Universities, academic institutes and hospitals in Japan are home to some excellent basic research. However, often, the outcomes of basic research cannot easily be translated into drug discovery or practical use of medical devices, the so- called “valley of death.” Furthermore, some latest medicines that have already been introduced for practical use overseas are sometimes difficult to use in Japan, the so- called “device lag.”
The process of development and practical use of medical devices involves the stages of basic research, translational research, clinical research and trials, regulatory approval by the government, and industrialization. Exploratory clinical research is important for the initial development and continuous improvements of medical devices. Investigator-initiated clinical trials are performed with the support of public funds, such as from the Japan Agency for Medical Research and Development (AMED), if the manufacturing and sales company cannot pay the expenses for a clinical trial. Biological safety tests fulfilling Good Laboratory Practice (GLP), clinical trials fulfilling Good Clinical Practice (GCP), and manufacture of devices fulfilling Quality Management System (QMS) are required based on regulations by the Pharmaceuticals and Medical Devices Agency (PMDA). Regulatory science is essential through the entire process mentioned above.
In this paper, the present status of innovative medical devices and related issues in Japan are described and strategies for the development and commercialization of medical devices are discussed, taking the artificial trachea as an example. Industry-academia-government-citizen collaboration will contribute to acceleration of the entire process, namely, from the stage of basic research to industrialization, for practical application of medical innovation for patients in need.
A 39-year-old female patient presented to us with a history of unilateral hearing loss ever since she was a child. Pure tone audiometry confirmed deafness of the affected ear. Both auditory brainstem response (ABR) and distortion-product otoacoustic emission (DPOAE) response were absent. Caloric test revealed severe canal paresis. Cervical vestibular evoked myogenic potentials (cVEMP) were also absent in the affected ear, even though the patient had never experienced balance problems. Her facial nerve function was normal. Computed tomography (CT) of the temporal bone revealed internal auditory canal stenosis on the affected side. Magnetic resonance imaging (MRI) failed to reveal the vestibulocochlear nerve on the affected side.
A diagnosis of congenital internal auditory canal (IAC) stenosis related to hypoplasia of the vestibulocochlear nerve was considered, given that the patient had no history of acquired disease that could be the cause of the hearing loss. A nerve defect is indicative of retrocochlear dysfunction, whereas absence of a DPAOE response suggests impairment of the membranous labyrinth despite normal radiological findings of the bony labyrinth.
Ramsay Hunt syndrome (Hunt syndrome) is characterized by herpetic lesions on the face, combined with VII and VIII cranial nerve involvement. It is caused by reactivation of varicella zoster virus (VZV), and is associated with multiple cranial polyneuropathy in 1.8%–3.2% of cases.
Herein, we report the case of a patient with human immunodeficiency virus (HIV) infection who presented with Hunt syndrome associated with multiple cranial nerve involvement. The patient, a 41-year-old male patient presenting with left earache, left hearing loss and swallowing difficulty, was diagnosed by physical examination as having involvement of the VIII, IX and X cranial nerves. This was an atypical case, that had been diagnosed as having Hunt syndrome three years ago and presented this time with VZV infection associated with several cranial nerve symptoms. Therefore, he was suspected as having immunodeficiency, and a blood test revealed the patient was HIV-antibody positive. In addition, during a careful medical interview, the patient admitted to being homosexual.
The possibility that atypical Hunt syndrome may be a feature of HIV infection, especially in young homosexual men, should be borne in mind.
Ophthalmic artery pseudoaneurysm is a rare vascular lesion. Herein, we describe a rare case of an infectious pseudoaneurysm caused by a frontal sinus cyst. An 87-year-old man diagnosed as having orbital cellulitis was admitted to our hospital. Paranasal sinus CT imaging showed a frontal sinus cyst and subperiosteal abscess. Emergency endoscopic sinus surgery was performed under local anesthesia. The frontal sinus was filled with viscous pus and the dura mater was exposed. Thereafter, although the fever resolved, the patient continued to have persistent left-sided exophthalmos, and a residual subperiosteal abscess was suspected. Direct orbital puncture of the subperiosteal abscess was performed, but arterial blood was drawn instead of pus. At this point, a pseudoaneurysm was suspected and a contrast-enhanced CT confirmed ophthalmic artery pseudoaneurysm. Intravascular treatment, including arterial embolization was considered, but endovascular treatment of a pseudoaneurysm carries a high risk if the ophthalmic artery is involved. Therefore, the ophthalmic artery pseudoaneurysm was treated conservatively, and the exophthalmos gradually improved. A repeat CT conducted about 3 months after the onset confirmed disappearance of the pseudoaneurysm.
Forestier’s disease is characterized by sustained bone formation at the anterior margin of the spine, and with progression, it may cause symptoms like dysphagia and dyspnea. We report a case of Forestier’s disease, in which tracheotomy was required prior to orthopedic surgery due to marked narrowing of the airway. The patient was a 68-year-old man. He was examined in our department for pharyngeal discomfort, wheezing and dyspnea that had begun 3 weeks ago. Laryngeal endoscopy revealed swelling of the mucosa on the posterior pharyngeal wall and restricted movement of the arytenoid due to compression. On a plain radiograph and CT of the cervical spine, bone growth and protrusion were observed on the anterior surface of the vertebral body from the 2nd to the 5th cervical vertebra, and Forestier’s disease was diagnosed. As the airway was markedly narrowed due to restricted vocal cord movement, tracheotomy was performed under local anesthesia. Thereafter, the bone growth on the anterior surface of the spine was resected at the department of orthopedic surgery. Postoperatively, the pharyngeal edema persisted and it took a month for closure of the tracheostoma. In cases of Forestier’s disease like the present one, where impaired movement of the vocal cords and pharyngeal edema are observed prior to surgery performed to resect hyperostosis in the anterior region of the spine, our experience suggests the necessity of actively considering tracheotomy, because extubation may be difficult.
Calcific tendinitis of the longus colli muscle is an inflammation of the longus colli muscle characterized by the acute onset of neck pain, swallowing pain, and limitations of neck movement. Rapid development of symptoms requires careful differential diagnosis from conditions such as retropharyngeal abscess.
We report two cases of calcific tendinitis of the longus colli muscle with an unusual location of the calcification. Both patients were referred to our hospital by an orthopedist, with the complaints of odynophagia, neck pain and limitations of neck movement. Contrast-enhanced computed tomography revealed calcifications anterior to the C4-C5 vertebral bodies and a low-density area without ring enhancement in the retropharyngeal space. We made the diagnosis of calcific tendinitis of the longus colli muscle and treated the patient conservatively.
It is not yet an adequately recognized disease among otolaryngologists. We reviewed 32 reported cases by otolaryngologists. The patients consisted of 18 men (56%) and 14 women (44%). The median age was 41 years (25–70 years old). Of the 32 patients, 17 cases (53%) were diagnosed as having calcific tendinitis of the longus colli muscle, 11 (34%) as having a retropharyngeal abscess; of the latter, 7 cases were treated by incision or puncture and drainage. In all 32 cases (100%), the calcifications were anterior to the C1-C2 vertebral bodies. The clinical presentations in our cases were similar to these reported cases. Careful differentiation is important to determine the appropriate treatment.
The patient was a 58-year-old man with contrast-agent allergy visited a nearby medical clinic with a one-week history of swelling of the neck. He was referred to our hospital with the diagnosis of a retropharyngeal abscess, because CT of the neck revealed a low-density area in the retropharyngeal space. His clinical presentation was, however, not typical for a retropharyngeal abscess, because he had no fever or neck pain. Because of the rather large swelling on the right side of the neck, we additionally performed a chest CT. Chest CT also revealed masses in the right supraclavicular space and mediastinum. Both diffusion-weighted imaging and apparent diffusion coefficient mapping on cervical MRI revealed high-intensity signals in retropharyngeal wall, suggesting that the retropharyngeal swelling represented stasis edema. We performed biopsy of the mass over the right clavicle and made the diagnosis of malignant lymphoma. Conditions that are visualized as low-density areas in retropharyngeal space on cervical CT can broadly be divided into abscess and edema. The two conditions can easily be differentiated by enhanced CT. However, our patient had contrast agent allergy, and we performed MRI as an aid to the diagnosis. Thus, we encountered a didactic case that underscored the importance of examining the whole body for clinical diagnosis.
We retrospectively analyzed the data of 140 patients with peritonsillar abscess treated at our hospital between October 2013 and August 2017. There were 102 males and 38 females, ranging in age from 15 to 85 years old, with a median age of 38 years. We examined 9 factors; the age, sex, affected side, history of diabetes, history of tonsillitis, smoking history, presence/absence of trismus, antibacterial drugs used, and the serum CRP.
Among the 140 patients, the right side was affected in 69 patients (49.3%), the left side in 67 patients (47.9%), and both sides in 4 patients (2.8%); 53 patients (37.9%) had a history of tonsillitis and 99 patients (70.7%) had a history of smoking. Bacteriological examination in 109 patients led to isolation of anaerobes in 57 patients (52.3%). Resistance to clindamycin was noted in 12.9% of patients. The average duration of hospitalization was 5.66 days. The duration of hospitalization was significantly longer in the group with trismus than in the group without trismus.
In the group treated with only antibiotics as the initial treatment, there were no significant difference in any of the characteristics between the group that needed/did not need additional surgical drainage.
Patients with familial adenomatous polyposis (FAP) are at an increased risk for thyroid cancer. FAP is known to be associated with a distinct histologic subtype of papillary thyroid carcinoma (PTC), the cribriform variant. We report the case of a 39-year-old female patient who had been diagnosed as having FAP when she was 18 years old and undergone total colectomy. Because she had nodules in the right lobe of the thyroid, a right thyroid lobectomy was performed at the same time. Twenty years later, she was detected to have polyps in the rectum, and a CT revealed nodules in the left lobe of the thyroid. Ultrasound revealed two well-circumscribed nodules with a smooth margin; fine needle aspiration cytology revealed Class IV cytology and PTC was suspected. A left thyroid lobectomy with paratracheal neck dissection was performed. Macroscopically, the resected specimen showed multiple white encapsulated nodules with well-defined borders. The histopathological diagnosis was papillary carcinoma, cribriform variant; there was no lymph node metastasis.
Because the ultrasonographic findings and macroscopic findings of the specimen were unusual for PTC (the common ultrasound findings are a hypoechoic texture, microcalcifications, and irregular margins), we reviewed the Japanese literature. We found 22 reports in the literature, with 24 cases of PTC associated with FAP. The ultrasonographic findings were described in 6 cases, and in all 6, the lesion was well-circumscribed with a smooth margin, mimicking the common findings of follicular tumors. The macroscopic findings were available for 18 cases and in all of them, the findings were consistent with those of encapsulated PTC. Although regular ultrasonographic screening of the thyroid is recommended for patients with FAP, we must be careful to not look out for the common findings of PTC, but for well-circumscribed nodules with a smooth margin.
We retrospectively analyzed the clinical characteristics and treatment outcomes of patients with maxillary sinus squamous cell carcinoma.
The patients were 22 newly diagnosed cases of maxillary sinus squamous cell carcinoma who were treated at our institute between 2005 and 2016. There were 19 males and 3 females, ranging in age from 45 to 83 years (average age 64.2 years). Our treatment protocol was as follows: All patients received chemoradiotherapy with weekly superselective intra-arterial administration of cisplatin (100–120 mg/body) (RADPLAT). Good responders at 30–40 Gy received additional radiotherapy (RADPLAT, ordinary chemoradiotherapy, or radiotherapy alone) until the total dose reached 72 Gy, whereas the other patients underwent radical surgery (partial maxillectomy, total maxillectomy or extended total maxillectomy). The latter patients were given postoperative (chemo)radiotherapy up to a total dose of 72 Gy, when histopathological examination revealed insufficient resection or a positive surgical margin.
The overall 5-year crude and disease-specific survival rates determined by the Kaplan-Meier method were 47.8% and 56.9%, respectively. The crude survival rate tended to be higher in T3 patients than in T4 patients (80.0% vs. 29.9%, p=0.077). Seven patients died of the primary disease. The cause of death was distant metastasis in 4 patients, recurrence of the primary lesion in 2 patients, and cervical lymph node metastasis in 1 patient.
These results suggest the importance of early detection and early treatment, and of the development of more effective treatment for advanced maxillary cancers, in order to further improve the survival rate.