Shinzo Tanaka

Alpha-Klotho as a regulator of calcium homeostasis

α-klotho was identified as a gene associated with premature aging–like phenotypes characterized by short lifespan. In mice, we found the molecular association of α-Klotho (α-Kl) and Na+,K+-adenosine triphosphatase (Na+,K+-ATPase) and provide evidence for an increase of abundance of Na+,K+-ATPase at the plasma membrane. Low concentrations of extracellular free calcium ([Ca2+]e) rapidly induce regulated parathyroid hormone (PTH) secretion in an α-Kl- and Na+,K+-ATPase–dependent manner. The increased Na+ gradient created by Na+,K+-ATPase activity might drive the transepithelial transport of Ca2+ in cooperation with ion channels and transporters in the choroid plexus and the kidney. Our findings reveal fundamental roles of α-Kl in the regulation of calcium metabolism.

Regenerative medicine of the trachea: the first human case.

Objectives: The objective of the present study was to demonstrate regenerative medicine of the tracheal tissue by using an in situ tissue engineering technique for airway reconstruction. Methods: Based on the previous successful experimental animal studies, the current regenerative technique was applied to repair of the trachea of a 78-year-old woman with thyroid cancer. A Marlex mesh tube covered by collagen sponge was used as a tissue scaffold. The operative intervention included right hemithyroidectomy, resection of the trachea, and tracheoplasty using the scaffold. The right half of three rings of the trachea was resected, and the scaffold material was sutured to the defect of the trachea. Results: After 2 weeks, the mesh collagen structure of the artificial material could be seen with endoscopy in most of the implanted area. The artificial material was covered with epithelial growth after 2 months. Epithelialization continued to cover the artificial material completely for 2 years without any complications. Conclusions: The current regenerative technique avoided tracheotomy, a second operation, and deformity. Good epithelialization has been observed on the tracheal luminal surface without any complications for 2 years. Although long-term observation is required, regenerative medicine of the tracheal tissue appears feasible for airway reconstruction.

Dysphagia following Various Degrees of Surgical Resection for Oral Cancer

Postoperative swallowing problems were investigated in 20 patients who had undergone various degrees of surgical resection for oral cancer. The swallowing problems were evaluated on the basis of type of food, degree of aspiration, and duration of postoperative nasogastric tube feeding. Two patients with tongue cancer who had had hemiglossectomy without reconstruction ate normal food without aspiration within a week after operation. Eight patients who had undergone two- to three-quarter glossectomy for tongue cancer ate gruel with no or occasional liquid aspiration. Among 4 patients who had had near-total or total glossectomy for tongue cancer, 3 ate thin gruel or liquid with occasional aspiration. The other could not eat orally because of consistent severe aspiration. One patient with mouth floor cancer underwent resection of the mouth floor in combination with hemiglossectomy and she ate gruel without aspiration. Among 5 patients with mouth floor cancer who had had surgical removal accompanied by near-total or total glossectomy, 3 ate gruel with no or occasional liquid aspiration, 1 ate thin gruel with no aspiration, and the other could not eat orally. A diagnosis of T4 lesions, extensive removal of the tongue base, removal of the geniohyoid and mylohyoid muscles, and removal of the lateral pharyngeal wall were significantly related to poor swallowing function.

Sulcus Vocalis: Functional Aspects

The vocal function of 126 patients with sulcus vocalis was evaluated with the use of a test battery of multidimensional evaluation items. Of the 126 patients, 31 had a unilateral sulcus and 95, bilateral lesions. The results were as follows. 1) The majority of the patients had a mild degree of hoarseness with a breathy quality. 2) An incomplete glottic closure, a small vibratory amplitude, and a small mucosal wave were frequently observed in the stroboscopic examination. 3) The maximum phonation time, fundamental frequency range, and sound pressure level range of phonation were decreased, whereas the airflow during phonation was increased. 4) The pitch perturbation quotient, amplitude perturbation quotient, and normalized noise energy were increased. 5) Abnormal test results were more frequent and more marked for bilateral lesions than for unilateral lesions.

A retrospective study of 66 esophageal reconstructions using microvascular anastomoses: problems and our methods for atypical cases.

We have studied 66 patients who underwent esophageal reconstruction using microvascular anastomoses. This series comprises 28 patients with reconstruction using a free jejunal interposition between the pharynx and the cervical esophagus following pharyngolaryngoesophagectomy for hypopharyngeal carcinoma and 38 atypical patients in whom other methods of reconstruction were used. Successful transfer was achieved in 98.5 percent (65 of 66). Issues concerning atypical reconstruction and our procedures in these cases are discussed. In order to obtain adequate tension in the jejunum on the anal side, in particular, since the anastomosis is located in a deep or narrow space, autosuture instruments were used. The anastomotic leakage rate was 2.8 percent (1 of 36); the stenosis rate was 2.8 percent (1 of 36). To prevent necrosis in the trachea, a greater omentum flap was used in three patients, a mesenterium flap in two, and a pectoralis major musculocutaneous flap in one. There were no significant complications. In patients with a short gastric pedicle or in those in whom a double cancer occurred in the hypopharynx and thoracic esophagus, a gastric pedicle and a free jejunum flap were used together. As a result of this method, the incidence of any reflux of digestive juice was reduced to 0 percent (0 of 6). To reduce the possibility of an ischemic complication at the oral end of the colonic pedicle, we added a microvascular anastomosis of the colonic pedicle, thereby reducing both leakage [0 percent (0 of 9)] and necrosis [0 percent (0 of 9)]. These procedures involving microvascular anastomoses have reduced the incidence of complications in esophageal reconstructions.

Transcutaneous Intrafold Injection for Unilateral Vocal Fold Paralysis: Functional Results

This paper presents the technique of transcutaneous intrafold silicone injection and the functional results of 44 procedures in 42 patients. The injection is given under local anesthesia with the patient in a supine position. The needle is inserted through the cricothyroid space. The location of the needle as well as the effect of injection is monitored by means of a fiberscope connected to a television camera and screen. The preoperative and postoperative vocal function was multidimensionally evaluated with the use of a test battery consisting of the maximum phonation time (MPT), mean airflow rate (MFRc), fundamental frequency (FO) range and sound pressure level (SPL) range of phonation, pitch perturbation quotient (PPQ), amplitude perturbation quotient (APQ), and normalized noise energy (NNEa). In the majority of the patients, MPT, FO range, and SPL range increased and MFRc, PPQ, APQ, and NNEa decreased postoperatively. In the overall evaluation based on the test values of these parameters, the result was excellent for 16 procedures, good for 16, fair for 7, and poor for 5. The most frequent cause of failure was an insufficient amount injected.

Basic fibroblast growth factor combined with atelocollagen for closing chronic tympanic membrane perforations in 87 patients.

Objective: To present the clinical results of closing chronic tympanic membrane (TM) perforations using basic fibroblast growth factor (bFGF) combined with an atelocollagen/silicone bilayer membrane patch. Study Design: Closure of TM perforations in 87 patients was attempted using bFGF, which is thought to promote the regeneration of TM tissues by facilitating the growth of fibroblasts and collagen fibers. Methods: Under an operating microscope, the margin of the perforation was trimmed, and a piece of an atelocollagen/silicone bilayer membrane was placed in the perforation with the silicon layer facing outward and then infiltrated with 0.1 ml of trafermin. Data obtained from patient records included patient age, perforation size, and duration of treatment, with a focus on hearing improvement and complete TM closure. Results: The mean perforation size before treatment was 14.4%. Complete closure of the TM perforation was achieved in 80 patients (92.0%), whereas pinholes remained in 5 patients (8.7%), and small perforations were observed in 2 patients (2.3%). In the patients with complete closure, the TM perforations closed after an average 1.8 treatments, and hearing improved by 13.6 dB. Conclusion: This study demonstrated that bFGF combined with atelocollagen is effective for the conservative treatment of TM perforation.

Harmonic‐intensity analysis of normal and hoarse voices

Objective evaluation of normal and hoarse voices is performed considering the characteristic that hoarse voices show a prominent fundamental frequency intensity compared with harmonics in the voice spectrum. The relative harmonic intensity Hr, obtained from a stable portion of the sustained vowel/a/, is defined as the intensity of the second and higher harmonics expressed as a percentage of the total voice intensity. Ninety-five percent of the normal voices examined have Hr larger than the critical value of 67.2%, whereas 90% of the hoarse voices have Hr smaller than the critical value. The harmonic-intensity analysis thus provides good discrimination between normal and hoarse voices.

Some Aspects of Vocal Fold Bowing

Bowing of the vocal fold frequently occurs in patients with vocal fold paralysis (VFP), those with sulcus vocalis, and those who have had laser surgery. Additionally, there are vocal folds that present bowing with no noticeable organic lesion. For the purpose of investigating the causes and mechanisms of vocal fold bowing, consecutive fiberscopic videorecordings of 127 patients with VFP, 33 with sulcus vocalis, 33 with laser surgery, and 33 with dysphonia having no clinically noticeable organic lesion were reviewed. Sixty-nine percent of the paralyzed vocal folds had bowing, and the occurrence of bowing was significantly related to the activity of the thyroarytenoid muscle as measured by electromyography. The cricothyroid activity had no significant relationship to vocal fold bowing. All vocal folds with sulcus presented with bowing. Thirty-five percent of the vocal folds that had had laser surgery had bowing. The extent of tissue removal was closely related to the occurrence of bowing. Twelve cases with no organic lesion had vocal fold bowing. Of these 12 patients, 8 were male and 9 were older than 60 years. Some aging process in the mucosa was presumed to be the cause of the bowing in this age group of patients without clinically noticeable organic lesions. Causes of vocal fold bowing in the younger group of patients without organic lesions were not determined in this study.

Vocal Cord Paralysis Caused by Esophageal Cancer Surgery

Esophageal cancer surgery was the cause of paralysis in 111 (16.7%) of 664 patients with vocal cord paralysis seen from 1981 to 1990 at Kurume University Hospital. Eighty-six patients had unilateral paralysis, whereas 25 had bilateral lesions. Of the 111, 95 (86%) had hoarseness and 59 (53%) had aspiration. The crude survival rate was 63% for 1-year, 32% for 3-year, and 22% for 5-year follow-up. The average life expectancy was short. The general condition was poor in many patients. Thirty-four of the 136 paralytic vocal cords (25%) recovered mobility. An intracordal silicone injection was done in 30 patients, and a medialization procedure was performed in 1. The vocal function was improved in the majority of cases. In 4 patients, severe aspiration persisted following intracordal injection. Of the 4, 1 had cricopharyngeal myotomy and laryngeal suspension and 2 underwent total laryngectomy. The fourth patient died of aspiration pneumonia. The results of the review of the 111 patients have led us to the following treatment policy for patients with vocal cord paralysis caused by esophageal cancer surgery. When the patient has aspiration, vocal cord medialization should be performed as early as possible. If severe aspiration persists even after the medialization procedure, some additional intervention, including cricopharyngeal myotomy, laryngeal suspension, laryngotracheal separation, or total laryngectomy, should be considered. When hoarseness is the only major problem, the prognosis of vocal cord paralysis should be determined on the basis of the state of the recurrent laryngeal nerve and, if available, electromyography findings. Vocal cord medialization is indicated for patients with a poor prognosis for paralysis, and also for those patients whose life expectancy is short.