Phosphorylcholine (PC) is a structural component of a variety of pathogens, and anti-PC immune responses have been shown to protect mice against invasive bacterial diseases. Transcutaneous immunization (TCI) is a novel route of vaccination involving application of a topical vaccine antigen on the skin.

TCI was performed on the back skin or auricular skin of BALB/c mice using PC-keyhole limpet hemocyanin (KLH) plus cholera toxin (CT). The serum IgG and IgA after TCI in the auricular and back skin were significantly higher than in the controls. The secretory IgA antibody levels in the nasal washings, saliva and BALF after TCI in the auricular skin and back skin were also significantly higher than in the controls.

These results suggest that TCI in the auricular skin and back skin using PC plus CT is a simple approach for inducing systemic and mucosal immune responses in BALB/c mice.

Eosinophilic otitis media and sinusitis are intractable disorders characterized by eosinophilic inflammation associated with bronchial asthma, which can be considered as a unified airway disease rather than as disorders with localized eosinophilic inflammation. The production of eosinophilic mucin and emergence of antibiotic-resistant bacteria at the site of inflammation are factors that make it difficult to treat eosinophilic otitis media and sinusitis. Therefore, development of a new topical agent with adequate antibacterial activity against the antibiotic-resistant bacteria and adequate efficacy for removing the viscous mucin is being sought. Therefore, we focused on lysozyme, which has already been used as a medical preparation, with its anti-inflammatory effects and antibacterial activity against some Gram-positive bacteria. In this study, we developed lysozyme-polysaccharide conjugates using the Maillard reaction to improve the aforementioned activities and examined the antibacterial activity against antibiotic-resistant bacteria and the inner ear toxicity of lysozyme-polysaccharide conjugates, for potential development of a cleaning agent for the middle ear. Testing of the antibacterial activity of lysozyme-chitosan conjugate showed antibacterial activities against MRSA and P. aeruginosa. In addition, the inner ear toxicity study in guinea pigs revealed no obvious inner ear toxicity. Therefore lysozyme-chitosan conjugate are useful as a topical therapeutic agent (cleaning agent) and their clinical application is expected in the future.

Hemilaryngectomy or total laryngectomy compromise the quality of life of patients with laryngeal cancer, and a regenerative strategy for the surgical defect is warranted. Since the larynx is a composite organ consisting of cartilage, muscle and mucosa, it is difficult to regenerate laryngeal tissues even with the use of currently available scaffolds derived from extracellular matrix (ECM), such as collagen, gelatin or hyaluronic acid. The recently developed decellularization technology allows preparation of a complete scaffold with preservation of the architecture of an organ with preserved ECM. Such bio-scaffolds contain very few surviving cells, therefore, the risk of immune rejection after transplantation is low. Decellularization of the larynx has been attempted using animal larynges with chemical or enzymatic decellularization methods. The important points in the methodology are to effectively eliminate cells, preserve the ECM as much as possible, and maintain the growth factors and vessels to the extent possible. Recellularization with autologous stem cells is possible after decellularization. The decellularization technology may provide a complete bioscaffold for the entire larynx.

In regard to management of the neck in cases of early oral cancer, the “wait and see” policy is not recommended, because of the high frequency (more than 20%) of occult cervical metastasis and the poor survival rates. Sentinel node navigation surgery (SNNS) has been mentioned as an alternative to elective neck dissection for identifying occult cervical metastasis in cases of early oral cancer, so as to reduce the functional and cosmetic morbidity arising from neck dissection.

At Fukushima Medical University hospital, we performed SNNS in 29 patients of early oral cancer (stage I: 14, stage II: 15) from 2000 to 2007. Tc-labeled phytate was injected as the radiotracer to detect sentinel nodes (SNs). The SNs were then examined histopathologically during surgery. Six cases (21%) were proven to show metastatic SNs, and neck dissections were performed, while in the remaining 19 (65.5%) patients, unnecessary neck dissection could be avoided. The 5-year overall survival rate in the SNNS group tended to be better than that in the historical control group, which consisted of 52 patients in whom the “wait and see” policy was adopted (96% vs. 84%, p<0.05).

In Japan, a multi-institutional phase II and III study of SNNS for head and neck cancer has been started, and SNNS is useful for taking appropriate decisions in regard to neck dissection in cases with early-stage tongue cancer.

Congenital hearing loss is one of the most common sensory disorders, with genetic causes accounting for 60–70% of cases. Although recent advances in the identification of deafness genes have resulted in more accurate molecular diagnosis, leading to better determination of suitable clinical interventions, difficulties remain with regard to the clinical application of these interventions, because of the extreme genetic heterogeneity of deafness.

We first applied the Invader assay for screening 46 known mutations of 13 known deafness genes based on the mutation spectrum in Japanese hearing loss patients. The Invader assay based screening enabled us to detect deafness gene mutations in 30% of the patients. In Japan, since 2012, genetic testing using the Invader assay for deafness has been covered by social health insurance.

Toward more effective genetic testing, we adopted next-generation sequencing analysis in order to diagnose common mutations responsible for deafness and discover rare causative gene mutations. Prior to its clinical application, we investigated the accuracy of this genetic testing. We compared the results of invader assay-based genetic screening, the accuracy of which has already been verified in previous studies, with those of next-generation sequencing-based genetic testing in a large population of Japanese deafness patients, which revealed a greater than 99.98% consistency of the results between the two genetic testing methods.

More than 100 years have passed since the establishment of caloric testing, and it remains an important examination for the evaluation of vestibular function, especially the functioning of the lateral semicircular canal. There are now two new tools to evaluate vestibular function. One is the test for vestibular evoked myogenic potentials (VEMP) and the other is the video head impulse test (vHIT). The former can evaluate the functions of the otolith organs and their afferents, and the latter the functions of each of the semicircular canals and their afferents. New disease concepts have been established by means of these new examinations: inferior vestibular neuritis is one such, and we report a case herein.

A 62-year-old female presented with a history of sudden-onset vertigo that had lasted for a day. She also complained of longstanding dizziness. The audiogram showed no abnormalities. No gaze, spontaneous or positional nystagmus was noted. The caloric test yielded normal results. Cervical VEMP were absent in the left ear, thus, dysfunction of the saccule was inferred. vHIT indicated low gain with catch-up saccade in the left posterior semicircular canal. Afferents from the posterior semicircular canal are carried by the inferior vestibular nerve, therefore, we diagnosed the patient as having inferior vestibular neuritis. She was followed up under treatment with an ATP administration and vitamin B12 supplementation. cVEMP and vHIT are necessary to diagnose inferior vestibular neuritis. These examinations may be indicated in patients presenting with sudden-onset vertigo in whom caloric testing yields normal results.

Pneumothorax may occasionally occur because of damage to the pulmonary apex during urgent tracheotomy. The reported frequency of unilateral pneumothorax after tracheotomy is 0.92–1.4%, while that of bilateral pneumothorax is much lower, at 0.4%.

Herein, we report a case of bilateral pneumothorax that occurred during tracheotomy performed for a huge polypoid vocal cord.

Respiratory tract obstruction occurred during the urgent tracheostomy, necessitating provision of breathing assistance. This led to the development of extreme negative pressure in the thoracic cavity and caused the alveolar and mediastinal pleurae to be sucked into the thoracic cavity, resulting in pneumothorax. A respiratory surgeon promptly performed tube thoracostomy on both sides, and the patient’s breathing improved.

Postoperative chest radiography helped in early diagnosis of the pneumothorax. The patient underwent laryngeal microsurgery for bilateral polypoid vocal cord resection under general anesthesia, with bilateral tube thoracostomy.

Histopathology revealed an inflammatory lesion arising from the right vocal cord, with no evidence of malignancy.

When a patient develops symptoms such as pain, dyspnea, decrease in oxygen saturation on pulse oxymetry, or tachycardia after tracheotomy, bilateral pneumothorax should be considered, and chest radiography should be performed for definitive diagnosis.

When pneumothorax occurs, it is necessary to take quick measures, such as drainage of the air by tube thoracostomy.

Cetuximab is one of the effective chemotherapeutic agents used for the treatment of head and neck squamous cell carcinoma (HNSCC). It was approved for use and began to be used in Japan in the year 2012. The most frequent adverse effect of cetuximab is skin rash, such as acneiform papules, which results from skin fragility developing as a result of inhibition of EGFR, and occurs in over 95% of patients treated with cetuximab. It commonly arises in seborrheic areas such as the face, scalp, precordium and back, while also rarely occurring on the buttocks and trochanteric areas, which are exposed to minor pressure and shear. These papules or pustules frequently develop into pressure sore-like ulcers due to the excessively fragile skin. These adverse events have been reported only in a few cases of non-small cell lung carcinoma treated with gefitinib and erlotinib, but never in association with the use of cetuximab.

Herein, we report two cases of HNSCC with pressure sore-like ulcers on acneiform papules caused by cetuximab.

Both the patients were elderly males with metastatic HNSCC who were receiving cetuximab-based chemotherapy. The patients presented with acneiform papules occurred on the buttocks and trochanteric areas, which had developed pressure-sore like ulcers, causing pain. The pain decreased the quality of life (QOL) of the patients, causing the patients to become intolerant to the treatment.

Pressure-sore like ulcers not only cause annoying pain and deterioration of the QOL of patients, but also lead to treatment failure and a poor prognosis. To prevent treatment failure caused by the adverse effects of cancer chemotherapy, it is important to adopt a multidisciplinary approach to the treatment.

Chromium is a heavy metal that shows superior corrosion resistance, rigidity and luster, and has been used in various industries as a plating material, oxidizer, catalyzer and pigment. Long-term exposure to hexavalent chromium (Cr (VI)) can cause dermatitis, skin ulcers, conjunctivitis, keratitis, nasal mucositis, and/or nasal septal perforation. In addition, exposure to Cr (VI) has also been reported to increase the risk for lung cancer among workers in the chromate-producing industry. Cr (VI) has been designated as a carcinogen for lung cancer by the International Agency for Research on Cancer. Cr (VI) has also been shown to be capable of inducing stomach and colon cancers, and less often, nasal and paranasal sinus malignancies.

Herein, we report a rare case of synchronous double cancer of the lung and nasopharynx arising in a chrome-plating worker. A 60-year-old man who had been working in the chrome-plating industry for 32 years was referred to our institute with a 5-month history of neck swellings and a nodular shadow on chest X-ray. Physical, rhinoscopic and endoscopic examinations showed enlarged walnut-sized cervical lymph nodes on both sides, a large nasal septal perforation, and an ulcerative tumor in the posterosuperior nasopharyngeal wall. Computed tomography and magnetic resonance imaging revealed multiple lymph nodes measuring 30 mm in maximum diameter on both sides of the neck, a weakly enhancing protuberance in the nasopharynx, and a 30-mm nodule with spicula and vascular convergence in the lower lobe of the left lung. Endoscopic biopsies were performed, and the nasopharyngeal and lung lesions were diagnosed histopathologically as nonkeratinizing carcinoma and squamous cell carcinoma, respectively. Thoracoscopic left lower lobectomy with hilar and mediastinal dissection was performed for the lung tumor, and the nasopharyngeal cancer was treated subsequently by induction chemotherapy followed by concurrent chemoradiotherapy. The posttreatment course was uneventful, and the patient has remained free of recurrence during the 6-month follow-up period since.

There are certain physical findings that help to distinguish benign from malignant parotid tumors. It is well known that pain/tenderness, fixation to surrounding structures, and facial weakness/paralysis are important symptoms and signs associated with parotid cancer. Among 149 cases of parotid cancer, pain/tenderness was present in 79 cases, and fixation to the surrounding structures was noted in 98 cases. Some degree of facial nerve dysfunction was noted in 27 cases, while, on the other hand, none of the 668 patients with benign parotid tumors showed any evidence of facial nerve dysfunction. All of these symptoms/signs associated with malignant parotid tumors were found at higher frequencies in histologically high malignancy grade tumors than in intermediate/low malignancy grade tumors. Adenoid cystic carcinoma is well known to be characterized histologically by perineural spread, and accounts for about 80% of all parotid tumors. Pain/tenderness has been noted in 88% of patients with adenoid cystic carcinoma, a higher rate as compared to that in parotid cancer patients as a whole. Awareness of the symptoms and signs associated with malignancy is the first step towards early diagnosis of malignant parotid tumors.

We retrospectively analyzed the treatment outcomes in patients with tongue cancer at our department. The patients were 50 newly diagnosed cases of tongue cancer who were treated at our department between 2005 and 2015. There were 40 males and 10 females, aged 34 to 88 years old (average age 63.0 years). Our treatment protocol was as follows: the first-line treatment was surgery in all except the M1 cases. The resection area of the tongue was determined by the size of the tumor; i.e., partial glossectomy for T1 lesions, partial glossectomy or hemiglossectomy for small T2 (<30 mm) lesions, hemiglossectomy for large T2 (≥30 mm) lesions, hemiglossectomy or subtotal glossectomy for T3 lesions, and (sub)total glossectomy for T4 lesions. Intra-arterial chemoradiotherapy was indicated for patients with unresectable T4 and those who were unsuitable for or refused surgery. Neck dissection was performed in patients with N(+) and/or ≥large T2 lesions. Patients with a positive surgical margin, extranodal spread of the tumor and/or ≥4 metastatic lymph nodes received postoperative chemoradiotherapy (61.2 Gy with daily carboplatin (25 mg/m²)).

The overall 3-year crude and disease-specific survival rates determined by the Kaplan-Meier method were both 72.1%. The overall 5-year crude and disease-specific survival rates were 63.1% and 68.8%, respectively. The 5-year disease-specific survival rates in the stage I, II, III and IV patients were 100%, 82.5%, 57.1% and 34.1%, respectively. The disease-specific survival rates were significantly higher in the stage I than in the stage III/IV patients, and significantly lower in the stage IV than in the stage II patients. In all, 15 patients died, 11 of them from local recurrence.

These results indicate that early detection and local control are important to achieve a better survival rate in patients with tongue cancer. To improve the local control rate, the resection area of the tongue, indications for neck dissection and postoperative chemoradiotherapy, and the regimen for concurrent chemotherapy should be reconsidered, all of which must be investigated in a future study.

Synovial sarcoma is a relatively rare soft tissue sarcoma, most commonly occurring in the para-articular regions of the extremities and also in the head and neck region. To the best of our knowledge, there have been only six reports of thyroid synovial sarcoma in the medical literature. We report the case of a 49-year-old man who presented to us with the chief complaint of a cervical mass and hoarseness of the voice. Total thyroidectomy was performed, and anaplastic thyroid carcinoma was suspected on the basis of the histopathological findings. The patient received adjuvant concurrent chemoradiotherapy and adjuvant chemotherapy. One year 10 months after the surgery, the patient was diagnosed as having lung metastases, however, because of the atypically slow progression of these lesions, we reexamined the pathological diagnosis. Finally, the histopathological diagnosis of synovial sarcoma was confirmed by TLE1 immunohistochemistry. It was thought that the diagnosis was difficult, because synovial sarcoma of the thyroid gland is extremely rare, and histopathologically, poorly differentiated synovial sarcoma shows less specific features.

Herein, we report a case of Lemierre’s syndrome with thrombosis of the anterior jugular vein. A 21-year-old man without any significant previous medical history presented to us with a history of fever and sore throat. While he complained of a severe sore throat, examination of the pharynx showed no clinically significant signs. However, we noticed a palpable induration on his right neck. Computed tomography (CT) showed anterior jugular vein thrombosis and multiple subpleural tumors. On the basis of these findings, we diagnosed the patient as having Lemierre’s syndrome. He was initiated on treatment with intravenous SBT/ABPC and oral warfarin. His symptoms rapidly improved in response to the treatment. When he initially presented to the hospital, his chest radiograph showed some nodules; post-treatment, these nodules had completely resolved. Anticoagulant therapy with warfarin was continued even after the patient was discharged. Lemierre’s syndrome is a disease that follows laryngopharyngeal infection and is characterized by thrombophlebitis of the internal jugular vein.

In this case, while the patient’s symptoms were very severe, examination of the pharynx scarcely revealed any clinically significant findings. However, we were able to diagnose Lemierre’s syndrome by CT based on the detection of the induration on his neck.

Introduction: Individualized maximum repeatable dose (iMRD) is the maximum dose at which a drug can be repeated in an individual to maintain the toxicity grade at 1 or lower. In this phase I study, the starting dose to estimate the iMRD in weekly paclitaxel treatment for recurrent and/or head and neck cancer patients was determined.

Patients and Methods: Patients were enrolled according to the modified Fibonacci method. Six patients were enrolled at the starting dose of level 0 (60 mg/m²). Weekly dose adjustments were made to maintain the toxicity at grade 1 or lower. The iMRD was estimated after the 6th infusion.

Results: One patient developed grade 3 neutropenia, while another developed grade 2 neutropenia that did not resolve within 2 weeks. The iMRD could be estimated in four of the six enrolled patients. The starting dose was determined to be level −1 (50 mg/m²).

Conclusion: A phase II study of weekly paclitaxel at the aforementioned starting dose to detect iMRD has been planned. In patients for whom the iMRD can be detected, tumor dormancy therapy with weekly paclitaxel can be continued without compromising the quality of life.