Twenty years of productive investigation have provided the basis for this review. While it is hoped that this update will provide us the opportunity to better appreciate Victor Negus' masterful contributions to this field, it will also provide me the opportunity to recognize the many Japanese co-workers who, by their skill, patience, dedication and humor, taught me to appreciate qualities of the larynx, both obvious and obscure.
The intrinsic laryngeal muscles have particular characteristics functionally, histochemically and ultrastructurally compared with common skeletal muscles. In the present study, age-related morphological changes of the subneural apparatus (SNA) is assessed of the cricothyroid (CT), thyroarytenoid (TA) and posterior cricoarytenoid (PCA) muscles in rats using scanning electron microscopy. The SNAs of these muscles were immature at 1 week postnatally showing single oval primary synaptic cleft and a small number of secondary synaptic clefts. At 4 weeks postnatally, structures of the SNAs of the CT and TA muscle became mature, while, those of the PCA muscle were delayed in maturation. In aged rats, the CT and TA muscles showed little age-related morphological change. However, the PCA muscle presented some changes including an increased number of depression-type primary synaptic clefts, multiple SNAs on muscle fiber, and thin muscle fiber containing immature SNA. The structure of the SNA was quantitatively analyzed by use of the following parameters, areas of primary and secondary synaptic clefts (APC and ASC, respectively) and length /width (L/W) ratio of the secondary synaptic clefts. APC was roughly constant througthout the tissue life. ASC and L/W ratio increased during the early postnatal period, while, it remained stable with aging. These findings suggest that age-related changes of the CT and TA muscles rarely occur, thereby contributing to their functional maintenance. However, in the PCA muscle, muscle fiber remodeling seems to occur more frequently than in the CT and TA muscles with aging.
Viscoelastic properties of the lamina propria of human adult vocal fold mucosa are essential for vibrating behavior. These viscoelastic properties depend upon the three-dimensional structure of the extracellular matrices. The complex of extracellular matrices is very important for the viscoelastic properties of the human adult vocal fold mucosa. Geriatric changes of each extracellular matrix and its threedimentional structure of the human adult vocal fold mucosa changed the structure and viscoelasticity of the human vocal fold mucosa as a vibrating tissue, and thus is one of the causes of geriatric changes of voice. Macula flavae of human vocal folds are involved in the metabolism of extracellular matrices and their geriatric changes.
1. The developmental transition of myosin heavy chain in rat laryngeal muscles The developmental transition of myosin heavy chain (MHC) isoforms within rats' posterior cricoarytenoid (PAC), thyroarytenoid (TA), cricothyroid (CT) and lateral cricoarytenoid (LCA) muscles were examined, using SDS-PAGE and western blot techniques. The muscles were microscopically dissected from animals on postnatal days 0, 3, 7, 10, 14, 21, 28, 35, 45, 55 and from adult animals. Silver stained SDS-PAGE gels of each muscle were analyzed densitometrically to measure the composition of MHC isoforms, and western blots were carried out to identify specific bands.The differentiation of superfast II L MHC isoform and transition from neonatal-embryonic to adult MHC isoforms occured first in TA followed by PCA, LCA and CT. Characterization of the internal laryngeal muscles, determined by the composition of MHC, were correlated with their function and differentiation reflected onset of function. 2. IGF-I gene therapy for laryngeal aging-related muscle atrophy The myotrophic effect of sustained local IGF-I production achieved by IGF-I gene transfer in denervated rat laryngeal muscle was investigated. Twenty-eight days after a single injection of IGF-I gene vector, IGF-I transfected animals had a significant improvement in muscle fiber diameter and motor endplate morphology. Although muscle atrophy was induced by denervation in our model, a recent report showed that IGF-I gene transfer augmented aging-related muscle atrophy and dysfunction in rats' hind limbs. The results would indicate that IGF-I gene therapy for laryngeal muscle may prevent or reverse aging-related changes.
Total laryngectomy is popular in the treatment of advanced (T3/T4) laryngeal squamous cell carcinoma (SCC) in Japan. In this study we compared the survival rates between young patients (under 64 years old) and elderly patients (over 65 years old) with advanced laryngeal SCC. Fifty-five patients with advanced laryngeal cancer were treated between 1984 and 1999 at the Department of Otorhinolaryngology, Fukui Medical University. All of the 55 cases were involved in the follow up. Although 85.7% of the young patients with advanced laryngeal cancer reached an overall survival rate of 5 years, 70.3% of older patients survived for that same length of time. All of patients with advanced laryngeal cancer underwent total laryngectomy with the exception of four extremely old patients (over 80 years old). Three patients were treated with only radiation therapy and one patient (92-year-old) was not treated. Three patients experienced a highly compromised quality of life until their death. No complications for total laryngectomy with the older patients were found. Tracheoesophageal shunt (T-E shunt) for the restoration of voice were utilized in 40 patients treated with total laryngectomy. Twenty-one young patients (81%) made good use of it, while 8 old patients (57%) used a shunt. We recently recommended elderly patients treated with total laryngectomy to use an electric artificial larynx. Only 4 patients (21%) used the electric larynx every day. These results suggest that the use of restored voice is dependent upon the individual character of the patient.
To determine the treatment modality for lymph node metastasis advanced laryngeal carcinoma in the elderly, we reviewed the clinical records of 206 patients with advanced laryngeal carcinoma who received initial treatment at Kurume University Hospital between 1979 and 1998. The results were as follows : (1) Even with the elderly patients, bilateral neck dissection against advanced supraglottic carcinoma and unilateral neck dissection against advanced glottic carcinoma might be necessary. (2) In cases of preventative neck surgery, limited dissection of lymph node from the upper, middle and lower neck produced satisfactory results. (3) With patients older than 75 or with patients who have severe health problems, flexible treatment modality should be adopted; for example, single laryngectomy without any management of the neck might be satisfactory for such high-risk groups so that their quality of life (QOL) may be sustained.
The aim of this article is to determine the impact of age on the radical treatment of locally advanced laryngeal cancer, which often requires a total laryngectomy. A retrospective study was performed on 207 patients with previously untreated T3/T4 laryngeal squamous cell carcinoma between 1984 and 1993. Those patients were divided into the following three groups based on age : group 1 consisted of 95 patients under 65 years of age, group 2 was comprised of 92 patients between the age of 65 and 79, and group 3 included 20 patients older than 79. The rate of radical treatment was 92% in group 1, 92% in group 2, and 65% in group 3. The cause-specific 5-year survival rate was 78% in group 1, 77% in group 2, and 31% in group 3. The median survival period in group 3 was 1.3 years, but all patients except for one were relieved from final agonies, such as dyspnea, pain, bleeding, and dysphagia. These results suggest that advanced age is not a determining factor when considering radical treatment in the patients aged under 80, and the radical treatment is meaningful in terms of quality of life for the patients 80 years of age and older.
Gastroesophageal Reflux Disease (GERD) patients who complain about otorhinolaryngologic symptoms, are labeled as having Laryngopharyngeal Reflux Disease (LPRD) in the United States and Europe. With GERD, the most definitive manifestation tools are upper gastrointestinal endoscopy and 24-hour ambulatory dual-probe pH monitaring. These diagnostic methods are uncomfortable to patients. In this time, investigation whether otorhinolaryngologist can diagnose LPRD or not is reported. Endoscopic reflux esophagitis in combinations of complicating symptoms and laryngeal findings are investigated in 41 patients, 26 male and 15 female, who complained globus sensation. Endoscopic reflux esophagitis is found in 15 out of 31 patients (48.3%). In laryngeal findings, arytenoid reddening, arytenoid swelling (AR and AS group), and interarytenoid pachydermia (IP group) are found in 34 patients (82.6%). In complicating symptoms, appearance or worsening of globus sensation after meals is found in 33 patients (80.5%). With investigation of combinations, endoscopic reflux esophagitis is found in 10 out of 14 AR and AS group patients (71.4%) and 10 out of 15 IP group patients (66.6%). Their data have no significance as compared with combinations of other symptoms. However, combinations of patients' complicating symptoms and laryngeal findings are very useful for diagnosis of LPRD. In particular, the appearance or worsening of globus sensation after meals is very useful in inquiry and arytenoid reddening, arytenoid swelling and interarytenoid pachydermia are very useful in laryngeal findings.
83 patients with laryngeal carcinoma received total laryngectomy at our clinic between 1988 and 1997. 50 were primary cases and the other 33 were secondary cases. 33 had supraglottic cancer, 48 had glottic cancer and 2 had subglottic cancer. Of the 50 primary cases, 18 had died; 12 from primary cancer and the other 6 from other causes. Of the 33 secondary cases, 8 had died; 3 from primary cancer and the other 5 from other causes. Among 15 patients who died from the primary cancer, 2 died from local recurrences, 8 died from cervical lymphonodes metastasis, and 5 died from distant metastasis. The most important factors for improving the prognosis after total laryngectomy are to control neck and distant metastasis.
A rare case of metastasis of laryngeal carcinoma to the thyroid gland was reported. The patient was a 60-year-old male, who had received radiotherapy for glottic T2NO carcinoma 6 months earlier. He complained of cervical lymphnode swelling and of a thyroid tumor. On, fine needle aspirationcytology, the tumor was diagnosed as metastatic squamous cell carcinoma. Histological examination showed the same histological type as the previous laryngeal carcinoma, which was moderately differentiated squamous cell carcinoma. Although a total thyroidectomy and a modified neck dissection were performed, he died of lung metastasis 5 months after the operation.
A double blind test was performed to evaluate the effectiveness of low reactive level laser (soft-laser) treatment for foreign-body sensation in the throat. One hundred and twenty patients with foreign-body sensation in the throat were studied. Sixty-six patients were treated with soft laser irradiation to the superior laryngeal nerve through the cervical skin. The other 54 patients served as a placebo group. The effectiveness of the treatment was compared between the two groups. An immediate remission of the foreign body sensation was observed in the patients with irradiation more than that of the placebo group. A significant difference of the remission of the foreign body sensation was observed just after the laser treatment (P=0.0175). No side effects were observed in any of the patients. It was concluded that soft-laser treatment was an effective and safe treatment for foreign-body sensation in the throat.
Over the past 23 years a clinical study of posterior glottic adhesion, involving 127 patients who visited the speech and voice clinic of Kurume University Hospital, was conducted. According to the patients' past history of tracheal intubation, recurrent surgical nerve dissection and spontaneous recorvery, they were divided into two groups; the adhesion group and the paralysis group. For these two groups, our observations consisted of the following : the position of the vocal cords; electromyograms (EMG) of the larynx, endoscopic evidence, indication of tracheostomy, vocal function and surgical treatment for glottic adhesion. In the adhesion group, there were many patients whose vocal cords were fixed at the paramedian position and had received tracheostomy. In vocal function tests, the MPT of the paralysis group was longer than that of the adhesion group.In most of the adhesion cases, surgical separation of the adhesion was ineffective. In the vocal cord paralysis group, many had spontaneous recovery of vocal function and, as a result, the tracheostomy could be closed. These findings indicated that vocal cord traction test under a direct laryngoscopy was a valuable preoperative method for discriminating between vocal cord adhesion and paralysis.
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