Preliminary results of a pilot study on the safety and efficacy of balloon dilatation of the Eustachian tube for nasopharyngeal cancer patients with chronic Eustachian tube dysfunction post irradiation.

OBJECTIVE: Eustachian tube dysfunction is a known complication following radiotherapy to the head and neck region. Unfortunately, treatment options are limited, with significant associated morbidity. Balloon Eustachian tube dilatation has been used successfully to treat Eustachian tube dysfunction; hence, this study aimed to determine the safety and efficacy of this method in treating Eustachian tube dysfunction in post-radiotherapy patients with nasopharyngeal carcinoma. METHOD: This interventional cohort pilot study on patients with Eustachian tube dysfunction compared those with nasopharyngeal carcinoma to patients without. Outcome assessment was based on tympanometry type and Eustachian Tube Dysfunction Questionnaire score. RESULTS: A total of 14 ears (12 patients) were tested. Only 14 per cent of the nasopharyngeal carcinoma cohort showed improvement, while 71 per cent of the non-nasopharyngeal carcinoma group were successfully treated. No significant adverse effect was reported in any patient during this study. CONCLUSION: Balloon Eustachian tube dilatation was not shown to be beneficial for post-radiotherapy Eustachian tube dysfunction in nasopharyngeal carcinoma patients in the preliminary stages of this pilot study.

[The treatment effect of eustachian tube atresia with laser and connical plastic tube after radiotherapy for nasopharyngeal carcinoma].

Objective: To investigate the method in treatment of Eustschian tube atresia caused by radiotherapy. Methods: Two cases diagnosed of Eustschian tube atresia following radiotherapy were retrospectively analyzed in Department of Otorhinolaryngology, Divided Hospital of Shanghai University Communication Affiliated First People Hospital in Apr. 2014 and Oct. 2015. Both cases were female, 65 and 64 years old, and accepted radiotherapy six and 20 years ago respectively. The pharyngeal orifices of Eustschian tube were found to be totally closed under endoscope. The closed Eustschian tubes were re-opened by laser and re-shaped by a slim and conical plastic tube for more than six months. They were followed up and evaluated over 12 months. Results: At six and 12 months after treatment, round mouths were formed in the pharyngeal orifice of Eustachian tube, and the patients had no resistance in Valsalva's test. No shrink or abnormal opening of orifice was found at follow-up of 20 and 12 months. Conclusion: The method of re-opening by laser and re-shaping by a slim and conical plastic tube is recommended to treat Eustschian tube occlusion caused by radiotherapy.

Incidence of long-term ipsilateral and contralateral ototoxicity following radiotherapy for nasopharyngeal carcinoma.

OBJECTIVE: To characterize the long-term adverse effects of radiotherapy on the ears in patients with nasopharyngeal carcinoma (NPC), we investigated ipsilateral and contralateral ototoxicities in the external, middle, and inner ear. METHODS: The records of 48 ears in 24 radiotherapy-treated NPC patients were retrospectively analyzed. Radiotherapy doses varied between 60 and 70 Gy in 2-Gy fractions at 5 fractions/week. Ototoxicities were identified by otoscope and pure-tone audiograms conducted at 2-3 month intervals for ≥12 months. The relationship between radiation dosage and sensorineural threshold deterioration was statistically compared using the Mann-Whitney U-test. RESULTS: Post-radiotherapy, 50% of all ears (3 of 6) that developed severe otitis externa were on the contralateral side. There was a post-radiotherapy increase in contralateral otitis media with effusion (OME) (1-7 ears), but a decrease in ipsilateral cases (16-12 ears), with 2 ears on either side subsequently developing chronic otitis media (COM). All ears that showed sensorineural hearing loss (SNHL) before radiotherapy exhibited a further threshold deterioration of more than 15 dB. No statistically significant difference (p=0.086) in average radiation dose was seen between ears with sensorineural threshold deterioration (50.0 Gy) and those without (48.2 Gy). CONCLUSION: Long-term ototoxicity following radiotherapy for NPC can occur in either the ipsilateral or contralateral ears. Pathophysiology varies between and within each side. The post-therapy increase in OME on the contralateral side was thought to be due to radiotherapy-induced Eustachian tube damage, and the sensorineural threshold deterioration in at least 4 ears was thought to be due to chronic cochlea damage secondary to COM.

A study of middle ear function in the treatment of nasopharyngeal carcinoma with IMRT technique.

PURPOSE: This study evaluates the difference in damage to middle ear function with CRT and IMRT techniques in the treatment of nasopharyngeal carcinoma (NPC). We explore the isthmus of the Eustachian tube (ET) as the key anatomic site for the prevention of radiation-induced otitis media with effusion. METHODS AND MATERIALS: Eighty-two patients with NPC were divided into two groups: 40 patients treated with CRT and 42 patients treated with IMRT. The difference between dosage over the middle ear cavity and the isthmus of the ET was evaluated in both CRT group and IMRT group. All patients underwent hearing tests including pure tone audiometry and impedance audiometry before and after RT. RESULTS: The dosage difference to the middle ear cavity and isthmus between these two groups was statistically significant (p<0.05). The difference in hearing test results between these two groups was also statistically significant (p<0.05). If we limited the dose to the middle ear cavity under 34 Gy and the dose to the isthmus under 53 Gy with IMRT, we may decrease radiation-induced OME even with the larger 2.25 Gy fraction size. CONCLUSIONS: IMRT may have better protected the middle ear function compared with the CRT technique, even with larger fraction sizes than for the conventional CRT technique.

Analysis of anatomical factors controlling the morbidity of radiation-induced otitis media with effusion.

PURPOSE: To analyze the anatomical factors controlling the morbidity of radiation-induced otitis media with effusion (OME) and determine how to best preserve middle ear function when treating nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Forty patients with nasopharyngeal carcinoma undergoing 3-D radiotherapy (RT) planning and curative RT were analyzed retrospectively. The difference in dosage over the middle ear cavity and the isthmus of the Eustachian tube (ET) was evaluated. Pure tone audiometry and impedance audiometry tests were performed before and after RT. RESULTS: Mean dosages over the isthmus of the ET for acoustic impedance and pure tone audiometry were recorded. Differences in dosage among the three classifications of unchanged, improved, and worsened ears were statistically significant. CONCLUSION: There was a correlation between the morbidity of radiation-induced OME and the radiation dosage over the middle ear cavities. Decreased OME morbidity was observed when the dosage over the isthmus of the ET was below 52 Gy and the dosage over middle ear cavity was below 46 Gy.

[Clinical application of incomplete tympanectomy for secretory otitis media in nasopharyngeal carcinoma after radiotherapy].

BACKGROUND & OBJECTIVE: Efficacy of previous treatments on secretory otitis media ears with severely damaged eustachian tube function after radiotherapy is limited. Tympan perforation can avoid relapse of secretory otitis media. This study was to explore clinical value of incomplete tympanectomy for secretory otitis media in patients with nasopharyngeal carcinoma (NPC) after radiotherapy. METHODS: After confirmed severely damaged eustachian tube function through comprehensive examinations, 16 NPC patients (18 ears) with secretory otitis media after radiotherapy received incomplete tympanectomy. All patients were followed up for more than 6 months. RESULTS: After operation, 11 of 18 (61%) ears remained tympan perforation, audition was improved at large in these ears, the average air-bone conduction difference decreased from 30.1 dB to 16.0 dB, other symptoms, such as aural fullness, tinnitus, and headache, basically disappeared. After operation, tympans closed up in 7 (39%) ears,the average air-bone conduction difference decreased from 33.0 dB to 32.1 dB. CONCLUSION: Incomplete tympanectomy may have a long and definite effect on secretory otitis media without any injury on audition after healing of tympan.

[The damaged types of eustachian tube function in the patients of nasopharyngeal carcinoma after radiotherapy].

OBJECTIVE: To study the types and the influences of eustachian tube function disorder in the patients of nasopharyngeal carcinoma(NPC) after radiotherapy. METHOD: Thirty-two patients of NPC (50 ears) that the eustachian tube function were damaged after radiotherapy were examined by general examination, audiometer test, tympanometry, Tubo-tymanoaerodynamic grapy (TTAG), sonotubometry and endoscope. RESULT: Two cases (4 ears) showed abnormal patency of eustachian tube, the patients' symptoms were lightly. The eustachian tube adhesion were found in five patients(7 ears), and 17 patients(27 ears) showed eustachian tube complete obstruction, eight patients (12 ears) showed eustachian tube uncompleted obstruction, they had the similitude symptoms. CONCLUSION: The damaged types of eustachian tube function in patients of NPC after radiotherapy are different, it will harm the ear function. Finding it out will help to choose the treating measures.

[Retrospective results of radiation therapy of the eustachian tube in chronic otitis media]. / Retrospektive Ergebnisse der perkutanen Strahlentherapie der Tuba Eustachii bei chronischer Otitis media.

BACKGROUND: The treatment results of symptomatic radiation therapy of the Eustachian tube in chronic otitis media had to be evaluated retrospectively. PATIENTS AND METHODS: Between 1980 and 1997, 66 patients were referred for therapy. The median age was 58 years. In the clinical presentation, all the patients had a hearing impairment, 35 patients complained of pain, 21 had otorrhea. In their history, 20 patients indicated chronic recurrent infections. The complaints lasted for 4.7 years in the median, primary conservative (adstringentia, antibiotics) and surgical treatment (paracentesis, tympanic tubule, tympanoplastic) did not lead to lasting cure. In 40 of 66 patients, finally radiation therapy was done of both Eustachian tubes. With opposed fields and cobalt-60 photons a total dose of 6 Gy at single doses of 1 Gy, three times a week, was applied. Under the causes for exclusion of radiation therapy were non-acceptance of the patients (nine), prior radiation therapies (six) or spontaneous improvement after initial presentation in our department. The treatment results were evaluated by interviews of the patients and regular otorhinolaryngological examinations. RESULTS: There were no side effects noticed. 28 of 40 (70%) patients reported a significant improvement that could be verified by objective otorhinolaryngological examinations. In the group of 26 nonirradiated patients, 22 could be interviewed indicating in 16 cases (72%) that the complaints were unchanged and chronic otitis media was lasting. In a subgroup analysis concerning the duration of otitis media radiation therapy proved more effective in an acute and subacute stadium of disease of up to 5 years duration, while the patients resistant to radiation therapy were entirely in a chronic stage of disease exceeding 5 years duration. CONCLUSIONS: Radiation therapy is an effective tool for symptomatic improvement of the therapy-resistant chronic otitis media. A dose of 6 Gy seems to be sufficient to achieve an antiinflammatory effect. Radiotherapy should be applied earlier after initial conservative and surgical treatment.

Histopathologic study of the human eustachian tube and its surrounding structures following irradiation for carcinoma of the oropharynx.

OBJECTIVE: To describe a histopathologic analysis of a human temporal bone demonstrating patulous changes of the eustachian tube (ET) and its surrounding structures following radiation therapy. DESIGN: Retrospective histopathologic case review and comparison with an age-matched control. SETTING: Elizabeth McCullough Knowles Otopathology Laboratory, University of Pittsburgh School of Medicine, Pittsburgh, Pa. RESULTS: A widened patulous ET was verified by demonstrating fibrous tissue replacement of the surrounding supporting structures related to the ET. The ET lumen was patulous and wider than the control case. Ostmann fatty tissue, the levator veli palatini muscle, and submucosal glands around the ET cartilage were replaced by dense connective tissue. CONCLUSION: This is the first histopathologic report, to our knowledge, demonstrating the effects on the ET lumen and supporting structures following acute weight loss, possible tumor infiltration, and radiation changes for carcinoma of the oropharynx.

Radiation dose to otologic structures during head and neck cancer radiation therapy.

BACKGROUND: Otologic structures are often contained within head and neck cancer radiation treatment ports. The dosimetry to otologic structures has not been routinely analyzed and radiation treatment planning does not currently attempt to specifically avoid the inner ear structures when dosimetry is calculated. Recent studies demonstrate that up to 30% of patients experience sensorineural hearing loss on multimodality therapy with cisplatin and radiation. METHODS: In the current case series, radiation dosimetry to otologic structures was calculated from computed tomogram treatment plans on patients. Fifteen nasopharyngeal, oral cavity, oropharyngeal, and hypopharyngeal cancer patients were analyzed. RESULTS: Between 8% and 102% of the total dose is delivered to the petrous bone/cochlea, with 4 of 15 patients getting more than 50% of the dose to at least one cochlea The mastoid air cells received between 3% and 75% of the total dose, with higher doses being delivered to patients with bulky high neck metastases or nasopharyngeal tumors. The eustachian tubes received between 20% and 102% of the total dose, with 10 of 15 patients receiving more than 50% of the dose to this anatomic site. CONCLUSION: We conclude that the cochlea and eustachian tubes receive significant radiation during treatment, particularly in nasopharyngeal cancer patients. Careful design of radiation treatment ports may allow for the reduction of radiation to hearing structures.

Patulous eustachian tube in long-term survivors of nasopharyngeal carcinoma.

This article reports on 21 long-term (10 years) survivors of nasopharyngeal carcinoma, divided into 2 groups: those subjected to an inflation-deflation test and a clearance function test in a longitudinal study, and those receiving sonotubometry in a cross-sectional study. On the inflation-deflation test, 12 (55%) out of 22 ears had a patulous eustachian tube, and on sonotubometry, 10 (50%) out of 20 ears also revealed a patulous eustachian tube. Except for 4 ears with chronic otitis media, the ears had resolved to a normal eardrum appearance at 10 years postirradiation. The phenomenon might be attributed to both restoration of the impaired tubal function and the development of a patulous tube.

Preservation of tubal function in patients with nasopharyngeal carcinoma, post-irradiation.

Nineteen nasopharyngeal carcinoma (NPC) patients were subjected to eustachian tube function testing before and 5 years after irradiation. Tubal patency and clearance function of the eustachian tube showed deterioration if maximum irradiation dosage was more than 70 Gy, whereas dynamic function of the eustachian tube was preserved. Development of middle ear complications in NPC patients post-irradiation was caused by both tubal and inflammatory factors. To preserve tubal function, maximum irradiation dosage to NPC should be limited to 70 Gy. To decrease the inflammatory reaction, firstly, middle ear effusion should be drained by repeated myringotomies instead of grommet insertion, and secondly, sinusitis should be evaluated and treated, because sinusitis can aggravate otitis media with effusion.

A 10-year longitudinal study of tubal function in patients with nasopharyngeal carcinoma after irradiation.

OBJECTIVE: To follow up the chronological change of tubal function in patients with nasopharyngeal carcinoma for 10 years after irradiation. DESIGN: Patients with nasopharyngeal carcinoma were subjected to eustachian tube function tests before irradiation and 6 months, 5 years, and 10 years after irradiation. SETTING: University hospital. PATIENTS: Ten patients (20 ears), 7 men and 3 women. RESULTS: Twelve (60%) of the ears had patulous tubes 10 years after irradiation, which might result from atrophy of peritubal tissues. The occurrence of a patulous tube was independent of the radiation dosage, but it was related to the interval since irradiation. CONCLUSIONS: Development of a patulous tube is associated with correction of organic obstruction of the eustachian tube. Resolution of the inflammatory reaction plays the most important role in recovery of function of the tube. Therefore, the prevalence of middle ear complications is low 10 years after irradiation.

Nasopharyngeal radium irradiation: fundamental considerations.

This article discusses the potential carcinogenic effects of radiation exposure from nasopharyngeal radium irradiation exposure and issues to consider when deciding whether to recommend screening for asymptomatic patients who have been treated by nasopharyngeal radium irradiation. The radiation exposure from the radium is primarily the result of gamma-rays, which are very penetrating. beta-Particles would affect only the tissues located within 1 cm of the eustachian tube orifice. On the basis of a quantitative risk assessment, the lifetime risk of brain cancer developing was estimated to be approximately 3 per 1000 persons, and the lifetime risk of a fatal cancer 5.6 per 1000 persons. When the medical benefits of screening asymptomatic patients are assessed, several factors, including the medical risks and benefits and cost-effectiveness of follow-up, should be considered.

Late health effects of radiation for eustachian tube dysfunction: previous results and ongoing study in The Netherlands.

To study the late health effects of nasopharyngeal radium irradiation, a nonconcurrent prospective study was conducted in The Netherlands. Exposed subjects (n = 2510) were treated unilaterally with nasopharyngeal radium irradiation at five ear, nose, and throat clinics between 1945 and 1965 and followed up through February 1, 1985. Unexposed subjects (n = 2199) were matched to treated patients according to clinic, year of birth, and first consultation within 5 years. No overall significant increase in cancer mortality was found. A statistically significant difference was noted only for cumulative all-site cancer incidence, with the exposed having twice as many verified cancers as the nonexposed. This excess risk was caused mainly by head and neck tumors and other tumors (lung, digestive tract, and urogenital system). The relative risk for these specific sites, however, was not significantly different from 1.00. These findings corroborate the hypothesis that there is some risk of tumor induction involved with nasopharyngeal radium irradiation at the dose level applied to this population. Because of ongoing interest in this subject, I plan to extend the follow-up of the cohort through December 31, 1995, and I am studying the possibility of expanding the study population.

Otitis media with effusion in patients with nasopharyngeal carcinoma, postirradiation.

Eighteen patients with nasopharyngeal carcinoma were subjected to eustachian tube function testing before and 6 months and 5 years after irradiation at the university hospital to investigate the chronological changes of tubal function induced by irradiation and to study the development of otitis media with effusion after irradiation. Improvement of tubal function was found 5 years after irradiation in those ears without otitis media. However, in patients who had otitis media with effusion after irradiation, deterioration of tubal function was persistent, and inflammatory reaction was detected in the upper respiratory tract, including the maxillary sinus and nasopharynx. Thus, the development of otitis media with effusion after irradiation in patients with nasopharyngeal carcinoma is attributable to both tubal and inflammatory factors. Insertion of a ventilatory tube in ears can relieve tubal obstruction but can possibly aggravate the inflammatory process. Therefore, it is our opinion that myringotomy plus local treatment may be preferable to insertion of a ventilatory tube in patients with nasopharyngeal carcinoma who have otitis media with effusion.

[Effects of therapy of laryngeal and hypopharyngeal cancers on eustachian tube function]. / Auswirkungen der Therapie von Larynx- und Hypopharynx-karzinomen auf die Funktion der Tuba Eustachii.

In a prospective investigation Eustachian tube function was tested before and after surgery and irradiation of patients suffering from carcinoma of the larynx or hypopharynx. Passive and active tubal parameters were determined using the dual-impedance method in a pressure chamber. In this test, passive tubal function is described by the spontaneous opening and closing characteristics of the tube by an overpressure in the middle ear. Active tubal parameters are determined by the facility of the tube to equalize an over- and underpressure in the middle ear by swallowing. Statistic evaluation was performed with Student's t-test. There were no significant alterations of passive or active tubal function after neck dissection with or without surgery of the primary tumour. On the other hand we observed significant deterioration of all tubal parameters immediately after a series of fractionated percutaneous telecobalt therapy (60 Gy). 2 out of 18 patients developed unilateral middle ear effusion during irradiation which was reversible within 6 months. In most patients we observed a total or at least partial restitution of passive tubal parameters during this time, which was statistically significant. The active tubal function was of minor reversibility. Whereas the facility to equalize a positive pressure in the middle ear was quite good after 6 months, only few patients were able to equalize a negative pressure. The temporary deterioration of passive tubal function may be caused by a marginal implication of the tube at the edge of the irradiation field and by increased lymphatic pressure in tubal tissue following a radiogenic swelling of the lymphatic vessels of the neck.(ABSTRACT TRUNCATED AT 250 WORDS)

Expression of sialic acids in the developing murine tubotympanum.

Sialoglycoconjugates in the developing murine tubotympanum were characterized using lectin histochemistry with wheat germ agglutinin (WGA), Limax flavus agglutinin (LFA), Sambucus nigra agglutinin (SNA), Maackia amurensis agglutinin (MAA), peanut agglutinin (PNA), and neuraminidase treatment. WGA, LFA, MAA, and neuraminidase-PNA labeled epithelial goblet cells, glandular mucous cells, and cell surfaces of adult and newborn murine tubotympanum. SNA did not label any secretory components. PNA labeled secretory cells and cell surfaces of the fetal tubotympanum without neuraminidase treatment. After birth, these secretory cells and cell surfaces were labeled with PNA only after neuraminidase treatment. These results revealed that: Sialoglycoconjugates are produced from glandular mucous cells and epithelial goblet cells and are present on cell surfaces and within the mucous blanket; their terminal tri-saccharide linkage appears to be the sequence Neu5Ac(alpha 2-3)Gal(beta 1-3)GalNAc; sialic acids appear before birth and gradually increase; terminal galactose residues are masked by sialic acids after birth.

Eustachian tube dysfunction in patients with nasopharyngeal carcinoma, pre- and post-irradiation.

Eustachian tube function tests were performed in 34 patients with nasopharyngeal carcinoma before and after irradiation. Tubal dysfunction prior to irradiation in these patients was due to functional impairment. However, tubal dysfunction after irradiation was due to both organic obstruction and functional impairment. Organic obstruction of the tube was found to be severe with higher dosages of irradiation (to 80 Gy) resulting in subsequent otitis media. In our experience, higher doses of irradiation should be avoided if possible, but insertion of a ventilation tube should be done if a high dose of irradiation is planned.

An improved technique for hyaluronan histochemistry using microwave irradiation.

A hyaluronan binding protein (HABP), extracted from cartilage, was biotin-labelled and used for histochemical localization of hyaluronan (HA) in tissue sections. Various tissues were fixed for a mixture of formaldehyde and glutaraldehyde during microwave irradiation. The microwave oven when set at 700 W and 45 degrees C yielded an intense and specific staining of HA. Under these conditions the relative proportion of the two aldehydes did not influence the staining intensity. Aldehyde fixation during microwave irradiation for HA histochemistry, (1) save time, (2) eliminates the use of cetylpyridinium chloride (CPC), and (3) improves the reproducibility.