RESUMEN
Clinically available hollow nerve guidance conduits (NGCs) have had limited success in treating large peripheral nerve injuries. This study aims to develop a biphasic NGC combining a physicochemically optimized collagen outer conduit to bridge the transected nerve, and a neuroconductive hyaluronic acid-based luminal filler to support regeneration. The outer conduit is mechanically optimized by manipulating crosslinking and collagen density, allowing the engineering of a high wall permeability to mitigate the risk of neuroma formation, while also maintaining physiologically relevant stiffness and enzymatic degradation tuned to coincide with regeneration rates. Freeze-drying is used to seamlessly integrate the luminal filler into the conduit, creating a longitudinally aligned pore microarchitecture. The luminal stiffness is modulated to support Schwann cells, with laminin incorporation further enhancing bioactivity by improving cell attachment and metabolic activity. Additionally, this biphasic NGC is shown to support neurogenesis and gliogenesis of neural progenitor cells and axonal outgrowth from dorsal root ganglia. These findings highlight the paradigm that a successful NGC requires the concerted optimization of both a mechanical support phase capable of bridging a nerve defect and a neuroconductive phase with an architecture capable of supporting both Schwann cells and neurons in order to achieve functional regenerative outcome.
Asunto(s)
Regeneración Nerviosa , Nervios Periféricos/cirugía , Prótesis e Implantes , Animales , Materiales Biocompatibles/química , Línea Celular , Colágeno/química , Ganglios Espinales/metabolismo , Laminina/metabolismo , Masculino , Neurogénesis , Fenobarbital/química , Ratas , Ratas Endogámicas Lew , Células de Schwann/metabolismo , Ingeniería de TejidosRESUMEN
Peripheral nerve injury presents significant therapeutic challenges for recovery of motor and sensory function in patients. Different clinical approaches exist but to date there has been no consensus on the most effective method of treatment. Here, we investigate a novel approach to peripheral nerve repair using olfactory derived stem (ONS) cells delivered in a biphasic collagen and laminin functionalized hyaluronic acid based nerve guidance conduit (NGC). Nerve regeneration was studied across a 10-mm sciatic nerve gap in Sprague Dawley rats. The effect of ONS cell loading of NGCs with or without nerve growth factor (NGF) supplementation on nerve repair was compared to a cell-free NGC across a variety of clinical, functional, electrophysiological, and morphologic parameters. Animals implanted with ONS cell loaded NGCs demonstrated improved clinical and electrophysiological outcomes compared to cell free NGC controls. The nerves regenerated across ONS cell loaded NGCs contained significantly more axons than cell-free NGCs. A return of the nocioceptive withdrawal reflex in ONS cell treated animals indicated an advanced repair stage at a relatively early time point of 8 weeks post implantation. The addition of NGF further improved the outcomes of the repair indicating the potential beneficial effect of a combined stem cell/growth factor treatment strategy delivered on NGCs. Stem Cells Translational Medicine 2017;6:1894-1904.
Asunto(s)
Regeneración Tisular Dirigida/métodos , Células Neuroepiteliales/trasplante , Traumatismos de los Nervios Periféricos/terapia , Trasplante de Células Madre/métodos , Animales , Células Cultivadas , Colágeno/química , Ácido Hialurónico/química , Laminina/química , Regeneración Nerviosa , Ratas , Ratas Sprague-Dawley , Nervio Ciático/lesiones , Andamios del Tejido/químicaRESUMEN
OBJECTIVES/HYPOTHESIS: Previous studies have reported variable results for the impact of bone invasion on survival in oral cancer. It is unclear whether bone invasion in small (≤4 cm) squamous cell carcinomas (SCC) of the oral cavity is an independent adverse prognosticator. Our objective was to investigate impact on survival of bone invasion in SCC of floor of mouth (FOM), lower alveolus (LA), and retromolar trigone (RMT) ≤4 cm in size. STUDY DESIGN: Retrospective study of 96 patients with SCC of the FOM, LA, and RMT undergoing primary surgical treatment. METHODS: Original pathology reports and slides were reviewed by three pathologists. Level of bone invasion was categorized as cortical or medullary. Main outcome measures were local control (LC) and overall survival (OS). RESULTS: Bone invasion was present in 31 cases (32%). On review of pathology slides, all cases of bone invasion demonstrated medullary involvement. Median follow-up was 36 months for all patients, and 53 months for patients not dying from cancer. Among tumors ≤4 cm, bone invasion was associated with significantly worse LC (P =.04) and OS (P =.0005). Medullary invasion (hazard ratio: 2.2, 95% confidence interval: 1.1-4.4, P =.03), postoperative radiotherapy (hazard ratio: 0.3, 95% confidence interval: 0.1-0.5, P <.001), and positive pathologic nodal status (hazard ratio: 4.1, 95% confidence interval: 1.9-8.6, P <.001) were independent predictors of worse OS among the entire cohort. CONCLUSIONS: Mandibular medullary bone invasion is a poor prognosticator in oral cancers, irrespective of small size of primary tumor. Such cases should be considered for postoperative radiotherapy. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:849-854, 2017.
Asunto(s)
Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/secundario , Neoplasias Mandibulares/secundario , Suelo de la Boca/patología , Neoplasias de la Boca/mortalidad , Neoplasias de la Boca/patología , Anciano , Carcinoma de Células Escamosas/cirugía , Estudios de Cohortes , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Irlanda , Estimación de Kaplan-Meier , Masculino , Neoplasias Mandibulares/cirugía , Persona de Mediana Edad , Suelo de la Boca/cirugía , Neoplasias de la Boca/cirugía , Análisis Multivariante , Invasividad Neoplásica/patología , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Medición de Riesgo , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Lymphomas frequently occur as extranodal lesions in the head and neck, but are rarely seen in the palate. We present a case of isolated diffuse type B-cell lymphoma of the palate, which occurred in a 28-year-old man. The patient had no history of immune compromise, and he presented to the emergency department with a 7-month history of a painful, non-healing ulcerative mass in the hard and soft palate. Positron emission tomography facilitated pretreatment assessment of the extent and activity of the lesion. Histopathological and immunohistochemical analyses of biopsied tissue confirmed a diagnosis of diffuse type B-cell lymphoma. The clinical findings and therapeutic challenges in this heterogeneous group of malignancies are discussed.
Asunto(s)
Linfoma de Células B Grandes Difuso/diagnóstico , Neoplasias Palatinas/diagnóstico , Adulto , Humanos , Masculino , Tomografía de Emisión de PositronesRESUMEN
BACKGROUND: Orbital exenteration is a disfiguring procedure most commonly performed for locally advanced or recurrent periorbital malignancies. METHODS: We performed a retrospective review of 22 patients who underwent orbital exenteration for advanced periorbital malignancy at our institution, by the senior author over a seventeen-year period. Specifically, we have reviewed the tumour histology along with stage at presentation, patient age, history of previous surgical intervention and surgical outcomes. The review highlighted two main groups who required orbital exenteration - patients with recurrent or locally advanced periorbital skin cancers, and patients with malignancy of the sinus. CONCLUSION: We discuss the presentation and management of the two pathological processes and highlight the importance of aggressive early management of periorbital malignancy with a view to prevention of exenteration and improving survival.
Asunto(s)
Neoplasias de los Párpados/cirugía , Evisceración Orbitaria/métodos , Neoplasias Cutáneas/cirugía , Diagnóstico Diferencial , Neoplasias de los Párpados/patología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Órbita , Estudios Retrospectivos , Neoplasias Cutáneas/patología , Resultado del TratamientoRESUMEN
OBJECTIVES: To establish a clinicopathological profile of malignant otitis externa (MOE) in an Australian tertiary referral institution. STUDY DESIGN: Retrospective cohort outcomes study. METHODS: 24 patients were identified with MOE between January 1998 and July 2007. Patients were classified into Radiological Grades I-IV. Laboratory investigations Including C-reactive protein (CRP), white cell count (WCC), glycosylated haemoglobin (HBA1c) and average glucose level over admission were recorded. RESULTS: Radiological Grade was significantly associated with duration of therapy (rank correlation 0.57, p = 0.004). CRP was a useful indicator confirming disease resolution. Diabetics with MOE had elevated average blood sugar levels during their Hospital admission (p < 0.001) and had poor overall glycaemic control represented by Elevated HBA1c scores (p < 0.001). CONCLUSIONS: Malignant otitis externa is a rare disease, which is best managed in a multidisciplinary team setting. This practical grading system can be used to predict the duration of therapy at time of diagnosis, which enables the efficient utilisation of Hospital resources. Poorly controlled diabetics are more susceptible to developing. MOE than diabetics with satisfactory glycaemic control and may represent a subgroup of more brittle diabetics. CRP combined with appropriate clinical and radiological investigations is useful in assessing disease resolution.