Objectives
To characterize fundamental late tissue effects in the human vocal fold following radiation therapy. To develop a murine model of radiation fibrosis to ultimately develop both treatment and prevention paradigms.
Design
Translational study using archived human and fresh murine irradiated vocal fold tissue.
Methods
1) Irradiated vocal fold tissue from patients undergoing laryngectomy for loss of function from radiation fibrosis were identified from pathology archives. Histomorphometry, immunohistochemistry, and whole-genome microarray as well as real-time transcriptional analyses was performed. 2) Focused radiation to the head and neck was delivered to mice in a survival fashion. One month following radiation, vocal fold tissue was analyzed with histomorphometry, immunohistochemistry, and real-time PCR transcriptional analysis for selected markers of fibrosis.
Results
Human irradiated vocal folds demonstrated increased collagen transcription with increased deposition and disorganization of collagen in both the thyroarytenoid muscle and the superficial lamina propria. Fibronectin were increased in the superficial lamina propria. Laminin decreased in the thyroarytenoid muscle. Whole genome microarray analysis demonstrated increased transcription of markers for fibrosis, oxidative stress, inflammation, glycosaminoglycan production and apoptosis. Irradiated murine vocal folds demonstrated increases in collagen and fibronectin transcription and deposition in the lamina propria. Transforming growth factor (TGF)-β increased in the lamina propria.
Conclusion
Human irradiated vocal folds demonstrate molecular changes leading to fibrosis that underlie loss of vocal fold pliability that occurs in patients following laryngeal irradiation. Irradiated murine tissue demonstrates similar findings, and this mouse model may have utility in creating prevention and treatment strategies for vocal fold radiation fibrosis.
ranchial arch abnormalities opening into the pyriform fossa are an important congenital cause of recurrent neck abscesses in children. The classification and naming of these anomalies is controversial because of the complex embryological development of the region involved. In 1972, Sandborn and Shafer 1 first described a neck mass caused by a sinus tract traveling from the left pyriform fossa to the superior pole of the left lobe of the thyroid. The lesion was classified as a fourth branchial pouch derivative, which became the widely used term for such structures. 1 Theoretically, a complete fourth branchial pouch fistula tract would begin at the pyriform fossa, exit the larynx near the cricothyroid joint, and pass between the superior and recurrent laryngeal nerves behind the body of the thyroid gland. The fistula would then make a convoluted journey toward the mediastinum before looping back and exiting anterior to the sternocleidomastoid muscle on the lower neck. 2 To our knowledge, a complete fistula tract naturally opening onto the neck has never been reported. To complicate matters, fistula tracts arising from the third branchial pouch theoretically would also start at the pyriform fossa. However, the tract would pass cranial instead of caudal to the superior laryngeal nerve.
2Because of the difficulty of distinguishing third and fourth pouch tracts, some authors have chosen to consider them a single entity. More recently, the thymopharyngeal duct, a third pouch derivative independent of the third and fourth fistula tracts, has been alternatively proposed as the cause of these lesions. 3 The thymopharyngeal duct is formed when the thymus descends from the third pouch through the fourth arch to fuse with its contralateral counterpart during fetal development. Failure of thymopharyngeal duct involution should lead to a sinus tract containing thymus-derived tissue starting at the pyriform fossa and descending in close association with the thyroid. OBJECTIVE To evaluate the long-term effectiveness of endoscopic cauterization as definitive treatment for pyriform fossa sinus tracts.
DESIGN, SETTING, AND PATIENTSRetrospective review of the medical records of 23 children (aged 7 months to 14 years) with pyriform fossa sinus tracts treated with endoscopic cauterization between 1995 and 2013 at a tertiary care children's hospital.INTERVENTION Endoscopic electrocauterization of pyriform fossa sinus tract opening.
MAIN OUTCOMES AND MEASURESRecurrence of symptoms after endoscopic treatment.RESULTS Twenty-one of 23 patients experienced no recurrence after their first endoscopic electrocauterization of the sinus tract. The 2 patients with recurrence experienced symptoms within 1 month of cauterization and were treated with either open excision or recauterization. Endoscopic cauterization was able to definitively treat 9 patients whose treatments with incision and drainage or open excision had failed. Mean (range) follow-up for the 15 patients with follow-up was 7.4 (0.10-14.2) years. No procedure-related morbidity was re...
Suburothelial injections of particulate poly(tetrafluoroethylene) (PTFE) is becoming a widely accepted treatment for a number of urological disorders. Because little is known about the long-term histologic morphology of the injection site, this animal study was performed. Three populations, each consisting of two mongrel dogs, five New Zealand White rabbits, and 10 BALB/c mice, were injected with poly(tetrafluoroethylene) particulate in a glycerine carrier (Polytef Paste) and were followed for a period of 1 week, 3 months, 6 months, and 1 year. Mice received one subcutaneous dorsal injection each, rabbits received two subareolar injections each, and dogs received three subareolar injections each in addition to two periurethral injections. Histologic examination of the biopsy sites revealed a persistent chronic inflammatory reaction with progressive growth of the involved tissue volume. In addition to giant cells and macrophages, lymphocytes became apparent at 3 months and constituted up to 40% of the cellular infiltrate by 1 year. Plasma cells were also noted at the 1-year period in the rabbit model. The progressive growth of the inflammatory pseudo-tumors evoked by injected PTFE may compromise the long-term safety of certain urological procedures involving particulate PTFE.
While multiple cysts may arise and serial intervention may be required, we believe that in association with broader clinical experience, the data presented here support aspiration and sodium morrhuate injection as a safe, minimally invasive, and efficacious technique in the treatment of benign lymphoepithelial cysts of the parotid gland in the HIV-positive population.
Radiotherapy results in significant vocal fold tissue changes. Having more precisely defined these changes, we plan continued investigation seeking targeted preventive and therapeutic interventions for improved vocal quality following radiotherapy.
Lymphatic malformations obstructing the larynx require a careful and often staged management approach. A proposed staging system helps to predict the need for tracheotomy and the likelihood of long-term tracheotomy dependence.
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