Louis D. Lowry

Randomized study of preoperative versus postoperative radiation therapy in advanced head and neck carcinoma: Long-term follow-up of RTOG study 73-03

This is a report of a 10-year median follow-up of a randomized, prospective study investigating the optimal sequencing of radiation therapy (RT) in relation to surgery for operable advanced head and neck cancer. In May 1973, the Radiation Therapy Oncology Group (RTOG) began a Phase III study of preoperative radiation therapy (50.0 Gy) versus postoperative radiation therapy (60.0 Gy) for supraglottic larynx and hypopharynx primaries. Of 277 evaluable patients, duration of follow-up is 9-15 years, with 7.6% patients lost to follow-up before 7 years. Loco-regional control was significantly better for 141 postoperative radiation therapy patients than for 136 preoperative radiation therapy patients (p = 0.04), but absolute survival was not affected (p = 0.15). When the analysis was restricted to supraglottic larynx primaries (60 postoperative radiation therapy patients versus 58 preoperative radiation therapy patients), the difference for loco-regional control was highly significant (p = .007), but not for survival (p = 0.18). In considering only supraglottic larynx, 78% of loco-regional failures occurred in the first 2 years. Thirty-one percent (18/58) of preoperative patients failed locally within 2 years versus 18% (11/60) of postoperative patients. After 2 years, distant metastases and second primaries became the predominant failure pattern, especially in postoperative radiation therapy patients. This shift in the late failure pattern along with the increased number of unrelated deaths negated any advantage in absolute survival for postoperative radiation therapy patients. The rates of severe surgical and radiation therapy complications were similar between the two arms. Because of an increased incidence of late distant metastases and secondary primaries, additional therapeutic intervention is required beyond surgery and postoperative irradiation to impact significantly upon survival.

Lipoinjection for unilateral vocal cord paralysis.

Injection of Teflon® paste is a commonly accepted procedure to improve the caliber of voice in unilateral vocal cord paralysis. There are several drawbacks to Teflon injection, among them respiratory obstruction (from overinjected Teflon) and unsatisfactory voice quality (Teflon causes stiffness of the vocal folds).

Hyposmia in allergic rhinitis

BACKGROUND The association between nasal allergy and loss or diminution of smell is frequently alluded to in the literature; however, neither the true prevalence of hyposmia in individuals with allergic rhinitis nor its bases have been established. METHODS We assessed olfactory threshold for phenylethyl alcohol in 91 patients with symptoms of allergic rhinitis and 80 nonatopic control subjects. To determine the degree to which nasal congestion contributes to hyposmia in allergic rhinitis, total nasal resistance was measured in 64 of the patients and 72 of the control subjects. RESULTS Olfactory thresholds were significantly higher in allergic patients than in control subjects (p < 0.001), with 23.1% of the patients demonstrating a clinically significant smell loss (defined as threshold at or above the 2.5th percentile of control values). Although nasal resistance was significantly higher among patients than among controls (p < 0.001), it was not related to olfactory threshold in either group. Clinical or radiographic evidence of sinusitis or nasal polyps or both in allergy patients was found to be significantly associated with hyposmia (p < 0.006). CONCLUSIONS The observed prevalence of hyposmia among patients with allergic rhinitis suggests that this is a major etiologic factor contributing to smell disorders. Sinusitis or nasal polyps or both may underlie many cases of allergy-related hyposmia.

Randomized preoperative and postoperative radiation therapy for patients with carcinoma of the head and neck: preliminary report.

Two hundred and ninety‐eight patients with squamous cell carcinoma of the oral cavity, oropharynx, supraglottic larynx, hypopharynx or maxillary sinus have been randomized for preoperative radiation therapy and surgery vs. surgery and postoperative radiation therapy plus, in the case of patients with lesions of the oral cavity and oropharynx, radical radiation therapy. Data have been analyzed on 243 patients in this interim report. The differences between the three groups with respect to local control and survival are not statistically significant at this time. Additional accrual and continued follow‐up are necessary to make definite treatment comparisons.

Vagal paraganglioma: The Jefferson experience☆

Vagal paraganglioma is a rare tumor of neural crest origin. Although the literature is in agreement with regard to epidemiology, diagnosis, and tumor biology, there is some controversy over treatment modalities for these patients. We performed a non-randomized retrospective study in a large single-institution series of patients (n = 19) in whom vagal paraganglioma was diagnosed. General statistics included age, male/female ratio, tumor size, and duration of follow-up. Other variables such as signs and symptoms at presentation, family history, multicentricity, metastatic disease, and secretion of catecholamines were included. CT scan, MRI, and angiography were used in combination for diagnostic purposes as well as for treatment planning. Preoperative embolization was performed in 5 of the more recently treated patients. Current issues regarding the use of preoperative embolization and choice of surgical approach were analyzed. In this article the possibility and sequela of vagus nerve–sparing procedures will be presented. Operative complications and postoperative morbidity related to cranial neuropathies will be discussed. The rationale for performing adjunct procedures, including cricopharyngeal myotomy and vocal fold medialization, to facilitate the rehabilitation of patients with postoperative cranial nerve deficits will be given. Our findings and recommendations will be compared with currently accepted treatment protocols in conjunction with a review of the literature.

Current national trends in the posttreatment follow-up of patients with squamous cell carcinoma of the head and neck☆

INTRODUCTION Follow-up of individuals treated for a primary squamous carcinoma of the upper aerodigestive tract is critical because of the high risk of development of either recurrent disease or a new primary tumor. A mail survey of physicians actively practicing head and neck surgery was undertaken. MATERIALS AND METHODS A multiple-choice survey was distributed to 400 members of the American Society for Head and Neck Surgery. Respondents indicated approach to post-treatment follow up. RESULTS Surveys were returned from 290 members (73%). Routine monthly follow up is advocated by 73% of respondents during the first postoperative year. Patients are followed every 2 to 3 months in the second postoperative year by 90% of respondents. During postoperative years, 3 to 5 patients are seen every 4 to 6 months by 97% of respondents. All respondents see patients either semiannually or annually for the remainder of their lives. Sixty percent of respondents advocate annual screening chest radiographs, whereas 14% do not order routine chest radiographs. The overwhelming majority of respondents reserve barium swallow and computed tomographic (CT) scans for evaluation of symptomatic patients. Similarly, nuclear imaging is reserved for patients with specific symptoms or abnormal laboratory tests. Blood tests most frequently monitored include complete blood cell count (CBC) (43%), thyroid function test (22%), and liver function test (20%). Follow-up endoscopic evaluation under anesthesia is reserved for symptomatic patients by over 95% of respondents. CONCLUSION These data demonstrate that head and neck surgeons rarely use supplemental studies other than chest radiograph during routine follow up. The authors speculate that routine chest radiograph may be valuable in screening for a second primary carcinoma. Techniques to screen for esophageal tumors remain contentious.

Clinical Disorders of Smell and Taste

Renewed attention to chemosensory dysfunction has revealed that a substantial portion of the population are affected during their lives, many simply as a result of aging. The authors discuss terminology, assessment, etiology, and prognosis and compare current understanding with that presented by Mackenzie in 1884.

Olfactory neuron-specific expression of NeuroD in mouse and human nasal mucosa.

Abstract. Human olfactory neuroepithelium (OE) is situated within the olfactory cleft of the nasal cavity and has the characteristic property of continually regenerating neurons during the lifetime of the individual. This regenerative ability of OE provides a unique model for neuronal differentiation, but little is known about the structure and biology of human olfactory mucosa. Thus, to better understand neurogenesis in human OE, we studied the expression of olfactory marker protein (OMP), TrkB and NeuroD in human nasal biopsies and autopsy specimens and compared these data with those obtained from normal and regenerating mouse OE. We show that NeuroD and TrkB are coordinately expressed in human OE. Thus, by using these markers we have been able to extend the known boundaries of the human OE to include the inferior middle turbinate. In normal mouse OE, TrkB and OMP expression overlap in cells closest to the superficial layer, but TrkB is expressed more strongly in the lower region of this layer. In contrast, NeuroD expression is more basally restricted in a region just above the globose basal cells. These characteristic expression patterns of OMP, TrkB and NeuroD were also observed in the regenerating mouse OE induced by axotomy. These results support a role of NeuroD and brain-derived neurotrophic factor (BDNF), the preferred ligand for TrkB, in the maintenance of the olfactory neuroepithelium in humans and mice.

The Evolving Etiology of Bilateral Vocal Fold Immobility

In the past, bilateral vocal fold immobility (BVFI) occurred most commonly after thyroidectomy. However, no large series documenting the etiology of adult BVFI has been published within the past fifteen years. This study reviews the etiologic patterns of BVFI at our institutions. We compare BVFI from before and after 1980. We also review combined studies of unilateral vocal fold immobility (UVFI) to compare and unilateral versus bilateral etiologic trends. In comparison with previously published series, fewer cases of BVFI present today as a complication of thyroid surgery and more as the result of malignancies and nonsurgical trauma. Unfortunately, BVFI caused by malignancy is not usually an initial sign of local disease, but an ominous sign of recurrence or metastases. In comparing UVFI and BVFI we found that thyroidectomy causes a higher percentage of BVFI than of UVFI. Over one-third of UVFI cases were caused by neoplasm which further underscores the potential seriousness of immobile vocal folds and the need for careful investigation.

Expression of the humanAchaete-Scute 1 gene in olfactory neuroblastoma (esthesioneuroblastoma)

Olfactory neuroblastoma (ONB) is a rare neuronal malignancy of the olfactory mucosal. Markers used in the diagnosis of ONB do not distinguish ONB from other neuronal tumors or tumors with neuroendocrine features thus making the diagnosis of ONB difficult. Using a modified RT-PCR technique, we show that the human homologue of theDrosophila achaete-scute geneHASH1 is expressed in 6 primary and one metastatic ONB specimens, whereas Olfactory Marker Protein (OMP) is not. Previous studies have shown thatHASH1 is expressed in immature olfactory neurons and is required for their development.OMP, whose function is unknown, is expressed exclusively in mature olfactory neurons. Together, these data suggest that ONB is derived from immature olfactory neurons of neuroectodermal origin. Analysis of RNA expression in primary tumor specimens and in an established cell line make this an ideal system to study olfactory growth and differentiation. Furthermore, these studies represent the first molecular genetic analysis of this rare and unusual neuronal tumor.