Nivolumab is a fully human immunoglobulin G4 monoclonal antibody that acts as an immunomodulator by blocking ligand activation of programmed cell death 1（PD-1） receptors on T cells. Nivolumab has immune-related adverse events （irAEs）. The irAEs, which have unique characteristics different from those seen in conventional cytotoxic anti-cancer agents, are sometimes observed in several sites such as the skin, gastrointestinal tract, liver, lung, muscle, nerve and endocrine systems. To safely use nivolumab, it is very important to understand the characteristics of irAEs and to manage them in clinical practice. Thus, it is essential to collaborate with medical oncologists. This review focuses on the importance of understanding the guideline on optimal usage of nivolumab and collaboration with medical oncologists and oral surgeons.

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Recently, nivolumab has been approved for use against platinum resistance recurrence or metastasis of head and neck cancer. The advantage of this drug was tested in the checkmate 141 trial （analysis of randomized, open-label, phase 3 trial). Nivolumab showed an increase in overall survival rate compared to other single drugs.
On the other hand, the side effects of this drug are a severe problem, especially on the immune system, such as immune related adverse events （irAEs). For this therapy, oral and maxillofacial surgeons need to collaborate. The most important points are:
1. Consulting with medical oncologists to judge the patient’s condition;
2. Monitoring the general health condition and irAEs with medical oncologists;
3. Consulting with other departments related to specific organs;
4. Understanding the overall state of the patient.
In future, combination therapy （nivolumab and other cytotoxic agents, concurrent or sequential） may shed light on the treatment of advanced head and neck cancers.

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Immune check point inhibitors （ICPi） have shown activity not only in malignant melanoma but also in lung cancer, renal cell carcinoma, urothelial carcinoma and so on. With regard to head and neck cancer （HNC）, ICPi improves survival for platinum refractory HNC and many clinical trials of ICPi for HNC are ongoing. In Japan, nivolumab, one of the PD-1 antibodies, has been approved since March 2017 and can now be used in clinical practice. On the other hand, ICPi may cause immune related adverse events （irAE）, sometimes resulting in severe sequelae. Thus, medical oncologists should closely support and collaborate with head and neck surgeons and oral and maxillofacial surgeons. In order to promote such collaboration, the Japanese Society of Medical Oncology （JSMO） has established the Head and Neck Cancer Collaborative program.

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The UICC TNM classification is based on criteria for evaluating the progress of oral cancer, and it was revised to the 8th edition in 2016. The depth of invasion （DOI） in T classification and the extra nodal extension （ENE） in N classification were newly introduced. In this study, 107 tongue squamous cell carcinoma cases who underwent surgery in our department were evaluated for TNM classification according to the 7th and 8th editions. We examined the relationship between TNM classification revision, cervical lymph node metastasis and survival rate.
There were cT classification changes due to the revision of the TNM classification in 17 cases （15.9％） and pT classification changes in 6 cases （5.6％）. The number of cases of cervical lymph node metastasis decreased in cT1 and pT1, and increased in cT2 and pT2. Two cases of cT4a and pT4a in the 7th edition were classified into cT3 and pT3 in the 8th edition, so the survival rate of cT3 and pT3 in the 8th edition was lower than in the 7th edition. Three cases of pN2b in the 7th edition were classified as pN3b in the 8th edition, and 3 cases were unhappy outcomes.
This review of the TNM classification of our tongue squamous cell carcinoma cases from the 7th edition to the 8th edition led mainly to the rise of stage. The 8th edition TNM classification faithfully reflects the progress in cervical lymph node metastasis and survival rate, and is considered to be practical.

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Essential thrombocythemia （ET） is a myeloproliferative neoplasm characterized by an increase in platelets due to abnormalities in bone marrow hematopoietic stem cells. Control of platelet count and antithrombotic therapy are important in the perioperative period because ET could cause bleeding and thrombosis. We report a case of performing surgery on mouth floor cancer accompanied by ET. A 70-year-old man was referred to our hospital in September 2016 for the indication of a tumor in the right mouth floor. A biopsy showed a pathological diagnosis of squamous cell carcinoma. The clinical diagnosis from imaging examinations was mouth floor cancer T2N1M0. He had been treated with hydroxycarbamide （HU） and dipyridamole since the diagnosis of ET in 2004. The platelet count was 94.1×10⁴/μl at the preoperative blood test, so we increased the dose of HU before surgery. As a result, the count decreased to 50.4×10⁴/μl on the day of the surgery. Also, we stopped dipyridamole before surgery. He underwent tracheostomy, functional neck dissection, partial resection of the mouth floor and tongue, and reconstruction with a radial forearm free flap in November 2016. When the platelet count increased postoperatively, HU was resumed. Furthermore, daltepalin sodium was started intravenously at the time when the amount of bleeding decreased. He had no perioperative complications due to the control of platelet count or antithrombotic therapy.

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We consider arterial injection chemoradiotherapy as a potential option, and present a case wherein superselective intra-arterial chemoradiotherapy via bilateral superficial temporal arteries was effectively used against hard plate cancer.
A 63-year-old female was enrolled in our hospital with the chief complaint of a mass in her left palate gingiva.　The mass measured 35×30mm, and had advanced from the left palate gingiva to the median region of the palate.　No metastasis to the cervical lymph node was observed.　She was pathologically diagnosed with squamous cell carcinoma based on the findings of a biopsy.　We scheduled her for arterial injection chemoradiotherapy with the expectation of preserving the function and form of the oral and maxillofacial area.　We placed catheters in both maxillary arteries close to both the superficial temporal arteries.　Anticancer drugs were given in divided doses to the right and left sides at a ratio of 1：1, with a total dosage of DOC：60mg/m² and CDDP：125mg/m².　The total radiation dose provided was 50Gy/25fr/5 weeks.　Hematopoietic disturbance was observed after treatment initiation and we discontinued the therapy after 5 weeks.　It has been 6 years since the patient underwent this therapy, and no recurrence or metastasis has been observed.

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Mandibular metastasis of hepatocellular carcinoma is relatively rare. Here, we report a case of metastasis of hepatocellular carcinoma to the mandibular bone, who was treated with radical resection to preserve and maintain quality of life （QOL）. An 80-year-old man was referred to our hospital due to swelling in the right molar region of the mandible. Medical history revealed hepatic cell carcinoma （HCC） and bladder cancer. A painless and elastic swelling measuring 33×24mm with normal mucosa was observed in the right molar region of the mandible. Computed tomography showed a round osteolytic lesion in the mandible. A diagnosis of metastatic tumor from HCC was made based on pathological examination of a biopsy specimen. The primary HCC had not been completely controlled. However, severe pain and difficulty in eating appeared with the sudden increase in tumor size after biopsy. Moreover, metastatic foci other than the mandibular bone were not evident. Therefore, selective neck dissection and segmental mandibular resection followed by reconstruction with a titanium plate and pectoral major musculocutaneous flap was carried out to preserve and maintain oral function and QOL. The patient survived 20 months after the surgery without recurrence of mandibular tumor or any cosmetic and oral functional problems.

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The lateral retropharyngeal node （LRPN） is located in the posterior pharynx space which surrounds the internal carotid artery and prevertebral muscle. LRPN is commonly referred to as the Rouviere lymph nodes. LRPN metastasis often occurs from pharyngeal cancer, but seldom occurs from oral cancer, extremely from tongue. The prognosis of the cancer with LRPN metastasis is poor because there is no appropriate treatment for them. We experienced a case of Rouviere lymph nodes metastasis from squamous cell carcinoma of the tongue successfully treated with concomitant Intensity Modulated Radiation Therapy （IMRT） and cetuximab. There was no recurrence during 3-years and 6-months follow-up period.

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