We have already reported that p16 positive/p53 negative oropharyngeal squamous cell carcinomas （OPSCCs）, which are supposed to represent HPV related OPSCCs with less influence of carcinogenesis （smoking）, showed extremely good prognoses. In this study, we clarify the characteristics of this category of OPSCC in comparison with other OPSCCs. This is a retrospective review of 100 consecutive cases with OPSCC between 2004 and 2016. Ninety-four cases were enrolled in this study. There were 45 cases with p16 positive/p53 negative OPSCC （category A） and 49 cases with other OPSCCs （category B）. We compared the survivals and the incidences of multiple malignancies between the categories. Forty-seven patients who received the neoadjuvant chemotherapy （NAC） were enrolled in another investigation. The relationships between the categories and the response of NAC measured by RECIST, the change of accumulation of FDG （SUV） in PET/CT, and pathological findings were examined. The patients in category A showed significantly better survival rates, including overall survival （OS）, disease-specific survival （DSS） and recurrence-free survival （RFS） （3-year OS：90％ versus 72％, p＝0.02, 3-year DSS：95％ versus 76％, p＝0.03, and 3-year RFS：88％ versus 52％, p＜0.01）. The patients in category A also demonstrated a lower incidence of multiple malignancy （12％ versus 45％, p＜0.01） in 5 years. The responses of NAC were significantly better in category A, when estimated using PET/CT （SUV diminishing rate＞55％＝81％ versus 47％, p＝0.04） and pathological findings （pathological response rate＝80％ versus 27％, p＝0.02）. We are now designing a de-intensive therapy for this category of advanced OPSCCs using transoral surgery and neck dissection in combination with NAC.

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We examine considerations for determining treatment strategies in sinonasal malignancies with skull base invasion. A retrospective study was conducted of 92 patients （including 68 sinonasal malignancies） who had been treated in Tohoku University Hospital. Twenty patients underwent skull base surgery after pretreatment diagnostic imaging for dural invasion. Gadolinium enhanced MRI showed dural enhancement in 18 of these patients. Subsequent histological examination indicated that 10 of these 18 had dural invasion. Low apparent diffusion coefficients （ADC） had been previously detected in these patients. Eighteen patients in our study had been treated with RADPLAT. In 7 of the 18 patients, computed tomography angiography （CTA） and digital subtraction angiography （DSA） revealed that the blood flow to the tumor was from a branch of an internal carotid artery such as the ophthalmic artery, rendering the treatment ineffective. Six of these 7 patients were T4b patients. For the 20 TPF-CCRT patients the five-year overall survival rate was 58.3％ and the five-year progression-free survival rate was 50％. Based on these results, we suggest that diagnostic imaging prior to either surgery or RADPLAT treatment is important. The combination of dural enhancement and low ADC appears to indicate that surgery is an appropriate treatment. ADC and DSA imaging is critical prior to RADPLAT since only tumors fed from the external carotid will respond to treatment. When surgery and RADPLAT are not indicated, TPF-CCRT would be the best treatment option.

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With the progress of genome research, precision medicine, which aims to select the optimal treatment based on genomic data from individual patients, is now attracting increasing attention in the field of cancer treatment. In the USA, a multiplex gene panel test using next-generation sequencing is now rapidly expanding in daily clinical practice. Our hospital has introduced a multiplex gene panel test （OncoPrime™）, which meets the Clinical Laboratory Improvement Amendment （CLIA） quality, for the first time in Japan since April 2015. Among 141 patients who received the OncoPrime™ test, some patients received clinical benefit from the therapy selected based on genomic data. We are now proceeding to develop a database system which integrates both genomic and clinical data of patients who receive a multiplex gene panel test in collaboration with six university hospitals. In the near future, precision medicine will play a pivotal role in the field of cancer treatment.

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Transoral surgery （TOS） for early laryngo-pharyngeal cancer has been reported, and is becoming a major strategy in the world. Recently, transoral robotic surgery （TORS） for laryngo-pharyngeal cancer is becoming popular as a new treatment modality, and surgical robots have become widely used around the world since receiving United States FDA approval in 2009, but they have not been approved by the Japanese FDA. In Japan, unique methods such as TOVS and ELPS have been developed due to the device-lag problem. When performing TOS, knowledge of transoral endoscopic anatomy is needed. The preparation of machines for TOS is complex. Therefore, TOS methods are often used at all facilities. This paper describes the transoral endoscopic anatomy, aspects of preparations for TOVS and ELPS, and the utility of the devices.

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Many kinds of pharmacotherapy have been approved as standard treatments for locoregionally advanced head and neck squamous cell carcinoma （LAHNSCC）, and treatment options have increased. However, in order to achieve the anticipated effect, we must comply with the eligibility criteria of phase 3 trials, and clarify the endpoint of treatment （improvement of survival time or organ/function preservation）, and consider stratification factors （surgical resectability, HPV status, or subsites）. Maintenance of QOL is an important role of medical treatment. Therefore, reduction of acute and delayed adverse events is an important issue. We reviewed previous phase 3 trials to find answers to these issues and clarified the role of pharmacotherapy as follows: 1） To explore patients in whom organs/function can be preserved by radiation therapy with induction chemotherapy, 2） To prolong the survival time of surgically unresectable disease and to improve organ and function preservation of surgically resectable disease with concurrent chemoradiotherapy （CCRT）, 3） To improve loco-regional control and prolong survival time of high-risk patients with postoperative CCRT, and 4） Standard fractionated CCRT is the most effective treatment to prolong survival time and improve organ and function preservation.

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A newly developed mobile-type cone-beam CT （mCBCT）, which was introduced to the Kyoto University Hospital as a part of the high-spec surgical room project, is presented. This is a cone-beam CT, which is compact and offers high image resolution, with superior stiffness and stability and so can be moved between operating theaters without calibration. Although there are limitations such as limited size of the field of view and the material of the operating table, the target organs of otorhinolaryngological surgeries are suitable for image acquisition by this machine. This paper describes clinical examples of intra-operative CT imaging by the mCBCT in sinusitis, cochlear implant, and parapharyngeal tumor cases.

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In recent years, 3-dimensional computed tomography （3D-CT） has made it possible to evaluate the form of facial bone in great detail, but CT can not be easily performed during surgery under general anesthesia. Although ultrasonic examination can be used for evaluation, it cannot obtain a whole image of the facial bones. Mobile intraoperative cone beam CT （3D Accuitomo MTM, J. Morita Mfg. Corp.） was introduced at Kyoto University Hospital in 2015, and is used in surgery for facial bone fractures and deformities. Intraoperative CT and the immediate reconstruction of 3D images enables precise intraoperative evaluations to be conducted. Mobile intraoperative cone beam CT seems to be useful for improving the accuracy and safety of surgery. Our experience of using mobile cone beam CT in plastic surgery is described.

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Differentiated thyroid carcinoma （DTC） is generally associated with an excellent prognosis. However, patients with invasion of the surrounding organs, including the upper aerodigestive tract, or certain aggressive microscopic variants are known to have a relatively poor prognosis and quality of life. Kinase inhibitor therapy was approved for patients with radioactive iodine-refractory DTC with metastatic, rapidly progressive, symptomatic disease and/or unresectable locally advanced recurrent disease. However, almost no studies have been conducted on whether locally advanced recurrent tumors are surgically resectable. Locally advanced recurrent tumors may invade great vessels （such as the carotid and vertebral arteries）, the parapharyngeal space, or the mediastinum, making surgical treatment challenging. Many patients with locally advanced recurrent tumors have concurrent distant metastases. Surgical decision-making in these patients must consider the prospects of complete resection, functional prognosis, and life expectancy. In our own experience, good local control can be achieved in patients with locally advanced recurrent disease that undergo complete resection. However, several mortalities were attributed to distant metastasis. Therefore, the optimal treatment for these tumors is complete surgical resection. The indications for surgery for locally advanced recurrent tumors should be investigated and discussed.

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Patients with head and neck cancer are often already malnourished before the start of treatment, therefore nutrition management is essential for enhancing the effectiveness of therapy. Carbohydrate metabolism in cancer cells is mainly anaerobic glycolysis with poor energy production efficiency, which contributes to an increase in energy consumption in cancer patients. When considering the nutrition management of cancer patients, the supply of nutrients to create an aerobic glycolysis-dominated environment is the key point.
Nutrition management before and after cancer treatment is also important. Anti-cancer drugs used in chemoradiotherapy are transported to the parts of the body by binding with albumin in the blood. Therefore, in the low albumin state, the blood concentration of the antitumor agent rises immediately and side effects easily develop. Malnutrition is regarded as one of the risk factors for complications in chemoradiotherapy. The importance of nutrition management in the perioperative period has been widely recognized in recent years. In the field of gastroenterological surgery, the postoperative early recovery protocol ″ERAS″ has already been generalized. However, in the field of head and neck surgery, standard perioperative management methods have not yet been established.

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A new manual on infection control of otolaryngological endoscopy has been published, in which chlorine dioxide is described as a second-line disinfectant after peracetic acid, orthophthalaldehyde and glutaraldehyde. Chlorine dioxide itself is not recognized as a high-level disinfectant, but its use for disinfecting gastrointestinal endoscopes is approved by the Japanese government. In this study, we investigated bacterial contamination of gastrointestinal endoscopes before/after disinfecting with chlorine dioxide. In 65 cases of upper gastrointestinal endoscopy and 60 cases of colonoscopy, 10ml of saline was injected into the channel of the endoscope and the washing solution was collected into culture media, before/after cleansing. Bacteria were identified in all cases before cleansing. In contrast, all of the upper gastrointestinal endoscopes and 59 of the 60 colonoscopes were negative for bacteria after cleansing. Only one case of colonoscope was positive for E. coli by enrichment culture. No damages to the endoscopic instruments were caused and no adverse events related to the skin and lungs of medical staff occurred in the endoscopy room. The cleansing and disinfecting device with chlorine dioxide was effective in eradicating bacteria on gastrointestinal endoscopes.

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Monopolar, bipolar and BiClamp® modes which can be used in VIO®3 are useful for head and neck surgery. The preciseSECT mode of a monopolar device is able to reduce carbonization of soft tissues and to detach tissues with a constant pressure. As a result, it is possible to stop bleeding effectively. The softCOAG® bipolar mode has functions for coagulating tissues without carbonizing soft tissues under low-temperature heating and is able to stop bleeding satisfactorily. By using the autoCUT bipolar mode, coagulated vessels can be cut without scissors. With regard to the thermoSEAL® mode, after placing the BiClamp® handpiece into the proper position on blood vessels with surrounding tissues and pushing the pedal, electrocoagulation without carbonization of soft tissues starts. Vessels are surely sealed and it is possible to cut them by scissors. Quick and reliable hemostasis can be achieved by beginners as well as veterans by using VIO®3, classic suture ligation techniques during operation are decreased, and effective operation can be completed quickly.

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Bone and soft tissue sarcomas originating from the head and neck account for about 1％ of all head and neck malignancies, and 15％ of all bone and soft tissue sarcomas, but the exact number of patients in Japan is unknown. Sarcomas have wide pathological variations and there are differences in standard treatment strategies depending on the pathological diagnosis, so a multidisciplinary team is needed for treatment. In the current review, the standard treatment strategy for sarcomas is discussed, especially the differences in non-surgical treatments based on the pathological diagnosis. Epidemiology and prognoses of each pathology are also reviewed.

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Typically, the treatment of oral cancer in very elderly patients should be by brief surgical therapy because chemotherapy and irradiation tend to be exhausting for them. The authors report here on a case they experienced in which the lost part of the maxilla after excision of maxillary gingival cancer in a very elderly patient was reconstructed using a nasolabial flap combined with pedicled buccal fat pad, and a positive outcome was achieved. The patient was an 87-year-old female. The chief complaint upon referral was gingival lesion on the maxillary left side, which was diagnosed by biopsy as squamous cell cancer. A TNM classification of T2N0M0 was decided after further evaluations. Under general anesthesia, partial maxillectomy and closure of oro-antral and oro-nasal communications using a nasolabial flap combined with pedicled buccal fat pad were performed. The combination flap became stable early in the postoperative period. Oral intake was allowed on day 7 and the patient was discharged on day thirteen after surgery. We conclude that this reconstructive surgery may be a useful method after excision of maxillary gingival cancer in very elderly patients.

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Enteral nutrition is often required for patients with head and neck cancer who are undergoing radiotherapy （RT）. In some cases, percutaneous endoscopic gastrostomy （PEG） tube placement before RT is preferred to reduce the severity of nutritional compromise. However, how factors influence the occurrence of dysphagia in these patients is unknown. Moreover, no appropriate guidelines have been established to predict whether a PEG tube should be placed or not. In this retrospective study, we examined 58 patients treated at the Department of Oral and Maxillofacial Surgery, Nara Medical University Hospital. The prediction model used in the multivariate studies included sex, Charlson Comorbidity Index, serum total protein, and range of RT as independent risk factors of dysphagia. The prediction model demonstrated good discrimination and calibration. Before RT, more attention needs to be focused on these risk factors of dysphagia during the therapy. We recommend using this prediction model when assessing the need for PEG placement.

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Salivary duct carcinoma （SDC） is an aggressive tumor with high rates of local recurrence and distant metastasis. Therapeutic options for the patient with local recurrence or distant metastasis of SDC are limited. Immunohistochemical studies have demonstrated that androgen receptor expression is high in SDC. We present a case of a 64-year-old man with locally advanced androgen receptor-positive submandibular gland SDC. He underwent submandibular gland resection with modified neck dissection and postoperative concurrent chemoradiation therapy. Local recurrences were observed 6 months later, and multiple bone metastases were found 17 months later. Then, anti-androgen therapy was started with oral bicalutamide （80mg/day）. Radiotherapy of 30Gy/10Fr was added for the treatment of his backache. After 7 months of bicalutamide treatment, MRI findings showed that the bone metastases had decreased obviously. Breast swelling appeared as a possible adverse effect. He continued bicalutamide treatment for more than 12 months.
We consider that anti-androgen therapy is a beneficial therapeutic tool for patients with progressive SDC.

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Anaplastic thyroid carcinoma （ATC） is an aggressive disease with poor prognosis. There are few reports on long-term survival by multimodal therapy. We report 21 cases of ATC treated in the Saitama Medical University International Medical Center from 2007 to 2015. Prognostic Index （PI）, inflammatory biomarkers, immune checkpoint molecule, and whether radical surgery was performed or not were evaluated.
The median survival time （MST） was 15.4 months in the radical surgery group, but was 2.6 months in the non-surgery group, showing a significant difference （p＜0.001）.
Of the 11 ATC patients, PD-L1 expression was seen in 6 （54.5％）. This result suggests that immunotherapy might be useful for these cases.

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Metastatic （M1） disease is the state in which a malignant tumor has generalized and the principal treatment is drug therapy. However, for head and neck cancer with distant metastases at initial presentation, local control is important for maintaining Quality of Life （QOL）. We retrospectively reviewed 11 cases of head and neck cancer with distant metastases at initial presentation at our hospital from January 2014 to June 2016. Initial treatments were classified as follows: no treatment group, drug therapy group, and chemoradiotherapy group. Local control rate and median survival time were 0％ and 4 months in the no treatment group, 0％ and 10 months in the drug therapy group, and 83％ and 20 months in the chemoradiotherapy group. Chemoradiotherapy was useful for long-term control of a locoregional site and for maintenance of QOL. In addition, chemoradiotherapy may be a useful treatment option for M1 disease patients for improving prognosis.

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Recently, it has been reported that a first-line treatment of platinum-based chemotherapy plus cetuximab improved outcomes for recurrent and/or metastatic head and neck cancer patients. The objectives of this study were to evaluate the results of palliative chemotherapy for recurrent and/or metastatic squamous cell carcinoma and to analyze the prognostic factors. We retrospectively examined 39 consecutive patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who received chemotherapy including cetuximab in a first-line setting. Patients consisted of 32 males and 7 females with a mean age of 68 years. The chemotherapy regimens included 5-FU/carboplatin plus cetuximab for 32 cases and paclitaxel plus cetuximab for 5 cases. The median overall survival and progression-free survival were 9.0 and 5.3 months, respectively. The incidence of grade 3 or 4 adverse events associated with chemotherapy including cetuximab was relatively low （12.8%）. These results suggested that 5-FU/carboplatin plus cetuximab as the first-line treatment was acceptable in terms of efficacy and safety. Univariate analysis revealed that patients with good performance status and those receiving second-line chemotherapy had significantly longer overall survival and progression-free survival. Multivariate analysis based on the variables with p < 0.15 on the univariate analysis （performance status, histologic type, contents of first-line regimen, with or without second-line chemotherapy） showed that good performance status and administration of second-line chemotherapy were independent factors for a better prognosis.

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There are four major treatments for head and neck cancer: surgery, chemotherapy, radiotherapy and palliative care. These treatments are associated with various acute and chronic oral complications, which lead to the suspension or discontinuation of treatment or deterioration of the patient’s quality of life. If patients manage to maintain good oral health and proper oral hygiene, complications can be minimized and treatment completed. Therefore, when head and neck cancer is diagnosed, we should refer patients to dentists who can provide oral management advice. The recent development and approval of various drugs, and the rapidly aging population in Japan, indicate that such collaboration between the medical and dental fields is more important than ever.
In this article, we summarize the characteristics of the oral cavity, the importance of oral management during chemotherapy or chemoradiotherapy for head and neck cancer, oral complications associated with molecular targeted drugs or immunotherapy for head and neck cancer, and the importance of medical and dental collaboration.

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