Cancer of the pharynx and larynx.

Carcinoma of the head and neck is among the most debilitating forms of cancer. Survival rates for these tumors vary and depend on the presence of early symptoms, anatomic accessibility, and lymphatic supply. Despite advances in therapy and novel surgical approaches, early diagnosis remains the best predictor of survival. This article reviews the diagnosis, staging criteria, and treatment strategies for nasopharyngeal carcinoma, hypopharyngeal carcinoma, and laryngeal carcinoma in an effort to heighten the clinical and endoscopic recognition of these lesions.

Molecular marker expression in oral and oropharyngeal squamous cell carcinoma.

OBJECTIVE: To determine the relative prognostic value of p53, cyclin D1, epidermal growth factor receptor (EGFR), and vascular endothelial growth factor (VEGF) expression in patients with oral and oropharyngeal squamous cell carcinoma. DESIGN: Retrospective cohort study. PATIENTS: Fifty-six patients with oral and oropharyngeal squamous cell carcinoma referred to the Department of Therapeutic Radiology at Yale-New Haven Hospital (Conn) between 1981 and 1992 who were treated with gross total surgical resection and postoperative external beam radiotherapy. RESULTS: Archival tumor tissue was stained with monoclonal antibodies directed against these 4 oncoproteins and scored for staining intensity and percent distribution by a pathologist blinded to the patients' clinical outcomes. Frequency of marker expression was 48% for p53, 20% for cyclin D1, 64% for EGFR, and 41% for VEGF. In multivariate analysis, EGFR positivity was protective against locoregional relapse (relative risk [RR], 0.27; 95% confidence interval [CI], 0.11-0.66; P =.002). In contrast, advanced N stage predicted poor locoregional relapse-free survival (RR, 1.94; 95% CI, 1.03-3.66; P =.04). Predictors of poor overall survival in multivariate analysis included VEGF positivity (RR, 3.53; 95% CI, 1.75-7.13; P<.001) and black race (RR, 2.48; 95% CI, 1.05-5.85; P =.04). Cyclin D1 and p53 expression were not significantly associated with prognosis in this cohort. CONCLUSIONS: In oral and oropharyngeal squamous cell carcinoma treated with surgery and postoperative radiotherapy, VEGF and EGFR expression may influence clinical outcome. If confirmed, these results have potential implications for the determination of patient prognosis and the development of biologically based pharmacotherapies.

Adenoid cystic carcinoma: a retrospective clinical review.

Adenoid cystic carcinoma (ACC) are uncommon tumors, representing about 10% to 15% of head and neck tumors. We compare the survival and control rates at our institution with those reported in the literature, and examine putative predictors of outcome. All patients registered with the tumor registry as having had ACC were identified. Demographic and survival variables were retrieved from the database. Additionally, a chart review of all patients was done to obtain specific information. Minor gland tumors were staged using the American Joint Committee on Cancer's criteria for squamous cell carcinomas in identical sites. Histopathologic variables retrieved included grade of the tumor, margins, and perineural invasion. Treatment modalities, field sizes, and radiation doses were recorded in applicable cases. An effort to retrieve archival tumor specimens for immunohistochemical analysis was undertaken. A total of 69 patients were treated for ACC from 1955 to 1999. One patient, who presented with fatal brain metastasis, was excluded from further analysis. Of the remaining 68 patients, 30 were men and 38 were women. The average age at diagnosis was 52 years, and mean follow-up was 13.2 years. Mean survival was 7.7 years. Overall survival (OS) rates at 5, 10, and 15 years were 72%, 44%, and 34%, and cause-specific survival was 83%, 71%, and 55%, respectively. Recurrence-free survival rates were 65%, 52%, and 30% at 5, 10, and 15 years, with a total of 29 of 68 (43%) eventually suffering a recurrence. Overall survival was adversely affected by advancing T and AJCC stage. Higher tumor grades were also associated with decreased OS, although the numbers compared were small. Primaries of the nasosinal region fared poorly when compared with other locations. Total recurrence-free survival, local and distant recurrence rates were distinctly better in primaries of the oral cavity/oropharynx when compared with those in other locations. Reduced distant recurrence-free survival was significantly associated with increasing stage. No other variables were predictive for recurrence. Additionally, we found that nasosinal tumors were more likely to display higher stage at presentation, and were more often associated with perineural invasion. Also of interest was the association of perineural invasion with margin status, with 15 of 20 patients with positive margins displaying perineural invasion, while only 5 of 17 with negative margins showed nerve invasion (P = 0.02). On immunohistochemistry, 2 cases of the 29 (7%) tumor specimens found displayed HER-2/neu positivity. No correlation between clinical behavior and positive staining could be demonstrated. Our data concur with previous reports on ACC in terms of survival and recurrence statistics. Stage and site of primary were important determinants of outcome. Grade may still serve a role in decision making. We could not demonstrate any differences attributable to primary modality of therapy, perhaps due to the nonrandomization of patients into the various treatment tracks and the inclusion of palliative cases. Similarly, perineural invasion, radiation dose and field size, and HER-2/neu positivity did not prove to be important factors in our experience.

Distant metastases from ear and temporal bone cancer.

Cancers of the temporal bone are rare. Cervical metastases occur in approximately 10% of cases and are much more likely once disease extends beyond the confines of the temporal bone. Nonlymphatic spread of squamous cell carcinoma is usually a late event resulting in metastatic deposits in the lung, bone, liver and brain. This chapter discusses detection of distant metastases and provides a recommended schedule for interval patient evaluation.

Glottic closing force in an anesthetized, awake pig model: biomechanical effects on the laryngeal closure reflex resulting from altered central facilitation.

Reflex sphincteric closure of the larynx, essential to lower airway protection, is most efficiently achieved through strong reflex adduction by both vocal cords. Because the conversion of a bilaterally evoked response to a unilaterally evoked one appears anesthesia-dependent, we hypothesized that central facilitation is an essential component of a bilateral adductor reflex and that its disturbance could result in weakened sphincteric closure. Six adult 50 kg pigs were used in this study. During electrical stimulation of the internal branch of the superior laryngeal nerve (iSLN) using bipolar platinum-iridium electrodes, the force of the evoked glottic closure response was measured using a pressure transducer positioned between both vocal cords, while electromyographic evoked response was recorded from both thyroarytenoid muscles under varying levels [0.5-1.0 minimal alveolar concentration (MAC)] of isoflurane anesthesia. The force of glottic closure appeared less under deep anesthesia, even with bilateral stimulation of the iSLN, than under light anesthesia with unilateral stimulation. As anesthetic levels approached 1.0 MAC, the glottic closing force decreased to 52-72% of the force measured under 0.5 MAC light anesthesia. Although it is generally understood that alteration of central facilitation by deepening anesthesia abolishes the crossed adductor reflex, the biomechanical effects of altered central facilitation on force differentials have never been previously demonstrated. Precise understanding of this effect may improve the prevention of aspiration in patients emerging from heavy sedation or under prolonged psychotropic control.

Critical role of central facilitation in the glottic closure reflex.

The sphincteric function of the larynx, essential to lower airway protection, is most efficiently achieved through strong reflex adduction by both vocal cords. We hypothesize that central facilitation is an essential component of a bilateral adductor reflex and that its disturbance could result in weakened sphincteric closure. Six adult 50-kg pigs underwent evoked response laryngeal electromyography under 0.5 to 1.0 minimal alveolar concentration (MAC) isoflurane anesthesia. The internal branch of the superior laryngeal nerve was stimulated through bipolar platinum-iridium electrodes, and recording electrodes were positioned in the ipsilateral and contralateral thyroarytenoid muscles. Consistent threshold responses were obtained ipsilaterally from 0.5 to 1.0 MAC anesthesia. However, the contralateral reflex responses approached 0% in successive trials as anesthetic levels approached 1.0 MAC. Alteration of central facilitation by deepening anesthesia abolishes the crossed adductor reflex, predisposing to a weakened glottic closure response. A precise understanding of this effect may improve the prevention of aspiration in patients emerging from prolonged sedation or under heavy psychotropic control.

Molecular markers in head and neck squamous cell carcinoma: their biological function and prognostic significance.

Head and neck squamous cell carcinoma affects more than 500,000 people worldwide each year. Despite optimal treatment with surgery, irradiation, and chemotherapy, disease recurrence and progression remains a common and challenging oncological problem. Recently, interest has developed in identifying novel molecular markers that allow identification of those patients at increased risk for locoregional recurrence and death. This article reviews several such molecular markers studied in head and neck cancer, including p53, angiogenesis-related markers, cyclin D1, and epidermal growth factor receptor. The biological function of these markers and the potential clinical implications are discussed. The purpose of this review is to update the otolaryngologist on a rapidly emerging segment of applied translational research in our field.

Efficacy of adjunctive cricopharyngeus myotomy in supraglottic laryngectomy.

This study investigates prospectively the effect of concurrent cricopharyngeus myotomy (CPM) on swallowing following horizontal supraglottic laryngectomy (SL) using fiberoptic, radiographic, and manometric evaluations and suggests possible mechanisms regarding the role of CPM following SL. Six patients undergoing horizontal SL between 1995 and 1997 were enrolled in a prospective evaluation with a followup of 0.5-2.25 years. Three patients underwent concurrent CPM and three did not. Fiberoptic, radiographic. and manometric assessments were performed postoperatively. Although mean resting pressures at the upper esophageal sphincter were reduced significantly by myotomy (12 mm Hg) compared with nonmyotomized patients (57 mm Hg), p < 0.01, no rehabilitative advantage was observed in the former group. In fact, of the myotomized patients, two required feeding gastrostomy tubes with resumption of an oral diet in one year and in two months, respectively, while the nonmyotomized patients were all capable of resuming a full oral diet within four weeks. It appears that CPM provides no rehabilitative advantage in patients undergoing SL.

Mandibular and temporomandibular joint arthropathy in the differential diagnosis of the parotid mass.

OBJECTIVE: To increase awareness of temporomandibular joint and mandibular disease in the overall evaluation and diagnosis of the parotid mass. STUDY DESIGN: We describe clinical presentations of pigmented villonodular synovitis and synovial chondrocalcinosis of the temporomandibular joint, as well as osteoma of the mandible, as they may initially suggest primary neoplasms of the parotid gland. CONCLUSIONS: Preauricular swelling is a common presenting symptom for patients visiting an otolaryngologist. Often this symptom is suggestive of a parotid mass. However, lesions of the temporomandibular joint and mandible may also present in this fashion.

Horizontal maxillotomy for exposure of the central skull base: the Yale experience.

Le Fort I osteotomy allows the surgeon to safely down-fracture the maxilla for wide exposure of the central skull base. This surgical approach is easily extended inferiorly to include the arch of C1, providing 8 cm of horizontal anterior exposure and 5 cm of posterior. Wide operative exposure and a low rate of complications afford superior functional and cosmetic preservation in removing tumors of the central cranial base.

Prognostic significance of vascular endothelial growth factor protein levels in oral and oropharyngeal squamous cell carcinoma.

PURPOSE: Vascular Endothelial Growth Factor (VEGF) promotes angiogenesis in many different tumor types. VEGF levels may affect tumor growth, metastatic potential, and response to radiotherapy. This study assesses the prognostic value of VEGF protein levels in a cohort of patients with oral and oropharyngeal squamous cell carcinomas. The relationships between clinical outcome and the covariables of tumor-node-metastasis stage, disease stage (I to IV), grade, margin status, race, sex, and age were also determined. PATIENTS AND METHODS: Chart review identified 77 patients with oral or oropharyngeal squamous cell carcinoma treated with gross total surgical resection and postoperative radiation between 1981 and 1992. Sufficient follow-up data and tumor tissue were available in 56 patients (73%). VEGF protein levels were determined using immunohistochemistry. The association between VEGF status, covariables, and outcome was assessed in a bivariate and multivariate model using two-sided statistical tests. RESULTS: Twenty-three tumors (41%) were positive for VEGF expression. VEGF-positive tumors were more likely to recur locally (relative risk [RR] = 3.08; 95% confidence interval [CI], 1.03 to 9.24) and distantly (RR = 4.62; 95% CI, 1.41 to 15.10). In bivariate analysis, VEGF positivity was the most significant predictor of poor disease-free survival (RR = 2.66; 95% CI, 1.27 to 5.56) and overall survival (RR = 3.21; 95% CI, 1.63 to 6.32). In multivariate analysis, VEGF positivity was the most significant predictor of poor disease-free survival (RR = 2.75; 95% CI, 1.30 to 5.79) and overall survival (RR = 3.53; 95% CI, 1.75 to 7.13). CONCLUSION: In this cohort, VEGF positivity was the most significant predictor of poor prognosis. VEGF status may prove to be an important prognostic factor in head and neck cancer.

Understanding the motor innervation of the human cricopharyngeus muscle.

A comprehensive understanding of the swallow mechanism continues to suffer from an incomplete appreciation of basic morphology and function. This article is intended to underscore our currently incomplete and pending understanding of cricopharyngeus motor innervation in humans. Given the critical function of this sphincteric muscle in the control of the proximal alimentary tract, a focused effort to unravel its motor innervation would go a long way to reduce the mystery of its overall role in normal and disordered function in patients.

Prognostic significance of cyclin D1 protein levels in early-stage larynx cancer treated with primary radiation.

Recent laboratory experiments have demonstrated that cyclin D1 levels (cycD1) can influence radiosensitivity. The purpose of the current study is to evaluate the prognostic significance of cycD1 for local recurrence in early-stage larynx cancer treated with primary radiation therapy. The study was conducted using a matched case-control design in 60 early-stage (T1-T2/N0) larynx cancer patients. All patients had squamous cell carcinoma of the larynx and were treated with primary radiation to a total median dose of 66 Gy in daily fractions of 2 Gy, without surgery or chemotherapy. Thirty patients who suffered a local relapse in the larynx after treatment served as the index case population. These 30 cases were matched by age, sex, site (glottic vs. supraglottic), radiation therapy technique/dose, and follow-up, to 30 control patients who did not experience a local relapse. Immunohistochemical staining from cycD1 was performed on the paraffin-embedded specimens. The pathologist, blinded to the clinical information, scored each of the specimens on a four-point intensity scale (0 = no stain, 1 = faint, 2 = moderate, 3 = strong) and percent distribution. Patients were considered to be positive for cyclin D1 if the staining was 2+ or greater with a percent distribution of at least 5%. By design of the study, the two groups were evenly balanced with respect to age, sex, stage, radiation dose, and follow-up. CycD1 levels correlated with proliferating cell nuclear antigen levels. Low levels of cycD1 significantly correlated with local relapse; 19/30 (63%) of the index cases stained negative, while only 10/30 (33%) of the control cases stained negative (P = 0.03). These data suggest that low levels of cycD1 correlate with relatively radioresistant early-stage larynx carcinoma. With larger more confirmatory clinical and laboratory data, this data may have significant clinical implications. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 22-28 (2000).

Sentinel lymph node radiolocalization in head and neck squamous cell carcinoma.

OBJECTIVES: To determine the feasibility of sentinel node radiolocalization in stage N0 in head and neck squamous cell carcinoma and to gain insight as to whether the sentinel node could be prognostic of regional micrometastatic disease. STUDY DESIGN: A prospective report on the application sentinel node radiolocalization in eight patients with N0 squamous cell carcinoma of the head and neck region. METHODS: For each patient a peritumoral submucosal injection of filtered technetium (99mTc) prepared with sulfur colloid was performed immediately following intubation. After at least 30 minutes, focal areas of accumulation corresponding to a sentinel node were marked on the skin surface. Complete neck dissections were performed, and the sentinel nodes were identified for later histological evaluation and comparison to the remaining lymphadenectomy specimen. RESULTS: Sentinel node radiolocalization accurately identified two or more sentinel lymph nodes in all eight cases. In one patient, two of the three lymph nodes containing micrometastatic disease were sentinel lymph nodes. There was no instance in which sentinel node was negative for micrometastatic disease while being positive in a nonsentinel lymph node. CONCLUSIONS: Accurate localization of the sentinel lymph node using radiolabeled sulfur-colloid is feasible in patients with squamous cell carcinoma of the head and neck region. Although sentinel node radiolocalization in head and neck squamous cell cancer may potentially reduce the time, cost, and morbidity of regional lymph node management, more experience with technique is required before its role can be determined.

Motor innervation of the human cricopharyngeus muscle.

Innervation of the human cricopharyngeus muscle remains historically controversial and unclear, encouraging numerous treatments inconsistently designed to pharmacologically or mechanically alter the contractile state of this muscle. Neuroanatomic controversy results from and is perpetuated by 1) use of nonhuman models, 2) observational misinterpretation of small-diameter, overlapping nerve fibers, and, most importantly, 3) lack of real-time verification of neural projections. We sought to overcome these difficulties by performing microdissections in 27 patients undergoing laryngectomy and using real-time electromyographic verification. We demonstrated 1) dual ipsilateral innervation by the pharyngeal plexus and recurrent laryngeal nerve, 2) segmental projection of the recurrent laryngeal nerve to anterior motor units, 3) pharyngeal plexus projection to posterior motor units, 4) absence of a sympathetic or external superior laryngeal nerve contribution, and 5) absence of contralateral innervation. Such dual ipsilateral innervation, segmentally projected, has not been previously described in any other form of neuromuscular organization. Neuroanatomic accuracy should improve diagnostic and therapeutic strategies for future management of pharyngeal dysphagia.

Evolving experience with direct puncture therapeutic embolization for adjunctive and palliative management of head and neck hypervascular neoplasms.

OBJECTIVES: The use of percutaneous, direct puncture therapeutic embolization (DPTE) of hypervascular head and neck neoplasms is a relatively new modality that may be used to supplement or supplant conventional endovascular transarterial embolization. Although the preliminary clinical experience reported by a single group has been favorable, extensive case series experience is lacking. This prompted us to review our recent clinical experience with these techniques to determine safety, efficacy, and emerging role in the overall neurointerventional therapeutic armamentarium. STUDY DESIGN: A retrospective analysis of the previous 34 consecutive cases of hypervascular tumors undergoing DPTE referred to our service for therapeutic devascularization was performed. METHODS: Complete case record review was undertaken. Twenty-six of 34 cases involved DPTE of head and neck neoplasms. Conventional diagnostic angiography was performed for therapeutic planning and to assist in precise localization. When performed, standard microcatheter transarterial embolization techniques were used either before or after attempted DPTE. Cyanoacrylate embolic mixtures (n-butyl cyanoacrylate [NBCA], lipiodol, powdered tungsten) were used in 21 of 24 cases, and absolute ethanol in 3 of 24. Direct puncture angiography of the targeted tumor neovasculature was always performed before DPTE. RESULTS: Twenty-four of 26 cases had technically successful DPTE. Combined transarterial embolization with DPTE was used in 16 of 24 cases, although for the last 12 cases, 9 were treated predominantly or exclusively by DPTE. There were no major or minor clinical complications, and there was one asymptomatic technical complication. Total or near-total devascularization was achieved in all cases. All preoperative cases had excellent hemostasis within the resected tumor bed. CONCLUSIONS: Our results lend further support to the safety and efficacy of DPTE in the management of hypervascular neoplasms of the head and neck. With our increasing experience, this technique is evolving into a primary therapeutic modality for optimal tumor devascularization.

Recurrent carotid blowout syndrome: diagnostic and therapeutic challenges in a newly recognized subgroup of patients.

BACKGROUND AND PURPOSE: To our knowledge, recurrent carotid blowout syndrome (rCBS) has not been well described. Our purpose was to review our institution's recent experience with patients who presented with multiple episodes of carotid blowout syndrome (CBS), and who were referred for emergent diagnostic angiography and endovascular therapy. METHODS: We retrospectively reviewed the last 46 consecutive patients who had a clinical diagnosis of CBS. All patients were examined and treated prospectively according to a standardized protocol. Most patients (43 of 46) had undergone extensive primary and salvage radical surgery with intraoperative brachytherapy or external beam radiation or both. The remaining three patients had either traumatic or iatrogenic CBS. RESULTS: Twelve patients (26%) in our series had more than one episode of CBS in which a total of 32 (20 recurrent) events were observed (average 2.7, range 2-4). Intervals of rCBS ranged from 1 day to 6 years. Thirteen (65%) of 20 recurrent events were attributed to progressive disease (PD), and seven (35%) of 20 to treatment failures (TFs). In the PD group, seven (54%) of 13 had recurrent ipsilateral disease, and six (46%) of 13 had recurrent contralateral disease. Etiologies of rCBS were as follows: seven exposed carotids; seven carotid pseudoaneurysms; eight small-branch pseudoaneurysms; five tumor hemorrhages; three hyperemic/ulcerated wounds; and one aortic arch rupture. Twenty-seven of 32 events were treated with endovascular therapy, which included the following: nine carotid occlusions; 11 small-branch embolizations; three transarterial tumor embolizations; one carotid stent; and two direct-puncture embolizations. Four of six TFs were retreated successfully with endovascular therapy; the remaining two TFs were managed successfully by surgery. In the PD group, hemorrhagic complications of rCBS were managed successfully in all but one patient, who died. No permanent neurologic or ophthalmologic complications occurred. CONCLUSION: Recurrent CBS is a frequently encountered problem in which most cases are caused by PD resulting from both multifocal iatrogenic arteriopathy and occasional wound complications that are characteristic of aggressively managed head and neck surgical patients. Initial TFs are encountered often as well. Despite the diagnostic and therapeutic challenges of rCBS, most cases can be retreated effectively.