The Global Experience of Laryngeal Transplantation: Series of Eleven Patients in Three Continents.

Background: The loss of laryngeal function affects breathing, swallowing, and voice, thus severely compromises quality of life. Laryngeal transplantation has long been suggested as a solution for selected highly affected patients with complete laryngeal function loss.

Objective: To obtain insights regarding the advantages, weaknesses, and limitations of this procedure and facilitate future advances, we collected uniform data from all known laryngeal transplants reported internationally.

A Heterotopic Mouse Model for Studying Laryngeal Transplantation.

Laryngeal heterotopic transplantation, although a technically challenging procedure, offers more scientific analysis and cost benefits compared to other animal models. Although first described by Shipchandler et al. in 2009, this technique is not widely used, possibly due to the difficulties in learning the microsurgical technique and time required to master it.

Safety and Feasibility of a Novel Esophageal Balloon for Circumferential Cytologic Sampling.

Objectives: A prior publication introduced the Strome-Blitzer balloon's ability to obtain circumferential esophageal cytologic sampling. This GLP study was requisite for FDA approval to determine if equivalent cell capture and cellularity was observed with the balloon compared to surface sampling brushes and to determine the balloon's usability for naive otolaryngologists.

Methods: Three naïve users tested the Hobbs brush and Strome-Blitzer balloon on 4 Yorkshire swine.

Validation of the use of a fluorescent PARP1 inhibitor for the detection of oral, oropharyngeal and oesophageal epithelial cancers.

For oral, oropharyngeal and oesophageal cancer, the early detection of tumours and of residual tumour after surgery are prognostic factors of recurrence rates and patient survival. Here, we report the validation, in animal models and a human, of the use of a previously described fluorescently labelled small-molecule inhibitor of the DNA repair enzyme poly(ADP-ribose) polymerase 1 (PARP1) for the detection of cancers of the oral cavity, pharynx and oesophagus. We show that the fluorescent contrast agent can be used to quantify the expression levels of PARP1 and to detect oral, oropharyngeal and oesophageal tumours in mice, pigs and fresh human biospecimens when delivered topically or intravenously.

Abrasion and blunt tissue trauma study of a novel flexible robotic system in the porcine model.

Objectives: The objective of this study was to determine if a flexible robotic system caused increased tissue reaction when accessing the oropharynx and hypopharynx compared to intubation controls in only 2 scenarios: high speed tissue impact and multiple unit insertions and retractions. The data obtained were submitted as part of the entirety of information submitted for FDA approval.

Methods: This study consisted of 5 groups of Yorkshire pigs (2 animals per group).

Metformin Prevents the Progression of Dysplastic Mucosa of the Head and Neck to Carcinoma in Nondiabetic Patients.

Objective: Metformin is an oral anti-hyperglycemic agent used to treat type 2 diabetes mellitus (DM). In vitro and animal models have shown that metformin can prevent the progression of oral lesions to carcinoma; however, there is conflicting data in the clinical literature regarding risk reduction for malignancy in head and neck cancer (HNC).

Study Design: Case series.

Directed balloon cytology of the esophagus: A novel device for obtaining circumferential cytologic sampling.

Objective: Current methods of obtaining esophageal cytology include brush biopsy and blind balloon sampling, among others. These methods can be time-consuming if performed in accordance with acknowledged standards. Further, exact site localization can prove to be difficult.

Total laryngeal transplant explanted: 14 years of lessons learned.

In 1998, the first successful total laryngeal transplant was performed. Outstanding voice quality and swallowing function were achieved, and over the subsequent 14 years, much was learned about tolerance of a transplanted larynx. After approximately a decade, a slowly progressive, chronic rejection process gradually rendered the organ nonfunctional, and the patient and his providers deemed him appropriate for explantation.

Ten-month laryngeal allograft survival with use of pulsed everolimus and anti-alphabeta T-cell receptor antibody immunosuppression.

Objectives: The risks of daily immunosuppression limit the use of laryngeal transplantation as a reconstructive option. Pulsed immunosuppressive dosing can lessen these risks. The study objective was to develop a long-term pulsing regimen that minimizes exposure to immunosuppressive agents.

Anti-αβ-T-cell receptor antibodies in the setting of laryngeal transplantation.

Inhibiting T-cell activation is critically important to the induction of transplantation tolerance. Monoclonal antibodies directed against the αβ-T-cell receptor have been shown to cause selective immunodepletion of this T-cell population and can provide long-term allograft acceptance. This article discusses the role of this promising immunosuppressive agent in scientific research and clinical utilization.

Long-term laryngeal allograft survival using low-dose everolimus.

Objective: The purpose of this study was to explore the mechanism and utility of everolimus as a single-agent therapy in preventing mouse laryngeal allograft rejection.

Study Design: Prospective animal study.

Setting: Academic research at a tertiary medical center.

Decoy NF-kappaB fortified immature dendritic cells maintain laryngeal allograft integrity and provide enhancement of regulatory T cells.

Objectives/hypothesis: The increased risk of malignancy associated with post-transplant immunosuppression limits the potential of laryngeal transplantation as a reconstructive option. This risk may be mitigated by utilizing decoy nuclear factor kappa B (NF-kappaB) immature dendritic cells (iDC) to provide donor-specific tolerance. The purpose of this study was to explore whether tolerogenic properties of iDC can be applied to composite tissue transplantation.

A new mouse laryngeal transplantation rejection grading system.

Objectives/hypothesis: Development of a rat laryngeal transplantation model allowed for the first total human laryngeal transplantation by the senior author in 1998. In an effort to further our knowledge of the immune system's role in laryngeal rejection, a change to the mouse model was required. Prior to initiating immunosuppressive research protocols, a reliable mouse larynx rejection classification had to be established.

Extent of neck dissection required after concurrent chemoradiation for stage IV head and neck squamous cell carcinoma.

Background: The management of initially bulky nodal disease after primary nonsurgical treatment for stage IV head and neck squamous cell carcinoma (HNSCC) continues to be a subject of debate.

Methods: A retrospective chart review of neck management in patients after chemoradiation was performed.

Results: Of the initially positive necks analyzed, 210/329 (65%) had a complete clinical response to treatment and 161 necks underwent neck surgery.

New mouse model for studying laryngeal transplantation.

Objectives: Laryngeal transplantation research has been studied in various animal models. For in-depth, immunology-based transplantation research, however, a thoroughly studied animal model must exist. The purpose of this study was to develop a reliable surgical technique in mice to serve as a model for further study of laryngeal transplantation.

Does vocal cord fixation preclude nonsurgical management of laryngeal cancer?

Objectives/hypothesis: To determine whether vocal cord fixation precludes nonsurgical management of T3/T4 laryngeal carcinoma.

Study Design: A retrospective chart review.

Methods: Between 1989 and 2005 patient records with T3/T4 squamous cell carcinoma of the larynx with vocal cord fixation at presentation were reviewed.

Induction with T-cell receptor antibody leads to long-term laryngeal allograft function.

Purpose: The use of induction therapy with alphabeta T-cell receptor (alphabetaTCR) monoclonal antibody in association with tacrolimus in an allogeneic rat laryngeal transplant model permits rigorous long-term evaluation of potential short-term synergism offered by these agents.

Materials And Methods: The allogeneic model consisted of 19 Brown Norway larynges transplanted to Lewis recipients. Treatment consisted of tacrolimus (1.

Laryngeal transplantation in the setting of cancer: a rat model.

Objective: Traditional immunosuppressive regimens make laryngeal transplantation in cancer patients prohibitive because of the increased risk of recurrence. Everolimus, a recently developed immunosuppressant, has demonstrated significant antitumor properties. The purpose of this study was to examine the effects of everolimus alone and in combination with other immunosuppressants on tumor growth in a combined laryngeal transplantation and tumor model.

Use of in situ hybridization to detect human papillomavirus in head and neck squamous cell carcinoma patients without a history of alcohol or tobacco use.

Context: Head and neck squamous cell carcinoma is commonly associated with tobacco and alcohol use. There are, however, a group of patients without a significant history of tobacco or alcohol use, and the etiology of these tumors is incompletely understood.

Objective: To examine tumors in this subpopulation for association with human papillomavirus (HPV) using newly available in situ hybridization probes.

Clinical predictors of larynx preservation after multiagent concurrent chemoradiotherapy.

Background: Determining which patients benefit from larynx preservation strategies remains problematic. We reviewed our experience using multiagent concurrent chemoradiotherapy to identify clinical predictors for success.

Methods: Cisplatin and fluorouracil were given during weeks 1 and 4 of radiation to 115 patients with locoregionally advanced larynx or hypopharynx squamous cell cancer without cartilage invasion or laryngeal destruction.

Donor bone marrow in laryngeal transplantation: results of a rat study.

Introduction: The concept of donor bone marrow transplantation has been successfully used in human solid organ transplantation to increase recipient chimerism. The development of recipient chimerism is associated with a decreased need for immunosuppression and even donor-specific tolerance. In this study, we attempted to augment recipient chimerism by the transfer of donor bone marrow at the time of rat laryngeal transplant.

Ansa cervicalis-to-recurrent laryngeal nerve anastomosis for unilateral vocal fold paralysis: experience of a single institution.

Objectives: One treatment option for unilateral vocal fold paralysis (UVFP) is ansa cervicalis-to-recurrent laryngeal nerve (ansa-RLN) anastomosis to provide reinnervation to the affected vocal fold. The advantages of this treatment approach are that it 1) provides vocal fold tone, bulk, and tension, 2) is technically simple, and 3) does not preclude other medialization procedures. We present all patients who have undergone ansa-RLN anastomosis for UVFP at our institution.

RAD inhibition of sarcoma growth: implications for laryngeal transplantation.

Purpose: Laryngeal transplantation has not been widely accepted because of concerns regarding accelerated tumor recurrences in the setting of nonspecific immunosuppression. Allotransplantation could potentially be offered to patients if immunosuppressive therapy could be demonstrated to exert tumor suppressive properties. Preliminary reports have demonstrated an antiproliferative effect of everolimus (RAD), a derivative of the immunosuppressant rapamycin.