Management of the N0 neck in oral cancer remains controversial. A number of studies, randomized controlled trials, and the National Comprehensive Cancer Network’s (NCCN) guideline recommend elective neck dissection. However, many questions remain unresolved. This study examined this issue and the therapeutic strategy for oral cancer with clinical N0 classification in Japanese clinical practice.

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We report the imaging procedures used in our department and diagnostic criteria of ultrasonography for detecting cervical lymph node metastasis from oral cancer. Our diagnostic criteria for B-mode US are: (1) lymph nodes with definite internal echoes are considered metastatic; (2) lymph nodes with hilar echoes are considered benign; (3) lymph nodes with long/short-axis ratios of ≥3.5 are considered benign. B-mode US is 66% sensitive and 98% positive predictor value in detecting metastasis. Our diagnostic criteria for Doppler US findings are: (1) lymph nodes with scattered blood flow signals in their parenchyma are considered metastatic; (2) lymph nodes with blood flow signals along their periphery are considered metastatic; and (3) lymph nodes with hilar signals branching radially from the hilus are considered benign. Overall sensitivity for combined B-mode with Doppler US was 84.1% which was significantly better than that for B-mode US alone. However, diagnostic accuracy depends on lymph node size. We therefore consider that vascularity within metastatic lymph nodes changes according to lymph node size and increases with angiogenesis during early-stage metastasis, which can be shown on Doppler US images. Increased blood flow in the parenchyma was a characteristic of Doppler US findings in small lymph nodes during early-stage metastasis. As the size of metastatic lymph nodes increased, blood flow signals became more scattered.
Follow-up US at four-week intervals is recommended at least during the first posttherapeutic year.
Doppler images on the invasion front of the tongue cancer are predictors of the pathological grade of malignancy and cervical lymph node metastasis.

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Whether management of N0 neck in patients with oral cancer should be done by observation or prophylactic neck dissection is controversial, as 20-30% of patients have occult cervical lymph node metastasis. Because ac-curate diagnosis of any metastasis is difficult despite the various imaging modalities available, sentinel lymph node biopsy (SLNB) using blue dye or a radioisotope (RI), or both, has recently been performed for these patients. However, SLNB using RI cannot always be performed at every institution. Therefore, as a method without using RI, we report SLNB using indocyanine green (ICG) fluores-cence imaging for N0 oral cancer patients.

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Cervical lymph node metastasis is an important prognostic factor in oral cancer. Whether patients with cN0 status should be treated with elective neck dissection or with therapeutic neck dissection after nodal relapse has been a matter of debate. Sentinel node biopsy (SNB) is a widely accepted procedure in various human malignancies. SNB has received considerable attention for its role in deciding whether to perform neck dissection. However, there are four issues in the current status of SNB in oral cancer: adopting the RI method, shine-through phenomenon, method of diagnosing occult metastasis, and establishment of EBM. This paper outlines the current status of SNB in oral cancer.

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Sentinel lymph node biopsy has been widely used in cancer treatment to assess lymph node metastasis at early stages. It has been reported that this procedure has an accuracy of greater than 95% in the evaluation of lymph node metastasis in patients with stage N0 carcinoma, especially in patients with malignant melanoma or breast carcinoma. Surgeons trace the sentinel lymph node using a gamma probe that can provide radioactivity counts in the operating theater. As surgeons are unable to visualize increased radioactivity with spatial resolution, a small gamma camera can be used for this purpose at the time of the biopsy. However, sentinel lymph nodes with increased accumulation cannot be defined with anatomical resolution. The blue-dye technique is often combined with the radioisotope method to improve sentinel lymph node detection. However, the blue-dye technique only enables the visualization of lymph flow and sentinel nodes within the incision area. Near-infrared (NIR) imaging using indocyanine green (ICG) was recently introduced as a new option for imaging sentinel lymph nodes due to deeper penetration of photons into living tissue. We developed a dual-modality imaging system, polyamidoamine (PAMAM)-coated silica nanoparticles loaded with ^99mTc and ICG, for depicting deeply situated sentinel nodes and fluorescent nodes and to enable simultaneous visualization at anatomical resolution. We conducted animal studies to test the feasibility and utility of this dual-modality imaging system. Furthermore, we are conducting a molecular target imaging study to detect sentinel lymph node metastasis. We also review recent developing molecular imaging modalities for depicting sentinel lymph node metastasis.

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The Japanese Society of Oral Oncology held its first workshop in 1993 on the T classification of lower gingival carcinomas, where 12 proposals were presented. We could not come to a conclusion and agreed to conduct further studies and collect many cases from nationwide surveys. There were 1,187 registered cases which were statistically analyzed by applying 12 proposals for the T classification in terms of T. The stage distribution, survival rate, factor analysis, mathematical quantification method II, partial correlation coefficient with surgical methods used for the primary site, multiple correlation coefficient with prognosis, and the level of mandibular canal (LMC) criteria were found to be the most appropriate criteria for the T classification of lower gingival carcinomas. Then, the local recurrence rate after surgical treatments in the registered cases was analyzed and the desirable mode of mandibulectomy by using LMC criteria, bone invasion level and bone invasion pattern to minimize local recurrence was analyzed by logistic regression analysis and proposed. The concept of LMC criteria and the proposed mode of mandibulectomy in the surgical treatment of lower gingival carcinomas have been adopted in the clinical practice guideline for oral cancer by the JSOT and JSOMS and in the general rules for clinical and pathological studies on oral cancer by the JSOT.

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Purpose: We performed a clinical study to evaluate the N classification.
Materials and methods: 281 cases of primary oral squamous cell carcinoma, which were surgically resected with neck dissection, were selected. Cases with pre-operative radiotherapy or that recurred after the surgery, were excluded.
Clinical examination and images such as US, CT, MRI, and PET/CT were used to diagnose metastasis of neck lymph nodes.
We studied the concordance rate of the clinical classification (cN), which expresses the existence and developed area of neck lymph node metastasis, and histopathological classification (pN). We also examined the accuracy of diagnostic tools.
Results: The concordance rate of cN and pN classification was 60.5％. cN1 showed the lowest concordance (30.2％).
The highest specificity of diagnostic accuracy was US, 86.3％, and the highest sensitivity was PET/CT, 74.7％.
Conclusions: It is necessary to select diagnostic tools based on their characteristics for accurate diagnosis for N classification.

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The standardization of pathological diagnosis in oral cancers and precancerous lesions is considered to be extremely important in achieving the mandate of the National Cancer Registry and standardization of cancer treatment. Problems in diagnostic systems include an issue in the diagnosis of oral cancer for the standardization of pathological diagnosis. The pathological diagnosis includes definitions and terminology in oral cancer, so the standardization of disease definitions and terminology is the foundation of standardization of diagnosis between clinicians and pathologists, and collaboration between pathologists and pathologists. From the global aspect, the terms and definitions used in the pathological diagnosis of oral cancers and precancerous lesions are based on the UICC classification for cancer staging and WHO classification for histopathology. Additionally, in Japan, the General Rules for Clinical and Pathological Studies on Oral Cancer (1st. ed) and the General Rules for Clinical Studies on Head and Neck Cancer (5th. ed) are used for the diagnosis of oral cancer. Some differences can be found in the staging, definitions, and terms used for diagnosis in these classification and rules. This situation concerning the criteria and terms used for pathological diagnosis could cause some misunderstanding in cancer treatment. Currently, the Japan Society for Oral Tumors has discussed revising the General Rules for Clinical and Pathological Studies on Oral Cancer. In order to standardize the diagnosis of oral cancer, we need to ensure consistency between Japan and international standards by revising the staging, definitions, and terms based on the UICC classification and WHO classification in the near future.

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Super-selective intra-arterial infusion chemotherapy using cisplatinum （CDDP） has been an established organ-preserving therapy for squamous cell carcinoma of the head and neck region. We have observed a constant treatment response in advanced cases of gingival cancer by combined intra-arterial and systemic chemotherapy. Our protocol consisted of intra-arterial infusion of docetaxel （DOC） and CDDP by the Seldinger method on day 1 followed by continuous intravenous instillation of 5-fluorouracil （5-FU） for 5 days from day 2. Radiotherapy was administered with 40 Gy. Of the 22 patients, complete and partial response was observed in 82％ and 18％, respectively. Five-year overall survival, disease-specific survival, and locoregional control were high at 88％. For intra-arterial infusion chemotherapy, detailed anatomical knowledge and identification of a feeding artery are necessary to eradicate the tumor with no neurological events.

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Extended surgery for patients with locally advanced oral cancer causes a marked loss of oral function, including swallowing and speech, and affects the quality of life. Retrograde superselective intra-arterial chemotherapy can be used to provide daily concurrent chemoradiotherapy for patients with oral cancer. We evaluated the therapeutic results and the rate of organ preservation in patients with advanced oral cancer treated with intra-arterial chemoradiotherapy. This treatment provides good overall survival and local control rates for patients with advanced oral cancer.
In this review, we introduce the therapeutic results in patients with advanced oral cancer treated with retrograde superselective intra-arterial chemoradiotherapy.

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Radiation therapy has been used as a curative treatment for head and neck cancer because of the complicated characteristics of this region. With the development of technology in recent years, IMRT （intensity modulated radiation therapy） and particle therapy have been increasingly used as radical treatment methods. IMRT, which can reduce the radiation dose to the surrounding normal tissue, plays an important role for locally advanced head and neck cancer.
Particle therapy has two advantages: a better dose distribution compared to conventional radiation therapy including IMRT, and stronger biological effects compared to photon therapy. Although particle therapy has been used for the treatment of non-squamous cell tumors which are radio-resistant, this therapy combined with chemotherapy will play an important role for locally advanced head and neck cancer.

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The principle of definitive radiotherapy is to control local lesions with doses up to the tolerated doses of irradiated normal tissues within radiation fields. When the therapeutic ratio is more than 1.0, lesions can be controlled without inducing adverse effects in normal tissues. However, when it is less than 1.0, lesions cannot be controlled with radiotherapy alone. The therapeutic ratio is much larger in boron neutron capture therapy (BNCT) for lesions where a sufficient amount of ¹⁰B can be selectively and homogenously delivered than any other radiotherapy modality. Thus, lesions can be controlled without any other adverse effect in normal tissues with BNCT. The key point for improving BNCT further is to develop a method to deliver neutrons to lesions as appropriately as possible and to deliver new ¹⁰B agents to lesions more selectively and homogeneously than at present.

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Immunoglobulin A vasculitis (IgAV), formerly called Henoch-Schönlein purpura, is an immune complex vasculitis that affects small vessels with dominant IgA deposits. Advanced cases progress to renal dysfunction, such as nephrotic syndrome and renal failure. We report the case of an 84-year-old Japanese woman with a squamous cell carcinoma (SCC) in the left maxillary gingiva who developed a bilateral purpuric rash of the lower limbs 33 days after surgery to treat SCC of the maxilla. IgAV was diagnosed based on the clinical symptoms and biopsy results. The patient received diaphenylsulfone and steroid therapy, which resulted in complete remission of the IgAV and renal dysfunction. After the treatments, neither the IgAV of the lower limbs nor the SCC of the maxilla recurred.

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We report two cases of lymphorrhea after neck dissection (ND) successfully treated with negative pressure wound therapy (NPWT). The first was a case of squamous cell carcinoma (SCC) of the left buccal mucosa with cervical lymph node metastasis (T2N2bM0) in a 71-year-old man. Lymphorrhea was continuously seen after ND. Ligation of the lymphorrhea site was thus performed when hemostasis was carried out for abnormal bleeding caused by rupture of the anastomotic vessel 12 days after ND. Lymphorrhea, however, continued after re-operation and NPWT was thus applied. One week later, lymphorrhea disappeared completely. The second was a case of late nodal metastasis of the tongue SCC in a 64-year-old man. Lymphorrhea continued for 15 days after ND. NPWT was thus used for 26 days, and lymphorrhea disappeared completely. These results suggest that NPWT could be a useful conservative treatment for lymphorrhea after ND.

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Two oral cancer patients with N3 lymph nodes in level II metastases were treated with superselective intra-arterial chemoradiotherapy. A total dose of 66Gy/33 fractions of external beam irradiation concurrent with 3 to 4 courses of intra-arterial chemotherapy infusion via the femoral artery with a combination of docetaxcel (40mg/m²) and nedaplatin (80mg/m²) was administered. All patients received anticancer drug infusion to the external carotid artery with a redistribution technique whereby embolization was applied in order to achieve an antitumor effect due to a high concentration. Both the primary tumor and huge lymph node metastases disappeared and neck dissection was not performed in any of the patients. Multiple distant metastases developed in one patient who received systemic chemotherapy unsuccessfully. There was no local recurrence in the primary tumor or lymph nodes. Superselective intra-arterial chemoradiotherapy was an effective treatment not only for primary disease but also for metastatic N3 lymph nodes.

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