Cancer of the nasal cavity and paranasal sinuses. A clinico-pathological study of 277 patients.

In the period 1963-1991, a total of 277 consecutive patients with malignant tumours of the nasal cavity and paranasal sinuses were treated at Aarhus University Hospital. The major histological types included squamous cell carcinoma (46%), lymphoma (14%), adenocarcinoma (13%), and malignant melanoma (9%). Kaplan-Meier estimates of 5-year corrected survival (death from cancer) showed the best prognosis for adenoid cystic carcinoma (87%), adenocarcinoma (65%) and lymphoma (56%), and the poorest prognosis for undifferentiated carcinoma (17%) and malignant melanoma (24%). The 5-year corrected survival for squamous cell carcinoma was 35%. Of the 180 patients with treatment failure, the vast majority occurred locally (n = 166); a minor proportion was regional (n = 23) or distant (n = 30). For the 195 patients with carcinoma, the following parameters were of statistical prognostic significance (5-year corrected survival): histological differentiation (moderate-well 65% vs. poor 22%), primary T-site (nasal cavity 56% vs. maxillary antrum 39% vs. other sinuses 24%), tumour stage (T2 68% vs. T3 37% vs. T4 29%), nodal stage (N0 48% vs. N1-3 21%), treatment (radiotherapy + surgery 56% vs. radiation alone 35%).

Culture of rabbit middle ear epithelial cells. A method for primary culture and subculture with identification, characterization and growth specification.

During the last decade middle ear epithelium has been cultured from various species. Until now, subcultivation has been achieved only with the use of a feeder-cell layer or conditioned medium. These factors are possible confounders in the in vitro model. On the other hand, subcultivation is necessary for exact quantitative studies. We present a reproducible culture method allowing subcultivation without feeder-cells or conditioned medium. The main features in our method are a low-serum, hormone-supplemented medium, an incubation temperature of 34 degrees C, fixation of explants, gentle trypsinization and replating with high cell density. Cells were identified by immunohistochemistry through a battery of monclonal antibodies. The percentage of epithelial cells in the subculture was 99.2%. To our knowledge, this is the first report describing subcultivation of middle ear epithelial cells exclusively in a completely controlled environment. These are optimal circumstances for future investigation and quantification of various factors influencing proliferation and differentiation of middle ear epithelium.

Biomechanical characteristics of the middle ear system measured by a new method. III: Comparisons with tympanometric measurements.

A new method for studying middle ear mechanics is reported in which we measured ear canal pressure changes due to tympanic membrane volume displacements. One feature of this pressure-volume relationship (PVR) is the determination of dynamic compliance of the middle ear system (MES). We found a significant correlation between dynamic compliance expressed by the PVR and static acoustic compliance by tympanometry. Another feature of the PVR was determination of the mechanical zero position of the tympanic membrane (TM) defined in terms of minimum hysteresis, which correlated significantly with the neutral position of the TM determined by tympanometry, but indicates a retracted position of the TM relative to tympanometry. Finally the hysteresis effect of the MES measured with the PVR was compared and found to fall within the range of peak difference found in bidirectional tympanometric recordings, which is also influenced by phase delay and semi-dynamic conditions.

The biomechanical characteristics of the middle ear system measured by a new method. II: Clinical application and normal material.

An instrument for measuring the pressure-volume relationship of the middle ear system was introduced earlier. This paper describes the practical application of the instrument and presents a normal material of 45 healthy young adults. Reflecting a slight increase in pressure in the ear canal during the measuring procedure, a series of curves is obtained, each representing a different position of the tympanic membrane. From these curves the zero curve is defined, representing the zero position of the drum. This curve is used to determine the variables of the pressure-volume relationship of the middle ear system: hysteresis, pressure range, Pec0, and compliance. The variables express objective and dynamic measures of the mechanical properties of the middle ear. The method had an acceptable repeatability and was found to be consistent with earlier investigations. It is easy to perform and causes the subject no discomfort. It is therefore considered useful for further investigation of middle ear physiology and pathophysiology.

Case-control study of squamous cell cancer of the oral cavity in Denmark.

A population-based case-control study was designed to examine if the risk of developing intra-oral squamous-cell carcinoma in Denmark was associated with occupation, marital status, residence, dental status, and exposure to coffee, tea, tobacco, and alcohol. Cases consisted of 161 consecutively-admitted incident patients with histologically verified, primary, intra-oral squamous-cell carcinoma treated at the Aarhus University Hospital from January 1986 to November 1990. For each case, three controls of the same gender and age were selected randomly from among nonhospitalized residents in the hospital's catchment area (some 1.4 m inhabitants). Four hundred of the selected 483 controls participated in the study. Risk was associated significantly with marital status, residence, dental status, alcohol consumption, and exposure to tobacco. When correcting for tobacco and alcohol consumption, only marital status and dental status remained significant. The association between risk and marital status was particularly prominent among divorced compared with married persons (odds ratio [OR] = 2.3, 95 percent confidence interval [CI] = 1.1-4.6). Persons with less than five teeth had an OR of 2.4 (CI 1.3-4.1) compared with persons with 15 or more teeth. Tobacco and alcohol exposure were the strongest individual risk-indicators in both lifetime and current consumption estimates, and their composite effect was particularly strong. Compared with nonusers, OR for tobacco (> 20 g/d) adjusted for alcohol = 5.8 (CI = 3.1-10.9); OR for alcohol (> 5 drinks/d) adjusted for tobacco = 8.4 (CI = 4.0-17.6). The OR for heavy users of tobacco and alcohol (> 20 g tobacco/d and > 5 drinks/d) was 80.7 (CI = 21.8-298.8). These results confirm that tobacco and alcohol contribute significantly to the risk of developing oral cancer. There were no significant differences between the risk estimates for the two genders or young and old persons. Two simulation studies indicate that the observed risk associated with tobacco and alcohol consumption cannot be explained reasonably by a high consumption among the 83 nonrespondents.

The influence of endotoxin upon middle ear fibroblasts cultured in normal middle ear gas and atmospheric air.

Otitis media represents a continuum of inflammatory stages frequently in association with bacteria and/or endotoxin. Furthermore, the disease is often treated with insertion of ventilation tubes, which causes hyperoxia relative to the physiological state in the tympanic cavity. The present study was undertaken to quantitate the interaction between endotoxin and relative hyperoxia in cultures of rabbit middle ear fibroblasts incubated in normal middle ear gas and atmospheric air, respectively. Growth was monitored by determination of DNA, cell protein and cell division. The synthetic activity was estimated by collagen production. The antioxidant defense was determined by measuring the intra-and extracellular concentrations of superoxide dismutase (SOD). The results demonstrated that hyperoxia significantly impaired the growth of middle ear fibroblasts, which was compensated for by addition of endotoxin stimulating the growth. The collagen synthesis increased significantly in atmospheric air with a synergistic effect of endotoxin. Hyperoxia induced intracellular SOD formation, while endotoxin tended to reduce the synthesis. Finally, exposure to atmospheric air caused significantly larger amounts of reducing agents extracellularly in cultures without endotoxin compared to endotoxin incubated cultures. It is suggested that endotoxin possess both synergistic and antagonistic potential as regards the effects of relative hyperoxia, and that the interaction between endotoxin and hyperoxia may be an important factor in otitis media.

Oral squamous cell cancer in non-users of tobacco and alcohol.

In a well-defined group of 161 consecutive patients with intra-oral squamous cell carcinoma we found 23 non-users of tobacco and alcohol. The non-users in this prospective study were compared with users of tobacco and alcohol in the study, and to a sex- and age-matched control group drawn at random from the Danish Central Citizenry Registration. The users in the patient group represented a significantly higher number than in the control group. As to non-users, women represented a higher number in the patient group compared with the control group. Among users and non-users differences were found in the location of the primary tumour and in the degree of differentiation of the tumour. Haematological status and liver function parameters were different in the two groups. There was no difference in dental or oral hygiene status or risk occupation among the groups. The stage and the course of the disease (corrected survival) showed only insignificant differences. The non-user group contained especially older women, and only one of them had anaemia.

Immunohistochemical quantitation of collagen types I, II, IV and V in the ventilated and non-ventilated rabbit middle ear with otitis media with effusion.

Morphometric quantitation of the area fractions of collagen types I, II, IV and V was determined in the normal rabbit middle ear mucosa and in relation to otitis media with effusion (OME) using a three-layered peroxidase-antiperoxidase technique. The effects of substituting normal low-oxygen middle ear gas (non-ventilated) with atmospheric air (ventilated) were studied in both healthy ears and ears with OME. Based upon previous histological examinations in rabbits, only ears with OME for more than 8 weeks were included to ensure the presence of chronic inflammation (COME). Atmospheric air was introduced into the middle ears by insertion of ventilation tubes or by an enlarged myringotomy. Collagen type I was predominant in all groups studied. The area fractions of collagen types I, II and IV were increased significantly in COME, with collagen type II elevated in particular. Ventilation of the normal ears resulted in a significantly increased area fraction of cells, while the area fractions and distributions of the collagen types were unaffected. None of the ventilated ears in COME improved or healed spontaneously. The total fraction of collagen in COME was not changed significantly by the introduction of atmospheric air. However, the individual distribution of the collagen types was altered, with significantly larger area fractions of types II and V found in ventilated ears with COME. Possible explanations for the differences found are discussed, including the role of oxygen-derived free radicals.

Superoxide dismutase in in vitro cultures of middle ear fibroblasts from the rabbit.

The present study was undertaken to establish whether intra- and extracellular concentrations of the antioxidative enzyme superoxide dismutase (SOD) in cultures of rabbit middle ear and skin fibroblasts were affected by increasing normal oxygen tensions from 7% to 21% and cause structural damage. The DNA amount was measured fluorometrically and intra- and extracellular concentrations of SOD were determined spectrophotometrically by the inhibition of formazan absorbance. Results demonstrated that SOD was located primarily intracellularly in middle ear fibroblasts and that exposure to atmospheric air gave rise to a significant increase in the SOD concentration from the 6th day following altered oxygen tension (P < 0.0044). Extracellular SOD was sparse in cultures at 7% oxygen whereas atmospheric air induced a significant increase in formazan absorbance from 5% to 60% (P < 0.0163). Inhibition studies indicated that the latter was partly the result of compounds with reducing capabilities similar to superoxide anions. These findings suggest that exposure of middle ear fibroblasts to atmospheric air may involve generation of oxygen-derived free radicals in vitro as well as in vivo but the complexity and significance of these changes need further investigation.

[Malignant parotid tumors. Therapeutic results and prognosis in 110 consecutive patients]. / Maligne parotistumorer. Behandlingsresultater og prognose hos 110 konsekutive patienter.

The UICC 1987 TNM classification system was used to retrospectively analyze the treatment results and prognostic factors in 110 consecutive patients diagnosed and treated from 1970 to 1986. Treatment consisted of surgery, radiotherapy, or a combination. Malignant mixed tumours were seen in 28% of the patients, mucoepidermoid tumours in 18%, adenoid cystic tumours in 15%, acinic tumours in 13%, undifferentiated tumours in 11%, adenocarcinomas in 10%, and other types in 5%. Ten-year corrected survival was 52%, and significant differences in survival were found between: 1. patients with disease stage I-IV (I: 85%, II: 69%, III: 43%, IV: 14%); 2. those with local tumour extension (34%) and without local tumour extension (79%); 3. patients with facial nerve palsy (0%) and without facial nerve palsy (57%); 4. those with low- or intermediate-grade tumours (69% combined) and those with high-grade malignant tumours (30%). Forty-five percent of the patients were cured after primary treatment, as were an additional 22% of those treated for local or neck node recurrences. It is concluded that there is a good correlation between TNM classification of UICC 1987 (stage and local extension of tumour) and prognosis, and that facial nerve palsy and grade of malignancy are important prognostic factors.

Accuracy of an automatic impedance apparatus in a population with secretory otitis media: principles in the evaluation of tympanometrical findings.

INTRODUCTION: The primary demand for a screening procedure for secretory otitis media (SOM) is to identify an objective test with sufficient sensitivity and specificity to meet the needs of the screening program. This study was designed to estimate the value of a portable automatic impedance apparatus to meet these needs. SUBJECTS AND METHODS: Two hundred twenty children with unilateral or bilateral SOM were evaluated in a double-blind, cross-sectional study. All have fulfilled two of the following three criteria for surgical intervention: (1) SOM by physical examination, (2) greater than 20 dB hearing impairment, and/or (3) adenoid symptoms. All ears were evaluated using tympanometry, following which myringotomy was performed. RESULTS: Otomicroscopy showed fluid behind the tympanic membrane in 393 ears. All underwent myringotomy. Thirteen percent (51 ears) were empty. Of the otomicroscopic findings consistent with SOM, 82% had B curves, 6% had C2 curves, 8% had C1 curves, and 4% had A curves. Both C2 and B curves were considered abnormal. Sensitivity of the apparatus is 94.4% and of the specificity is 52.9%. There was no statistical correlation between tympanometrical findings and fluid viscosity. RESULTS: A test intended for screening has to be simple, easy, and quick to perform. Furthermore, the test should have high sensitivity. The automatic impedance apparatus is able to meet these demands; however, the individual results have to be confirmed by another method, eg, otomicroscopy, pure-tone audiometry, and/or manual tympanometry.

A functional evaluation of patients treated for oral cancer. A prospective study.

The oral function of 81 consecutive patients with intraoral squamous cell carcinoma was assessed at diagnosis and during the follow-up 1-2 years after diagnosis. Patients received either radiotherapy, surgery, or radiotherapy and surgery. Speech function and tongue mobility were better among patients who received radiotherapy alone than among patients treated with surgery or combined therapy. Subjective complaints about mucositis, poor dental status, and loss of teeth were most pronounced among patients who received radiotherapy. Patients with tumor recurrence reported a poorer quality of life and found it more difficult to accept their treatment than patients with successful primary therapy. Patients with stage I tumors, notably patients treated with surgery, felt that their quality of life was good after treatment.

Auditory brain stem responses in patients after radiation therapy for nasopharyngeal carcinoma.

BACKGROUND: The study evaluated the incidence and severity of brain stem myelopathy occurring after radiation exposure in a cohort of patients who received external radiation exposure for nasopharyngeal carcinoma (NPC). METHODS: Brain stem function was investigated by auditory brain stem responses (ABR). RESULTS: Four of 21 patients who could be examined had aberrations in ABR. Three patients showed highly abnormal ABR, with no distinctive patterns or peaks. Two of these patients also showed clinical symptoms of brain stem dysfunction, including multiple palsies in cranial and peripheral nerves, whereas the third patient had no clinical signs of brain stem disorders. The fourth patient had minor conduction delays in ABR. The remaining group of 17 patients who could be examined had ABR latency and transmission times similar to those of the control group. None of these patients had neurologic symptoms. Dose-response analysis showed that patients who received radiation doses of 59 Gy or less to the brain stem had normal ABR, whereas four of six patients who received a dose of 68 Gy had manifest or subclinical brain stem dysfunction. CONCLUSIONS: The results emphasize the importance of protecting the brain stem from high-dose radiation when possible. The results also demonstrate the usefulness of ABR as a supplement to the clinical examination of patients with possible myelopathy occurring after radiation exposure.

Histological examination of the rabbit middle ear in secretory otitis media with and without a ventilation tube.

To study the time-related histopathological lesions in secretory otitis media as it develops into the chronic stage, including the influence of ventilation of the middle ear, we examined the middle ear mucosa in a rabbit model. The observation period was from two weeks until 18 months. The histological method applied included haematoxylin-eosin and Sirius red staining for morphometric quantification of the goblet cells, the thickness of the connective tissue layer, the area fractions of blood vessels, inflammatory cells, fibroblasts and collagen fibres. In conclusion, the middle ear mucosa in secretory otitis media exhibited inflammatory changes correlating with the duration of the disease. Ventilation of the middle ear in secretory otitis media did not improve the changes.

Malignant parotid tumors in 110 consecutive patients: treatment results and prognosis.

The UICC 1987 classification system was used to retrospectively analyze the treatment results and prognostic factors in 110 consecutive patients. All of the patients had malignant parotid tumors which had been diagnosed and treated during the period from 1970 to 1986. Treatment consisted of surgery, radiotherapy, or a combination. Malignant mixed tumors were seen in 28% of the patients, mucoepidermoid tumors in 18%, adenoid cystic tumors in 15%, acinic tumors in 13%, undifferentiated tumors in 11%, adenocarcinomas in 10%, and other types in 5%. Ten-year corrected survival rate was 52%, and significant differences of survival were found between: 1. patients with disease stages I through IV (I: 85%; II: 69%; III: 43%; IV: 14%); 2. those with local tumor extension (34%) and without local tumor extension (79%); 3. patients with facial nerve palsy (0%) and without facial nerve palsy (57%); and 4. those with low- or intermediate-grade malignant tumors (69% combined) and those with high-grade malignant tumors (30%). After primary treatment, 45% of the patients were cured, and, additionally, 22% were salvaged after local or neck node recurrences. It is concluded that there is a good correlation between TNM classification of UICC 1987 (stage and local extension of tumor) and prognosis, and that facial nerve palsy and grade of malignancy are important prognostic factors.

Sensori-neural hearing loss in patients treated with irradiation for nasopharyngeal carcinoma.

The present investigation has been carried out to evaluate the sensitivity of the inner ear to irradiation. Cochlear function was tested in a cohort of 22 patients before and 7-84 months after receiving external irradiation for nasopharyngeal carcinoma. The pre-irradiation sensori-neural hearing threshold at 500, 1000, 2000, and 4000 Hz was used as a baseline for the individual patient, and the observed sensori-neural hearing loss (SNHL) was calculated as the difference between pre- and post-irradiation values. The pre-irradiation hearing level or patient age was not correlated with the actual SNHL. In contrast, there was a significant correlation between the total radiation dose to the inner ear and the observed hearing impairment. SNHL was most pronounced in the high frequencies, with values up to 35 dB (4000 Hz) and 25 dB (2000 Hz) in some patients. The latent period for the complication appeared to be 12 months or more. The deleterious effect of irradiation on the hearing should be kept in mind both in treatment planning and in the follow-up after radiotherapy.

Malignant tumours in patients with a history of multiple laryngeal papillomas: the significance of irradiation.

For a period of more than 30 years irradiation was used in the treatment of multiple laryngeal papillomas, especially in children. The treatment was discontinued because a number of irradiated patients developed laryngeal carcinomas. There are however a number of reports of laryngeal and even bronchial carcinomas arising in patients with laryngeal papillomas who had not been irradiated. In addition, HPV type 11 has recently been found in laryngeal papillomas as well as in laryngeal and bronchial carcinomas, subsequently arising in the same patients, both irradiated and non-irradiated. The analysis of a series of 113 patients with laryngeal papillomas has shown that irradiated patients have a 16-fold increased risk of a subsequent carcinoma in the respiratory system.

Acoustic rhinometry used as a method to monitor the effect of intramuscular injection of steroid in the treatment of nasal polyps.

Acoustic rhinometry is a new method which describes the geometry of the nasal cavity and the epipharynx. The method, based on the reflection of an acoustic signal entered into the nasal cavity, can be used to evaluate the cross-sectional area of the nasal cavity as a function of distance from the nostril. The method has, together with nasal expiratory peak flow (NPF) and nasal index based upon a self assessment score, been used to evaluate, in an objective and dynamic way, the effect of systemic treatment of nasal polyps with steroids in a series of eight patients with recurrent nasal polyposis. The study shows a significant relationship between these three parameters before and after systemic treatment of nasal polyps with steroids. It is concluded that in this study acoustic rhinometry had an accurate and objective method for measuring the geometry of the nasal cavity before and after treatment for processes which block the nasal cavity.