Ryusuke Shodo

High-resolution imaging by scanning electron microscopy of semithin sections in correlation with light microscopy

In this study, we introduce scanning electron microscopy (SEM) of semithin resin sections. In this technique, semithin sections were adhered on glass slides, stained with both uranyl acetate and lead citrate, and observed with a backscattered electron detector at a low accelerating voltage. As the specimens are stained in the same manner as conventional transmission electron microscopy (TEM), the contrast of SEM images of semithin sections was similar to TEM images of ultrathin sections. Using this technique, wide areas of semithin sections were also observed by SEM, without the obstruction of grids, which was inevitable for traditional TEM. This study also applied semithin section SEM to correlative light and electron microscopy. Correlative immunofluorescence microscopy and immune-SEM were performed in semithin sections of LR white resin-embedded specimens using a FluoroNanogold-labeled secondary antibody. Because LR white resin is hydrophilic and electron stable, this resin is suitable for immunostaining and SEM observation. Using correlative microscopy, the precise localization of the primary antibody was demonstrated by fluorescence microscopy and SEM. This method has great potential for studies examining the precise localization of molecules, including Golgi- and ER-associated proteins, in correlation with LM and SEM.

Clinicopathological features of mucoepidermoid carcinoma

OBJECTIVE We aimed to examine the clinical usefulness of a new World Health Organization classification scheme for salivary gland mucoepidermoid carcinoma, and to identify the factors most strongly associated with prognosis and outcome. METHODS The clinicopathological features of 45 patients who received treatment for mucoepidermoid carcinoma between 1986 and 2010 were retrospectively investigated. RESULTS The overall disease-specific 5-year survival rate was 81.8 per cent. The rate for patients with low-grade tumours (92.5 per cent) was significantly higher than that for patients with intermediate or high-grade tumours (52.2 per cent). Univariate analysis revealed that five factors were significantly associated with five-year survival: age, tumour stage classification, lymph node status, histological grade and treatment method. Four factors were significant in multivariate analysis: age, sex, tumour stage classification and lymph node status. CONCLUSION The new World Health Organization classification was useful in predicting disease progression in patients with mucoepidermoid carcinoma. Patients with high-grade tumours or other prognostic factors positively associated with disease progression should be carefully evaluated and monitored.

A case of fatal interstitial pneumonia during treatment of radiotherapy plus cetuximab for patient with head and neck carcinoma

We report a case of fatal interstitial pneumonia in a patient treated with radiotherapy plus cetuximab for head and neck carcinoma. The patient was an 86-year-old man with laryngeal squamous cell carcinoma (T2N0M0). Cetuximab was given in combination with radiotherapy; however, the patient developed dyspnea on day 30 and computed tomography findings confirmed a diagnosis of interstitial pneumonia. Noninvasive positive pressure ventilation was immediately started in conjunction with steroid pulse and endotoxin adsorption therapy. This led to temporary relief of symptoms. However, a subsequent relapse was resistant to steroid pulse therapy, and the patient died from interstitial pneumonia on day 47.

Multicenter phase I/II study of chemoradiotherapy with high-dose CDDP for head and neck squamous cell carcinoma in Japan

OBJECTIVE Recent data indicated that concurrent chemoradiotherapy (CCRT) using high dose cisplatin (CDDP) is the most useful treatment for advanced head and neck squamous cell carcinoma (SCC). Regarding the dose of CDDP, 100mg/m2 is most recommended in Western countries. However, in terms of a balance of efficacy and adverse events, appropriate dose of cytotoxic drugs such as CDDP may be different among the different ethnic groups. In this multicenter phase I/II study, we aimed to identify the optimal dose of CDDP in CCRT for patients with advanced head and neck SCC in the Japanese. METHODS Patients were eligible for inclusion if they had head and neck SCC that was treated with radical CCRT comprising whole-neck irradiation of the primary lesion and level II-IV lymph nodes on both sides. For the phase I study, a CDDP dose was 70mg/m2 for level 0, 80mg/m2 for level 1, and 100mg/m2 for level 2. Maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) were examined by phase I trial, by which CDDP dose for phase II was determined. The primary endpoint for the phase II was CCRT completion rate, and the secondary endpoint was full-dose-CCRT completion rate, the percentage of patients receiving a total CDDP dose of ≥200mg/m2, response rate, and incidences of adverse events. RESULTS A CDDP dose of 100mg/m2 was the MTD for phase I, and the recommended dose for phase II was 80 mg/m2. Forty-seven patients were evaluated in the phase II trial. CCRT completion rate, full-dose-CCRT rate, and the percentage of patients receiving a total CDDP dose of ≥200mg/m2, were 93.6%, 78.7%, and 93.6%, respectively. One patient (2.1%) developed grade 2 renal dysfunction, and no patient developed febrile neutropenia or a grade 4 adverse event. CONCLUSION The present phase I study indicated that a CDDP dose of 80mg/m2 is the optimal dose in terms of safety. The phase II study revealed that CCRT completion rate, response rate, and rates of adverse events were not inferior for a CDDP dose of 80mg/m2 as compared with a dose of 100mg/m2, and a dose of 80mg/m2 is therefore recommended in CCRT for the Japanese. This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR; identification No. UMIN000010369).

Asymptomatic diffuse idiopathic skeletal hyperostosis as a potential risk for severe dysphagia following partial laryngopharyngectomy

Abstract Diffuse idiopathic skeletal hyperostosis (DISH) is a common disease in which ossification lesions occur in the bones including the vertebrae. Dysphagia may occur in advanced cases, but there are few cases that require treatment. A 68-year-old man was diagnosed with hypopharyngeal cancer of the left pyriform sinus and asymptomatic DISH on the anterior cervical vertebrae. Due to prior history of radiation, partial laryngopharyngectomy was performed. After surgery, severe dysphagia and aspiration pneumonia occurred, and the patient needed to undergo total laryngectomy. It was determined that dysphagia was due to multiple factors, including insufficient laryngeal elevation and esophageal compression by osteophytes of DISH. Asymptomatic DISH can cause severe dysphagia after partial laryngopharyngectomy. We suggest that evaluation of the swallowing function and surgical options, including laryngeal suspension and cricopharyngeal myotomy should be considered when performing partial laryngopharyngectomy in patients with DISH, even if they demonstrated no difficulties in swallowing before treatment.

Clavicle fracture with osteomyelitis after neck dissection and post-operative radiotherapy: case report

BACKGROUND Non-traumatic bone fractures in cancer patients are usually pathological fractures due to bone metastases. In head and neck cancer patients, clavicle stress fractures may occur as a result of atrophy of the trapezius muscle after neck dissection in which the accessory nerve becomes structurally or functionally damaged. CASE REPORT A 71-year-old man underwent modified radical neck dissection with accessory nerve preservation and post-operative radiotherapy for submandibular lymph node metastases of tongue cancer. Four weeks after the radiotherapy, a clavicle fracture, with osteomyelitis and abscess formation in the pectoralis major muscle, occurred. Unlike in simple stress fracture, long-term antibiotic administration and drainage surgery were required to suppress the inflammation. CONCLUSION As seen in the present patient, clavicle stress fractures may occur even after neck dissection in which the accessory nerve is preserved, and may be complicated by osteomyelitis and abscess formation owing to risk factors such as radiotherapy, tracheostomy and contiguous infection.