Point-of-care Analysis for Non-invasive Diagnosis of Oral cancer (PANDORA): A technology-development proof of concept diagnostic accuracy study of dielectrophoresis in patients with oral squamous cell carcinoma and dysplasia.

BACKGROUND: Delays in the identification and referral of oral cancer remain frequent. An accurate and non-invasive diagnostic test to be performed in primary care may help identifying oral cancer at an early stage and reduce mortality. Point-of-care Analysis for Non-invasive Diagnosis of Oral cancer (PANDORA) was a proof-of-concept prospective diagnostic accuracy study aimed at advancing the development of a dielectrophoresis-based diagnostic platform for oral squamous cell carcinoma (OSCC) and epithelial dysplasia (OED) using a novel automated DEPtech 3DEP analyser. METHODS: The aim of PANDORA was to identify the set-up of the DEPtech 3DEP analyser associated with the highest diagnostic accuracy in identifying OSCC and OED from non-invasive brush biopsy samples, as compared to the gold standard test (histopathology). Measures of accuracy included sensitivity, specificity, positive and negative predictive value. Brush biopsies were collected from individuals with histologically proven OSCC and OED, histologically proven benign mucosal disease, and healthy mucosa (standard test), and analysed via dielectrophoresis (index test). RESULTS: 40 individuals with OSCC/OED and 79 with benign oral mucosal disease/healthy mucosa were recruited. Sensitivity and specificity of the index test was 86.8% (95% confidence interval [CI], 71.9%-95.6%) and 83.6% (95% CI, 73.0%-91.2%). Analysing OSCC samples separately led to higher diagnostic accuracy, with 92.0% (95% CI, 74.0%-99.0%) sensitivity and 94.5% (95% CI, 86.6%-98.5%) specificity. CONCLUSION: The DEPtech 3DEP analyser has the potential to identify OSCC and OED with notable diagnostic accuracy and warrants further investigation as a potential triage test in the primary care setting for patients who may need to progress along the diagnostic pathway and be offered a surgical biopsy.

Cycling-Related Injuries During COVID-19 Lockdown: A North London Experience.

Objectives: There has been a notable surge in cycling injuries during the COVID-19(SARS-CoV-2 virus) pandemic. Cycling in general increased during lockdown as a leisure & fitness activity along with reduction in the use of public transport for commuting. We investigated the bicycle-related maxillofacial injuries & associations presenting through our emergency department(ED) which covers more than 1.6 million of London population. Study Design/Methods: A retrospective observational study was undertaken in the Barnet General Hospital ("hub") which receives all maxillofacial referrals from 6 "spoke" hospitals & other urgent primary/community care practices in North London area between 16 March 2020 & 16 July 2020. All data corresponding to cycling injuries during the lockdown period was analyzed with the aid of trauma database/trust-wide electronic patient records. Results: Twenty-two patients (6.7%) with cycling-related injuries out of a total of 322 patients who attended during the 4 months study period with maxillofacial emergencies were identified. Average age of patient cohort was 35.4 years, mainly consisting of adult males (77%). Seven patients had minor head injury and 1 patient suffered traumatic brain injury. About 59% patients did not wear a protective helmet & 3 patients had heavy alcohol/recreational drug intoxication during the accidents. Four patients needed inpatient admission and treatment under general anesthesia. Conclusions: Based on our humble study, we advocate the need for robust road & personal safety measures with mandatory government legislations, policing of drug intoxication & encouragement of physical & mental health improvement measures during these unprecedented times & beyond.

Small cell neuroendocrine tumour of the anterior tongue: A case report.

INTRODUCTION: Neuroendocrine carcinomas (NECs) are rare in the oral cavity. There is ambiguity regarding the classification of these tumours, but their aggressive nature is recognised throughout the literature. Merkel cell carcinoma (MCC) is rare and more frequent in skin, though it has also been described intra-orally. High grade neuroendocrine tumours (HGNEC) and MCCs behave aggressively and aggressive treatment strategies have been advocated. We describe the first small cell HGNEC on the anterior tongue. PRESENTATION OF CASE: We present the first report of a pT1pN1M0 small cell HGNEC in a 75 year old man on the left lateral anterior tongue. This was widely resected with 20mm peripheral and deep margins to achieve disease clearance. Selective neck dissection of levels 1-4 was also carried out. DISCUSSION: Histological analysis of the tumour confirmed a primary poorly differentiated neuroendocrine tumour of small cell type (small cell HGNEC). Resected node bearing tissue from levels 1-4 confirmed metastasis to a level III node with no extra capsular spread giving a pT1pN1M0 classification. Margins of 11.7mm from the invasive tumour to mucosal margin medially and 7.0mm for the deep margin despite surgical 20mm margin resection. To the best of our knowledge small cell neuroendocrine carcinoma has not been described in the anterior tongue. CONCLUSION: The aggressive nature of this tumour type mandates aggressive surgical resection with margins similar to those now recommended for skin Merkel cell carcinomas. We advocate a wide excision margin of 20mm to give adequate clearance, with neck dissection in order to pathologically stage this cancer type.

First report of squamous cell carcinoma arising within an intraoral radial forearm free flap.

INTRODUCTION: Oral epithelial dysplasia within free tissue reconstructions of the oral cavity has been reported. We report a case where squamous carcinoma arose within radial forearm skin transferred to the oral cavity 23 years previously. After a thorough literature search we believe this is the first report of such a phenomenon. PRESENTATION OF CASE: A 62-year-old man presented to our service with pain and a new mass in the left floor of mouth. The floor of mouth had been reconstructed with a radial forearm free flap (RFFF) 23 years earlier following resection of a mucosal squamous cancer. This new mass was within the reconstruction tissue. Biopsy showed multiple areas of dysplasia and a single new focus of invasive carcinoma. This new tumour was excised and reconstructed with a contralateral nasolabial flap. Formal histology showed an arrector pili muscle adjacent to invasive cancer. Some years earlier dysplasia had been noted in the free flap skin component. DISCUSSION: The skin component of free tissue transfer reconstruction flaps has been shown to develop epithelial dysplastic change. This has been found to be associated with similar levels of p53 mutation and increased Ki-67 expression within this intraoral skin and adjacent dysplastic mucosa. Our case demonstrates similar levels of expression of mutated p53 and Ki-67 in in situ epithelium and in invasive tissue perhaps supporting the idea of expansion of premalignant cells into the skin flap epidermis. CONCLUSION: We have shown for the first time that a new SCCa has developed within the cutaneous component of a free tissue transfer flap. With improved longevity of patients treated with primary surgery for oral cavity SCCa there is need for vigilance in monitoring for this cancer recurrence site.

LIHNCS - Lugol's iodine in head and neck cancer surgery: a multicentre, randomised controlled trial assessing the effectiveness of Lugol's iodine to assist excision of moderate dysplasia, severe dysplasia and carcinoma in situ at mucosal resection margins of oral and oropharyngeal squamous cell carcinoma: study protocol for a randomised controlled trial.

BACKGROUND: Oral cavity and oropharynx cancer are increasing in incidence worldwide but survival outcomes have not significantly improved over the last three decades. The presence of dysplasia or carcinoma in situ at surgical margins following resection of squamous carcinoma of the mucosal surfaces of the head and neck has been shown to be associated with a higher incidence of local recurrence and reduced survival. While invasive carcinoma in mucosal surfaces can usually be distinguished from adjacent normal mucous membrane, pre-malignant disease is much less readily distinguished at operation. We describe a protocol for a randomised, controlled trial in which we will assess the effectiveness of Lugol's iodine staining in allowing visualisation and excision of cancer margin dysplasia at time of primary surgery. METHODS/DESIGN: We will recruit 300 patients diagnosed with oral cavity or oropharynx squamous cell carcinoma. All participants will be planned for primary surgery with curative intent. After completion of baseline assessment participants will be randomised into either a standard surgical treatment arm or surgical treatment including Lugol's iodine staining. DISCUSSION: This paper describes the rationale and design of a unique trial in head and neck surgical oncology. If margin dysplasia visualisation with Lugol's iodine allows complete excision of high-risk, pre-cancer mucosa at time of primary surgery, this may lead to a reduction in local recurrence and improved survival. TRIAL REGISTRATION: Current Controlled Trials ISRCTN03712770.