The clinical research environment in Japan has changed significantly in recent years. In particular, the enforcement of the Clinical Trials Act on April 1, 2018 is considered a major turning point. One of the reasons for this change is that several inappropriate clinical research cases, such as the Diovan affairs, occurred between 2013 and 2014. In those cases, the relationship between researchers and pharmaceutical companies, involving data manipulation, opaque scholarship endowments and several university institutions, attracted attention and became a social issue. In light of these research irregularities, the Ministry of Health, Labour and Welfare （MHLW） concluded that laws and regulations were necessary to restore trust in clinical research, and after revising and tightening the ethical guidelines, the Clinical Trials Act came into effect.
While all those involved in clinical research must understand the requirements of this law and respond appropriately, the burden on researchers has increased significantly due to the large number of documents and complexity of this law, leading to the stagnation and delegitimization of clinical trials. The major features of this law are that: the responsibility for clinical research has been consolidated in the hands of the principal investigator, researchers must submit their study plans to the MHLW through the Certified Review Board approved by the MHLW, and the flow of conflicts of interest has been defined in detail.
This report describes the history of changes in clinical trial regulations in the clinical research environment up to the passage of the Clinical Trials Act in clinical research ethics, and outlines the Clinical Trials Act.

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Clinical research begins with a “question” in daily clinical practice. In order to solve and verify these questions, clinical research is conducted. This paper describes an outline and the practice of clinical research. Doctors, dentists, and others engaged in medical care are “scientists”. Those who do science are true “medical practitioners”. Desk studies are important in science, but without practice, one is not a medical scientist. We need to acquire knowledge, apply the knowledge to practice, and experience a lot in clinical practice. From this experience, we can identify problems and then try to solve them. This process is called “clinical research”. The results are then generalized and make a significant contribution to medicine. It is important to read a lot of literature, eagerly do clinical practice, observe and identify well, think deeply, and work hard on clinical research.

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Antiplatelet drugs are used to treat and prevent arterial thromboses such as cerebral infarction, myocardial infarction, and peripheral arterial thrombosis. There are no clear criteria for determining whether the administration of antiplatelet agents should be continued at the time of surgery in view of the onset of thrombosis/embolism or discontinued due to the risk of major bleeding. In this article, we report on our clinical examination of the safety of neck dissections under the continuous administration of antiplatelet drugs.
The study included 23 subjects who met the criteria from among those who underwent surgery for primary oral cancer, experienced subsequent metastases to the cervical lymph nodes, and underwent unilateral total neck dissections alone at our department from July 2010 to December 2020. We divided the subjects into a group which orally ingested antiplatelet drugs and a group without oral administration of the same drugs and compared them retrospectively. There were 6 cases in the oral administration group and 17 cases in the group without oral administration. Intraoperative bleeding, postoperative drainage, postoperative Hb, and rate of change in RBC did not differ significantly between the two groups. No onset of postoperative bleeding, postoperative hemorrhagic complications, or thromboembolic complications were observed in either group.
This study demonstrated that neck dissections can be performed under the continuous administration of antiplatelet drugs. However, postoperative bleeding following neck dissections may be life-threatening due to airway obstruction. If antiplatelet drugs are continued, careful intraoperative hemostasis and strict postoperative management are vital. Due to the small sample size of this study, we believe a multicenter accumulation of subjects is needed for further examinations.

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von Willebrand disease （vWD） is a hypothrombotic dysfunction caused by a quantitative decrease or qualitative abnormalities in von Willebrand factor （vWF） and may hinder hemostasis during surgery. We report the safe achievement of hemostasis during reconstructive surgery for lower gingival carcinoma in a patient with vWD by clotting factor replacement therapy. The patient was a 63-year-old man. He had been diagnosed with vWD when treated for lung cancer in the past. At the first visit to our department, vWF ristocetin cofactor activity （vWF: RCo） was less than 6％, vWF antigen quantification （vWF: Ag） was 26％, and factor Ⅷ activity （FⅧ: C） was 75.1％. Reconstructive surgery was planned after induction chemotherapy for right mandibular gingival squamous cell carcinoma （T4bN2bM0）. Freeze-dried concentrated human blood-coagulation factor Ⅷ 2000 unit/body was administered from 2 days before surgery. On the day before surgery, vWF: RCo increased to 158％, vWF: Ag to 275％, and FⅧ: C to 110％. We performed neck dissection, mandibular segment resection, and reconstruction by a titanium plate and rectus abdominis flap with good hemostasis, and there was no postoperative bleeding.

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Pulmonary lymphangitis carcinomatosis is a condition in which cancer cells invade the lymphatic vessels and cause multiple emboli, and has an extremely poor prognosis clinically. The most common primary sites of pulmonary lymphangitis carcinomatosis are the breasts, stomach, and lungs. The number of cervical lymph node metastases, extranodal invasion, and metastasis to levels Ⅳ and Ⅴ have been reported to be involved in the distant metastasis and prognosis of oral squamous cell carcinoma. We report a case of pulmonary lymphangitis carcinomatosis after treatment of multiple cervical lymph node metastasis from tongue cancer. Multiple cervical lymph node metastasis appeared in a 72-year-old male patient 4 months after partial resection for T2N0M0 oral tongue squamous cell carcinoma. We diagnosed rT0N3bM0 oral tongue squamous cell carcinoma, and he underwent radical neck dissection under general anesthesia. Histopathological examination revealed 47 metastatic lymph nodes in the dissected tissue and concurrent chemoradiotherapy was performed as postoperative adjuvant therapy. He complained of increased sputum and respiratory distress on the sixth day after the end of therapy. A chest CT scan showed thickened alveolar septa in both lungs, pleural effusion and enlarged hilar lymph nodes. Based on the findings of pleural effusion cytology and chest CT, we diagnosed pulmonary lymphangitis carcinomatosis. Sixteen days after the onset of respiratory symptoms, he died due to respiratory failure.

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We report a case in which nivolumab exhibited a complete response to cervical and distant metastases of tongue cancer. Regular follow-up started after 2 years of administration.
A 70-year-old man underwent surgery, including reconstruction, under the diagnosis of advanced tongue squamous cell carcinoma of T3N2bM0. After the operation, neck recurrence was confirmed. Therefore, we completed simultaneous chemoradiotherapy with cisplatin; however, positron emission tomography–computed tomography （PET–CT） confirmed metastasis to cervical and paratracheal lymph nodes, so nivolumab was selected. The tumor gradually shrank with this drug, and a complete response was diagnosed after 1 year of administration. This drug was administered for 2 years and was then terminated. After 1 year and 4 months, no obvious recurrence or metastasis was observed.
Nivolumab is an expensive drug; however, there is no standard for the administration period. The establishment of a standard for the administration period is awaited, as well as a more careful examination of the therapeutic effects of this drug.

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