Acquired nasopharyngeal stenosis after radiation treatment for nasopharyngeal carcinoma.

INTRODUCTION: Nasopharyngeal stenosis (NPS) is a rare and morbid complication following radiation therapy for nasopharyngeal carcinoma. This review provides an update on management and prognosis. METHODS: A comprehensive PubMed review using the terms "nasopharyngeal stenosis," "choanal stenosis," and "acquired choanal stenosis" was performed. RESULTS: Fourteen studies identified 59 patients who developed NPS after radiotherapy for NPC. 51 patients underwent endoscopic nasopharyngeal stenosis excision by cold technique (80-100% success). The remaining 8 underwent carbon dioxide (CO2) laser excision with balloon dilation (40-60% success). Adjuvant therapies included postoperative topical nasal steroids in 35 patients. The need for revision was 62% in the balloon dilation group, vs 17% in the excision group (p-value <0.01). CONCLUSION: When NPS occurs after radiation, primary excision of scarring is the most effective method of management with less need for revision surgery relative to balloon dilation.

A nano-enhanced vaccine for metastatic melanoma immunotherapy.

Aim: Despite the huge advancements in cancer therapies and treatments over the past decade, most patients with metastasized melanoma still die from the disease. This poor prognosis largely results from resistance to conventional chemotherapies and other cytotoxic drugs. We have previously identified 6 antigenic peptides derived from melanomas that have proven efficacious for activating CD4+ T cells in clinical trials for melanoma. Our aim was to improve pharmacodynamics, pharmacokinetic and toxicological parameters by individually encapsulating each of the 6 melanoma helper peptides within their own immunogenic nanoliposomes. Methods: We modified these liposomes as necessary to account for differences in the peptides' chemical properties, resulting in 3 distinct formulations. To further enhance immunogenicity, we also incorporated KDO2, a TLR4 agonist, into the lipid bilayer of all nanoliposome formulations. We then conducted in vivo imaging studies in mice and ex vivo cell studies from 2 patient samples who both strongly expressed one of the identified peptides. Results: We demonstrate that these liposomes, loaded with the different melanoma helper peptides, can be readily mixed together and simultaneously delivered without toxicity in vivo. These liposomes are capable of being diffused to the secondary lymphoid organs very quickly and for at least 6 days. In addition, we show that these immunogenic liposomes enhance immune responses to specific peptides ex vivo. Conclusion: Lipid-based delivery systems, including nanoliposomes and lipid nanoparticles, have now been validated for pharmacological (small molecules, bioactive lipids) and molecular (mRNA, siRNA) therapeutic approaches. However, the utility of these formulations as cancer vaccines, delivering antigenic peptides, has not yet achieved the same degree of commercial success. Here, we describe the novel and successful development of a nanoliposome-based cancer vaccine for melanoma. These vaccines help to circumvent drug resistance by increasing a patient's T cell response, making them more susceptible to checkpoint blockade therapy.