Faculty Bibliography

OBJECTIVES/HYPOTHESIS: To optimize decellularization of porcine vocal folds (VF) and quantify human bone marrow-derived mesenchymal stem cell (BM-MSC) interactions with this matrix to provide a foundation for regenerative approaches to VF repair. STUDY DESIGN AND METHODS: Vocal folds were dissected from porcine larynges and three decellularization protocols were compared, each consisting of washes and mechanical agitations with different combinations of reagents. DNA content was analyzed via Quant-iT Picogreen assay and hematoxylin and eosin staining. Bone marrow-derived MSCs were then seeded onto the decellularized VF matrices. Morphology, metabolic activity, DNA content, and gene expression were assessed using LIVE/DEAD Cell Viability, alamarBlue Cell Viability Assay, Quant-iT Picogreen assay, and, respectively. RESULTS: The most successful decellularization protocol removed 95% DNA content within 1 day, compared to several days required for previously described protocols. Histology confirmed the retention of extracellular matrix (ECM) and its components, including glycosaminoglycans, collagen, and fibrin, while void of nuclear/cellular content. Decellularized scaffolds were then seeded with BM-MSCs. Similar DNA quantities were observed after 24 hours of seeding within the VF-ECM scaffold when compared to cells on tissue culture plastic (TCP). LIVE/DEAD staining of the seeded VF-ECM confirmed excellent cell viability, and the metabolic activity of BM-MSCs increased significantly on VF-ECM compared to TCP. Endoglin gene expression decreased, suggestive of differentiation. CONCLUSION: Porcine VFs can be efficiently decellularized within 5 hours using a combination of sodium deoxycholate and peracetic acid. Decellularized VF-ECM supported attachment and growth of human BM-MSCs, with evidence of differentiation. LEVEL OF EVIDENCE: N/A Laryngoscope, 2015.

OBJECTIVES: To introduce the conceptual, theoretical, and practical foundations of a novel approach to voice therapy, called conversation training therapy (CTT), which focuses exclusively on voice awareness and efficient voice production in patient-driven conversational narrative, without the use of a traditional therapeutic hierarchy. CTT is grounded in motor learning theory, focused on training target voice goals in spontaneous, conversational speech in the first session and throughout. CTT was developed by a consensus panel of expert clinical voice-specialized speech-language pathologists (SLPs) and patients with voice problems. STUDY DESIGN: This is a prospective, clinical consensus design. METHODS: A preliminary CTT approach to voice therapy was developed by the first and last authors (J.G-S. and A.I.G.) and incorporated six interchangeable tenets: clear speech, auditory/kinesthetic awareness, rapport building, negative practice, basic training gestures, and prosody. Five expert voice-specialized clinical SLPs (consensus group) were then presented CTT and a discussion ensued. Later, an informal interview by a neutral third party person occurred for further recommendations for CTT. RESULTS: The CTT approach was modified to reflect all the consensus groups' recommendations, which included the need for more detail and rationale in the program, troubleshooting suggestions, and the concern for potential challenges for novice clinicians. CONCLUSIONS: CTT is a new therapy approach based on motor learning theory, which exclusively uses patient-driven conversational narrative as the sole therapeutic stimuli. CTT is conceptually innovative because it represents an approach to voice therapy developed without the use of a traditional therapeutic hierarchy. It is also developed using input from patients with voice disorders and expert clinical providers.

BACKGROUND: The classic form of Chediak-Higashi syndrome (CHS), an autosomal recessive disorder of lysosomal trafficking with childhood onset caused by mutations in LYST, is typified ophthalmologically by ocular albinism with vision loss attributed to foveal hypoplasia or nystagmus. Optic nerve involvement and ophthalmological manifestations of the late-onset neurodegenerative form of CHS are rarely reported and poorly detailed. METHODS: Case series detailing ophthalmological and neurological findings in three adult siblings with the late-onset form of CHS. RESULTS: All three affected siblings lacked features of ocular albinism and demonstrated significant optic nerve involvement as evidenced by loss of colour and contrast vision, central visual field loss, optic nerve pallor, retinal nerve fibre layer thinning by optical coherence tomography (OCT) and abnormal visual evoked potential, with severity corresponding linearly to age of the sibling and severity of neurological disease. Further, unusual prominence of a 'third line' on macular OCT that may be due to abnormal melanosomes was seen in all three siblings and in their father. Neurological involvement included parkinsonism, cerebellar ataxia and spastic paraparesis. CONCLUSIONS: This report expands the ophthalmological phenotype of the late-onset neurodegenerative form of CHS to include optic neuropathy with progressive vision loss, even in the absence of ocular albinism, and abnormal prominence of the interdigitation zone between cone outer segment tips and apical processes of retinal pigment epithelium cells on macular OCT.

OBJECTIVES/HYPOTHESIS: To evaluate the safety and efficacy of acoustic and electric sound processing for individuals with significant residual low-frequency hearing and severe-to-profound high-frequency sensorineural hearing loss. STUDY DESIGN: Prospective, single-arm repeated measures, single-subject design. METHODS: Fifty individuals, >/= 18 years old, with low-frequency hearing and severe high-frequency loss were implanted with the Cochlear Nucleus Hybrid L24 implant at 10 investigational sites. Preoperatively, subjects demonstrated consonant-nucleus-consonant word scores of 10% through 60% in the ear to be implanted. Subjects were assessed prospectively, preoperatively, and postoperatively on coprimary endpoints of consonant-nucleus-consonant words, AzBio sentences in noise, and self-assessment measures. RESULTS: Significant mean improvements were observed for coprimary endpoints: consonant-nucleus-consonant words (35.8 percentage points) and AzBio sentences in noise (32.0 percentage points), both at P < 0.001. Ninety-six percent of subjects performed equal or better on speech in quiet and 90% in noise. Eighty-two percent of subjects showed improved performance on speech in quiet and 74% in noise. Self-assessments were positive, corroborating speech perception results. CONCLUSION: The Nucleus Hybrid System provides significant improvements in speech intelligibility in quiet and noise for individuals with severe high-frequency loss and some low-frequency hearing. This device expands indications to hearing-impaired individuals who perform poorly with amplification due to bilateral high-frequency hearing loss and who previously were not implant candidates. LEVEL OF EVIDENCE: 2b. Laryngoscope, 2015.

BACKGROUND: Surgical access to metastases in the retropharyngeal lymph nodes (RPLN) could be difficult. Transoral robotic surgery (TORS) can be utilized to access RPLNs. The purpose of this study was to describe a TORS approach to RPLN dissection. METHODS: Case series of patients undergoing RPLN dissection by TORS, compared to matched controls (1:2). RESULTS: Twelve patients underwent robotic RPLN dissection. Median age was 63 (43-73). Pathology was oropharyngeal squamous cell carcinoma (OPSCC) in 9 and papillary thyroid cancer (PTC) in 3. The feeding tube dependence length was 12 days (1-46) on average. Complications occurred in 8 (66%); most commonly, aspiration pneumonitis (6). In comparison to the matched controls (24), there was no difference in length of stay or feeding tube dependence. Complications were higher in OPSCC patients. CONCLUSION: TORS is feasible for accessing RPLN. The procedure is well tolerated in PTC patients; OPSCC patients are at increased risk of complications

In this first paper of the 'Do You Know Your Guidelines' series, we review National Comprehensive Cancer Network (NCCN) recommendations and underlying evidence for the follow-up and surveillance of head and neck cancer survivors. The goals of follow-up and surveillance care are to 1) Maximize long-term oncologic outcomes of therapy with appropriate evaluation for recurrence; 2) Maximize functional and quality of life outcomes, while 3) Minimizing unnecessary and harmful low-value care. Finding the right balance of testing and surveillance is a challenge for providers and patients. Herein we review all NCCN recommendations for head and neck cancer survivors. We pay particular attention to an area of controversy: the use of ongoing surveillance imaging, in particular PET/CT scans

BACKGROUND: There is limited data on whether recurrent human papilloma virus (HPV) associated oropharyngeal carcinoma (OPSCC) is associated with higher surgical salvage rates. This study aimed to determine the success rate of salvage surgery for locally recurrent oropharynx cancer and factors influencing the outcome including p16 status. METHODS: All patients who underwent salvage surgery for locally recurrent or persistent oropharynx cancer after (chemo)radiotherapy between 2000-2012 were included. The Kaplan-Meier analysis was used to determine overall and recurrence-free survival. Univariable analysis was performed using Cox proportional hazards regression. RESULTS: Thirty-four patients underwent salvage surgery. Five patients (14.7%) were tracheostomy dependent and 22 (64.7%) gastrostomy tube dependent after salvage surgery. Post-operative complications occurred in 15 patients. Recurrence-free survival after salvage surgery was 28% and 19% at 3 and 5 years, respectively. The presence of nodal disease at the time of local recurrence, close or positive margins and lymphovascular invasion were the only factors associated with worse survival on univariable analysis. HPV status based on p16 testing was not associated with either overall or recurrence-free survival. CONCLUSION: Surgical salvage for OPSCC after failure of radiotherapy (+/- chemotherapy) is feasible. Patients that may benefit from surgery include those without regional recurrence and/or those in whom negative margins can be obtained. However, patients may be tracheotomy or gastrostomy tube dependent. p16 status did not appear to have prognostic impact in the salvage setting, however larger series are required to assess this relationship

Treatment for intracranial germ cell tumors includes platinum-based chemotherapy and external beam radiation therapy, which are risk factors for hearing loss. In patients who experience significant sensorineural ototoxicity due to cochlear hair cell injury, dose reduction of chemotherapy may be necessary. This report describes an adolescent male, with excellent treatment response for an intracranial nongerminomatous germ cell tumor, who developed sensorineural hearing loss, which was central rather than cochlear in origin and unrelated to carboplatin. This patient highlights the need to carefully differentiate the type and etiology of sensorineural hearing loss in patients with brain tumors receiving ototoxic chemotherapy.

OBJECTIVE:The tumour-node-metastasis staging system has a dynamic structure that is continuously being updated as scientific data develops. This review discusses some suggested revisions on tumour-node-metastasis staging of human papillomavirus negative upper aerodigestive tract cancers. METHODS:The seventh edition of The American Joint Committee on Cancer Staging Manual was reviewed and important issues that could be considered for revision were identified and discussed. RESULTS:According to our assessment of the oncological outcomes of previous studies, the following factors should be considered for revision: anterior commissure involvement and subglottic extension in laryngeal cancers; underlying bone involvement in hard palate and upper alveolar ridge cancers; tumour thickness in oral cancers; and extracapsular spread and carotid artery involvement in neck metastases. CONCLUSION/CONCLUSIONS:Sufficient data on the prognostic importance of these issues have been reported. Suggested revisions in line with current knowledge on the clinical behaviour of upper aerodigestive tract cancers would improve the relevancy of staging.

OBJECTIVE:In a human cadaver study, a single-port operator-controlled flexible endoscope (Flex® System), facilitated with a high-definition camera and two accessory channels was tested for skull base surgery. DESIGN/METHODS:Skull base surgery was performed on human cadavers (n=4) using the Flex® System. A modified surgical midfacial approach, performed by rigid standard tools, was used for access to the sinus system, the skull base, and the middle cranial fossa. RESULTS:Endoscopic skull base visualization with the Flex® System is feasible. Surgical procedures performed included extended sinus surgery, anterior skull base approach, and visualization of the brain stem in the posterior cranial fossa. Important landmarks of the anterior skull base were visualized and manipulated by flexible compatible tools. CONCLUSION/CONCLUSIONS:The Flex® System allows for manipulation of the anterior skull base and visualization of the posterior cranial fossa in a preclinical setting. Further studies as well as development of supplemental tools are in progress.