Faculty Bibliography

During germ-cell migration in the mouse, the dynamics of embryo growth cause many germ cells to be left outside the range of chemoattractive signals from the gonad. At E10.5, movie analysis has shown that germ cells remaining in the midline no longer migrate directionally towards the genital ridges, but instead rapidly fragment and disappear. Extragonadal germ cell tumors of infancy, one of the most common neonatal tumors, are thought to arise from midline germ cells that failed to die. This paper addresses the mechanism of midline germ cell death in the mouse. We show that at E10.5, the rate of apoptosis is nearly four-times higher in midline germ cells than those more laterally. Gene expression profiling of purified germ cells suggests this is caused by activation of the intrinsic apoptotic pathway. We then show that germ cell apoptosis in the midline is activated by down-regulation of Steel factor (kit ligand) expression in the midline between E9.5 and E10.5. This is confirmed by the fact that removal of the intrinsic pro-apoptotic protein Bax rescues the germ-cell apoptosis seen in Steel null embryos. Two interesting things are revealed by this: first, germ-cell proliferation does not take place in these embryos after E9.0; second, migration of germ cells is highly abnormal. These data show first that changing expression of Steel factor is required for normal midline germ cell death, and second, that Steel factor is required for normal proliferation and migration of germ cells.

A rarely diagnosed etiology of dysphagia is a pharyngeal diverticula occurring after anterior cervical fusion. Here we review 2 cases where patients developed pharyngeal diverticula following anterior cervical fusion. The first patient was a 28-year-old female who presented with regurgitation following C5 through C6 cervical fusion. She was diagnosed with a pharyngeal diverticulum and underwent open repair, but began to experience symptoms again a few months later. A barium swallow showed a recurrent pharyngeal diverticulum. Endoscopic repair was attempted; however, because of the thick scar band between the diverticulum and the esophagus, the operation had to be converted to an open repair with cricopharyngeal myotomy. The second case involved a 63-year-old male who presented with dysphagia and regurgitation 6 months after anterior cervical fusion. Esophagram demonstrated a small diverticulum at the right lateral border of the upper esophagus. Open repair of the diverticulum with cricopharyngeal myotomy was successfully performed. Pharyngeal diverticula after anterior cevical fusion have only been reported in 2 prior cases in the literature. Here we describe 2 additional cases at our institution, both requiring open repair. Radiographic studies demonstrate the diverticulum at the site of scarring from the cervical fusion. Because of the thick scar band and the atypical location of these diverticula, endoscopic repair with stapping (as done for Zenker's diverticula) may not be feasible. These cases highlight the importance of considering a diverticulum in the differential of posoperative patients presenting to the otolaryngologists with complaints of dysphagia following cevical spine surgery.

OBJECTIVE: The objective of this cohort study from a tertiary academic university practice was to identify differences in patients' perceived quality of life after either chemoradiation or surgery and radiation for advanced-stage oropharyngeal carcinoma. METHODS: From institutional databases, thirty-five patients were identified who had undergone either primary chemoradiation or primary surgery and postoperative radiation for advanced oropharyngeal cancer (stage II-IV). Patients voluntarily responded by mail using the University of Washington quality-of-life instrument version 4 (UW-QOL). Data were analyzed using chi and Wilcoxon tests. RESULTS: There were 17 patients who underwent chemoradiation and 18 patients who underwent surgery and postoperative radiation. All surgical patients had undergone free-flap reconstruction. Patients completed the UW-QOL an average of 25 months after treatment. There was no statistically significant difference between the two groups with regard to any specific domain, including pain, appearance, swallowing, chewing, speech, saliva, or mood. There was a trend toward significance for taste (P = .07) with chemoradiation patients reporting poorer taste function. The lack of difference in the patients' perception of appearance and swallowing was rather surprising given the vastly different treatment modalities. Respondents reported equivalent overall quality of life in response to global quality-of-life questions. CONCLUSION: Most patients with advanced oropharyngeal carcinoma report good quality of life after treatment, regardless of treatment modality. Although the short-term side effects of treatment may be different between the groups, long-term quality of life is remarkably similar whether the patients choose primary chemoradiation or surgery with postoperative radiation.