We conducted a multicenter retrospective observational study to evaluate the safety and effectiveness of cetuximab against oral cancer. Adverse events and clinical outcomes were retrospectively evaluated in 145 patients who underwent radiotherapy and chemotherapy using cetuximab between December 2012 and June 2014.
Sixty-five patients underwent radiotherapy combined with cetuximab and 80 received chemotherapy with cetuximab. All patients were hospitalized during the first administration of cetuximab. The main Grade ≥ 3 adverse events caused by cetuximab were infusion reaction, acneiform rash and interstitial pneumonia in 3.4%, 5.5%, and 2.1% of the patients, respectively. Interstitial pneumonia developed in five patients who were treated with both radiotherapy and cetuximab. The overall response rate to both radiotherapy and cetuximab was 64.8%, with one-year progression-free survival and overall survival rates of 24.1% and 51.8%, respectively. These rates were 54.5%, 25.0% and 58.6%, respectively among the patients treated only by chemotherapy using cetuximab, cisplatin (or carboplatin) and 5-FU. Cetuximab was well-tolerated, feasible and effective against oral cancer.

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The Edogawa-ward Dental Association has carried out group checkups for oral cancer since 2011 under the slogan “Have a checkup while you’re healthy.” In 2013, Japan’s first “Oral Cancer Checkup Navigation System” was jointly established with Tokyo Dental College. The Association considered the achievements of this checkup and the navigation system. Persons wishing to receive a group checkup applied by directly calling the Association. For individual checkups, residents of Edogawa ward aged 40 years or older were sent a checkup voucher and the checkup was performed at cooperating medical offices. As a result, 886 persons received a group checkup from 2011 to 2015, and two cases of oral cancer (0.23%) were discovered. Since 2015, 1,416 persons received individual checkups and two cases of oral cancer (0.14%) were discovered.
Edogawa ward obtained a higher rate of detecting oral cancer than other areas (0.1%) and the checkup is considered to have contributed to early detection. Furthermore, Tokyo Dental College functions as a control center in the navigation system, answering questions from general dental clinics regarding checkups. By using this system, one can get support for more detailed examinations and referrals to higher medical institutions, and hear opinions of specialists from the chair side. The system should be expanded throughout Japan and standardized checkup procedures should be established.

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We started screening for oral cancer as a cooperative enterprise by the Kanagawa branch of the Japanese Society of Oral and Maxillofacial Surgeons and the Kanagawa Dental Association in 2006. This enterprise of Kanagawa prefecture consists of a workshop for members of the Kanagawa Dental Association and screening for oral cancer by double-checking by an authorized oral surgeon and certified dentists.
A summary of the enterprise and the results of screening are as follows:
1)1,302 dentists were certified as screening personnel in nine years, which is equivalent to 35% of all members of the Kanagawa Dental Association.
2)Screening for oral cancer was performed 158 times in total in nine years.
3)7,199 people (male 2,150 and female 5,049) were examined by screening in nine years and the average age was 64.7 years old.
4)Of the total, 81.4% were normal, follow-up was necessary for 11.8%, and a detailed examination was necessary for 6.5%.
5)Nine cases were diagnosed as oral cancer: 5 cases with tongue cancer, and 1 case each with cancer of the floor of the mouth, mandible, palate and soft palate.
It is important to analyze and utilize these data effectively. We consider that both group and individual examinations will be started in several areas in the near future.

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We started oral cancer screening in cooperation with a local dental association in 1990, and thus 25 years passed in 2016. Departments of oral surgery in the three hospitals attached to our university cooperated and performed oral cancer screening in their respective regional areas. An oral cancer screening trial was started in Chiba city and spread to 14 cities in Chiba Prefecture in 2015, and group medical examinations were performed one to three times a year in each region. We checked 7,030 in group medical examinations from 1992 through 2008 in the whole of Chiba prefecture. Oral mucosa diseases were detected in 707 cases, including 8 cases of oral cancer and 60 cases of precancerous lesion. The overall discovery rate of oral cancer was 0.11%, which was similar to the rate for each year. In addition, we worked on the following to spread oral cancer screening: a) Distributing information and raising awareness of oral cancer among citizens, b) providing lifetime education about diagnosis of oral cancer to general dentists, c) explaining to administrative organizations about the importance of oral cancer prevention and early detection, and d) developing inspection equipment and laboratory procedures for early detection of oral cancer. As a result of these activities, we started to carry out individual examinations for oral mucosa disease in the dental clinic with the assistance of government budget in four cities.

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We report two types of oral cancer examinations in Iwate prefecture. One is individual examinations starting from 2010 and the other is group examinations starting from 2011.
The individual examinations for oral cancer by members of the Iwate Dental Association were performed during routine dental treatment at private clinics. We supported them by making examination manuals and receiving patients. The members of the Iwate Dental Association consulted us about 59 patients, and 52 patients (88.1%) were treated in Iwate Medical University Hospital in 2010 and 2011. Out of the 52 patients, 8 patients (15.4%) had pathological oral cancer.
he group examination was conducted as a cohort study of oral mucosal diseases at Otsuchi-cho in Iwate prefecture. The subjects were 2,001 residents in this town. At the first examination in 2011, 2 subjects (0.10%) had a diagnosis of oral cancer, 9 (0.45%) had leukoplakia and 6 (0.30%) had oral lichen planus. From 2012 to 2015, 2 subjects (0.14%) had a diagnosis of oral cancer, 32 (2.32%) had leukoplakia and 23 (1.66%) had oral lichen planus. The yearly average number of subjects was 1,382.
For earlier detection of oral cancer, individual oral cancer examinations by general dentists during routine dental treatment are effective. From our cohort study, we calculated the incidence rates of oral cancer, leukoplakia and oral lichen planus; we will obtain more precise incidence rates and/or factors of oral mucosal diseases in our further studies.

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For the 5 years between January 2010 and December 2014 at the Department of Oral and Maxillofacial Surgery, Gunma University Hospital, oral oncologic surgery was carried out for 376 patients, of whom 3 (0.8%) had recurrence of the primary lesion even though treatment was comprehensively performed according to the oral cancer treatment protocol. No cervical recurrence was observed. Of the 3 patients, only 1 who underwent salvage surgery survived.
Comprehensive evaluation of the 3 patients showed a complex of highly aggressive pathological characteristics such as INFc (diffuse infiltration of cancer cells) and 3 or more buddings as cytobiological characteristics, a clinical stage requiring semiglossectomy of the tongue or more invasive surgery, progression to the mandibular gingiva requiring mandibular segmental resection, and cervical lymph node metastasis. Even when complete resection is confirmed based on surgical specimens at the first treatment in such patients, it might be necessary to regard them as high-risk patients for recurrence and consider postoperative treatment for both the primary lesion and neck. In addition, even when recurrence is observed, if surgery is possible, as in Patient 3, salvage might be achievable.
In both cases, an appropriate treatment plan should be formulated before surgery based on the cytobiological and clinicopathological characteristics of the tumor, and measures to prevent tumor recurrence should be taken.

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The aim of this study was to evaluate retrospectively the outcomes of patients with stage IV advanced oral and maxillofacial cancer (OMFC) primarily treated with induction chemotherapy using TPF (TPF-ICT), and the efficacies of salvage surgical treatment. Forty-nine cases were treated with TPF-ICT. The therapy is very effective against OMFC, but the side effects are very severe.
The response rate for primary region and cervical region cancers were 57.1% and 65%, respectively.
The most commonly observed Grade 3-4 side effects included leucopenia (75.5%), hemoglobin decrease (32.7%), and thrombocytopenia (22.4%). Other toxicities included renal failure, nausea, vomiting, and diarrhea. Neuropathy was diagnosed in 19 (38%) patients.
If the response is poor or the side effects are severe, the therapy will be followed by another therapy such as radiotherapy or surgical therapy. Six cases received salvage surgery following TPF-RT (radiotherapy) and 31 cases received salvage surgery following TPF alone.
Patients with OMFC who received salvage surgery following TPF alone (31 cases) and CCRT-HFT (42 cases) were compared. The operation time, hemorrhage volume, complications, and success rate of free flap were not different in the two groups.
In the two groups (TPF-ICT vs. CCRT-HFT), survival analysis after salvage surgery was performed using the Kaplan-Meier method and the 2- and 3-year overall survival rates were (70.5% vs. 52.1%) and (59.2% vs. 50%), respectively.
The efficacy of TPF-ICT against advanced OMFC was suggested in this study.

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We evaluated 27 cases of salvage surgery for recurrent oral squamous cell carcinoma.
The 1yOS was 75% and 2yOS was 61%. Mean PFS was 10.9 months (2.6–61.3 m).
A pathological resection margin of positive or close, and the primary site in the tongue, oral floor and buccal mucosa were considered as poor prognostic factors. The primary site of re-recurrence in almost 88% of cases was located in the posterior region or parapharyngeal space, so safe setting of the posterior margin and extended dissection of the parapharyngeal space should be considered.

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Recently, primary treatment for oral cancer has been generally established with improvements in the therapeutic outcome. However, the outcome of treatment for recurrence must be improved to further improve the therapeutic results. In this study, patients who underwent salvage surgery for local (primary region) or regional (neck region) recurrence of oral cancer after radical treatment were evaluated. The subjects were 381 patients who underwent radical surgery or achieved CR by chemoradiotherapy or radiotherapy performed as radical treatment at our department between January 1999 and December 2012. Local or regional recurrence was noted in 87 of the 381 patients with a recurrence rate of 22.8%. Recurrence was observed only in the primary region in 57, only in the neck region in 15, and in the primary region and in the neck region in 8, and recurrence in the primary region was accompanied by neck metastasis in 7. Salvage surgery was performed in 45 (51.7%) of the patients with recurrence. In the patients who underwent salvage surgery, the 3-year survival rate was 71.3%, and 3-year re-recurrence rate was 30.1%. A period from initial treatment to recurrence (disease-free interval) of 12 months or longer was a favorable prognostic factor. Since relatively good outcomes were obtained by surgery in recurrent cases, indications for surgery should be evaluated with sufficient consideration of these results.

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The Japanese Society of Oral Oncology has established a working group for the guideline for odontogenic tumor.
We studied 5231 patients with odontogenic tumor. Histologically, the tumors contained 28.3% ameloblastoma, 24.4% keratocystic odontogenic tumor and 20.9% odontoma. Of these, we studied 947 patients with ameloblastoma. Histologically, solid/multicystic type was observed in 74.9%, unicystic type in 17.1%, desmoplastic (des) type in 4.1%, and extraosseous/peripheral type in 3%. The treatment modalities for ameloblastomas were both conservative surgery (83.6%) and radical surgery (73.8%). Finally, we have published the guideline for ameloblastoma in Japan.

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As ameloblastoma almost always arises in the intraosseous maxillomandibular region, inspection and palpation are not effective in the diagnosis.
In the clinical practice guideline for ameloblastoma, intraoral radiography, CT, and MRI are useful diagnostic modalities overall. However, it is necessary to use the diagnostic modality in different ways depending upon the situation of the patient.
This guideline demonstrated that the discrimination of ameloblastoma from keratocystic odontogenic tumor, dentigerous cyst, and radicular cyst is important in clinical image diagnosis.
Regarding the relationship between image findings and prognosis, the recurrence ratio of multicystic ameloblastoma is higher than that of the unicystic type. Moreover, the prognosis of malignant ameloblastomas is generally poor.
Malignant ameloblastomas are divided into two types, metastasizing ameloblastoma and ameloblastic carcinoma. Metastasizing ameloblastoma showed benign findings on the images but metastasized to other organs. In ameloblastic carcinoma, bone destruction and invasion into surrounding tissues were generally seen on the images.

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Four subtypes of ameloblastoma (solid/multicystic type, extraosseous/peripheral type, desmoplastic type, unicystic type) that were described in the 2005 WHO classification of odontogenic tumors are associated with their biological behaviors, which underlines the importance of histopathological diagnosis of ameloblastoma in the determination of therapeutic strategy. The distinction of odontogenic carcinomas from ameloblastoma is made by recognizing various histopathological features suggestive of malignancy such as cellular atypia. Odontogenic carcinoma contains several entities that are classified according to the histological features and clinical history. Because of their rarity, clinical differences between behaviors of odontogenic carcinoma subtypes have not been clearly demonstrated. More data should be collected to assess the clinical significance of the classification of odontogenic carcinoma.

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In designing guidelines for the treatment of ameloblastoma, we aimed to clarify the indications of two surgical methods, conservative surgical treatment and jaw resection, and to assess the reliabilities of both methods.
Clinical question 1: In which cases should we perform conservative surgical treatment?
The conservative surgical treatment is indicated for the extraosseous/peripheral type and unicystic type, and some cases of the solid/multilocular type. In the unicystic type, the method is fixed in detail due to the subtype. Curettage, ostectomy of surrounding bone, chemical cauterization by Carnoy's solution, or cryosurgery are recommended to follow the tumor enucleation since a high rate of recurrence was reported in conservative surgical treatments such as curettage or simple enucleation.
Clinical question 2: In which cases should we perform jaw resections?
Jaw resection can be applied to every type of ameloblastoma, especially the solid/multilocular type and desmoplastic type. Though this is a highly radical therapy, the patient's state such as age, gender, and general condition have to be taken into account.
Regarding assessments of clinical questions 1 and 2, both are judged as grade C1 recommendation, which means, “Although there is little evidence to support a positive recommendation, it can be considered. Each method is potentially effective.”

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Burkitt lymphoma is a highly malignant B-cell tumor characterized by rapid progression. The patient was an 18-year-old boy who had mental paresthesia and spontaneous pain of the mandible as initial symptoms. We initially considered that he might have a malignant tumor, so we performed several examinations. We recognized radiographic changes in his mandible, but were unable to find any tumor lesions or lymph node swelling in his maxillofacial or cervical area. Therefore, we performed further examinations to determine the diagnosis. Around the same time as these initial examinations, several generalized lesions became obvious clinically. He was ultimately diagnosed with Burkitt lymphoma. His condition improved after the administration of CODOX-M/IVAC chemotherapy, and subsequent PET-CT imaging showed there had been a complete response. However, the lesion recurred, and he died one year after his first visit. Narrowing the differential diagnosis in the present case would have been difficult, especially given that the invisible malignant lymphoma occurred in the head and neck area. However, if a patient has a subjective symptom such as mental paresthesia, when cancer cannot be ruled out clinically, the tumor may be a hematopoietic malignancy, a malignant lymphoma, or possibly a distant metastasis of another organ malignancy. In such cases, performing an early general examination such as a PET-CT may lead to a more rapid diagnosis.

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Intramuscular lipoma of the tongue is rarely reported in the literature. We treated an 83-year-old man with an intramuscular lipoma of the mobile tongue. The patient consulted our hospital with a chief complaint of swelling of the tongue. T1- and T2-weighted MRI clearly showed a mass lesion, with a tumor size of 28×19×31mm. The tumor was excised under general anesthesia. Histopathological examination showed proliferation of mature adipose cells, including bundles of muscle fibers. On the basis of the results of histopathological examination, we diagnosed an intramuscular lipoma arising from the tongue. There have been no signs of recurrence as of 10 months after surgery.
A review of the Japanese literature showed 10 cases of solitary intramuscular lipoma of the tongue.

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Symmetric lipomatosis of the tongue (SLT) is defined as an infiltrative growth of mature adipose tissues into bilateral tongue muscle. Here, we report a case of SLT presenting as macroglossia and review the literature. The patient was a 71-year-old man who had multiple painless elastic soft masses in the bilateral tongue borders. The patient's tongue was wider than the mandibular dental arch due to the exophytic masses of the tongue, so-called macroglossia. Magnetic resonance imaging revealed poorly marginated masses of the bilateral tongue borders with low signal intensity in T2 fat suppression images and high in both T1 and T2 weighted images. The biopsy specimen was diagnosed as lipoma. Because the tumor masses were located in the bilateral border of the tongue, the patient was diagnosed as SLT.
As he had taken anti-coagulant agents for chronic atrial fibrillation, airway obstruction by postoperative bleeding and edema was feared. The debulking operation of the masses was performed twice under general anesthesia. The extirpated specimens showed lesions consisting of mature adipose tissues in muscular layer. No apparent capsule structure was noted.
Between 1947 and 2015, 45 cases of benign symmetric lipomatosis, symmetric lipomatosis of the tongue, bilateral lipomatosis of the tongue, and so on were reported. The pathogenesis of SLT is still unknown. No regrowth has been found in the last two years.

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