Role of radiotherapy in adenoid cystic carcinoma of the head and neck.

This study retrospectively reviewed 183 cases of adenoid cystic carcinoma treated over 40 years. The local recurrence free survival rate was 68.2 per cent at five years and 40.8 per cent at 10 years. At 10 years, local recurrence free survival was significantly worse following radiotherapy alone (0 per cent), compared with surgery alone (41.8 per cent, p = 0.004) or combined with post-operative radiotherapy (43.5 per cent, p = 0.001). Neither tumour stage three or four, perineural invasion, solid subtype nor involved margins predicted local recurrence. Treatment with radiotherapy alone resulted in worse survival than surgery alone (p = 0.002) or combined with post-operative radiotherapy (p = 0.001). Survival rates following local recurrence (n = 34) were higher following surgery (p = 0.006) but not significantly improved following radiotherapy (p = 0.139). Chemotherapy for distant metastases did not prolong survival (p = 0.747) but did result in improved eating and aesthetics scores, while decreasing overall physical health. These results indicate that surgery is preferable for primary and recurrent adenoid cystic carcinoma of the head and neck. The incidence of local recurrence following surgery and postoperative radiotherapy was similar to surgery alone cases although the latter had less adverse prognostic features. Contemporary chemotherapy may benefit quality of life but not survival in patients with distant metastases due to adenoid cystic carcinoma of the head and neck.

Correlation of clinicopathological features with immunohistochemical expression of cell cycle regulatory proteins p16 and retinoblastoma: distinct association with keratinisation and differentiation in oral cavity squamous cell carcinoma.

BACKGROUND: The p16 and retinoblastoma (Rb) gene products are part of the retinoblastoma pathway controlling the G1-S transition of the cell cycle. Few studies on the expression of p16 and retinoblastoma proteins in oral cavity squamous carcinomas have been conducted. AIM: To correlate the expression of p16 and retinoblastoma proteins to clinicopathological characteristics in these tumours. METHODS: 45 patients with resected oral cavity squamous carcinoma were selected, for whom this was the initial treatment and who were followed up for 5 years or until death. Immunohistochemical stains with antibodies to the Rb and p16 gene products were carried out on paraffin wax-embedded tissue. Data on clinicopathological features such as tumour differentiation, nodal status, stage and survival outcome were collected. RESULTS: Retinoblastoma expression was seen in 39 of 45 (87%) patients and p16 expression in 6 of 45 (13%) patients. A significant inverse correlation was observed between retinoblastoma and p16 expression as nearly all retinoblastoma negative cases were p16 positive, and vice versa. When examined for clinicopathological correlates, it was found that all 39 tumours that expressed retinoblastoma displayed marked keratinisation and were of low-moderate histological grade. Conversely, five of the six tumours that expressed p16 were found to be poorly differentiated, with minimal keratin expression. CONCLUSIONS: Salient relationships were seen between expression of retinoblastoma and p16 and keratinisation. A marked loss of keratin production was evident in the tumours that expressed p16. Tumours expressing retinoblastoma were seen to exhibit more widespread keratinisation. In addition, an inverse staining pattern was found for retinoblastoma and p16 as retinoblastoma-expressing tumours were nearly universally p16 negative and vice versa. No correlation of expression of either p16 or retinoblastoma was found with survival or stage. A link between the histologically observable morphology and expression of cell cycle regulatory protein with the expression of p16 and retinoblastoma has been suggested with keratinisation and differentiation of status.

The 'parachute' bolster technique for securing intraoral skin grafts.

Successful skin grafting of intraoral defects can be challenging. The tie-over bolster method is the most popular technique in use today. We describe an alternate method of securing intraoral skin grafts--the "parachute" bolster technique--and we present a case report.

Differential expression of ras signal transduction mediators in verrucous and squamous cell carcinomas of the upper aerodigestive tract.

CONTEXT: ras gene mutations and expression of its gene product have been described in verrucous and squamous cell carcinomas. Other downstream signal-transduction mediators, extracellular signal-regulated kinases 1 and 2 (ERK-1 and ERK-2) and Raf-1, have not yet been as extensively studied. OBJECTIVE: To determine patterns of expression of ERK-1, ERK-2, and Raf-1 in verrucous and squamous cell carcinomas of the upper aerodigestive tract. DESIGN: Seventeen verrucous carcinomas and 10 squamous cell carcinomas of the upper aerodigestive tract were examined for the immunohistochemical expression of ERK-1, ERK-2, and Raf-1 product. RESULTS: Raf-1 expression was intensely expressed in the most basal portions of the epithelium in verrucous carcinomas, but was minimally expressed in the suprabasalar areas. Anti-Raf-1 staining of the squamous cell carcinomas was diffuse and patchy throughout the tumor cells and was weak in intensity. There was no geographic preference of staining. The cytoplasmic expression of both ERK-1 and ERK-2 was predominantly negative in the most basal layers of the epithelium in the verrucous carcinomas, but was positive in the suprabasalar region of the epithelium. Immunohistochemical expression of ERK-1 and ERK-2 in the squamous carcinomas was diffuse throughout the tumor. CONCLUSION: There is strong correlation of the geographic expression of these mediators of ras signal transduction in verrucous and squamous carcinomas, but the cause of these differences remains unclear at present. The expression of these mediator proteins may have potential for diagnosis, as well as in understanding the biologic behavior of these lesions.

National survey of head and neck verrucous carcinoma: patterns of presentation, care, and outcome.

BACKGROUND: Verrucous carcinoma is distinguished by controversy regarding appropriate diagnosis and treatment. This study provides a contemporary survey of demographics, patterns of care, and outcome for this disease in the United States. METHODS: The National Cancer Data Base had 2350 cases of verrucous carcinoma of the head and neck diagnosed between 1985 and 1996. Statistical procedures included chi-square analyses, Student t tests, and relative survival. RESULTS: Tumors originated most frequently in the oral cavity (55.9%) and larynx (35.2%). Although most patients were male (60.0%), oral cavity tumors were more common among older females. The most prevalent treatment was surgery alone (69.7%), followed by surgery combined with irradiation (11.0%) and irradiation alone (10.3%). For oral cavity tumors, surgery alone was more common among early (85.8%) than advanced cases (56.9%); a larger proportion of advanced disease received radiation alone or surgery and irradiation combined. Most laryngeal tumors were treated with surgery (60.3% for early and 55.6% for advanced disease), but a higher proportion received radiation alone or surgery combined with radiation compared with oral cavity cases. Five-year relative survival was 77.9%. For localized disease, survival after surgery was 88.9% compared with 57.6% after irradiation. CONCLUSIONS: Demographic differences implicate different mechanisms of carcinogenesis for verrucous carcinoma arising in the oral cavity and the larynx. Although selection bias may account for the differences observed, patients receiving initial treatment with surgery had better survival than those treated with irradiation, especially for cases originating in the oral cavity.

Esthesioneuroblastoma: the University of Iowa experience 1978-1998.

OBJECTIVE: Esthesioneuroblastoma is rare and the best treatment has yet to be defined. The purpose of this study is to analyze the natural history, treatment, and patterns of failure of esthesioneuroblastoma treated at one institution. METHODS: Between 1978 and 1998, 13 patients with esthesioneuroblastoma were identified using the University of Iowa Tumor Registry. All patients were staged according to Kadish criteria. Mean follow-up was 6.3 years. Six patients had 5 or more years of follow-up and four had follow-up exceeding 9.5 years. One patient was lost to follow-up at 36 months. RESULTS: No patients had Kadish stage A disease, five were stage B, and eight stage C. Overall actuarial 5- and 10-year survival rate was 61% and 24%, respectively. Disease-free survival rate at 5 and 10 years was 56% and 42%, respectively. Seven patients have died, three of intercurrent disease and three of disease progression, one with an unknown disease status. Six patients remain alive, three without evidence of disease and three have experienced a local or regional recurrence. Five patients who were initially controlled developed recurrence, three local only, one locoregional, and one regional and distant. Median time to failure was 96 months. All patients with follow-up exceeding 12 years have experienced either a local or regional recurrence. Survival after salvage therapy in these patients ranged from 3 to 12 years. CONCLUSION: Esthesioneuroblastoma has a long natural history characterized by frequent local or regional recurrence after conventional treatment. Successful retreatment can lead to prolonged survival.

Vocal process granuloma.

BACKGROUND: This review article reports the evolution of knowledge regarding the benign proliferations of the posterior glottis commonly termed "vocal process granuloma". METHODS: A comprehensive review of publications addressing lesions of the posterior glottis is affected to analyze the contemporary management of vocal process granuloma. RESULTS: Contemporary management emphasizes interventions to decrease irritation to the posterior glottis. Multiple causes of this irritation preclude use of a single management plan that will successfully address all cases. CONCLUSIONS: Management to diminish laryngopharyngeal reflux, as well as to correct vocally abusive behavior, will appropriately address the majority of vocal process granuloma. Surgical removal is best reserved for cases when conservative management fails, when airway obstruction is a concern, or when a biopsy is needed to establish the diagnosis. Ancillary measures that may be beneficial in specific cases include the use of steroids, antibiotics, membranous vocal fold augmentation, and laryngeal botulinum neurotoxin injection.

Human papillomavirus and risk of laryngeal cancer.

We determined the relationship between human papillomavirus (HPV) infection and the HPV types detected in 44 patients with squamous cell carcinoma, 10 laryngeal leukoplakia patients, and 12 patients evaluated for benign laryngeal conditions (controls). The sources of HPV DNA were from brushings from the upper respiratory tract and lesion (benign or malignant), oral rinses, and biopsies of patient lesions. Polymerase chain reaction (PCR) and DNA sequencing were used to identify and type HPV. We detected HPV in 25.0% (11/44) of patients with laryngeal cancer, in 30.0% (3/10) of patients with laryngeal leukoplakia, and in 16.7% (2/12) of noncancer controls. Patients with cancer were not more likely to be identified with oncogenic HPV types ( 18.2%) than either the leukoplakia group (20%) or the control group (16.7%). An increased risk of disease was associated with current tobacco use and former alcohol drinking in cancer patients versus controls and in leukoplakia patients versus controls (all p < .05). After we controlled for tobacco and alcohol effects on the risk of disease, exposure to oncogenic HPV types was associated with an increased risk of laryngeal cancer (odds ratio = 3.0) and of laryngeal leukoplakia (odds ratio = 6.0) compared to controls, although the results were not statistically significant. This study suggests that although HPV infection and HPV oncogenic types are not found at a higher frequency in laryngeal cancer or laryngeal leukoplakia as compared to controls, infection is associated with an increased risk of disease after controlling for the effects of alcohol and tobacco use.

Functional magnetic resonance imaging using iron oxide particles in characterizing head and neck adenopathy.

OBJECTIVES: In lymph nodes harboring metastases the reticuloendothelial system is replaced by tumor cells and does not concentrate iron particles. This study assesses the value of contrast magnetic resonance imaging (MRI) using ultrasmall superparamagnetic iron oxide particles (Combidex, Advanced Magnetics, Inc., Cambridge, MA) to characterize and stage neck nodes. STUDY DESIGN: Prospective analysis of neck imaging by Combidex MRI, with correlation from pathological assessment of resected lymph nodes. METHODS: Nine patients underwent MRI and subsequent bilateral neck dissections (three), unilateral neck dissections (five) or fine-needle aspiration (one). Each case was evaluated for the number, location, MRI characteristics, and pathological assessment of lymph nodes. RESULTS: Forty-nine separate nodal levels were evaluated with both Combidex MRI and pathological assessment. The presence of metastatic nodal involvement among 45 levels was correctly assessed by the Combidex MRI (three false-negative results, one false-positive result; sensitivity, 84%; specificity, 97%). Analysis was possible for 101 of the individual lymph nodes identified by MRI that could be correlated with individual nodes pathologically examined. Combidex MRI assessment was correct for 99 nodes (one-false positive result, one false-negative result; sensitivity, 95%, specificity, 99%). Standard MRI interpretation without Combidex identified that 12 of 18 nodes (67%) that were greater than or equal to 10 mm (greatest dimension) contained tumor, whereas 9 of 83 nodes (ll%) that were less than 10 mm contained tumor. CONCLUSIONS: Combidex MRI provides functional information to characterize lymph nodes in the clinical staging of squamous cell carcinoma of the head and neck. The inability of MRI to identify small lymph nodes restricts the usefulness of this technique.

Arytenoid adduction combined with Gore-Tex medialization thyroplasty.

OBJECTIVE: To describe the technique of combined Gore-Tex medialization thyroplasty with arytenoid adduction and to determine the long-term vocal outcome of patients treated for unilateral vocal cord paralysis with this procedure. STUDY DESIGN: A retrospective chart review and patient reevaluation for patients treated at The University of Iowa Hospitals and Clinics between May 1995 and June 1999. METHODS: The review addressed patient demographics, perioperative and long-term complications, and voice outcomes. Details of the surgical technique are provided within the manuscript. RESULTS: Seventy-two Gore-Tex medialization procedures were completed. Arytenoid adduction was included in 22 of these procedures. This subset of patients was compared with the patients treated with Gore-Tex alone. No major postoperative complications occurred in either group. Preoperative and postoperative voice and videostroboscopy data were available for 19 arytenoid adduction patients and 25 Gore-Tex alone patients. On a seven-point scale (6 [severely abnormal] --> 0 [normal voice]), the average patient rating of voice dysfunction improved from 4.2 to 1.6 (arytenoid adduction) and 4.5 to 2.8 (Gore-Tex alone). Maximum phonation time improved from 6.9 seconds to 16.7 seconds in the arytenoid adduction group. Subjective voice assessment employing the four-point GRBAS scale (3 [severely abnormal] --> 0 [normal]) identified average improvement from an overall grade of 2.1 to 0.8 arytenoid adduction and 2.2 to 1.5 in the Gore-Tex alone group. Improvement was identified in the vocal quality of breathiness from 1.9 to 0.2 (arytenoid adduction) and 1.9 to 0.9 (Gore-Tex alone). CONCLUSIONS: The combined technique of Gore-Tex medialization thyroplasty and arytenoid adduction provide functional results that appear to exceed the improvement attained with medialization alone.

National cancer database report on chondrosarcoma of the head and neck.

BACKGROUND: Management of chondrosarcoma of the head and neck is largely based on single-institution reports with small numbers accrued over several decades. METHODS: The American College of Surgeons' National Cancer Data Base included 400 cases of chondrosarcoma of the head and neck diagnosed between 1985 and 1995. Chi square analyses of selected contingency tables and Wilcoxon regression analyses of selected survival stratifications were performed. RESULTS: Histologic types included conventional (80.8%), myxoid (10.5%), and mesenchymal (8.8%). The mesenchymal and myxoid subtypes were rare among white patients (17.1%) and more common among African-American (31.8%) and Hispanic patients (44.9%). Treatment was most commonly surgery alone (59.5%) and surgery with irradiation (21.0%). Disease-specific survival was 87.2% at 5 years and 70.6% at 10 years. Worse 5-year survival was associated with higher grade (67.3%), regional or distant spread (71.0%), and the myxoid (45.0%) or mesenchymal (53.2%) subtypes. CONCLUSIONS: Chondrosarcoma of the head and neck encompasses a variety of lesions that differ substantially by demographic and tumor characteristics. Individual tumors can be classified further according to site of origin, histologic subtype, and tumor grade, which can be used to predict biologic behavior and prognosis.

Laryngeal cancer cost analysis: association of case-mix and treatment characteristics with medical charges.

OBJECTIVES: To examine the relationship of various pretreatment case-mix characteristics and treatment modalities with medical charges incurred during diagnosis, treatment, and 2-year follow-up for patients with laryngeal cancer. DESIGN: Retrospective chart review and billing record analysis. METHODS: The charts and billing records of patients diagnosed with laryngeal cancer at the University of Iowa Hospitals and Clinics (UIHC) between January 1, 1991 and December 31, 1994 were reviewed. The independent variables included various pretreatment patient-mix and tumor characteristics (age, AJCC TNM clinical stage, smoking history, ASA class, and comorbidity as defined by Kaplan-Feinstein grade) as well as type of treatment. The dependent variables included total physician, office, and university hospital-based charges incurred during the pretreatment evaluation and 0- to 3-, 3- to 12, and 12- to 24-month billing periods after the initiation of cancer-directed therapy. Total 1-year and 2-year charges were also evaluated. Univariate and multivariate analyses were used to investigate the relationships between dependent and independent variables and to develop models predictive of management charges during the individual and total billing periods. RESULTS: Pretreatment charges showed no significant associations (P < .05) with any of the independent variables. Multiple regression analyses indicated that comorbidity, stage, and initial treatment modality were significant variables in one or more of the models predicting charges incurred during the 0- to 3-month, 3- to 12-month, total 1-year, and total 2-year billing periods. The models yielded R2 values for the total 1- and 2-year billing periods of 0.5246 and 0.5055, respectively. CONCLUSIONS: This work supports continued study of measures that may result in earlier detection of laryngeal cancer as a potential means of reducing management charges. These results also indicate that a more accurate method of stratifying the disease severity of laryngeal cancer patients for reimbursement purposes would include measurements of the severity of the index disease as well as comorbid diseases.

Modulations in respiratory and laryngeal activity associated with changes in vocal intensity during speech.

We tested the hypothesis that different strategies are used to alter tracheal pressure (Pt) during sustained and transient increases in intensity. It has been suggested that the respiratory system plays the primary role in Pt changes associated with alteration in overall intensity, whereas laryngeal adjustment is primary for transient change in Pt related to emphasis. Tracheal pressure, obtained via tracheal puncture, airflow (U), and laryngeal electromyography from the thyroarytenoid muscle (TA EMG) were collected from 6 subjects during sentence production at different intensity levels and with various stress patterns. Using a technique described in a previous study, we computed lower airway resistance (Rlaw) from measures of Pt and U obtained during a sudden change in upper airway resistance. We used this resistance value, together with direct measures of Pt and U during speech, to derive a time-varying measure of alveolar pressure (Pa), the pressure created by respiratory muscle activity and elastic recoil of the lungs. Pa provided a measure of respiratory drive that was unaffected by laryngeal activity. Laryngeal airway resistance (Rlx) and TA EMG provided measures of laryngeal activity. The results of this study indicated that, contrary to the outcome predicted by the hypothesis, there was no difference in the strategies used to alter Pt during sustained and transient increases in intensity. Although changes in both Pa and Rlx contributed to increase in Pt, the contribution of Pa was substantially greater. On average, Pa contributed to 94% and Rlx to 6% of the increase in Pt associated with vocal intensity. A secondary purpose of the study was to determine the extent to which laryngeal muscle activity was related to Rlx during speech. We found TA EMG activity increased with intensity but was not well correlated with Rlx, suggesting that when it contracts, the TA muscle may affect intensity by loosening the cover, which allows for greater amplitude of vocal fold vibration, without necessarily increasing laryngeal airway resistance.

Assessing head and neck cancer patient outcome domains.

BACKGROUND: The purpose of this study was to assess the relative importance on patients' lives of multiple outcomes resulting from the management of head and neck cancer (HNC). METHODS: HNC patients filled out a disease-specific quality of life (QOL) survey covering 5 domains (speech, eating, aesthetics, pain/discomfort, and social/role functioning). Logistic regression was used to determine which of these domains best predicted the patients' response to a single, overall QOL assessment. RESULTS: In univariate analyses, all 5 domains were significantly correlated to QOL (p<.0001), with correlation coefficients ranging from.48 for eating to.64 for social/role functioning. Logistic regression indicated that speech and eating best predicted QOL (R(2) =.4647), with odds-ratios of 2. 96 for speech and 2.49 for eating. CONCLUSIONS: These data demonstrated that, for this group of patients, speech has the most impact on well-being, whereas eating has a substantial, unrelated influence. This is important information in counseling patients about treatment plans that have different levels of impairment.

Estimation of alveolar pressure during speech using direct measures of tracheal pressure.

The pressure in the alveoli of the lungs, created by the elastic recoil of the lungs and respiratory muscle activity, is referred to as alveolar pressure (Pa). The extent to which tracheal pressure (Pt) approximates Pa depends on the resistance to airflow offered by structures above and below the point at which tracheal pressure is measured. An understanding of the relationship among Pa, Pt, and upper and lower airway resistance, and how these values fluctuate during speech, could aid in interpretation and modeling of speech aerodynamics. The purpose of this study was to (a) obtain values for lower airway resistance (Rlow), (b) use these Rlow values to estimate Pa during speech, and (c) quantify the degree to which Pt approximates Pa during production of voiced and voiceless sounds, in comparison to inhalation. In addition, the results were discussed in terms of the degree to which the respiratory system functions as a pressure source. Tracheal pressure (obtained with tracheal puncture) and airflow were measured during sentence production in 6 subjects. Using a technique introduced in this paper, Rlow was determined from measures of tracheal pressure and flow obtained during a sudden change in upper airway resistance because of release of a voiceless plosive. Mean Rlow values ranged from 0.14 to 0.32 kPa/(l/s). Each subject's mean Rlow was used to derive a time-varying measure of Pa during speech from continuous measures of tracheal pressure and airflow. Pt was approximately 95% of Pa during phonation (i.e., when the vocal folds were adducted), 75% of Pa during release of the voiceless stop consonant /p/, and 55% of Pa during inhalation (i.e., when the vocal folds were abducted). Therefore, the degree to which the respiratory system functioned as an ideal pressure source varied during speech. The ability to estimate Pa provides a measure of the pressure produced by the respiratory system that is not influenced by laryngeal activity.

Vocal fold paralysis secondary to cardiac countershock (cardioversion).

Application of electrical energy to the heart is effective in treating many dysrhythmias. There are, however, also disadvantages associated with cardioversion. Employment of external electrical current has been shown to induce epicardial and myocardial damage at the site of electrode application. We present the only case in the English literature of vocal fold paralysis in which the single identified associated event was cardioversion. In this case of temporary vocal fold paralysis, there was no invasive procedure to directly damage the nerve. Echocardiography of the patient revealed a large left atrium, placing the recurrent laryngeal nerve in an abnormal anatomic position where it was vulnerable to the electric current.

Increased stability of airflow following botulinum toxin injection.

OBJECTIVES: The purpose of this study was to determine whether stability of airflow, as well as mean airflow, increased following botulinum toxin injection to laryngeal and extralaryngeal muscles in persons with spasmodic dysphonia (SD), some with associated vocal tremor (VT). STUDY DESIGN: Aerodynamic data were collected from five subjects before and at 2, 4, and 8 weeks after they received treatment by each of two different arms in an injection protocol in a crossover study. One arm of the protocol involved treatment of the thyroarytenoid muscles only. The other arm involved treatment of both the thyroarytenoid muscles and the strap muscles. METHODS: Measures of mean airflow and coefficient of variation (COV) of airflow during phonation were obtained. A decrease in the COV of airflow would indicate increased stability of phonatory airflow. RESULTS: Before treatment, all subjects with SD/VT exhibited mean airflows that were similar to controls. The COV of airflow ranged from normal to substantially elevated. Following botulinum injection, mean airflow characteristically increased and COV of airflow decreased. CONCLUSIONS: This finding suggests there is a change in the type, as well as the level, of activity in the muscles of speech production following botulinum toxin injection. The increase in airflow stability identified could be due to increased stability of the laryngeal system and possibly of the respiratory system as well.