Regeneration of Vocal Fold Mucosa Using Tissue-Engineered Structures with Oral Mucosal Cells.

OBJECTIVES: Scarred vocal folds result in irregular vibrations during phonation due to stiffness of the vocal fold mucosa. To date, a completely satisfactory corrective procedure has yet to be achieved. We hypothesize that a potential treatment option for this disease is to replace scarred vocal folds with organotypic mucosa. The purpose of this study is to regenerate vocal fold mucosa using a tissue-engineered structure with autologous oral mucosal cells. STUDY DESIGN: Animal experiment using eight beagles (including three controls). METHODS: A 3 mm by 3 mm specimen of canine oral mucosa was surgically excised and divided into epithelial and subepithelial tissues. Epithelial cells and fibroblasts were isolated and cultured separately. The proliferated epithelial cells were co-cultured on oriented collagen gels containing the proliferated fibroblasts for an additional two weeks. The organotypic cultured tissues were transplanted to the mucosa-deficient vocal folds. Two months after transplantation, vocal fold vibrations and morphological characteristics were observed. RESULTS: A tissue-engineered vocal fold mucosa, consisting of stratified epithelium and lamina propria, was successfully fabricated to closely resemble the normal layered vocal fold mucosa. Laryngeal stroboscopy revealed regular but slightly small mucosal waves at the transplanted site. Immunohistochemically, stratified epithelium expressed cytokeratin, and the distributed cells in the lamina propria expressed vimentin. Elastic Van Gieson staining revealed a decreased number of elastic fibers in the lamina propria of the transplanted site. CONCLUSION: The fabricated mucosa with autologous oral mucosal cells successfully restored the vocal fold mucosa. This reconstruction technique could offer substantial clinical advantages for treating intractable diseases such as scarring of the vocal folds.

New technique for laryngotracheal mucosa transplantation. 'Stamp' welding using indocyanine green dye and albumin interaction with diode laser.

OBJECTIVE: To investigate (1) the possibility of survival of free mucosa "stamp" grafts fixed in the airway with a new technique using indocyanine green-dyed albumin solder activated with a diode laser and (2) the degree of improvement of wound healing in the airway by applying modified microskin transplantation techniques from burn surgery to cover a relatively large wound with a few small pieces of mucosa anchored in place with the previously mentioned technique. DESIGN: Three (one control and two experimental) rectangular (10 x 8 mm) wounds in tracheal mucosa were produced in four experimental animals (dogs) using a carbon dioxide laser. The control wound was left uncovered. In the first experimental wound, a mucosal flap was raised and then fixed in place by a trapdoor flap method. In the second experimental wound, two small (each 2 x 3 mm) autogenous mucosa grafts were anchored onto the surface with indocyanine green-dyed albumin activated with an 810-nm diode laser. Histomorphologically, the postoperative results from three wounds were compared. RESULTS: The experimental wounds were completely covered by regenerated squamous cells in 1 week and by ciliated epithelium in 2 weeks after the operation despite the discrepancy in size of the graft to wound area (1:6.7) covered with the stamp mucosa. No thermal damage from the diode laser was noted in the second experimental wounds. In the control wounds, no coverage was observed at 1 week, and only squamous cells were noted 2 weeks postoperatively. All the wounds had normal ciliated epithelium coverage at 4 weeks. CONCLUSIONS: Transplanted stamp grafts provided similar or better healing than trapdoor flap transplants. This new technique made endoscopic mucosal grafting possible and offers a potential breakthrough in the management of laryngotracheal stenosis.

Idiopathic progressive subglottic stenosis: findings and treatment in 52 patients.

Rarely, patients develop severe idiopathic subglottic stenosis. In 34 years, we have observed this disorder in 52 patients. All but 1 of the patients were female--a finding that suggests a hormonal cause. Without treatment, the airway progressively narrows--in some cases, until the patient requires tracheotomy. Laser submucosal resection and rotation mucosal flaps open and stabilize the airway and provide effective palliation. However, unlike traumatic subglottic stenosis, which has been cured with this technique, the idiopathic form causes submucosal fibrosis that regenerates spontaneously. Thus, treatment helps, but does not cure, the patient. The characteristic pathological finding is of submucosal dense fibrotic tissue with evidence of chronic inflammation. The clinical findings and treatment are here discussed.

Vocal cord reconstruction to treat aspiration caused by a post-intubation posterior glottic furrow.

OBJECTIVE: To present the case of a premature child with a furrow in the posterior vocal cord as a result of prolonged intubation, with symptoms of aspiration and poor voice, treated with a novel method of vocal cord reconstruction. METHODS: The vocal cord was reconstructed endoscopically by freeing up the edge of cord remnant and suturing this to a flap of inter-arytenoid mucosa to create a new cord. RESULTS: The resulting neo-cord was able to achieve full glottic closure with resolution of aspiration, and this was also accompanied by improvement in voice quality. CONCLUSION: The described vocal cord reconstruction method proved to be a useful treatment for aspiration and poor voice caused by a post-intubation vocal cord furrow.

Laryngeal flap for hypopharynx reconstruction.

Hypopharynx repair following resection of a pyriform sinus carcinoma may be accomplished primarily or involve a more extensive procedure, such as a free intestinal graft. Described herein is a laryngeal flap which may be used to repair a hypopharyngeal defect when a strip of mucosa, too narrow for a primary repair, is left. This method has been used successfully in 4 patients and has saved these patients from more extensive repairs.

A comparison of surgery and radiotherapy in the management of advanced pyriform fossa carcinoma.

This retrospective study analyses the outcome of treatment of 61 patients with advanced carcinoma of the pyriform fossa. Thirty-two patients (group 1) underwent surgery and postoperative radiotherapy and 29 patients (group 2) had induction chemotherapy followed by radiotherapy. The local recurrence-free survival at 5 years from the completion of therapy for group 1 was 54%, compared to 61% for group 2. The 5-year neck recurrence-free survival for groups 1 and 2 were 54% and 59%, respectively. The 5-year overall survival rates for groups 1 and 2 were 19% and 14%, respectively. Non-surgical therapy for advanced stage pyriform fossa cancer provides survival comparable with that achieved with the standard approach of surgery and postoperative radiotherapy. We advocate radical irradiation as the method of choice because it provides nodal coverage to the bilateral jugular chains and retropharyngeal nodes, all known to be at risk for metastases, and is associated with lower morbidity compared to surgery. But, however, despite the therapy, the outcome is poor.

Differential major histocompatibility complex class II locus expression on human laryngeal epithelium.

The survival of a laryngeal allograft will be dependent on the immunological composition of the donor larynx and, in particular, on the expression of major histocompatibility complex (MHC) class II antigens on professional and non-professional antigen-presenting cells. Laryngeal and tonsillar biopsies from normal individuals aged 18-78 years were processed and prepared for quantitative, multiple-colour immunofluorescence using mouse antihuman monoclonal antibodies to human leucocyte antigen (HLA)-DR, HLA-DQ and CD45. The laryngeal epithelium expressed HLA-DR locus products at variable levels, but expression of HLA-DQ was virtually absent. Tonsillar epithelial cells expressed HLA-DR at the basal layer only, while HLA-DQ was similarly not expressed. In contrast, both HLA-DR and -DQ locus products were present on lamina propria and intraepithelial leucocytes in both laryngeal and tonsillar mucosae, although at varying levels. The finding that laryngeal epithelial cells express MHC class II antigens has implications for the survival of laryngeal allografts and suggests that they may require significant immunomodulation. In addition, antigen presentation by epithelial cells has been hypothesized to contribute to the immunoregulatory function of mucosal tissues, and the finding that HLA-DQ locus products are only expressed at low levels by laryngeal epithelium raises questions about the repertoire of peptides to which the mucosal immune system can respond.