Inoperable oropharyngeal carcinoma treated with concomitant irradiation, mitomycin C and bleomycin - long term results.

Patients with inoperable head and neck tumors were treated concomitantly with radiochemotherapy with mitomycin C and bleomycin in our prospective randomized clinical trial (1991- 1993). For the subgroup of patients with oropharyngeal carcinoma the results with radiochemotherapy were significantly superior to irradiation alone. Such scheme of treatment was then adopted as standard method. Here we present the long-term results and dose- response relationships in patients with inoperable oropharyngeal carcinoma treated by the same radiochemotherapy scheme till 1997. Ninety-five patients with stage III and IV inoperable oropharyngeal squamous cell carcinoma were treated with curative intent, concomitantly with supra-voltage irradiation 2 Gy/day 5 times weekly to 60-73 Gy, bleomycin 5 mg 2 times weekly and. one application of mitomycin C 15 mg/m(2) after 10 Gy. Logistic dose- response curve was calculated. Median follow-up was 85 months. The loco-regional control, disease- free survival and overall survival at 5 years were 55%, 51% and 32% (95% CI: 44-67%, 41-62%, 22-42%), respectively. The probability of new primary malignancy at 5 years was 23%. In multivariate analysis performance status, biological equivalent dose, dose of bleomycin, and stage were identified as independent prognostic factors for loco-regional control, disease-free, and overall survival. Th gamma-value of dose response curve was 2.86. The outcome of the disease was directly proportional to intensity of irradiation and chemotherapy. It appears that in our concomitant radiochemotherapy MiC increased radioresponsiveness of the tumor by its effect on hypoxic fraction.

Radiotherapy, combined with simultaneous chemotherapy with mitomycin C and bleomycin for inoperable head and neck cancer--preliminary report.

PURPOSE: Prospectively designed randomized clinical study was undertaken to assess the efficacy of simultaneous application of irradiation, Mitomycin C, and Bleomycin in treatment of patients with inoperable head and neck carcinoma. METHODS AND MATERIALS: Between March 1991 and October 1993, 49 patients with inoperable head and neck carcinoma were randomly assigned to receive either radiation therapy alone (group A) or radiotherapy combined with simultaneous application of Mitomycin C and Bleomycin (group B). Patients in both groups were irradiated five times weekly with 2 Gy to the total dose of 66-70 Gy. Chemotherapy regimen included intramuscular application of Bleomycin 5 units twice a week, with the planned dose being 70 units and Mitomycin C 15 mg/m2 applied intravenously after delivery of 9-10 Gy of irradiation. The application of Mitomycin C was planned to be repeated on last day of radiotherapy in the dose of 10 mg/m2. In attempt to enhance the effect of chemotherapeutic drugs, patients in group B received also Nicotinamide, Chlorpromazine, and Dicoumarol. RESULTS: The difference in complete response rate between both treatment groups (24% in group A and 63% in group B) was statistically significant (p = 0.015). The difference in response rate was much more pronounced in patients with oropharyngeal carcinoma only (18% in group A compared to 81% in group B; p = 0.0003), while for all other subgroups added together, there was observed no benefit of multidrug therapy. Median follow-up was 18 months. Disease-free survival of patients in group A (9%) was significantly lower then in group B (48%) (p = 0.001). The difference between both treatment groups was even greater in patients with oropharyngeal carcinoma only: disease-free survival of these patients in group B was 66%, while in group A, all recurred (p = 0.00001). CONCLUSION: From results of our prospective randomized study it seems that the group of patients that received multidrug treatment with Mytomycin C, Bleomycin, Nicotinamide, Chlorpromazine, and Dicoumarol as enhancers of radiotherapy fared better than patients treated by radiotherapy alone.

Concomitant radiotherapy with mitomycin C and bleomycin compared with radiotherapy alone in inoperable head and neck cancer: final report.

PURPOSE: To compare the efficacy of concomitant irradiation with mitomycin C and bleomycin in patients with inoperable head and neck carcinoma with radiotherapy alone. METHODS AND MATERIALS: Between March 1991 and December 1993, 64 patients with inoperable head and neck carcinoma (41 with oropharyngeal site) were randomized to radiotherapy alone (group A) or radiotherapy combined with simultaneous application of mitomycin C and bleomycin (group B). In both groups patients were irradiated five times weekly with 2 Gy to a total dose of 66-70 Gy. The planned concomitant treatment in group B was: bleomycin 5 units twice a week i.m., total dose 70 units, mitomycin C 15 mg/m2 i.v. after delivery of 10 Gy, and 10 mg/m2 i.v. on the last day of radiotherapy. To enhance the effect of these two drugs, patients received also nicotinamide, chlorpromazine, and dicoumarol. Because significantly better results were achieved in arm B for patients with inoperable oropharyngeal carcinoma, the study was closed and such patients were after December 1993 routinely treated with the combined therapy (as in arm B). Until October 1996, we treated and followed up 48 such consecutive patients. RESULTS: Median follow-up of our study patients is 42 months. Complete remission (CR) rate in group A was 31% and in group B 59% (p = 0.04); disease-free survival (DFS) in group A was 8% and in group B 37% (P = 0.01); and overall survival (OS) was 7% in group A and 26% in group B (p = 0.08). CR rate for patients with oropharyngeal carcinoma was 29% in group A (N = 21) and 75% in group B (N = 20) (p = 0.007); DFS in group A was 10% and in group B 48% (p = 0.001); and the OS was 10% in group A and 38% in group B (p = 0.019). In patients with inoperable oropharyngeal carcinoma treated after December 1993, complete remission was achieved in 32/48 (67%, 95% CI: 52%-80%). DFS at the median follow-up of 14 months was 60% (95% CI 43-77%) and OS 58% (95% CI 42-74%). CONCLUSION: From the results of our study it seems that the concomitant treatment significantly improves CR rate, DFS, and OS in patients with inoperable oropharyngeal carcinoma in comparison with radiotherapy alone.

Voice quality after radiation therapy for early glottic cancer.

OBJECTIVE: To evaluate the voices of irradiated patients with early glottic carcinoma and to compare these with the voices of healthy volunteers. DESIGN: Case-control study. SETTING: University Department of Otorhinolaryngology and Cervicofacial Surgery, University of Ljubljana, Ljubljana, Slovenia. SUBJECTS AND METHODS: The voice samples (sustained vowel) of 50 patients (44 men and 6 women) who had been irradiated for T1 (43 subjects) or T2 (7 subjects) glottic squamous carcinoma at least 1 year prior to the study were analyzed with the Multi-Dimensional Voice Program (Kay Elemetrics Corp, Lincoln Park, NJ) and compared with those of a normal group of 50 age- and sex-matched volunteers. Average fundamental frequency, jitter, shimmer, noise-to-harmonic ratio, and degree of voiceless elements were determined. In the irradiated group, videostroboscopy was performed. The patients assessed their voice fatigue. RESULTS: The irradiated subjects demonstrated significantly higher values for jitter, shimmer, and degree of voiceless elements than did the healthy volunteers. The values for noise-to-harmonic ratio were higher in the irradiated group, but the difference was not significant (P =.08). The values for fundamental frequency were almost equal in both groups. In most of the irradiated subjects, some irregularities of the vocal fold vibration were noticed. Many of these patients also reported voice fatigue. CONCLUSIONS: Radiation therapy for early glottic cancer results in poorer voice quality compared with normal age- and sex-matched speakers. In most of the irradiated patients, greater than normal effort in voice production was found based on patient assessment. This may result from stiffness of the vibratory source and inadequate compensatory maneuvers in phonation. We suggest that voice therapy during and after radiation therapy may result in better voice quality.

Role of surface EMG in diagnostics and treatment of muscle tension dysphonia.

In muscle tension dysphonia (MTD) excessive tension of both the internal and external laryngeal muscles is observed. In the present pilot study, 9 pairs of surface electrodes were used to determine the electromyographic (EMG) characteristics of different muscles in the perioral area and anterior neck before and during phonation. Eleven patients with MTD and 5 normal speakers were included within the study. The results show a 6-8-fold increase of EMG activity and/or an alternation of the EMG activity level in the perioral and supralaryngeal muscles before and during phonation in most of the patients with MTD. It is not clear whether these muscles are activated as compensation for excessive tension of internal laryngeal muscles, or whether they are responsible for some of the voice disorders.

Amyloidosis of the larynx.

Amyloidosis of the larynx is an uncommon disease and mainly a local occurrence. Hoarseness is the prevalent symptom. Surgical excision of the amyloid masses is the treatment of choice. In the present paper, the authors describe seven cases treated in the last twenty years.

Cowden's disease--its importance for otolaryngologists.

Cowden's disease is a rare predominantly inherited disease, characterized by mucocutaneous lesions, gastrointestinal polyposis and benign or malignant thyroid and breast tumours. The report deals with a typical case of this disease with emphasis on its importance for otolaryngologists.

Laryngo-tracheo-bronchopathia chondro-osteoplastica.

Two cases of laryngo-tracheo-bronchopathia chondro-osteoplastica (LTBCOP) are discussed regarding the pathogenesis of the disease. Our observations support the belief that chronic irritation of the perichondrium in the region of subglottis, trachea and bronchi plays an important role in the aetiology of this disease.

Does it make sense to preserve the stapedial muscle during surgical treatment for otosclerosis?

Our study aimed to show whether it is useful to preserve the stapedial muscle during the surgical treatment of otosclerosis. The study was carried out on 67 patients with tympanoscopic evidence of otosclerosis. In group A (34 patients) the stapedial muscle was intra-operatively preserved as follows: the stapedial suprastructure with preserved muscle tendon was transpositioned onto the longer arm of the incus and secured with a wire loop. The mean uncomfortable level for sounds was measured after surgery and the results of group A patients were compared with those obtained in group B (33 patients, who underwent standard surgery). One month after surgery, in group A patients, the cochleostapedial reflex was evoked in 21 patients (61.8 per cent) and two months later in 32 patients (94.1 per cent). One month after operation, in group A patients the mean uncomfortable level was 108.8 dB, while three months later it increased to 114.1 dB. In group B, the relevant values were 97.8 dB one month after surgery, and 98.0 dB three months later. Our presumption that stapedial muscle preservation is necessary has been proved by the fact that the patients with the preserved muscle had a higher noise discomfort threshold.

Laryngeal chondrosarcoma: is conservative surgery adequate treatment?

A case of laryngeal chondrosarcoma in a 63-year-old woman is presented. The report illustrates most of the features of this rare neoplasm, the difficulties in the histopathological evaluation and supports the previous ones that recommend an initial conservative attitude towards low grade laryngeal chondrosarcomas.

Topographic anatomy of the external branch of the superior laryngeal nerve. Its importance in head and neck surgery.

The authors have studied the anatomy of the external branch of the superior laryngeal nerve in its entirety on 40 fresh cadavers, and they have drawn the following conclusions: the nerve ramifies from the vagus immediately below the nodose ganglion or in the ganglion itself. The nerve splits into two branches approximately 1.5 cm below the ganglion nodosum. In four cases, both branches originated from the vagus itself. In one case, anastomosis of the external branch of the superior laryngeal nerve with the recurrent nerve was found. The external branch of the superior laryngeal nerve is not usually severed at supraglottic laryngectomy but the nerve is at risk during neck dissections, resection of Zenker's diverticula and thyroidectomy. An accurate knowledge of its course should reduce the incidence of injury to the branches of the superior laryngeal nerve during surgery.

Novel connexin 30 and connexin 26 mutational spectrum in patients with progressive sensorineural hearing loss.

OBJECTIVE: Mutations in the gap junction protein beta-2 gene ('GJB2') are known to be responsible for mild to profound congenital and late-onset hearing loss. This study aimed to investigate the molecular basis of progressive hearing loss compared with non-progressive hearing loss. METHODS: Following clinical otorhinolaryngological evaluation, a genetic analysis was performed in a cohort of 72 patients with progressive sensorineural hearing loss. RESULTS: Pathological genotypes were established in 16 patients (22.2 per cent). Six different gap junction protein beta-2 gene mutations were detected in 15 patients, with the c.35delG mutation responsible for 56 per cent of the mutated alleles. A novel gap junction protein beta-6 gene ('GJB6') mutation (p.Met203Val) was observed in one patient with mild progressive hearing loss. CONCLUSION: Analyses of gap junction protein beta-2 and -6 genes revealed that similar pathological genotypes, occurring with similar frequencies, were responsible for progressive hearing loss, compared with reported genotypes for non-progressive hearing loss patients. Thus, genotype cannot be used to differentiate non-progressive from progressive hearing loss cases; in this study, patients both with and without an established pathological genotype had a similar clinical course.

Salivary gland tumours as second neoplasms: two cases and literature review.

OBJECTIVES: Patients who survive malignant tumours have an increased risk of second neoplasms, including those of the salivary glands. Mucoepidermoid carcinoma of the parotid gland is by far the most common type of second salivary gland tumour; other types have rarely been reported. We describe here two patients with a second tumour of the salivary glands. CASE REPORTS: The first patient was a 22-year-old woman with a low grade mucoepidermoid carcinoma of the parotid gland, which developed 21 years after completion of chemoradiotherapy for acute lymphoblastic leukaemia. The second patient was a 40-year-old woman with an epithelial-myoepithelial carcinoma of the buccal mucosa, which arose 11 years after treatment for two malignant neoplasms - retroperitoneal liposarcoma and squamous cell carcinoma of the uterine cervix. CONCLUSIONS: It is mandatory that survivors of cancer should be monitored carefully, so that the complications related to their previous disease and therapy are detected early and managed properly.

Effects of recurrent otitis media in infancy on auditory perception and speech.

INTRODUCTION: Recurrent otitis media is commonly encountered in children before 3 years of age. Conductive hearing loss up to 40 dB is frequently associated with suppurative otitis media. Good hearing is believed to be critical to the development of normal language. This study was undertaken to evaluate the effect of recurrent otitis media on auditory perception and speech. PATIENTS AND METHODS: The experimental group consisted of 33 children with a history of at least three episodes of acute otitis media before 2 years of age. A control group of 29 children experienced one or fewer episodes of otitis media in the first 2 years of age. At the time of investigation, all children were 8 to 10 years of age and had attended similar pre-school, kindergarten, and elementary school programs. None showed evidence of mental retardation nor behavioral or emotional disorders. Speech ability was assessed by a battery of tests specific for Slovene language. Subtests of the Wechsler Intelligence Scale for Children were used as well as the Reading and Writing Test. RESULTS: Auditory perception disorders were evident in 88% of children investigated who had a history of at least three episodes of otitis media by 2 years of age. Decreased auditory stimulation during the time of auditory maturation could prevent the development of these functions completely. No statistically significant differences were observed in the development of articulation. These observations underscore the importance of early management of recurrent otitis media during the first 2 years of age.

Pure tone audiogram and speech audiometry in patients with hereditary motor and sensory neuropathy.

The goal of our work was to determine hearing thresholds in patients with hearing impairment due to hereditary motor and sensory neuropathy (HMSN I). In assessment of auditory function we used two methods: pure tone and speech audiometry. Pure tone audiometry was performed using air and bone conducted signals. Speech comprehension was defined with a test battery of monosyllabic words unknown to the patient. By comparing the results of these methods we were able to differentiate whether the hearing loss was of cochlear or retrocochlear origin. We tested 5 patients with HMSN I associated with difficulty in speech understanding. The tests showed mild to severe elevation of pure tone thresholds but no speech perception in any of tested patients. We suggest that this type of hearing impairment be due to the disorder of the auditory nerve function--a neuropathy of the auditory nerve as part of HMSN.

Autofluorescence imaging in the diagnosis of laryngeal cancer.

Differences in autofluorescence (fluorescence without photodynamic drugs) between normal and malignant tissues offer new possibilities in detecting and localizing early laryngeal carcinoma. Autofluorescence imaging was performed using a modified fluorescence endoscopy system from Xillix Technologies (Richmond, Canada). Fluorescence was induced by blue light at 442 nm and captured by an image-intensified camera through a laryngeal telescope. The images were then processed by the system and displayed on a video monitor. Normal tissue appeared green while malignant sites appeared reddish-brown. The autofluorescence imaging technique was compared to standard microlaryngoscopy in 108 patients with laryngeal pathologies (in 74 of whom malignancy was suspected). The acquired reflectance and fluorescence images of each lesion were assessed independently as malignant or not malignant by three ENT specialists who were familiar with the procedure but were not provided with clinical data or histopathological information concerning the lesion. The assessments of pathology were determined from the two imaging modalities and were compared to histopathological findings of the biopsy specimens taken from the lesion. The present study showed that autofluorescence imaging can be a useful complementary method to microlaryngoscopy for detecting and delineating laryngeal malignancies. If in the future, the device can be developed for use in an outpatient office, a significant improvement can be made for the early detection of laryngeal malignancies.

[Laryngeal mucosal changes experimentally produced by endogenous and exogenous factors in mice (author's transl)]. / Veränderungen an der laryngalen Mäusechleimhaut als Folge endogener und exogener Faktoren.

Experimentally an attempt was made to demonstrate the effects of exogenous factors on the hormonally altered laryngeal mucosa of mice. Albany mice were divided into 4 groups of 8. In the first group of males, testosterone was injected daily; in the second group of males, no testosterone was given; in the third group of females with previously removed ovaries, testosterone was given daily; and, in the fourth group of females, no testosterone was given. All 4 groups were exposed to cigarette smoke for one hour daily for six weeks. Histopathological examination of the mucosa showed that the larynx can be considered a "target" organ for male hormones and that exogenous factors produce changes that lead to malignancy.

[Testosterone--an etiological factor in the development of laryngeal carcinoma?]. / Testosteron--aetiologischer Faktor bei der Entwicklung des Larynxkarzinoms?

To evaluate the etiological connection between the development of hyperplastic lesions of the laryngeal mucosa (including cancer) and the male sex hormones, the authors determined the level of testosterone in the serum of patients with cancer of the larynx (25 women and 25 men) and patients with hyperplastic lesions of the mucous membrane of the larynx (15 women and 15 men). In patients who suffered from cancer of the larynx the serum level of testosterone was significantly increased compared to the control group. In the patients who had hyperplastic lesions (including precancerous lesions) of the laryngeal mucosa the differences in the concentration of the serum testosterone were not statistically significant from the control group. The same was also true of the testosterone-estradiol index. The results of the study do not help to explain the success of hormonal therapy for hyperplastic lesions of the laryngeal mucosa. The authors consider that endogenous factors, especially the male sex hormones, should be taken more into account, alongside exogenous factors, in the genesis of laryngeal cancer.