Slide tracheoplasty for the treatment of tracheoesophogeal fistulas.

PURPOSE: The purpose of this study is to determine the surgical outcome of slide tracheoplasty for the treatment of tracheoesophageal (TE) fistula in pediatric patients. METHODS: After internal review board approval, the charts of pediatric patients (0-18years old) who had undergone slide tracheoplasty for tracheoesophageal fistula were retrospectively reviewed. Patient information and surgical outcomes were reviewed. RESULTS: Nine patients underwent slide tracheoplasty for correction of TE fistula. In five patients the original TE fistula was congenital. Other causes included battery ingestion, tracheostomy tube complications, foreign body erosion, and an iatrogenic injury. The average age at repair was 48±64 months (range: 1-190). Seven patients had undergone previous TEF repair either open or endoscopically. There were no recurrences after repair. Two patients had sternal periosteum interposed between the esophagus and trachea. There were no TEF recurrences. A single patient had dehiscence of the tracheal anastomosis and underwent a second procedure. CONCLUSION: Slide tracheoplasty is an effective method to treat complex TE fistulas. The procedure was not associated with any recurrences. This is the first description of a novel, effective, and safe method to treat TE fistulas.

Primary intraosseous cavernous hemangioma of the zygoma: a case report and literature review.

Intraosseous hemangiomas are rare. We report the case of a 47-year-old man who presented with a gradually enlarging left zygomatic mass that had caused pain, deformity, and superficial soft-tissue swelling. Computed tomography revealed a well-circumscribed 2.0 × 2.5-cm mass with a ground-glass matrix in the left zygoma. Following surgical excision, the patient's symptoms resolved. Findings on pathologic examination of the excised tissue were consistent with an intraosseous cavernous hemangioma. We describe the features of this rare case, we discuss the pertinent radiologic features and pathophysiology of intraosseous hemangiomas, and we review the available literature.

p75(NTR) expression and nuclear localization of p75(NTR) intracellular domain in spiral ganglion Schwann cells following deafness correlate with cell proliferation.

Spiral ganglion Schwann cells (SGSCs) myelinate spiral ganglion neurons (SGNs) and represent a potential source of neurotrophic support for SGNs. Deafening due to loss of hair cells results in gradual degeneration and death of SGNs. Successful efforts to maintain or regenerate a functional auditory nerve may depend on a healthy population of SGSCs, yet the responses of SGSCs to neural injury remain largely unknown. Here we investigate the role of p75(NTR) in SGSC responses to gradual denervation. Following deafening, SGSCs in the osseous spiral lamina (OSL) and, subsequently, in Rosenthal's canal (RC) expressed elevated p75(NTR) compared to hearing controls. p75(NTR)-positive cells co-labeled with S100 and RIP antibodies (Schwann cell markers), but not with anti-neurofilament. The pattern of p75(NTR) expression mirrored the pattern of neural degeneration, beginning in the OSL of the cochlea base and later extending into the apex. SGSCs expressed sortilin, a p75(NTR) co-receptor for pro-neurotrophins. Both pro-nerve growth factor (pro-NGF) and pro-brain derived neurotrophic factor (proBDNF) induced apoptosis in cultured SGSCs. Deafened animals exhibited significantly higher levels of SGSC proliferation (as measured by BrdU uptake) compared to hearing animals while total Schwann cell density remained stable, suggesting a tight regulation of SGSC proliferation and cell death. SGSCs undergoing cell division lose p75(NTR) expression from the cell surface and demonstrate nuclear localization of the intracellular domain (ICD), raising the possibility that p75(NTR) cleavage and ICD nuclear localization regulate SGSC proliferation. These results suggest that p75(NTR) contributes to SGSC responses to deafening and neural degeneration.

Human Chondrosarcoma Cells Acquire an Epithelial-Like Gene Expression Pattern via an Epigenetic Switch: Evidence for Mesenchymal-Epithelial Transition during Sarcomagenesis.

Chondrocytes are mesenchymally derived cells that reportedly acquire some epithelial characteristics; however, whether this is a progression through a mesenchymal to epithelial transition (MET) during chondrosarcoma development is still a matter of investigation. We observed that chondrosarcoma cells acquired the expression of four epithelial markers, E-cadherin,desmocollin 3, maspin, and 14-3-3σ, all of which are governed epigenetically through cytosine methylation. Indeed, loss of cytosine methylation was tightly associated with acquired expression of both maspin and 14-3-3σ in chondrosarcomas. In contrast, chondrocyte cells were negative for maspin and 14-3-3σ and displayed nearly complete DNA methylation. Robust activation of these genes was also observed in chondrocyte cells following 5-aza-dC treatment. We also examined the transcription factor snail which has been reported to be an important mediator of epithelial to mesenchymal transitions (EMTs). In chondrosarcoma cells snail is downregulated suggesting a role for loss of snail expression in lineage maintenance. Taken together, these results document an epigenetic switch associated with an MET-like phenomenon that accompanies chondrosarcoma progression.

Pediatric endoscopic airway management with posterior cricoid rib grafting.

OBJECTIVES/HYPOTHESIS: To confirm and extend reported successful treatment of posterior glottic stenosis in pediatric patients using endoscopic laser division of the posterior cricoid plate with augmentation using costal cartilage. STUDY DESIGN: A retrospective chart review and case series. METHODS: Medical records were examined to determine the surgical indications, outcomes, and postoperative complications of this procedure. RESULTS: Twelve patients underwent the procedure, six females and six males, with an average age of 7 years (range, 2-26 years). There were 8/12 (67%) patients successfully decannulated after being tracheostomy dependent. There were no consistent anatomic abnormalities or surgical findings predictive of failure to decannulate. Average hospital stay was 3.6 days (range, 2-9 days). There were no deaths or other major complications; one patient had extrusion. CONCLUSIONS: Endoscopic posterior cricoid grafting is a valuable surgical option for patients with posterior glottic stenosis. The procedure is associated with low morbidity and permits decannulation in the majority of patients.

Use of the King LT for emergency airway management.

OBJECTIVE: To discuss the role of the King LT reusable supraglottic airway in emergency airway management. DESIGN: Retrospective case series review. SETTING: Tertiary academic medical facility. PATIENTS: We studied patients who presented to the emergency trauma center having undergone intubation at an outside facility or at the scene of the incident. The otolaryngology service was consulted for definitive management of the airway. MAIN OUTCOME MEASURE: Airway evaluation and management once the King LT has been placed. RESULTS: Six patients with known prehospitalization use of the King LT presented to the emergency trauma center and subsequently required emergency tracheostomy for establishment of a secure airway. Fiberoptic and/or direct laryngoscopic evaluation performed with the tube in place failed to reveal whether safe oral endotracheal intubation could be performed because of visualization problems. Examination after tracheostomy and removal of the King LT revealed that in 2 patients, orotracheal intubation would have been difficult or impossible, whereas another 4 patients could have been intubated. One patient had prehospitalization placement of a King LT, which resulted in subcutaneous emphysema because of placement within the mediastinum. The patient was able to be successfully intubated and did not require tracheostomy. CONCLUSIONS: The King LT offers benefits in emergency situations, but evaluation of the airway is challenging and often necessitates tracheostomy for establishment of a safe and secure airway. Even if tracheostomy is not required, serious complications may occur.

p75NTR and sortilin increase after facial nerve injury.

OBJECTIVES: After axotomy, Schwann cells (SCs), required for successful nerve regeneration, undergo a number of cellular changes including dedifferentiation, proliferation, expression of molecules that support axon growth, and apoptosis. This study investigated the role of p75, sortilin, and proneurotrophins in SC survival after facial nerve (FN) axotomy. STUDY DESIGN: Preliminary animal study. METHODS: With use of FN SCs, expression of p75 and its coreceptor sortilin were quantified by immunofluorescence on days 12, 22, and 52 after axotomy in vivo and by Western blot in vitro. Contralateral FNs served as a control. SC apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). To verify a causative role for p75 in FN SC death, cultured FN SCs were treated with pro-nerve growth factor (NGF), and apoptosis was determined by TUNEL. RESULTS: Expression of p75 and sortilin increased in FN SCs distal (P < .05) to the axotomy compared with the contralateral controls for all time points. SC apoptosis also significantly increased in the distal segment compared with the contralateral and proximal portions (P < .05). ProNGF, a p75 ligand, increased apoptosis and p75 expression in primary FN SC cultures. CONCLUSION: FN axotomy increases p75 and sortilin expression in SCs, which correlates with increased apoptosis. These findings suggest roles for p75 and sortilin in SC loss after FN injury. Sortilin is a novel target in promoting FN healing after injury.

Increased iodine uptake in thyroid carcinoma after treatment with sodium butyrate and decitabine (5-Aza-dC).

OBJECTIVE: To determine if epigenetic-modifying drugs can increase iodine uptake in thyroid carcinoma cell lines. STUDY DESIGN: Human thyroid carcinoma cell lines were tested for iodine uptake before and after treatment with epigenetic-modifying agents. RESULTS: Thyroid carcinoma cell lines DRO and 2-7 had high levels of DNA methylation (74% and 80%) compared with normal thyroid tissue (6%) (P < 0.05). This finding correlated with low levels of sodium iodide symporter (NIS) expression in the untreated thyroid carcinoma cell line. Combination treatment with the epigenetic-modifying agents 5-aza-2'-deoxycytidine and sodium butyrate resulted in increases in NIS messenger RNA levels, global histone acetylation, and 9- and 8-fold increases in I(125) uptake for the DRO and 2-7 cells, respectively. CONCLUSIONS: Epigenetic-modifier drugs represent a novel adjuvant treatment for those patients with radioablation-resistant thyroid cancer. SIGNIFICANCE: Epigenetic-modifying agents show potential for treatment of radioablation-resistant thyroid cancer.

A role for epigenetics in hearing: Establishment and maintenance of auditory specific gene expression patterns.

Epigenetics is a large and diverse field encompassing a number of different mechanisms essential to development, DNA stability and gene expression. DNA methylation and histone modifications work individually and in conjunction with each other leading to phenotypic changes. An overwhelming amount of evidence exists demonstrating the essential nature of epigenetics to human biology and pathology. This field has spawned a vast array of knowledge, techniques and pharmaceuticals designed to investigate and manipulate epigenetic phenomena. Despite its centricity to molecular biology, little work has been conducted examining how epigenetics affects hearing. In this review, we discuss both the basic tenets of epigenetics and highlight the most recent advances in this field. We discuss its importance to human development, genomic stability, gene expression, epigenetic modifying agents as well as briefly introduce the expansive field of cancer epigenetics. We then examine the evidence of a role for epigenetics in hearing related processes and hearing loss. The article concludes with a discussion of areas of epigenetic research that could be applied to hearing research.

AP-2 participates in the transcriptional control of the amyloid precursor protein (APP) gene in oral squamous cell carcinoma.

Amyloid precursor protein (APP) has been implicated in squamous cell carcinoma. In this study we show that forced expression of the transcription factor activating protein 2alpha (AP-2alpha) results in significantly increased steady state levels of APP mRNA in human keratinocytes. Sequence analysis of the 5' end of the human APP gene revealed five putative binding sites for AP-2, suggesting that APP is a direct target for transactivation by AP-2. AP-2 protein bound at least 3 of these putative promoter elements in vitro as determined by electrophoretic mobility shift assay. Chromatin immunoprecipitation (ChIP) analysis showed that these binding sites were occupied by AP-2 in cells, thus indicating the relevance to AP-2 binding in vivo. We then analyzed APP and AP-2 mRNA and protein expression in squamous cell carcinoma tumor samples. Analysis of RNA extracted from human tissue showed a significant positive correlation between AP-2alpha and APP mRNA expression. Immunohistochemical staining of tumor samples also demonstrated a positive correlation which was substantiated through western blot studies. Taken together, these findings demonstrate a role for the transcription factor AP-2alpha in the regulation of APP gene expression in human keratinocytes.

Bone cements: review of their physiochemical and biochemical properties in percutaneous vertebroplasty.

Percutaneous vertebroplasty is an effective treatment for aggressive vertebral hemangiomas, osteoporotic vertebral compression fractures, spinal metastases, and myelomas. As percutaneous vertebroplasty is more commonly performed to treat various forms of back pain, new or modified cements are being used. This review examines the physiochemical and biomechanical properties of various bone cements and additives.