Does BRAF mutation status and related clinicopathological factors affect the recurrence rate of ameloblastoma? A systematic review, meta-analysis and metaregression.

OBJECTIVES: This review aims to analyse the recurrence rate in BRAFv600e+ and BRAFv600e- ameloblastomas and explore its association with clinicopathological variables. METHODS: A comprehensive search was conducted using databases including PubMed, Embase, Cochrane Central Register of Controlled Trials, Clinicaltrials.gov, Google Scholar and grey literature, without any limitation on start date or language up to 20 June 2023. A random effect meta-analysis was conducted and Metaregression analyses were performed based on available clinicopathological factors. RESULTS: Fifteen studies met the criteria for meta-analysis of outcomes. There was no significant difference in overall recurrence rates between the two groups (risk difference = 0.001, p-value = 0.987). Increasing male:female ratio in the BRAFv600e+ group was associated with a lower reported recurrence, suggesting a higher recurrence rate in females. The odds of having mandibular lesion were four times higher in BRAFv600e+ cases compared to BRAFv600e- cases (confidence interval: 2.121-7.870, p < 0.001, I2 = 28.37%). CONCLUSION: Within the BRAFv600e+ group, females showed a higher reported recurrence rate. This specific clinical group may benefit from BRAFv600e mutation investigation and potential upscaled surgical treatment and additional BRAF inhibitor therapy, which needs validation in future studies.

Intermittent PI3Kδ inhibition sustains anti-tumour immunity and curbs irAEs.

Phosphoinositide 3-kinase δ (PI3Kδ) has a key role in lymphocytes, and inhibitors that target this PI3K have been approved for treatment of B cell malignancies1-3. Although studies in mouse models of solid tumours have demonstrated that PI3Kδ inhibitors (PI3Kδi) can induce anti-tumour immunity4,5, its effect on solid tumours in humans remains unclear. Here we assessed the effects of the PI3Kδi AMG319 in human patients with head and neck cancer in a neoadjuvant, double-blind, placebo-controlled randomized phase II trial (EudraCT no. 2014-004388-20). PI3Kδ inhibition decreased the number of tumour-infiltrating regulatory T (Treg) cells and enhanced the cytotoxic potential of tumour-infiltrating T cells. At the tested doses of AMG319, immune-related adverse events (irAEs) required treatment to be discontinued in 12 out of 21 of patients treated with AMG319, suggestive of systemic effects on Treg cells. Accordingly, in mouse models, PI3Kδi decreased the number of Treg cells systemically and caused colitis. Single-cell RNA-sequencing analysis revealed a PI3Kδi-driven loss of tissue-resident colonic ST2 Treg cells, accompanied by expansion of pathogenic T helper 17 (TH17) and type 17 CD8+ T (TC17) cells, which probably contributed to toxicity; this points towards a specific mode of action for the emergence of irAEs. A modified treatment regimen with intermittent dosing of PI3Kδi in mouse models led to a significant decrease in tumour growth without inducing pathogenic T cells in colonic tissue, indicating that alternative dosing regimens might limit toxicity.

How effective is 5-Fluorouracil as an adjuvant in the management of odontogenic keratocyst? A systematic review and meta-analysis.

Odontogenic keratocyst (OKC) is known for its benign but aggressive clinical behaviour, and presents a challenge in its management due to high recurrence rate following surgical intervention. The sourcing of Carnoy's solution, the widely used adjunct in OKC treatment, has lately become difficult especially after its banning by the United States Food and Drugs Agency (FDA). This has generated interest in exploring alternative chemical agents such as 5-Fluorouracil (5-FU) and Modified Carnoy's solution (MCS). We conducted a systematic review and meta-analysis to assess the effectiveness of 5-FU as an adjunct following surgical intervention of OKC. A protocol was registered in PROSPERO prior to the literature search. All studies reporting the use of 5-FU in OKC treatment were included in the initial search of multiple literature databases. Of the 148 initially identified articles, three met the criteria for the final appraisal. The relevant data were extracted and a meta-analysis was undertaken in relation to recurrence rate and nerve paraesthesia. There were no recurrence observed in cases treated with 5-FU (n=56), and the incidence of nerve paraesthesia was 20% (none permanent). This systematic review has revealed early encouraging results for 5-FU as an adjunct, however a caution is recommended due to overall low quality of evidence related to individual studies. We present the cumulative evidence on the effectiveness of 5-FU in OKC treatment with discussion on its mechanism of action, safety profile, application protocol, and the implications for clinical practice.

Dental emergencies presenting to maxillofacial units during the COVID-19 pandemic: a five-centre UK hospital study.

Introduction Coronavirus disease (COVID-19) represents an unprecedented challenge to healthcare. Provision of dental services was significantly affected, with limited provision for emergencies resulting in patients increasingly attending hospitals.Objectives and methods The aim of the study was to assess the provision of emergency dental services by the maxillofacial departments during the initial COVID-19 pandemic lockdown in the United Kingdom. At the outset of the first lockdown, we initiated a prospective study to monitor the presentation and management of dental emergencies at five hospital trusts. Data were collected onto an online live database until the lockdown relaxation.Results Of a total of 211 dental emergencies, 156 were infection-related, 42 were trauma-related and 12 were cases of post-operative complications. A proportion of patients (76%) could have been treated in primary care, with 52% of presentations having already been 'triaged' on several occasions by urgent dental hubs and given multiple antibiotic courses, rather than any direct treatment.Conclusion There is a need to restructure emergency dental service provision as well as planning for possible further COVID-19 spikes and future pandemics.

Should we recruit trainees into the Oral and Maxillofacial Surgery pathway at the beginning of the second degree to ensure the long term viability of the specialty?

There has been a sustained decline in the number of trainees applying for entry into the Oral and Maxillofacial Surgery (OMFS) training program, which has sparked further debate on the issue of OMFS training and the future of the specialty in the United Kingdom. Here I discuss the option of recruiting the trainees into the program at the beginning of their second degree to streamline the training, and to improve the recruitment drive to ensure long term viability of the specialty.

The versatility of the Karapandzic flap: A review of 65 cases with patient-reported outcomes.

OBJECTIVE: The Karapandzic flap is an established technique for reconstruction of large lip defects and in our experience is particularly valuable in repair of the upper lateral lip and the commissures as well. We present our experience in a case series of 65 patients under one consultant. METHOD: This is a retrospective study of patients who underwent Karapandzic flap repair for lip defects following cancer resection from 2007 to 2014 in North Yorkshire. A data collection tool was used which incorporated patient demographics, tumour location, histology, complications, resection margins and recurrence including functional and aesthetic outcomes. The Patient and Observer Scar Assessment Scale (POSAS) was used to assess postoperative outcome at more than 1 year. RESULTS: The clearance rate was 98.4%. For those with a follow-up greater than 1 year, there was no recurrence or surgical revision, whilst the most common concern was temporary lip paraesthesia. The mean POSAS scores were low for both patients and observers reflecting a high satisfaction rate. CONCLUSION: The technique of Karapandzic flap reconstruction for defects in both upper and lower lip allows adequate margin clearance with a low level of complications. The advantages of this technique include preservation of both function and sensation utilising local tissue to allow successful aesthetic outcomes.

Antimicrobial prophylaxis in open reduction and internal fixation of compound mandibular fractures: a collaborative regional audit of outcome.

We conducted a regional 2-stage prospective audit involving 5 different maxillofacial units in the Yorkshire region of the UK to evaluate the effectiveness of perioperative antimicrobial prophylaxis in the treatment of mandibular fractures. In the first stage (145 patients) we surveyed current practice concerning antimicrobial prophylaxis and found out the current infection rate after open reduction and internal fixation (ORIF) of mandibular fractures. In the second stage (157 patients) we implemented a common antimicrobial protocol in all units and recorded the infection rates using the new regimen. In the first stage a wide range of antimicrobial prophylaxis was used in different units. The agreed perioperative antimicrobial protocol in the second stage was to begin amoxicillin or clarithromycin and metronidazole intravenously on admission and include 2 postoperative doses. The infection rates were 10.3% and 8.9%, respectively, and the difference between the two groups was not significant (χ(2)=0.051, df=1, p=0.83). The infection rate in the Yorkshire region was similar to results from other centres. We recommend short perioperative antimicrobial prophylaxis with a maximum of 2 postoperative doses after ORIF of mandibular fractures.