Laryngeal cancer is one of cancers located superficially. one can easily detect lesions endoscopically and get histo-pathologic diagnosis by punch biopsy through endoscopy. Few are left for further diagnostic imaging work-up, but evaluation of sub-glottic spread by conventional radiography is one of weak-points of endoscopy. Conventional tomography, dual-energy projection radiography, or three-dimensional CT are useful to evaluate sub-glottic extension of the tumor. CT and MRI are powerful tools in evaluating submucosal extension of the tumor. CT and MRI, as well as ultrasound, are helpful for the diagnosis of metastatic lymphadenopathy. The clinical significance and limits of each modality were discussed.

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The significance of nucleolar organizer regions (NORs) and nuclear DNA contents was assessed for proliferative activity and biological behavior in 25 supraglottic and 73 glottic laryngeal carcinomas. The numbers of NORs stained by a silver colloid staining method were counted and nuclear DNA contents were assayed by cytofluorometry. Cytofluorometric study demonstrated that as the differentiating grade of tumors became poorer, the percentage of tumors with aneuploid tended to increase. Moreover, as T categories and Stage grouping advanced in supraglottic carcinomas, the frequency of tumors with aneuploid tended to be higher. The difference of survival rate was not significant between tumors with diploid and those with aneuploid. AgNOR staining method revealed that as the differentiating grade of glottic tumors became poorer, the mean AgNOR number was higher. Moreover as T, N categories and Stage grouping advanced, the mean AgNOR number tended to be higher. More interestingly, the mean AgNOR number was significantly higher in the group with lymph node metastasis than in the non-metastatic group. There was no significant difference between tumors with low AgNOR counts (under mean) and those with high AgNOR counts (over mean). These studies indicate that AgNOR staining method has an advantage over DNA cytofluorometric analysis in the prediction of lymph node metastasis.

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Fifteen supraglottic squamous-cell carcinomas were investigated for the immunohistochemical localization of the basement membrane components (BMCs), type IV collagen and laminin in the BM surrounding the cancer nest. Expression of the tumor supressor gene p53 and infection of huamn papillomavirus type 16 (HPV-16) were also examined in the cancer cells. A regular and continuous staining for BMCs was present, but p53 expression and HPV-16 infection were nondetectable, in normal suprragolottic epithelium. The distribution of BMCs was related to the lympho node metastasis (LNM) with a decreased immunostaining being evident in LMN-positive cancers. On the other hand, cancers showing suffiecient BMC deposition were poorly metastatic. Eight of 15 cancers (53%) exhibited elevated p53 expression and HPV-16E6 was detected in 4 of 15 (26%), one of which exhibited elevated p53 expression. Both the elevated p53 expression and the detection of HPV-16 E6 were found to correlate with poor distribution of BMCs surrounding the cancer nest. From the above, LMN may be more accurately diagnosed by these examinations.

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We investigated the activities of cathepsin B, L and type IV collagenase in tissue homogenate in 26 cases with head and neck cancer and 7 cases with normal mucosa. Activities of both cathepsin and type IV collagenase in the cancer tissue were much higher than those in the normal tissue. The correlation between the size of cancer mass and activity of cathepsin was positive in cancer tissue. The type IV collagenase tendended to show high activity in the cases with cervical lymphnode metastais. There was no significant relation between cathepsin and type IV collagenase. We also investigated of the immunohistological localization and continuity of type IV collagen. Discontinuity (brekes and abscence) of type IV collagen was significantly correlated with cervical lymphnode metastasis and the cases of discontinuity had high activity of type IV collagenase. These results suggested that the activity of cathepsin might participate in local invasion, while type IV collagenase might be associated with lymphmode metastasis of cancer. Both cathepsin and type IV collagenase could be useful biochemical tumor markers to represent the groth and metastasis.

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Three parameters of epithelial dysplasia of the larynx, namely, the expression of oncogene product (ras p21, EGF-R), nuclear DNA contents measured by flowcytometry and the proliferating activity (Ki-67, PCNA), were examined to determine the appropriate clinical treatment and the prognosis. Dysplasia was classified into low grade and high grade depending upon the degrees of cellular atypia and polarity-disorder in the depths of the epithelium. Fourteen of 20 cases with high grade dysplasia and 7 of 21 cases with low grade dysplasia were positive to ras p21. Two of 6 cases with high grade dysplasia and 1 of 5 cases with low grade dysplasia were positive to EGF-R. Four of 8 cases with high grade dysplasia and 2 of 7 cases with low grade dysplasia had a DNA aneuploid pattern as determined by flow cytometric DNA analysis. High grade dysplasia had higher Ki-67 and PCNA labeling indeces than low grade dysplasia. These three parameters may be useful in deciding the therapeutic modalities and the prognosis of dysplasia.

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The embryological function of the larynx is to serve as a protective reflex excecutor. Regarding this reflex glottic closure, the ascending input system from the peripheral laryngeal mucosa to the medulla oblongata was quantitatively and qualitatively clarified from functional and anatomical aspects in felines. After tracheostomy and exposure of the larynx, quantitative stimuli were applied to the laryngeal mucosa by a pressure stimulating apparatus. Unit discharge of the superior laryngeal nerve (SLN) was recorded at a presynaptic area close to the synaptic linkage area of the nucleus solitarius by the microelectrode extracellular method. Furthermore, for the purpose of clarifying the laryngeal receptor, micro-frozen sections were stained utilizing an immunohistochemical staining method of protein gene product (PGP 9.5), CGRP and SP. It was found that the afferent nerve fibers of the SLN were concentrated in the interstitial subnucleus (ni) of the nucleus solitarius. Presynaptic nerve fibers responded to chemostimulation such as pure water and/or a pressure stimulus from a limited area of the base of epiglottis, ary-epiglottic folds and arytenoid region. However, the threshold of response to mucosal mechanical stimuli at the true vocal folds was very high. The electrophysiological results reflected the immunohistochemical study. Positive stained nerve fibers were present at the vocal process and arytenoid region reflecting glottic intradermal fine nerve fibers.

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Eleven adult cats were anesthetized with intramuscular injection of Ketamine hydrochloride. Electrically induced vocalization was performed after Kanai's methode. (stimulating location APO, L4.5-5.5, H-3.5-6.0) The internal branch of the superior laryngeal nerve was cut and the peripheral stump was placed on a pair of silver recording electrodes. Then afferent discharges from laryngeal sensory receptors during electrically induced vocalization were recoded.
In this study, 16 single afferent discharges were obtained. They were classified into four groups. Discharge rate of the first group corresponded to the fundamental frequency change during evoked vocalization. Discharge rate of the second group showed augmentation during evoked vocalization but was not correlated with the fundamental frequency change. Discharge rate of the third group decreased during evoked vocalization. Receptors of the fouth group showed activities only at the initiation time of the evoked vocalization.
In 3 out of 7 successfully investigated cases, we observed that the pitch of evoked vocalization decreased after section of the internal branch of the superior laryngeal nerve. In the other cases, we observed hoarseness and an increase of the induced vocalization cycle.
These results suggest that central nerve system receives real time informations from the larynx during evoked vocalizatios and laryngeal sensory receptors play some role in the control mechanism of phonation.

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The mucosal upheaval (MU) where the mucosal wave starts and propagates upward appears on the lower surface of the vocal fold during vibration. We investigated the location of the MU in response to variations in vocal fold tension and to contraction of the thyroarytenoid muscle (TA). Fresh excised larynxes (seven canine and four human) were used in the experiment. The lower surface of the vocal fold was tattooed with india ink as a reference point. Vocal fold vibration was observed either by high-speed filming or by videostroboscopy. Vocal fold tension was increased by cricothyroid approximation and TA contraction was obtained by its direct electrical stimulation. When vocal fold tension increased, the MU appeared medially or upward compared to its original position. With TA contraction, the lower surface of the vocal fold bulged medially and thus horizontal amplitude of the vibration became smaller. When TA contracted, the MU appeared less prominent and was located more downward compared to its position without TA contraction. These were basically common findings to both canine and human excised larynxes. Moreover, vocal fold vibration was stroboscopically observed through a tracheostoma in twelve patients. The MU occurred on the lower surface of the vocal fold as seen in the excised larynx and the mucosal wave was elicited upward from the MU.

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Over-adduction of unaffected vocal fold in unilateral recurrent laryngeal nerve paralysis has been thought to be a compensatory function to decrease glottic incompetence. Using a videorecording of laryngeal fiberstroboscopy, 120 patients with unilateral recurrent laryngeal nerve paralysis were examined and 51 patients had a remarkable over-adduction of unaffected fold during phonation. However, closure of the posterior glottis was imperfect in all patients with over-adduction. The over-adduction was recognized in a number of patients soon after the onset of paralysis. In 13 patients, there was no over-adduction in spite of a marked chink of posterior glottis. Eight of them had clinical findings that suggested an existence of latent disturbance of the recurrent laryngeal nerve on the unaffected side. Examinations of maximum phonation time, mean flow rate, voice range and acoustic analyses revealed that the vocal function was worse in cases with marked over-adduction of the unaffected vocal told than those without over-adduction. The results suggested that over-adduction of unaffected fold is not a compensatory behavior and it tends to occur when the paralyzed fold is fixed away from the midsagittal plane.

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A number of clinical techniques have been used to evaluate the motor system for deglutition. However, any effective clinical evaluation procedure for the function of the laryngeal sensory system has not been established. We previously reported on evoked potentials on the dural surface elicited by electrical stimulation of the superior laryngeal nerve (SLN) as a reflection of activities in the brain stem and cortex in anesthetized cats. This evoked potential was named LSEP (Laryngeal Sensory Evoked Potential). In this study, we have attempted to establish a less invasive procedure for measuring LSEP. The procedures adopted were, 1) recording from the surface of the scalp using chlorided silver disc electrodes and 2) stimulation by inserting a bipolar platinum hooked wire electrode into the laryngeal mucosa. Evoked potentials were detected using these less invasive procedures, and the response morphologies and relative timing of LSEP components were quite similar to those obtained with the previous technique in a given cat. The amplitude of potentials were slightly lower, and the latencies were slightly longer in the less invasive techniques than in the previous method. These results suggest that this LSEP method might be applicable to humans as a non-invasive method for evaluating the function of the laryngeal sensory pathway.

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One Year after transection of the left superior and recurrent laryngeal nerves of cats reflex arcs between the internal branch of the right superior laryngeal nerve and the left intrinsic laryngeal muscles were recognized electromyographically. Possible participation of the right recurrent laryngeal nerve, the bilateral vagosympathetic trunks, and the left superior cervical ganglion and nodose ganglion was suggested. Moreover, the reflex arcs between the internal branch of the right superior laryngeal nerve and the right, intact intrinsic laryngeal muscles were recognized despite the transection of the right recurrent laryngeal nerve. At the neuromuscular junctions of the right, intact intrinsic laryngeal muscles an increase in the size of postsynaptic area devoid of nerve terminals was observed.

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Several studies of the activity of human cricothyroid muscles during sleep have been reported. Eight adults in good health aged 36 to 61 years were subjected in this study. The activity of the cricothyroid muscle was investigated during sleep and the influence of carbon dioxide inhalation upon the cricothyroid activity was electromyographically determined. During sleep, a slight degree of cricothyroid activity was observed for inspiration. Carbon dioxide inhalation caused an increase in the cricothyroid activity during inspiratory phases.

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We have been using CO₂ laser surgery for laryngeal diseases since 1982. A total of 57 patients were treated with this procedure, including one patient with adult papilloma, four with intubation granuloma, 32 with vocal cord leukoplakia and 20 with glottic cancer. The results lead us to the following conclusions :
1. Laser treatment is indicated for benign diseases, such as papilloma, granuloma and vocal cord leukoplakia, and Ti cancer.
2. Careful determination of the extent of lesion before surgery and long-term postoperative follow-up are essential in cases of histopathologically atypical disease and cancer.
3. Laser treatment also appears to be useful from the standpoint of quality of life in elderly patients and in those patients to whom other therapeutic methods are not applicable.

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During the period from 1981 to 1989, a total of 52 patients with T1 glottic laryngeal cancer (40 patients of T1a and 12 of T1b) received definitive irradiation therapy in our clinic. In 7 patients, residual tumor was recognized histologically by microscopic biopsy 2 to 3 weeks after radiation therapy. Of these 7 patients, 4 were treated by laser surgery and 2 underwent total laryngectomy. One patient refused further treatment but he is still alive without any sign of recurrence. On the other hand 5 patients developed local recurrence following irradiation therapy. Four of the 5 patients underwent total laryngectomy and the other received additional irradiation. The median interval to the local recurrence was 18 months (ranging from 10 to 28 months). The final local control rate for the present series was 96.1% and voice preservation rate was 88.5%.

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Juvenile laryngeal papilloma is a histologically benign epithelial tumor. The tumor is usually multiple, affects predominantly the glottis, and recurrs frequently following excision. The authors treated six patients with juvenile laryngeal papilloma in the past 15 years. Repeated surgical removals or vaporizations with the use of CO₂ laser under microendoscopic control have been chiefly employed. In four of the six patients, more than five years have passed since the tumor disappeared. Interferon was given to one of the four and was thought to be effective. These four patients maintained a good phonatory function. Two patients have been still being treated, one of them with laser surgeries and the other with laser surgeries and interferon. All six patients did not undergo tracheostomy. Goals of treatment for this disease are maintenance of an adequate airway patency, preservation of voice and eradication of papillomas. Although many modalities of treatment have been reported in the literature, surgical removal with the use of CO₂ laser combined with interferon administration seems to be the choice at present. Tracheostomy should be avoided because it may cause tumor dissemination to the tracheobronchial tree.

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A laryngeal involvement of systemic lupus erythematosus (SLE) is rare except that acute laryngitis occasionally occurs. A 28-year-old woman who had SLE developed hoarseness. A bamboo-joint-like lesion was noted at the middle of the bilateral vocal cords. Histologically the lesion was located subepithelially and it consisted of fibrous tissue and many plasma cells. Immunohistological analysis revealed IgA and IgG in some of the plasma cells. The anti-ribonucleoprotein antibody showed high index one year before the onset of hoarseness. It was assumed that the lesion was re lated with SLE. The lesion was excised under the laryngo-microsurgery and hoarseness improved.

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There have been various indices obtained by acoustic voice analyses for objective evaluation of hoarseness. It is desirable to obtain easily indices of hoarseness which contain as many characteristics of pathological voices as possible. The cepstrum analysis has been applied recently and appears to be one of such indices. The height of the dominant cepstral peak (C1) is known to vary in relation to period and amplitude perturbation (PPQ, APQ) of pathological voices. In this study, relationships between C1 and PPQ, APQ were investigated for synthetic voices and normal and pathological human voices. In the study using synthetic voices, C1 decreased as PPQ increased.
APQ, however, was not markedly related to C1. In the analysis of the acoustic speech signals which were obtained from 100 normal adults and 105 patients with various laryngeal diseases, both PPQ and APQ were related to C1. The results indicate that the cepstrum is useful for objective evaluation of hoarseness.

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It has been known that the height of the dominant cepstral peak (C1) is related to perturbation of acoustic speech. In this paper, the possibility of applying C1 to evaluate hoarseness was investigated clinically.
The voice materials were obtained from 100 normal adults for control, and from 105 patients with various laryngeal diseases. The acoustic speech signals were analyzed. The normal group was differentiated from the laryngeal disease group by C1 as well as by PPQ and APQ. However, C1 was the most effective factor to distinguish the normal group from the laryngeal disease groups. On the other hand, C1 increased after laryngomicrosurgery of benign laryngeal lesions. As the degree of perceived hoarseness increased, C1 decreased.
The results suggest that cepstrum might be useful for the screening of pathologic voice, assessment of the success of surgeries for benign lesions of vocal cords, and psychophysical measurement of hoarseness.

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