Degradation of extracellular matrix (ECM) components by matrix metalloproteinases (MMPs) is critical for tumor cell invasion and metastasis. Disruption of the basement membrane is a crucial step for tumor progression. Of the MMPs, MMP-2 is notable because its activity degrades type IV collagen, a major component of the basement membrane. MT1-MMP has been recognized as a key factor for pro-MMP-2 activation. Recent studies have revealed that tumor cells utilize MMPs, such as MMP-2, produced by neighboring stromal cells including fibroblasts rather than by tumor cells themselves for tumor progression, invasion, and metastasis. It has also been found that tumor cells can stimulate stromal cell production of MMPs via soluble factors such as cytokines or through cell-cell interaction mediated by cell adhesion molecules such as EMMPRIN. EMMPRIN, belonging to immunoglobulin superfamily, is a transmembrane glycoprotein with two extracellular domains and a short cytoplasmic domain. Several investigators have reported that expression of EMMPRIN is enriched in a variety of human carcinomas and that it contributes to tumor invasion and metastasis by stimulating nearby fibroblasts to increase secretion of MMPs. In our study, we confirmed that EMMPRIN is highly expressed with laryngeal cancer cells and is involving the production of MMPs from fibroblasts. Further research would clarify the role of EMMPRIN in the mechanism of cancer invasion and its role in metastasis in more detail. Such additional research might demonstrate that EMMPRIN would be a new target in the treatment of cancer.

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For the development of the human gene therapy for laryngeal paralysis, the therapeutic effects of gene transfer into the following parts were investigated in rat laryngeal paralysis model : denervated rat laryngeal muscle, rat nucleus ambiguus after vagal avulsion, and rat recurrent laryngeal nerve fiber injured by being crushed.
Four weeks after IGF-I gene transfer into denervated rat laryngeal muscle, IGF-I transfected animals had a significant improvement in muscle fiber diameter and motor endplate morphology.
Two and four weeks after GDNF gene transfer into rat nucleus ambiguus after vagal avulsion, GDNF gene transfected animals had a significantly larger number of surviving motor neurons. Simultaneous BDNF gene transfer enhanced these neuroprotective effects of GDNF gene transfer.
Two and four weeks after GDNF gene transfer into crush injured rat recurrent laryngeal nerve fiber, significantly faster nerve conduction velocity and better vocal fold motion recovery were observed in GDNF gene transfected animals.
These results indicate that gene therapy for laryngeal paralysis may provide tremendous opportunity for the augmentation of current surgical treatment modalities or even eliminate the need for surgical treatment.

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[in Japanese]

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[in Japanese]

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Unilateral vocal fold paralysis or vocal fold atrophy with a small to moderate glottic gap is a good indication for type I thyroplasty. Advantages and disadvantages of several materials used for type I thyroplasty were discussed in the symposium. The procedure for type I thyroplasty using Gore-Tex^® sheets was presented in the video.

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We performed arytenoid adduction in combination with type I thyroplasty under local anesthesia for the treatment of breathy hoarseness due to unilateral vocal fold paralysis. To facilitate access to the muscular process of the arytenoid cartilage and to decrease discomfort of the patient, we sometimes removed the posteroinferior part of the thyroid ala including the inferior cornu. After that, mild rotation of the thyroid cartilage provided an operative field sufficient for reaching the muscular process. Patients underwent multi-slice computed tomographic (CT) scanning during phonation when the operation was planned. The line starting at the midpoint of the midline and parallel to the line connecting the inferior tubercle and the bottom of the midline was considered the reference line. The tip of the vocal process of the arytenoid cartilage on the healthy side was projected to the thyroid ala on the paralyzed side based on CT data. Distances of the projection from the reference line and from the midline were calculated with the aid of a CT workstation. Then, type I thyroplasty window was designed, based on these distances. After clinical use of this method, although the number of patients was small, we found that it could determine the location of the upper edge of the vocal fold during phonation. Removal of cartilage, which was often ossified, was performed utilizing an otologic drill under microscopic control.

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Iwamura first reported Lateral cricoarytenoid muscle-Pull (LCA-Pull) for unilateral vocal cord paralysis in 1996. The lateral cricoarytenoid muscle is most important for vocal cord adduction. Treatment aims at reproducing natural adduction by pulling the lateral cricoarytenoid muscle. This result in the vocal fold being shifted medially and the difference in the vertical position being corrected. For surgical treatment of unilateral vocal cord paralysis, thyroplasty type I or fat injection has been indicated when the vertical vocal cord position is about the same and when distance between the vocal processes is short. Arytenoid adduction was employed when the vertical position is different. Both types of patient can be managed by LCA-pull, since the procedure leads to the reproduction of natural adduction. Another advantage is the simplicity of the surgical method, in which a small opening is made in the thyroid cartilage for traction and fixation of the lateral cricoarytenoid muscle. Consequently, the incidence of airway complications due to postoperative edema is low. Because the operation is done through the lamina of the thyroid cartilage, scarring due to previous cervical surgery won't be an additional factor in the level of surgical complication.

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We described the method for combination of two operations, the lateral cricoarytenoid muscle (LCA) pull-surgery and Isshiki's thyroplasty of type I.The indication of this procedure is when there is a noticeable displacement of the arytenoid cartilage. This displacement is judged by the level difference or large inter-arytenoid distance. The LCA pull-surgery is one of the arytenoid adduction methods that the nylon-threads sutured to the lateral cricoarytenoid muscle are pulled antero-caudally without exposing the muscular process through the window in the thyroid ala. Since the operating field is similar to that of type I thyroplasty, this method reduces the damage to the surrounding tissues, compared with the method through posterior edge of the thyroid ala. The combination of thyroplasty of type I is performed in the same operating field by a slight enlargement of the window in the thyroid ala. Since the procedure do not need to rotate the thyroid cartilage, we can reduce the discomfort of the patients under topical anesthetic conditions.

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The laryngeal surface of the epiglottis contains a large number of taste buds. Some investigators have considered that epiglottal taste buds may have a function as chemical sensors to initiate the reflex reaction to protect the airway, but little is known about their functional role. As an initial step in a study to understand the function of laryngeal taste buds, the surface morphology, number, and location of rat epiglottal taste buds throughout development were observed by scanning electron microscopic techniques. The diameters of epiglottal taste buds were about 1/3 the size of lingual taste buds. Taste pores were found among most of the epiglottal taste buds. Microvilli projected from the taste pores. A rapid increase in the number of epiglottal taste buds occurred at about 12 weeks of age, and a rapid decrease occurred after about 30 weeks of age. The maximal number of epiglottal taste buds was counted during the period between about 12-20 weeks of age. This period of age may coincide with a peak of rat developmental stages. High-density regions of taste buds on the laryngeal surface of the epiglottis were located around the base of epiglottis. Since epiglottal taste buds seem to be in an optimal location for contact with food, it is suggested that they have an important role as a chemical receptor to protect the upper airway.

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Subluxation of the arytenoid cartilage is an usual laryngeal injury that can occur following blunt trauma or medical instrumentation to the laryngeal cavity, for example endotracheal intubation. It is desirable for the reduction technique of the arytenoid cartilage subluxation to be performed easily without physical damage to the patient.
First, we morphologically observed and studied a model of the posterior arytenoid cartilage subluxation that had been extracted and prepared from human cadaver. This model demonstrated that the arytenoid cartilage had been displaced behind the posterior edge of the cricoid cartilage with the posterior cricoarytenoid muscle of the affected side. We could reduce the dislocated arytenoid cartilage manually with ease.
From these results, we have developed a new manual reduction technique for posterior arytenoid cartilage subluxation. The reduction procedure is follows.
(1) Turn over the patient's larynx manually for the affected faces from the surface.
(2) The dislocated arytenoid cartilage can be palpated at the inside of the thyroid cartilage lamina of the affected side (with tenderness).
(3) Pushing the dislocated arytenoid cartilage antero-medially, the affected arytenoid cartilage can be reduced manually by applying pressure until a clicking sound or response is achieved.
We performed the above procedure for 7 patients and found that their posterior arytenoid cartilage subluxation could be reduced with ease resulting in improvement of their symptoms (hoarseness, aspiration, odynophagia).

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Five cases of recurrent laryngeal cancer, occurring 5 or more years after having radiotherapy for the treatment early glottic cancer of the larynx, are reported.
Case I received irradiation for glottis T1aN0 of the left vocal cord. Thirteen years later, a total laryngectomy was performed for cancer of the right vocal cord extending to the subglottis.
Case II received irradiation for glottis T1aN0 of the right vocal cord. Thirteen years later, reradiation was performed for cancer of the right vocal cord and false cord. Ultimately, a total laryngectomy was required and performed three years after the re-radiation.
Case III received irradiation for glottis T1aN0 of the left vocal cord. Nine years later, an emergency tracheotomy followed by a total laryngectomy was performed for a subglottic tumor.
Case IV received irradiation for glottis T1aN0 of the left vocal cord. Five years and 4 months later, glottis T2N0 of the left vocal cord was detected. The patient expired of progressive prostate cancer.
Case V received irradiation for anterior subglottis T1N0. Eight years later, a total laryngectomy was performed for glottis T3N0 of the left vocal cord.
There are three possible causes for carcinogenesis for these cases : late recurrence (persistence of the original carcinoma), radiation induced cancer and multicentric cancerization. Long-term followup seems to be necessary even with early stage laryngeal cancer patients.

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Emergency tracheotomies were performed in 22 cases because of dyspnea due to upper airway stenosis. In 15 of those cases, tracheotomies were first tried and successfully performed. With 7 other cases, tracheal intubasions were done prior to their tracheotomies, however, in 2 cases with deep neck abscess, tracheal intubation was impossible because of severe laryngeal edemas. In one case, a percutaneous cricothyroid puncture was successfully performed. We understood that performing a percutaneous cricothyroid puncture was necessary in some cases. Training in various types of airway maintenance techniques and accurately choosing from among them is required for emergent treatment of airway obstruction.

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An epiglottic cyst is one of the more common laryngeal diseases; however, its treatment is not always easy. We reported here two cases of enormous epiglottic cyst.
The first case was a 75-year-old woman who has been complaining of an abnormal feeling in her pharynx for ten years. An extremely large cyst was found in the epiglottis with a smooth surface and a wide stalk stem. Two thirds of the vocal cord were not observable. In order to avoid rupturing the cyst, an intranasal intubation was performed while guided by endoscopy. The cyst was entirely removed by laryngomicrosurgery. She discharged 10 days after surgery.
The second case was a 53-year-old man. A giant cyst was found coincidentally with a photogastroscope during a medical examination. He had not complicated of any laryngeal symptoms. The cyst was poorly mobile and had a wide stalk. The day before surgery, a puncture of the cyst was performed under topical anesthesia using indirect laryngoscopy to reduce the volume. An oral intubation was then done for general anesthesia. The cyst was entirely removed by laryngomicrosurgery without any problem. He was discharged three days after surgery.

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A rare case of idiopathic central vocal fold adhesion with no history of laryngeal treatment is reported. A 61-year-old male who suffered hoarseness for 1 year after a severe cough was referred to our center.
Laryngostroboscopic examination during phonation revealed that the area around the center of the vocal folds was adherent. Microlaryngosurgery via direct laryngoscopy was performed under general anesthesia. Removal of the adherent lesion in the center of the membranous portion of the vocal folds detached the vocal folds effectively and improved his dysphonia markedly.
Histopathological examination showed regeneration of the stratified squamous epithelium of the vocal folds with mild inflammatory change. There was no evidence of malignancy. No recurrence of the adhesion has been observed for 1 year after the operation.

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A case of severe polypoid corditis causing dyspnea and acute pulmonary edema was reported.
A 66-year old female was admitted to our hospital because of dyspnea. She was treated for bronchial asthma before admission. Her glottis was obstructed by severe polypoid corditis. A tracheotomy was performed immediately, however, data from blood gas analysis revealed hypoxemia and acidosis after the tracheotomy and chest X-rays showed pulmonary edema. She was treated with mechanical ventilation. 21 days after our initial treatment, her polypoid corditis was treated surgically by laryngomicrosurgery.
The tracheal stoma was closed without any trouble. Her vocal cords and voice returned to normal. It is necessary to recognize that upper airway obstruction may sometimes be misdiagnosed as asthma. The mechanisms underlying pulmonary edema cause by upper airway obstruction were discussed.

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A rare case of paraganglioma of the larynx is presented. A 41-year-old man had complained of a severe sore throat. At another clinic, a fiberscopic examination revealed a tumor on the vestibular fold. The tumor was resected by laryngeal microsurgery. The pathological diagnosis of the tumor was paraganglioma. One year later, he complained of a severe sore throat again and visited our clinic. Fiberscopic examination revealed a tumor extending from the left arytenoid to the vestibular fold. Enhanced CT imagery showed a mass on the left arytenoid. An excisional biopsy was performed via laryngeal microsurgery. The pathological diagnosis was paraganglioma. The patient underwent thyrotomy (laryngofissure) and resection of the tumor after tracheostomy. The resulting pathological report indicated the presence of paraganglion cells. For the management of laryngeal paraganglioma, it is difficult to pathologically distinguish between benign and malignant cells by appearance. Malignant cases tends to have severe sore throats. A clinically severe sore throat and local recurrence suggest malignant paraganglioma; therefore, long term observation for local recurrence and metastasis is required. The patient in our study has been well for the last year without any evidence of recurrence or metastasis. If a patient complains of a severe sore throat that appears to be incompatible with local findings, we must consider the possibility of laryngeal paraganglioma as a diagnosis.

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