Despite recent advances in both surgery and chemoradiotherapy, mortality rates for advanced cancer remain high. There is a pressing need for novel therapeutic strategies; one option is systemic oncolytic viral therapy. Intravenous administration affords the opportunity to treat both the primary tumour and any metastatic deposits simultaneously. Data from clinical trials have shown that oncolytic viruses can be systemically delivered safely with limited toxicity but the results are equivocal in terms of efficacy, particularly when delivered with adjuvant chemotherapy. A key reason for this is the rapid clearance of the viruses from the circulation before they reach their targets. This phenomenon is mainly mediated through neutralising antibodies, complement activation, antiviral cytokines, and tissue-resident macrophages, as well as nonspecific uptake by other tissues such as the lung, liver and spleen, and suboptimal viral escape from the vascular compartment. A range of methods have been reported in the literature, which are designed to overcome these hurdles in preclinical models. In this paper, the potential advantages of, and obstacles to, successful systemic delivery of oncolytic viruses are discussed. The next stage of development will be the commencement of clinical trials combining these novel approaches for overcoming the barriers with systemically delivered oncolytic viruses.

The incidence of postoperative complications was influenced by the pathology, with inflammatory lesions significantly increasing the risk of facial nerve dysfunction and other complications, but also by variations in surgical practice, such as parotid duct ligation. Overall, the incidence of permanent facial paralysis was less than 2%, but temporary nerve palsy was common at 40%, with most patients regaining normal function within 1 year of the operation.

This study demonstrates that MIVAT is as safe as the existing gold standard operation. Furthermore, it has better cosmetic and pain outcomes for patients when compared to conventional surgery. MIVAT is a promising new technique, with obvious benefits over the established surgery, for small-volume thyroid disease that mainly affects a young female patient population.

Tumor-targeting oncolytic viruses such as vaccinia virus (VV) are attractive cancer therapeutic agents that act through multiple mechanisms to provoke both tumor lysis and anti-tumor immune responses. However, delivery of these agents remains restricted to intra-tumoral administration, which prevents effective targeting of inaccessible and disseminated tumor cells. In the present study we have identified transient pharmacological inhibition of the leukocyte-enriched phosphoinositide 3-kinase δ (PI3Kδ) as a novel mechanism to potentiate intravenous delivery of oncolytic VV to tumors. Pre-treatment of immunocompetent mice with the PI3Kδ-selective inhibitor IC87114 or the clinically approved idelalisib (CAL-101), prior to intravenous delivery of a tumor-tropic VV, dramatically improved viral delivery to tumors. This occurred via an inhibition of viral attachment to, but not internalization by, systemic macrophages through perturbation of signaling pathways involving RhoA/ROCK, AKT, and Rac. Pre-treatment using PI3Kδ-selective inhibitors prior to intravenous delivery of VV resulted in enhanced anti-tumor efficacy and significantly prolonged survival compared to delivery without PI3Kδ inhibition. These results indicate that effective intravenous delivery of oncolytic VV may be clinically achievable and could be useful in improving anti-tumor efficacy of oncolytic virotherapy.

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Objective: To investigate the current practice of intratympanic steroid (ITS) injection for sudden sensorineural hearing loss (SSNHL) in the United Kingdom and link the data with data from the United States and continental Europe. Methods: A survey of 21 questions was distributed to members of the British Society of Otology using an online survey platform via ENT UK. Data obtained from UK otolaryngologists (n = 171) were integrated with previously published data from other countries, including the United States (n = 63) and continental Europe (n = 908). Results: In the United Kingdom, 62% of responding otolaryngologists use ITS injection for SSNHL, while 38% do not. Of those using ITS, 59% use it as first-line treatment, either using it in conjunction with oral steroids (51%) or using it as monotherapy (8%). Of those that use ITS, a majority (83%) use it as salvage therapy when primary treatment with systemic steroids has failed, and similar results are found in the continental Europe and US surveys. The most commonly used preparation is dexamethasone. Responses to questions regarding treatment regimes used are enlightening and show considerable variation in the treatment regimes used within and between countries. Conclusions: There is a wide variation in practice with regards to ITS for SSNHL hearing loss in the United Kingdom, United States, and continental Europe. In the absence of protocols or definitive guidance from published literature, knowledge of contemporary practice may help guide or encourage reevaluation of clinical practice and will help guide the design of future clinical trials.

The optimal treatment of this condition should be local excision, but patients with this condition should be followed up for primary site recurrence and axillary metastasis, because there is greater incidence than with BCC at other anatomical sites. Furthermore, proven axillary metastasis should be surgically treated.

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