Taku Yamashita

Selective Activator Protein-1 Inhibitor T-5224 Prevents Lymph Node Metastasis in an Oral Cancer Model.

Activator protein‐1 (AP‐1) is a transcriptional factor that regulates the expression of various genes associated with tumor invasion and migration. The purpose of our study was to assess the therapeutic effects of a novel selective AP‐1 inhibitor, T‐5224, in preventing lymph node metastasis in head and neck squamous cell carcinoma (HNSCC) in an orthotopic mouse model. We assessed the effect of T‐5224 on HNSCC cell invasion, migration, proliferation, and MMP activity by carrying out an in vitro study using an invasion assay, scratch assay, WST‐8 assay, and gelatin zymography. We also observed morphological changes in HNSCC cells by time‐lapse microscopy. Furthermore, cervical lymph node metastasis was assessed using an orthotopic tumor model of human oral squamous cell carcinoma cells (HSC‐3‐M3) injected in the tongue of a BALB/c nude mouse. T‐5224 (150 mg/kg) or vehicle was given orally every day for 4 weeks. Animals were killed and assessed for lymph node metastasis by H&E staining of resected lymph nodes. T‐5224 significantly inhibited the invasion, migration, and MMP activity of HNSCC cells in a dose‐dependent manner; there was no significant influence on cell proliferation. The antimetastatic effect of T‐5224 was also confirmed in our animal study. The rate of cervical lymph node metastasis in the model was 40.0% in the T‐5224‐treated group (n = 30) versus 74.1% in the vehicle‐treated group (n = 27; P < 0.05). In conclusion, T‐5224 inhibited the invasion and migration of HNSCC cells in vitro, and prevented lymph node metastasis in head and neck cancer in an animal model.

Clinical features and treatment outcomes of Japanese head and neck cancer patients with a second primary cancer

It has been well established that patients with head and neck cancer (HNC) have an elevated risk of developing a second primary cancer (SPC), owing to the common carcinogenic risk factors, including tobacco and alcohol consumption, and inactive aldehyde dehydrogenase‐2 genotype. Here we investigated the current state of SPC in Japanese HNC patients.

A retrospective study of treatment for curative synchronous double primary cancers of the head and neck and the esophagus

OBJECTIVE Curative synchronous double primary cancers of the head and neck and the esophagus (CSC-HE) are frequently detected, but a standard treatment remains to be established. We studied the clinical course to explore appropriate treatment strategies. METHODS We retrospectively studied consecutive 33 patients who had CSC-HE. The disease stage was classified into 4 groups: group A, early head and neck cancer (HNC) and early esophageal cancer (EC); group B, early HNC and advanced EC; group C, advanced HNC and early EC; and group D, advanced HNC and advanced EC. As induction chemotherapy, the patients received 3 courses of TPF therapy (docetaxel 75mg/m2 on day 1, cisplatin 75mg/m2 on day 1, and 5-fluorouracil 750mg/m2 on days 1-5) at 3-week intervals. The clinical courses and treatment outcomes were studied according to the disease stage of CSC-HE. RESULTS The disease stage of CSC-HE was group A in 1 patient (3%), group B in 9 patients (27.3%), group C in 3 patients (9.1%), and group D in 20 patients (60.6%). The median follow-up was 26months, and the 2-year overall survival rate was 67.4%. In groups A, B, and C, the 2-year overall survival rate was 83.3%. In group D, the 2-year overall survival rate was 62.6%. Ten of 20 patients in group D received induction chemotherapy with TPF, and 6 patients were alive and disease free at the time of this writing. CONCLUSION The treatment outcomes of patients with CSC-HE were relatively good. TPF induction chemotherapy might be an effective treatment for patients with advanced HNC and advanced EC.

Salvage Transoral Videolaryngoscopic Surgery for radiorecurrent hypopharyngeal and supraglottic cancer

OBJECTIVE To evaluate the feasibility of Transoral Videolaryngoscopic Surgery (TOVS) for radiorecurrent supraglottic and hypopharyngeal cancer, and to compare survival and complications between primary and radiorecurrent cases. METHODS Twelve cases of salvage TOVS for radiorecurrent cancer and 53 cases of TOVS as an initial treatment (primary cases) were evaluated. Days to resume soft diet, Functional Outcomes of Swallowing Scale (FOSS), postoperative complications, epithelization days and survival outcomes were assessed by retrospective chart review. RESULTS FOSS score was significantly worse in salvage cases compared with primary cases. Bleeding and airway compromise was slightly greater in salvage cases than in primary cases; however, this was not statistically significant. Wound healing was significantly delayed in salvage cases compared with primary cases (P<0.001). In primary cases, wounds were re-epithelized within 60 days in 83% of patients and within 90 days in almost all patients, while in salvage cases 42% of patients required more than 90 days for wound healing. In salvage cases, the 5-year overall survival, disease specific survival rate, local control rate, and laryngeal preservation rate was 85.7%, 85.7%, 62.5%, and 78.0%, respectively, and 85.7%, 98.0%, 91.3%, and 97.8%, respectively, for primary cases. Local control rate was significantly better in primary cases than in salvage cases. CONCLUSION Salvage TOVS was feasible in highly selected cases. After serial transoral surgery, the final laryngeal preservation rate was satisfactory. Swallowing function in salvage cases tended to be worse than in primary cases, and a significantly longer time was required for wound healing.