, respectively. No SSI were reported. Baseline characteristics of median age, American Society of Anesthesiology, wound class, and gender did not differ between groups. Groups were found to have differed in type of procedure performed, with a predominance of vocal fold excision and superficial injection in Group 1, injection laryngoplasty using autologous fat graft and laryngeal reconstruction in Group 3, and a combination of procedure types in Group 2. Laser treatment with CO2 and/or KTP was utilized in 35% of procedures. The mean operative times (total time in which the laryngoscope remained in the oral cavity) for Groups 1, 2, and 3 were 29 (SD = 13), 42 (SD = 23), and 73 minutes (SD = 78), respectively; this was significantly different among the three groups (P < 0.0001). By logistic regression models, operative time was not significantly associated with the overall use of antibiotics (Χ2 = 1.81, P = 0.18) or corticosteroid (Χ2 = .05, P = .82) prescriptions during follow-up. In Groups 1, 2, and 3, 11%, 14%, and 10% of patients, respectively, required a follow-up antibiotic prescription for non-SSI and 11%, 12%, and 0% of patients, respectively, required a follow-up corticosteroid prescription within 30 days postoperatively. There was no significant difference in patients with diabetes or pulmonary comorbidity and patients without comorbidity in use of postoperative antibiotic (P = .45) or corticosteroid (P > .99) prescription. Within 30 days of follow-up, patients in Group 1 experienced VF hemorrhage (defined as any subepithelial blood in the area of excision) at an incidence of 19%. Complications within 30 days of follow-up showed an incidence of substantial pain ranging between 2%-4% and respiratory or oropharyngeal infection between 10%-12%. Two patients in Group 2 reported emergency department visits for dyspnea. One patient in Group 3 was admitted for tongue and floor of mouth swelling secondary to prolonged suspension. There were no incidents of SSI in this cohort. The need for follow-up antibiotic and/or corticosteroid prescription did not differ in relation to use or non-use of perioperative antibiotics, and neither did the incidence of respiratory or oropharyngeal infection. Longer operative time was associated with both peri- and postoperative antibiotic use, but there is no evidence yet that antibiotic use was necessary. These findings suggest that avoidance of routine perioperative and/or postoperative antibiotics may be appropriate; and further research should be encouraged.

Vocal Fold Reconstruction Using an Autologous Pedicled Fat Flap in a Rabbit Model.

We evaluated the efficacy of a vocal fold reconstruction technique using a vascularized autologous pedicled fat (PEFA) flap in a rabbit model of vocal fold paralysis. Animal model. The study included 30 male New Zealand White rabbits; 20 received vocal fold reconstructions (PEFA group) and 10 served as normal controls (control group). The right recurrent laryngeal nerve was resected, and simultaneous PEFA flap reconstruction was performed. The PEFA flap, including a pre-epiglottic fat and thyroid perichondrium, was elevated and implanted through a window at the inferior border of the thyroid cartilage. Histological and high-speed video analyses of vocal fold vibration were performed 1 month after PEFA reconstruction. The maximum amplitude of vocal fold vibration and the dynamic glottal gap were used to assess vocal fold vibration. The histological findings showed that the lamina propria ratio (lamina propria pixels/total vocal fold pixels) and the total number of vocal fold pixels were similar between the PEFA and control groups. Vocal fold vibration analyses indicated that the maximum amplitude differences in the vibration were slightly lower in the PEFA group. However, the dynamic glottal gap of the vocal fold was not significantly different between the PEFA group and the control group. The PEFA flap vocal fold reconstruction technique maintained the vocal fold area without a significant reduction in vocal fold vibration in a rabbit model. NA Laryngoscope, 130:1770-1774, 2020.

Magnetic Tissue Engineering of the Vocal Fold Using Superparamagnetic Iron Oxide Nanoparticles.

Losing one's ability to speak, because of tissue deficiency at the vocal fold (VF), leads to serious impairment in the quality of life. Until now, there is no successful approach for regenerating the VF. The aim of this study was to show the advantage of magnetic nanoparticles in the generation of scaffold-free three-dimensional (3D) VF cell constructs by magnetic tissue engineering (MTE). Rabbit VF fibroblasts were used to establish MTE: after cellular uptake of superparamagnetic iron oxide nanoparticles (SPIONs), cells can be controlled with a magnetic field thereby forming solid 3D cell structures. To transfer this method into human cells, SPIONs were adapted accordingly and tested for their influence on human VF (hVF) cells and for their ability to perform MTE with hVF cells. Of interest, the cell number and the magnet's shape influence the form of the rabbit VF cell construct. After successful characterization of hVF cells, biocompatibility analyses revealed no significant influence of SPIONs on them, thus 3D hVF cell constructs could be successfully generated by MTE. These basic results are important to develop MTE as an innovative method to regenerate functional VFs. We expect that in vivo studies, including MTE as an elegant, far-field controlled and touchless technology, will translate MTE VF bioconstructs into reconstructive laryngeal medicine. Impact Statement This study aims at nanotechnology for regenerative medicine by magnetic tissue engineering (MTE). New approaches for vocal fold (VF) reconstruction are desperately needed. Superparamagnetic iron oxide nanoparticles offer innovative, scaffold-free potentials for tissue engineering: MTE. By using MTE we could generate functional multilayered human VF cell constructs, which can consequently be used to regenerate the voice in patients with VF injuries.

Neues Verfahren zur Liposuktion und Fettaugmentation nach Chordektomie

Lipoinjections into the vocal folds are well established in otorhinolaryngology. Currently, lipofilling in patients with surgical defects after laser cordectomy is discussed. We describe a new device for liposuction and lipofilling for primary vocal fold reconstruction after laser cordectomy. A patient with a surgical defect after pT1a glottic cancer is presented. Primary lipoinjection after laser cordectomy was documented as a safe and easy method to reconstruct the surgical defect. No relevant complications have been observed.

Tissue-Engineered Vocal Fold Mucosa Implantation in Rabbits.

To assess phonatory function and wound healing of a tissue-engineered vocal fold mucosa (TE-VFM) in rabbits. An "artificial" vocal fold would be valuable for reconstructing refractory scars and resection defects, particularly one that uses readily available autologous cells and scaffold. This work implants a candidate TE-VFM after resecting native epithelium and lamina propria in rabbits. Prospective animal study. Research laboratory. Rabbit adipose-derived stem cells were isolated and cultured in three-dimensional fibrin scaffolds to form TE-VFM. Eight rabbits underwent laryngofissure, unilateral European Laryngologic Society type 2 cordectomy, and immediate reconstruction with TE-VFM. After 4 weeks, larynges were excised, phonated, and examined by histology. Uniform TE-VFM implants were created, with rabbit mesenchymal cells populated throughout fibrin hydrogels. Rabbits recovered uneventfully after implantation. Phonation was achieved in all, with mucosal waves evident at the implant site. Histology after 4 weeks showed resorbed fibrin matrix, continuous epithelium, and mildly increased collagen relative to contralateral unoperated vocal folds. Elastic fiber appearance was highly variable. Inflammatory cell infiltrate was limited to animals receiving sex-mismatched implants. TE-VFMs were successfully implanted into 8 rabbits, with minor evidence of scar formation and immune reaction. Vibration was preserved 4 weeks after resecting and reconstructing the complete vocal fold cover layer. Further studies will investigate the mechanism and durability of improvement. TE-VFM with autologous cells is a promising new approach for vocal fold reconstruction.

Functional and Histological Evaluation following Canine Vocal Fold Reconstruction Using Composite Thyroid Ala Perichondrium Flaps.

We evaluated the effects of vocal fold reconstruction using a composite thyroid ala perichondrium flap (CTAP) after unilateral vocal fold stripping in beagles. We hypothesized that CTAP would improve glottic closure, decrease phonation threshold pressure, and decrease perturbation. In addition, vocal folds with CTAP would exhibit neovascularization and fat with increased von Willebrand factor (vWF) and smooth muscle actin (SMA), reflecting neoangiogenesis and flap viability. Randomized controlled trial using beagles. University laboratory. Ten beagles underwent unilateral vocal fold stripping. Dogs in the scar-only group (n = 5) were sacrificed at 1 month. Dogs in the CTAP group (n = 5) underwent ipsilateral reconstruction with CTAP at 1 month and were sacrificed at 2 months. Excised larynx experiments evaluated vocal fold vibration using aerodynamic, acoustic, and mucosal wave measurements. Qualitative evaluation of vocal fold morphology and quantitative analysis of elastin, collagen, glycosaminoglycans, vWF, SMA, and hyaluronic acid were performed. Phonation threshold pressure (P = .005), percent jitter (P = .010), percent shimmer (P = .007), and open quotient (P = .007) were lower in the CTAP group. Neovascularization (P = .0079) and fat (P = .1667) occurred more with CTAP, although the difference in fat was not significant. von Willebrand factor was higher with CTAP vs contralateral normal fold (P = .110), although not statistically significant. Smooth muscle actin was higher with CTAP vs contralateral normal fold (P = .038) and scarred vocal folds (P = .022). Composite thyroid ala perichondrium flap restored glottic closure and vibratory periodicity following vocal fold scarring. Additional investigation on biologic response is warranted. Composite thyroid ala perichondrium flap offers an autologous, vascularized implant that can improve both vocal fold structure and function.

Functional and Histological Evaluation following Canine Vocal Fold Reconstruction Using Combined Thyroid Ala Perichondrium Flaps

Objectives: (1) Perform vocal fold reconstruction using composite thyroid ala perichondrium (CTAP) flaps in beagles following unilateral vocal fold stripping; (2) Evaluate aerodynamic, acoustic, vibratory, and histologic changes in canines undergoing CTAP-based vocal fold reconstruction compared to a control group undergoing injury alone. Methods: Unilateral vocal fold stripping was performed on ten beagles. Dogs healed for 1 month and were divided into 2 groups. Dogs in the control group (n = 5) were sacrificed. Dogs in the experimental group (n = 5) underwent ipsilateral vocal fold augmentation with a CTAP flap and recovered for 1 month prior to euthanasia. After euthanasia, larynges were harvested for excised larynx evaluation of vocal fold vibration using aerodynamic, acoustic, and mucosal wave measurements. Histological analysis was then performed on anterior, middle, and posterior sections of the vocal fold. Changes in the injured fold were compared between the control and experimental groups. Comparisons with the contralateral normal fold were made within the control and experimental groups. Results: Phonation threshold pressure was significantly lower in the treatment group ( P = .005). Percentage jitter ( P = .010) and shimmer ( P = .007) were also lower in the treatment group. Open quotient was significantly higher in the control group ( P = .007). Histological staining results were inconsistent, and gross analysis revealed evidence of surgical implantation without restoration of normal vocal fold architecture. Conclusions: CTAP-based vocal fold augmentation restored glottic closure and vibratory periodicity following vocal fold scarring. Additional investigation on biologic response is warranted. CTAP flaps offer an autologous, vascularized implant that can improve both vocal fold structure and function.

Elucidation of soft tissue flap histologic margins within a canine vocal fold.

Histologic identification of implanted soft tissues in experimental animal models can be challenging, as donor tissue often strongly resembles the recipient bed. We have encountered this dilemma following implantation of a Composite Thyroid Ala Perichondrium flap (CTAP) into a vocal fold. The CTAP procedure is the first to utilize a vascularized flap for vocal fold reconstruction, making data to confirm or refute its viability critical. The current study evaluated several tissue stains to define precisely the histologic margins of CTAPs at two weeks post-implantation in a canine model. Initial testing exposed canine cadaveric tissues to four stains (tattoo ink, Congo red, 4'6-diamidino-2-phenylindole, and henna) across four time periods. Tattoo ink alone withstood histologic processing. An exposure of 1 minute adequately delineated CTAP boundaries. The study concluded with a canine in vivo evaluation of a CTAP exposed to tattoo ink for 1 minute. After a two-week recovery period, vocal folds were harvested and evaluated histologically. Tattoo ink proved to be a safe and effective histologic marker in vivo, where the histologic margins of the implanted CTAP were clearly demarcated by a thin band of tattoo ink, soft tissue reactions were minimal, and interference with standard, special, or immunohistochemical stain assessments did not occur. Tattoo ink provides a reliable means of demarcating a CTAP within a vocal fold and demonstrated that CTAPs survive transplantation. Further, tattoo ink demarcation may serve as a useful histologic marker for those wishing to assess tissue implants in other in vivo models.

Ocena jakości głosu po usunięciu nowotworów T1 i T2 głośni z jednoczesną rekonstrukcją fałdu głosowego uszypułowanym płatem z mięśnia mostkowo-tarczowego

IntroductionIn recent years there has been an increasing number of cases of cancer, including cancer of the larynx. The choice of treatment should be primarily dictated by the complete elimination of cancer, but from the point of view of the patient, an important factor to keep in mind, is the quality of the voice that will be created at the end of the therapeutic process. AimThe aim of this study was to evaluate the voice quality of patients after partial surgery of the larynx with vocal fold reconstruction pedunculated sterno-thyroid muscle flap. Materials and MethodsThe study included 30 men aged 53–72 years who were treated at the Clinic of Otorhinolaryngology Department of Medical-Dental Medical University of Warsaw on account of cancer of the larynx, qualified according to the TNM classification T1 or T2. The radical removal of cancer was associated with resection of one vocal fold, laryngeal pouches and ventricular fold. In 15 patients, included to the group I at the end of phase oncology surgery, a reconstruction of “vocal fold” pedunculated sterno-thyroid muscle flap were performed simultaneously. The group II consisted of 15 patients who underwent surgery that removed only the cancerous lesions. Impact assessments arising after surgery of voice disorders on quality of life were made using the self-test failure of the voice (Voice Handicap Index in the Pruszewicz modification). The nature of the created voice was studied using GRBAS scale. All patients performed the laryngostroboscope examination. With “IRIS” program, prepared by a team at Wrocław University of Technology, the voice was recorded, and then was subjected to acoustic analysis. In addition, noise level and the maximum phonation time was measured. ResultsThe results indicate that the patients of group I gained a better voice confirming the values of objective acoustic analysis. The assessment made by the scale GRBAS patients who supplemented the resulting loss after tumour removal, with much less hoarseness of voice, did not have the hyperkinesis and there was no puff character. They had the better flow of voice and phonation time of vowels “a” was much longer. The assessment of quality of life of patients in group I made in a test of the VHI was higher than in group II. The laryngostroboscope examination confirmed a good phonatory occlusion and a nearly regular, healthy vocal fold vibration in patients who had received flap of muscle. ConclusionsEvaluation of the quality of voice after removing the tumor multiplicity in the glottis with simultaneous reconstruction “vocal fold” has confirmed that this is a very good surgical technique, which allows radically curing cancer for the simultaneous preservation of a good voice. The operation has limited indications for radiotherapy because of the desire to preserve the phonatory function of the larynx, and thus avoids the negative effects of radiation.

Vocal fold reconstruction: A novel flap

Vocal fold reconstruction: A novel flap

Controlled release of hepatocyte growth factor from a bovine acellular scaffold for vocal fold reconstruction

A bovine acellular scaffold was found to facilitate tissue remodeling in a rat model of vocal fold injury, whereas hepatocyte growth factor (HGF) has been shown to have an antiscarring effect in the larynx. This study examined the loading and release kinetics of HGF in vitro, and the potential of the acellular scaffold as a timed-release system for the delivery of HGF in vivo. Bilateral wounds were created in the posterior vocal folds of 20 rats, with HGF-loaded acellular scaffolds implanted into the wounds unilaterally, and scaffolds without HGF implanted into the contralateral vocal folds as control. The rats were humanely sacrificed after 3, 7, 30, and 90 days and their larynges were examined histologically and immunohistochemically. Expressions of key matrix proteins in the vocal fold coronal sections were quantified by digital image analysis. Results demonstrated a gradual, sustained release of HGF for at least 7 days in vitro, consistent with the detection of glycosaminoglycans inherent of the scaffold. In rat vocal folds implanted with HGF-loaded scaffolds, apparently fewer inflammatory cells were observed 3 days after surgery when compared to the control. The mean relative densities of collagen III and hyaluronic acid were significantly lower than those of the control 7 days after surgery. Scaffold implants were apparently degraded by 3 months in all animals, with no evidence of fibrosis or calcification. These data suggested that the bovine acellular scaffold could be promising for the exogenous delivery of select growth factors in vivo.

A bovine acellular scaffold for vocal fold reconstruction in a rat model

With a rat model of vocal fold injury, this study examined the in vivo host response to an acellular xenogeneic scaffold derived from the bovine vocal fold lamina propria, and the potential of the scaffold for constructive tissue remodeling. Bilateral wounds were created in the posterior vocal folds of 20 rats, and bovine acellular scaffolds were implanted into the wounds unilaterally, with the contralateral vocal folds as control. The rats were humanely sacrificed after 3 days, 7 days, 1 month, and 3 months, and the coronal sections of their larynges were examined histologically. Expressions of key matrix proteins including collagen I, collagen III, elastin, fibronectin, hyaluronic acid, and glycosaminoglycans (GAGs) were quantified with digital image analysis. Significant infiltration of host inflammatory cells and host fibroblasts in the scaffold implant was observed in the acute stage of wound repair (3 days and 7 days postsurgery). The mean relative densities of collagen I, collagen III, and GAGs in the implanted vocal folds were significantly higher than those in the control after 3 days, followed by gradual decreases over 3 months. Histological results showed that the scaffolds were apparently degraded by 3 months, with no fibrotic tissue formation or calcification. These preliminary findings suggested that the bovine acellular scaffold could be a potential xenograft for vocal fold regeneration.

Controlled release of hepatocyte growth factor from a bovine acellular scaffoldfor vocal fold reconstruction

Controlled release of hepatocyte growth factor from a bovine acellular scaffoldfor vocal fold reconstruction

Pore Architecture of a Bovine Acellular Vocal Fold Scaffold

An acellular xenogeneic scaffold derived from the bovine vocal fold lamina propria has shown some promise for in vitro vocal fold tissue engineering. To further explore the potential of the scaffold for cellular attachment, migration, and infiltration, as well as the transport of oxygen, proteins, and nutrients in vivo, this study examined the architecture of pores in the scaffold in terms of several key parameters. Porosity was determined using a standard fluid replacement method with a pycnometer. Average pore size and the pore size distribution were assessed using digital image analysis of scanning electron micrographs. The intrinsic permeability to water was measured using a custom-built hydrostatic pressure apparatus as an estimation of the overall porous nature of the acellular scaffold. The results indicated that the bovine acellular scaffold has a reasonably high porosity (90.49 +/- 4.33%), a proper pore size distribution (>60% of the pores with equivalent diameters > or =10 microm and < 100 microm) that could facilitate cellular attachment and infiltration, as well as a relatively high intrinsic permeability (0.21-3.21 darcy) for the transport of soluble factors. These findings offered preliminary support of the potential of the scaffold for facilitating functional extracellular matrix remodeling in vocal fold reconstruction.

Clinically evaluated procedure for the reconstruction of vocal fold vibrations from endoscopic digital high-speed videos

Investigation of voice disorders requires the examination of vocal fold vibrations. State of the art is the recording of endoscopic high-speed movies which capture vocal fold vibrations in real-time. It enables investigating the interrelation between disturbances of vocal fold vibrations and voice disorders. However, the lack of clinical studies and of a standardized procedure to reconstruct vocal fold vibrations from high-speed videos constrain the clinical acceptance of the high-speed technique. An image processing approach is presented that extracts the vibrating vocal fold edges from digital high-speed movies. The initial segmentation is principally based on a seeded region-growing algorithm. Even in movies with low image quality the algorithm segments successfully the glottal area by an introduced two-dimensional threshold matrix. Following segmentation, the vocal fold edges are reconstructed from the computed time-varying glottal area. The performance of the procedure was objectively evaluated within a study comprising 372 high-speed recordings. The accuracy of vocal fold reconstruction exceeds manual segmentation results obtained by clinical experts. The algorithm reaches an information flow-rate of up to 98 images per second. The robustness and high accuracy of the procedure makes it suitable for the application in clinical routine. It enables an objective and highly accurate description of vocal fold vibrations which is essential to realize extensive clinical studies which focus on the classification of voice disorders.

A Biodegradable, Acellular Xenogeneic Scaffold for Regeneration of the Vocal Fold Lamina Propria

A novel method for preparing an acellular xenogeneic extracellular matrix scaffold for tissue engineering was developed. Bovine vocal fold lamina propria specimens were treated with high-concentration sodium chloride, nucleic acid digestion, and ethanol dehydration for decellularization and removal of immunogenic foreign epitopes. Human vocal fold fibroblasts from primary culture were seeded onto the acellular scaffolds and cultured for 21 days. The decellularized and the recellularized scaffolds were examined by light microscopy, fluorescent microscopy, and scanning electron microscopy. Collagen synthesis and release by fibroblasts were quantified by the Sircol assay, whereas the synthesis and release of hyaluronic acid, decorin, and fibronectin were assessed by enzyme-linked immunosorbent assays. Viscoelastic shear properties of the scaffolds were quantified by a simple-shear rheometer at frequencies of up to 250 Hz. Preliminary results showed that a biodegradable, acellular extracellular matrix scaffold with an intact basement membrane and 3-dimensional structure of the matrix proteins was engineered. Vocal fold fibroblasts readily attached to and infiltrated the scaffold with high viability and active protein synthesis, demonstrating the biocompatibility. The elastic shear modulus and dynamic viscosity of the acellular scaffold and the fibroblast-repopulated scaffold were comparable to those of the human vocal fold cover. These findings support the potential of the scaffold as a xenograft for vocal fold reconstruction and regeneration.

A new method of vocal fold reconstruction using a pharyngeal myo-mucosal flap

A new method of vocal fold reconstruction using a pharyngeal myo-mucosal flap

VOCAL FOLD SCAR: Evaluation and Treatment

This article provides the framework for the comprehensive evaluation and treatment of patients with vocal fold scar. Nonsurgical and surgical treatment methods are discussed including the use of voice therapy, singing voice therapy, phonosurgical collagen injection, and fat graft vocal fold reconstruction.