Critical Airway Compromise due to a Massive Vagal Schwannoma.

We describe the case of a 37-year-old man with a slowly enlarging neck lump and compressive symptoms. He presented to a separate institution 10 years prior where an observational approach was advocated. Following preoperative investigations and embolization, an 11cm vagal schwannoma was excised and vagus nerve was sacrificed. Although conservative management is appropriate for a select patient population, surgical excision is treatment of choice for cervical neurogenic tumours and paraganglionomas and must be considered in young patients or rapidly expanding tumours to avoid compressive symptoms, as in this case.

Unilateral cochlear implantation in children with a potentially useable contralateral ear.

Increasingly, children are considered for a unilateral CI, even if the contralateral ear falls outside current audiological guidelines, especially if they are not considered to be reaching their educational potential. The primary aim was to investigate the benefit of unilateral CI in children currently outside UK [National Institute for Health and Care Excellence Technology Appraisal Guidance. 2009. Cochlear implants for children and adults with severe to profound deafness. NICE technology appraisal guidance [TAG166]. Available January 29, 2016 from http://www.nice.org.uk/ta166 ] audiological guidelines in the contralateral ear. The secondary aim was to measure compliance. A retrospective case review with standard demographic data was performed. Forty-seven children were identified as having received a unilateral CI with the contralateral ear falling outside of current UK audiological criteria. These children were allocated to two groups; with hearing between 50 and 70 dB, and 70 and 90 dB at 2 and 4 kHz in the contralateral ear, respectively. Categories of auditory performance (CAP) were assessed. Pre- and post-operative CAP scores demonstrated a statistically significant improvement in auditory perception. We would suggest that assessing candidacy in individual ears and subsequent unilateral CI, has given these children a benefit they may not otherwise have acquired if they only had bilateral hearing aid.

Non-viral immune electrogene therapy induces potent antitumour responses and has a curative effect in murine colon adenocarcinoma and melanoma cancer models.

Antitumour efficacy of electroporated pEEV, coding for granulocyte-macrophage colony-stimulating factor and the B7-1 costimulatory immune molecule (pEEVGmCSF-b7.1) in growing solid tumours, was investigated and compared with a standard plasmid. Application of pEEVGmCSF-b7.1 led to complete tumour regression in 66% of CT26-treated tumours and 100% in the B16F10-treated tumours at day 150 post-treatment. pEEVGmCSF-b7.1 treatment was found to significantly enhance levels of both innate and adaptive immune populations in tumour and systemic sites, which corresponded to significantly increased tissue levels of proinflammatory cytokines including interferon-γ (IFN-γ) and interleukin-12 (IL-12). In contrast, pEEVGmCSF-b7.1 treatment significantly reduced the T-regulatory populations and also the anti-inflammatory cytokine IL-10. Upon further characterisation of functional immune responses, we observed a significant increase in cytotoxic (CD107a+) and IFN-γ-producing natural killer cells and also significantly more in IL-12-producing B cells. Importantly, splenocytes isolated from pEEVGmCSF-b7.1-treated 'cured' mice were tumour-specific and afforded significant protection in a tumour rechallenge model (Winn assay). Our data indicate that electroimmunogene therapy with the non-viral pEEVGmCSF-b7.1 is able to induce potent and durable antitumour immune responses that significantly reduce primary and also secondary tumour growth, and thus represents a solid therapeutic platform for pursuing future clinical trials.

Enhancement of electroporation facilitated immunogene therapy via T-reg depletion.

Regulatory T cells (T-regs) can negatively impact tumor antigen-specific immune responses after infiltration into tumor tissue. However, depletion of T-regs can facilitate enhanced anti-tumor responses, thus augmenting the potential for immunotherapies. Here we focus on treating a highly aggressive form of cancer using a murine melanoma model with a poor prognosis. We utilize a combination of T-reg depletion and immunotherapy plasmid DNA delivered into the B16F10 melanoma tumor model via electroporation. Plasmids encoding murine granulocyte macrophage colony-stimulating factor and human B71 were transfected with electroporation into the tumor and transient elimination of T-regs was achieved with CD25-depleting antibodies (PC61). The combinational treatment effectively depleted T-regs compared to the untreated tumor and significantly reduced lung metastases. The combination treatment was not effective in increasing the survival, but only effective in suppression of metastases. These results indicate the potential for combining T-reg depletion with immunotherapy-based gene electrotransfer to decrease systemic metastasis and potentially enhance survival.