Consultant Oral & Maxillofacial Surgeon

Professor & Head of Academic Department of Surgery, University of Portsmouth

Former Editor of The British Journal of Oral & Maxillofacial Surgery 

Unit: Portsmouth

Correspondence Address:  Maxillofacial Unit, Queen Alexandra Hospital, Portsmouth PO6 3LY

Professor Peter Brennan has been a consultant Oral and Maxillofacial Surgeon at Portsmouth Hospitals NHS Trust since 2002. He is also honorary Professor of Surgery and Head of the Academic Department of Surgery, at the University of Portsmouth. He qualified with honours in both medicine (1994) and dentistry (1987) gaining distinctions and winning many prizes in subjects including anatomy, pharmacology, anaesthetics, surgery, obstetrics and gynaecology and ophthalmology. He was awarded the gold medal for outstanding performance in the intercollegiate exit FRCS examination in oral and maxillofacial surgery.

Peter Brennan’s main clinical interests are head and neck malignancy, reconstructive free flap surgery and neck lumps. In a research capacity, he has ongoing projects in both basic science and clinical research. The basic science research is two-fold: the role of nitric oxide in oral cancer biology and adhesion molecules in cancer. He is a research supervisor, an examiner for higher research degrees and has published over 220 papers to date covering many aspects of oral and maxillofacial surgery, not exclusively cancer. He has published in the prestigious journal Cancer Research, in collaboration with Professor Salvador Moncada’s laboratory at the Wolfson Institute, London.

Peter Brennan’s research has been awarded both National and International research prizes, and he has lectured extensively in the UK and abroad. He is an assessor for several grant awarding bodies. He is committed to teaching and education, and is an examiner  for the MRCS. He reviews for many general and specialist journals and is Editor of the British Journal of Oral and Maxillofacial Surgery. He is an editor of the textbook Operative Oral and Maxillofacial Surgery: 2nd Edition and the new Oxford Handbook for Oral & Maxillofacial Surgery - which specifically targets Foundation Year Doctors and Dental Foundation Year 2 Dentists.

Peter has many outside interests but has a particular passion for the wines of Bordeaux and Burgundy

Peter Brennan’s research has been awarded both National and International research prizes, and he has lectured extensively in the UK and abroad. He is an assessor for several grant awarding bodies. He is committed to teaching and education, and has recently been appointed as Chair to the Court of Examiners at the Royal College of Surgeons of England for the MRCS examination. He reviews for many general and specialist journals and is the Editor of the British Journal of Oral and Maxillofacial Surgery. Peter has many outside interests but has a particular passion for the wines of Bordeaux and Burgundy

Six key words that describe my research interests.

Angiogenesis, adhesion molecules, radiology, education

How I first began pursuing research:

Became interested at dental school, and subsequently while working in general surgery for the great Professor Sir Roy Calne, FRS in Cambridge. He showed that it was possible to combine a busy surgical job with research, and was hugely inspirational, having been the first to use cyclosporine in transplant surgery.

What higher research degree did you pursue ?

 MD

Which university were you registered with for your higher research degree.

London

My supervisor/s

Professor Salvador Moncada, FRS, Professor JD Langdon

My higher degree thesis abstract

Since its discovery as a biological messenger in 1987, nitric oxide (NO) has undergone an image change. Formerly regarded as a toxic pollutant gas, it has now become the subject of intense research in many fields of medicine and science. NO has a vast range of physiological and pathological actions, many of which are still poorly understood. It has a complex role in the biology of cancer, being implicated in both progression and inhibition of tumour growth.

Although NO is produced by an enzyme family called NO synthase (NOS), most cancer research has been directed towards the isoenzyme NOS2, which produces sustained concentrations of NO. There are only a few published studies on the action of NO and NOS in the head and neck. Furthermore, there would appear to be no reports that have investigated the possible correlation of NOS2 with p53, p21 and cellular proliferation in oral cancer.

NOS2, p53, p21, and Ki-67 protein expression was assessed with immunochemistry and Western blotting in 56 cases of oral squamous cell carcinoma. In selected cases, the citrulline assay technique was also used to determine NOS2 activity. Exons 5-8 of the p53 gene were studied by polymerase chain reaction (PCR) and sequencing.

Significant correlations were found between NOS2 expression and enzyme activity (P<0.001), NOS2 and lymph node status (P<0.005) and NOS2 and p53 expression (P<0.001). No correlations were found between NOS2 and other clinical and pathological parameters.

These findings, together with some additional electron microscopy work that has been performed in relation to NOS2 expression, are discussed in relation to the biology of cancer. Inhibition of NOS2 could have future therapeutic applications in head and neck and other cancers. Further work will be directed to the effects of NOS2 at a cellular level in oral cancer.

My main sources of research funding

RCS research fellowship, BAOMS research grants

My clinical commitment during my research period

During my one year fellowship, I maintained a clinical commitment (and salary) with regular on call work.

An account of my current and ongoing research

As a result of being honorary editor of BJOMS (an unpaid position taking up about 15 hours of my time per week) and working a busy NHS job, my basic science research has suffered recently! I am still very active in clinically based research projects, mainly at the pathology-surgery and imaging-surgery interface.

Current active grants and project titles

£50K BAOMS- tumour stromal reaction to oral SCC

£10K- supervising an SpR on the oral mucosal reaction to bisphosphonates

My  advice for budding OMFS researchers.

Give it some serious thought. Once you decide to do a higher degree or similar, your peers will expect you to achieve this and blame you if you don’t. Plan things carefully, choose a good and enthusiastic supervisor who can keep you on track. Don’t loose touch with the clinical side, which after all is what drives most of us. Try and get as many good quality papers as you can and collaborate with colleagues on projects to share tasks and papers!!

Delighted to speak to any colleagues who would like an informal chat/advice

Any difficulties encountered when returning back to Specialist training (if any) ?

Found it difficult to return to surgery at the same level of competence and didn’t appreciate that inevitably skills would need sharpening up again! However, within a few weeks, the operative skills were at the level they had been before taking the year out!

Best five papers published:

1. McLeod NM, Jess A, Anand R, Tilley E, Higgins B, Brennan PA. Role of chest CT in staging of oropharyngeal cancer: a systematic review. Head Neck. 2009;31:548-55

2. Shang ZJ, Ethunandan M, Górecki DC, Brennan PA. Aberrant expression of beta-dystroglycan may be due to processing by matrix metalloproteinases-2 and -9 in oral squamous cell carcinoma. Oral Oncol. 2008;44:1139-46

3. Brennan PA, Oeppen RS, Bater MC, Khosla N, Davies B, Puxeddu R, Atchley J. CT and duplex scanning: a comparison of imaging techniques for evaluation of the carotid tree in head and neck cancer patients. Oral Oncol. 2008;44:1009-13

4. Brennan PA, Mackenzie N, Oeppen RS, Kulamarva G, Thomas GJ, Spedding AV.Prospective randomized clinical trial of the effect of needle size on pain,sample adequacy and accuracy in head and neck fine-needle aspiration cytology.Head Neck. 2007;29:919-22

5. Quintero M, Brennan PA, Thomas GJ, Moncada S. Nitric oxide is a factor in the stabilization of hypoxia-inducible factor-1alpha in cancer: role of free radical formation. Cancer Res. 2006;66:770-4.

My current involvement in  clinical trials:

SEND Trial- second highest recruiter of patients to date.

Several other trials as lead investigator planned

Any additional comments/ suggestions ?

Enjoy it, and when you are having a bad day, don’t let it get you down. Remember you are doing this over and above the requirements for training and you are going to make a real difference both to development of our specialty and to furthering knowledge in your chosen area.

Professor in the Faculty of Health, Edge Hill University
Consultant Maxillofacial Surgeon at the University Hospital Aintree and Honorary Reader, University of Liverpool

Unit: Evidence-Based Practice Research Centre (EPRC) and Regional Oral and Maxillofacial Unit, Liverpool, L9 1AE, UK

Correspondence Address:  Evidence-Based Practice Research Centre (EPRC), Faculty of Health,  Edge Hill University, St Helens Road, Ormskirk, L39 4QP and Regional  Oral andMaxillofacial Unit, University Hospital Aintree, Liverpool, L9 1AE, UK

Simon qualified from Sheffield University Dental School in 1984. He became a Fellow of the Dental Faculty of the Royal College of Surgeons England in 1988 and qualified with honours from Birmingham University Medical School in 1990.  In 1994 he passed his general surgical fellowship from the Royal College of Surgeons England and in 1997 won the gold medal in the Intercollegiate Oral and Maxillofacial exit examination.  In January 1999 Simon was appointed Consultant Oral and Maxillofacial Surgeon at the University Hospital Aintree and Honorary Reader, University of Liverpool. He is part of the multidisciplinary head and neck team and specialises in oral and oropharyngeal cancer and microvascular free tissue reconstruction. He has an interest is in health related quality of life following oral cancer and in 2000 was awarded his MD from the University of Birmingham. In 2002 he was awarded a Hunterian Professorship from the Royal College of Surgeons of England for his research into the relationship between function and quality of life following primary surgery for oral and oropharyngeal cancer. In November 2006 he joined Edge Hill University, Faculty of Health and has a Chair in the Evidence based Practice Research Centre (www.edgehill.ac.uk/eprc).

He is very active in the field of outcomes research and has published widely on this topic (www.headandneckcancer.co.uk). In the year end 2009 he had published 172 journal articles with a further 12 in press, 7 book chapters and 1 book. He has been invited to speaker at many national and international scientific meetings. In 2009 he gave the Nunn Lecture at the annual scientific meeting of the British Association of Head and Neck Oncologists. He has organised six International H&N HRQOL workshops hosted at Liverpool the last being in November 2008. He is currently Chairman of the BAOMS Clinical Effectiveness Sub-committee. He is also an invited member of the H&N Group of the National Cancer Research Institute and sits on the Survivorship subgroup. Since 2005 he has been Clinical Director of the Regional Maxillofacial Unit. In 2006 he was awarded the prestigious BAOMS Surgery Prize in recognition of the contribution he has made to the speciality. He is a founder invited member of the International Academy of Oral Oncology and also more recently the International Head and Neck Scientific Group.

Six key words that describe my research interests.

Patient Reported Outcomes; Quality of life, Clinical and functional outcomes, Patient and carer experience, questionnaire validation, Qualitative research methods

How I first began pursuing research:

Quality of life and functional outcomes following head and neck cancer was very much in its infancy and had the possibility of shaping patient care. Psychological aspects of patients treatment, their perceived response and how this differed form the clinical team was of great interest to me. This field of clinical research was relatively new to BAOMS and not part of an established research portfolio in Liverpool. Hence I needed period of research that did not require major financial support and that was possible to undertake during higher surgical training.

My supervisors

These were given to me following registration of the MD to Birmingham University, the University from which I received my medical degree. The supervisors were John Watkinson and Stephen Dover.

My higher degree thesis abstract

MD Birmingham

Abstract:  - 3 sources

1.Rogers SN. The importance of function and quality of life in oral cancer. 2002, Astroglobe Limited ISBN 0-9522839-1-3

2.Rogers SN, Patel M, Lowe D, Brown JS, Vaughan ED. Clinical function after primary surgery for oral and oropharyngeal cancer: an 11-item examination. Brit J Oral Maxillofacial Surg 2002; 40: 1-13.

3. RogersSN, Lowe D, Fisher SE, Brown JS, Vaughan ED. Health related quality of life and clinical function in patients treated by primary surgery for oral cancer. Brit J Oral Maxillofacial Surg 2002; 40:11-18

My main sources of research funding

National Institute for Health Research: Programme grants for applied research.  REF: RP-PG-0707-10034 Project Title: Evidence based health care for major congenital and acquired problems of the head and neck. December 2007/ March 2008. Co-applicant: 2.2 million

My clinical commitment during my research period

Full time clinical

An account of my current and ongoing research

Very busy through activity at the Regional Unit and the EPRC. 15 papers published to date in 200, 15 in 2008, a further 13 accepted for publication Further information is available from two websites:  www.headandneckcancer.co.uk
and www.edgehill.ac.uk/eprc

My future planned research

Patient Concerns Inventory

Fear of Recurrence

Psychosocial interventions

Involvement in patient reported outcomes as part of NCRI type RCT clinical trials

Multidisciplinary and multi-institutional collaboration

Current active grants and project titles

Naseem Ghazali and Anastasios Kanatas undertaking MDs under my supervision on further development of the Patient Concerns Inventory. This project won the Best use of IT in patient and citizen involvement in healthcare in the E-Health Insider National Awards 2010 in association with BT June 2010 (winner).

National 2-year bisphosphonate induced jaw necrosis registration project. Co-applicant in the H&N 5000 study (National Institute for Health Research: Programme grants for applied research.  REF: RP-PG-0707-10034 Project Title: Evidence based health care for major congenital and acquired problems of the head and neck). 

My  advice for budding OMFS researchers.

It takes determination and personal drive. Do research you believe in and have a real interest for. Don’t  let anyone put you off once you have made a decision. Set realistic goals and timelines. It is not easy to do ‘cutting edge’ research at any stage so if it is hard as a trainee it will be very hard as an ‘academic consultant’.

Any difficulties encountered when returning back to Specialist training (if any) ?

I never left specialty training as my research was clinically based and necessitated longitudinal evaluation over several years.

Best five papers published:

1.Rogers SN, Brown JS, Woolgar JA, Lowe D, Magennis P, Shaw RJ, Sutton D, Errington D, Vaughan D. Survival following primary surgery for oral cancer.Oral Oncol. 2009; 45:201-211. 

2.Rogers SN, El-Sheikha J, Lowe D. The development of a Patients Concerns Inventory (PCI) to help reveal patients concerns in the head and neck clinic.Oral Oncol. 2009; 45: 555-561

3.Rogers SN, Lowe D Screening for dysfunction to promote MDT intervention using the University of Washington Quality of Life questionnaire (UW-QOL) Archives of Otolaryngology Head & Neck Surg.2009; 135: 369-375.

4.Rogers SN,  Ahad SA,  Murphy AP. A structured review and theme analysis of papers published on 'quality of life' in head and neck Cancer: 2000 to 2005. Oral Oncology 2007; 43:843-868. ‘This was one of the 20 most downloaded articles from ScienceDirect in 2007. 

5.Rogers SN, Gwane S, Lowe D, Humphris G, Yueh B, Weymuller EA .The addition of mood and anxiety domains to the University of Washington Quality of Life Scale. Head Neck 2002; 24: 521-529

Mark McGurk

Unit:  University College Hospital, London

Tel: 020 7403 3876

email

Specialities: 
Mouth cancer (oral cancer), Head and Neck Cancer, Salivary gland cancer, Head and Neck Centre

Correspondence Address:  HCA Healthcare UK, Outpatients and Diagnostic Centre, The Shard, St Thomas' Street, London SE1 9BS

Professor McGurk undertook his undergraduate BDS degree at Sheffield University in 1976. This was followed by 3 years of junior surgical posts in oral and maxillofacial a six month period visiting maxillofacial units in the United States. He returned to Sheffield to complete a medical degree in 1984.  He held a lecturer post at Manchester University and was awarded a DLO and an MD during this period.  He was appointed consultant oral and maxillofacial surgeon to Queen’s Medical Centre, Nottingham in 1991, and in 1992 professor of oral and maxillofacial surgery at the King’s College London - Guy’s and Thomas’ Hospitals Foundation Trust. He moved to UCLH in September 2016.  

Professor McGurk’s clinical practice has centred on head and neck cancer surgery and minimally invasive management of salivary gland disease.  His research has focused on early diagnosis of head and neck cancer, factors leading to complications of the surgery and the introduction of minimally surgery to the head and neck cancer.

He has championed minimally invasive surgery for benign parotid tumours and obstructive salivary gland disorders.  He has led a European trial in  sentinel node biopsy which has led to a 75% reduction in neck dissection for early mouth cancers (first in the UK).   His work has changed the practice of salivary gland surgery away from excision to the gland preservation surgery (first in the UK).   

Professor McGurk lectures widely at national and international conferences and runs annual master classes on salivary gland surgery in London, Paris and Erlangen for maxillofacial and ENT consultants.

Professor McGurk is keen to promote academic development within oral and maxillofacial surgery.  He believes the development of an academic career can best be pursued in the SpR training years by combining clinical and academic training. 

Professor McGurk has published extensively (http://www.ncbi.nlm.nih.gov/pubmed) with 190+ original articles in peer-reviewed journals; 5 major academic textbooks on cancer and salivary gland disease and contributed to 8 major academic textbooks.  He has been awarded BMA Medical Book Award 2013 Highly Commended Surgical Specialties. 

Professor McGurk is a board member of Project Harar, which is a charity that works in Ethiopia and arranges regular treatment for patients with facial deformity in that country.   Each year he leads a surgical mission of doctors and nurses to work with the Ethiopian surgeons to treat complex cases. Approximately 50 patients are treated over a 2 week period each year. 

Key words that describe Professor McGurk's research interests:

Minimally invasive, salivary glands, sentinel node biopsy, 3D intraoperative navigation

Higher Research Degree:

MD, DLO

Name of University:

Sheffield

Main sources of research funding:

Both local and national

Current and ongoing research:

3D intraoperative navigation system for sentinel node biopsy and dual markers (radioactive and fluorescent) to track the target molecule sentinel node biopsy, minimally invasive salivary treatment (tumours and stones), microendoscopy.

Best five papers published:

A comprehensive list is available here

Involvement in clinical trials:

CI for EORTC approved multinational Sentinel European Node Trial (SENT).

CR-UK Comprehensive Cancer Imaging Centre with SNB an important componen. 

PET imaging of thyroid and parotid cancer with F-18-tetrafluoroborate,

Deep sequencing of tumour and plasma DNA for monitoring squamous cell cancer.

PET imaging of thyroid and parotid cancer with F-18-tetrafluoroborate.

Fluorescent guided sentinel node biopsy.

Deep sequencing tumour and plasma DNA for monitoring squamous cell cancer. 

Development of  navigation guided SNB.

Professor McGurk would be interested in subscribing to a blog with regards to research within the specialty and is happy to be contacted for advice by maxillofacial trainees  - note this contact would be via the baoms office 

NCRI/N Associate Director for Patient and Public Involvment.

Clinical Research Fellow, University of Leeds

Hon Senior Clinical Research Fellow, University of Bradford

Unit: NCRN Co-ordinating Centre, University of Leeds, University of Bradford

Correspondence Address:  Section of Experimental Therapeutics, Leeds Institute of Molecular Medicine, University of Leeds, Room 6.01, Clinical Sciences Building, James’s University Hospital, Beckett Street, Leeds, LS9 7JT

Six key words that describe my research interests.

Impact of H&N Cancer. Patient perspectives. QoL/PROs.

Premalignancy and genomics.

Optical diagnostic technology in non-invasive assessment of cells and tissue.

How I first began pursuing research:

Always interested in how we work towards better ways to manage our patients with their interests fully considered. I was fortunate in meeting some leading scientists and it rather went on from there.

Working with the NCRI/N has been important as it brings our disciplines together in a collaborative forum to develop good research. I have been part of the Clinical Studies Group since 2003 and currently Chair the Survivorship Sub-group. 

What higher research degree did you pursue

PhD Leeds

MSc Birmingham (by research) 1983

My PhD supervisors:

Professor Galina Velikova, University of Leeds

Professor Peter Selby, University of Leeds

My main sources of research funding

CRUK, Yorkshire Cancer Research, Macmillan Cancer Support, BAOMS, Charitable Trustees of Leeds Teaching Hospitals NHS Trust.

My clinical commitment during my research period

I worked as a NHS Consultant with an interest in Maxillofacial Oncology from 1992-2000 and then as a Clinical Academic Maxillofacial Surgeon until 2009. I have now taken early retirement from my clinical post as a result of osteoarthritis limiting the ability to do practical surgery. 

An account of my current and ongoing research

Patients opinions on measurement of QoL and possible development of communication tools for clinic.

Development of new and updated EORTC modules for H&N Cancer and Oral Health Assessment.

Raman Spectroscopy in the Diagnosis of Cancer.

High throughput sequencing genomics in premalignant disease.

My future planned research

To work with the NCRI/N in the field of patient and public involvement in cancer research.

Honorary Consultant in Oral & Maxillofacial Surgery

Correspondence Address: Guy’s Tower, Great Maze Pond, London SE19NU

 Six key words that describe my research interests.

Oral carcinoma, precancer, molecular pathogenesis, novel treatments

How I first began pursuing research:

I began my research career in the usual way, helping consultants conduct clinical trials, analyse patient data and writing drafts of the report. This was at a time when significant progress was being made unravelling the molecular basic of immune interactions and the first two oncogenes had just been discovered. The possibility of applying molecular techniques to analyse tissues was very new. These new areas for research interested me, but I found it very difficult to be considered seriously as a candidate for a PhD as I had no practical laboratory expertise.

To address this I decided to take an MSc in immunology, which included practical elements. The MRC funding scheme to allow clinicians to undertake a PhD was well established, but there was very significant competition for posts.  When I had completed my MSc I returned to a clinical post and found a PhD indirectly by applying to an advertisement for research fellows at ICRF, now CRUK. The post that I applied for had already gone to an applicant from the US, who had funding to cover his salary. Nevertheless this gave me the chance to meet Group Leaders who were looking to recruit new PhD students.

As I recall I started my PhD on "soft monies" and subsequently applied for an MRC Training Fellowship.

What higher research degree did you pursue?

M Phil initially as there was insufficient substance to the first project that I registered for and this was felt to be adequate for my needs. Subsequently I   discovered that it was necessary to have a PhD to bid independently for research grants, so I have an MSc, MPhil and PhD!

My Supervisors

Fiona Watt, Marc Feldman

My higher degree thesis abstract

PhD University of London

The aim of this investigation was to study the expression and responsiveness to growth factors in normal transformed and malignant keratinocytes. The proliferation of epithelial cells can be influenced by a variety of mitogens, hormones and polypeptide growth factors. Epidermal growth factor (EGF) is one such polypeptide that stimulates cell growth in a wide range of tissue types. The location of the epidermal growth factor receptor (EGFR) in normal human skin and oral mucosa from different sites has been determined by immunohistochemistry, EGF binding studies and an immuno-ultrastructural technique. Basal cells were always found to express EGFR while suprabasal cells showed equivalent, variable or no receptor expression. As cell proliferative capacity is predominately associated with basal cells the expression of EGFR appears to be a necessary but insufficient indicator of cell proliferative capacity.

Marked tissue differences in the pattern of EGFR expression in epidermis orthokeratinised, parakeratinised and non-keratinised oral mucosa were consistently observed suggesting that the pattern of expression may be related to the type of epithelial keratinisation that occurs.

Expression of immunoreactive EGFR in all squamous cell carcinoma (SCC) has also been determined. While the distribution and intensity of receptor expression varied between patients with SCC there was no correlation between the level of receptor expression and tumour behaviour.

Cultured human keratinocytes, epidermis and SCCs were also analysed for the presence of transcripts and protein for the transforming growth factors alpha (TGFa) and beta (TGFb). Both growth factors were detected in cultured keratinocytes, which have receptors for and respond to these ligands. Additionally transcripts for TGFa were found preferentially in the basal, proliferative compartment of these epithelia. Similarly both growth factors were detected in SCCs and a highly significant inverse correlation was found between the levels of TGFa alpha and expression of the EGFR in these carcinomas. It is concluded that the data for TGFa are consistent with the existence of autocrine growth control loop influencing cell proliferation in both normal and malignant epithelial cells, a process that in normal keratinocytes and responsive SCCs might be modified by TGFb.

Since epithelial cells appear to synthesise a variety of growth factors, cultured keratinocytes and SCC lines were also assayed for evidence of the production of platelet-derived growth factor, insulin-like growth factor, fibroblast growth factor and the cytokines interleukin 1 (IL1), interleukin 6  (IL6) and tumour necrosis factor (TNF). Synthesis and IL1 and IL6 were demonstrated. The rate of secretion of IL1 and IL6 was increased in response to a variety of cytokines and mitogens. IL1 and IL6 had no effect on the proliferation of keratinocytes or SCC cell lines tested. While it seems unlikely these cytokines could influence keratinocyte proliferation in vivo, the capacity of keratinocytes to synthesise and release IL1 and IL6 supports the observation that the keratinocytes may play an important role in augmenting an immune or inflammatory response.

The effect of expression of the ras, myc and SV40T oncogenes on growth factor production by keratinocytes has also been studied. These oncogenes were introduced into keratinocytes using retroviral vectors. Infected cells show an increased rate of proliferation and altered growth properties when compared to the parent cells. A reduction in the rate of secretion of TGFa and a more variable change in the rate of secretion of TGFb was observed following infection of cells with retroviral vectors. These cells remain sensitive to the growth inhibitory effects of TGFb and TNF. It is concluded that alteration in the rates of secretion of TGFa and b are unlikely to be responsible for the altered growth characteristic of these

My main sources of research funding

MRC, cancer charities, various NHS supported schemes

My clinical commitment during my research period

An honorary contract during my PhD to allow for access to patients, case notes etc.

An account of my current and ongoing research

The overarching theme of my research is to unravel the molecular basis of oral cancer and to use this information to investigate why tumours recur despite seemingly adequate treatment. This led to studies that identified the importance of precancerous changes in tissues surrounding a tumour and to unravel the molecular basis of this field cancerisation in the mouth. Based on the published findings, a clinical trial was devised to establish whether the presence of cancer-causing mutations, in the tissues that surrounds a tumour, is more reliable in terms of identifying patients at high risk of tumour recurrence than conventional light microscopy. This study was established as collaboration with 2 overseas units, so that preliminary findings might be validated at different geographical locations. The UK arm of this l study is now adopted by the National Cancer Research Network (NCRN). At present information about the extent of field change can only be used to the guide the need for frequent follow-up. However, a very positive final study outcome supports the need to act on this information to develop new treatments that can eliminate precancerous patches from the remaining oral epithelia to prevent recurrence.

In parallel with this I have collaborated with local, national and international Pls to simplify molecular tests to detect field change and develop additional strategies so that every case can be tested, to facilitate translation of marker-discovery research from the laboratory to the clinic. Aspects of this involved the use of sophisticated pan-genome platforms to identify the genes that are pivotal for tumour development. This led very recently to the discovery of a gene that shows altered expression in cancers of all squamous epithelia. The function of this gene in normal oral epithelia has not been established reported, but the available information suggests that it may act as a brake to cell migration and have an important role in wound healing.

My future planned research

The next step is to carry out more detailed functional studies to conclusively establish the role of this gene in oral health and disease. This will include testing the hypothesis that loss of function of this gene product in cancer leads to invasion and metastasis and is thus responsible for a key aspect of tumour behaviour. The way in which this gene is deleted also provides a cancer-specific marker, which can be used to increase the number of molecular tests available to detect precancerous change in the oral epithelia where malignant progression is likely.

My  advice for budding OMFS researchers

Often the only way to start is to help with a study designed by someone else, but as soon as possible try to conduct research that interests you.

Make sure that you get a link with a well-funded unit where there are lots of researchers who can help

Make sure that you get a supervisor who knows about your chosen subject and can help you find other contacts as most likely you will need help from different experts as your project evolves

My current involvement in  clinical trials:

Do molecular diagnostics identify patients at increased risk of developing locoregional recurrence?

Best five papers published

Thurlow JK,  PeñaMurillo CL,  Hunter KD  Buffa FM,  Patiar S,  Betts G, West CML, Harris AL Parkinson EK,  Harrison PR,  Ozanne BW, Partridge M, Kalna G.  Spectral clustering of microarray data elucidates the roles of microenvironment remodelling and immune responses in survival of head and neck squamous cell carcinoma   Journal Clinical Oncology.  2010

Huang X, Pateromichelakis S, Hills A, Sherriff M, Lyons A, Odell E, Morgan P, Harrison P, Partridge M. p53 mutations in deep tissues are more strongly associated with recurrence than mutation-positive mucosal margins. Clinical Cancer Research  2007 13: 6099-6106. 

Gaballah K, Costea DE, Hills A, Gollin SM, Harrison P, Partridge M.  Tissue engineering of oral dysplasia Journal Pathology  2008 215  280-289. 

Gaballah K, Hills A, Curiel D, Hallden G, Harrison P. Partridge M. Lysis of dysplastic but not normal oral keratinocytes and tissue-engineered epithelia with conditionally replicating adenoviruses. Cancer Reearch 2007 67:7284-94.

Partridge M, Pateromichelakis S, Phillips E, Emilion GG, A’Hern RP, Langdon JD.   A case-control study confirms that microsatellite assay can identify patients at risk of developing oral SCC within a field of cancerisation. Cancer Reearch 2000, 60: 3893-3898

Honorary Senior Lecturer, Surgery, Imperial College School of Medicine

Clinical Director Head and Neck Directorate, NWLH NHS Trust

Unit: North West London Regional Maxillofacial Service

Correspondence address: Northwick Park and St Mark’s Hospitals

Watford Road, HA1 3UJ. Manolis.heliotis@nhs.net

Mr Heliotis qualified in Medicine at the University of Stellenbosch in the beautiful Cape and in Dentistry at the University of the Witwatersrand in vibrant Johannesburg, where he was also born. He is a consultant Maxillofacial surgeon and the Clinical Director of the Head & Neck Division at Northwick Park and St Mark's Hospitals in North West London. He teaches and supervises clinical fellows, SHO’s and higher surgical trainees and co-supervises MS and PhD students at Imperial College at the Biological Systems Engineering Laboratory (BSEL).

Mr Heliotis has a scientific publication record of over 20 years in the basic science and clinical application of bone and tissue regeneration, having worked in leading laboratories which pioneered growth factor development with landmark publications in this field with non-human primates and clinically in humans thereafter.

Mr Heliotis is an Honorary Senior Clinical Lecturer at Imperial College London. In his research capacity he works with an established leading laboratory, The Biological Systems Engineering Laboratory (BSEL) headed by Prof. A. Mantalaris at Imperial College London. The BSEL is an inter-disciplinary facility with collaborators coming from Engineering, Medicine as well as Natural Sciences.  

Laboratory profile: Currently, the laboratory consists of 4 postdoctoral fellows and 12 PhD students.  The BSEL has state-of-the-art 2,000 ft2 experimental research facilities for bioprocess engineering. It is equipped with a GLP HEPA-filtered tissue culture room, an EPICS ALTRA flow cytometer/sorter, image-analysis fluorescent microscopes, a molecular biology laboratory (including real time PCR), and material fabrication/characterisation equipment. BSEL has a NovaBio Bioprofiler which allows for the online or offline characterisation of culture media (glucose, glutamine, ammonia, lactate, pH, pO2, PCO2, and ions). Imperial facilities include proteomics, multi-photon microscopy, SEM & TEM facilities, and DNA microarray analysis.

The added research advantage of Northwick Park s that it is the hub for the CLRN in North West London at Northwick Park Hospital, making access to clinical trials advise, translational research support and infrastructure available on site, adjacent to the Maxillofacial unit.

Manolis is CLRN lead for the oral section of the CLRN in North West London.

Six key words that describe my research interest:

Bone regeneration, Tissue Engineering, Regenerative Medicine, Bioreactors, Organogenesis

How I first began pursuing research:

I started in research as an undergraduate during my first degree, in my final 18 months of reading dentistry in South Africa, in 1989, in the illustrious Dental Research Institute, one of the most established, long running and productive MRC laboratories in South Africa headed at the time by Professor Peter Cleaton-Jones. Tissue regeneration had a particularly fascination to me, at a time when it was a science fiction fantasy as none of the morphogens, pathways and mechanisms involved in tissue regeneration had been unlocked. I wanted to understand and overcome the mechanisms that inhibited our ability in post-natal life to regenerate our tissues and organs. I had the good fortune of having come across a scientist/surgeon of exemplary drive, ability and vision and who was soon after to become one of the pioneers in our understanding of bone regeneration, Professor Ugo Ripamonti who heads the Bone Research Laboratory.

After graduating with a BDS, I was awarded an MRC scholarship to pursue laboratory based research for one year under his supervision and embarked on a Masters through research only. Subsequently as a medical undergraduate I continued throughout working in the lab during holidays on bone regeneration and completed my Research Masters degree.  I participated in the earliest discoveries in this field with seminal papers in non-human primates, taking scientific findings in the lab and translating them into pre-clinical animal studies.

My higher degree:

MSc (1991-1994) by research only, University of the Witwatersrand, South Africa. Thesis title: “The interaction of bone extracellular matrix components with tissues and cells of muscular and vascular origin. An in vitro investigation.”

Sources of Research:

National and International

Five best publications

1: Prostaglandin E2 Receptors as Potential Bone Anabolic Targets - Selective EP4 Receptor Agonists. Pagkalos J, Leonidou A, As-Sultany M, Heliotis M, Mantalaris A, Tsiridis E. Curr Mol Pharmacol. 2011 Jun 25. [Epub ahead of print] PMID: 21787288

2: Pagkalos J, Cha JM, Kang Y, Heliotis M, Tsiridis E, Mantalaris A. Simvastatin induces osteogenic differentiation of murine embryonic stem cells. J Bone Miner Res. 2010 Nov;25(11):2470-8. PubMed PMID: 20564244.

3: Ripamonti U, Ferretti C, Heliotis M. Soluble and insoluble signals and the induction of bone formation: molecular therapeutics recapitulating development. JAnat. 2006 Oct;209(4):447-68. Review. PubMed PMID: 17005018; PubMed CentralPMCID: PMC2100361.

4: Heliotis M, Lavery KM, Ripamonti U, Tsiridis E, di Silvio L. Transformation of a prefabricated hydroxyapatite/osteogenic protein-1 implant into a vascularised pedicled bone flap in the human chest. Int J Oral Maxillofac Surg. 2006 Mar;35(3):265-9. Epub 2005 Oct 28. PubMed PMID: 16257511.

5: Ripamonti U, Heliotis M, Rueger DC, Sampath TK. Induction of cementogenesis byrecombinant human osteogenic protein-1 (hop-1/bmp-7) in the baboon (Papio ursinus). Arch Oral Biol. 1996 Jan;41(1):121-26. PubMed PMID: 8833601.

Why do I do research and why am I looking for surgeons to do a PhD?

I already supervise post-graduate research. I do it because I love it and it gives me the intellectual stimulation that comes from driving forward surgical innovation in regenerative medicine. It is a fantastic feeling to be at the forefront of developments that shape medical practice. I have some of the best international infrastructure as well as fantastic, friendly, world-class collaborators at Imperial and internationally for the basic science component, which is fundamental to anything scientifically meaningful. I combine this with one of the largest Maxillofacial units in the UK, providing the human resource for trials and translational research and above all a supportive environment.

We are ideally placed to support highly selected self-motivated individuals who wish to push the boundaries of tissue regeneration in surgery and expand their horizons academically. Candidates can potentially be at the forefront of surgical innovation in this field.

I am looking for higher surgical trainees or those studying for their second degree to slot into selected PhD programmes in the hope of being able to teach what I already do, promote the field of regenerative surgery and develop the next generation of thinking surgeons who will maintain an impetus for continuing developments.

Above all, I recommend it for the fun, joy, camaraderie and satisfaction that it gives when you publish something of unique value that remains in the literature for ever and above all when it is subsequently accepted by our peers and put into surgical practice.

Consultant Head & Neck/Maxillofacial Surgeon

Honorary Senior Lecturer Department of Cancer Studies & Molecular Genetics 

Regional Head & Neck Oncology Lead for National Institute of Health Research, UK. 

Head of Leicester Maxillofacial Research Group. University Hospitals of Leicester NHS Trust

Correspondence Address:  Maxillofacial Unit, University Hospitals of Leicester NHS Trust, Leicester Royal Infirmary, Leicester LE15WW email

Chris Avery has been a Consultant Maxillofacial Surgeon at the University Hospitals of Leicester NHS Trust since 2000 and is Honorary Senior Lecturer in the Department of Cancer Studies & Molecular Genetics. I studied dentistry at Bristol (1984) and read Medicine at Cambridge (1992), gaining many prizes. I was awarded the gold medal for the FDSRCS (England) examination. My research qualifications include Master of Surgery (MChir) and Doctorate of Medicine (MD).

The main areas of clinical research include head and neck malignancy, reconstructive free flap surgery, management of morbidity at the flap donor site, novel surgical techniques, PEG feeding, salivary gland surgery and other related topics. Laboratory based research includes the biomechanical aspects of plate reconstruction at the radial free flap donor site and the mandible using a finite element analysis model. Basic oncology projects include the role of EMT proteins in oral cancer. I act as a supervisor for higher research MEng, MD and PhD degrees.

I have published over 70 original papers and leading review articles covering many aspects of oral and maxillofacial surgery, not exclusively cancer, and have contributed several book chapters. 

There is a strong personal commitment to supporting trainee surgeons who want to present work at the BAOMS Annual Scientific Meeting and other International surgical meetings. Leicester has the consistently featured within the top 5 units for the number of presentations at BAOMS over the last decade and has a very high rate of successful conversion to publication 1-3. There are two maxillofacial clinical research fellows and these positions have been used by trainees to further their research interests often before taking a substantive higher surgical training post.  

 Chris Avery has a young family and many outside interests including playing football at the lowest competitive level!

1      Collier JM, Vig N, Hammond D. Publish or perish? Br J Oral Maxillofac Surg. 2010 Oct;48(7):540-3.

2      Avery C, Clifford N, Thakrar M, Neal CP, Brennan P. Leading Article: Trends in presentations at BAOMS Annual Scientific Meetings. Face Mouth & Jaw Surg 2011;1:38-47.

3      Avery C, Clifford N, Neal CP. Oral & Maxillofacial surgery “presentation hotspots” in the UK over the last decade from the BAOMS annual meetings. Br J Oral Maxillofac Surg 2013;51:453-456.

Six key words that describe my research interests.

Flap, reconstruction, morbidity, oncology, biomechanical, gastrostomy.

How I first began pursuing research:

I have always been interested in clinical and basic science. Ideas that have a practical impact on surgical practice are particularly appealing. Having published within every surgical placement has broadened my range of surgical interests.  Working on the transplant team with Professor Sir Roy Calne FRS, in Cambridge, was inspiring and consolidated my desire to become a properly trained surgeon with a broad and deep range of surgical skills whilst retaining an active interest in research.

Higher research degree:

MChir [Master of Surgery] and MD [Doctor of Medicine].

Higher research degree University:

Cambridge and Leicester

Supervisor/s:

I supervised myself

Higher degree thesis abstract:

The radial free flap is the flap of choice for reconstruction of the majority of soft tissue defects of the oral cavity. My MChir Thesis reviewed the significant incidence of donor site morbidity associated with the conventional fasciocutaneous and osteocutaneous versions of the flap. The work includes one of the first detailed descriptions of the suprafascial dissection technique and anatomy of the septocutaneous flap. The first description of prophylactic internal fixation of the radial osteocutaneous donor site is included and this technique is now widely used to substantially reduce the incidence of fracture. A biomechanical laboratory model was developed to investigate the strengthening effects of different types of bone plates. Wound management and surgical techniques were developed to further minimise morbidity by improving the success rate of skin grafting at the radial donor site. My MD thesis developed these themes and also included our finite element analysis model of the radius and mandible which has been used to study the complex biomechanics of plate fixation.

Main sources of research funding:

My clinical and laboratory studies did not require substantive grants but minor support from the Maxillofacial department, Synthes (UK) and BAOMS.  

Clinical commitment during research period:

I undertook my research thesis whilst a full-time Consultant Surgeon within a unit without an established track record of research, which is not ideal. We have now established a maxillofacial research group with International collaboration.

Current and ongoing research:

There are several ongoing clinical research and audit projects related to various aspects of free and pedicle flap surgery, novel surgical techniques, use of percutaneous endoscopic gastrostomy and improving outcomes for the oncology patient.

Biomechanical studies are in co-operation with the Professor Jingzhe Pan, Head of Mechanical Engineering in Materials at the University of Leicester. Professor Pan has expertise in the modelling of biomaterials for orthopaedic fixation and tissue engineering, bioresorbable materials and finite element analysis modelling. This often involves working with post-graduate engineering students.

One of our oncology higher surgical trainee’s, Mr Alistair Fry, is undertaking an MD based on a oncology molecular biology study of the role of EMT related proteins in oral squamous cell carcinoma. The laboratory work is in collaboration with Dr Eugene Tulchinsky, Head of EMT research at Leicester University and with Professor Ian Mackenzie at the Blizard Institute, London who has an interest in Stem Cells and EMT.

Current active grants and project titles:

BAOMS – Investigation of the role of ZEB1 and ZEB2 (SIP 1) in Epithelial Mesenchymal Transition in Oral Squamous Cell Carcinoma Progression.

2013 BAOMS Maxillofacial Research Grant and the 2014 Royal College Surgeons Research Fellowship [https://www.rcseng.ac.uk/fds/news/2014-fds-research-fellowship-awarded].

Advice for OMFS researchers:

Decide if you want to be an academic or a surgeon with an academic interest. I have always considered myself to be the latter and find the clinical element of my work to be an extremely important source of professional satisfaction.

All seemingly good ideas should be subjected to early critical analysis by both yourself and colleagues so that unsuitable projects may be eliminated at an early stage.

Projects should be well defined, topical, achievable, presentable and ultimately publishable. I hope that a paper may change the clinical practice of my colleagues as there is no more critical audience than your surgical peers.

Try to avoid multi-centre trials or projects that involve your peers collecting data. They are often happy to have their name on your paper but less enthusiastic about doing the work so the project may fail!  

All trainees have a CV with a list of work in progress but few have successfully published in a respected peer reviewed journal. Will this be you when sitting down for a consultant interview?

If you can work within an environment that nurtures research and has a proven track record of success then you will find there is much support and wise counsel readily available.

Difficulties encountered when returning back to Specialist training:

My difficulty was that the opportunities for undertaking research whilst obtaining a full surgical training were limited at that time but opportunities have since increased substantially. I undertook the bulk of my Thesis research work whilst a Consultant. This had the advantage that I had not compromised my surgical training and I had a reliable financial income but was challenging. Although I successfully supervised myself this is not to be recommended. Ideally you should combine clinical work with research in a department with an established research programme and financial support.

 Best ten papers published 2010-2014:

Avery C. A Review of the Radial Free Flap: Still Evolving or Facing Extinction? Part One. Soft Tissue Radial Flap. Br J Oral Maxillofac Surg 2010;48:245-252. http://dx.doi.org/10.1016/j.bjoms.2009.09.004

Avery C. A Review of the Radial Free Flap: Still Evolving or Facing Extinction? Part Two. Osteocutaneous Radial Flap. Br J Oral Maxillofac Surg 2010;48:253-260.http://dx.doi.org/10.1016/j.bjoms.2009.09.017

Avery C, Crank S, Neal CP, Hayter JP, Elton C.The use of the pectoralis major flap for advanced and recurrent head and neck malignancy in the medically compromised patient. Oral Oncol 2010:46:829-833.http://dx.doi.org/10.1016/j.oraloncology.2010.08.004

Avery C, Martin T, Parmar S. The use of the anatomically contoured low profile unilocking titanium radial plate for prophylactic internal fixation of the radial osteocutaneous donor site. Br J Oral Maxillofac Surg 2011;49:152-153. http://dx.doi.org/10.1016/j.bjoms.2010.01.013

Avery C. The sternocleidomastoid perforator flap. Br J Oral Maxillofac Surg 2011;49:573-575. http://dx.doi.org/10.1016/j.bjoms.2010.09.008

Avery C, Sundaram K, Jasani V, Peden A, Neal CP. A comparison of sensory recovery at the subfascial and suprafascial donor sites of the free radial flap. Br J Oral Maxillofac Surg 2012:50:495-499. http://dx.doi.org/10.1016/j.bjoms.2011.10.011

Bujtar P, Simonovics J, Sandor G, Jingzhe P, Avery C. Refinements in osteotomy design to improve structural integrity: a finite element analysis. Br J Oral Maxillofac Surg 2013:51:479-485. http://dx.doi.org/10.1016/j.bjoms.2012.09.015

Avery C, Bujtar P, Simonovics J, Sándor G, Pan J, Váradi K. A finite element analysis of bone plates available for prophylactic internal fixation of the radial osteocutaneous donor site using the sheep tibia model. J Med Eng Phy 2013:35:1421-1430. http://dx.doi.org/10.1016/j.medengphy.2013.03.014

Avery C, Ghandi N, Peel D, Neal CP. Indications and outcomes for 100 patients managed with a pectoralis major flap within a UK maxillofacial unit. Int J Oral Maxillofac Surg 2014: 43: 546–554. http://dx.doi.org/10.1016/j.ijom.2013.10.009

Bujtar P, Simonovics J, Váradi K, Sándor G, Avery C. The biomechanical aspects of reconstruction for segmental defects of the mandible: a finite element study to assess the optimisation of plate and screw factors. J Craniomaxfac Surg 2014:6:855-862. http://dx.doi.org/10.1016/j.jcms.2013.12.005

Consultant Oral & Maxillofacial Surgeon

Unit: Guy’s and St Thomas’Hospital

Correspondence address: Maxillofacial Department, Bermondsey Wing, London SE1 9RT

andrew.lyons@gstt.nhs.uk

Six key words that describe my research interest

Osteoradionecrosis, Trimus, fibrosis, Growth factors, genotypes

My foray into research began with:

SNP analysis of transforming growth factor gene in patients with and without osteoradionecrosis

My higher degree abstract

FIBROSIS AFTER RADIOTHERAPY IN THE HEAD AND NECK HAS A DISTINCT GENOTYPE DEPENDENT CAUSE

Radiotherapy damage has been described as being almost synonymous with fibrosis. In the head and neck, damage by fibrosis may present as both osteoradionecrosis ( ORN) or trismus. Fibrosis can be increased by the action of the transforming factor beta 1 (TGFβ1). A number of studies have shown that radiotherapy to the lungs increases both the levels of this growth factor and the degree of symptomatic fibrosis within the lungs particularly in individuals with a specific polymorphism in the TGFβ1 gene. A retrospective case control study was therefore undertaken to assess the influence of this polymorphism on ORN following radiotherapy.

This showed that ORN was related to the SNP at -509 of the TGFβ1 gene, heterozygotes (CT) had an odds ratio (OR) of 3.6 homozygotes (TT) had an OR of 5.8 compared to individuals with CC. This has been published in the International Journal of Radiation Oncolology Biology and Physics.

These odds ratios were probably reduced by the influence of post radiotherapy dentro-alveolar surgery. Hence the study is being expanded to include a prospective cohort and at the same time increase the number of participants entered into the first study. As in the first study blood is taken and analysed for the SNP, and the patient monitored for ORN development for at least 2 years following radiotherapy

After finalisation of the first ORN study trismus is also assessed at least 6 months after completion of radiotherapy in 47 patients. Of this group 20 were homozygous (CC) for the TGFβ1(C-T) variant allele, 12 were heterozygous (CT) and 15 were homozygous  (TT). These groups were similar in profile for age, sex, tumours stage, tumour site, type of resection and dose of radiotherapy as in the ORN study .Mean measurements of mouth opening varied significantly between the genotypes (p=0.003), with the largest measurements observed in those who were homozygous (CC) (mean 25.5), and the smallest in those homozygous (TT) for  the TGFβ1(C-T) variant allele (mean=12.5).  This has been presented at BAOMS and at the American Association of Oral and Maxillofacial Surgery.

Hence despite this small sample, it was demonstrated that the degree of trismus following radiotherapy was related to a specific genotype, with clear implications for the treatment of head and neck cancer, and this too is now being assessed prospectively in patients undergoing radiotherapy, as are other outcomes such as speech and swallowing. In view of the large number of patients treated at the Trust recruitment is not a problem and the project continues to flourish

Sources of funding

John Anderson Cancer Research Trust

Inman Trust

Facial Research Foundation

Five best publications

Lyons AJ. Perforator flaps in head and neck surgery. Int J Oral Maxillofac Surg. 2006 Mar;35(3):199-207.

Cell adhesion molecules, the extracellular matrix and oral squamous carcinoma. Lyons AJ, Jones J.  Int J Oral Maxillofac Surg. 2007 Aug;36(8):671-9.

Osteoradionecrosis of the jaws: current understanding of its pathophysiology and treatment.

Lyons A, Ghazali N. Br J Oral Maxillofac Surg. 2008 Dec;46(8):653-60. Factors Affecting Survival and Usefulness of Implants Placed in Vascularized Free Composite Grafts Used in Post-Head and Neck Cancer Reconstruction.

Fenlon MR, Lyons A, Farrell S, Bavisha K, Banerjee A, Palmer RM. Clin Implant Dent Relat Res. 2009 Oct 16. [Epub ahead of print]

Osteoradionecrosis in Head-and-Neck Cancer Has a Distinct Genotype-Dependent Cause. Lyons AJ, West CM, Risk JM, Slevin NJ, Chan C, Crichton S, Rinck G, Howell D, Shaw RJ. Int J Radiat Oncol Biol Phys. 2011 Jun 25. [Epub ahead of print]

My advice for budding OMFS researchers

Keep trying and don’t be put off if BAOMS don’t fund your research as they have a poor grasp of science

PhD Student, Institute of Child Health, Great Ormond Street Hospital

Unit: University College London

Six key words that describe my research interests.

Craniofacial Surgery, Genomics, Clefts, Dental Implants, Bone Regeneration

How I first began pursuing research:

I first started doing research during my dental undergraduate days where I was working with A/Prof Stephen Hsu on a project looking at the prevention of root caries using Lasers. During my medical undergraduate days I tried to get involved in laboratory research however it was probably close to impossible as I was working nights as a maxillofacial clinical fellow and being a vice-warden in a Halls of Residence.

I managed to get dedicated time to do research during my medical student elective where I spent two months in Hospital for Sick Kids in Toronto.  I worked under the supervision of a Plastic Surgery Fellow Dr David Chong and Dr Christopher Forrest, Programme Director of the Craniofacial Programme. We looked at CT scans of normocephalic skulls and children who had sagittal craniosynostosis and tried to create a form of analysis useful for Craniofacial Surgeons to allow objective description of the vault appearance and thus enable a clinician to record improvement, recurrence and also thus aid in planning for surgery. Whilst I was working on the data of these children, I was wondering what the genetic basis of these syndromes was. More interestingly whilst some of these syndromes had a genetic basis, some still had not been found although it was pretty clear that there was some form of inheritance in families with affected probands and either or parents.

Research degree (in progress)

PhD (London) 2010-13

Supervisors

Mr Jonathan Britto

Dr Erwin Pauws 

My main sources of research funding

Singapore Minstry of Health, National Research Foundation Scholarship British Association of Oral & Maxillofacial Surgeons Endowments Grant

My clinical commitment during my research period

None

An account of my current and ongoing research

I am looking at known genes implicated in Craniofacial Syndromes. There are still many  patients whom still do not have a genetic diagnosis. Using new advances in molecular genetics we hope that we will be able to identify novel genes that are involved and certainly looking at the possibility of other transcription factors upstream and downstream of the coding regions of the well characterised genes.

I am studying in detail the pathogenesis of Crouzon-like craniofacial syndromes caused by activating mutations in FGFR2 through a transgenic mouse model. In addition I aim to study human suture material from patients undergoing surgery in the craniofacial unit at Great Ormond Street hospital (GOSH). Combined with current knowledge, gained from investigations into the role of FGF/FGFR signalling in craniofacial development, the questions asked in this proposal have the potential to be translated into novel clinical treatment strategies to enhance or replace current approaches for the treatment of Crouzon-like syndromes.

My  advice for budding OMFS researchers.

Research opportunities do not just drop into your lap. You truly have to find something that interests you – almost to the point of the question bugging you and making you think and asking yourself why and why not. This is certainly before you realize that although you want to do research now, you have to apply for time off training or somehow squeeze it into your clinical life and worse, apply for funding. Funding seems to be a major hurdle for most researchers. The truth is that you will get funding if you have a good project and your supervisor’s support. However there are deadlines for all of this. The key therefore is to plan ahead if you know you are potentially considering this route of excellence.

 Research your potential supervisor very well. That would be the first research process one should undergo. A good research supervisor has a track history of successfully supervising other trainees. The lab should have a history of publications and collaborative work. Certainly there should also be a long list of previous grants and plans for future grant applications. Also ensure that there is already some form of outline prepared for your higher research degree as such things do not happen overnight. There will be a large amount which your supervisor has to do on your behalf before he/she kickstarts you into cruise mode. This includes abstract design and feasibility of the project. Go and read about the papers your supervisor has published. That way you get up to speed on what has been done in the lab since the beginning.

Go and get generic skills in research by reading books on statistics and your subject of interest early. This will include looking up papers on your pet interest. Print these papers or make sure that you can go back to this. Recording everything and ensuring that you can trace them back is essential in research. You never know when your luck will change and something truly novel might be accidentally discovered.

Oh yes..find someone local to latch onto for Specialty Training concerns as you will need to keep your hands in the specialty – at least at a very minimum else there will be a fear of returning to the specialty after the long higher research degree.

Any difficulties encountered when returning back to Specialist training (if any) ?

I will be returning to Specialist Training in 2013 and hope to have a seamless entry. I intend to keep close association with the specialty through regular meetings with consultants in clinics/ theatres and my oncalls.

Best five papers published:

Jerjes W, Jerjes WK, Swinson B, S Kumar. Leeson R, Wood PJ, Kattan M, Hopper C. "Midazolam in the reduction of surgical stress: a randomized clinical trial." Oral Surgery Oral Medicine Oral Pathology Oral Radiology and Endodontology  2005: 100:564-70

N Shah, J V Tighe, A W Barrett, S Kumar, JP Allen. "Bilateral intraparotid and extraparotid Warthin’s tumours"  British Journal of Oral & Maxillofacial Surgery (Short Communication) 2005 October

S Kumar, M Cameron, N Shah. "How to become an oral & maxillofacial surgeon" British Medical Journal Career Focus 2006; 332:36-37  

W Jerjes, B Swinson, DR Moles, M El-Maaytah, B Banu, M Kumar, M Al Khalwalde, M Vourvachis, H Hadi, S Kumar, C Hopper. "Permanent sensory nerve impairment following third molar surgery: A prospective study." Oral Surgery Oral Medicine Oral Pathology Oral Radiology and Endodontology 2006 Oct; 102(4) 1-7

Chong D, Kumar S, Forrest CR and Armstrong D. Extended strip craniectomy for sagittal synostosis: outcome measure based on morphometric CT based analysis. Canadian Journal of Plastic Surgery 14: 101, 2006.

Wellcome Trust-FDS Research Training Fellow

Registered for PhD 2010

 Research Title: The Epigenetics of HPV16-mediated Oral & Oropharyngeal Squamous Cell  Carcinoma

University of Liverpool

Supervisors: Mr Richard Shaw, Dr Janet Risk, Dr Triantafillos Liloglou

Funding: Wellcome Trust-FDS Fellowship

Email: schache@liverpool.ac.uk

Unit: University of Liverpool / University Hospital Aintree

Six key words that describe my research interests.
HPV, Epigenetics, Head & Neck Oncology

How I first began pursuing research:
I had previously developed an interest in pursuing a research component to my higher surgical training but a move to the Mersey Region part way through SpR training opened the first specific opportunity to follow this through. I had undertaken clinically based research wherever possible and had remained open to potential opportunities.

A successful year as a clinical research fellow (CRF) in Liverpool provided an ideal environment and basis from which to seek research funding and with the support of the Wellcome-FDS fellowship I was able to register for a higher degree. This initial CRF allowed development of basic laboratory/research skills and also production of pilot results that were useful for funding applications – several of the funding bodies will look more favorably on individuals who have already gained experience and results

My main sources of research funding
Wellcome Trust-Faculty of Dental Surgery Fellowship. 
(2-year fellowship covering consumables/lab costs and clinical salary)

My clinical commitment during research period
I maintain an on call commitment for both clinical and financial reasons. The fellowship funding allows complete focus on research work during normal working hours and is essential for uninterrupted progress now that I have registered for a PhD.
In my first year of OOPR, I was employed as a Clinical Research Fellow, a post which included 0.6 research & 0.4 clinical with an additional 1 in 5 on-call commitment. This OMFS CRF in Liverpool involved 1 fixed day per week in the central outpatients centre for UHA and 1 fixed day per week in a "spoke" unit providing outpatient, GA DSU & MOS service.  

An account of my current and ongoing research
My PhD is focused on HPV16 mediated Oropharyngeal SCC. More particularly, I aim to clarify the epigenetic alterations that occur in HPV+ OPSCC, both within the viral and host genomes, and the potential mechanisms through which the virus brings about these changes.
The research has fallen into two parts; the first being development of an understanding of the relative incidence of HPV16 in OPSCC within a UK population and defining the best test for HPV status, the results of which are published in Clinical Cancer Research (ref. below). The second part involves epigenetic analysis of an expanded cohort of clinical samples alongside established HPV+ cell lines. Further research avenues are also evolving over time. These include attempts to establish primary cell cultures direct from HPV + HNSCC clinical samples and also via a xenograft model, and expanding HPV-related research collaborations with individuals and groups both within the UK and internationally.

My advice for budding OMFS researchers:
Pursue interests early but don’t commit to just anything/everything. Involvement in clinical based research is important even if the projects are modest in size. Take advice from more than one (well informed) source. Plan ahead as Out of Programme applications (OOPR) can take time.
Under no circumstances neglect your clinical training. You have a finite period as an SpR and the early training is vital and it is what you’ll need as a consultant. Certainly consider/request that time out in research in not counted towards CCT. Opportunities, such as part clinical/part research Clinical Research Fellow posts are an excellent way to determine if a higher degree or further research is "for you". They also give you an opportunity to seek funding from a relatively informed position.

Look closely at the place that you wish to undertake research in and the individuals who may be able to guide you with either your own research ideas or assist you in developing a topic/idea. I would certainly suggest that you talk to people who have undertaken research recently and more importantly in that unit/research area.

Any difficulties encountered when returning back to Specialist training (if any)?
None expected. Training Programme Director and Educational Supervisors are kept in the loop about plans and developments so there are no surprises for anyone when re-entering the training pathway.

Best five papers published:

Schache AG, Liloglou L, Risk JM, Filia A, Jones TM, Sheard J, Woolgar JA, Helliwell TR, Triantafyllou A, Robinson M, Sloan P, Harvey-Woodworth C, Sisson D, Shaw RJ. Evaluation of human papillomavirus diagnostic testing in Oropharyngeal Squamous Cell Carcinoma: Sensitivity, specificity, and prognostic discrimination. Clin Cancer Res. 2011 Oct 1; 17(19)

Schache AG, Hall G, Woolgar JA, Nikolaidis G, Triantafyllou A, Lowe D, Risk JM, Shaw RJ, Liloglou T. Quantitative promoter methylation differentiates carcinoma ex pleomorphic adenoma from pleomorphic salivary adenoma. Br J Cancer. 2010 Dec 7;103(12):1846-51.

Schache AG, Lieger O, Rogers P, Kelly A, Newman L, Kalavrezos N. Predictors of swallowing outcome in patients treated with surgery and radiotherapy for advanced oral and oropharyngeal cancer. Oral Oncol. 2009 Sep;45(9):803-8.

Schache A, Thavaraj S, Kalavrezos N. Osseointegrated implants: a potential route of entry for squamous cell carcinoma of the mandible. Br J Oral Maxillofac Surg. 2008 Jul;46(5):397-9

Lord R, Nair S, Schache A, Spicer J, Somaihah N, Khoo V, Pandha H. Low dose metronomic oral cyclophosphamide for hormone resistant prostate cancer: a phase II study. J Urol. 2007 Jun;177(6):2136-40

Professor Anastasios Kanatas FRCS, MD

Consultant Maxillofacial Oncologist

Unit: Leeds Teaching Hospitals

Correspondence Address: Leeds General Infirmary, St James's Institute of Oncology and Leeds Dental Institute, Great George Street, LS1 3EX

Anastasios is an Oral and Maxillofacial Surgeon with special interests in Head and Neck Oncology and reconstruction. He received his training in the UK (Liverpool and Leeds), USA and Germany. He is the author of over 200 publications in international peer-reviewed journals, two books and several book chapters. He is a Deputy Editor of the British Journal of Oral and Maxillofacial Surgery. Professor Kanatas is the director of the international QOL workshop and co-director of flap / microsurgery courses in Germany.

Key words that describe my research interests:

Reconstructions, Patient Reported Outcomes, Patient and carer experience, Transplants, Stem cell regeneration

How I first began pursuing research:

Guided by enthusiastic peers

Research degree:

MD from the University of Liverpool

My higher degree thesis abstract:

Treating cancer is still based on three options-surgery, radiotherapy, and chemotherapy. However, these may simply treat the disease, rather than the person. The oncology community is increasingly recognising the benefits to be gained from holistic cancer care. It is recognised that every patient has different issues at different times in the cancer journey. There can be unmet needs that may be difficult to identify in a busy clinic. There are barriers to an effective patient with cancer and carer consultation. There is reliance on verbal communication but certain patient issues could be considered taboo. The addition of a patients concerns inventory (PCI) to the management of patients with head and neck cancer aims to formulate an individualized record of their concerns, needs and priorities that can be used as a structure to help guide out-patient consultations and promote multidisciplinary care. In its current form the head and neck PCI derives itself from a synthesis of issues covered in other HR-QOL questionnaires, as well as from groups such as the laryngectomy support group, head and neck support group, patient research forum, hospital volunteers, ward and out-patient staff and the multidisciplinary head and neck team. The data collected using the head and neck PCI has indicated that such a tool may have significant clinical implications. The aim of this work is to develop the PCI and to evaluate its impact to patient care.

Supervisors:

SN Rogers, G Velikova, B Roe, RJ Shaw, D Lowe

My main sources of research funding:

Various up to 1.7 million

My clinical commitment during my research period:

Full time clinical but taken 3 months out of programme

An account of my current and ongoing research:

Free flap development, the vessel depleted neck, genomics, clinical trials, questionnaire validation, Stem cell regeneration.

My advice for budding OMFS researchers:

Seek and work with established and committed colleagues

Best five papers published:

1.    Improving quality of life through the routine use of the patient concerns inventory for head and neck cancer patients: a cluster preference randomized controlled trial. Rogers SN, Lowe D, Lowies C, Yeo ST, Allmark C, Mcavery D, Humphris GM, Flavel R, Semple C, Thomas SJ, Kanatas A. BMC Cancer. 2018 Apr 18;18(1):444

2.    Genomic analysis to assess disease progression and recurrence in patients with oral squamous cell carcinoma.   Kanatas A, Chengot P, Ong TK, Ho MW, Sethi N, Taylor M, Glover A, Wood HM. Br J Oral Maxillofac Surg. 2018 Apr;56(3):198-205.

3.     Influence of tumor volume on survival in patients with oral squamous cell carcinoma. Mücke T, Mitchell DA, Ritschl LM, Tannapfel A, Wolff KD, Kesting MR, Loeffelbein DJ, Kanatas A.   J Cancer Res Clin Oncol. 2015 Jun;141(6):1007-11. 

4.    How will I be after my operation for oral cancer? Kanatas A, Singh P, Lowe D, Rogers SN. Br J Oral Maxillofac Surg. 2015 Jul;53(6):538-45.

5.    Incidence and outcome for patients with occult lymph node involvement in T1 and T2 oral squamous cell carcinoma: a prospective study. Mücke T, Mitchell DA, Wagenpfeil S, Ritschl LM, Wolff KD, Kanatas A. BMC Cancer. 2014 May 20;14:346.

SpR in Oral & Maxillofacial Surgery, BAOMS/Saving Faces-FSRF Research Fellow

Unit: University of Liverpool & Aintree Hospital

Correspondence Address:  Applied Cancer Biology Research Group, Division of Surgery and Oncology, School of Cancer Studies, Cancer Research Centre. University of Liverpool. 200 London Road. Liverpool L3 9TA

Six key words that describe my research interests
Cancer, Metastasis, Biomarkers, Molecular, Organotypics, Pathways

How I first began pursuing research:
I completed a Medical Research Council funded intercalated degree in Cellular and Molecular Pathology as a dental undergraduate, which gave me a valuable insight to research. From this I realized that the fundamentals of pursuing a successful research experience and training was a project that interests you.

My planned higher degree thesis
PhD April 2010-13 University of Liverpool

My supervisor/s
Professor Ross Sibson
Mr Richard Shaw
Dr Janet Risk

Abstract:

Oral Squamous Cell Carcinoma (OSCC) is the commonest form of head and neck cancer and has a highly heterogenous clinical outcome. Studies carried out in Liverpool have conclusively demonstrated that extra-capsular spread (ECS) in cervical metastasis is the single most important prognostic factor (ECS+ve 23% 5yr OS vs. ECS-ve 60% 5yr OS). Our hypothesis is that molecular events in key pathways are associated with this aggressive metastatic phenotype.  An 8-gene expression signature has been identified from a larger 29-gene panel associated with ECS in OSCC by microarray analysis of primary tissue (n=55). A classification model highlighted pathways involved in extracellular matrix and cytoskeletal remodelling as being associated with the development of ECS.

My main sources of research funding
 
2010 Royal College of Surgeons of England Research Fellowship
2010 BOAMS Endowments Grant
2011 BAOMS/Saving Faces-Facial Surgery Research Foundation Research Grant

My clinical commitment during my research period
Nil

An account of my current and ongoing research
 
The aims of my PhD project are to test the following hypotheses:

To test whether a gene expression signature is better than the current clinical preoperative methods for predicting ECS

To test whether the ECS phenotype is associated with cells having characteristic behaviour in in vitro models

Clinical data, with pathology and outcomes, has been obtained from case note review. This has confirmed the significance of ECS as an adverse prognosticator in OSCC. Radiological assessment (MRI) demonstrates a sensitivity of only 6.8% for ECS. A validation series of 93 samples, including 55 from the original discovery series, has been produced for use in single gene assays (Taqman©). The quantitative rtPCR assays have been completed for 8 genes, 2 endogenous controls and an exogenous control. Data analysis including predictive and diagnostic value is pending.   Additional genes will be contrasted and compared depending on their specificity, sensitivity and as suggested by further analysis of the pathways implicated.

Organotypic culture invasion assays have been chosen for functional assays, using cell lines developed from primary cell culture. Primary cell culture of normal tissue and primary tumour tissue collected from 30 patients has produced 9 primary keratinocyte cell lines (2 from N0 tumours, 4 from tumours with ECS and 3 from normal tissue) with 23 fibroblast populations (13 N0, 1 N+, 8 ECS+ and 1 from normal tissue). Cell phenotypes have been confirmed by immunohistochemistry. These primary cell lines offer a unique resource to further our knowledge of epithelial and mesenchymal interactions. Preliminary data shows increased proliferation of tumour compared to normal keratinocytes and short tandem repeat profiling for 4 of the cell lines has demonstrated genetic stability up to passage 12.   Transfection of selected instances of the cell lines has been successful at rates of 17% and 31% using a SCneo construct. Ongoing work is characterising the fundamental cell biological properties of these cell lines as a point of reference for interventional investigations to follow.

My future planned research

Validated targets will be analysed using IHC on tissue microarrays (TMA) prepared for the same cohort.  This will enable determination of the clinical applicability of targets in the pathological setting with cores from both the tumour centre and the advancing front from primary sites as well as metastatic nodes, with and without ECS.  The effect of manipulating expression of 4 genes from the ECM remodelling pathway (identified from further investigations of the expression data and including serpine which was part of the predictive signature) will be investigated in relation to the fundamental properties of the cells (invasion, motility, apoptosis, proliferation).   Keratinocyte and fibroblast primary cell lines from different primaries (ECS –ve vs ECS +ve) will be compared using invasion assays.   Oral cancer cell lines, cells from adjacent normal tissue, control fibroblasts (human fetal foreskin) will be included in the comparisons.

My advice for budding OMFS researchers.

Find a project that interests you at a centre and with a supervisor who has a proven track record in research and make sure the project has achievable goals.

Best five papers published:

Dhanda J, Shaw R.(2011) The Genetics and Epigenetics of Head and Neck Cancer. In J Bernier (Ed). Head and Neck Cancer: Multimodality Management. (1st Ed)  NK Springer-Verlag

Dhanda J, Cooper C, Allen A, Speculand B. Techniques of Temporomandibular Joint Replacement in the Edentulous BJOMS (2011) in press corrected proof doi:10.1016/j.bjoms.2010.10.011

Dhanda J, Opie N, Webster K, Tanday A, Mumtaz S, Visram S . The Impact of Modernising Medical Careers on Basic Surgical Training Experience of Oral and Maxillofacial Higher Surgical Trainees. BJOMS (2011) 49L1):62-64

R Shaw, J Dhanda. Hyperbaric Oxygen in the Management of Late Radiation Injury to the Head and Neck. Part I: Treatment. BJOMS (2011) 49(1):2-8

Dhanda J, Hall T, Wilkins A, Mason V, Catling J.  Patterns of Treatment of Osteoradionecrosis with Hyperbaric Oxygen Therapy in the United Kingdom BJOMS (2009) 47(3)210-3

Specialty Registrar in Oral and Maxillofacial Surgery

Unit: North Manchester - North West Rotation
Correspondence Address:  Appt 15, Valley Mill, Park Road, Elland, HX5 9GY

Email: kyzasp@hol.gr

Six key words that describe my research interests

Evidence based medicine, cancer, biomarkers, meta-analysis, prognosis, angiogenesis

How I first began pursuing research:

I have actually been involved in research since my first degree, in Dentistry. At that time I utilized my free time to perform non-systematic reviews on (what I thought they were) interesting maxillofacial issues. Soon I realized that this is not research, but an easy way to publish poor quality papers. I am actually proud I have numerous manuscripts of non-systematic reviews in my hard drive, but never published them! However, this was the spark to push me further in searching what research actually is. During my degree in medicine, I had the lack to meet Prof. John PA Ioannidis, a world-leading expert in evidence-based medicine, and this was the initiation of my involvement in real research.

My higher degree thesis abstract

PhD Thesis 2002-2007, University of Ioannina

Abstract: Angiogenesis and Lymphangiogenesis in Head and Neck Squamous Cell Carcinoma

Angiogenesis is the propelling force for tumor growth and metastatic dissemination in solid neoplasms. This process is tightly controlled by numerous positive and negative angiogenic factors and their receptors, the interaction of which regulates the cascades enabled in tumor neovascularization. Among the factors causing tumor angiogenesis, vascular endothelial growth factor (VEGF) is considered as a leading candidate.VEGF induces the proliferation, differentiation, and migration of vascular endothelial cells, increases the permeability of the capillaries, and also enhances the survival of endothelial cells by preventing their apoptosis. It has been proposed that the quantification of angiogenesis by the assessment of microvascular density (MVD), as well as the evaluation of VEGF immunohistochemical expression may have prognostic value in a number of malignancies, including head and neck squamous cell carcinoma (HNSCC).

Lymph node metastasis is a frequent reason for adverse clinical outcome in many epithelial neoplasms, including HNSCC. The mechanisms underlying the capability of epithelial neoplasms to metastasize via lymphatic vessels have not yet been fully elucidated. There is great debate about whether cancer cells can metastasize by expansion and invasion of pre-existing peritumoral lymphatics or by the formation and invasion of new lymphatics within tumours (lymphangiogenesis). Currently, researchers probe into the mechanisms of lymphangiogenesis. Central to these efforts was the discovery of lymphatic endothelium markers, such as LYVE-1, the antibody against podoplanin, D2-40, prox-1 and VEGFR-3.

We aimed to study angiogenesis and lymphangiogenesis in 81 formalin-fixed, paraffin embedded archival tissue blocks of HNSCC specimens, applying immunohistochemical techniques. We evaluated the expression of VEGF and its receptors (VEGFR-1 and VEGFR-2) by squamous cancer cells and assessed MVD with the use of both the traditional endothelial markers CD31 and CD34, as well as with the use of the newly proposed marker CD105 (endoglin). We also addressed the impact of hypoxia-induced angiogenic pathway by examining the expression of HIF-1a. Furthermore, we studied lymphangiogenesis, using immunostaining for the specific lymphatic endothelium marker podoplanin, and assessed intratumoral and peritumoral lymphatic density (ILD and PLD), and also quantified lymphatic invasion. Active lymphangiogenesis was examined with double staining with podoplanin and the cell proliferation marker Ki-67. We also addressed the diagnostic accuracy of two of the so called "specific" lymphatic endothelial markers, podoplanin and D2-40. Moreover, we assessed the expression o VEGF-C and its possible correlation with COX-2 expression, in order to investigate the impact of the prostaglandin pathway in lymphangiogenesis. Finally, we evaluated the correlation between cell-cell adhesion and lymphangiogenesis by examining the expression of dysadherin and E-cadherin along with lymphatic density. Dysadherin is a recently characterized cancer-associated cell membrane glycoprotein that acts as an "anti-adhesion molecule'' by deactivation of E-cadherin a posttranscriptional manner.

VEGF overexpression was associated with advanced clinical stage, positive surgical margins and worse overall survival. The prognostic significance of VEGF in HNSCC was further supported by the synthesis of the results of all the studies addressing this issue, with the method of meta-analysis.  The estimated risk of death in 2 years was 1.88 fold higher in the VEGF-positive patients (95% CI: 1.43-2.45, p<0.001, random effects calculations). VEGF overexpression was also significantly associated with higher MVD, when the last was determined with CD105. CD105 was intensively expressed in intratumoral blood vessels, whilst vessels at the adjacent normal mucosa were only rarely expressing this marker. MVD determined with CD105 (but not with CD34 or CD31) was associated with worse overall survival in our cohort of patients. The investigation for VEGF receptors revealed the existence of these receptors in cancer cell membranes, besides vascular endothelium. High expression of VEGF was strongly correlated with high expression of VEGFR-2 (but not VEGFR-1) on the cancer cells (p<0.001). The co-overexpression of both the protein and VEGFR-2 was associated with higher tumor proliferation rate, as indicated with ki-67 (P<0.001). These results suggest that an autocrine VEGF loop, mediated via VEGFR-2, probably exists in HNSCC. Squamous cancer cells probably produce VEGF not only to induce neoplastic angiogenesis, but also to enhance their uncontrolled proliferation. Studying the hypoxia-induced tumor angiogenic pathway, we observed a statistically significant association between HIF-1a and VEGF expression in tumors located in the lower lip, but not the rest. These findings support the hypothesis that tumor angiogenesis is close related, but not strictly dependent, on the hypoxic conditions of tumors' microenvironment.

Double staining with podoplanin / ki-67 revealed the existence of proliferating intratumoral lymphatics, in which tumour emboli were occasionally observed. High ILD and PLD were both significantly associated with the presence of lymph node metastasis (x2 test, p < 0.001 and p = 0.007, respectively) and there was a significant correlation between high ILD and lymphatic invasion. Patients with higher intratumoral lymphatic density exhibited shorter overall survival. These results indicate that lymphangiogenesis indeed occurs in HNSCC; that newly formed vessels are targets of invasion by cancer cells; and that intratumoral lymphatic density might be used as a criterion to separate patients at higher risk of an adverse clinical outcome. Reservations about the existence of lymphangiogenesis in tumors are boosted by the absence of quantitative data about the diagnostic accuracy of lymphatic endothelium markers. We therefore compared the diagnostic accuracy of the antibody against podoplanin and the commercially available D2-40, employing Bayesian statistics to account for the absence of a gold standard. Both antibodies had extremely high specificity (99.7% and 98.8% for podoplanin and D2-40, respectively) and very high sensitivity (92.6% and 97.3% for podoplanin and D2-40, respectively). These results suggest that both antibodies are excellent lymphatic endothelium markers. Results for VEGF-C revealed that the expression of this protein marches with COX-2 overexpression (p<0.001), and both are strongly correlated with the presence of lymph node metastasis (p<0.001). Studies performed after the publication of our results confirmed these observations and support the hypothesis for a prostaglandin-mediated lymphangiogenic pathway, in which COX-2 stimulates VEGF-C up-regulation. Finally, the examination of cell-cell adhesion along with the micro-lymphovasculature environment in HNSCC revealed, besides an impressive reverse association between increased dysadherin expression and decreased E-cadherin expression (x2 p<0.001), a strong association between higher dysadherin expression with high ILD (x2, P = 0.001) and the presence of lymph node metastasis (x2 p=0.02) Surprisingly, dysadherin-positive cancer cells usually gathered around areas of high intratumoral lymphatic vessel concentration, surrounding and invading small intratumoral lymphatics. Thus, the loss of intercellular adhesiveness and increased dysadherin expression seems to be related to lymphangiogenesis in HNSCC.

In summary, angiogenesis and lymphangiogenesis seem to play a crucial role in HNSCC. Further understanding the mechanisms underlying these procedures will aid the incorporation of novel prognostic tools into clinical practice and help the development of drugs targeting several of their critical steps in order to improve patient's outcome. 

My main sources of research funding

Department of Pathology, Medical School, University of Ioannina, Greece Scientific Committee: European Union (EDAP) No 1495 program

My clinical commitment during my research period

None

An account of my current and ongoing research

Participating in Cochrane's Prognosis Method Group which aims in improving the overall quality of prognosis research by publishing a series of papers/recommendations.

Active peer-reviewer in a variety of journals (more than 20), including BMJ and Br J Cancer

Empirical evaluation of the evidence behind the use of prophylactic antibiotics in mandible fractures (meta-analysis submitted for publication)

Evaluation of diagnostic accuracy of Sestamibi scan in parathryroid adenomas (protocol currently prepared) 

My future planned research

Unfortunately, there is increasing evidence to suggest that many interventions employed in our specialty lack strong evidence based support. My intention is to try to identify such areas and try to design/execute trials that may give answers to many clinical questions/debates. Whether this is possible during my intensive SpR training, I don't know. 

Current active grants and project titles

No active grants

My advice for budding OMFS researchers

1. It's very easy to perform "research" and even easier to publish something in a peer-reviewed journal. It's very difficult to perform real research and extremely difficult to publish something important in a well-respect journal. It's even more difficult to achieve recognition of your research work (i.e. many citations), but is certainly rewarding. 

2. Research is somehow similar to surgery. If your teacher knows, you will learn. The opposite stands true as well.

3. Audit IS NOT research. It is a tool for quality improvement and a contractual obligation for doctors. Mixing audit and research results in poor quality for both. 

4. Common is common in medicine, and simple should stay simple in research.

5. READ general medical and surgical journals; not only journals from our specialty. Some of the greatest achievements from OMFS researchers inevitably will be published in high impact journals. 

Best six papers published:

1. Kyzas PA, Evangelou E, Denaxa-Kyza D, Ioannidis JP. 18F-fluorodeoxyglucose positron emission tomography to evaluate cervical node metastases in patients with head and neck squamous cell carcinoma: a meta-analysis. J Natl Cancer Inst. 2008 May 21;100(10):712-20. Epub 2008 May 13.
2. Kyzas PA, Denaxa-Kyza D, Ioannidis JP. Almost all articles on cancer prognostic markers report statistically significant results. Eur J Cancer. 2007 Nov;43(17):2559-79. Epub 2007 Nov 5.
3. Kyzas PA, Loizou KT, Ioannidis JP. Selective reporting biases in cancer prognostic factor studies. J Natl Cancer Inst. 2005 Jul 20;97(14):1043-55.
4. Evangelou E, Kyzas PA, Trikalinos TA. Comparison of the diagnostic accuracy of lymphatic endothelium markers: Bayesian approach. Mod Pathol. 2005 Nov;18(11):1490-7.
5. Kyzas PA, Geleff S, Batistatou A, Agnantis NJ, Stefanou D. Evidence for lymphangiogenesis and its prognostic implications in head and neck squamous cell carcinoma. J Pathol. 2005 Jun;206(2):170-7.
6. Kyzas PA, Cunha IW, Ioannidis JP. Prognostic significance of vascular endothelial growth factor immunohistochemical expression in head and neck squamous cell carcinoma: a meta-analysis. Clin Cancer Res. 2005 Feb 15;11(4):1434-40.

More than 450 citations so far.

NIHR Academic Clinical Fellow in Surgery, School of Medicine and Leeds Teaching Hospital NHS Trust

Current MD(res) Student at Department of Surgery, University College London Medical School (finishing in Dec 2011)

Co-Editor-in-Chief of Head and Neck Oncology (peer-reviewed PubMed Journal)

Email: waseem_wk1@yahoo.co.uk

Unit: UCLH Head and Neck Unit, London

UCL Department of Surgery, London

List 6 key words that describe your research interests:

Head and neck oncology

TMJ surgery

Dentoalveolar surgery

Lasers, Photodynamic therapy and photochemical internalization

Optical diagnostics

Maxillofacial trauma

Describe briefly how you first began pursuing research

I started my research career soon after qualifying in dentistry. I joined an MSc programme in Oral and Maxillofacial Surgery at University College London. During the course I learned the basics of clinical research and managed to publish few papers and present my research work.

What higher research degrees did you pursue? List your supervisor/s

MSc OMFS: Mr Colin Hopper

MD(res): Mr Colin Hopper, Prof Stephen Bown

PhD: Prof Peter McCarthy, Mr Colin Hopper

Describe any form of clinical commitment during your research period.

Previously Senior Clinical Research Fellow at UCLH Head and Neck Centre and Senior Clinical Research Associate at UCL Department of Surgery, UCL Medical School.  

Currently NIHR ACF in Surgery, Leeds Teaching Hospitals NHS Trust and Leeds Medical School

In the process of completing my MRCS so I can return to oral and maxillofacial surgical training

Give an account of your current and ongoing research.

I have published about 120 articles. 100 of them were in peer-reviewed PubMed Journals.

I have been given 15 Grants, Awards & Commendations mostly by the British Association of Oral and Maxillofacial Surgeons

I have given over a hundred oral communications and poster presentations in national and international meetings

I have completed 15 audit studies

I have co-authored 6 book chapters

I have published over 160 abstracts in various medical and surgical journals

I have contributed to several national and international courses and conferences

I have fellowships with the Higher Education Academy, Academy of Medical Educators and Institute of Clinical Research.

Give an account of your future planned research

-Systematic approach to polytrauma patients

-Management of critically ill surgical patients

-Systematic reviews in oral and maxillofacial/head and neck surgery

Do you have any advice for budding OMFS researchers?

Work with established and committed colleagues

Please list the best papers you have published

Jerjes W, Upile T. Use of medical titles by non-doctors can mislead patients. BMJ. 2011 Jul 20;343:d4241.

Jerjes W, Upile T, Hamdoon Z, Mosse CA, Akram S, Morley S, Hopper C. Interstitial PDT for vascular anomalies. Lasers Surg Med. 2011 Jul;43(5):357-65.

Jerjes W, Upile T, Hamdoon Z, Al-Khawalde M, Morcos M, Mosse CA, Hopper C. CO(2) laser of oral dysplasia: clinicopathological features of recurrence and malignant transformation. Lasers Med Sci. 2011 Apr 15.

List your involvement in any on-going trials

An open, phase I, dose-escalating study to evaluate the safety and tolerance of Amphinex based Photochemical Internalisation (PCI) of bleomycin in patients with local recurrence or advanced/metastatic, cutaneous or sub-cutaneous malignancies.

Carried out at University College Hospital London 2009-2011

My role: sub-investigator

Principal investigator: Mr Colin Hopper

Clinical Research Fellow in Oral & Maxillofacial Surgery
Unit:     Merseyside Regional Maxillofacial Unit

Correspondence Address:  Regional Maxillofacial Unit, University Hospital Aintree, Lower Lane, Liverpool L9 7AL

Email : naseemghazali@doctors.org.uk
 

Six key words that describe my research interests.

Head and neck cancer survivorship 

How I first began pursuing research

I had a taster of research during my Masters in Science (Oral Surgery) stint at the Eastman Dental Institue, University of London in 1998 prior to medical school. My research project was an in vitro evaluation of the molecular mechanisms behind therapeutic ultrasound in osteoradionecrosis.
I promptly applied for the Out of Programme for Research option having completed the FRCS(OMFS) exam to enrol in a higher academic research degree at the University of Liverpool which has a strong research profile in basic science research, clinical trials and in quality of life research in head and neck oncology in October 2010.    

List your supervisor/s

Prof SN Rogers, Prof B Roe, Mr RJ Shaw, Dr J Risk

My higher research degree

I am currently pursuing an MD degree.

University that I am registered with for your higher research degree

University of Liverpool

My main sources of research funding

BAOMS Endowments Grant

My clinical commitment during my research period

2 sessions per week

An account of my current and ongoing research

The over-arching theme of my MD project is the provision of a personalised and holistic approach to support and care in head and neck cancer survivorship. Two areas are evaluated. The major work involves evaluating the roll out of the Head and Neck Cancer Patient Concerns Inventory, a holistic assessment tool for highlighting items of patient concern in the context of an outpatient consultation in Maxillofacial and Otolaryngology oncology clinics through a prospective, non-randomised control trial. It is hoped that this tool will facilitate patient-doctor communication, reduce the likelihood of unmet needs and enable a personalised, patient-driven consultation.  The second element to this study involves a pilot study evaluating the role of genetic polymorphisms underlying radiotoxicity in head and neck cancer patients, a phenomenon that often results in poorer health-related quality of life in cancer survivors. It is hoped that the findings may form the basis of genetic testing to determine predisposition to radiotoxicity, which can influence treatment decision making and planning of supportive care following completion of treatment.

An account of my future planned research

My future research plan is to continue work in head and neck cancer survivorship based on the work that I am currently involved in.

My current active grants and project titles

British Association of Oral & Maxillofacial Surgery Endowment grant: £21,874 for 'Personalising Head and Neck Cancer Sumivorship: Evaluating the Head and Neck Patient Concerns Inventory and the Role of Genetic Polymorphyisms in Radiotoxicity and Health-related Quality of Life'

Best five papers published

1. Bekiroglu F, Ghazali N, Laycock R, Katre C, Lowe D, Rogers SN. Adjuvant radiotherapy and health-related quality of life of patients at intermediate risk  of recurrence following primary surgery for oral squamous cell carcinoma. Oral Oncol. 2011 Aug 8. [Epub ahead of print]

2. Ghazali N, Kanatas A, Langley DJ, Scott B, Lowe D, Rogers SN. Treatment referral before and after the introduction of the Liverpool Patients Concerns Inventory (PCI) into routine head and neck oncology outpatient clinics. Support Care Cancer. 2011 Jul 3. [Epub ahead of print]

3. Flexen J, Ghazali N, Lowe D, Rogers SN. Identifying appearance-related concerns in routine follow-up clinics following treatment for oral and oropharyngeal cancer. Br J Oral Maxillofac Surg. 2011 Jun 14. [Epub ahead of print]

4. Lyons A, Ghazali N. Osteoradionecrosis of the jaws: current understanding of its pathophysiology and treatment. Br J Oral Maxillofac Surg. 2008; 46(8):653-60.

5. Ghazali N, Bakri MM, Zain RB. Aggressive, multifocal oral verrucous leukoplakia: proliferative verrucous leukoplakia or not? J Oral Pathol Med. 2003;32(7):383-92.