RESUMO
Background: An advanced stage, centrally localized invasive tumor is a major cause of sudden death in lung cancer patients. Currently, chemotherapy, radiotherapy, laser ablation, or surgical resection if possible are the available state-of-the-art treatments but none of these guarantee remedy or long-term relief and are often associated with fatal complications. Allowing localized chemotherapy, by direct and confined drug delivery only at the tumor site, could be a promising option for preoperative down staging or palliative therapy. Here we report the localized and targeted application of intra tumor delivery of chemotherapeutics using a novel device based on the principle of electrospray. Methods: C57BL/6J mice were injected with Lewis lung carcinoma cells subcutaneously. After 15 days, the animals were anesthetized and the tumors were exposed by skin incision. Tumors were electrosprayed with 100 µg cisplatin on days 0 and 2, and tumor volumes were measured daily. Animals were sacrificed on day 7 after the first electrospray and tumors were analyzed by immunohistochemistry. Results: In this proof-of-concept study, we report that the tumor volume was reduced by 81.2% (22.46 ± 12.14 mm3) after two electrospray mediated Cisplatin deliveries, while the control tumor growth, at the same time point, increased by 200% (514.30 ± 104.50 mm3). Moreover, tunnel and Caspase-3 positive cells were increased after Cisplatin electrospray compared to other experimental groups of animals. Conclusion: Targeted drug delivery by electrospray is efficient in the subcutaneous mouse model of lung cancer and offers a promising opportunity for further development toward its clinical application.
RESUMO
BACKGROUND: The vacuum bell (VB) is a valid and the only non-invasive treatment for pectus excavatum (PE). To elevate the sternum the patient himself creates a differential negative pressure inside the VB using a hand pump. A distance and differential pressure measuring device (DPMD) enables us for the first time to assess objectively those parameters. METHODS: After approval by the institutional review board, 53 patients recruited from our outpatient clinic were included in this retrospective study and distributed into three groups (group 1 aged 6 to 10years; group 2 aged 11 to 15years; group 3 aged 16 to 20years). Sternum elevation and differential negative pressure inside the VB compared to atmospheric pressure were assessed with the DPMD, a device developed by engineers at the University of Applied Sciences, Northwestern Switzerland. Pressure-elevation curves were recorded during VB therapy. For statistical comparison of the groups, analysis of variance was used. Post-hoc analysis was performed using the Tukey-Kramer test. A p-value of less than 0.05 was considered to be statistically significant. RESULTS: The VB therapy was monitored in 53 children (39 males, 14 females) aged from 6 to 20years (average, 14years). Relationships were established between the differential negative pressure inside the vacuum bell, the elevation of the sternum, and the patient's age. The younger the patient, the lower is the differential negative pressure difference required to obtain a complete elevation of the sternum. Patient's age, weight, the pectus depth, the differential negative pressure inside the VB, and the elevation of the sternum were correlated. When comparing the depth 25 of the pectus excavatum to the patient's age, a statistically significant difference was verified between the groups 3 and 1 (p=0.0291) and 3 and 2 (p=0.0489). The older the patient, the deeper is the pectus excavatum. However, no statistically significant difference between the groups was found when comparing the sternum elevation to the patient's age (p=0.4574) and the elevation to pressure ratio to the patient's age (p=0.8048). The sternum elevation and the elevation to pressure ratio are independent of the patient's age. CONCLUSIONS: DPMD supplies objective data of the elevation of the sternum and the related pressure inside the VB during its application. Correlation between the patient's age, the elevation of the sternum and the pressure inside the VB were demonstrated, but additional data are needed to better understand their relationship and their impact in the treatment of PE by VB. STUDY TYPE: Diagnostic Study. LEVEL OF EVIDENCE: IV.