RESUMEN
Despite aggressive treatment with radiation and combination chemotherapy following tumor resection, the 5-year survival rate for patients with head and neck cancer is at best only 50%. In this study, we examined the therapeutic potential of localized release of diclofenac from electrospun nanofibers generated from poly(D,L-lactide-co-glycolide) polymer. Diclofenac was chosen since anti-inflammatory agents that inhibit cyclooxygenase have shown great potential in their ability to directly inhibit tumor growth as well as suppress inflammation-mediated tumor growth. A mouse resection model of oral carcinoma was developed by establishing tumor growth in the oral cavity by ultrasound-guided injection of 1 million SCC-9 cells in the floor of the mouth. Following resection, mice were allocated into four groups with the following treatment: 1) no treatment, 2) implanted scaffolds without diclofenac, 3) implanted scaffolds loaded with diclofenac, and 4) diclofenac given orally. Small animal ultrasound and magnetic resonance imaging were utilized for longitudinal determination of tumor recurrence. At the end of 7 weeks following tumor resection, 33% of mice with diclofenac-loaded scaffolds had a recurrent tumor, in comparison to 90%-100% of the mice in the other three groups. At this time point, mice with diclofenac-releasing scaffolds showed 89% survival rate, while the other groups showed survival rates of 10%-25%. Immunohistochemical staining of recurrent tumors revealed a near 10-fold decrease in the proliferation marker Ki-67 in the tumors derived from mice with diclofenac-releasing scaffolds. In summary, the local application of diclofenac in an orthotopic mouse tumor resection model of oral cancer reduced tumor recurrence with significant improvement in survival over a 7-week study period following tumor resection. Local drug release of anti-inflammatory agents should be investigated as a therapeutic option in the prevention of tumor recurrence in oral squamous carcinoma.
Asunto(s)
Carcinoma de Células Escamosas/tratamiento farmacológico , Diclofenaco/farmacología , Neoplasias de la Boca/tratamiento farmacológico , Nanofibras/química , Animales , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Inhibidores de la Ciclooxigenasa/administración & dosificación , Inhibidores de la Ciclooxigenasa/farmacocinética , Inhibidores de la Ciclooxigenasa/farmacología , Diclofenaco/administración & dosificación , Diclofenaco/farmacocinética , Implantes de Medicamentos , Liberación de Fármacos , Humanos , Inflamación/complicaciones , Inflamación/tratamiento farmacológico , Ratones Desnudos , Neoplasias de la Boca/mortalidad , Neoplasias de la Boca/patología , Neoplasias Experimentales/tratamiento farmacológico , Poliglactina 910/química , Tasa de Supervivencia , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVES: The collection of bone debris during the preparation of sinus floor augmentations is a commonly used technique for avoiding autologous bone transplants and thereby reducing donor site morbidity. However, the collected bone debris has a higher risk of bacterial contamination. The aim of this retrospective study was to analyse whether the use of a bone filter had an impact on the infection rates after sinus floor augmentation. MATERIALS AND METHODS: A retrospective analysis was conducted of 340 sinus floor elevations (136 using a bone filter) in 249 patients. The sinus floor elevations were performed with the lateral approach. RESULTS: Localised infection occurred in 7.0 % (24 of 340) of the sinus floor elevations. In 40.0 % of the cases, a bone filter was used, and in this group, the infection rate was 13.0 %. In the control group, the infection rate was 4.0 %. One hundred one patients received bone transplants from the iliac crest, and these patients had a lower infection rate of 2.0 %. Stepwise factor reduction, according to Akaike, showed the use of a bone filter to be the most relevant factor for postoperative infection. CONCLUSIONS: To reduce the amount of bacteria, full-mouth disinfection with chemical agents and a strict aspiration protocol should be used when a bone filter is applied. Antibiotic prophylaxis should be prescribed to reduce the risk of postoperative infections further. CLINICAL RELEVANCE: In use of a bone filter, there is the possibility of higher infection rates of sinus floor augmentations.