The Epstein-Barr virus （EBV） is closely associated with the pathogenesis of nasopharyngeal carcinoma （NPC）. NPC is radiosensitive and chemosensitive, and so various combinations of RT and chemotherapy such as concurrent chemoradiotherapy, adjuvant chemotherapy, and alternating chemoradiotherapy have been investigated. In this study, we evaluated the efficacy of alternating chemoradiotherapy in patients with NPC.
We recruited NPC patients who were receiving alternating chemoradiotherapy at Kanazawa University Hospital. Alternating chemotherapy was performed by initially administering chemotherapy and then performing radiotherapy （wide field）, chemotherapy, radiotherapy （shrinking field）, and chemotherapy. Every patient received chemotherapy with cisplatin （days 6, 7） and 5-fluorouracil （days 1-5）. From 2013, we changed from radiotherapy with shrinking field to intensity modulated radiotherapy. No fatal toxicities related to the treatment were observed. The 3-year PFS and OS were over 70%. Alternating chemoradiotherapy led to similar or higher survival rates compared with concurrent chemoradiotherapy. The number of chemotherapy courses was found to have a significant impact on OS and PFS. We also analyzed the prognosis and acute toxicities and efficacy with or without IMRT, but did not find any significant difference. Perhaps the observation time with patients who received IMRT was short.
On the other hand, there is little doubt regarding the need for concurrent chemotherapy. There has been uncertainty about the magnitude of the benefit attributed to the adjuvant phase. It would be ideal if we could select high-risk patients only to avoid unnecessary toxicities. For this purpose, blood EBV-DNA quantification is the best method to distinguish NPC patients from those with other diseases and healthy controls. Blood EBV-DNA quantification is also useful to detect the recurrence of NPC. However, blood EBV-DNA quantification reflects dead NPC cells, and so does not reflect the viability of cancer. We also assess new biomarkers, miRNA quantification, to detect recurrent NPC patients.

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We investigated the treatment outcomes in 88 patients with hypopharyngeal squamous cell carcinoma （HPSCC） treated with transoral laser microsurgery （TLM） and 53 patients with locally advanced laryngeal squamous cell carcinoma （LALSCC） treated with selective radiotherapy and concomitant intra-arterial cisplatin （RADPLAT） from 2001 to 2017. Based on the tumor–node–metastasis （TNM） staging, the HPSCC patients were classified into seven groups: Tis （n＝24）, T1 （n＝27）, T2 （n＝30）, T3 （n＝7）, N0 （n＝73）, N1 （n＝5）, and N2a-b （n＝10）. Likewise, the LALSCC patients were classified into the following seven groups: T2 （n＝10）, T3 （n＝39）, T4a （n＝4）, N0 （n＝44）, N1 （n＝1）, N2b （n＝5）, and N2c （n＝3）. The 5-year local control, disease-specific survival （DSS）, and overall survival （OS） rates of the patients with HPSCC were 81.0%, 92.8%, and 76.2%, respectively, while the 5-year laryngectomy-free survival （LFS） and laryngo-esophageal dysfunction free survival （LEDFS） rates were 75.2% and 62.5%, respectively. The 5-year locoregional control, DSS, and OS of patients with LALSCC were 84.5%, 86.7%, and 81.6%, respectively, while the 5-year LFS and LEDFS rates were 78.7% and 76.6%, respectively. None of the patients presented with a pharyngeal fistula or persistent dysphagia after the TLM. The incidence rates of grade 3 or 4 tumors in patients who received RADPLAT were much lower than those reported previously. TLM and RADPLAT are feasible and safe for laryngeal preservation.

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Squamous cell carcinoma （SCC） of the temporal bone is extremely rare, making it difficult to establish standard treatment guidelines. In this report, we reviewed the records of 103 temporal bone SCC patients treated between 1999 and 2018 at Kyushu University Hospital. The primary diseases were classified as T1 in 13 patients, T2 in 19 patients, T3 in 21 patients and T4 in 50 patients. The disease-specific survival rate was 92％ in T1, 87％ in T2, 87％ in T3 and 37％ in T4. Generally advanced temporal bone SCC has a poor survival rate. However, resection with a tumor-free surgical margin significantly improved patient survival even in advanced cases. Thus, radical surgery with a tumor-free margin could be a standard therapy even for cases of advanced temporal bone SCC.

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Recently, human papilloma virus （HPV） has been found to be a causative agent of oropharyngeal carcinoma. However, the mechanism of HPV carcinogenesis and the relationship with HPV and clinical features of oropharynx cancer are uncertain. In cervical cancer, which is the same as HPV carcinogenesis, HPV persistently infects cervical epithelial cells, and two oncoproteins E6/E7 of HPV inactivate the tumor suppressor gene p53/Rb, respectively. As a result, abnormally proliferating cells are generated, which develop cancer through integration of the HPV genome into the host genome. APOBEC3, which originally provides endogenous immunity against viral infection, induces genetic mutations in the genomes of HPV and host cells, and could be involved in the above process.

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10 years have passed since the head and neck cancer specialist system was established We evaluated the situation of the equalization of head and neck cancer treatment from the viewpoint of local cancer centers. There are four treatment areas in Miyagi Prefecture: two in the Sendai area and one in each of the other treatment areas （5 in total）. In addition, a total of seven hospitals, including Tohoku University Hospital and Miyagi Prefectural Cancer Center, which are core hospitals of the prefectural alliance for cancer treatment, provided cancer treatment. Three training facilities designated by the Japan Society of Head and Neck Surgery were accredited: Tohoku University Hospital, Miyagi Prefectural Cancer Center （both are prefectural cancer medical care cooperation base hospitals） and Sendai Medical Center. Only about 10％ of the patients received treatment at institutions other than those designated by the Japan Society of Head and Neck Surgery. In addition, because the area does not have enough specialists relative to its size, one method to equalize the medical care for head and neck cancer is the transfer of specialists to areas where head and neck cancer treatment is not available to provide medical care at regional base hospitals.

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Nivolumab was approved for platinum refractory recurrent and metastatic head and neck carcinoma in 2017. Pembrolizumab as first-line treatment for recurrent and metastatic head and neck carcinoma was reported in 2019 and it is predicted that the first-line treatment will change. Many immune-related adverse events were reported by immune checkpoint inhibitors. Therefore, we should start administering steroid to control inflammation and severe IrAE. In addition, some patients should be put on steroid for a long time because of anti-inflammation. Furthermore, when cisplatin, which is one of the key drugs for head and neck cancer, is administered, steroid can prevent delayed nausea.
Here, we review the important points and observations on the use of steroid against irAE.

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Metastasis of the lateral retropharyngeal lymph nodes （LRPNs） from oral squamous cell carcinoma is very rare, and there are few case reports in the literature. In this study, we researched reported cases in the Japanese literature, including our own cases, to confirm the clinical characteristics of oral cancer patients with LRPN metastases. We analyzed: age and gender of the patients, primary tumor locations, T-stage, histological differentiation, N-stage, number and size of LRPN metastases, LRPN metastasis side （ipsilateral or contralateral to the primary site, neck metastasis）, duration from treatment of the primary site and neck or neck metastasis to LRPN metastasis, relationship between late LRPN metastasis and treatment methods of the primary site and/or neck, treatment methods of LRPN metastases, treatment results, survival time from detecting LRPN, and prognosis. As a result, only 22 cases could be analyzed. LRPN metastasis develops less frequently in oral squamous cell carcinoma, may develop contralaterally （23％）, and is correlated with low survival rate （18％）. Surgical treatment is suggested as a better method because of its high control rate of LRPN metastasis （80％）. However, in order to improve prognosis, earlier detection by imaging diagnosis should be performed.

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Objective: The objective of this study was to evaluate the safety of chemoradiotherapy with high-dose cisplatin （high-dose CDDP + RT） for squamous cell carcinoma of the head and neck in a community hospital.
Patients and Methods: A total of 18 patients who underwent high-dose CDDP+RT in our department between September 2015 and August 2018 were considered for this study. Treatment completion was defined as the delivery of full-dose irradiation and a cumulative cisplatin dose of more than 200mg/m².
Results: Of the 18 patients, 16 patients （88.9%） received more than 200mg/m² of cisplatin dose and 11 patients （61.1%） received 300mg/m². Full-dose irradiation was performed in all patients and thus the treatment completion rate was 88.9%. Grade 3/4 acute toxicity included neutropenia （50%）, febrile neutropenia （11%）, thrombocytopenia （11%）, nausea （28%） and mucositis （23%）.
Conclusions: High-dose CDDP + RT at a community hospital is feasible.

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Because malignant tumor cells cause the production of blood coagulation agent and activation of platelet-induced agglutination, cancer patients are in a state of hypercoagulability and easily develop thrombosis. We report four cases who developed thrombosis during treatment for head and neck cancer. In two cases, clots formed in lower limb arteries; in the other two cases, clots formed in the pulmonary artery and brachial vein. Two cases recovered and remain alive now, but two cases died suddenly within a few days from the onset of thrombosis. There are various types of patients with thrombosis, and the treatment and severity differ accordingly. However, cases that develop thrombosis are forced to discontinue cancer treatment and may die suddenly. Since it is predicted that the number of patients with cancer who survive for a long time will increase in the future, greater awareness of thrombosis as a disease state is needed.

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The background, treatment outcome, and state of postoperative ingestion/swallowing were investigated in 6 patients treated with partial frontolateral laryngectomy between 2006 and 2017. All patients were male aged 54-83 years old （median: 71 years old）. The histopathological diagnosis was spindle cell carcinoma in one patient and squamous cell carcinoma in all other patients. Two patients received primary treatment and the stage was T1a, respectively, and 4 patients received second-line treatment for recurrence and the stage was T1a in one and T2 in 3. The time to recurrence after primary treatment in patients treated for recurrence was 12-110 months （median: 40.5 months）. No patient died of the laryngeal cancer after partial frontolateral laryngectomy. The survival times in 6 patients after partial frontolateral laryngectomy ranged from 16 months to 162 months （median: 34 months）.
The postoperative ingestion/swallowing function was mostly favorable, but one patient required intervention with swallowing rehabilitation by a speech-language-hearing therapist. However, all patients were able to eat normal home-cooked food after discharge and no patient developed aspiration pneumonia after discharge.
Postoperative recurrence occurred in only one patient. The possibility of radiation-induced cancer and the presence of subglottic downward advancement were considered as the causes.

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Thyroid follicular tumors are divided into follicular adenoma and follicular carcinoma. Cell heterogeneity does not contribute to discrimination between benign and malignant. For the pathological diagnosis of follicular carcinoma, it is necessary to confirm at least one of capsular invasion/vascular invasion of tumor cells or metastasis to the outside of the thyroid gland. Many researchers have examined this aspect of follicular tumors, and as a result, it is considered that there is a significant difference between follicular cancer and benign nodal lesion, but that this difference alone is insufficient for discriminating between benign and malignant.
Since examined improve the diagnostic accuracy of preoperative examination of follicular carcinoma by evaluation of a combination of these test results. Based on the possibility of application to multi-modality imaging, we report the results of our study.
Patients with thyroid follicular lesions and benign nodular lesions who underwent surgery in our department between March 2015 and July 2018 were targeted. The breakdown was 10 cases of follicular cancer （minimally invasive 6, oxyphilic cell carcinoma 3, widely invasive 1）, and 25 cases of benign follicular tumor （adenomatous nodules 9, adenomatous goiter 8, follicular adenoma 6, oxyphilic cell adenoma 2）. We conducted blood flow imaging analysis by ultrasonic examination, 201Tl late image accumulated findings by RI examination, and diffusion weighted image （DWI） and ADC value by MRI examination. In this study, results were obtained by combining the three methods to improve the accuracy of diagnosing follicular cancer. The multi-modality assessment was considered to contribute to treatment strategies for follicular lesions.

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We retrospectively reviewed the records of 68 patients with oropharyngeal squamous cell carcinoma who had undergone initial treatment in the Department of Otolaryngology, Head and Neck Surgery, Hamanomachi Hospital between 2009 and 2017. We compared therapeutic outcomes of p16-positive with p16-negative cases, referring to Unio Internationalis Contra Cancrum （UICC） diagnostic criteria version 7 and 8. Of 68 （58.5％） patients, 38 were diagnosed as p16-positive. The 3-year disease-specific survival rate of all patients, p16-positive, and p16-negative patients were 78.5％, 74.1％, and 84.7％, respectively. Referring to UICC version 8, the 3-year disease-specific survival rate （3DSS） of p16-negative patients in each clinical stage was stageⅡ: 100％, stageⅢ: 66.7％, and stageⅣa: 70.6％, whereas 3DSS of p16-positive patients was stage I: 93.8％, stageⅡ: 83.3％, stageⅢ: 77.1％, and stageⅣ: 0％.

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We report the usefulness of the combined application of the pedicled buccal fat pad flap （BFPF） and the “mucosal defect covered with fibrin glue and polyglycolic acid sheet （MCFP）” method in covering defects after oral cancer resection. Six cases are included in this report, in which the combined method was used to cover the mucosal defect after oral cancer resection. The ages of the patients ranged from 70 to 82 years old. The origins of tumor were upper gingiva in 2 cases （T2 and T3）, lower gingiva in 1 （T3）, hard palate in 1 （T3）, buccal mucosa in 1 （T3）, and oral floor in 1 （rT3）. The performed operations included partial maxillectomy in 3 cases and neck dissection in 3. The wound was epithelialized in 23 to 178 days. Oral intake was regained in 4 to 15 days postoperatively, without permanent dependence on tube-feeding. The postoperative speech function was moderate or excellent by Hirose’s criteria. Combining the BFPF and the MCFP method enhances their potential as a minimally invasive method for mucosal defects after oral cancer resection.

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We report a case of malignant peripheral nerve sheath tumor （MPNST） at the ethmoid sinus. A 64-year-old man visited our hospital because of protrusion of his left eye. MRI scan revealed that a tumor of the ethmoid sinus had invaded the left eye socket and the bone at the skull base. Pathological examination revealed that the tumor was MPNST. We resected the tumor including the left eyeball and skull base bone. After resection, we reconstructed his left eye socket for an ocular prosthesis with a free flap.

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Carotid sinus syndrome （CSS） is a well-known disease that may accompany repeated syncope attacks. Although rare, CSS may be caused by head and neck cancers. We report the case of a 50-year-old man with platinum-refractory residual oropharyngeal carcinoma who developed CSS. He manifested repeated syncope attacks with bradycardia, and underwent pacemaker implantation. Bradycardia disappeared after implantation, but syncope attacks remained due to a decrease in blood pressure. Computed tomography （CT） and positron emission tomography-CT revealed left neck lymph node metastasis with carotid artery invasion, which was considered to be the cause of CSS, and multiple lung metastases. We then administered nivolumab as first-line palliative chemotherapy to relieve CSS. Four courses of nivolumab were given and then stopped because of drug-induced pneumonia. After nivolumab treatment, the syncope attacks disappeared, pain was alleviated, and his condition improved.
To the best of our knowledge, this is the first report of a case of CSS due to a residual tumor immediately after definitive chemoradiotherapy. Pacemaker implantation and nivolumab turned out to be effective for treating platinum-refractory recurrence with CSS in this patient. The present case also suggests that we should suspect CSS upon encountering a head and neck cancer patient with repeated syncope attacks.

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Three cases of advanced maxillary sinus cancer with orbital invasion were treated with intra-arterial （IA） chemoradiation therapy including internal carotid arterial infusion to preserve ocular function. One case needed total maxillectomy with exenteration and two cases were inoperable. Two cases received alternating chemo-radiotherapy with two courses of intra-venous chemotherapy （TPF; taxotere, cisplatin, 5FU）. IA infusion of CDDP （35-50mg/m²/week） was administered through the microcatheter from the external carotid arterial sheath （ECAS） inserted into the superficial temporal artery. Total CDDP dose was 175-400mg/m², and total CDDP dose to the internal carotid artery was 80-115mg/body. Intensity modulated radiation therapy （IMRT） was applied to three cases without exceeding the maximum dose to the optic nerve of more than 60Gy. Although the follow-up period was short, local control within the orbita and ocular functions were preserved in three cases. IA chemoradiation therapy including internal carotid arterial infusion might be useful to preserve ocular function.

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