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Biomedical subjects

Masaru Yamashita

Publications and source records attributed to Masaru Yamashita.

13 recordsLinked to original sources

Genetic mutations in metastatic adenocarcinoma of unknown primary.

INTRODUCTION: Although several genomic alterations have been reported in adenocarcinoma of unknown primary (ACUP), molecularly targeted therapies are not yet clinically established, and comprehensive genomic profiling (CGP) is rarely used in daily practice. AIM: We aimed to clarify the molecular landscape and prognostic impact of key mutations in recurrent or metastatic ACUP. MATERIALS AND METHODS: Data from 480 consecutive ACUP patients registered in Japan's National Cancer Center (C-CAT) between June 2019 and August 2025 were analyzed. Somatic mutations were identified using the FoundationOne CDx platform. Overall survival (OS) was assessed by Kaplan-Meier analysis, log-rank tests, and multivariate Cox proportional hazards modeling. RESULTS: The most frequent alterations were TP53 (59.4%), KRAS (31.5%), CDKN2A (26.3%), KMT2D (22.3%), LTK (17.9%), NOTCH3 (16.9%), STK11 (16.3%), CDKN2B (15.8%), ERBB2 (15.4%), and GNAS (15.2%). Patients harbored an average of 17.3 9.9 mutations. Mutations in GNAS (p = 0.046) and PIK3CA (p = 0.025) were associated with better OS, whereas ARID1A (p = 0.049) and NOTCH1 (p = 0.038) predicted worse OS. In Cox analysis, hazard ratios (HR [95% CI]) were 0.57 (0.36-0.92, p = 0.020) for GNAS, 0.57 (0.33-0.96, p = 0.033) for PIK3CA, 1.98 (1.27-3.09, p = 0.0024) for ARID1A, and 1.84 (1.17-2.91, p = 0.0090) for NOTCH1. CONCLUSIONS: GNAS and PIK3CA mutations were linked to favorable outcomes, while ARID1A and NOTCH1 alterations indicated poor prognosis in ACUP. These results highlight the prognostic significance of specific genomic alterations and support integrating CGP into the clinical management of ACUP.

Humans↗

A case report of myasthenia gravis localized to the larynx.

This report describes a very rare case of myasthenia gravis (MG) localized to the larynx, with the onset of dyspnea requiring tracheotomy. The vocal cords of this patient were fixed in the paramedian position. Under fiberscopic observation, improvement of laryngeal function was demonstrated after intravenous injection of edrophonium. However, no voice change occurred. The posterior crico-arytenoid muscle has the sole responsibility of abducting the vocal cord; thus, it is concluded that the dyspnea was caused by the selective paralysis of this muscle. We suggest that MG should be considered in cases of vocal cord paralysis of unknown etiology.

Aged↗

Cranial bone regeneration using a composite scaffold of Beta-tricalcium phosphate, collagen, and autologous bone fragments.

OBJECTIVE: The aim of our study was to examine the tissue response and new bone formation induced by beta-tricalcium phosphate (beta-TCP), collagen, and autologous bone fragments with fibrin glue implanted into a cranial bone defect. MATERIALS AND METHODS: Granulated beta-TCP and collagen from porcine skin were mixed and freeze-dried. The weight ratio of both materials was 98:2. The composite scaffold for bone regeneration was composed of this artificial material and autologous bone fragments. Five adult beagle dogs were used. A cranial bone defect (2 cmx2 cm) was created in each dog. The animals were divided into two groups. In group 1 (n=3), the cranial bone defect was closed by replacing the original free bone flap, and the residual fissure and burr holes were filled with the composite scaffold with fibrin glue. In group 2 (n=2), the bone defect was closed only by replacing the original free bone flap. Three months after the treatment, computed tomography and histologic examinations were done in all animals. RESULTS: In all dogs in group 1, the defects were almost closed by new bone; whereas in group 2, the defects were filled with fibrous tissues instead of bone. CONCLUSION: This study showed that the composite scaffold made of beta-TCP, collagen, and autologous bone fragments with fibrin glue enabled reconstruction of cranial bone defects without the usual fixation materials.

Animals↗

Photocoagulation of microvascular and hemorrhagic lesions of the vocal fold with the KTP laser.

OBJECTIVES: Ectasias and varices of the vocal fold are microvascular lesions that are often due to chronic abuse of the voice, and are occasionally encountered in association with other disorders such as polyps, Reinke's edema, and hematoma. The KTP laser can be used for photocoagulation of small vascular lesions, because the laser beam is well absorbed by hemoglobin, and damage to the epithelium is minimal. The present pilot study examined how the KTP laser could be used for microvascular lesions and their associated lesions. METHODS: Twelve patients who had undergone phonomicrosurgery were enrolled in the present study. The microvascular lesions were treated by photocoagulation with the laser set at a low power of 1.5 W in the continuous mode, while preserving the epithelium, and associated lesions were then treated by microdissection with cold instruments. The postoperative phonatory function was assessed by maximum phonation time, a perceptual test rating (GRBAS scale), and stroboscopy. RESULTS: The procedures were completed successfully in all cases. An exceptional case of a small hemorrhagic polyp allowed treatment with the laser only. The postoperative stroboscopic findings, maximum phonation time, and perceptual test rating all showed significant improvement compared with the preoperative state. No adverse effects, such as scarring or reduction of the mucosal wave, were observed in the current series. CONCLUSIONS: KTP laser photocoagulation is a relatively simple and safe procedure for treating microvascular lesions of the vocal fold. It is not recommended for photocoagulation of hemorrhagic polyps or hematomas, because such lesions have little blood flow inside and thus photocoagulation is usually impossible or requires too much laser energy. However, photocoagulation of perimeter or feeding vessels of such disorders may facilitate the following procedure by avoiding unnecessary bleeding, as well as preventing recurrence of hemorrhagic lesions.

Adult↗

Schwannoma of the nasal septum removed with endoscopic surgery.

A 50-year-old woman presented with a 30-year history of nasal obstruction. She had been treated for paranasal sinusitis at other hospitals and she was referred to our hospital for further examination. Flexible endoscopy revealed a mass in the posterior aspect of the right nasal cavity to the posterior aspect of the left nasal cavity around the posterior edge of the nasal septum.

Cartilage Diseases↗

Regeneration of mastoid air cells in clinical applications by in situ tissue engineering.

OBJECTIVES: To regenerate of the mastoid air cells and their functions for the treatment of incurable otitis media. MATERIALS AND METHOD: In situ tissue-engineered mastoid air cells using three-dimensional hydroxy apatite (3D-HA) of honeycomb-like structure were used as artificial pneumatic bones. This 3D-HA is made of calcium phosphate and has a high ratio of micropores, 90%. Its surface is coated with collagen. Ten patients (4 males, 6 females) for this clinical study were randomly selected among the patients with severe cholesteatoma, adhesive otitis media, and purulent chronic otitis media, and they were to be received a staged operation. At the first stage of tympanoplasty, collagen-coated 3D-HA was put into the newly opened mastoid cavity, and it was fixed by fibrin glue. Recovery of mastoid aeration and regeneration of the pneumatic air cells of the mastoid cavity were estimated by images of high-resolution computed tomography (HRCT) after the first operation. At the second stage of operation, histopathologic examinations of specimens of HA taken from the reopened mastoid cavity were performed. RESULTS: Aerations in the mastoid cavity were observed in 9 of the 10 patients within 12 months after the second operation. Moreover, the pneumatic structure in the mastoid cavity was partially regenerated in five patients. In these successful cases, mucosa with newly formed capillaries was observed on the surface of the implanted HA at the second stage of operation. In the failure cases, however, connective tissues and granulations invaded the space of the 3D-HA. They were observed as soft-tissue density areas in the HRCT scan images. CONCLUSIONS: This study indicates that mucosa can grow on the surface of implanted artificial 3D-HA and can have a gas exchange function in the newly opened mastoid cavity. These tissue-engineered mastoid air cells may be a possible treatment for intractable otitis media.

Adult↗

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.

Aged↗

Destiny of autologous bone marrow-derived stromal cells implanted in the vocal fold.

OBJECTIVES: The aim of this study was to investigate the destiny of implanted autologous bone marrow-derived stromal cells (BSCs) containing mesenchymal stem cells. We previously reported the successful regeneration of an injured vocal fold through implantation of BSCs in a canine model. However, the fate of the implanted BSCs was not examined. In this study, implanted BSCs were traced in order to determine the type of tissues resulting at the injected site of the vocal fold. METHODS: After harvest of bone marrow from the femurs of green fluorescent transgenic mice, adherent cells were cultured and selectively amplified. By means of a fluorescence-activated cell sorter, it was confirmed that some cells were strongly positive for mesenchymal stem cell markers, including CD29, CD44, CD49e, and Sca-1. These cells were then injected into the injured vocal fold of a nude rat. Immunohistologic examination of the resected vocal folds was performed 8 weeks after treatment. RESULTS: The implanted cells were alive in the host tissues and showed positive expression for keratin and desmin, markers for epithelial tissue and muscle, respectively. The implanted BSCs differentiated into more than one tissue type in vivo. CONCLUSIONS: Cell-based tissue engineering using BSCs may improve the quality of the healing process in vocal fold injuries.

Animals↗

Regeneration of mastoid air cells: clinical applications.

The objective of this study was to establish a method for regenerating mastoid air cells and their functions for clinical use in incurable otitis media. For this clinical study three patients (one male, two female) were randomly selected from patients with severe cholesteatoma about to undergo staged operations. Hydroxy-apatite in three-dimensional, honeycomb-like structures (3D-HA) were used as artificial pneumatic bones. This 3D-HA is made of calcium phosphate and has a high percentage of micropores (90%). Its surface is coated with collagen. At the first stage of tympanoplasty, collagen-coated 3D-HA was put into the opened mastoid cavity and fixed by fibrin glue. Recovery of mastoid aeration and regeneration of the pneumatic air cells of the mastoid cavity were estimated on CT scan images after the first operation. Aeration was recovered in all cases. The mastoid air cells were regenerated in two cases. In the failed case, subcutaneous connective tissues and granulations invaded into the spaces of the 3D-HA. This study demonstrated that mucosa would grow on the surface of a 3D-HA implant and could provide gas exchange functions in the newly opened mastoid cavity. This tissue engineering method may be a possible treatment for intractable otitis media.

Aged↗

Tissue engineering for the regeneration of the mastoid air cells: a preliminary in vitro study.

Mastoid is a pneumatic bone, composed of small interconnecting chambers covered by a mono-layer of mucosa with an abundant blood supply. One of its main functions is gas exchange according to the concentration/pressure gradient. The final goal of our research project is to regenerate mastoid air cells and their unique physiologic functions. The aim of the present study is to determine appropriate cultivating conditions for the cells cultured on the surface of artificial hydroxyapatite. In our in vitro experiment, to imitate the skeleton of mastoid bone, we used two types of three-dimensional hydroxyapatite (3D-HA), i.e. with a high (90%) and low (60%) percentage of micropores. The former type was divided into two groups: collagen-coated and non-coated. Canine mucosal- and bone marrow-derived stromal cells (BSCs), from the oral floor and femur respectively, were harvested and cultured on the 3D-HA under different conditions. To estimate the proliferation/distribution of the cultured cells over the surface of the 3D-HA, these cells were stained with the dye DiI and hematoxylin-eosin. There were no significant differences in the proliferation of cultured cells on the 3D-HA with high and low percentages of micropores. Collagen-coated HA was a better material for the cultured cells compared with the non-coated HA. Co-cultured mucosal and BSCs proliferated better than those cultured separately. In conclusion, this tissue engineering technique may be applied for the regeneration of mastoid air cells.

Animals↗

Bilateral vocal fold paralysis and adhesion in anterior spinal artery syndrome.

The purpose of this report is to present a rare case of anterior spinal artery syndrome (ASAS) in which there proved to be a combined lesion of paralysis and adhesion. A 26-year-old woman with a history of ASAS complained of difficulty of tracheal decannulation. In 1988, she was intubated and underwent tracheotomy because of respiratory muscle weakness, and she was decannulated in 1990. In 1998, she had cesarean delivery under general anesthesia, and postdelivery dyspnea necessitated tracheotomy again. On her first visit to us, endoscopic examination revealed bilateral vocal fold immobility at the midline without an apparent web. Direct laryngoscopy under general anesthesia revealed a posterior glottic adhesion and scarring, which were treated by excision of the scar and local steroid injection. The left vocal fold gradually regained mobility, permitting decannulation 3 months after treatment. This complicated vocal fold immobility was found to be due to adhesion and partial paralysis combined.

Adult↗

[Influence of electromagnetic waves on portable electronic instruments in medicine].

In this work, we considered the effect of electromagnetic compatibility (EMC) on electronic instruments used in medical facilities. We simulated and measured the intensity distribution of the electromagnetic field around portable phones and examined the influence of electromagnetic field on telemeter-type electrocardiograms (ECG) and computer display cathode ray tubes (CRT) when portable phones were brought close to them. Results showed that the waves observed on ECG are affected up to a distance of 55cm (3.55E+03V/m) from the portable phone, and the grid of the computer display is affected up to a distance of 9cm (7.16E+04V/m) in the front and 14cm (2.97E+04V/m) in the back. Therefore, to reduce electromagnetic intensity (EMI) maintaining a distance far enough from the source is effective.

Cell Phone↗