Takuya Tachikawa

Neoglottic formation from posterior pharyngeal wall conserved in surgery for hypopharyngeal cancer

OBJECTIVE To describe a new treatment modality of hypopharyngeal cancer consisting of total laryngectomy plus partial pharyngectomy (TLPP) conserving the posterior wall of the pharynx vertically for voice restoration. METHODS Review of hospital charts, TLPP was undertaken in 15 of 54 patients. Surgical modalities of reconstruction subsequent to TLPP were indicated on the basis of the width of posterior pharyngeal wall conserved during surgery. Posterior pharyngeal walls of width 3 cm or larger were sutured in primary closure. If the width of posterior wall was less than 3 cm, a free forearm flap or free jejunal flap was patched to the wall. Tracheo-esophageal shunt with a voice prosthesis was performed 3 weeks after surgery. RESULTS The Kaplan-Meier method indicated no difference in survival rate between patients with TLPP (46.4%) and the remaining patients (47.4%). Nine of 15 patients with TLPP (two patients with primary closure, three with free forearm flap, and four with free jejunal flap) were examined for voice restoration and fluoroscopy of the neopharynx. Eight of the nine patients, in whom more than 2 cm of the posterior pharyngeal wall had been conserved, demonstrated a good speech rating, maximum phonation time and neoglottic formation by the posterior pharyngeal wall. CONCLUSION The combination of conservation of the posterior pharyngeal wall, patch graft and a voice prosthesis is a useful method that offers sufficient quality of phonation without deterioration of survival rate for patients with hypopharyngeal cancer.

Local injection of OK-432/Fibrinogen gel into head and neck carcinomas

Immunotherapy with biological response modifiers (BRM) is a possible strategy against head and neck solid tumours. However, the rapid disappearance of BRM from the tumour area is one of the reasons for its limited clinical application. In this pilot study, fibrinogen gel containing OK-432 (a compound composed of attenuated Streptococcus pyogenes), an inducer of natural killer cells and T-cell cytotoxity, was injected directly into head and neck solid tumours of 15 patients. A dose of 5 Klinische Einheiten (KE) of OK-432 was reconstituted in 1 ml aprotinin and mixed with fibrinogen, the latter to maintain the OK-432 locally. 3 patients showed tumour regression, and in addition, we observed histological changes in the injected tumour of all patients. These results suggest that OK-432/fibrinogen gel generates a local immune response, leading to tumour regression.

Intracellular Calcium Changes and Chemosensitivities of Human Epidermoid Carcinoma Cell Lines after Exposure to Cisplatin

In order to elucidate the mechanisms of cisplatin (cis-diamminedichloroplatinum; CDDP)-resistant tumor cells, we previously established a CDDP-resistant KB cell line (KBrc cells) from a parental KB cell line derived from epidermoid carcinoma (KB cells). The KBrc cells were resistant to 5 kinds of platinum (Pt) drugs. Intracellular Pt concentrations in KBrc cells were lower than in KB cells. Decrease of intracellular Pt concentrations was one of the CDDP-resistant mechanisms. When we measured changes of intracellular calcium ion concentration ([Ca2+]i) during exposure to high-dose CDDP, a sustained elevation of the [Ca2+]i level was observed in the KB cells. These results suggest that the mechanisms underlying CDDP resistance involve changes in calcium channels and an alteration of calcium homeostasis in the tumor cell line.

Inhibition of Head and Neck Tumor Cell Colony Growth by Lymphokine Activated Killer Cells

The antiproliferative effect of lymphokine activated killer (LAK) cells on head and neck tumor cells has not previously been elucidated. We studied the inhibitory effects of recombinant interleukin-2 activated lymphocytes on tumor colony formation in semisolid agar, using head and neck tumor cells prepared from established tumor cell lines (K562, HT29, HLaC78) and xenografted head and neck squamous cell carcinomas on nude mice (XKN, XLL, XFL, XKF). LAK cells demonstrated a significant inhibitory effect on colony formation. The effects of LAK cells on cultured tumor cell lines were evaluated in a dose dependent manner using effector: target ratios. In addition, the colony formation of tumor cells derived from xenografted nude mouse was inhibited by LAK cells. These results suggest that LAK cells generate an antiproliferative effect on head and neck tumor cells.

Influence of LAK cells on expression of HLA-DR antigen on laryngeal carcinoma cell line in new culture systems

SummaryWe demonstrated the enhancement of HLA-DR antigen expression on cultured laryngeal carcinoma cells (Hep 2) by in vitro cultivation with LAK cells using flow cytometric and immunohistological analysis. For in vitro cultivation of tumor cells with LAK cells, we used newly developed experimental systems (the Transwell double-dish system and experimental three-dimensional tumors). In flow cytometric analysis, expression of HLA-DR antigen on tumor cells was compared before and after co-cultivation with LAK cells. When tumor cells were cultured separately with LAK cells in a Transwell Petri dish and the expression of HLA-DR antigen on tumor cells was analyzed by flow cytometry, the expression of HLA-DR antigen on tumor cells was increased in a dose-dependent manner related to the number of LAK cells used. Furthermore, when anti-interferon-γ monoclonal antibody was added to the experimental system, enhancement of HLA-DR antigen expression was blocked. These findings were consistent with immunohistological studies, in which experimental three-dimensional Hep 2 cell tumors were established in double-layered agar with/without being co-cultivated with LAK cells. The expression of HLA-DR antigen in this system was significantly increased when compared to such expression before cultivation with LAK cells. These findings suggested that the culture systems employed in this study could be a possible model for examining solid tumor in vivo biological responses. This enhanced expression of HLA-DR antigen may also represent one of the multifactorial responses seen with adoptive LAK cell immunotherapy for solid tumors.

Chemosensitivity Testing of Human Mouth Carcinoma Cell Line

The chemosensitivity of KB cells derived from oral epidermal carcinoma to various antitumor agents was analyzed using the MTT[3-(4,5-dimethyl-2-thiazoyl)-2,5-diphenyl-2H tetrazolium bromide] assay. Optical density (OD) for MTT assay was measured with dual wavelengths. The chemosensitivity of the drugs was evaluated by the 50% OD (OD50) of each drug concentration in the control group. Five platinum (Pt) drugs and 3 anthracycline (AC) drugs were used in this study. The chemosensitivity differed among the 5 Pt drugs. No significant difference was observed among the 3 AC drugs. A linear increase in OD corresponding to an increase in number of cells was observed. When 0.1 M sodium succinate (S.S.) was added to 0.4% MTT, the sensitivity increased five-fold compared to the control group without S.S. The MTT assay is a precise, rapid, easy and inexpensive experimental system useful for evaluation of antitumor drug sensitivity on tumor cell lines.

Magnetic Resonance Imaging of Head and Neck Lesions

Magnetic resonance imaging (MRI) provides high tissue contrast resolution. The structure of soft tissues is clearly demonstrated, so MRI is now one of the most advanced topographical imaging methods. In this study, we used the short TI inversion recovery sequence (STIR method), which is called “fat suppression imaging”, to examine 26 patients (19 males and 7 females) 29 to 80 years of age. The resolution of the soft tissue structures was investigated by analyzing only the contrasts of the lesions, which were divided into 4 Grades according to Roberts classification.Excellent contrast was obtained by the STIR method in almost all the patients. Of the 26 patients, 22 has good contrast, i.e. Grade 2 or more. The contrast of thyroid tumor by STIR was almost the same as that by the short SE sequence, but the contrast of parotid and tongue tumors by STIR was better than that by the short SE sequence. The contrast of parotid tumor by STIR was better than that by the long SE sequence, but the contrasts of thyroid, tongue and neck tumors by STIR was almost the same as that by the long SE sequence.The S/N ratio of the imaging quality by STIR sequence was inferior to that of conventional MRI.However, the imaging quality has improved with advances in the equipment in recent years. The STIR method is expected to be a useful pulse sequence in MRI because it provides high resolution of tissue contrasts