A review of recent advances in histopathological assessment of head and neck squamous cell carcinoma.

Squamous cell carcinoma (SCC) is the most common non-cutaneous head and neck (H&N) malignancy. Referrals for suspected SCC are seen by oral and maxillofacial surgery (OMFS) surgeons and represent the bulk of 2-week wait referrals. The diagnosis and treatment of SCC is heavily influenced by national and international guidelines. The majority of research and funding is directed towards this condition. This has led to continuous changes to update these guidelines. However, there remain areas of controversy and conflicting evidence. This article summarises articles pertinent to pathologists between 2016 and 2018 published in the leading British OMFS journal. A total of 22 published articles relating to the histopathology of non-cutaneous H&N SCC were selected.

Recent advances in the histopathological assessment of salivary disease.

BACKGROUND: Salivary gland disease includes a wide range of unique and rare conditions that are treated by ear, nose and throat (ENT), oral and maxillofacial surgeons (OMFS) and oral medicine specialists. Histopathological diagnosis is pivotal to making a diagnosis and treatment planning. There is a vast range of conditions and controversies in the histopathological assessment of salivary gland diseases. Most colleagues in oral pathology and oral medicine work closely with the OMFS but might have missed some of the recent articles published by the speciality. METHODS: We reviewed articles thought to be relevant to oral medicine and pathology specialists published over an 8-year period between 2012 and 2019 in the leading British Journal of Oral and Maxillofacial Surgery (BJOMS). RESULTS: A total of 44 published articles relating to the histopathology of salivary glands disease were selected. Papers were published on population studies, benign and malignant tumours, sialadenitis, metastasis to the parotid gland and cytology. The publication type and numbers published were as follows: review (n = 9), meta-analysis/randomised controlled study (n = 1), retrospective study (n = 10) and case report/technical notes (n = 23). CONCLUSIONS: The greatest proportion of publications published in BJOMS were case reports. This emphasises the paucity of consensus and the need for development in this field. Salivary gland disease remains an area with many controversies and would benefit from further research.

Neuroprotective arylpiperazine dopaminergic/serotonergic ligands suppress experimental autoimmune encephalomyelitis in rats.

Arylpiperazine-based dopaminergic/serotonergic ligands exert neuroprotective activity. We examined the effect of arylpiperazine D2 /5-HT1A ligands, N-{4-[2-(4-phenyl-piperazin-1-yl)-ethyl}-phenyl]-picolinamide (6a) and N-{3-[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-picolinamide (6b), in experimental autoimmune encephalomyelitis (EAE), a model of neuroinflammation. Both compounds (10 mg/kg i.p.) reduced EAE clinical signs in spinal cord homogenate-immunized Dark Agouti rats. Compound 6b was more efficient in delaying the disease onset and reducing the maximal clinical score, which correlated with its higher affinity for D2 and 5-HT1A receptors. The protection was retained if treatment was limited to the effector (from day 8 onwards), but not the induction phase (day 0-7) of EAE. Compound 6b reduced CNS immune infiltration and expression of mRNA encoding the proinflammatory cytokines tumor necrosis factor, IL-6, IL-1, and GM-CSF, TH 1 cytokine IFN-γ, TH 17 cytokine IL-17, as well as the signature transcription factors of TH 1 (T-bet) and TH 17 (RORγt) cells. Arylpiperazine treatment reduced apoptosis and increased the activation of anti-apoptotic mediators Akt and p70S6 kinase in the CNS of EAE animals. The in vitro treatment with 6b protected oligodendrocyte cell line OLN-93 and neuronal cell line PC12 from mitogen-activated normal T cells or myelin basic protein-activated encephalitogenic T cells. In conclusion, arylpiperazine dopaminergic/serotonergic ligands suppress EAE through a direct neuroprotective action and decrease in CNS inflammation. Arylpiperazine dopaminergic/serotonergic ligands reduce neurological symptoms of acute autoimmune encephalomyelitis in rats without affecting the activation of autoreactive immune response, through mechanisms involving a decrease in CNS immune infiltration, as well as direct protection of CNS from immune-mediated damage. These data indicate potential usefulness of arylpiperazine-based compounds in the treatment of neuroinflammatory disorders such as multiple sclerosis.

Interactions of N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-2-aryl-2-yl-acetamides and 1-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-3-aryl-2-yl-ureas with dopamine D2 and 5-hydroxytryptamine 5HT(1A) receptors.

It is suggested that the ratio of dopamine D(2) to 5-hydroxytryptamine 5-HT(1A) activity is an important parameter that determines the efficiency of antipsychotic drugs. Here we present the synthesis of N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-2-aryl-2-yl-acetamides and 1-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-3-aryl-2-yl-ureas and their structure-activity relationship studies on dopamine D(2) and 5-hydrohytryptamine 5-HT(1A) receptors. It was shown that ligand selectivity and affinity strongly depends on their topology and the presence of a pyridyl group in the head of molecules. Molecular modeling studies using homology modeling and docking simulation revealed a rational explanation for the ligand behavior. The observed binding modes and receptor-ligand interactions provided us with a clue for optimizing the optimal selectivity towards 5-HT(1A) receptors.

MRCS Performance by OMFS trainees: an update and call to action.

Completion of the Intercollegiate Membership of the Royal College of Surgeons (MRCS) examination is a prerequisite for completion of specialty surgical training in UK. The aim of this study was to compare MRCS performance of OMFS trainees to trainees in other specialities over the past 13 years. Differential attainment (DA) was noted in MRCS Part A (MCQ) pass rates. There was no statistically significant difference in MRCS Part B pass rates. The reasons for this DA are currently unknown and require further investigation. It has been suggested that this may be due at least in part to competing time, family and financial obligations, which increase over time.

Hypoxia mimetics restore bone biomineralisation in hyperglycaemic environments.

Diabetic patients have an increased risk of fracture and an increased occurrence of impaired fracture healing. Diabetic and hyperglycaemic conditions have been shown to impair the cellular response to hypoxia, via an inhibited hypoxia inducible factor (HIF)-1α pathway. We investigated, using an in vitro hyperglycaemia bone tissue engineering model (and a multidisciplinary bone characterisation approach), the differing effects of glucose levels, hypoxia and chemicals known to stabilise HIF-1α (CoCl2 and DMOG) on bone formation. Hypoxia (1% O2) inhibited bone nodule formation and resulted in discrete biomineralisation as opposed to the mineralised extracellular collagen fibres found in normoxia (20% O2). Unlike hypoxia, the use of hypoxia mimetics did not prevent nodule formation in normal glucose level. Hyperglycaemic conditions (25 mM and 50 mM glucose) inhibited biomineralisation. Interestingly, both hypoxia mimetics (CoCl2 and DMOG) partly restored hyperglycaemia inhibited bone nodule formation. These results highlight the difference in osteoblast responses between hypoxia mimetics and actual hypoxia and suggests a role of HIF-1α stabilisation in bone biomineralisation that extends that of promoting neovascularisation, or other system effects associated with hypoxia and bone regeneration in vivo. This study demonstrates that targeting the HIF pathway may represent a promising strategy for bone regeneration in diabetic patients.

Enhanced photodynamic therapy and fluorescence imaging using gold nanorods for porphyrin delivery in a novel in vitro squamous cell carcinoma 3D model.

Nanocomposites of gold nanorods (Au NRs) with the cationic porphyrin TMPyP (5,10,15,20-tetrakis(1- methyl 4-pyridinio)porphyrin tetra(p-toluenesulfonate)) were investigated as a nanocarrier system for photodynamic therapy (PDT) and fluorescence imaging. To confer biocompatibility and facilitate the cellular uptake, the NRs were encapsulated with polyacrylic acid (PAA) and efficiently loaded with the cationic porphyrin by electrostatic interaction. The nanocomposites were tested with and without light exposure following incubation in 2D monolayer cultures and a 3D compressed collagen construct of head and neck squamous cell carcinoma (HNSCC). The results showed that Au NRs enhance the absorption and emission intensity of TMPyP and improve its photodynamic efficiency and fluorescence imaging capability in both 2D cultures and 3D cancer constructs. Au NRs are promising theranostic agents for delivery of photosensitisers for HNSCC treatment and imaging.

Epidemic of Zika virus and maxillofacial surgery.

Zika is a RNA virus spread by the ubiquitous Aedes mosquitoes. It was first discovered in Uganda in 1947, and arrived in south-east Asia by the middle of the 20th century. In 2014 the virus started to spread across the Pacific Islands to reach South America. Since then it has spread rapidly northwards, and reached Mexico and the Caribbean in November 2015. Clinically it presents as a self-limiting febrile illness. However, there is increasing evidence of a link between Zika virus and the Guillain-Barré syndrome, and maternal Zika virus infection and microcephaly of the fetus.

Cross-specialty developments: a summary of the mutually relevant recent literature from the journal of plastic, reconstructive and aesthetic surgery.

Keeping abreast of current developments is increasingly challenging when the volume of specialty articles being published is rising exponentially, and it is most acute when surgical specialties overlap, as in the case of head, neck, and facial reconstructive surgery. Here, the potential for missing key developments presents a compelling case for a summary article that highlights articles likely to be of mutual relevance. We evaluated 129 original studies and 6 reviews published in the Journal of Plastic, Reconstructive, and Aesthetic Surgery between September 2012 and August 2014, and summarised the main papers of interest and merit under the subheadings of head and neck reconstruction, cleft lip and palate, craniomaxillofacial surgery, facial palsy, facial trauma, and aesthetic surgery. Most of the evidence presented (86%) is level 4.

Recent advances in the management of oral and maxillofacial trauma.

This review summarises recently published papers on maxillofacial trauma in 2 widely read journals: the British Journal of Oral and Maxillofacial Surgery (BJOMS) and the International Journal of Oral and Maxillofacial Surgery (IJOMS). Since a large proportion of the injuries seen in oral and maxillofacial surgery (OMFS) departments are fractures of the facial skeleton, we primarily focus on their assessment and treatment, but also cover problems that affect the temporomandibular joint (TMJ) (including ankylosis), military injuries, polytrauma, and the use of perioperative drugs. Between 2012 and 2013, 121 articles were published in the 2 journals. Most of the research concerned mandibular fractures, particularly those involving the condyle, but epidemiological studies and midfacial fractures were also well represented. Even though the incidence of facial injury is high, it is difficult to collect data particularly when long-term evaluation is required, as rates of compliance and attendance at follow up tend to be low. The number of large-scale studies was therefore small. A concerted effort to collaborate nationally and across specialties to undertake larger studies will help to improve outcomes.

Tetracycline: a cure all?

Tetracyclines are used to treat a range of oral conditions. Their efficacy in the treatment of periodontitis is well established, and they are authoritatively recommended in the management of avulsed teeth. There is a growing evidence base to support the use of tetracycline to treat recurrent aphthous stomatitis, but its use in white spongy naevus is limited to a handful of case reports. The mechanism of action in these conditions is either unknown or indicated to be through the inhibition of matrix metalloproteinases (MMP). The use of a single agent to treat diverse oral conditions has important implications for oral medicine.

Regenerative nanotechnology in oral and maxillofacial surgery.

Regenerative nanotechnology is at the forefront of medical research, and translational medicine is a challenge to both scientists and clinicians. Although there has been an exponential rise in the volume of research generated about it for both medical and surgical uses, key questions remain about its actual benefits. Nevertheless, some people think that therapeutics based on its principles may form the core of applied research for the future. Here we give an account of its current use in oral and maxillofacial surgery, and implications and challenges for the future.

Molecular modeling of 5HT2A receptor - arylpiperazine ligands interactions.

In this paper, we report the molecular modeling of the 5HT2A receptor and the molecular docking of arylpiperazine-like ligands. The focus of the research was on explaining the effects the ligand structure has on the binding properties of the 5HT2A receptor and on the key interactions between the ligands and the receptor-binding site. To see what the receptor­ligand interactions were, various substituents were introduced in one part of the ligand, keeping the rest unchanged. In this way, using a docking analysis on the proposed 5HT2A receptor model, we identified key receptor­ligand interactions and determined their properties. Those properties were correlated with experimentally determined binding affinities in order to determine the structure to activity relationship of the examined compounds.

Analysis of the compatibility of dental implant systems in fibula free flap reconstruction.

As a result of major ablative surgery, head and neck oncology patients can be left with significant defects in the orofacial region. The resultant defect raises the need for advanced reconstruction techniques. The reconstruction in this region is aimed at restoring function and facial contour. The use of vascularised free flaps has revolutionised the reconstruction in the head and neck. Advances in reconstruction techniques have resulted in continuous improvement of oral rehabilitation. For example, endosteal implants are being used to restore the masticatory function by the way of prosthetic replacement of the dentition. Implant rehabilitation usually leads to improved facial appearance, function, restoration of speech and mastication. Suitable dental implant placement's site requires satisfactory width, height and quality of bone. Reconstruction of hard tissue defects therefore will need to be tailored to meet the needs for implant placement.The aim of this feasibility study was to assess the compatibility of five standard commercially available dental implant systems (Biomet 3i, Nobel Biocare, Astra tech, Straumann and Ankylos) for placement into vascularised fibula graft during the reconstruction of oromandibular region.Radiographs (2D) of the lower extremities from 142 patients in the archives of the Department of Radiology in University College London Hospitals (UCLH) were analysed in this study. These radiographs were from 61 females and 81 males. Additionally, 60 unsexed dry fibular bones, 30 right sided, acquired from the collection of the Department of Anatomy, University College London (UCL) were also measured to account for the 3D factor.In the right fibula (dry bone), 90% of the samples measured had a width of 13.1 mm. While in the left fibula (dry bone), 90% of the samples measured had a width of 13.3 mm. Fibulas measured on radiographs had a width of 14.3 mm in 90% of the samples. The length ranges of the dental implants used in this study were: 7-13 mm (Biomet 3i), 10-13 mm (Nobel biocare), 8-13 mm (Astra Tech), 8-12 mm (Straumann ) and 8-11 mm (Ankylos).This study reached a conclusion that the width of fibula is sufficient for placement of most frequently used dental implants for oral rehabilitation after mandibular reconstructive procedures.

Stratification of the risk of serious allergic cutaneous reactions with therapeutic management of trigeminal neuralgia.

Patients with the HLA-B*1502 allele have a high risk of serious allergic cutaneous reactions from antiepileptic drugs used in the management of trigeminal neuralgia. Awareness of this uncommon but potentially fatal reaction will help to avoid the use of these drugs in patients from racial groups at high risk.

Stem cells in head and neck squamous cell carcinoma.

The existence of a small subpopulation of tumourigenic cancer stem cells in the bulk of human head and neck squamous cancers (SCC) has been recognised in recent reports. This subpopulation has self-renewal properties and is responsible for the production of differentiated daughter cells that form the bulk of the tumour. Stem cells in head and neck SCC can be identified functionally using their self-renewal properties, or by their characteristic surface markers. As their resistance to contemporary cancer treatments may eventually lead to the failure of treatment there is an urgent need to better understand their biology with the ultimate goal of developing new diagnostic markers and curative cancer treatments.