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Resection of the submandibular gland is generally undertaken as an integral component of level I neck dissection for oral cancer. However, it is unclear whether lymph nodes are present within the submandibular gland which may form the basis of lymphatic spread. Our purpose was to investigate the frequency of lymph nodes within the submandibular gland, and the incidence and mechanism of submandibular gland involvement in floor of mouth cancer. Retrospective review of 177 patients with oral cancer undergoing neck dissection. Original pathology slides of floor of mouth cases were re-reviewed by two pathologists to determine frequency of intraglandular lymph nodes, and incidence and mechanism of submandibular gland involvement by cancer. The overall incidence of cervical metastases was 36.4 %, of whom 44 % had level I metastases. Level I metastases were significantly more common in floor of mouth than tongue cancers (p = 0.004). Among 50 patients with floor of mouth cancer undergoing re-review of pathology slides, intraglandular lymph nodes were not found in any of 69 submandibular glands. Submandibular gland involvement by cancer was present in two patients, representing 1 % of all oral cancers, and 4 % FOM cases. Mechanisms of involvement were direct extension, and by an apparent novel mechanism of carcinoma growing along bilateral Wharton's ducts. Despite the high incidence of level I metastasis in floor of mouth, lymphatic metastases to submandibular gland are unlikely based on absence of intraglandular lymph nodes. We describe a previously unreported mechanism of submandibular gland involvement.

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PURPOSE: Electrochemotherapy (ECT) is the application of electric pulses to tumour tissue to render the cell membranes permeable to usually impermeant hydrophilic anti-cancer drugs, thereby enhancing cytotoxic effects. We sought to ascertain whether ECT can be an effective palliative treatment for cutaneous metastases of breast cancer. METHODS: This work reports data from the European Standard Operating Procedures for Electrochemotherapy trial (EudraCT Number: 2004-002183-18). In combination with systemic and/or intratumoural bleomycin, optimised electric pulses were delivered to locally recurrent or metastatic cutaneous breast cancer lesions. Follow-up continued until December 2014. RESULTS: Between February 2004 and December 2014, twenty-four patients were treated. All patients had received prior multimodal therapy. In total, the patient cohort had, or developed, 242 lesions. Two hundred and 36 lesions were treated, with 34 lost to follow-up. An objective response was seen in 161 of 202 lesions (79.7%), with a complete response observed in 130 (64.3%). Thirty-nine lesions (19.3%) did not respond, while 2 (1%) progressed following ECT. 17 (73.9%) patients received two or fewer treatments. A minimum of a partial response was seen in at least 50% of treated lesions in 18 of the 24 (75%) patients. Smaller lesions were more likely to have an objective response (Chi-square test for trend, p < 0.001). CONCLUSIONS: Electrochemotherapy is an effective treatment for cutaneous breast cancer lesions that have proven refractory to standard therapies. As smaller lesions were found to be more responsive, we suggest that ECT should be considered as an early treatment modality, within multimodal treatment strategies.

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OBJECTIVE: To assess the compliance with cochlear implantation (CI) in children subsequently diagnosed with autism spectrum disorder (ASD). METHODS: This was a retrospective case review and survey performed at a tertiary referral centre. Children meeting the criteria for CI who were implanted between 1989 and 2015 and who subsequently received a diagnosis of ASD were included. The primary outcome measure was to assess compliance with CI in children subsequently diagnosed with ASD. Secondary outcome measures included assessment of pre-CI risk factors that may have identified children at higher risk of a subsequent diagnosis of ASD, as well as the benefit obtained by these children following CI. RESULTS: 1050 children were implanted between 1989 and 2015. Of these, 22 children were diagnosed with ASD after receiving their CI. The average age at implantation was 2.6 years (median 3, range 1-8 years). The average age for diagnosis of ASD was 5 years, approximately 2 years (median 22 months, range 2-85 months) following CI. Of these, 16/22 (712.7%) regularly use their CI. 6/22 (27.2%) children became non-users of their implant. Some degree of verbal communication was used by 13/22 (59%) of our studied group. CONCLUSION: There is a range of level of disabilities in ASD, with some relatively minor social communication difficulties through to severe language, cognitive, and behavioural difficulties. Compliance with CI is variable and appears to correlate with the severity of the ASD. Preoperative counselling should include information about the possible impact of later diagnosed disabilities such as ASD on performance.

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BACKGROUND AND STUDY AIMS: Targeted delivery of specific chemotherapeutic drugs into tumors can be achieved by delivering electrical pulses directly to the tumor tissue. This causes a transient formation of pores in the cell membrane that enables passive diffusion of normally impermeant drugs. A novel device has been developed to enable the endoscopic delivery of this tumor permeabilizing treatment. The aim of the preclinical studies described here was to investigate the efficacy and safety of this nonthermal ablation system in the treatment of gastrointestinal cancer models. METHODS: Murine, porcine, and canine gastrointestinal tumors and tissues were used to assess the efficacy and safety of electroporation delivered through the special device in combination with bleomycin. Tumor cell death, volume, and overall survival were recorded. RESULTS: Murine tumors treated with electrochemotherapy showed excellent responses, with cell death being induced rapidly, mainly via an apoptotic-type mechanism. Use of the system in canine gastrointestinal cancers demonstrated successful local endoluminal tumor resolution, with no safety or adverse effects noted. CONCLUSIONS: Electroporation via the new device in combination with bleomycin offers a nonthermal tumor ablative approach, and presents clinicians with a new option for the management of gastrointestinal cancers.

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Nonviral plasmid DNA gene therapy represents a promising approach for the treatment of many diseases including cancer. Intracellular delivery of DNA can be achieved with the application of electroporation, which facilitates the initial transport of exogenous DNA across the cell membrane into the cytoplasm. However, it does not guarantee further transport of the DNA from the cytoplasm to the nucleus for subsequent mRNA expression, resulting in varying degrees of exogenous gene translation and a major limitation in comparison to viral approaches. To overcome these expression difficulties, we developed a proof-of-concept vector enhanced expression vector (EEV), which incorporates elements from viral systems including nuclear localization sequences and a viral replicase from the Semliki Forest virus. The replicase allows for cytoplasmic mRNA expression and bypasses the need for nuclear localization to generate high levels of gene expression. We have demonstrated that our EEV is capable of achieving high levels of expression in a variety of tissue types. Antitumor effects of pEEV were demonstrated by the delayed growth and increased survival of the nontherapeutic pEEV-treated CT26 tumor model. Using a novel endoscopic electroporation system, EndoVe, we demonstrate and compare, for the first time, both standard cytomegalovirus (CMV) promoter-driven plasmid and EEV gene expression in intraluminal porcine tissues. Our EEV plasmid displays reliable and superior expression capability, and due to its inherent induced oncolytic activity in transfected cells, it may enhance the efficacy and safety of several cancer immunogene therapy approaches.

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PURPOSE: The aim of this review article is to provide a concise overview of the pre-clinical development of electrochemotherapy (ECT), its present utility in clinical practice and to examine its potential application to therapeutic modalities in the future. RESULTS: Results from the ESOPE trial demonstrate an 85% objective response rate (ORR) in solid cutaneous and subcutaneous tumours of varying histologies, that would previously have been recalcitrant to conventional therapies. Experimentally, neoadjuvant immunogene therapy of primary cancers has been found to be effective against minimal residual disease in metastatic models. As such, combinations of electrogene delivery and electrochemothearpy offer exciting possibilities for both local and systemic control of heretofore incurable cancers. CONCLUSIONS: Electrochemotherapy is a quick, safe, inexpensive treatment modality that has been shown to give consistently reproducible results in the treatment of solid cutaneous and subcutaneous malignant tumours. To date, its clinical license has limited its application to a palliative setting. Future work includes looking to extend this therapeutic profile to the management of primary tumours and earlier stage disease, as well as examining the potential for combining electrochemotherapy with gene and immunotherapies and developing novel electrode designs to facilitate the application of this treatment to internal cancers.

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