RESUMEN
Glial cells were investigated to elucidate their involvement in mechanisms underlying oral cancer pain. Squamous cell carcinoma (SCC-158) was inoculated into the lower gingiva of male Fisher rats. Pharmacological and immunohistochemical studies were performed to examine the roles played by TRPV1 and TRPV2 expressed in neurons and satellite glia in trigeminal ganglia (TG), and microglia and astrocytes in trigeminal spinal nucleus caudalis. Inoculation of SCC-158 into the lower gingiva induced marked mechanical allodynia in the whisker-pad skin area on days 16 through 28, and in the submandibular skin area on days 10 through 20. Cutaneous allodynia was diminished by systemic morphine administration. The number of TRPV1 and TRPV2-positive neurons in trigeminal ganglia increased in the medium and large cell groups on day 14 after tumor inoculation. The number of satellite glial cells encircling the medium and large trigeminal ganglion neurons increased on day 28 after tumor inoculation. In this gingival cancer pain model, microglia and astrocytes in trigeminal spinal nucleus caudalis were not activated, although they were reported to be activated in neuropathic and inflammatory pain models. These results suggest that TRPV1 and TRPV2 upregulation in trigeminal ganglion neurons may play an important role in inducing the mechanical allodynia observed in experimental models of oral squamous cell carcinoma. In addition, activation of satellite cells seems to be involved in the maintenance of mechanical allodynia, which could be the potential therapeutic target for oral cancer pain.
RESUMEN
BACKGROUND: The aim of this retrospective observational study was to evaluate toxicities, overall survival, and locoregional control in elderly oral squamous cell carcinoma patients who had undergone retrograde intra-arterial chemotherapy combined with radiotherapy. METHODS: Thirty-one elderly patients over 80 years old with oral squamous cell carcinoma were enrolled in present study. The treatment schedule consisted of intra- arterial chemotherapy (docetaxel, total 60 mg/m2; cisplatin, total 150 mg/m2) and daily concurrent radiotherapy (total, 60 Gy) for 6 weeks. RESULTS: The median patient age was 82.5 years old (range, 80-88 years). Of the 31 patients, six (19%) had stage II, 6 (19%) had stage III, 17 (55%) had stage IVA, and 2 (6%) had stage IVB. The median follow-up period for all patients was 37 months (range, 7-86 months). The 3-year overall survival and locoregional control rates were 78% and 81%, respectively. The major acute grade 3 adverse events were oral mucositis in 22 (71%) patients, neutropenia in 16 (52%), and dermatitis in 11 (35%). With respect to late toxicities, 1 patient (3%) developed grade 3 osteoradionecrosis of the jaw. No grade 4 or higher toxicities were observed during the treatment and follow-up periods. CONCLUSIONS: Retrograde intra-arterial chemotherapy combined with radiotherapy was effective in improving overall survival and locoregional control even for elderly patients.