Surgical Research Report 2017/18
The Royal College of Surgeons of England Contents
4 Chairman’s Introduction
6 Research Fellows’ Reports
60 Pump Priming Reports
68 Surgical Trials Initiative
72 Clinical Effectiveness Unit
76 Research in the Faculty of Dental Surgery
80 Prizes & Travelling Awards
82 Higher Degrees for Intercalated Medical Students
92 Elective Prize Reports
102 Lectures Delivered in 2015–2016
103 Fundraising in Focus
104 Picture Gallery
2 3 Chairman’s introduction
Research is not an optional add-on, it is the very lifeblood of surgery. We need to introduce new technologies safely and effectively, we need to understand basic mechanisms of disease and we need to do the things we are doing now, but better. Most important of all, we need to inspire the surgeons of the future to see this as part of their mission in improving the experience and standards of care for our patients.
Neil Mortensen Chairman, Research Fellowship and Lectureship Selection Group
4 The Royal College of Surgeons The Surgical Trials Initiative introduced Professor Sir Peter Morris who with through its Research Fellowship in 2012 has developed rapidly. There great foresight started the Research scheme has committed more than are now seven chosen Surgical Trial Fellowship scheme in 1993 has £40million to support over 700 Centres in the UK and there are 15 recently retired as Director of the individual trainee members during appointed Surgical Specialty Leads Centre for Evidence in Transplantation. the past 24 years, and this year we with the task of promoting trials and We are particularly grateful to Claire have approved a further £2million trial recruitment, and providing a link Large who has retired as CEO of funding for some 30 new Research between surgeons, investigators the Dunhill Medical Trust, who have Fellowships. The quality of the and the trials centres. Some 25,746 been major supporters of the College applicants has been outstanding and patients have been recruited to 85 research initiatives in research related most are either starting or completing trials across the surgical specialties. to the elderly. a PhD, which now means three A particular success has been the Martyn Coomer and Jonathan years of funding. The College does development of trainee research Fountain and their staff have worked not undertake the research itself but collaboratives. We are especially tirelessly to underpin all this activity. provides seedcorn funding for grateful to the Rosetrees Trust for Jonathan has moved on to a new job start-up projects which then attract their support for these developments. for which we wish him all the best. funding from such bodies as the Professor Derek Alderson has been Wellcome Trust, CRUK and MRC. We need to inspire the inspiring our focus on surgical trials and Professor Dion Morton as Director This yearly round of appointments surgeons of the future in depends on our many donors to whom of Clinical Research has with great we remain immensely grateful, but improving the experience energy and enthusiasm helped make we can always do so much more. and standards of care for it happen. We have added to our Research our patients To all our many funders we are most Fellowship partnerships the British grateful and hope that on seeing our Society of Endovascular Therapy many successes you will continue to (BSET), the Virginia Mason Hospital The Surgical Technology Evaluation help us with our work. Seattle, and Addenbrooke’s Charitable Portal (STEP) is run jointly with the Trust. Two novel Fellowships in Clinical NIHR to help with the rapid assessment Leadership have been introduced with of new technologies and was launched the Faculty of Medical Leadership earlier this year. This will provide and Management and McKinsey. Our technology companies with access to prestigious Fulbright Fellowship to the clinical advice and appropriate patient USA agreement has been renewed. groups to ensure the safe introduction of new procedures. The Clinical Effectiveness Unit (CEU), a joint programme with the London Over the last 20 years many University School of Tropical Medicine and Departments of Surgery have been Hygiene, continues to provide a closed or subsumed into larger major focus for national audits in groupings with a consequent loss oesophagogastric, bowel, breast of surgical academic leadership. and prostate cancer, as well as If these exciting new programmes are vascular surgery, cleft lip and palate, to be successful this decline needs emergency laparotomy and falls and to be reversed and in 2017/2018 the fractures. These important studies College is planning to establish new provide the facts on which to base chairs in surgical clinical research. health policy and improve outcomes We need to raise some £2.5million. for our patients.
Over the last 20 years many University Departments of Surgery have been closed or subsumed into larger groupings with a consequent loss of surgical academic leadership.
5 Fellowships are awarded to subscribing members of the College in a training post, or trainees who have passed the MCQ papers and will sit the final MRCS examination at this College. All applications are rigorously assessed by a panel of experts to ensure that the research, surgeon, supervisor and facilities are of a high standard, and that the proposed work will be valid, beneficial and original. The fellowships cover salary, on-costs and some running expenses. Fellows may study any aspect of surgery or surgical care including basic science, diagnosis, treatment, surgical technology, logistics or audit.
6 Research Fellows’ Reports
Zaid Awad Dafydd Edwards Elizabeth Maughan Bynvant Sandhu Marc Bailey Jason Fleming David Metcalfe John Saunders Basil Bekdash Mathew Gardiner Anita Mohan Annabel Sharkey James Berry Katherine Gash Aadil Mumith James Singleton John Broomfield Michelle Griffin Suzanne Murphy Anna Slovick Marc Bullock Rachael Harrison Sumit Nandi Peter Szatmary Andrew Cowie Jasmine Ho Liza Osagie Tanujan Thangarajah Helen Cui Amel Ibrahim James Paget Peter Vaughan-Shaw Andrew Currie Zita Jessop Karl Pang Christopher Wearn Praveena Deekonda Matthew Kirkman Keval Patel Michelle Wilkinson Harveer Dev Kathryn Lynes Henrietta Poon Hugh Wright Nicholas Eastley Dermot Mallon Jason Powell Rasheed Zakaria Ellie Edlmann Gulraj Matharu Stuart Roberts
7 Structured, rigorous and validated assessment which integrates simulation and workplace modules can help deliver better surgical training. Better training equates to better and safer patient care.
A comprehensive evaluation of workplace and simulation-based assessment in otolaryngology training
FELLOWSHIP/SPONSOR: 2. Utilisation, reliability and 2. Cold steel tonsillectomy Colledge Family Fund validity of Clinical Evaluation simulator: using silicone to Exercise in otolaryngology train future trainees, Annual SUPERVISORS: training. Awad Z, Hayden L, Meeting of the Faculty of Surgical Neil S Tolley, Paul Ziprin and Muthuswamy K, Tolley NS. Trainers, RCSEd, Edinburgh Ara Darzi Clin Otolaryngol. DOI: 10.1111/ 22 Oct 2014 SITE OF WORK: coa.12400 PRIZES: Imperial College London PRESENTATIONS: 1. Nan Blofeld Travelling PUBLICATIONS: 1. Construct validity of cadaveric Fellowship, University College 1. Construct validity of cadaveric temporal bone simulation in London Hospitals Charity, temporal bones for training and mastoidectomy training, Annual Feb 2015 assessment in mastoidectomy, Meeting of the Faculty of Surgical 2. HCA International Traveling Awad Z, Tornanri C, Ahmed S, Trainers, RCSEd, Edinburgh Fellowship Grant, HCA Tolley NS. Laryngoscope. DOI: 22 Oct 2014 International Foundation, Zaid Awad 10.1002/lary.25310 Oct 2014
The otolaryngology curriculum requires piloted and models were tested for Sixty trainees and 40 consultants trainees to show evidence of operative feasibility, face, content and construct participated in the process and found competence before completion validity, before being incorporated into it of great educational value. of training. The General Medical the North London training programme. We concluded that assessment with Council recommended that structured The outcomes of workplace- and structured feedback is integral to surgical assessment be used throughout training simulation-based assessments of all core training. Assessment using validated to monitor and guide trainee progression. and specialty otolaryngology trainees simulation modules can complement Despite the reduction in operative were collated and analysed. that undertaken in the workplace. The exposure and the variation in trainee The outcomes of 6,535 workplace- outcomes of structured assessments performance, a ‘one size fits all’ approach based assessments were analysed. can be used to monitor and guide continues to be applied. The number of The strengths and weaknesses of trainee trajectory at individual and procedures performed remains the main four different assessment tools were regional level. The derived learning indicator of competence. highlighted. Validated platforms utilising curves can shape and audit future Our objectives were to analyse the cadavers, animal tissue, synthetic otolaryngological training. utilisation, reliability and validity of material and virtual reality simulators workplace-based assessments in were incorporated into the curriculum. otolaryngology training, to identify, develop and validate a series of simulation platforms suitable for incorporation into the otolaryngology curriculum and to develop a model of interchangeable workplace- and simulation-based assessment that reflects the trainee’s trajectory, audit the delivery of training and set milestones for modular learning.
We used a detailed review of the literature, identified a list of procedure- specific assessment tools, as well as simulators suitable to be used as assessment platforms. A simulation- integrated training programme was A group of trainees practicing micro-laryngeal procedures under faculty supervision
8 Targeting Ca2+ channels to attenuate AAA growth
FELLOWSHIP/SPONSOR: PUBLICATIONS: 2. Assessment of novel Joint RCS/Circulation Main paper from the work therapeutics for AAA with 3D Foundation Fellowship has been submitted to Nature ultrasound in mice. British Communications. Details of the Medical Ultrasound Society, SUPERVISORS: paper remain confidential at Cardiff, Wales, Dec 2015 Professor David J Beech FMedSci present. I am the lead author. PRIZES: PRESENTATIONS: 1. James Ellis Award Sept 2015 SITE OF WORK: 1. Inhibition of pathological LIGHT Building, Leeds Institute 2. David Gamble Charitable vascular smooth muscle cell of Cardiovascular & Metabolic Trust Award Sept 2015 remodelling as a treatment Medicine, University of Leeds strategy for abdominal aortic FURTHER FUNDING: aneurysm. International Meeting Medical Research Council, on Aortic Diseases, Liege Belgium, University of Leeds for MRC: 12 months, UoL: five years Marc Aaron Sept 2016 Bailey
An abdominal aortic aneurysm, or AAA, is a ballooning of the aorta – the main blood vessel in the body. The condition is silent but can be deadly if the expanding vessel ruptures. In the UK we have a national screening programme for AAA but can only offer surgical repair when the AAA is large and the risk of rupture greater than the risks associated with surgery. My work centres around developing a medical therapy that could be used to slow the growth of these small aneurysms to prevent progression to surgical intervention or rupture. This will reduce exposure to intervention which is reducing mortality, morbidity and improving quality of life.
The idea of the project is to target a calcium channel in the vascular smooth muscle cells to prevent their dysfunctional remodelling behaviour. Marc performing invivo ultrasound of an experimental aneurysm Our group previously identified that I discovered that by using this approach, This award helped me to attract funding a calcium channel called Orai1 controls AAA progression could be reduced by from the Medical Research Council to cell function in vascular cells pertinent 40%. This is a new area of research but continue to develop the small molecule to disease. In this project I used there is emerging evidence from other Orai1 inhibitors and the University of mouse models of AAA and ultrasound groups around the world that modifying Leeds to validate our findings using gene imaging to track disease progression. the response of the vascular cells in the manipulation techniques. I have recruited A potent and specific Orai1 inhibitor was aorta might slow disease progression a team of PhD students from the basic developed and delivered to the animals in AAA. sciences who will continue the project. only after aneurysms had formed – mirroring the human situation.
Blocking the Orai1 calcium channel slows aneurysm progression by 40%.
9 The majority of patients who develop type I diabetes will do so in childhood or early adult life but do not have access to an appropriate way to replace the lost insulin producing cells (β-cells).
Pre-conditioning of islets of Langerhans for use in an implantable bioartificial pancreas
FELLOWSHIP/SPONSOR: Joint BAPS/RCS Research Fellowship SUPERVISORS: Professor Paul RV Johnson and Dr Daniel Brandhorst SITE OF WORK: Nuffield Department of Surgical Sciences, University of Oxford
Basil Bekdash
There are currently no effective and acceptable treatments to reverse or prevent this lost insulin, meaning patients require a lifetime of monitoring and artificial insulin replacement. Even with the best care and control, this is imperfect and leads to long- term complications. Some patients also experience loss of awareness of low blood sugar with potentially life-threatening consequences. Transplantation of the destroyed cells from another person (pancreatic islet transplantation) is an existing treatment for some patients. Basil meeting members of the public at an open engagement event at OCDEM (Oxford Centre for Diabetes Endocrinology and Metabolism) donated cells in an artificial implant. One of the many remaining challenges This allows them to monitor sugar levels is producing, selecting and optimising and produce appropriate levels of insulin tissue for these purposes and this is the but prevents contact with the patient’s focus of ongoing research. immune system cells and prevents them destroying the transplant.
If this goal is achieved not only will Basil preparing a donor pancreas for patients potentially be free of the need islet transplantation to take insulin, they will also avoid the side effects of the drugs necessary for My work has been related to the current transplantation treatments. development of a means of protecting It might also then be suitable for younger donor cells from destruction by the patients, including newly diagnosed transplant recipient’s immune system. children and adolescents. One approach is to physically separate The islet transplant group and colleagues donor and recipient cells by placing the from OCDEM
10 The role of visceral peritoneum in inflammatory responses and healing in the injured abdomen
FELLOWSHIP/SPONSOR: FURTHER FUNDING: Joint RCS/Military The National Institute for Health Research Fellowship Research Surgical Reconstruction and Microbiology Research SUPERVISORS: Centre (NIHR SRMRC) University Professors GL Carlson, Hospital Birmingham, Drummond Midwinter & Warhurst, Foundation Trust and HM Forces and Dr Herrick SITE OF WORK: Salford Royal Foundation Trust
James Berry
Peritoneal adhesions are bands of is important to improve the patient’s fibrous tissue that join abdominal quality of life. However, mechanisms organs to each other or the abdominal behind adhesion formation are complex wall and occur in over 90% of patients and poorly understood and few reliable following surgery and may cause methods of reducing adhesion significant health problems, such as formation exist. pain, infertility, intestinal fistulae and The abdominal organs have different bowel obstruction. Adhesion-related tendencies to form adhesions, with small bowel obstruction occurs in 10% of the bowel being most likely. The cells patients following abdominal surgery and lining the abdominal organs and wall is a significant burden on patients and – mesothelial cells – are thought to be healthcare resources. Adhesions are responsible for controlling inflammation particularly severe following abdominal that leads to adhesions. infection, trauma and repeated surgery. This increases the risk of unplanned To date, research has mainly Dissecting peritoneum from the bowel injury, further infection and concentrated on animal models and bowel specimen fistula formation. Reducing adhesions cell lines. The human small bowel lining, Our data suggests that visceral visceral peritoneum, has not been peritoneum is capable of producing a investigated and may behave differently pro-inflammatory response to infection to abdominal wall lining, parietal which is controlled through a specific peritoneum, predisposing it to adhesions. receptor, not previously identified in We have created a new model studying human mesothelial cells. Blocking this inflammation in humans. Using visceral receptor may be important in reducing and parietal peritoneum, donated from inflammation and adhesions. Further patients undergoing planned surgery, studies are planned comparing visceral we are investigating the reaction of and parietal peritoneum, and what effect each surface to infection with the aim of biological implants, used in abdominal understanding how adhesions develop wall reconstruction, have on this and potential targets to reduce formation. response. The project has gained further funding for an additional researcher and investigations are ongoing.
James at the Camp Bastion Hospital
The visceral peritoneum elicits a proinflammatory response to infection that promotes adhesion formation through modification of the fibrinolytic system. 11 Evidence shows that hip labral tears may be present in up to 55% of patients presenting with hip pain.
Can hip arthroscopy prevent hip arthritis?
FELLOWSHIP/SPONSOR: Joint RCS/Arthritis Research Trust Fellowship SUPERVISORS: Professor S. Glyn-Jones SITE OF WORK: Nuffield Orthopaedic Centre, Oxford
John A. J. Broomfield
This research is a trial to investigate surgical treatments for tears of the labrum of the hip. The labrum is a cartilage structure which encircles the hip socket to provide a ‘seal’ and contribute to the joint stability. Injuries to this structure may occur as a result of prolonged degeneration or as a consequence of injury to the joint.
There are two common approaches to treating this problem: to repair the labrum or remove the damaged portion. This project aims to identify whether the outcome from one surgery is superior to the other. Research patient consultation This will be achieved by randomly allocating patients to one of the two years, meaning there will be a large treatments and subsequently comparing research team with clearly defined roles their outcomes both in terms of patient to complete this study. reported measures and appearance Currently patients struggle for many of joint tissues using scans. The two months, and often years, because there is treatments being investigated have no robust evidence available to clinicians both been shown to be effective for the to inform their treatment. The results of treatment of this problem, but they have the project will provide, for the first time, never been directly compared to each a clear clinical message as to the best other before and therefore this study treatment for this problem, which will is the first to definitively address improve the patients’ journey from injury this problem. to treatment and through to recovery. This project will take 18 months to fully This will mean a better, more streamlined, recruit sufficient patients to satisfy the pathway to the most effective treatment John undertaking a clinical examination requirements to demonstrate reliable for patients, thereby expediting their results. The trial will have an overall recovery and return to normal activity. duration of approximately three to four
12 Identification and characterisation of deregulated long non-coding RNAs during colorectal cancer progression – interplay between tumour stroma and epithelium
FELLOWSHIP/SPONSOR: PUBLICATIONS: PRESENTATIONS: RCS Fulbright Scholar Award 1. Bullock MD, Silva AM., MD Anderson Cancer Centre Kanlikilicer-Unaldi P, Filant J, Seminar. ‘The clinical roles of SUPERVISORS: Rashed MH, Sood AK, exosomal non-coding RNAs in Professor George Calin Lopez-Berestein G, Calin GA. cancer’ Houston Feb 2015 SITE OF WORK: Exosomal non-coding RNAs: PRIZES: MD Anderson Cancer Centre, Diagnostic, prognostic and 1. NIHR Clinical Lectureship Houston, Texas therapeutic applications in cancer. Award. July 2015 Non-coding RNA 2015: 1; 53-68 2. Wessex Medical Research 2. Silva AM, Bullock MD, Calin Innovation Award. June 2015 GA. The clinical relevance of long non-coding RNAs in cancer. FURTHER FUNDING: Cancers 2015: 7; 2169-2182 NIHR for four years and Wessex Marc David Medical Research for two years Bullock
As the 2014-2015 Fulbright-RCS Furthermore, long non-coding RNAs Scholar, I undertook a period of are promising prognostic and diagnostic post-doctoral research training in markers, and they are potentially the Department of Experimental targetable by drugs. As such, this Therapeutics at the MD Anderson research may be adapted in future to Cancer Centre in Houston. Under the help improve and extend the lives of supervision of Professor George A patients with colorectal cancer. Calin, a world expert in experimental The Fulbright experience was cancer treatment, I characterised the overwhelmingly positive. On a expression of a class of molecule professional level, I was able to use called long non-coding RNAs in human technology unavailable to me in the colorectal cancer using technology UK to generate highly novel and purpose-built for the task. interesting data, helping me secure a Long non-coding RNAs have only NIHR Clinical Lectureship position at my recently been discovered and are home institution and additional funding generating increasing research interest. to support my research in the UK. Although it is known that they perform Furthermore, in six months I published important roles in both normal and two articles as first author and contributed diseased tissues, relatively little is known to several other manuscripts published about their contribution to cancer spread. high impact peer-review journals. Marc teaching on a surgical skills course in By focusing on long non-coding RNAs In the coming years, this highly Toamasina in Madagascar. A collaboration in the tissues surrounding the tumour, productive relationship with the host between ASGBI and Texas-based charity this was an opportunity to better laboratory will continue to underpin my Mercy Ships understand the biology of colorectal program of research. I will also have the cancer metastasis and conduct opportunity to share my new research research in a novel field with significant skills with colleagues at the University translational promise. of Southampton.
Understanding the role of novel molecules called long non-coding RNAs during colorectal cancer spread – the contribution of cancer cells and the tissues which surround a cancer. 13 At the time of diagnosis less than 1 out of 3 patients with oesophageal cancer will be able to have curative surgery.
Stromal targeting in oesophageal cancer
FELLOWSHIP/SPONSOR: PRESENTATIONS: PRIZES: Joint RCS/Arthritis Research 1. Developing model systems to 1. Developing model systems Trust Fellowship understand the functional and to understand the functional clinical significance of somatic and clinical significance of SUPERVISORS: genetic variations in oesophageal somatic genetic variations in Associate Professor cancer – Moynihan Prize Session, oesophageal cancer, Best Poster T J Underwood ASGBI International Surgical Prize, 8th National Barrett’s SITE OF WORK: Congress 2014, Harrogate Symposium, London, April 2014 Department of Experimental 2. Stromal targeting with 2. Shortlisted for Moynihan Prize Pathology, Cancer Sciences phosphodiesterase type 5 session ASGBI International Division, University of inhibitors in oesophageal Surgical Congress 2014 & 2015 Southampton adenocarcinoma – Moynihan Prize Session, ASGBI PUBLICATIONS: International Surgical Congress 1. Strategies to improve outcomes 2015, Manchester Andrew Stuart in esophageal adenocarcinoma. Cowie Cowie A, Noble F, Underwood T. Expert Rev Anticancer Ther. 2014 Jun;14(6):677-87. doi: 10.1586/14737140.2014.895668. Epub 2014 Mar 2013
Oesophageal (gullet/food pipe) cancer is The major focus of cancer research anti-cancer therapies. We are currently the most rapidly rising cancer in Western over the past three decades has been working with the Southampton Clinical males and the UK has the highest cancer cells themselves. However, Trials Unit to design the first human trial incidence of any country in the world. cancer cells do not exist in isolation and of phosphodiesterase type 5 inhibitors for Despite advances in modern surgery and attention is being increasingly paid to the stromal targeting in oesophageal cancer. medicines we have failed to significantly tumour stroma; this is the ‘soil’ in which impact upon survival from this dreadful the cancer grows. The major cell type cancer with less than one in six people in the stroma is the cancer associated living for five years or more after fibroblast (CAF), a ‘normal’ cell type diagnosis. Research into new treatments that has been hijacked by the cancer for this disease is urgently needed. to support its own development. CAF play a vital role in cancer invasion and spread. A CAF-rich stroma is associated with poor survival in aggressive cancers. We have shown this to be the case in oesophageal cancer. No currently licensed medicines target the cancer stroma and we have been working on this in cancer of the oesophagus.
Our work has focused on using drugs from the ‘Viagra family’ Andrew discussing oesophageal cancer research with a patient (phosphodiesterase type 5 inhibitors) to target CAF. We have used complex 3D tissue culture techniques to study the potential of these drugs in changing the interaction between the cancer cells and Andrew collecting fresh tissue from a the stroma. We have shown that these resected oesophageal cancer drugs can reverse the support of CAF to cancer cells and increase sensitivity to
14 Activity monitoring: profiling patient performance
FELLOWSHIP/SPONSOR: Helen W Cui, Georgina S.J. Kirby, PRESENTATIONS: RCS Research Fellowship Karl Surmacz, John Griffiths, 1. ‘Working towards a personalised supported by the Sorab (Soli) Caroline Hargrove, Benjamin surgical pathway’, Oxford Jamshed Lam Legacy W Turney. Paper in submission Innovation Society Technology to British Journal of Anaesthesia Showcase, Said Business School, SUPERVISORS: Oxford, July 2016 Mr Benjamin Turney 2. Preoperative home activity monitoring: predicting patient 2. ‘How Fit is Your Patient? Using SITE OF WORK: risk for major elective surgery. Activity Monitoring to Assess the Churchill Hospital, Oxford Georgina S.J. Kirby, Helen W. Cui, Surgical Patient’ , World Congress of Endourology, ExCel Centre, PUBLICATIONS: Karl Surmacz, John Griffiths, London, October 2015 1. Can preoperative home Benjamin W. Turney, Caroline activity monitoring help Hargrove, Freddie C. Hamdy determine cardiorespiratory Paper in submission to the Annals fitness before major surgery? of Biomedical Engineering Helen Cui A study of the feasibility and utility of a wearable accelerometer in the preoperative setting.
The assessment and care of the we also need to be able to accurately surgical patient in the period before measure progress of recovery after the and after the operation is just as crucial patient leaves hospital. Research on this to ensuring a good outcome of surgery is currently centred around asking for for the patient as the operation itself. patient feedback in the form of Patient A key step in the preoperative period is Reported Outcomes questionnaires. to be able to accurately risk assess a We are building on this area of research patient so that adequate preparations by using a novel fitness assessment can be made to optimise patient tool, a small, wearable three-axis health and fitness before undergoing accelerometer, to monitor daily surgery. An assessment of the patient’s activity levels at home in comparison physical fitness, in terms of heart and to established methods of fitness lung function is a crucial part of this assessment. We have shown in process. Research in this area has our preliminary study of 50 patients investigated a range of methods, from wearing the activity monitor for three Hub for patient use to transmit live activity questionnaires asking the patient to days before and after surgery, that we data for processing and feedback report their activity levels, to the more can identify key measures of activity detailed cardiopulmonary exercise test level that reflect patient fitness both where maximum effort is demonstrated before and after surgery. The next on an exercise bike. With regards to step is to utilise activity monitoring the postoperative period, in order to in trying to improve patient fitness be able to provide information about before surgery so that they are better a patient’s likely recovery and function, prepared to undergo surgery. The aim is to personalise perioperative care for patients by using targeted intervention based on individual fitness assessment. Further research into continuous home activity monitoring will develop the ability to provide more accurate monitoring techniques and personalised feedback to benefit the care of the surgical patient.
Wearable activity monitor
Daily activity monitoring of surgical patients at home before their operation reveals new parameters that can be used to predict patient fitness with up to 83% accuracy compared to standard exercise testing. 15 Around 1000 patients a year need a colectomy for endoscopically-unresectable polyps. Colectomy causes complications in up to 40% of patients, when a local full-thickness resection would suffice.
Developing innovative risk-reducing surgery for colonic polyp excision
FELLOWSHIP/SPONSOR: 2. Currie A, Brigic A, PRIZES: Joint RCS/Dunhill Medical Blencowe NS, Potter S, Faiz 1. ACPGBI Poster Prize – Trust Fellowship OD, Kennedy RH, Blazeby JM. Digestive Disorders (2015) Systematic review of Federation international SUPERVISORS: surgical innovation reporting in meeting, London 2015 Professor Robin Kennedy and laparoendoscopic colonic polyp Mr Omar Faix 2. American College of Surgeons resection. British Journal of Poster of Exceptional Merit – SITE OF WORK: Surgery. 102: e108-16 American College of Surgeons St Mark’s Hospital, London PRESENTATIONS: Clinical Congress, Chicago 2015 PUBLICATIONS: 1.American College of Surgeons FURTHER FUNDING: 1. Currie A, Burling D, Mainta E, Clinical Congress, McCormick Pelican Cancer Foundation Ilangovan R, Moorghen M, Place West Convention Center, Lung P, Faiz OD & Kennedy Chicago, Illinois, USA. Andrew Currie RH (2016) An analysis of the October 2015 accuracy of CT colonography 2. Digestive Disorders Federation when defining anatomy for novel International Meeting, ExCel full thickness colonic excision Centre, London. June 2015 techniques in early colonic neoplasia. Colorectal Disease. Epub Feb 29 2016
Half of 70-year-olds have precancerous Recognising these risks, we have bowel polyps, which if left could cause developed a new full-thickness laparo- symptoms and shorten life. Bowel endoscopic excision of the colon (FLEX) cancer screening is diagnosing an procedure using a telescope and ‘key- increasing number of these benign, hole’ surgery (laparoscopy) to create a but precancerous large bowel (colon) folded disc of bowel containing the polyp. polyps that cannot be managed by If successful, FLEX could allow patients telescopic (endoscopy) means. to avoid the risk of major bowel resection.
New surgical approaches need to be measured and gradually introduced by necessity. The current work was developed in conjunction with the RCS Bristol Surgical Trials Unit. We undertook Andy undertaking a colonoscopy for a a prospective, protocol-based descriptive patient with polyps cohort in which all participating patients Importantly, through the award of received the FLEX procedure. The combined laparoscopic and endoscopic competitive national funding, we have views of the FLEX procedure in action We have now undertaken this procedure been able to register the study of FLEX on in ten patients with complex benign the National Institute for Health Research The standard surgery for these patients polyps that would otherwise need radical (NIHR) Clinical Research Portfolio which is removal of large sections of bowel surgery and in seven of these patients the will enhance recruitment. By leading a (segmental colectomy), resulting in lesion has been successfully removed national roll-out of the procedure, around complications in up to one third of with the FLEX technique – with the other 1000 patients per year will be spared the patients, some of which can be very three undergoing standard radical surgery risks of major surgery for benign polyps serious. Long-term problems, such as under the same anaesthetic. In all in the UK and achieve faster healing and increased bowel frequency and diarrhoea, these patients we were able to remove recovery. If we can adapt the technique although uncommon, can be disruptive to the polyp completely and successfully to treat early bowel cancer, around 4000 patients’ lives after colectomy. close the defect without post-operative more patients a year, with early bowel cancer, could benefit from FLEX. 16 surgical complications. Assessing damage control after inadvertent vessel injury in the subpial tumour resection trial using the NeuroTouch simulator
FELLOWSHIP/SPONSOR: FURTHER FUNDING: RCS Harry Morton Association of Surgeons in Travelling Fellowship Training (ASiT) Surgical Training and Research Grant 2015 and SUPERVISORS: University of Exeter Medical Dr Rolando Del Maestro School – Dean’s Individual Career SITE OF WORK: Development Fund 2015/16 Neurosurgical Simulation For the duration of the placement Research and Training Centre at the Montreal Neurological Institute, Canada
Praveena Deekonda
I received an RCS Harry Morton Travelling Fellowship to support a seven- week placement at the Neurosurgical Simulation Research and Training Centre at the Montreal Neurological Institute, Canada. The NSRTC, in conjunction with researchers at the National Research Council of Canada developed a virtual reality simulator, capable of simulating neurosurgical operations, including endovascular, spinal and cranial procedures. Deemed to be one of the best neurosurgical simulators currently available, NeuroVR uses stereovision Group picture of some of the lab members at the NSTRC this summer and a range of surgical tools capable of giving force and haptic feedback metrics to assess safe surgical technique comparing performance amongst groups to simulate a realistic environment for and the development of proficiency of participants based on their level of neurosurgical procedures. performance benchmarks. experience. I also worked on assessing the response to the damage and the The NSRTC recently completed their methods taken to cauterise the bleed subpial tumour resection trial, where and control the damage. medical students, senior and junior neurosurgical residents and consultant Virtual reality surgical simulation is still a neurosurgeons were recruited to developing field, and as a medical student undertake a tumour debulking task. this was an unparalleled opportunity As part of my placement I worked on for me. In addition to the placement, the data analysis of this study, and the I also got to learn about the rich history development of novel metrics to analyse of the Montreal Neurological Institute Practicing subpial tumour resection using performance during the scenario. In and explore the beautiful city of Montreal. the NeuroVR simulator particular I worked with an MSc student For more information on the NSTRC and on assessing the damage made to a The NSRTC developed a series NeuroVR, please visit neurosim.mcgill.ca of module scenarios and have run large vessel in the surgical field, and validation studies. Past work has involved measurement of bimanual psychomotor performance, development of novel
The goal of McGill’s Neurosimulation Research Centre is to enhance resident training and ultimately increase patient safety through virtual reality simulation. 17 One in every seven men will receive a diagnosis of prostate cancer. In common ‘localised’ forms, we still cannot predict who will benefit most from surgery, radiotherapy, or medical treatment.
DNA repair defects in prostate cancer: a pathway to personalised therapy
FELLOWSHIP/SPONSOR: 2. C. Z. Zhang et al, PRIZES: RCS Fulbright Scholar Award Chromothripsis from DNA 1. Royal Society of Medicine damage in micronuclei. Nature Urology short papers: first SUPERVISORS: 522, 179-184 2015 – Pellman prize 2015 Professor Dipanjan Chowdhury Lab (Harvard) 2. Lister Surgical Sciences, SITE OF WORK: PRESENTATIONS: Royal College of Surgeons Harvard Institute of Medicine, 1. Dev H. et al. (2014) Targeting of Edinburgh 2014 Dana Farber Cancer Institute, DNA repair pathways in prostate Harvard University, USA FURTHER FUNDING: cancer BAUS: Academic Meeting, Wellcome Trust Clinical PhD PUBLICATIONS: London, UK Fellowship, University of 1. D. H. Lee et al, 2. Dev H. et al. (2014) Paper: Cambridge for three years Dephosphorylation enables the Ataxia Telangiectasia Mutated recruitment of 53BP1 to double- (ATM) inhibition sensitises strand DNA breaks. Molecular cell Castrate Resistant Prostate Cancer Harveer S Dev 54, 512-525 (2014) – Chowdhury to Poly(ADP-ribose) polymerase 1 Lab (Harvard) (PARP1) inhibition Royal Society of Medicine: Surgery, London, UK
As we age we accumulate ‘mutations’ complex mutational landscapes seen in our DNA, and if enough critical in prostate cancer. If confirmed, this genes are affected these cells will activity may also reveal 53BP1-related grow uncontrollably and lead to cancer. tissue biomarkers as predictors of a response to PARP inhibitors. Researchers have now established the importance of mutations in the very Hence, understanding 53BP1 and genes involved in detecting and repairing BRCA1 dysfunction in prostate cancer DNA damage, such as BRCA1, which is enables molecular characterisation defective in many breast and prostate of a patient’s biopsy, in order to guide cancers. Cancers with BRCA1 mutations their optimal management. My aim are exquisitely sensitive to drugs (PARP is to continue to work within surgical inhibitors) that cause DNA damage and and scientific teams to establish require intact repair pathways to survive. personalised therapies in prostate By understanding all the critical factors cancer, and minimise treatment failure. involved in BRCA1-related DNA repair pathways, we will establish: (1) how Harveer with a colleague demonstrating the successful genetic manipulation of mutations in specific repair genes cause cancer cells widespread chromosomal-instability (CIN), a hallmark of cancer; and (2) function. Among these is a key whether gene mutations identified from mediator of DNA repair, 53BP1, which biopsies could predict the successful antagonises BRCA1. I am looking at how response to radiotherapy or specific the inappropriate activation of 53BP1 drugs, or their failure and hence need in cells leads to CIN. I have engineered for immediate radical surgery. cancer cell models in which we can Harveer Dev (left) with Professor Dipanjan precisely turn on 53BP1 thus mimicking I have spent a year working with leading Chowdhury (right) at Harvard Medical a potentially aberrant pathway underlying groups at the Dana-Farber Cancer School, where he conducted cutting-edge the development of prostate cancer. Institute and Harvard University to cancer research Using single-cell sequencing we predict establish factors that regulate BRCA1 that this mechanism will reproduce the
18 Telomere characteristics and genetic profile of high-grade soft tissue sarcomas
FELLOWSHIP/SPONSOR: PUBLICATIONS: Freemasons’ Fund for Surgical 1. Soft tissue sarcoma. Eastley N, Research with the support of the Green PN, Ashford RU. BMJ. 2016 Arthritis Research Trust Feb 24;352:i436 SUPERVISORS: 2. Extra-abdominal Desmoid Mr Robert Ashford Fibromatosis: A review of management, current guidance SITE OF WORK: and unanswered questions. The East Midlands Sarcoma N Eastley, T McCulloch, C Elser, Service & The University I Hennig, J Fairbairn, A Gronchi, of Leicester R Ashford. European Journal of Surgical Oncology, 10.1016/j. ejso.2016.02.012 Nicholas Eastley
Soft tissue sarcomas (STSs) can affect patients at almost every age, and carry a significant morbidity and mortality. Their relative rarity means they have often been neglected compared with other more common cancers in terms of academic research.
STS treatment generally involves surgery to remove the tumour and radiotherapy. Following treatment 50% of STSs return (recur). This either occurs at the same place as the original tumour (local recurrence) or at a different part of the body (metastatic recurrence), and in both cases is a difficult problem to manage. Local recurrence often requires additional surgery, whilst metastatic recurrence almost always proves incurable with a three-year survival of just 25%.
The ability of clinicians to offer curative surgery to patients that recur is dependent on early diagnosis. In cases of local recurrence earlier diagnosis also reduces the likelihood of an amputation being required. This is obviously beneficial to patients individually, and Nick supervising a junior surgeon removing a soft tissue tumour society in general. At present no reliable Data emerging from our research has Following validation by other groups in tests (biomarkers) exist to allow clinicians already identified ctDNA in STS patients larger, multi-centre trials, these results to diagnose recurrence. This is partly the for the first time, and may identify may provide clinical oncologists and cause of a lack of standardised follow up specific ctDNA characteristics that surgeons with novel tools to predict or in the UK, and the reason why local and may hold a role as future biomarkers diagnose STS recurrence earlier than distant recurrence is often extensive at of STS recurrence. current means. the time of diagnosis.
Over 70% of patients with advanced soft tissue sarcomas carry detectable tumour-derived circulating cell free DNA. 19 On average, every neurosurgical unit in the UK will receive at least one referral a day for a patient suffering from a Chronic Subdural Haematoma (CSDH).
How does dexamethasone alter the inflammatory response in chronic subdural haematoma?
FELLOWSHIP/SPONSOR: Subdural Haematoma (Dex-CSDH PRESENTATIONS: RCS Rosetrees Surgical trial) – a progress update. Abstract 1. Oral presentation of work Research Fellowship in: Proceedings of the 2016 Spring was presented at the SBNS Meeting of the Society of British (Society of British SUPERVISORS: Neurological Surgeons. British Neurological Surgeons) Professor P Hutchinson Journal of Neurosurgery, April conference, 20th April 2016, SITE OF WORK: 2016; 30(2): 130-186 Newcastle Academic Division of 2. Chari A, Hocking K, 2. A poster presentation at the Neurosurgery, Department of Edlmann E, Turner C, Santarius EANS (European Association Neurosurgery, Addenbrooke’s T, Hutchinson PJ, Kolias AG. of Neurological Surgeons) Hospital, Cambridge Core Outcomes and common data conference, 4th-8th September, Biomedical Campus elements in chronic subdural Athens, Greece haematoma (CODE-CSDH): PUBLICATIONS: PRIZES: A systematic review of the 1. Edlmann E. et al. Randomised, First place in poster literature focusing on baseline Ellie Edlmann double blind, placebo-controlled competition at the National and peri-operative care data trial of a 2-week course of Neurotrauma conference 2015 elements. J Neurotrauma. Dexamethasone for adult patients 2015 Nov 5. Epub ahead of print with a symptomatic Chronic
Chronic subdural haematoma (CSDH) is recover from their CSDH to understand a neurosurgical condition where layers of if dexamethasone treatment confers blood and fluid build up on the surface of a significant benefit. CSDH and its the brain. It typically affects people aged complications can be life-threatening, over 65 and is often initiated by minor and this risk is highest in patients head trauma. It has become apparent in requiring more than one operation. recent years that following this traumatic Therefore, introduction of a drug which injury, there is an abnormal inflammatory either prevents the need for surgery or reaction that causes a collection can be used in combination with surgery Ellie assessing CSDH images prior overlying the brain to grow over weeks, to prevent recurrences could have a to surgery resulting in compression of the brain. significant effect on patient survival Urgent surgery is often needed, and blood samples and testing them and long-term outcome. carrying risks, and even after surgery in the Neurochemistry laboratory. This the collection can return in up to 20% of is the first time such samples will be patients. There is a need to investigate tested for dexamethasone, which will why and how this inflammatory reaction increase understanding of how this drug occurs and how it can be targeted to penetrates spaces around the brain and develop new treatments for CSDH. which cells it targets. This information A drug, dexamethasone, has anti- will also be applicable to other brain inflammatory effects and I am currently conditions, such as brain tumours, helping to test it in CSDH patients in where dexamethasone is used. the Dex-CSDH trial. As part of my 152 patients have been recruited to the research on this drug I also want to Ellie reviewing a post-operative patient on Dex-CSDH trial, which will continue for the ward understand how it enters the spaces a further two years. I will be collecting around the brain and what inflammatory and analysing samples throughout the cells it targets in this condition. This trial and assessing how well patients involves collecting intra-operative fluid
20 An investigation into the formation of heterotopic ossification in amputees from recent military operations in Afghanistan
FELLOWSHIP/SPONSOR: PRESENTATIONS: PRIZES: Joint RCS/Military 1. Heterotopic ossification from 1. Philip Fulford Prize – Research Fellowship blast amputees is truly bone: Best Research Paper, quantitative and qualitative Combined Services SUPERVISORS: characterisation of its organic Orthopaedic Society, 2016 Colonel/Professor Jon Clasper and non-organic components. 2. Montefiore Memorial Medal, SITE OF WORK: D.S. Edwards, A Karunaratne, 2014. ‘Awarded annually to a The Royal British Legion Centre .A. Forsberg, T Davis, J.C. Clasper, surgeon in the RAMC who has for Blast Injury Studies A.M.J. Bull. BOA Congress by his/her surgical practice, (BORS Research Free Paper), research and application PUBLICATIONS: Liverpool, 2015 been considered to most have 1. What Is The Magnitude And 2. Risk stratification for distinguished him/herself in Long-Term Economic Cost Of Care heterotopic ossification in residual the subject of Military Surgery’ Of The British Military Afghanistan limbs of blast related military Amputee Cohort? Edwards DS, FURTHER FUNDING: amputations. D.S. Edwards, Major Dafydd Phillip RD, Bosanquet N, Bull AMJ, Drummond Committee, J.C. Clasper, A.M.J. Bull. Society Clasper JC. Clin Orthop Relat Res. Royal Army Medical Corps Edwards of Military Orthopaedic March 2015; DOI 10.1007/s11999- Charity, the Royal British Surgeons, Florida, 2015 and BOA 015-4250-9 Legion & the Royal Centre Congress (Trauma Free Papers), for Defence Medicine 2. Heterotopic Ossification In Liverpool, 2015 Victims Of The London 7/7 Bombings. Edwards DS, Clasper JC, Patel HD. Journal of the Royal Army Medical Corps. 2015 Feb 2. doi: 10.1136/jramc-2014-000370
The use of the Improvised Explosive Device and the resultant large cohort of multiple amputees defined the conflict in Afghanistan. Conditions not previously seen in common medical practise have subsequently surfaced. Heterotopic Ossification (HO) is one of those conditions. HO is the formation of bone at sites other than the skeletal system. This causes difficulty to the patient during Taff experimenting at the Diamond Light Source particle accelerator rehabilitation through pain, pressure and molecular level. Measured variables The research concludes that formation sores, and infections requiring surgery were evaluated to examine how HO of HO is systemically driven by the large to excise the problematic lesion, further behaves under mechanical stimulus injury burden and this can be predicted delaying recovery. when compared to normal bone. in injuries above a certain threshold. After the withdrawal of British troops from Imaging techniques used included Local factors, such as zone of injury Afghanistan it was possible to calculate Backscattered Electron Microscopy and subsequent amputation, direct us the entire amputee cohort and the HO and Synchrotron small-angle X-ray to the location where HO will form. scattering imaging. Information on the burden. This was in order to identify It is hoped that we can identify patients mineral density and the orientation of the risk factors for the formation of HO and at risk and manipulate the mechanical collagen molecules provides clues to its calculate the clinical consequence and drivers in the re-modelling of HO in order origin and metabolism both of which, it workload in managing these patients to prevent localised wound problems. The is hypothesised, can be manipulated to developing HO. research was performed in collaboration benefit the patient. The research is unique with the US Naval Medical Research Furthermore this research used novel and the first of its kind. bio-imaging techniques to analyse the Center, Silver Spring. appearance of HO at the microscopic
Over 60% of British Military amputees from the conflict in Afghanistan suffer from the formation of Heterotopic Ossification in their wounds. 21 There are over 600,000 new diagnoses of head and neck cancer every year worldwide yet the five-year survival has remained around 50% for over three decades.
Tensin regulation of tumour cell movement: a link between metabolism and motility
FELLOWSHIP/SPONSOR: PRESENTATIONS: PRIZES RCS Research Fellowship 1. CTEN (C-terminal Tensin-like) Winner of the Angell James regulates head and neck cancer Prize (Otolaryngological SUPERVISORS: invasion and survival; NCRI Research Society) Mr Dae Kim, Dr Jeremy Blaydes Cancer Conference 2015 October 2015 and Professor Gareth Thomas 2. The role of Tensin in head and Runner up of the Rosetrees SITE OF WORK: neck squamous cell carcinoma; Prize (RCS) December 2015 University of Southampton, Faculty of Head & Neck Research Academic Cancer Sciences Meeting, MD Anderson Cancer FURTHER FUNDING: Center, 2015 MRC Clinical Research Training Fellowship
Jason Charles Fleming
Head and neck cancer is the fifth Our early research into pathways affected most common cancer and the sixth by altered metabolism identified changes most common cause of cancer-related in a number of proteins important for cell mortality in the world. Existing treatments contacts and movement (focal adhesion often result in severe side effects adaptor proteins). These proteins including loss of swallowing or voice, are therefore important mediators of as well as cosmetic problems. New cancer cell invasion. Further functional treatment targets are therefore urgently experiments showed that through required. Cancer cells have a unique way manipulation of the relative amounts of of producing energy (metabolism) with these proteins, tumour cell metabolism high glucose uptake and we can visualise was able to influence cell behaviour, this with modern imaging techniques. including how aggressively it invaded However, it is becoming clear that rather surrounding tissue. than being simply a marker for detection, In order to demonstrate the clinical the way that tumour cells use glucose relevance of this new biological finding, may fundamentally affect their behaviour. we studied the presence of these proteins Our initial research indicated that head of interest in a large series of head and and neck cancer cells demonstrated neck cancer patients including long-term a unique metabolic signature, and that follow-up data. Interestingly, we were this profoundly affected the way the able to demonstrate that high levels of 3D synthetic tumour model helping us to cells moved and interacted with their these same proteins that were regulated study cancer invasion surrounding environment. We therefore by metabolism resulted in a reduction in proceeded to explore this relationship to patient survival. The significance of both further understand what factors affect these laboratory and clinical results offer the invasion and spread of cancer cells exciting possibilities for using metabolic around the body, which is ultimately markers as both new diagnostic and responsible for over 90% of tumour- treatment targets with the potential related deaths. to reduce side effects.
22 Lubrication approaches for articular cartilage regeneration (self-repair) and alleviation of osteoarthritis
FELLOWSHIP/SPONSOR: FURTHER FUNDING: Joint RCS/Daniel Turnberg UK/ Arthritis Research UK and Middle East Travel Fellowship The Leverhulme Trust, for an artist in residence. She has been SUPERVISORS: working on various aspects of Professor Jacob Klein osteoarthritis including our (Weizmann Institute of Science) research and the clinical condition & Professor Tonia Vincent – see images (University of Oxford) SITE OF WORK: Weizmann Institute of Science, Israel
Matthew David Gardiner
Osteoarthritis (OA) is the most common Synovial joints (e.g. hip, knee, finger Our longer-term plan is to investigate degenerative joint disease worldwide. joints) are very well-lubricated. Delivering whether these unique liposomes offer Patients with the condition suffer from improved lubrication to the diseased joint a potential treatment option for OA. The pain and disability. Unfortunately the may help overcome the increased shear fellowship has enabled application for treatment options are limited and there forces experienced by the cartilage cells further funding to support this project. are no drugs to treat the disease. Joint and promote repair. replacement surgery is often performed The Centre for OA Pathogenesis at the in severe cases. Kennedy Institute of Rheumatology is collaborating with Professor Jacob Klein (Weizmann Institute of Science) to investigate a new form of lubrication. The lubrication uses liposomes, which are small bubbles made of the same material as a cell membrane. The liposomes attract water molecules, creating a ‘hydration shell’. When under pressure and exposed to sideways force, Osteoarthritis of the base of thumb surfaces coated with the liposomes have A trapeziectomy (Images courtesy of very low friction. OA was once considered a passive Francesca Corra, Leverhulme Trust Artist disease of ‘wear and tear’, resulting To date the liposomes have been in Residence, Kennedy Institute of Rheumatology) from joint surfaces grinding against tested in the laboratory. My project is one another. Recent research shows to investigate their treatment potential that OA is due to mechanical sensing in a mouse model of OA. I worked of the cells within cartilage, causing with Ronit Goldberg at the Weizmann them to produce enzymes that start Institute to develop a method for tracking its breakdown. Abnormal sideways fluorescently labelled liposomes in forces (shear) appear to promote the the mouse knee joint. This provides release of degrading enzymes whereas information about how long they compressive forces might promote remain in the joint and whether they cartilage protection. are absorbed by the joint tissues.
In the UK, 1 in 5 adults aged 50–59 and up to almost 1 in every 2 adults aged 80+ have painful osteoarthritis in one or both knees. 23 Aspirin enhances the response to radiation treatment in colorectal cancer cells, causing a two-fold increase in cancer cell death.
A novel role for prostaglandins in promoting colorectal cancer stem cells
FELLOWSHIP/SPONSOR: PRESENTATIONS: PRIZES: RCS Research Fellowship 1. Aspirin enhances the response 1. The John of Arderne Medal to radiation in colorectal cancer and a travelling fellowship to SUPERVISORS: cells. Association of Surgeons the following year’s overseas Mr Michael Thomas and of Great Britain and Ireland, meeting, Royal Society of Professor Ann Williams Manchester, 2015 Medicine, 24 April 2015 SITE OF WORK: 2. Colorectal cancer and Aspirin: 2. RCS Rosetrees Essay Prize University of Bristol, School of can you teach an old drug Cellular and Molecular Medicine new tricks? Royal Society of FURTHER FUNDING: Medicine Coloproctology Section, The David Telling Charitable Cambridge, 2015 Trust Research Grant and the Above and Beyond Charitable Trust Research Grant for one year Katherine Jane Gash
Each year in the UK around 40,000 My research is focused on developing To translate this clinically I am currently people are diagnosed with colorectal ways of sensitising colorectal cancer stem running an NIHR portfolio adopted study cancer. Regrettably, some patients are cells to chemo-radiotherapy; rendering at six NHS sites, (ASPIRE: ASPirin & resistant to current therapies and many them less able to survive, and thus unable Irradiation in REctal cancer), analysing develop recurrent disease or metastases, proliferate and drive tumour growth. tumour tissue from patients with rectal culminating in an overall five-year survival cancer and investigating the impact Most colorectal cancers have elevated rate of only 55%. This highlights the of taking aspirin or NSAIDs during levels of prostaglandin, which enhances urgent need to improve the efficacy of chemo-radiotherapy on tumour response. the activity of two pathways (LGR5 and current treatment modalities. BCL-3), which promote colorectal cancer This exciting work may further justify stem cell function and survival. NSAIDS the use of aspirin as a novel treatment (such as aspirin) work by reducing adjunct in colorectal cancer and has huge prostaglandin levels. potential to improve treatment response, having an immeasurable positive impact Through a series of laboratory on both cancer patients and their families. experiments with colorectal cancer cells, I have demonstrated that treatment with Katherine and supervisor Mr Mike Thomas Aspirin reduces activity in these pathways looking at a rectal cancer endoscopically (LGR5 and BCL-3), and reduces cancer cell survival. Fundamental to this are cells within colorectal cancers, known as cancer By replicating the radiotherapy that stem cells, which trigger cancer cells to patients receive, using a laboratory multiply and subsequently fuel tumour irradiator, I have shown that when growth; leading to recurrence or metastatic colorectal cancer cells are treated disease. Chemo-radiotherapy works by with aspirin prior to radiation, there is targeting cells that it ‘sees’ as living, but a two-fold increase in cell death. This the cancer stem cells are able to become is compelling evidence supporting the dormant and evade treatment. notion that aspirin has an efficacious Katherine and a patient who has recovered role in colorectal cancer treatment. from colorectal cancer discussing the treatment he has undergone
24 Outcomes of Rectal Cancer Management – Analysis of the US National Cancer Database
FELLOWSHIP/SPONSOR: PUBLICATIONS: PRESENTATIONS: 2. K Gash, RP Kiran. RCS Fulbright Scholar Award 1. K Gash, RP Kiran. Factors 1. K Gash, K. Suradkar, Formation of Kock Pouch associated with response to RP Kiran. Outcomes of Rectal (Continent Ileostomy). SUPERVISORS: neo-adjuvant radiotherapy in Trauma Injuries: the USA Association of Coloproctology Professor R.P. Kiran patients with rectal cancer National Trauma Data Bank. of Great Britain and Ireland, SITE OF WORK: 2. K Gash, K. Suradkar, Association of Coloproctology Edinburgh, July 2016 Columbia University Medical RP Kiran. Rectal trauma of Great Britain and Ireland, Center/New York Presbyterian injuries: outcomes from the U.S. Edinburgh, July 2016 Hospital, New York, USA National Trauma Data Bank
The Fulbright/RCS Scholarship enabled Regrettably, colorectal cancer is the In addition, I analysed data from the me to embark on a six-month period of second most common cause of cancer National Trauma Data Bank investigating research at Columbia University Medical death in the UK and 34% of all colorectal outcomes from rectal trauma and Center, New York. This afforded me cancers arise in the rectum. Patients with created videos of innovative surgical the fantastic opportunity to carry out a advanced rectal tumours often receive techniques, including construction of series of epidemiological studies using pre-operative (neo-adjuvant) chemo- Kock Pouches and colonoscopy tips the largest cancer database in the world, radiotherapy, which has been widely and tricks. working in an outstanding department, demonstrated to improve oncological Receiving the Fulbright/RCS scholarship with forward-thinking, innovative outcomes. However, there is significant has significantly enhanced my research academic surgeons. We utilised the US disparity in how well tumours respond training and established an ongoing National Cancer Database (NCDB) to (Tumour Regression Grade), with some international collaboration. It also address some of the most important demonstrating complete regression enabled me to complete a Value-Based clinical questions regarding the optimum (which is associated with better survival Healthcare Course at Harvard University, treatment for patients with rectal cancer. rates), while others exhibit no response. participate in a Fulbright Seminar in San The reasons for such varied regression Diego and volunteer on the medical team are poorly understood. at the largest marathon in the world. Further, tumours that respond well can potentially be removed via ‘local excision’ i.e. trans-anally, thus avoiding much of the morbidity associated with radical surgery. However, it is essential that local excision does not subsequently compromise oncological outcomes.
Therefore, we identified:
1. Factors predictive of complete response to neo-adjuvant radiotherapy.
2. Adequacy of local excision vs. surgery according to Tumour Promoting patient and public involvement – Regression Grade and T-stage, ‘the walk through colon’ at bowel after neo-adjuvant radiotherapy. cancer awareness day at New York Presbyterian Hospital 3. Impact on Tumour Regression Grade and patient outcomes, including local excision rates, according to the modality of neo-adjuvant therapy administered. Katherine outside New York Presbyterian Hospital/Columbia University Medical Center
Each year in the UK 16,000 people die from colorectal cancer.
25 Each year worldwide thousands of surgical operations are required to restore nasal defects caused by cancer, trauma, burns and congenital deformities.
Development of a nasal hybrid construct using nanocomposite material and stem cells
FELLOWSHIP/SPONSOR: 2. Griffin M, Kalaskar DM, PRIZES: Freemasons’ Fund for Butler PE, Seifalian AM. The use 1. UCL Berkeley Fellowship, Surgical Research of adipose stem cells in cranial 1st October 2014 facial surgery. Stem Cell Rev. SUPERVISORS: 2. RCS Rosetrees Essay Prize, 2014;10:671-85 Professors Alexander Seifalian and 23rd March 2015 Peter Butler PRESENTATIONS: FURTHER FUNDING: 1. Characterisation of the SITE OF WORK: Medical Research Council, Biomechanical Properties Centre for Nanotechnology & Action Medical Research of Human Nasal Cartilage – Regenerative Medicine, UCL and Royal Free Charity for ESPRAS 2014 two years PUBLICATIONS: 2. Facial Implants Using 1. Griffin MF, Butler PE, Nanocomposite Polymer – Seifalian AM, Kalaskar DM ESPRAS 2014 Control of stem cell fate by Michelle Griffin engineering their micro and nanoenvironment. World J Stem Cells. 2015;7:37-50
The devastating facial disfigurement The main risk of placing nasal implants that results causes huge psychological beneath the skin for patients requiring and physical difficulties for patients. nasal reconstruction is the failure of the The significant impact on patient’s implant to integrate with the surrounding self-esteem affects their social life, tissue and cause infection. I discovered interpersonal relationships and their that adding adipose-derived stem cells ability to work. Current surgical to my nasal implants could overcome treatment involves harvesting tissue these complications and provide better from elsewhere in the body and using outcomes for patients. this material to carve a new nose. These Due to the successful nasal implant techniques cause pain, can fail and are prototypes I created during my fellowship associated with many surgical risks. I was able to secure further funding to Artificial materials are available as an A desktop 3D printer built during the take the POSS-PCU nose implants to alternative but they result in high levels RCS fellowship clinical trial. of infection, have an unnatural look My first task was to modify the POSS- and feel and thus are not acceptable PCU material so it had similar properties alternatives. With current surgical to natural nose cartilage to minimise techniques failing to repair nasal defects, failure and infection risks. I changed there is an urgent need to find an the structure, mechanical and surface alternative synthetic material. properties to mimic natural nose cartilage. I then developed a desktop 3D Our research team develops human printer that could produce POSS-PCU organs using a unique man-made implants that are personalised for each material, polyhedral oligomeric patient undergoing nasal reconstruction. silsesquioxane-poly(carbonate-urea) This means I can take a pre-operative urethane (POSS-PCU). We have already CT scan of a patient and design the A 3D printer used to optimise the utilised POSS-PCU to replace patient’s nose specifically for each patient using POSS-PCU nasal implant prototypes organs that have failed, including the POSS-PCU, resulting in fewer world’s first synthetic windpipe, tear postoperative complications and duct and lower leg artery. My fellowship better aesthetic outcomes. aimed to develop POSS-PCU into a material that restores nasal defects.
26 Engineered scaffolds for preservation of gliding tissue interfaces
FELLOWSHIP/SPONSOR: 2. Free Radical Polymerization PRIZES: Blond McIndoe for the Controlled and Facile 1. Best oral presentation at Research Fellowship Production of a Cell Repellent Future Investigators of and Antifouling Surface in 2 - Regenerative Medicine, Spain, SUPERVISORS: and 3D Systems, RH Harrison, September 2014, ‘Engineering Professor Molly Stevens R Chapman, AJ Gormley, Gliding Surfaces; Focusing of SITE OF WORK: LW Chow, JAM Steele, M Mahat, the Human Hand’, RH Harrison, Imperial College London L Podhorska, SP Hettiaratchy, R Chapman, AJ Gormley, IE Dunlop, MM Stevens. Tissue SP Hettiaratchy, IE Dunlop, PUBLICATIONS: Engineering: Part A (Volume 21, MM Stevens 1. Modular and Versatile Spatial Issue S1 pS-307) 2015 2. BAPRAS Travelling Bursary Functionalization of Tissue for Presentation Overseas Engineering Scaffolds through PRESENTATIONS: (February 2016) for presentation Fiber-Initiated Controlled Radical 1. Tissue Engineering and at TERMIS World Congress, Polymerisation, RH Harrison, Regenerative Medicine Boston, USA, September 2015 Rachael Helen JAM Steele, R Chapman, International Symposium World Harrison AJ Gormley, LW Chow, MM congress (TERMIS-WC), Boston FURTHER FUNDING: Mahat, L Podhorska, RG Palgrave, USA, September 2015. Future Imperial College Bursary Scheme, DJ Payne, SP Hettiaratchy, Investigators of Regenerative funded by the Engineering and IE Dunlop, MM Stevens. Advanced Medicine, Girona Spain, Physical Sciences Research Functional Materials (Volume 25, September 2014 Council (EPSRC) for two years Issue 36 p5748-5757) 2015
Tendons are tissues that connect muscles Taking into account the high functional extremely versatile and different aspects to bones: when a muscle contracts, demand of the hand, this project has of the design can be simply modified this pulls on the associated tendon and designed and produced a scaffold for different applications. We hope this results in bone and joint motion. Tendon with a non-stick surface (resistant to will allow easy adaption to applications continuity and a smooth gliding surface cell and protein attachment) and an beyond the hand. are therefore essential for movement. opposing cell-sticky surface (to promote cell attachment). In the hand, tendons run close to the skin and are commonly cut as a result The bulk of the scaffold is made using of injury. When cut, the tendon ends a process called electrospinning. This spring apart leaving a surgical repair produces a flat sheet of very fine fibres essential to restore function. However, that is made of two different dissolving these repairs often result in patients being materials; one on each surface. One left with reduced hand function due to surface has cell-sticky peptides within scar tissue compromising the tendon’s the material, promoting cell attachment. gliding surface. Through this fellowship The opposing surface has a reactive I have designed a bilayer scaffold to offer group from which a non-stick surface protection from this scarring to reduce can be grown using a specialist chemical the impact such injuries can have. reaction. This prevents cell and protein attachment to that region of the scaffold.
This scaffold could be used to improve outcomes for patients with tendon injuries, as the non-stick surface will prevent scar tissue tethering the tendon’s gliding surface. The opposing Rachael discussing current post-operative cell-sticky surface may support tendon management of tendon repair patients with healing; together improving outcomes a senior hand therapist for patients. The design of the scaffold is Rachael undertaking the plastic’s trauma list with a consultant hand surgeon, where patients with injured tendons are typically operated on In excess of 30 million tendon injuries occur globally each year; essential surgical repair is often complicated with scarring to the tendon surface resulting in reduced hand function. 27 Production of functional engineered tissue is currently 100% limited by the lack of adequate vascularisation.
Angiogenesis into tissue engineered decellularised scaffolds
FELLOWSHIP/SPONSOR: PRESENTATIONS: RCS Research Fellowship Is hypoxic cells the key to supported by the Rosetrees Trust angiogenesis of tissue engineered constructs in regenerative SUPERVISORS: medicine research? Ho, Jasmine; Professor Martin Birchall Stamati, Katerina; Birchall, SITE OF WORK: Martin; Cheema, Umber. UCL Stanmore, London BAPRAS/RBSPS Summer Scientific Meeting, Bruges, June 2015 FURTHER FUNDING: From MRC for 3 years
Jasmine Onn Yee Ho
One of the major obstacles for growing new artificial organs is the provision of blood supply to the vital cells during the period of initial implantation into a patient. Without adequate blood supply, implant with cells would fail in the body. Hence, the aim of my research is to increase the understanding of how we can improve new blood vessel growth during the crucial time of integration of implanted tissue-engineered constructs by evaluating the ability of these constructs to promote blood vessel growth and identified ways to potentiate this process via the use of cells.
Through my research, I demonstrated that a tissue engineered trachea scaffold had retained the amount of matrix proteins which allowed for the support of Holding a tissue engineered trachea with UCL collaborators Umber Cheema and Katerina new blood vessel growth (angiogenesis). Stamati working on tissue engineered scaffolds using bioreactors This was confirmed when the scaffold was implanted into a chick embryo in the field of regenerative medicine, research, with conceivable benefit model. The addition of cells such as as the processing of cells using such of translation and integrating such human bone marrow-derived stem cells techniques to promote blood vessel techniques into a clinical setting in helped promote new vessel formation in growth is still relatively new. In addition, the future. collagen scaffolds. Building on published I carried out a pilot study using novel The long-term implication from this literature, my research confirmed that photoacoustic imaging technique on research will help the development of next placing these cells in a state of low our tissue-engineered scaffolds in a generation tissue engineered constructs oxygen tension helped enhance the mouse model which showed promising which would vastly benefit from the process of angiogenesis by an increased preliminary data. This modality of outcome from this ongoing research. release of necessary growth factors monitoring blood vessel growth has from the cells. This has significance huge implications to this field of
28 Towards bioengineering personalised facial bone implants for the treatment of congenital midface defects in children
FELLOWSHIP/SPONSOR: Bulstrode NW, Britto JA, PRESENTATIONS: Blond McIndoe Dunaway D, Hammond P, 1. Relating Bone Structure Research Fellowship Ferretti P. Original research To Surgical Outcomes In article. Journal of Cranio- Sagittal Craniosynostosis. SUPERVISORS: Maxillofacial Surgery. In press Rodriguez-Florez N, Ibrahim A, Professor Patrizia Ferretti, Jeelani NUO, Ferretti P, Mr Neil Bulstrode and 2. Adipose regeneration Dunaway D. 27th EURAPS Professor Peter Hammond and implications for breast reconstruction: update and Annual Meeting. Bruxelles. SITE OF WORK: the future. Combellack EJ, 26-28th May 2016 UCL Great Ormond Street Jessop ZM, Naderi N, Griffin M, 2. Towards Bioengineering Institute of Child Health Dobbs T, Ibrahim A, Evans S, Personalised Facial Bone Burnell S, Doak SH, Whitaker IS. Implants. Ibrahim A, Suttie M, PUBLICATIONS: Gland Surg. 2016 Apr 5. Review. Bulstrode NW, Britto JA, 1. Combined soft and skeletal PMID: 27047789 Dunaway D, Hammond P, tissue modeling of normal and Ferretti P. 28th Head Group Amel Ibrahim dysmorphic midface postnatal Meeting. Jan 2016. London development. Ibrahim A, Suttie M,
This project aims to alleviate the suffering Previous studies have attempted to model and pain caused by facial deformities the face although these have usually by providing a more accurate and less been in adults or used less sophisticated invasive treatment alternative to current approaches. This is the first model of the surgical reconstruction options. soft tissues and the bone in unaffected children as well as those with Treacher Routine CT scans were used to build Collins Syndrome and Hemifacial a model of the midface in children Microsomia. Furthermore, the work on with and without deformities. Stem bone tissue engineering using fat derived cells derived from fat were compared stem cells utilises a novel scaffold and alongside other types of stem cells (from shows survival in mouse studies that bone) to assess their ability to engineer has not been published before. The next Before treatment bone on a biodegradable scaffold. This stage would be further optimisation of scaffold was further optimised to improve the tissue engineering and modelling blood supply and cell growth. Tissue protocols in order to generate full- engineered bone samples were tested sized pre-shaped facial bones that can for safety and survival by implanting in eventually be evaluated in clinical trials. mice for three months. Children born with midface deformities This work led to the generation of a model currently need surgery to restore function that accurately described the difference and harmony to the face. These surgeries between children with and without are often invasive and require multiple deformities and highlighted the limitations operations to refine the outcome as the of current reconstructive options. The child grows. This research combines model was used to 3D-print a mould of facial computer modelling technology and a facial bone demonstrating that this can After treatment tissue engineering techniques to lay the be used to pre-shape tissue engineered Children born with Treacher Collins foundations for generating facial bones implants. This work has also shown that syndrome have malformed or absent facial personalised to the child’s needs. This fat-derived stem cells can be grown on bones which in the case of the child above has the potential to provide a lifelong a biodegradable scaffold and induced to can lead to visual loss if untreated. Current minimally invasive custom-shaped tissue engineer bone which is capable of treatment options are invasive and involve bone implant that grows with the child. survival and establishing its own blood multiple surgeries throughout childhood Ultimately this would reduce the need for supply when implanted in a mouse. invasive and multiple surgeries enabling normal play, school and life beyond.
1 in 1000 babies is born with a head or face deformity, which can lead to visual, speech, feeding, hearing or emotional problems and require multiple invasive surgeries to correct. 29 Ear deformities through trauma (including burns and animal bites) and skin cancer affect more than 1 in 500 people.
Design, biofabrication and characterisation of a new class of durable auricular implants
FELLOWSHIP/SPONSOR: 2. Jessop ZM, Al-Himdani S, implications in cartilage The Dr Shapurji H Modi Memorial Whitaker IS. Translating Tissue tissue engineering. British Research Fellowship Engineering from Bench to Association of Plastic and Bedside - Producing “Off the Reconstructive Surgeons SUPERVISORS: Shelf” Reconstructive Solutions. (BAPRAS) Summer Meeting, Professors Charles Archer, Frontiers in Surgery 25-27th June 2015, Bruges Iain S Whitaker & Cathy Thornton PRESENTATIONS: PRIZES: SITE OF WORK: 1. Jessop ZM, Javed M, Morgan S, 1. RCS Norman Capener Reconstructive Surgery & Zhang Y, Combellack EJ, Travelling Fellowship Regenerative Medicine Research Khan I, Whitaker IS. A novel Group Institute of Life Sciences, 2. GDST Emerging Talent in isolation protocol for auricular Swansea University & The Welsh Technology Award cartilage derived stem cells Centre for Burns & Plastic Surgery 3. Cutlers’ Surgical Prize (CDSCs) and implications in for Innovation PUBLICATIONS: cartilage tissue engineering. Zita M Jessop 1. Jessop ZM, Javed M, Otto IA, European Association of Plastic FURTHER FUNDING: Morgan SR, Breugem CC, Surgeons (EURAPS), 28-30th May Medical Research Council Archer CW, Khan IM, Kon M, 2015, Edinburgh Clinical Research Training Whitaker IS. Regenerative 2. Jessop ZM, Javed M, Morgan Fellowship for three years Medicine in combination with S, Zhang Y, Combellack EJ, Khan 3D Printing: A paradigm shift in I, Whitaker IS. A novel isolation reconstructive surgery. Stem cell protocol for auricular cartilage research & therapy derived stem cells (CDSCs) and
Loss of part, or all, of the ear following The next steps will be to optimise trauma or surgery produces disfiguring the growth of these cells to produce defects which often have a profound larger three-dimensional pieces of effect on quality of life and associated cartilage that can be used in patients. psychosocial problems. Patient’s If successful, this research has wide undergoing ear reconstruction require implications in improving the outcomes long-term, stable repair. The current of facial reconstruction following cancer, gold standard is to perform surgery by trauma or degenerative conditions. using the patient’s own rib cartilage to reconstruct these defects. Donor cartilage however is limited in supply, tends to get reabsorbed over time and its harvest is associated with complications Zita performing ear reconstructive surgery including pain, lung damage, chest with supervisor, Professor Iain Whitaker contour deformity and scarring. Synthetic Our aim is to use the patients’ own ear materials have been shown to pose the cartilage stem cells in order to tissue Hosting international collaborators at the risk of infection, extrusion and foreign engineer durable cartilage for ear Welsh Centre for Burns and Plastic Surgery body reaction. reconstruction. We have so far been able The current generation of tissue to isolate these ear cartilage stem cells engineered cartilage, using unrelated from a tiny sample of the patient’s own cells and materials, tends to be fragile cartilage and grow them in the lab to and easily breakable. Once implanted produce millions of cells. These cells have into animals or humans it tends to the ability to produce cartilage pellets and undergo shrinkage and collapse, react to tissue-specific developmental resulting in sub-optimal reconstruction. cues in order to regulate normal ear growth over the lifetime of the patient.
30 Fellowship in healthcare management
FELLOWSHIP/SPONSOR: PUBLICATIONS: PRESENTATIONS: RCS/McKinsey Fellowship in Kirkman MA, ‘Developing 1. Leadership and Management. Healthcare Management management skills as a surgical Invited Oral Presentation. trainee’, Bulletin of The Royal International Surgical Training SUPERVISORS: College of Surgeons of England Programme Annual Symposium, Martyn Coomer (RCS) and John 2016; 98(8):364-7. DOI: 10.1308/ Royal College of Surgeons of Drew (McKinsey) rcsbull.2016.14 England, London, 2016 SITE OF WORK: 2. Healthcare Management. McKinsey & Company, London Invited Oral Presentation. Third National NHS Leadership Meeting, Clinical Leadership
Forum, Hammersmith Hospital, London, 2016 Matthew Kirkman
I stepped out of neurosurgical training for 12 months to complete the Healthcare Management Fellowship, based at the management consultancy McKinsey and Company.
My first project involved a comprehensive review of a large teaching hospital’s entire operations to understand why they had not achieved the 4 hour A&E target once in the prior 18 months. I was able to subsequently lead in the implementation of several quality improvement initiatives there, contributing to improved performance. In another project, I was able to develop materials for a leadership and development One of the regular Knowledge Breakfasts arranged by McKinsey’s Healthcare Practice. programme for a large Clinical These meetings are frequented by, and offer the opportunity to network with, internal and Commissioning Group. A particular external experts on various topics relevant to improving healthcare highlight of the Fellowship was being able on a set of professional standards to to contribute to the financial turnaround ensure timely review of A&E patients of a large acute NHS Trust that I had by the medical and surgical specialties. worked at myself several years ago. This was something that had not In every project I completed, my clinical been possible for a long time before and surgical experience was greatly McKinsey’s involvement. respected by both my colleagues at My experience was both enjoyable and McKinsey and also the healthcare educational, and I learnt much more organisations we assisted. It genuinely about the high-level political and financial felt like I was making a positive impact on construct of the NHS than was possible Matthew with the Organising Committee the NHS, although sometimes the routes as a surgical trainee. The networking and co-speakers at the Third National NHS to success were less tangible than others; opportunities were also unparalleled. Leadership Meeting in the hospital struggling to meet the Going forward, I hope to use the skills and four-hour A&E target, I facilitated a board knowledge acquired from the fellowship meeting where clinical directors from to continue improving performance and A&E, medicine and surgery sat down quality in the NHS. together for the first time and agreed
An exciting and unique opportunity to step out of surgical training and improve healthcare from a different perspective. 31 Despite recent improvements in treatments for rectal cancer, 20-30% of patients undergoing surgery for rectal cancer are still left with a permanent stoma.
Determinants of sphincter preservation in low rectal surgery for cancer
FELLOWSHIP/SPONSOR: Joint RCS/David Johnston Research Fellowship SUPERVISORS: Mr Mohamed Thaha SITE OF WORK: National Centre for Bowel Research & Surgical Innovation, Barts and The London School of Medicine & Dentistry, Queen Mary University London
Kathryn Lynes
Rectal cancer is common, with over The operation that most patients undergo An appreciation of the impact of these 14,000 people diagnosed each year for rectal cancer is an anterior resection. problems on post-operative quality in the UK. Restoration of gastro- Unfortunately this surgery frequently of life will encourage a more careful intestinal continuity, with preservation leads to disrupted bowel function, with assessment of functional outcomes of sphincters and avoidance of a patients suffering from incontinence, during cancer follow-up, allowing permanent colostomy, remains a priority urgency and unpredictability, a problem identification of patients who may benefit in rectal resection. However, sphincter known as ‘low anterior resection from treatment. A further research project preservation is currently not achieved syndrome’ (LARS). These problems are is aiming to identify biomarkers that in a large proportion of cancer patients believed to be fairly common following can help to stratify use of pre-operative (especially those with distal rectal surgery but follow-up appointments have radiotherapy, which is known to affect tumours) due to a variety of reasons. traditionally concentrated on ensuring bowel function. Future work will focus These include concerns about cancer that the cancer has not returned and on prospective determination of the risk recurrence and post-operative function. have not reviewed functional outcomes factors for poor post-operative function. in sufficient detail. Because of this we are unsure exactly how common the problems described are.
We have carried out an epidemiological study including >1000 patients who have undergone surgery for rectal cancer, allowing us to determine how many patients have ongoing bowel symptoms. In these survivors, who are all more than one year post surgery, over 40% of patients suffer from major LARS, Kate at The Blizard Institute and a further 22% from minor LARS. Kate analysing ultrasound and manometry Ongoing analysis of the results will focus data in the GI Physiology lab on determining the effect that these problems have on cancer survivors’ quality of life.
32 Computational analysis of HLA alloantibody binding and HLA immunogenicity
FELLOWSHIP/SPONSOR: 2. Mallon DH, Bradley JA, 2. British Society for RCS Research Fellowship Taylor CJ, and Kosmoliaptsis Histocompatibility and supported by the Rosetrees Trust V. Structural and electrostatic Immunogenetics Annual analysis of HLA B-cell epitopes: Conference 2015, Cambridge. SUPERVISORS: inference on immunogenicity HLA immunogenicity can be Vasilis Kosmoliaptsis and prediction of humoral predicted by quantification SITE OF WORK: alloresponses. Current Opinion of structural and surface Addenbrooke’s Hospital, in Organ Transplantation. 2014 electrostatic potential Cambridge 19:420-427 differences between donor and recipient HLA molecules PUBLICATIONS: PRESENTATIONS: 1. Mallon DH, Winn PJ, 1. World Transplant Society PRIZES: Bradley JA, Taylor CJ, and Congress, July 2014, San 1. The Kevin Burnand Prize for Kosmoliaptsis V. Three- Francisco. Tertiary Structure Translational Science, Society dimensional structural modelling and Electrostatic Potential of Academic & Research Dermot Mallon and calculation of electrostatic of HLA B-cell Epitopes Reveal Surgery (SARS) conference, potentials of HLA Bw4 and the Molecular Basis for January 2016 Bw6 epitopes to explain the Alloantibody Binding and 2. Shortlisted for Scientist of molecular basis for alloantibody Epitope Immunogenicity the Year from British Society binding: towards predicting HLA for Histocompatibility and antigenicity and immunogenicity. Immunogenetics (BSHI) Transplantation. 2015 27;99(2) conference, September 2015
Renal transplantation prolongs and The principal aim of my research is I anticipate that my research will inform improves quality of life of patients to improve the existing method for deceased-donor allocation policy in the with chronic end-stage renal failure. determining tissue compatibility in near future and help improve long-term Approximately 3,200 kidney transplants kidney transplantation. Our previous outcome and access to transplantation for are performed each year in the UK but studies have shown that the degree patients undergoing renal transplantation, despite efforts to increase the availability of donor and recipient matching can both nationally and internationally. of donor organs, the size of the kidney be assessed based on structural and transplant waiting list has remained physicochemical differences between largely unchanged. Although early results their histocompatibility proteins. I have after transplantation are excellent, long- used advanced computational molecular term outcomes have remained static and modelling techniques, assisted by over 30% of kidney transplants fail within laboratory analysis of protein structure, ten years. This is due to a process called to assess donor-recipient compatibility. ‘chronic rejection’ which occurs mainly This work led to the description of a novel due to development of antibodies against computerised matching algorithm which the donor organ. The risk of antibody- was then used to predict alloantibody mediated rejection can be offset by responses and long-term graft outcome ensuring donor kidneys are allocated to following transplantation in a national recipients with a good tissue-match but cohort of kidney transplant recipients current methods for determining tissue in collaboration with NHS Blood and Antibody hla interaction figure compatibility are inadequate. Another Transplant. My approach was shown to implication of tissue incompatibility and have significant advantages compared to donor-specific antibody development is the current histocompatibility strategy. that they compromise access to future re-transplantation should the first kidney transplant fail.
One third of all kidney transplants fail after ten years due to chronic rejection.
33 Approximately 1.5 million metal-on-metal hip replacement patients are at risk of developing abnormal reactions to metal however, current patient follow-up recommendations are not evidence-based or cost-effective.
Optimal follow-up of patients with metal-on-metal hip replacements
FELLOWSHIP/SPONSOR: 2. Matharu GS, Pandit HG, Murray PRIZES: Joint RCS/Arthritis Research DW, Treacy RBC. The future role 1. Naughton Dunn Club Meeting Trust Fellowship of metal-on-metal hip resurfacing. Podium Presentation Prize (1st International Orthopaedics 2015 place), Birmingham, June 2015 SUPERVISORS: Professor David Murray PRESENTATIONS: 2. The London Hip Meeting & Associate Professor 1. What are the optimal blood Registrar Poster Prize Hemant Pandit metal ion thresholds for (3rd place), London, April 2015 identifying patients with failed SITE OF WORK: FURTHER FUNDING: metal-on-metal hip replacements? Oxford Orthopaedic Arthritis Research UK Matharu GS, Berryman F, Engineering Centre (OOEC), for 18 months Clinical Brash L, Pynsent PB, Treacy RB, Nuffield Department of Research Fellowship Dunlop DJ. European Federation Orthopaedics, Rheumatology of National Associations of and Musculoskeletal Sciences Orthopaedics and Traumatology (NDORMS), University of Oxford Gulraj Singh (EFORT) 16th Annual Congress, Matharu PUBLICATIONS: Prague, Czech Republic. May 2015 1. Matharu GS, Berryman F, 2. Follow-up of metal-on-metal Brash L, Pynsent PB, Treacy RB, hip replacement patients is Dunlop DJ. Predicting high currently not evidence based blood metal ion concentrations or cost effective. Matharu GS, following hip resurfacing. Hip Mellon SJ, Murray DW, Pandit International 2015 HG. British Hip Society Annual Meeting, London. March 2015
Approximately 1.5 million patients follow-up did not reflect the best in the UK alone could save at least worldwide have metal-on-metal hip available evidence, nor was it £13,600,000 over five years. replacements for arthritis. Unfortunately financially sustainable. This research proposes an evidence- many have failed earlier than expected A study assessing optimal blood metal based approach for the follow-up of due to abnormal reactions to metal. ion cut-offs for identifying abnormal metal-on-metal hip replacement patients, These reactions can be painful and reactions to metal in 598 patients which will hopefully improve the clinical often require further operations. Little is observed that the specific cut-off values and cost-effectiveness of the care known about outcomes following further varied according to implant design. delivered to the many patients with operations; however, observations These implant specific cut-offs were these implants. suggest most patients do poorly. more effective than currently proposed To identify abnormal reactions to metal fixed cut-off values. earlier, worldwide authorities have In 40 metal-on-metal hip patients published follow-up recommendations requiring further surgery for problematic for patients. These recommend annual hips it was demonstrated that the review for most patients with blood most effective imaging techniques for tests for metal ion levels and hip scans. identifying abnormal reactions to metal However, it remains unclear if this is the was a combination of ultrasound and best way to follow up patients. Many magnetic resonance imaging. of these tests may be unnecessary. This research aimed to identify how After repeating ultrasound scans in 152 best to follow up metal-on-metal hip patients with pain-free metal-on-metal replacement patients. hips it was concluded that one in three Discussing the design of a metal-on-metal patients did not require any follow-up for A critical review of current metal-on- hip resurfacing with a colleague at least five years following initial review. metal follow-up guidance issued by five Implementing this recommendation worldwide authorities demonstrated
34 A natural-synthetic hybrid scaffold for paediatric tracheal replacement surgery
FELLOWSHIP/SPONSOR: 2. A Polymeric Approach to FURTHER FUNDING: Lady Wolfson One Year Airway Tissue Engineering: The The Wellcome Trust Research Fellowship Best Biodegradable Material for (Research Training Fellowship) Paediatric Application, Teoh GZ, for 28 months SUPERVISORS: Maughan E, Tavakoli M, Paolo De Coppi and PRIZES: Birchall M, Seifalian A. Annals of Martin Birchall 1. The Kevin Burnand Prize for Chemical Research, March 2016 Translational Science, Society SITE OF WORK: PRESENTATIONS: of Academic & Research Institute of Child Health, London 1. Quantitation of Residual Surgery (SARS) conference, PUBLICATIONS: Detergent in Decellularised January 2016 1. Mesenchymal stem cell Organs for Tissue Engineering 2. Shortlisted for Scientist of homing and immunomodulatory with Gas Chromatography-Mass the Year from British Society properties in cancer therapies: Spectrometry, 28th International for Histocompatibility and searching for the perfect balance, Symposium on Pediatric Surgical Immunogenetics (BSHI) Elizabeth Da Silva Lourenco, S, Research, Dublin September 2015 conference, September 2015 Maughan Maughan E, Janes S, Cell & Genne 2. A Tissue-Engineered Rabbit Therapy Insights. 2015; 1(2), 173- Model for Paediatric Airway 192 doi: 10.18609/cgti.2015.024 Tissue Engineering, presented to the Academic Laryngology Department of UC Davis, USA July 2015
Infants born with severe congenital in our animal models and in the clinical tracheal (windpipe) abnormalities may setting. Synthetic polymeric scaffolds not survive once separated from their show excellent ‘made-to-measure’ placental blood supply, and will usually strength and patency; however, they require lifesaving interventions as soon rarely show significant ingrowth of cells as, or even before, they are born. There or tissue integration. is also a growing cohort of children The specific aim of this RCS Fellowship who have developed acquired tracheal was to create a natural-synthetic problems from intubation trauma, hybrid scaffold for paediatric tracheal oesophageal reconstructions and replacement that could combine the extrinsic pressure from nearby tumours advantages, and negate drawbacks, or infection. of these two strategies. This builds on This project aimed to explore the tissue a multitude of data from our UCL Airway engineering field to manufacture a Tissue Engineering group and other tracheal scaffold as an alternative to International investigations into the conventional transplantation. Tissue- power of hybrid scaffolds. engineered windpipes do not require This Fellowship has generated enough immunosuppression, and by sustainably research questions for two postdoctoral regenerating an organ, the need for serial researchers to continue parallel work ‘upsizing’ re-transplantation as the child in decellularised gel scaffolds and grows is avoided. It is well-established improved synthetic nanocomposites. that biologically-derived ‘decellularised’ I am continuing to work alongside Elizabeth at the Institute of Child Health, scaffold materials encourage cell these collaborators as I progress into working on decellularised tissue gelation ingrowth and integration, but they are my Wellcome-funded PhD project, for often mechanically weak. Moreover, which the data accrued during this RCS stents usually need to maintain a patent Fellowship has been invaluable. airway, a strategy which can cause serious morbidity in its own right both
Congenital anomalies affecting the airway may affect up to 1:1000 pregnancies, but in the rare severe cases where a transplant is required, appropriately-sized donors are almost impossible to come by. 35 Patients with ‘routine’ conditions that require prompt treatment (e.g. hip fracture and acute appendicitis) undergo operations later and have worse outcomes in busy US trauma centres. However, there is no evidence that such patients are disadvantaged in UK Major Trauma Centres.
Regionalisation of trauma services in the United Kingdom and United States
FELLOWSHIP/SPONSOR: 2. Metcalfe D, Gabbe BJ, 2. Metcalfe D, Zogg CK, RCS Fulbright Scholar Award Perry DC, Harris MB, Ekegren Scott JW, Olufajo OA, C, Zogg CK, Salim A, Costa ML. Haider AH, Havens JM, SUPERVISORS: Quality of hip fracture care in Rios Diaz AJ, Yorkgitis B, Professor Ali Salim major trauma centres: a national Salim A. Disparities in failure SITE OF WORK: observational study. Bone Joint J. to rescue for injured patients. Center for Surgery and Public 98B(3):414-9 Oral presentation. 11th Annual Health, Brigham & Women’s Academic Surgical Congress, PRESENTATIONS: Hospital, Boston, USA Jacksonville, FL, USA, 2-4th 1. Metcalfe D, Perry DC, February 2016 PUBLICATIONS: Bouamra O, Salim A, Woodford M, 1. Metcalfe D, Olufajo OA, Edwards A, Lecky FE, Costa PRIZES: Zogg CK, Gates, JD, Weaver MJ, ML. Regionalisation of major 1. Orthopaedic Trauma Society Harris MB, Rios Diaz AJ, trauma services in England: a ‘Best Paper’ Prize 2016 Haider AH, Salim A. Are older post-implementation analysis. 2. Oxford-UCB Prize David Metcalfe adults with hip fractures Academy of Medical Sciences Fellowship 2016 disadvantaged in level 1 trauma Spring Meeting, London. 25th centers? Med Care. In Press February 2016. Abstract indexed FURTHER FUNDING: in The Lancet UCB (Union Chimique Belge) Pharma for three years
It is increasingly recognised that patients fractures that were treated in trauma with complex needs (e.g. heart attack centres spent longer in hospital, were or severe injuries) are best treated in more likely to be re-admitted, and had specialist hospitals. This has driven a higher rates of blood clots (deep vein trend for one or two large hospitals in thromboses and pulmonary emboli). each region to deliver the majority of Patients with appendicitis were more complex services. Although additional likely to stay in hospital longer and to resources have been invested in such have infection spreading throughout their hospitals, they have become busier and abdomen (generalised peritonitis) than had to restructure to accommodate new those treated in non-trauma hospitals. services. My aim was to understand how Interestingly, this pattern was not seen in various patient groups have been affected the UK. Although Major Trauma Centres by this trend towards ‘regionalisation’. (MTCs) were launched across England I used a number of large databases that in 2012, the reconfiguration did not have were based on insurance claims (USA) any measurable impact on the care and submissions by NHS hospitals for of older adults with hip fractures. One performance monitoring (UK). possible explanation is that UK hospitals are financially incentivised (through The results suggested that patients with the Best Practice Tariff) to ensure that acute appendicitis and older adults with patients with hip fractures receive their hip fractures might be disadvantaged David in theatre during fixation of a operation promptly, whereas there is by treatment in a regional trauma hip fracture no equivalent scheme in the US. This centre. Both groups spent more time research did, however, suggest that the waiting for an operation than those who quality of care for patients with severe were treated in non-trauma hospitals. injuries has improved in new MTCs. In addition, patients with isolated hip
36 Abdominal-based perforator flap breast reconstruction: Evaluation of anatomical studies and contemporary imaging techniques to optimise outcomes
FELLOWSHIP/SPONSOR: Selection in Single Dominant 2. Mohan AT, Zhu L, Blond McIndoe DIEP breast reconstruction: Vijaysekaran A, Wang Z, Research Fellowship Algorithmic approach to maximize Saint-Cyr M. The Single efficiency and safety has been Dominant Perforator DIEP SUPERVISORS: built and requires approval. Plast Breast Reconstruction: Michel Saint-Cyr Reconstr Surg A Review of Clinical Outcomes SITE OF WORK: and Risk Factors. Accepted PRESENTATIONS: Mayo Clinic, MN, USA to American Society of 1. Mohan AT, Zhu L, Michalak Reconstructive Microsurgery G, Lachman N, Saint-Cyr M. PUBLICATIONS: ASRM 2016, Arizona, USA 1. Mohan AT, Saint-Cyr M. Quantitative assessment of Advances in ImagingTechnologies single dominant perforator for Planning Breast Reconstruction. territories in bilateral DIEP breast Gland Surg. 2016 Apr;5(2):242- reconstruction using indocyanine 54. doi: 10.3978/j.issn.2227- green fluorescence angiography Anita Tanniru 684X.2016.01.03 and 4D CT imaging. World Society of Reconstructive Microsurgery Mohan 2. Mohan AT, Zhu L, Wang Z, WSRM, Mumbai, India Vijayasekaran A, Saint-Cyr M. Techniques and Perforator
Approximately 18,000 women per year This study closely examined patterns distribution of blood flow. It has undergo complete removal of the breast of blood supply (inflow and outflow) provisionally highlighted that different tissue, (a mastectomy) and the rate of from the single vessels (perforators) of patterns seen in blood flow were bilateral operations has tripled over abdominal tissue on which these flaps potentially related to concentration the last decade. Breast reconstruction are based to outline key patterns in their of linking vessels that made up the is an important consideration after vascular ‘roadmap’ within the skin and vascular roadmap. mastectomy and can improve the fat that may influence overall flap design. Examination of these linking vessels patient’s psychosexual wellbeing, and This was achieved through a series of on flap vascularity will have pertinent their overall psyche in response to breast anatomical cadaveric and intraoperative implications in the design of all flaps cancer management and recovery. patient studies, combining the use of used in reconstructive surgery. The advanced imaging techniques using 3D aim is to advance knowledge to allow and 4D Computed Tomographic (CT) surgeons to transplant tissue with a angiography to visualise the distribution robust and predictable blood supply that and patterns of the small vessels in the will help reduce complications, reduce skin and fat in detail. morbidity, associated healthcare costs We also reviewed the real-time and improve patient outcomes. dynamics of the flap’s blood supply using intraoperative imaging in a prospective patient cohort study and correlated this with the underlying anatomy. This Anita in the anatomy laboratory at Mayo Clinic working on cadaveric specimens study helped to better understand the ‘vascular roadmap’ of the skin and fat of The lower abdomen offers an ideal abdominal flaps and how that roadmap site for taking tissue that is suitable for could influence the flow and distribution breast reconstruction providing long- of blood in and out the tissue. lasting results, good cosmesis and Preliminary results demonstrated that natural looking appearance. The use Anita receiving a prize for best resident oral location and size of perforators alone of lower abdominal tissue for breast presentation at the Chang Gung Mayo Clinic did not explain the overall extent and reconstruction is based on transferring Reconstructive Symposium, Taiwan skin and fat with its delicate blood supply from small vessels and sparing the underlying rectus muscle.
Around 50,000 women are newly diagnosed with breast cancer per year in the UK and there is a lifetime risk of 1 in 8. 37 Survivorship of an orthopaedic implant is dictated by its fixation to bone; 30% of massive bone cancer prostheses do not integrate with the surrounding bone, of which 1 in 4 fail.
Enhancing osteointegration using selective laser-sintered porous titanium alloy combined with solution deposited coatings
FELLOWSHIP/SPONSOR: PUBLICATIONS: 2. Optimising osteointegration Enid Linder and the Arthritis 1. The use of a novel laser with 3D printed components: Research Trust Fellowship sintered porous collar in A FEA and histological study, optimising osteointegration Mumith A, Fromme P, Blunn SUPERVISORS: of endoprostheses, Mumith A, G, Aston W, Briggs T, Shah A, Professor Gordon Blunn and Coathup M, Fromme P, Coathup M, British Orthopaedic Dr Melanie Coathup Aston W, Briggs T, Shah A, Research Society (BORS) and SITE OF WORK: Blunn G, Combined International British Orthopaedic Association John Scales Centre for Biomedical Society of Limb Salvage (ISOLS) & (BOA) Annual meeting Engineering, Institute of Musculoskeletal Tumour Society September 2015 – Liverpool, UK Orthopaedics and Musculoskeletal (MSTS) Meeting October 2015 – FURTHER FUNDING: Science, Royal National Orlando, Florida, USA Orthopaedic Research UK, Scat Orthopaedic Hospital Bone Cancer Trust for one year Aadil Mumith
Massive bone tumour endoprostheses The next phase is to study the effect of (synthetic inserts) integrate with the our coatings on human stem cells. We skeleton via a collar sprayed with predict that our coatings induce greater hydroxyapatite (a major component differentiation of stem cells into bone and essential ingredient of normal cells than coatings currently available. bone), which encourages bone to We aim to translate the results of our attach onto its surface. research to benefit patients who undergo Our research aimed to design and test operations using endoprostheses within a new collar covered with an enhanced the next three to five years. We hope to bone growth boosting coating to improve reduce the need for highly complex integration of endoprostheses. We re-operations needed for implant. have produced a novel collar that is completely porous and manufactured from 3D-printed titanium allowing us to customise every facet of the collar structure to optimise the design, structures has historically been a maximising bone attachment. Arrow indicating current solid collar design Tissue analysis and X-rays of specimens as part of a distal femoral endoprosthesis from our study, confirm that these in a patient collars allow bone to permeate through structures has historically been a the collar, creating fusion between challenge. However, our research has the implant and bone. Our design has enabled us to coat porous structures integrated to greater than what has been in full, with a variety of coatings. We recommended by computer modelling, have incorporated other elements, most leading to a more durable implant. notably strontium, of which its bone Aadil with his supervisors Professor Gordon growth properties are currently utilised Implants that are coated with Blunn (President of the British Orthopaedic in osteoporosis treatment. This we hope hydroxyapatite commercially use a Research Society) and Dr Melanie will further augment bone regeneration, technique that coats the outer surface Coathup (Head of Centre for Cell & Tissue and not the inner pores. Coating porous attachment and overall integration. Research, UCL)
38 Circulating tumour DNA (ctDNA) in melanoma – a non-invasive biomarker of disease
FELLOWSHIP/SPONSOR: 2. Murphy S, Corrie P, Durrani FURTHER FUNDING: Jersey H&S Charitable Trust Fund A. Management of metastatic Addenbrooke’s Charitable Trust melanoma; a network perspective (12 months) & Cancer Research SUPERVISORS: on the changing surgical UK (four months) Dr Nitzan Rosenfeld, landscape. European Society Dr Pippa Corrie and of Plastic Reconstructive and Mr Amer Durrani Aesthetic Surgeons (ESPRAS). SITE OF WORK: Edinburgh, July 2014 Cancer Research UK, PRIZES: Cambridge Institute, The 1. Douglas Murray Prize, Eleventh University of Cambridge West Midlands Plastic Surgery PRESENTATIONS: Meeting. Birmingham, 13th 1. Murphy S, Durrani A, Corrie September 2014 P, Rosenfeld N. ‘Liquid biopsy’ in 2. Health Education East of Suzanne melanoma – circulating tumour England Celebration of Success Murphy DNA as a biomarker of disease. Annual Awards, winner of best British Association of Plastic Leadership Poster. The Wellcome Reconstructive and Aesthetic Trust Conference Centre, Surgeons (BAPRAS), President’s Cambridge. 26th September 2013 Prize Section. Birmingham, November 2015
Melanoma, a highly invasive form of skin carry risks, and are uncomfortable for melanoma patients during their treatment cancer, continues to increase in incidence the patient. The aim of our study was to and follow-up. We have shown that faster than any other malignancy in the look at circulating tumour DNA (ctDNA) changes in the ctDNA concentration UK. It is the fifth most common cancer in the blood and urine of patients with precede progression seen on CT scans in the UK with approximately 37 people melanoma as a non-invasive way of as well as elevated LDH levels in the being newly diagnosed every day. In tracking the genetic finger-print and blood. Developing a technique to detect 2012 there were in excess of 13,000 new burden of disease. ctDNA in the blood and urine of diagnoses and over 2,000 deaths from melanoma patients has the potential Using ‘TAm-Seq’, a method developed the disease. The best prognosis is seen to revolutionise the management of by the Rosenfeld Group in Cambridge, when lesions are detected early and this life-threatening disease. we successfully tracked multiple surgically removed prior to metastasis. mutations in the plasma and urine of Metastatic melanoma has been notoriously difficult to treat since it is resistant to conventional chemotherapy and radiotherapy. However, the discovery of hotspot mutations (e.g. BRAF V600E) along with the development of new targeted therapies and immunotherapies, has improved the prognosis for these patients. Nevertheless, most patients develop resistance and eventually succumb to their disease.
Currently there is no blood test which can be used to monitor patients. Therefore, the detection of progression can be delayed. In addition, when a patient develops progressive disease they often require biopsies to check the genetic Suzanne working in the laboratory with members of the Rosenfeld Group mutation profile of their tumour to guide any further therapy. Biopsies are invasive,
Melanoma is the most invasive form of skin cancer, accounts for over 2000 deaths per year in the UK and its incidence continues to rise faster than any other malignancy. 39 FIve-year survival for pancreatic cancer is 4%. New approaches are required and nanoparticle- based treatment could provide a potential solution.
Treatment of pancreatic cancer using gemcitabine-loaded superparamagnetic nanoparticles [SPIONs]
FELLOWSHIP/SPONSOR: PRESENTATIONS: PRIZES: Freemasons’ Fund for Surgical 1. European Pancreatic Club 1. Young Researcher Travel Research with the support of the Annual Conference, Toledo, Award (European Pancreatic Jersey H&S Charitable Trust Spain 2015 Club 2015) SUPERVISORS: 2. National Cancer Research 2. BASO~ACS Best Poster Prize Mr Christopher Halloran Initiative (NCRI) Cancer (NCRI Cancer Conference 2014) Conference, Liverpool 2014 SITE OF WORK: Royal Liverpool University Hospital / University of Liverpool
Sumit Nandi
Pancreatic cancer is difficult to diagnose To investigate the aims, pancreatic Pancreatic cancer outcomes are dismal and challenging to treat. Despite advances cancer cells were grown to form tight, and urgent attention is needed to attempt in surgical and chemotherapy treatments, dense spheroids. When chemotherapy- to improve this. Nanoparticle-based its survival rates have barely improved loaded nanoparticles were introduced chemotherapy treatments have huge since the 1970s, with only around the architecture of the ‘artificial tumour’ potential to improve patients’ quality 4% of patients surviving five years. was successfully disrupted. Furthermore, of life, by providing a more precise or Current chemotherapy agents also have an artificial circulation model was personalised chemotherapy regime, a poor response rate; possibly due to constructed, which continuously flowed without the unwanted side effects from ineffectiveness at penetrating pancreatic nanoparticles over tumour cells, with delivery of conventional chemotherapy. cancers as there is an unusually poor some being exposed to a magnetic field. blood supply and dense environment Encouraging results were demonstrated, surrounding tumours. Consequently, fresh showing that tumour cells are still approaches in targeting chemotherapy to destroyed with flowing nanoparticles; these cancers are required. but that death is accelerated with the use of a magnet – as the nanoparticles Our project investigates a novel iron are iron-based. core nanoparticle complex loaded with gemcitabine (commonly used This is a completely novel project and chemotherapy agent) to precisely thorough investigation is required. target, deliver its drug and kill The project will continue to explore the Sumit presenting his poster at the 2015 pancreatic cancer cells. Previous effects of the nanoparticles and future European Pancreatic Club, Spain work has demonstrated successful work is commencing in animal models. destruction of cancer cells in a static or 2D environment. During my fellowship, we have developed our knowledge by investigating their cell-killing capabilities in a 3D model and an artificial circulation, attempting to mimic blood circulation.
Experimental set-up of the artificial circulation model
40 Parathyroid hormone enhances osseointegration of a mesenchymal stem cell coated implant
FELLOWSHIP/SPONSOR: Freemasons’ Fund for Surgical Research SUPERVISORS: Professors Gordon Blunn & Timothy Briggs SITE OF WORK: Institute of Orthopaedics & Musculoskeletal Science, UCL FURTHER FUNDING: From Rosetrees Trust and Gwen Fish Trust for two years Liza Osagie
There are 150,000 hip replacements performed annually in the UK. This number is set to increase 300% by 2030, with a failure rate over 11%. One cause of failure is bone thinning; thus, attention has been turned to methods that can improve bone-implant fixation.
Within our ageing population, osteoporosis leads to one in four suffering an age-related fracture. As such, patients are at an 11% lifetime risk of fracturing around a hip implant.
Treatment of these fractures is often complex, with 10% of patients dying Liza presenting at a Freemasons’ meeting within 30 days of the operation. My work aims to enhance fracture I have investigated the mechanical healing and implant fixation using stem characteristics of our fracture fixation cells (MSCs) and parathyroid hormone device and replicated findings in (PTH) in a rat. I have obtained MSCs a computer programme. This allows from the bone, fat and muscle of adult us to alter the device in a computer and osteopenic rats; demonstrating the model and create the optimum optimal dose of PTH to turn them into construct to allow bone formation. bone forming cells, and the ability for Future works will use young and PTH to enhance cell migration to sites osteoporotic rats, injecting MSCs into of increased bone turnover (i.e. fracture the fracture gap, with injections under sites or around implants). the skin of PTH to accelerate healing. I have demonstrated the capacity for My work utilises clinically relevant PTH to turn fat cells into bone producing therapies to answer a growing patient cells; this is important in the context of need, with the aim of improving osteoporosis, where patients have a orthopaedic outcomes, and wider higher concentration of fat cells, thus implications for bone formation. hindering bone formation. Liza listening to Lord Cadogan at the Freemasons’ HQ
Over 150,000 hip replacements are performed in the UK annually; 11% of these will fail, and 11% will fracture around the implant. 41 Up to 1-in-4 flap breast reconstruction patients that subsequently undergo radiotherapy as part of their cancer treatment develop significant fibrosis.
Optimising a radioprotective gene therapy strategy in free flaps for translation
FELLOWSHIP/SPONSOR: PUBLICATIONS: Joint RCS/BAPRAS The tumour microenvironment Research Fellowship after radiotherapy: mechanisms of resistance and recurrence. SUPERVISORS: Barker HE, Paget JT, Khan AA, Professor Kevin Harrington and Harrington KJ. Nature reviews Mr Paul Harris Cancer 2015;15:409-25 SITE OF WORK: FURTHER FUNDING: Royal Marsden Hospital and the Wellcome Trust Clinical Research Institute of Cancer Research Fellow for 33 months
James Paget
Reconstructive surgery plays an project was to combine radioprotective a number of functions in immune cell important role in the breast cancer care gene-therapy with microvascular surgical recruitment to damaged tissue and in later pathway. In particular, reconstruction with techniques to give cancer patients a more fibrotic development. However, a high the patient’s own tissue at the time of durable reconstruction. proportion of immune biology occurs in cancer surgery has become a standard the first few days to weeks after damage. Using a validated experimental model of care in the UK. 50% of patients have We therefore explored earlier changes of radiation fibrosis in reconstructed high-risk cancer and undergo subsequent in CXCL12 in our microsurgical model tissue, we identified that CXCL12 plays radiotherapy; 25% of these cases develop across the first few days to weeks using an important role in the established unwanted fibrotic changes, patient a combination of messenger RNA and post-irradiation biological landscape at dissatisfaction and the need for revision protein assays. six months. It is a secreted signalling surgery. The overarching goal of this protein, called a chemokine, which has These results demonstrated that the greatest change occurs at one week after irradiation. This time point also correlates with the infiltration of the flap with innate immune cells, particularly macrophages, which are known to play a central role in wound healing and are attracted to CXCL12.
To target this therapeutically, we have developed a modified lentivirus that decreases CXCL12 production, and which will be delivered to the reconstructed tissue in isolation during surgery. Its efficacy at reducing CXCL12 has been confirmed in cell culture (see figure) and we will explore its effects in our model against fibrosis, including the link to macrophage biology, across the remainder of my PhD.
Confocal microscope images of cultured cells demonstrate our novel therapy working against the target protein
42 Evaluation of the diagnostic role of a small RNA within PCA3 in prostate cancer
FELLOWSHIP/SPONSOR: PUBLICATIONS: PRESENTATIONS: Freemasons’ Fund for Surgical 1. Identification and diagnostic 1. 30th European Urology Research with the support of the performance of a small RNA Association Congress Rosetrees Trust within the PCA3 and BMCC1 (International), Mar 20-24 gene locus that potentially 2015. IFEMA, Madrid, Spain SUPERVISORS: targets mRNA. Cancer Epidemiol Professor James Catto 2. BAUS Academic Meeting Biomarkers Prev. Drayton RM, (National), Dec 2 2014. Royal SITE OF WORK: Rehman I, Clarke R, Zhao Z, College of Surgeons, London Department of Oncology Pang K, Miah S, Stoehr R, and Academic Urology Unit, Hartmann A, Blizard S, Lavin M, PRIZES: University of Sheffield Bryant HE, Martens-Uzunova ES, European Urology Association Jenster G, Hamdy FC, Gardiner RA, 2015, Best Poster of Session Catto JW. 2014 Nov 12 (1st Prize) 2. ‘Science made simple’- FURTHER FUNDING: Karl Pang MicroRNA and Urothelial cell The Urology Foundation carcinoma. Miah S, Pang K, Catto for 12 months J. BJU Int. 2014 May:113(5):811-2
Prostate cancer (PCa) is the most of infection/bleeding/pain and patient replace the current test. We identified common cancer in men and is the second anxiety. Therefore, better markers are a shorter form, which we termed short- most common cause of cancer death needed to improve patient selection PCA3 and showed that its urinary levels after lung cancer. In the UK, there were for rPBx. are increased in PCa samples. ~42,000 cases diagnosed in 2011 and Prostate Cancer Antigen-3 (PCA3) is ~11,000 deaths in 2012. an urinary marker used to stratify men The investigation of PCa is based on for rPBx; however, it is used in selective digital rectal examination, blood tests, and countries and not in the UK because its a prostate needle biopsy (PBx). However, biological role is unknown and it’s a long not all men with abnormal blood tests molecule that is prone to breakdown who undergo a PBx have cancer. This by urinary enzymes. Urine is treated may be due to initially falsely abnormal chemically to prevent breakdown, which blood tests, as markers can be raised ensures a high cost. We searched the in infection and benign prostate disease PCA3 molecule using computer analyses as well. Unnecessary repeat PBx (rPBx) to find an alternative shorter form, which increases healthcare costs and risks may avoid breakdown and potentially
Analysing a CT scan from a patient with prostate cancer
We explored functions of short-PCA3 and found that it had the ability to interact with other molecules involved in PCa biology. We analysed potential molecule targets and showed that molecule, ‘SOX11’ was decreased in PCa urinary samples. Unravelling biological mechanisms in PCa would allow further investigation into therapeutic agents.
Reviewing urological patients on a ward round
The discovery of our new marker (termed short-PCA3) may improve selection of patients for prostate biopsy. This marker appears to target other molecules involved in prostate cancer biology. 43 Less than 1 in 8 men with prostate cancer actually have a form of the disease which requires aggressive treatment, identifying this group is of critical importance.
The translational potential of circulating tumour DNA in urological cancers
FELLOWSHIP/SPONSOR: X Chin, M Kerger, A Warren, PRIZES: Jersey DBP Surgical Trust D Neal, V Gnanapragasam, 1. Academic BAUS conference. N Rosenfeld, J Pedersen, A Ryan, Oral presentation prize (runner SUPERVISORS: I Haviv, A Costello, N Corcoran, & up) RCS 2015 Nitzan Rosenfeld C Hovens. Nat Comms. 2015.6:6605 2. Rosetrees Essay Award SITE OF WORK: 2. The translational Potential (runner up) RCS 2016 Cancer Research UK of Circulating Tumour DNA in FURTHER FUNDING: Cambridge Institute Oncology. Patel KM & D.W.Y. Cambridge Cancer Centre Tsui. Clin Biochem. 48(15):957–61 PUBLICATIONS: for three years 1. Tracking the origins and PRESENTATIONS: drivers of subclonal metastatic 1. Circulating tumour DNA as a expansion in prostate cancer. diagnostic aid in prostate cancer, M Hong, G Macintyre, D Wedge, poster presentation. European PV Loo, KM Patel, S Lunke, Association of Cancer Research, Keval M Patel L Alexandrov, C Sloggett, University of Cambridge 2013 M Cmero, F Marass, D Tsui, 2. Academic BAUS conference, S Mangiola, A Lonie, H Naeem, podium presentation runners-up N Sapre, P Phal, N Kurganovs, prize RCS 2015
Prostate cancer is the most common This project aimed to investigate whether stored blood prior to their initial attempt cancer in men and more are being the levels or types of mutations detected at curative surgery) we were able to diagnosed each year. Fortunately only non-invasively from blood samples, detect mutations in the TP53 gene about 12% of those diagnosed have an a method used in other types of cancers, directly from the blood sample. aggressive form that could limit their could identify men with aggressive We are continuing to work on this to see lifespan, with the majority having a prostate cancer. if the test results can be reproduced in a relatively indolent form. During the course of this project we larger cohort. If the blood test is able to found that a gene called TP53, which distinguish between men with aggressive plays a pivotal role in other cancers, and indolent forms of prostate cancer, tends to be mutated in men who we could more accurately target which have aggressive prostate cancer. men need aggressive treatment and Furthermore, we found that in two out of which do not. three men (for whom we had historically
Keval in the laboratory
Current methods do not always accurately differentiate between these aggressive and indolent cancers. Therefore, many patients who actually have indolent disease, are over-treated whilst those harbouring aggressive prostate cancer are not treated aggressively enough. Keval receiving a pot of jam in thanks for the talk he gave to the Cambridgeshire Prostate Cancer Support Association
44 Pre-injury statins in early resuscitation of complex battlefield injuries
FELLOWSHIP/SPONSOR: PUBLICATIONS: FURTHER FUNDING: Joint RCS/Military 1. Shock: aetiology and The project is part of the Research Fellowship pathophysiology, Emrys Kirkman, Combat Casualty Care Henrietta Poon, James D Ross Programme funded by SUPERVISORS: & Sarah Watts Submitted by the MoD M Midwinter, E Kirkman, invitation for inclusion in War S Watts, P Harrison Trauma: Principles and Practice SITE OF WORK: of Management (OUP) Defence Science and Technology 2. Intravenous fluids: starches, Laboratory, Porton Down, H Poon, S Watts & E Kirkman. Wiltshire Submitted by invitation for inclusion in Key Topics in Trauma
Henrietta Poon
Severe trauma is commonly associated with direct tissue injury and blood loss. As a consequence of excessive bleeding, cardiovascular reflexes in the body reduce blood flow to some organs in order to preserve the delivery of oxygen to other organs that are most critically dependent on oxygen, such as the brain. When blood flow is re-introduced during resuscitation, a secondary injury characterised by inflammation and damage to the lining of blood vessels (the endothelium) occurs. This is known as ischaemia-reperfusion injury (I-R).
I-R is worse at prolonged periods of reduced blood flow and may be worsened by some forms of injury, such as explosive injuries that cause particular damage and inflammation in key organs Logistic constraints in austere terrain and potentially long evacuation times, such as the lungs, reduce the amount especially at entry operations of oxygen transferred into the blood and modify cardiovascular reflexes. My study aims to assess the effects of Assessment of inflammatory response statins on secondary inflammation in two based on a range of mediators such as This is a particular problem in military models of complex trauma in terminally cytokines and endothelial damage are medicine where timelines to evacuate anaesthetised rats in a randomised, ongoing. If we find reduced inflammation casualties to hospitals may be long placebo-controlled, blinded prospective in the groups given statin this will provide in the early stages of conflict, and trial. Both models involve tissue injury, the proof of principle that statins may be where explosions may be the primary haemorrhage and resuscitation phase; of benefit in complex trauma. mechanism of injury. but one of the models has an additional Statins could be beneficial since there blast injury. is a substantial body of evidence suggesting that they can reduce I-R in other (non-trauma) circumstances, and there is also some evidence that statins may help in models of simple trauma (principally haemorrhage).
Widespread inflammatory responses, initiated by poor blood flow and subsequent resuscitation in trauma patients, is the cause of significant morbidity and delay in recovery after severe injury. 45 Cancer of the larynx (voice box) affects several thousand adults in the UK each year and has a poor prognosis; subglottic stenosis affects 1-2% of children admitted to a neonatal intensive care unit and can lead to life threatening breathing difficulties.
Development of a primary subglottic epithelial culture for the study of upper airway host defences
FELLOWSHIP/SPONSOR: PRESENTATIONS: PRIZES: Shears Northern 1. Powell J, Garnett J, Verdon B, 1. David Howard Prize, British Research Fellowship Wilson J, Pearson J, Ward C. Laryngological Association A human in vitro model of the annual meeting, poster SUPERVISORS: subglottic airway. 29th September presentation prize, Professor Jeff Pearson, 2015, American Academy of November 2015 Dr Chris Ward and Otolaryngology - Head and Neck Professor Janet A Wilson 2. Munro Black Prize, Northern Surgery (AAO-HNS) Annual Deanery Otolaryngology SITE OF WORK: Meeting, Dallas, USA oral presentation prize, Institute of Cell and Molecular 2. Powell J, Garnett J, November 2015 Biosciences, Newcastle University Verdon B, Wilson J, Pearson J, Ward C. A primary in vitro FURTHER FUNDING: PUBLICATIONS: model of the Subglottic Airway. Wellcome Trust for three years Powell J, Garnett J, Verdon B, 9th October 2015, ORS Autumn Wilson J, Pearson J, Ward C. Meeting, Liverpool Jason Powell A human in vitro model of the subglottic airway. Otolaryngol Head Neck Surg. 2015; 153(1s):83
The subglottis is located in the voice box, in a special way that makes them behave in the upper airway. It is a crucial area like they are in the body. In this special for the development of certain types of culture system the cells are exposed to infection, inflammation and cancer. Study air above and nutrients below, like in the of these diseases is limited by the lack airway. In these physiological conditions of a relevant human model. We aimed to the cells became a ‘living’ throat lining. develop a ‘living’ model of the subglottis The cells specialise into groups with using a few thousand human cells, taken different roles, such as secretory cells. from brushings of the throat. These cells also produced mucus spontaneously which is critical for lining I took brushings from the subglottis of the throat. They also produce small patients undergoing a throat examination. hair cells called cilia that are critical for These cells were grown in the laboratory clearing particles that might be inhaled into the airway.
I have set up reproducible protocols for the collection and growing of subglottic cells, for the first time ever to our knowledge. I have performed multiple assessments to ensure these cells are representative of the area they came from Jason receiving the David Howard Prize in humans. Therefore this model can be with Professor Janet Wilson used to study a multitude of diseases in the upper airway.
This is not the end of this work. I have obtained further funding to utilise this unique model in the study of preventing infection in the upper airway. This work aims to prevent critically ill patients Jason preparing to take a cell brushing in in hospital developing serious life theatre using a laryngoscope threatening infections. This will contribute toward me also completing a PhD. 46 Neuroinflammation and neurodegeneration after blast traumatic brain injury
FELLOWSHIP/SPONSOR: PUBLICATIONS: FURTHER FUNDING: Joint RCS/Military 1. Roberts SA. 100 Years of British Ministry of Defence for Research Fellowship military neurosurgery: on the completion of PhD shoulders of giants. Journal of SUPERVISORS: the Royal Naval Medical Service. Professor David Sharp & Surgeon 2015; 101.1: 20-27 Captain Mark Midwinter 2. Penn-Barwell JG, Roberts SA, SITE OF WORK: Midwinter MJ, Bishop JR. The Computational, Cognitive Improved survival in UK and Clinical Neuroimaging combat casualties from Iraq Laboratory, The Hammersmith and Afghanistan: 2003-2012. Hospital, London The journal of trauma and acute care surgery 2015; 78(5): 1014-20 Stuart Alexander Gordon Roberts
Over 400 UK and 2,000 US soldiers have This study involves 20 soldiers Soldiers are young, so long-term been fatally wounded by blast injuries with blast TBI. Positron Emission physical, cognitive, behavioural and since 2001. Figures show 70% of injuries Tomography (PET) imaging measures psychological effects are devastating and resulted from explosive weapons such as activated microglia, which are markers under-recognised. TBI has resulted in Improvised Explosive Devices (IEDs) or of neuroinflammation. Magnetic a ‘silent epidemic’ of disability, and can Rocket Propelled Grenades (RPGs). The Resonance Imaging (MRI) measures lead to neurodegenerative conditions, most common mechanism of Traumatic structure and function. We use this to including Alzheimer’s disease. Improving Brain Injury (TBI) was also exposure to assess haemorrhage, white matter the understanding of these effects blast; and TBI has been described as the damage and metabolites indicative represents an aspect of our duty of care ‘signature injury’ of recent conflicts. of neuroinflammation. Sampling to our service personnel, so that they Cerebrospinal Fluid (CSF) permits may be afforded the best prevention and The aim of this research is to investigate analysis of neurodegenerative markers treatment strategies into the future. if blast TBI causes chronic inflammation (such as tau). Genotyping investigates and degeneration of the brain. We if particular genes (i.e. APOE4) lead envisage improved understanding of to poor outcomes, assessing whether long-term consequences of blast TBI, metabolic syndrome, a condition allowing for targeted follow-up of soldiers, causing inflammation in the body, mitigation therapies and improved influences neuroinflammation and battlefield resuscitation strategies. neurodegeneration.
Initial findings show extensive white matter injury after blast. We will explore the relationship between this and neuroinflammation. PET has shown neuroinflammation persists many years after non-blast TBI in civilians. This is the first study of neuroinflammation and neurodegeneration in military TBI.
Moving the soldier into the PET scanner Performing a lumbar puncture looking for looking for neuroinflammation neurodegeneration in an injured soldier
70% of head injuries in Iraq and Afghanistan were as a result of blast injury.
47 1 out of 5 pancreas transplants are complicated by clot formation in the organ, potentially resulting in failure of the transplant or a second operation for the patient.
Reduction of allograft thrombosis in pancreas transplantation
FELLOWSHIP/SPONSOR: Frances and Augustus Newman Foundation Fellowship SUPERVISORS: Professors Vassilios Papalois and Charles Pusey SITE OF WORK: Chelsea & Westminster Hospital
Bynvant Sandhu
Pancreas transplantation offers a life My research involved investigation The problem of clot formation in the changing treatment for patients with of injurious clotting pathways during transplanted organ is not confined to aggressive diabetes by allowing them storage of the organ prior to transplant pancreas transplants. This methodology to become insulin independent. This and immediately upon transplantation will be applicable to research involving means no longer requiring multiple daily of the organ into the recipient. other organs also, such as liver and injections and importantly, reduces the kidney transplants. We tested a unique anti-coagulant risk of cardiovascular disease associated compound with the ability to bind to with diabetes. blood vessels in the organ and therefore Pancreas transplantation does however act specifically at the site of injury. carry significant risks, including clot Using cellular models, we were able formation within the organ. This poses to demonstrate effective binding of the a significant threat to the pancreas drug and reduction of clot formation. and may result in patients requiring Our research also demonstrated a second operation or ultimately losing that blocking clotting pathways had the transplant. the additional beneficial effect of reducing inflammation in the organ. Inflammation in a transplanted organ triggers an immune response in the patient, ultimately damaging the organ. Therefore, targeting clotting pathways provides a potentially critical strategy for improving outcomes in organ transplantation. Testing of the anticoagulant drug in the whole organ is ongoing. Bynvant speaking to a young patient after a successful pancreas transplant By reducing the degree of injury incurred by the organ during storage and at the time of transplantation Bynvant helping a colleague to prepare we hope to improve both short and a pancreas prior to transplantation longer term outcomes for pancreas transplant recipients.
48 Using 3D in vitro tumour models to develop personalised treatment of oesophago-gastric cancer
FELLOWSHIP/SPONSOR: PRESENTATIONS: PRIZES: Frances and Augustus Newman 1. Developing personalised 1. Leonardo Da Vinci Prize, Foundation Fellowship treatment for oesophago-gastric Royal Society of Medicine cancer using 3D in vitro tumour for the Rotary Societies of SUPERVISORS: models. Saunders JH, Onion Europe, 2015 Dr Anna Grabowska D, Parsons S, Grabowska A. (Associate Professor) 2. The Sue Watson Postgraduate European Association of Cancer Research Prize, University of SITE OF WORK: Research (Goodbye Flat Biology: Nottingham, 2015 Division of Pre-Clinical Oncology, 3D Models and the Tumour Cancer Biology, University of Microenvironment). Berlin, FURTHER FUNDING: Nottingham, Queens Medical Germany. Nov 2014 University of Nottingham for one year Centre, Nottingham 2. The value of adjuvant chemotherapy in oesophago- gastric cancer Saunders John Saunders JH, Bowman CR, Soomro I, Madhusudan S, Parsons SL ASGBI 2015 International Surgical Congress. April 2015
Patients with oesophago-gastric cancer that human cancer cells, if grown in a This study aims to determine whether (OG cancer) routinely undergo pre- laboratory without the local environment the OG cancer chemo-sensitivity operative chemotherapy; however, and support from other cancer demonstrated in the laboratory 3D-TGA half will not respond and so suffer from associated cell types found in patients, matches with the clinical response chemotherapy side effects as well as respond differently to chemotherapy to chemotherapy. If this can be experiencing further tumour progression. from those same cancer cells grown in a demonstrated, we can use this data We have developed 3D in vitro tumour complex microenvironment more closely to support a large clinical trial that models to study the mechanisms of drug resembling their original surroundings. will enable delivery of personalised resistance in tumours. We hypothesise chemotherapy for patients with OG We have developed a laboratory that these models will more closely cancer, within the next five years. method to grow the patient’s own cells reflect the behaviour of individual human (both cancer cells and other supporting cancer chemotherapy responses, and be cells) directly from patient tumours. We able to predict each patient’s individual have used these to establish novel 3D chemotherapy response, thus providing tumour growth assays (3D-TGA) that personalised treatment for OG cancer. provide a humanised tumour micro- Cancers grown in the laboratory have environment for individual patient’s been used to try to predict chemotherapy cancer cells. Importantly this assay is response without success. It is now clear rapid, requires only small amounts of cancer tissue, and allows numerous drugs and combinations to be tested simultaneously, unlike traditional laboratory models. Our results (in multiple cancer types) have shown that with this 3D humanised tumour micro environment, the cancer cells’ sensitivity to the chemotherapy drugs more accurately reflects the high level of chemotherapy resistance Consenting a patient for endoscopy and seen in patients. study participation Analysing the growth of the patient’s individual 3D cancer clusters
There are 15,000 new diagnoses of oesophago-gastric cancer per year in the UK, but less than half of these will respond to chemotherapy. 49 Despite the global asbestos ban in 1999, the incidence of malignant pleural mesothelioma continues to increase; the UK currently has the world’s highest incidence with 65,000 expected deaths by 2050.
Interrogating mesothelioma genomics for personalised radical surgery and secondary prevention
FELLOWSHIP/SPONSOR: 2. Bilancia R, Sharkey AJ, 2. Does the Timing of Jersey H&S Charitable Trust Fund Waller DA. 2015. Thoracoscopy Chemotherapy Affect Outcome in the diagnosis and treatment following Radical Surgery SUPERVISORS: of MPM. In: Malignant Pleural for MPM? 12th International Professor Dean Fennell Mesothelioma: Present Status Mesothelioma Interest Group SITE OF WORK: and Future Directions. Bentham Conference. Cape Town, South University of Leicester and Science Publishers 2016 Pp. 399- Africa. October 2014 University Hospitals of Leicester 411 (13) PUBLICATIONS: PRESENTATIONS: 1. Sharkey AJ, Tenconi S, Nakas 1. What Are the Risks and A, Waller DA. The Effects of An Benefits of Extended Pleurectomy Intentional Transition From Decortication for Mesothelioma? Extrapleural Pneumonectomy A Review of the Largest To Extended Pleurectomy- Institutional Series in the UK. Annabel Decortication. Eur J Cardiothorac 16th IASLC World Conference Sharkey Surg June 2016 on Lung Cancer. Denver, USA. September 2015
Malignant pleural mesothelioma is a To allow the accurate development of relatively rare but almost invariably fatal a prognostic tool I needed to determine cancer affecting the membrane lining of the amount of genetic variation between the lungs and abdomen, often associated different areas of the tumour. For this with prior exposure to asbestos. The use I recruited 60 patients for complex of radical surgery in the treatment of this genetic analysis of multiple regions of the disease remains controversial, as this tumour. This ongoing work has allowed major operation shows markedly differing me to determine the genetic evolution of outcomes. As no clinical reason for this mesothelioma and therefore the potential has been found, we assume it is due to variability within tumours. which I am currently analysing, and genetic differences within the tumours. Annabel in the laboratory I will also be able to identify new targets For patients to benefit from a high-risk for chemotherapy treatments for patients surgical resection, we needed to find a have identified at least one new possible in the adjuvant setting, or who have way to determine which have the best treatment target which I am currently relapsed following surgery or first line prognosis tumours, prior to selection testing in the laboratory. therapy. I now have data for six patients for surgery. Using data from patients who have undergone radical surgery, I identified two cohorts of matched patients with good or poor survival and disease recurrence outcomes. Analysis of these cohorts identified the overall number of CNVs (copy number variations) can predict outcome following surgery and several specific CNVs correlate with survival or recurrence outcomes.
Along with my new knowledge of the genetic evolution of these tumours, and therefore the degree of variability within them, these results have allowed me to start developing a tool which should The Leicester Thoracic Surgical team performing a radical resection for mesothelioma predict prognosis from a single biopsy.
50 Blast-mediated traumatic amputation: underlying mechanisms and associated injuries
FELLOWSHIP/SPONSOR: study of fatal injury patterns in 2. Blast-mediated traumatic Joint RCS/Military victims of improvised explosive amputation: evidence for a new Research Fellowship devices. BMJ Open. 3.8 2013. injury mechanism. Orthopaedic PMID: 23906957 Trauma Association Annual SUPERVISORS: Scientific Meeting, Phoenix, Colonel Jon Clasper MBA DPhil 2. Singleton JAG, Gibb IE, Arizona, USA Oct 2013 DM FRCSEd(Orth) L/RAMC & Bull AMJ, Clasper JC. Blast- Professor Anthony Bull PhD DIC mediated traumatic amputation: PRIZES: ACGI BEng CEng FIMechE evidence for a revised, multiple 1. Combined Services injury mechanism theory. J Orthopaedic Society 2014: SITE OF WORK: Royal Army Med Corps (2014), Peter Templeton memorial prize Centre for Blast Injury Studies, jramc-2014. PMID: 24408908 (best presentation) Imperial College London PRESENTATIONS: 2. Defence Medical Services PUBLICATIONS: 1. Battlefield injury clinical Awards 2013: Montefiore 1. Singleton JAG, Gibb IE, research. NATO Symposium, memorial prize (best military James Hunt NCA, Bull AMJ, Clasper JC. Human Injury Assessment surgical trainee) Identifying future ‘unexpected’ in Vehicle Explosions, ICL, Singleton FURTHER FUNDING: survivors: a retrospective cohort London, Jun 2013 The Ministry of Defence for the duration of the project
Improvised explosive devices (IEDs) were used, if available. The CT scans injuries occur, we can use that knowledge came to prominence in Iraq in the 1990s were carried out in the British Military to find ways to try to prevent these injuries and early 2000s, and became the main Hospital, Camp Bastion, Afghanistan, or decrease their severity to save limbs weapon used against British troops and within hours of the soldier dying. These and lives. vehicles in the more recent conflict in scans provided never before available Afghanistan. IEDs caused over 50% of detail of the exact injury patterns of all recent UK combat deaths with 61% these traumatic amputations, along of casualties sustaining at least one with information on other injuries such traumatic amputation (TA). Until recently as to the lungs. With such sensitive there was little high quality clinical data data, much work was required to gain to aid understanding of how explosions permission to access this data, and cause TAs. to satisfy the necessary military oversight that all data would be kept anonymised whilst also forming the basis of presentations, publications and a research doctorate. Scrutinising the imaging and associated data took several months.
Analysis of these scans along with other post mortem and incident data showed 21.9% of all TAs occurred through joints, far more common than the previously An IED strike on a foot patrol in Afghanistan, reported rate of 1.3%. There was also 3D Reconstruction of post mortem CT of showing the size of blast involved no link found between blast lung injury an IED casualty showing right through Analysis of battle casualty’s post mortem and traumatic amputation, which was knee amputation and left high above-knee CT scans was a crucial part of this clinical previously thought to be the case. This amputation research. From November 2007, such fundamentally changed our knowledge scans became part of the Coroners’ of what components of the blast were inquest that happens for every combat capable of causing TAs and by better death. Before this, simple X-ray images understanding how these devastating
1 in 4 traumatic amputations occurred through joints, showing explosion-mediated flail to be a valid injury mechanism. 51 1 in 4 of the UK population are affected by hay fever (allergic rhinitis) caused by grass pollen.
Low dose intradermal allergen immunotherapy in the treatment of seasonal allergic rhinitis (hayfever): a double-blind randomised control trial
FELLOWSHIP/SPONSOR: Stephen J Till. ‘Protocol for 2. ‘Pollen low dose intradermal The Dr Shapurji H Modi Memorial a double-blind randomized therapy evaluation (PollenLITE): Research Fellowship controlled trial of low dose a double-blind randomised intradermal grass pollen placebo-controlled trial of low- SUPERVISORS: immunotherapy versus a dose intradermal grass pollen Dr Stephen Till & Professor histamine control on symptoms immunotherapy in seasonal Stephen Durham and medication use in adults allergic rhinitis’ European SITE OF WORK: with seasonal allergic rhinitis Academy of Allergy and Clinical King’s College London, (PollenLITE).’ Clinical and Immunology Congress, Vienna, Guy’s hospital Translational Allergy 2013, 3:27 June 2016 PUBLICATIONS: PRESENTATIONS: PRIZES: 1. Slovick A, Durham S, Till S. 1. ‘Efficient Clinical Trial 1. Barry Kay Award: First prize, ‘Grass Pollen Immunotherapy for Recruitment using integrated for oral presentation in adult the treatment of Allergic Rhinitis.’ website and media-based allergy section, British Society Anna Slovick BMJ Nov 2014; 349: g6586 strategy: experience from 2 of Allergy & Clinical Immunology, randomised controlled trials’ & Sep 2015 2. Slovick A. Abdel Douiri, ‘A randomized placebo-controlled Joanna Kelly Andrea Guerra, 2. Royal Society of Medicine trial of intradermal allergen Rachel Muir, Konstantinos Allergy Section, ‘President’s immunotherapy for seasonal Tsioulos, Caroline Murphy, Prize day presentation’ runner-up, grass pollen allergy’ European Mohamed H Shamji, Sun Ying, Mar 2015 Rhinology Society Congress, Stephen R Durham and Stockholm, Jul 2016
Five million people in the UK have hay The severity of hay fever symptoms and fever, which significantly affects their usage of allergy medications was then quality of life, such as their sleep, ability recorded. We also performed experiments to work or attend school. In such to see the effect of the new vaccine on the people, an allergy vaccine (called immune system. ‘immunotherapy’) may reduce the allergic The results of the study conclusively response to grass pollen. Although current showed that the new approach had no vaccines are effective they are expensive benefit in reducing hay fever symptoms and involve frequent visits to specialist or need for medications. Unexpectedly, clinics for injections or daily self-dosing symptoms in the nose were actually with tablets or drops for several years. modestly worse in those who had the Poster to attract participants to PollenLITE Based on encouraging results from a grass pollen injections. Our experiments clinical trial pilot study, we undertook a clinical trial also indicated a small stimulation effect of a potentially new and very different on the immune system. form of grass pollen immunotherapy. These results have implications for The new approach involved giving very other future research in this area, as small grass pollen doses (thousands there are many trials and companies of times less than existing methods) by developing intradermal and epidermal injections directly into the top most skin immunotherapies, which may prove layer (called the dermis). We recruited 93 detrimental to those with allergies. participants who were randomly selected These results also make an important to receive seven such injections every scientific contribution to our understanding two weeks before the 2013 summer grass of mechanisms that can drive allergies. pollen season, or seven dummy injections.
52 The role of neutrophil extracellular traps in the management of acute pancreatitis
FELLOWSHIP/SPONSOR: PUBLICATIONS: PRESENTATIONS: Freemason’s Fund for 1. Xiong J, Szatmary P, 1. International Association Surgical Research Huang W, de la Iglesia-Garcia of Pancreatologists Annual D, Nunes QM, Xia Q, Hu W, Meeting 2015, Shanghai, China SUPERVISORS: Sutton R, Liu X, Raraty MG; Professor Robert Sutton 2. American Pancreatology ‘Enhanced Recovery After Surgery Association Annual Conference SITE OF WORK: Program in Patients Undergoing 2015, San Diego, USA The National Institute for Health Pancreaticoduodenectomy: Research Liverpool Pancreas A PRISMA-Compliant Systematic PRIZES: Biomedical Research Unit Review and Meta-Analysis.’ 1. International Association Medicine 2016; 95(18):e3497 of Pancreatologists Young Investigator Award, 2015 2. Ke N, Su A, Huang W, Szatmary P, Zhang Z; ‘Regulating 2. European Pancreas Club the expression of CD80/CD86 Young Investigator Award, 2015 Peter Szatmary on dentritic cells to induce immune tolerance after xeno-islet transplantation.’ Immunobiology 2016; 221(7):803-12
Acute pancreatitis is a potentially severe, debilitating inflammatory condition of the pancreas. It may result in prolonged hospitalisation with numerous surgical interventions, leaving those who survive with crippling complications. Current best treatment aims to support failing organs allowing them to recover, but no specific and effective therapy is available.
Newly identified functions of neutrophils – first responder cells of the immune system – that protect from infection and injury in others diseases appear to contribute to injury to the pancreas Peter providing a clinical perspective for patient-driven service improvements at the National and other organs. Modulation of these Pancreas Patient Forum 2015 in Liverpool functions could lead to the development of novel therapies. This project aimed to By measuring novel inflammation the course of the disease, reduce many assess the role of these novel pathways pathway-specific markers in patient’s of the long-term complications and in the management of acute pancreatitis. blood, this project was able to greatly improve patients quality of life. demonstrate similar effectiveness to Patients admitted with acute pancreatitis current strategies 24 hours earlier, today are routinely assessed whether widening the window for potential their disease is a mild, self-limiting form therapy. It further demonstrated that or a much more severe variety. If severe, modulating these pathways is effective they face a one in five chance of death, in reducing severity of the disease in or the prospect of multiple surgical experimental models, paving the way procedures, months of hospitalisation for future clinical trials. and a future of chronic pain, malnutrition and diabetes severely limiting their Treatment strategies resulting from this Peter presenting RCS-funded research at the quality of life. Current assessment work may therefore, not only lead to first meeting of the International Association strategies are highly effective in better and earlier disease stratification, of Pancreatologists hosted by China in predicting severe disease from 48 hours but may allow treating physicians to alter Shanghai in 2015 after admission, but much less so early on in the presentation.
1 in 5 patients admitted with acute pancreatitis develop the severe form of the disease; 1 in 5 of those die, without effective treatment being available. 53 Rotator cuff tears affect 30-50% of patients over the age of 50 years and are a common cause of function-limiting pain and weakness of the shoulder.
Tendon reattachment using demineralised bone matrix and mesenchymal stem cells
FELLOWSHIP/SPONSOR: 2. Thangarajah T, Pendegrass C, 2. Thangarajah T (speaker), Joint RCS/Arthritis Research Shahbazi S, Lambert SM, Pendegrass C, Shahbazi S, Trust Fellowship Alexander S, Blunn GW. Lambert S, Alexander S, Augmentation of Rotator Blunn GW. Tendon Reattachment SUPERVISORS: Cuff Repair with Soft Tissue to Bone in an In Vivo Ovine Professor GW Blunn Scaffolds. Orthopaedic Journal Model Using Allogenic and SITE OF WORK: of Sports Medicine 2015 Xenogenic Demineralized Bone John Scales Centre for Biomedical June;3(6):2325967115587495 Matrix. European Orthopaedic Engineering, Institute of Research Society’s 23rd Annual PRESENTATIONS: Orthopaedics and Musculoskeletal Meeting, Bristol, September 1. Thangarajah T, Pendegrass Science (IOMS), Royal National 2nd-4th 2015 C, Shahbazi S, Lambert S, Orthopaedic Hospital, University Alexander S, Blunn GW. Tendon College London Reattachment to Bone in an In PUBLICATIONS: Vivo Ovine Model Using Allogenic Tanujan 1. Thangarajah T, Pendegrass and Xenogenic Demineralized Thangarajah C, Shahbazi S, Lambert SM, Bone Matrix. 26th Congress of Alexander S, Blunn GW. Tendon the European Society for Shoulder Reattachment to Bone in an Ovine and Elbow Surgery (SECEC/ Model of Tendon Retraction ESSSE), Italy-Milan, September Using Allogenic and Xenogenic 16th-19th 2015 Demineralized Bone Matrix Incorporated with Mesenchymal Stem Cells. PLoS ONE 2016
a 500% rise in the rate of rotator cuff then used to evaluate the effect of DBM repair since 2001; however, failure of and stem cells. This showed that the tendon-bone fixation occurs in up to 90% combination of DBM and stem cells of cases. This results in poor functional could regenerate ‘normal tissue’, and outcomes, revision surgery, and further therefore presents an exciting prospect costs to the NHS. To address this high for the future. failure rate, several scaffolds have been We hope that this work is a prelude developed in order to enhance healing to clinical translation with the ultimate by ‘bridging the gap’ between tendon and goal of reducing the failure rate bone. None though have been able to following rotator cuff repair and produce a strong interface with a similar improving surgical outcomes. structure to the uninjured tissue, and so failure rates are still high. Tanujan detaching the supraspinatus tendon from its bony insertion in a The tendon biology group at the IOMS rat’s shoulder have developed a novel biological scaffold made from demineralised bone Shoulder pain causes approximately matrix (DBM). Previous studies have 1% of adults in the UK to present to their demonstrated that DBM can successfully General Practitioner annually and costs regenerate a damaged tendon and the NHS £310 million per year. Rotator withstand the high forces normally borne cuff disease accounts for the majority of by it. My Fellowship expanded upon these and is found in 54% of those over this work in order to examine DBM in the age of 60 years. Patients typically conditions akin to those observed in present with severe pain, which can the clinical setting following a rotator negatively impact quality of life and lead cuff tear. The initial stages involved the The New Royal National Orthopaedic to surgery. In the UK there has been development of a rat model, which was Hospital (RNOH)
54 Investigation of gene-environment interactions between Vitamin D and colorectal cancer susceptibility genetic variants in large bowel epithelium
FELLOWSHIP/SPONSOR: 2. Vaughan-Shaw PG, Wheeler 2. Vaughan-Shaw PG, RCS Research Fellowship JMD, Borley NR. The impact of a Fitzpatrick D, Farrington SMF, supported by the Harold dedicated multidisciplinary team Dunlop MG. Investigation into Bridges Bequest on the management of early rectal the in vitro and ex vivo effects cancer. Colorectal Disease 2015, of Vitamin D treatment on SUPERVISORS: 17(8):704-709 selective gene expression. Professor Malcolm Dunlop Presented at Academy of Medical and Dr Susan M Farrington PRESENTATIONS: Sciences Meeting for Clinician 1. Timofeeva M, Zgaga L, SITE OF WORK: Scientists in Training, London, Ooi LY, Vaughan-Shaw PG, Colon Cancer Genetics Group February 2015 Theodoratou E, Walker M, and Academic Coloproctology, Tenesa A, Farrington SM, FURTHER FUNDING: Institute of Genetics and Campbell H, Dunlop MG. From MRC Clinical Research Molecular Medicine, Western Susceptibility to colorectal cancer Training Fellowship for General Hospital is influenced by interaction two years Peter PUBLICATIONS: between genetic variants and Vaughan-Shaw 1. Vaughan-Shaw PG, Walker M, plasma Vitamin D level. European Ooi LY, Farrington SM, Gilber N, Society of Human Genetics Dunlop MG. A simple method to meeting, Glasgow June 2015 overcome the inhibitory effect of heparin on DNA amplification. Cellular Oncology 2015, DOI: 10.1007/s13402-015-0250-8
Recent studies have shown that Vitamin Data analysis involving thousands of D level may combine with genetic factors other genes and genetic mutations to influence risk of bowel cancer. This are ongoing. project investigates the effect of Vitamin The final part of my project investigates D on certain important genes. Ultimately, the effect of a 12-week course of high- Vitamin D may be used to prevent bowel dose Vitamin D on gene activity. I have cancer in patients with the highest recruited 40 patients and shown that on genetic risk. average we can double Vitamin D level The first part of my project involved the with supplementation. I have also shown treatment of several bowel cancer cell an increase in the expression of the lines with Vitamin D. These experiments Vitamin D receptor in bowel tissue with showed that Vitamin D increased the analysis of other genes ongoing. expression of CDH1 in a number of To date I have shown that Vitamin D bowel cancer cell lines. This gene codes treatment increases the activity of a for the protein E-cadherin which has gene relevant to cancer prevention in several anti-tumour properties. bowel cancer cell lines, while Vitamin D Next I undertook a clinical study of the supplementation improves Vitamin D effect of Vitamin D level on gene activity. status in study participants. Further Research nurse sampling blood from study patient for Vitamin D level I have recruited over 150 patients, both analysis aims to determine the with and without bowel cancer. Analysis effect of Vitamin D supplementation to date shows that a quarter of those on gene activity and ultimately sampled are Vitamin D deficient, while support a randomised study of the activity of the CDH1 gene appears Vitamin D supplementation on to be associated with Vitamin D level in bowel cancer prevention. blood but not bowel tissue samples.
There are over 40,000 new cases of bowel cancer in the UK each year, with significant associated death and disability. 55 Annually in the UK 13,000 people sustain burn injuries requiring hospital admission with an estimated annual NHS cost of £140 million.
Metabolomics as an approach to the prediction and diagnosis of sepsis following thermal injury
FELLOWSHIP/SPONSOR: PRESENTATIONS: Presentation. British The Lord Leonard and Lady 1. Severe burn injuries: Applying Burn Association 47th Annual Estelle Wolfson Research metabolomics to study longitudinal Meeting, Birmingham, Fellowship supported by the changes and prediction of clinical May 2015 Rosetrees Trust outcomes. W. Dunn, C.M Wearn, PRIZES: P. Hampson, J. Allwood, SUPERVISORS: 1. Jackson Prize for Best Burns R. DiGuida, J. Hazeldine, Mr Naiem Moiemen (Clinical Research Paper, SARS Annual M Fitzpatrick, N. Moiemen Supervisor) and Dr Warwick Dunn Meeting, January 2015 and J.M. Lord. Metabolomics, (Academic Supervisor) San Francisco, July 2015 2. Mercian Travelling Fellowship SITE OF WORK: Prize, National Plastic and 2. A non-targeted metabolomics Healing Foundation Centre for Reconstructive Surgery (NPRAS) analysis of urine and plasma to Burns Research, Queen Elizabeth Meeting, September 2014 study longitudinal metabolic Hospital Birmingham and Centre changes following a burn injury FURTHER FUNDING: for Translational Inflammation Christopher in adults. W. Dunn, C.M Wearn, There is continued funding for Research (CTIR), University P. Hampson, J. Allwood, the overarching observational Wearn of Birmingham R. DiGuida, J. Hazeldine, study (SIFTI study) from The M Fitzpatrick, N. Moiemen and Healing Foundation J.M. Lord. Awarded Best Oral
Patients with severe burns are at hyperthermia, muscle wasting and loss of previously studied in burns which are increased risk of complications during lean body mass. These responses result occurring over the first six months their recovery. The severity of injury in in immune system dysfunction, which in post injury. these patients results in system-wide combination with major skin loss, leaves Additionally the data has enabled us to activation of the immune and endocrine patients at risk of infections and sepsis identify a number of potential biomarkers systems. These responses contribute to with high mortality. that could be measured routinely to the development of significant metabolic Compared to other populations of diagnose and monitor sepsis. We are dysfunction, termed ‘hypermetabolism’. critically ill patients, burn injured currently preparing a grant application to patients experience a higher incidence analyse biological samples from the entire of sepsis and poorer outcomes with SIFTI cohort of 150 patients to validate mortality rates in the range 28-65%. our findings, with a view to developing The diagnosis of sepsis in patients with a personalised healthcare approach to severe burns is challenging, owing to burns, nutritional support, and for the the systemic responses masking the diagnosis and treatment of sepsis. normal clinical signs used to diagnose infection and sepsis.
We developed a prospective multi-centre observational study to investigate these key responses to severe burn injury in Giving a presentation about the WHO adults and children (SIFTI study). Blood Surgical Safety Checklist to a group of and urine samples from a cohort of 48 surgical residents as part of an Introduction patients were analysed using a technique to Surgical Skills Workshop in Lima, Peru called metabolomics, which analyses the majority of small products of metabolism The consequences of hypermetabolism simultaneously. This untargeted approach for the patient include persistently has led us to identify novel changes Christopher presenting research findings at elevated blood glucose levels, increased the American Burn Association 47th Annual in a number of metabolite classes not metabolic rate, elevated heart rate, Meeting, Chicago
56
57
5 year survival rates of less than 50%. than less of rates survival year 5
have still melanoma and sarcoma advanced treatment,
the 15–39 age group. Despite current expert multimodality multimodality expert current Despite group. age 15–39 the
melanoma and it is a significant cause of cancer deaths in in deaths cancer of cause significant a is it and melanoma
In the UK there are over 1,500 deaths a year from from year a deaths 1,500 over are there UK the In
in side effects. side in
increase any without radiotherapy,
further enhanced with the addition of of addition the with enhanced further
to current standard therapies, which was was which therapies, standard current to
significantly improved survival compared compared survival improved significantly
and Joan Kyula – post-doctoral researcher post-doctoral – Kyula Joan and virus delivered by ILP, have already led led already have ILP, by delivered virus oncolytic virotherapy by ILP resulted in in resulted ILP by virotherapy oncolytic
RCS fellow and another PhD student in the lab lab the in student PhD another and fellow RCS experiments, testing oncolytic vaccinia vaccinia oncolytic testing experiments, animal model of ILP. The delivery of of delivery The ILP. of model animal
scientific officer, Michelle, Aadil Khan previous previous Khan Aadil Michelle, officer, scientific The promising results from these these from results promising The side laboratory experiments and in an an in and experiments laboratory side
Roulstone – scientific officer, David Mansfield – Mansfield David officer, scientific – Roulstone
increased cancer cell killing both in bench bench in both killing cell cancer increased
to improve outcomes for patients. for outcomes improve to
leader Professor Kevin Harrington, Victoria Victoria Harrington, Kevin Professor leader
oncolytic vaccinia virus and radiotherapy radiotherapy and virus vaccinia oncolytic
way of finding new potential therapies therapies potential new finding of way
clinical trials. From left PhD supervisor, team team supervisor, PhD left From trials. clinical
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Testing new cancer therapies in this this in therapies cancer new Testing radiotherapy and surgery. and radiotherapy Targeted Therapy Team, ICR scientific retreat retreat scientific ICR Team, Therapy Targeted
relapses and it does not improve survival. survival. improve not does it and relapses alone and in combination with with combination in and alone
to 80% of patients, the disease often often disease the patients, of 80% to cells, cancer kill and target naturally
symptoms and saves the limb in up up in limb the saves and symptoms virotherapy, which are viruses that that viruses are which virotherapy,
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limb perfusion (ILP) to deliver a new new a deliver to (ILP) perfusion limb
of cancer therapy. cancer of
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to improve ILP. This model is currently currently is model This ILP. improve to high doses of chemotherapy directly to to directly chemotherapy of doses high
excellent model for testing new therapies therapies new testing for model excellent specialist surgical procedure that delivers delivers that procedure surgical specialist
animal model of ILP, providing an an providing ILP, of model animal therapy. Isolated limb perfusion (ILP) is a a is (ILP) perfusion limb Isolated therapy.
patient benefit. patient project which developed the current current the developed which project spread and poor response to standard standard to response poor and spread
phase I clinical trial with the potential for for potential the with trial clinical I phase previous RCS fellowship sponsored sponsored fellowship RCS previous carries a poor prognosis because of rapid rapid of because prognosis poor a carries
to NHS ethics and MHRA approval for a a for approval MHRA and ethics NHS to This research has progressed from a a from progressed has research This Advanced melanoma and sarcoma sarcoma and melanoma Advanced
2015 Feb 15;136(4):965-76. doi: doi: 15;136(4):965-76. Feb 2015
addition of oncolytic vaccinia vaccinia oncolytic of addition extremity sarcoma. Int J Cancer. Cancer. J Int sarcoma. extremity
and Research Fund for two years two for Fund Research and
Hayes AJ, Harrington KJ. The The KJ. Harrington AJ, Hayes survival in a rat model of advanced advanced of model rat a in survival
Lectureship Bull M Lucy Dr
RoulstoneV, Yu YA, Szalay AA, AA, Szalay YA, Yu RoulstoneV, tumour targeting and prolongs prolongs and targeting tumour
FURTHER FUNDING: FUNDING: FURTHER
Khan AA, Mansfield DC, Kyula J, J, Kyula DC, Mansfield AA, Khan
oncolytic vaccinia virus improves improves virus vaccinia oncolytic
2. Wilkinson MJ, Pencavel T, T, Pencavel MJ, Wilkinson 2.
Wilkinson tumour necrosis factor-alpha and and factor-alpha necrosis tumour therapeutic strategies therapeutic
limb perfusion with melphalan, melphalan, with perfusion limb
Therapeutics. Oral Presentation Oral Therapeutics. improve the efficacy of both both of efficacy the improve
Jennifer
Hayes AJ, Harrington KJ. Isolated Isolated KJ. Harrington AJ, Hayes Replicating Oncolytic Virus Virus Oncolytic Replicating to perfusion limb isolated
Aguilar RJ, Chen NG, Szalay AA, AA, Szalay NG, Chen RJ, Aguilar 7th International Meeting on on Meeting International 7th by virotherapy oncolytic of Michelle
Karapanagiotou EM, Roulstone V, V, Roulstone EM, Karapanagiotou 2013, Quebec City, Canada – – Canada City, Quebec 2013, delivery the on presentations
Mansfield DC, Khan AA, Seth R, R, Seth AA, Khan DC, Mansfield and soft tissue sarcoma. June June sarcoma. tissue soft and City, Canada for oral and poster poster and oral for Canada City,
Wilkinson MJ*, Pencavel T*, T*, Pencavel MJ*, Wilkinson to treat extremity melanoma melanoma extremity treat to Virus Therapeutics, Quebec Quebec Therapeutics, Virus
PUBLICATIONS: in combination with radiotherapy, radiotherapy, with combination in Meeting on Replicating Oncolytic Oncolytic Replicating on Meeting
of oncolytic virotherapy, alone and and alone virotherapy, oncolytic of Wuxi APPTEC, 7th International International 7th APPTEC, Wuxi
and The Royal Marsden Hospital Marsden Royal The and
perfusion to assess the efficacy efficacy the assess to perfusion Award: Travel Sponsored
The Institute of Cancer Research Research Cancer of Institute The
clinical model of isolated limb limb isolated of model clinical PRIZES: PRIZES:
SITE OF WORK: WORK: OF SITE
Hayes AJ, Harrington KJ. A pre- A KJ. Harrington AJ, Hayes
Congress Poster Presentation Poster Congress
Roulstone V, Yu YA, Szalay AA, AA, Szalay YA, Yu V, Roulstone Professor Kevin Harrington Kevin Professor
Amsterdam, European Cancer Cancer European Amsterdam,
Khan AA, Mansfield DC, Kyula J, J, Kyula DC, Mansfield AA, Khan SUPERVISORS:
sarcoma. September 2013, 2013, September sarcoma.
T, Pencavel MJ, Wilkinson 1.
model of aggressive extremity extremity aggressive of model Research Fellowship Research
PRESENTATIONS:
delays tumour growth in a rat rat a in growth tumour delays Wolfson Estelle Lady
Jul 22. PMID:24978211 22. Jul perfusion chemotherapeutics chemotherapeutics perfusion and Leonard Lord The
2014 Epub 10.1002/ijc.29059. virus to standard isolated limb limb isolated standard to virus FELLOWSHIP/SPONSOR:
chemotherapy, radiotherapy and surgical resection surgical and radiotherapy chemotherapy,
by isolated limb perfusion, alone and in combination with with combination in and alone perfusion, limb isolated by Pre-clinical evaluation of oncolytic virotherapy delivered delivered virotherapy oncolytic of evaluation Pre-clinical There are 5,000 hospital admissions and 300 deaths from burns in the UK each year.
Investigation of the molecular effects of cooling human burns
FELLOWSHIP/SPONSOR: 2. Guidelines for the excision of 2. A validated human model for Enid Linder Research Fellowship cutaneous squamous cell cancers cooling partial thickness burns, in the United Kingdom: the best EH Wright, D Furniss, AL Harris, SUPERVISORS: cut is the deepest, AA Khan, Society of Academic Research Professors Dominic Furniss M Potter, JJ Cubitt, BJ Khoda, Surgery (SARS) Royal College and Adrian Harris J Smith, EH Wright, G Scerri, of Surgeons of England, SITE OF WORK: A Crick, OC Cassell, PG Budny. 6-7th January 2016 Weatherall Institute of Molecular JPRAS 2013; 66, 467-71 PRIZES: Medicine and Stoke Mandeville PRESENTATIONS: Paton Masser prize by BAPRAS Hospital, Buckinghamshire 1. A validated human model for in May 2016 PUBLICATIONS: cooling partial thickness burns, FURTHER FUNDING: 1. Cooling of Burn Injuries: EH Wright, D Furniss, AL Harris, Restore Burn and Wound Mechanisms and Models, Winter Scientific Meeting of the Research Charity for 1 year EH Wright, AL Harris, D Furniss. British Association of Plastic, Edmund Hugh Burns, 41(5), 882-889 Reconstructive, and Aesthetic Wright Surgeons, Birmingham 25-27th November 2015
Each year in the UK 250,000 people We want to understand burning, and For the first time we have an insight into sustain a burn, 175,000 attend A&E, how cooling benefits burns, and to do so the gene activation in the first few hours 13,000 are admitted to hospital, 1,000 using live human skin normally discarded after burning, and how cooling changes with life-threatening injuries, and 300 during reconstructive breast surgery them. Pharmacological targeting these die of burns. While the majority require in volunteers. We have necessary processes could improve healing and little treatment, and suffer no long-term ethical approval. outcomes for the thousands of burn problems, a significant number require patients every year, who require hospital The burns are created after anaesthesia, surgery, intensive care treatment, admission, surgery, or even die from and half the burns are cooled. Both steps and protracted rehabilitation and their injuries. use novel, purpose-built apparatus, further surgery. giving paired burns from the same People have been treating burns with volunteer in which we can compare the cold water for over 2,000 years, and it effects of burning and cooling. This has is effective in reducing burn damage never been done before. to the skin, scarring, and the need for Cooling reduced the clinical severity skin-grafting. Its mechanism is not fully of the burns, but we were also able to understood, and has been investigated demonstrate a significant reduction in the almost entirely in animals. amount of damage seen in cooled burns, compared to untreated counterparts, with less blockage of the microscopic blood vessels in the skin. Hugh examining a photograph of a Comparison of gene activation in normal microscope section showing a burn blister skin, burns, and cooled burns, showed at three hours after injury. (This has never genes related to heat damage, blood been seen in a human subject before, and clotting, and wounding were significantly represents the basis for the entire project) activated in burns, while those related to normal skin function significantly deactivated. Cooling significantly reversed Hugh discussing the project with HRH the some of these burning-related changes. Duke of Kent, who is the patron of Restore, who funded part of the project
58 Invasiveness of brain metastases and implications for clinical management
FELLOWSHIP/SPONSOR: 2015 Jan;121(2):421-2. doi: PRESENTATIONS: RCS Research Fellowship 10.1007/s11060-014-1642-8. Epub 1. World Federation of 2014 Oct 30. PubMed PMID: Neurosurgical Societies. SUPERVISORS: 25351580; PubMed Central Rome, 2015 Professor Philip Rudland & PMCID: PMC4311059 Mr MD Jenkinson 2. National Cancer Research 2. Zakaria R, Jenkinson MD. Using Institute. Liverpool, 2015 SITE OF WORK: ADC Maps with Structural Scans PRIZES: University of Liverpool & to Improve Intraoperative Biopsy Society of British Neurological The Walton Centre NHS Specimens in Brain Metastases. Surgeons, Sir Hugh Cairns’ Foundation Trust Neuroradiol J. 2014 Sep;27(4):422- Essay Prize 2014 4. doi: 10.15274/NRJ-2014-10075. PUBLICATIONS: Epub 2014 Aug 29. PubMed 1. Zakaria R, Jenkinson MD. FURTHER FUNDING: PMID: 25196614; PubMed Central Diffusion weighted MRI is a The Medical Research Council, PMCID: PMC4236864 promising imaging biomarker in Clinical Research Training Rasheed brain metastases. J Neurooncol Fellowship for two years Zakaria
The brain is a major site of secondary spread for some of the most common cancers like breast, lung and melanoma. The number of people with this spread of cancer to the brain, so-called metastases, is rising and the symptoms, such as weakness, headache and fits have a devastating effect on patients and their carers. Currently there is great uncertainty for patients suffering from brain metastases because we do not have any good markers of prognosis or response to the main treatments: surgery and radiotherapy. Doctors have to estimate how long an individual patient might survive using crude information like age and how many metastases are present. We use these estimates to come Rasheed at a meeting of the Liverpool neuro-oncology patient group – discussing the to a decision about how aggressively to planned research and getting feedback on what issues affect patients and their carers treat our patients, with huge implications Since almost all patients with metastases on particular types of MRI scans, called for their length and quality of survival. undergo an MRI scan of the brain, we are diffusion-weighted scans, are strongly trying to develop markers of prognosis linked to how aggressively the tumour using data from these scans. Next, we behaves and how long a patient survives want to understand what is actually after neurosurgery. Confirmation of happening in the tumour and surrounding such markers would greatly improve the brain tissue that is being measured on quality of life for our patients because we those scans, so we will need to look at could give them a clearer idea – just from samples of brain metastases removed that first MRI scan – of their estimated during neurosurgery. survival and then make better decisions about who should undergo aggressive We have some promising results treatments like surgery and radiotherapy suggesting that changes at the boundary and who may not benefit from this. between the metastasis and the brain
Rasheed at a brain metastases planning workstation theatre
Up to 40% of patients with cancer may develop brain metastases causing significant morbidity and mortality. 59 The Pump Priming award is given to Reports assist newly appointed consultants and senior lecturers (appointed since 2006) in surgery, who are working at hospitals and universities within the UK, in the early stages of their independent research careers. Awards are used exclusively to support the award holder’s own research and not for personal salaries. They may be used, amongst other things, for small items of equipment, for consumables or for technical assistance. All award winners are members or fellows of The Royal College of Surgeons of England.
60 Pump Priming Reports
Aina Greig Siong Seng Liau Sam Oussedik Chris Peach Stuart Smith
61 Over 10,000 children undergo surgery to repair a nail bed injury in the UK every year and this is the commonest hand injury in children.
Nail bed INJury Analysis (NINJA) Pilot Study: Should the nail plate be replaced or discarded after nail bed repair in children?
SPECIALTY: Jonathan Cook, Cushla Cooper, PRESENTATIONS: Plastic Surgery Aina Greig. Pilot and Feasibility 1. Update on the NINJA trial – Studies. 2015, 1:29. DOI: 10.1186/ the first Reconstructive Surgery CURRENT POSITION: s40814-015-0025-z URL: http:// Trials Network trial. Aina Greig, Consultant Plastic Surgeon www.pilotfeasibilitystudies.com/ Abhilash Jain, Dominic Furniss, SITE OF WORK: content/1/1/29 Claire Zweifel, Richard Pinder, Evelina London Children’s 2. Surgical treatment of David Beard, Jonathan Cook, Hospital, Guy’s and St Thomas’ paediatric nail bed injuries in Adam Sierakowski, Matt Gardiner NHS Foundation Trust, London the United Kingdom: Surgeon RSTN Session, BAPRAS, Royal and patient priorities for future College of Surgeons, London, PUBLICATIONS: research. Adam Sierakowski A, 26 November 2014 1. Nail bed INJury Assessment Matthew Gardiner, Abhilash Jain, 2. Update on the NINJA Pilot (NINJA-P) Study: Should Aina Greig; Nail bed INJury trial – follow up. Aina Greig, the nail plate be replaced or Analysis (NINJA) Collaborative Abhilash Jain, Dominic Furniss, discarded after nail bed repair Group. J Plast Reconstr Aesthet Claire Zweifel, Richard Pinder, Aina Greig in children? Study protocol for a Surg. 2016 Feb;69(2):286-8. doi: David Beard, Jonathan Cook, pilot randomised controlled trial. 10.1016/j.bjps.2015.10.025. [Epub Adam Sierakowski, Matt Gardiner Abhilash Jain, Adam Sierakowski, 2015 Oct 30] RSTN Session, BAPRAS, Matthew Gardiner, David Beard, Birmingham, 26 November 2015
The nail bed is the soft area beneath the hard fingernail, and is commonly injured in children. During surgery, the nail is taken off and the cut stitched up. The nail can either be replaced or discarded. Some doctors think that the replaced nail acts as a splint to hold open the nail fold while a new nail grows. Others think that it may cause infections, leading to pain and abnormal nail growth, requiring extra general practice and hospital visits. From our research, children, their parents and carers value most the long- term cosmetic appearance.
A consensus meeting with the British Society for Surgery of the Hand, Royal College of Surgeon, and British Association of Plastic, Reconstructive and Aesthetic Surgeons recognised that the management of nail bed injuries lacked strong clinical evidence. We obtained funding from the BSSH in May 2014 and from the RCS in December 2014, to perform a Pilot Multicentre The nail is regrowing after nail bed repair
62 Aina assessing a child’s finger after nail bed repair in clinic
Randomised Controlled Trial, to assess The pilot trial showed the feasibility of the practicalities of running a trial that timely recruitment to a larger study. addresses the question ‘Should the nail A definitive trial is required to confirm a plate be replaced or discarded after nail possible benefit from replacing the nail bed repair in children?’ (NINJA-P). plate, specifically whether there is any The Co-Chief Investigators (Aina Greig difference in appearance or infection and Abhilash Jain) engaged with Oxford rate. We have worked with the Research Surgical Intervention Trials Unit to Design Service to host a focus group undertake project management. (six parents, one toddler) to discuss the The NINJA-P trial: full study plan with Patient and Public Involvement. Two ‘lay applicants’ have • Was the first trial chosen to be been included on the grant application supported by the Reconstructive to perform a definitive trial with a larger Surgery Trials Network (RSTN) study population. An application for • Was adopted onto the NIHR Clinical funding for a NIHR Research for Patient Research Network Portfolio Benefit Grant has been submitted March 2016. • Recruited 60 patients in three months Successful nail bed repair in a child
• Across four centres (GSTT, Hull, Oxford, Chelmsford)
• Followed-up patients up for four months
63 Pancreatic cancer (UK incidence ~9000 per year) urgently requires new therapies as <10% of these patients survive for five years.
A novel model of familial pancreatic cancer to explore genomic instability as a mechanism for pancreatic tumourigenesis
SPECIALTY: HPB (Hepatopancreatobiliary) Surgery CURRENT POSITION: Honorary Consultant Hepatobiliary and Pancreatic Surgeon SITE OF WORK: University Department of Surgery, University of Cambridge, Addenbrooke’s Hospital
Siong S. Liau
Pancreatic ductal adenocarcinoma (PDA) is a uniformly lethal disease with the overall five-year survival rate of less than 5%. There is an urgent need for better treatment and this is unlikely to come from surgical treatment alone.
The aggressive biology coupled with the genetic complexity of PDA makes this disease difficult to treat. It is clear that approximately 10-15% of patients with PDAs have a hereditary component (i.e. inherited a defective gene). One of these potential genes is the partner and localiser of BRCA2 (PALB2) gene, which is a gene involved in DNA repair process. In this study, we have successfully developed novel genetically-engineered mouse models (GEMMs) of PALB2 in pancreatic ductal adenocarcinoma.
Our results have shown that PALB2 is a gene critical in the development of PDA. These GEMMs develop PDA with a similar disease spectrum to humans. The impact of the findings of this model is Siong performing a Whipple’s pancreaticoduodenectomy obvious as for the first time we are able to PALB2 GEMMs will provide unequivocal PDAs and finally, the GEMM will understand the biological impact of such evidence for the roles of PALB2 as a represent an efficient resource for a genetic mutation on pancreatic cancer major genetic player in PDA formation, future testing of identified PALB2- development. More importantly, we will speed up the process of personalised related targeted therapies. be able to test and personalise therapy drug discovery for PALB2-mutated for PDA with specific PALB2 mutations.
64 Can adipose derived vascular fraction, extracted from adipose tissue prevent osteoarthritis of the knee?
SPECIALTY: Trauma and Orthopaedics CURRENT POSITION: Consultant Orthopaedic Surgeon SITE OF WORK: University College Hospital, London
Sam Oussedik
Knee osteoarthritis has a colossal questionnaires over the course of disease burden. The evidence 12 months. The study seeks to take describes the lifetime risk of developing advantage of DGEMRIC technology, symptomatic knee osteoarthritis is 50%, a distinctive form of an MRI scan. with 50% developing before age 55. In the ADVENT study, DGEMRIC will The corresponding burden on knee be used to establish cartilage loss and replacement surgery is equally massive osteoarthritis progression and whether with estimates suggesting the incidence the stem cells can arrest or reverse of total knee replacement will rise to 1.2 progression of osteoarthritis. and 3.4 million patients in the UK and We have identified our patient cohort for the US respectively by the year 2030. the study and have submitted an ethics Treatment options at present are limited, application for review, for which we await advising activity avoidance, analgesia or a decision. We have also sought an locally acting steroid injections whilst additional research grant to cover some those with symptomatic osteoarthritis of the study costs. Additionally, we are are counselled regarding surgery. also seeking to set up a randomised controlled trial in which we will compare Many patients may have pain which the stem cell treatment to a placebo in cannot be controlled by medication but patients with arthritis of both knees. unfortunately they are not suitable for surgery owing to a myriad of reasons. The research concerns a very novel therapy, with the use of innovative MRI Our study evaluates the use of stem imaging, which can have far reaching cells, harvested from the fat cells of the implications for the significant problem patient’s body. After preparation, these of the treatment of knee osteoarthritis, stem cells are injected into the patient’s addressing the problem of young people affected knee on a one-off basis. Our with knee arthritis, whilst also relieving the aim is to establish whether there are any X-rays demonstrating arthritis of the knee, burden on the knee replacement surgeon clinical or radiological improvements, in two views, characterised by joint space and hospital services. evaluated according to patient’s outcome narrowing and the formation of bony spurs
The lifetime risk of developing symptomatic knee osteoarthritis is 50%, with 50% developing before age 55.
65 15% of planned orthopaedic operations are for removal of metallic implants which can be associated with significant side effects. Bioresorbable implants will prevent the need for further surgical procedures.
OsteoFix: novel bioresorbable composite implants for osteoporotic bone fixation
SPECIALTY: accelerated environment for bone PRESENTATIONS: Trauma and Orthopaedic Surgery fixation application. Proceedings 1. Novel biodegradable and of the 2016 Industrial and Systems bioactive implants for fracture CURRENT POSITION: Engineering Research Conference, fixation. Altamimi, A.A, Peach Consultant Trauma and edited by Y. Guan and H. Liao, C., Domingos, M., Bartolo, Orthopaedic Surgeon Anaheim, USA, 2016 P.J. Industrial & Systems SITE OF WORK: 2. Altamimi, A.A., Peach, C., Engineering Research Manchester Biomanufacturing Domingos, M., Bartolo, Conference (ISERC) 2016, Centre, School of Mechanical, P.J. Degradable vs. non-degradable Anaheim, California, USA Aerospace and Civil Engineering, bone fixation implants: a 2. Novel biodegradable and University of Manchester computational study. Proceedings bioactive implants for fracture of the 2nd International fixation. Altamimi, A.A, Peach PUBLICATIONS: Conference on Progress in C., Domingos, M., Bartolo, 1. Altamimi, A.A, Peach C., Additive Manufacturing (PRO-AM P.J. International Conference Domingos, M., Bartolo, P.J. The 2016). Edited by C.C. Kai et al. on Biofabrication. Utrecht, Chris Peach evaluation of Poly(e-caprolactone) Research Publishing, 2016 Netherlands. Nov 7-9th 2015 degradation kinetics in an
The aim of this research was to A common surgical procedure inserts develop a customised, biocompatible, metallic plates which act as fracture bioresorbable and bioactive bone stabilisers to enable bone healing. fracture fixation implant that is capable There is substantial evidence of implant of replacing current metallic implants. failure in osteoporotic patients as well as implants frequently needing It is estimated that 27.5 million people in removal. Approximately 15% of planned the European Union have osteoporosis, orthopaedic operations are for removal of a condition that resulting in low-density metallic implants. Over 80% of patients, bones with poor mechanical properties when questioned, would like to be leading to fractures. The annual cost considered for a bioresorbable implant of treating these fractures in the EU or be involved in a trial to evaluate one. will rise to an estimated £60 billion However, surgeons have had concerns From right to left: Professor Paulo Bartolo, per year by 2025. over the potential inferior biomechanical Chris Peach and Abdulsalam Abdulaziz characteristics, consequences of implant Al-Tamimi with new equipment purchased degradation in addition to higher implant for research projects from pump priming costs with bioabsorbable materials. grant from the RCS
Therefore our research focuses on the these initial studies we have been able development of bioresorbable implants to select a suitable material and plate for fracture fixation surgery which would design for further evaluation and testing. prevent the need for implant removal and These preliminary studies have enabled develop technology to make these plates us to apply for larger grants to allow us bioactive, being capable of delivering to continue these exciting investigations osteoporosis treating medications to which will hopefully culminate in clinical the immediate area. testing. Further work includes topological optimisation of current implants to Mr Chris Peach discussing the need for Our main investigations to date have develop design parameters, finite removal of metalwork from the shoulder evaluated the biomechanical and element models of degradation and after fracture treatment with patient at the biological characteristics of Poly biomechanical characteristics of new University Hospital of South Manchester (ε-CaproLactone) (PCL), Hydroxyapatite material designs. and Magnesium as novel materials for implant manufacturing. Based on
66 Evaluating the efficacy of PLGA/PEG chemotherapy delivery into the surgical cavity using an orthotopic brain tumour resection model
SPECIALTY: vivo effects against glioblastoma 2. Smith SJ, Kelly JC, Gould Neurosurgery Annals of the Royal College of T, Rahman R Incorporation of Surgeons 2014;96:495-50 nanoparticle conjugated peptides CURRENT POSITION: into a moldable neurosurgcially Clinical Associate Professor PRESENTATIONS: applied polymer paste as a of Neurosurgery 1. Smith SJ, Gould TW, Barrett localised dual-layered therapeutic DA, Shakesheff KM, Grundy RG, SITE OF WORK: strategy for malignant glioma Rahman R Delivery of multiple Children’s Brain Tumour Research Poster SCIDOT San Antonio, chemotherapeutic agents into Centre, University of Nottingham USA 2015 rodent brain using a biodegradable PUBLICATIONS: and self-sintering PLGA/PEG FURTHER FUNDING: Surgical delivery of drug releasing neurosurgical system Poster Hermes Enterprise Fellowship poly(lactic-co-glycolic acid)/ SCIDOT San Antonio, USA 2015 for one year poly(ethylene glycol) paste with in Stuart Smith
Malignant brain cancer kills 3500 people of a biodegradable paste that can be in the speed of tumour growth. This per year in the UK, of all ages, causing surgically implanted by the neurosurgeon is an ongoing project that involves the highest number of cancer-related during resection of a brain tumour. The collaborations between many different deaths in the under 40s. Neurosurgery paste then gradually dissolves, releasing scientific and clinical teams, including augmented by radiotherapy and chemotherapy directly into the brain the surgical research group, which I lead. chemotherapy is only partially effective where it can act to kill cancer cells, whilst We continue to fine tune the paste to and most patients die within 18 months also avoiding toxic side effects from the achieve the maximal release of drug and of diagnosis. drug in other parts of the body e.g. the to study which might be the best drugs to bowel or bone marrow. deliver to the brain using this technology. Preparations are underway to develop The funding provided has allowed us the paste to a point where it can be to use the paste within a tumour model used in a trial in brain tumour patients, of the malignant brain cancer. Initial where we hope it will extend life for those results have been very promising and suffering from this terrible disease. we have seen significant reductions
Neurosurgical resection of a malignant brain tumour
Chemotherapy drugs penetrate poorly into the brain because of a natural block called the blood brain barrier. Direct implantation of chemotherapy releasing material at surgery can bypass the blockade, allowing the drugs to better kill tumour cells, whilst minimising side effects for the patient. This project has aimed to further the development Stuart in the laboratory placing tumour cell samples into liquid nitrogen for storage
Malignant brain tumour survival is poor, surgical delivery of drugs to the brain will help by getting. chemotherapy to the growing tumour. 67 Surgical Trials Initiative
Surgical Trials Initiative The programme has far exceeded expectations in the four years since it was launched, with seven Surgical Trials Centres (STC) and ten Surgical Specialty Leads (SSL) now working on developing and delivering high-quality randomised trials across all specialties. The work of STCs and SSLs in conjunction with regional research collaboratives means support is provided for feasibility, pilot and safety studies, which often lead to randomised clinical trials.
The success of the initiative is down to the hard work of the STCs and SSLs as well as the generous support received from Rosetrees Trust, as well as other Jane Blazeby (Bristol STC director) training trainees on how to recruit patients on to trials, charities and surgical societies. as part of the BOSTIC workshops run jointly by Oxford and Bristol
researchers attending from across • The Surgical Technology Evaluation Update the globe and work is under way Portal will be further promoted • The joint trials portfolio of the seven to launch an international network and targeted communications to Surgical Trials Centres has a total across three globes; Europe, UK-based SMEs will be distributed. of 85 clinical trials, of these 42 are America and Australasia. Plans for specialty-specific events between SMEs and clinical open and recruiting patients, 34 • Joint RCS/Royal College of researchers from RCS/NIHR are in follow-up and a further nine Anaesthetists applications to infrastructures are being developed, trials have completed follow-up. carry out perioperative systematic to assist SMEs in developing their The STCs also have 35 trials reviews were advertised and four ideas efficiently for patient benefit. which are currently in ‘set-up’ successful teams, led by trainees, and are being developed. were selected. These teams have • Following the first meeting to • A total of over 25,000 patients joined the already existing evidence discuss launching an RCS have been recruited to this joint synthesis groups who are working International Surgical Trials portfolio for trials in the ten different with the Clinical Effectiveness Unit at Network in June, further meetings specialties. On average patients are the RCS, to carry out these reviews. with the American and Australasian being recruited from 14 hospitals, Colleges have taken place and plans with an average of 15 investigators Plans are progressing. (surgeons, trainees) working on • There is grEeat interest from surgical each trial. • To further encourage the development of clinical trials and the specialty associations regarding • The RCS/NIHR Surgical Technology initiative as a whole, the RCS the creation of new SSL posts in Evaluation Portal completed is raising funds to recruit professorial specialties not currently represented a successful pilot where eight chairs in surgical clinical research at in the initiative. Following further applications from SMEs were Universities hosting RCS Surgical discussions, an advertisement will processed. The portal was launched Trials Centres. These posts will be be placed for the roles in 2017. by George Freeman MP at the jointly funded for a period of four NIHR ten-year anniversary event years, after this period the funding in May 2016. will be covered by the University • The first RCS International Surgical partner, alone. The first of these Trials Network meeting was held chairs will be advertised and in June 2016, with 50 surgical appointed in the first half of 2017. 68 The views of a Surgical trials are viewed. In the near future this The Oxford Surgical Interventional Trials Trials Centre Director – teaching package (and the RCS badge) Unit (SITU) maintains a spearheading Professor David Beard will be projected onto the international and innovative role in the RCS initiative. stage. New consultants are coming With our registered trial unit partnerships In its fourth year since inception through with a knowledge and thirst (with OCTRU and CSM) and continued The Royal College of Surgeons clinical for evaluation. Imparting this knowledge collaboration with other units, we hope to trials initiative is enjoying developmental has been rewarding and fun, especially make a substantial impact on the world stability alongside sustainable growth. to the many and varied surgical of surgical evaluation. The focus has The initiative’s impact on surgical speciality groups. changed from development to output and research is becoming ever-more sustainability. The vision is that within ten On that note the role of the RCS Surgical evident and important. years surgical trials will have caught up Specialty Leads (SSLs) has consolidated (and perhaps exceeded in some ways) and they are effectively prioritising the our pharmacological counterparts. There best projects to portal through to the has never been a more exciting time to surgical centres. This increased maturity be involved in surgical science and the has created efficiencies within the evaluation of surgical treatment. system. Only the best and truly fundable trials attract attention and resources. 1. Use of a modified Delphi approach The linkages have also facilitated to develop research priorities for the Association of Coloproctology of Great the growth of a national surgical Britain and Ireland. Tiernan J, Cook trials network that is both active and A, Geh I, et al. Colorectal Disease. influential. We hope the enthusiasm 2014;16(12):965-970. doi:10.1111/ and effective SSL input will continue. codi.12790 2. A national patient and public colorectal With regard to specific topics, there research agenda: Integration of have been advances in many areas, consumer perspectives in bowel especially in methodology and design; disease through early consultation. how to deal with waiting lists; the ethical McNair AGK, Heywood N, Tiernan J, Verjee A, Bach SP, Fearnhead NS. and design challenges of placebo control On behalf of ORACLE Collaboration. groups; the utilisation of qualitative Colorectal Disease Accepted Author research; standardisation of treatment Manuscript. doi:10.1111/codi.13564 In times of evidence-based medicine, and the further efforts into delineating limited resources and the increasing the need and positioning of pilot and demand to show value for money, let feasibility studies. alone efficacy, the field of surgery was There is more collaboration at higher in clear need of a strong policy on levels and the surgical research evaluation. The surgical community sadly community has substantial visibility at still lags well behind pharmacological the international and national clinical intervention in terms of formal and trials conferences. The suggestion that rigorous assessment of the treatments the UK is currently an international provided. The RCS Surgical Research leader of surgical trial research would be Committee has stepped up to the plate not be outlandish. The international push and laudably (and audibly, cf. Professor has resulted in several new international D Morton) grasped this thorn. It has set collaborations and trials being funded, about putting real effort into promoting all evidenced at the recent International and facilitating surgical research. The Trials Day at the Royal College. response, including the initiation and continued support of the What comes next? five original Surgical Trials Centres, We need to sustain the new culture now joined by York and Leeds, has throughout the whole of surgical been hugely successful. sciences and begin to consider sub In the last few years we have seen speciality division. Some specialities exceptional output from all centres. already enjoy an established research Success in funding trials has risen and trials platform. Others will benefit and the original quizzical looks from further support and attention. There generated from submissions involving are several sub specialities that are surgical intervention have been replaced only just setting out on their journey of by understanding and respect. The evaluation. The incorporation of corollary advent and success of several new initiatives such as IDEAL, COMET training courses for surgical trainees and the increasing importance of (including our own BOSTIC course qualitative research will help the cause. with our close colleagues in Bristol) We hope no stone of surgical practice is changing the face of how surgical will remain unturned. Why we do research
69
The views of a Surgical Specialty Lead – Mr Simon Bach.
The first Surgical Sandpit, Sheffield 2013
Three years ago, possibly four, I sat the notion of holding meetings where six themed trials workshops at RCS down with colleagues and discussed attendees were charged with providing all with 170 delegates drawn from diverse how we might do more to promote content while facilitators kept proceedings backgrounds including patients, charity high-quality, patient-centred research on track. I also thought that research representatives, patient associations, in our subspecialty. We contemplated should be inspiring, even fun. We clinical academics, NHS clinicians and a framework that would help promote devised an iterative programme of group nursing staff. The response from the the latent talent of fellow clinicians, working that began by brainstorming, community has been tremendous and I trainees and students, identify new followed by prioritisation of ideas, through thank all of those who have taken part, strategies to improve patient care, and to development and presentation of especially the trainees who have worked assemble teams capable of delivering fledgling research schemes. The event hard to support patient events. Hopefully this work. These discussions coincided was supported by experienced surgical they have enjoyed the experience as with my appointment as RCS colorectal trialists (David Jayne and Dion Morton) much as I have. subspecialty lead and the provision of as well as enthusiastic methodologists The Bowel Disease Research foundation flexible funding to launch the initiative. from the Birmingham Clinical Trials Unit have been utterly fantastic and trustees Key alliances were formed with our (Laura Magill). It is perhaps poignant that have attended every Delphi event. professional association the ACPGBI I am writing this review while travelling (Nicola Fearnhead), trainee collaborative back from the NIHR HTA, PREPARE networks (so many inspiring individuals) ABC launch meeting, hosted by James and the Bowel Disease Research Hernon at RCS. This prehabilitation study Foundation Charity (Azmina Verjee, was conceived at the very first ‘Surgical John Northover and Asha Senapati). Sandpit’ event and grew from there. The RCS became an excellent base Buoyed by the feedback received from for our subsequent exploits. our first outing, and convinced that this was a winning formula, we set about delivering an ambitious plan to promote wider engagement in surgical research Delphi Games icebreaker, RCS 2016 amongst clinicians and patients. The Delphi format was born or rather They were quick to recognise the borrowed. We conducted a Delphi research mandate provided by this Exercise of the ACPGBI membership to initiative and have focused their funding determine research priorities, created strategy for 2016 upon answering Delphi the Oracle of Delphi to learn what questions. This year nine Delphi projects patients thought, appointed over 70 received pump priming funding from The Oracle of Delphi deep discussion, Delphi Champions, and held the RCS the BDRF, while more substantial funds RCS 2015 Delphi Games, which were themed were allocated to run the HiP study trials workshops similar in format to (Dale Vimalchandran). BDRF have also Our first meeting took place in Oct the original ‘sandpit’ event where our supported GRANULE (Aneel Bhangu 2013 in Sheffield. We christened it the Champions met to formulate and grow and Simon Bach) a practical workshop ‘Surgical Sandpit’ a euphemism for their plans. In two years, we have run for medical students that teaches how stripping away inhibitions and playing three patient and public events capturing to approach recruitment of patients into with new ideas. I was attracted to the views of over 400 participants, and randomised trials; expertly supported by
70 Jane Blazeby and staff from the MRC GlobalSurg: building a In an effort to build capacity, GlobalSurg Methodology Hub in Bristol. The NIHR platform for high quality will develop a range of overseas ‘Hubs’ have already funded three major Delphi global research in surgery that will coordinate local project delivery initiatives, PREPARE ABC (James and scientific strategy through smaller Hernon), CIPER (Neil Smart) and LEGO and rural ‘Spoke’ hospitals. The Hubs (Hugh Paterson). Cancer Research UK By Aneel Bhangu & James Glaseby will vary in size and capacity according have funded the international STAR- Supported by the RCS, GlobalSurg is to need, with some running within their TREC study exploring organ-sparing an international collaboration of surgical own country and some into neighbouring treatment for early rectal cancer (Simon researchers aiming to give grass-root countries. A Global Surgery Policy Bach and David Sebag-Montefiore). surgeons in low and middle income Consortium will be convened by our External Advisory Board, supported I will end by saying how much I have countries (LMIC) the opportunity to by the Royal College of Surgeons of enjoyed this process, meeting patients participate in major projects. The England, to create guidelines and guide and having them help design studies wider research network now includes policy. These will be used to impact on from the ground up has been a over 3000 clinicians in more than 60 the wider collaborative of over 400 revelation. Similarly, the practical training countries. The project is continuing its LMIC hospitals. for medical students will hopefully efforts to develop international surgical signpost surgery as a forward looking research, relevant to low and middle- The GlobalSurg scientific strategy is and creative career choice. I thank all of income countries, by establishing centred around a four-step Prioritisation you who have taken part and encourage sustainable overseas research Hubs. Cycle. These cycles will be led by those of you who have not to come along GlobalSurg is extending its platform to LMIC Hubs: in 2017. deliver prioritisation cycles and clinical 1. Workshops, to identify and plan research for surgical innovation in low research to be conducted across and middle income countries. This the network. will enable leadership of GlobalSurg to be transferred from the UK into 2. Information Gathering, including a sustainable low-middle income feasibility studies and analysis country-(LMIC) led structure, capable of ‘big data.’ of delivering high-quality interventional, observational and health service 3. Evidence Generation, through delivery research. randomised trials. 4. Sustainability, through long-term funding, training, and policy formation.
Want to read more? Visit www.globalsurg.org, or contact us at [email protected]
Research fellowships and opportunities now available.
GlobalSurg launch meeting in Birmingham attended by 60 medical professionals including 25 surgeons from 12 countries. (Right) Professor Chris Lavy and Murat Akkulak at the launch of the meeting. (Left) Group sessions at the meeting
71 Clinical Effectiveness Unit David Cromwell
Professor David Cromwell Director of the CEU
The Clinical Effectiveness Unit (CEU) is Audit and research approach, and proposed as a new an academic collaboration between the measure the proportion of women who College and the Department of Health The core activity of the CEU is to conduct have retained a breast (either through Services Research and Policy within the national clinical audits and research conserving surgery or reconstruction) London School of Hygiene and Tropical projects. Many of the national audits four years from the date of initial breast Medicine (LSHTM). Since its creation in form part of the Government’s National cancer surgery. 1998, it has become a national centre Clinical Audit and Patient Outcomes This novel measure provided a fresh of expertise on conducting large-scale Programme (NCAPOP), which is playing insight into the patterns of breast cancer studies into the quality of surgical care, an increasingly important role in the surgery. Using data from 2008 and 2009, something that has been built on its Government’s strategy to improve the the project revealed that the proportion multi-disciplinary approach and its outcome of secondary care. The CEU of women with a breast at four years was close relationship with the College and is conducting national clinical audits in strongly related to their characteristics. Specialty Associations. Another key bowel cancer, oesophago-gastric cancer, Among women under 70 years who element of its success has been its ability prostate cancer, and vascular surgery, had no medical conditions apart from to give opportunities to surgical trainees as well as supporting others such as the their breast cancer, the proportion was to work on national studies and enrol national emergency laparotomy audit. 79.3%. But, for women aged 70 or over, in higher research degrees. The CEU The CEU has also been undertaking work it was only 52.6%. If women had other currently has four trainees among its on the quality of surgical care delivered conditions, the figures in each age group 20 staff members. to breast cancer patients. The ‘Breast were lower again. The proportion with a Cancer Outcomes project’ uses data on breast at four years was 64.0% in women activity within English NHS hospitals to under 70 years with comorbid conditions examine the patterns and outcomes of and 38.2% in women aged 70 and over. surgery among women having breast These differences did not seem to be conserving surgery, mastectomy, and solely a reflection of a woman’s fitness breast reconstruction procedures. The for surgery or her preferences because majority of the research was carried out the proportions within each group varied by Ms Jo Mennie, a surgical trainee, with across regions within England (the support from the Association of Breast highest and lowest regions differed by at Surgery, British Association of Plastic, least 15% for all four groups) and regions Reconstructive and Aesthetic Surgeons tended to have high or low proportions (BAPRAS) and was part-funded by consistently across all four patient groups. Johnson & Johnson. This breast cancer project was A particular focus of this work has stimulated by the work that the CEU been to develop ways of describing undertook on the Mastectomy and Breast Kate Walker and Angela Kuryba from CEU the care pathway followed by women Reconstruction Audit between 2007 and with Professor Ian Bissett, a colorectal with breast cancer, given the multiple 2011. It also played an important role surgeon visiting from the University of potential options women have in breast in us successfully bidding for the new Auckland to discuss bowel cancer research cancer treatment. As part of this, Jo national clinical audit of breast cancer identified that current studies have in older patients with the Association of tended to examine one type of surgical Breast Surgery. This clinical audit began procedure, which leads to only a partial in April 2016. Jo Mennie gained her PhD understanding of this complex clinical in October 2016. practice. Consequently, she aimed to describe the patterns of breast cancer A brief description of other major CEU surgery using a more comprehensive projects undertaken in 2015-16 is given in Box 1.
72 Box 1: Major CEU projects undertaken in 2015-16
National Bowel Cancer Audit The audit has been reporting on the care delivered to patients with bowel cancer, and the outcomes of treatment, since 2002. The audit is delivered with the Association of Coloproctology of Great Britain and Ireland and NHS Digital.
National Prostate Cancer Audit This is the first national clinical audit of the care that men receive following a diagnosis of prostate cancer. The audit is managed as a partnership between a team of clinical, cancer information and audit experts from the British Association of Urological Surgeons, the British Uro-oncology Group, the National Cancer Registration Service and the CEU.
National Oesophago-Gastric Cancer Audit This audit has been running since 2011 providing information on the care delivered to patients with cancer of the oesophagus or stomach. It is being carried out in partnership with the Association of Upper Gastrointestinal Surgeons, the British Society of Gastroenterology, the Royal College of Radiology, and NHS Digital.
National Audit of Breast Cancer in Older Patients The CEU, in collaboration with the Association of Breast Surgery, began this audit in April 2016. It will investigate why older women with breast cancer appear to have worse outcomes than younger women. The patterns of breast cancer care received by women aged 70 years and over will be compared with the care given to women diagnosed aged 50-69 years.
CRANE Database This is a registry of all children born with cleft lips and palates in England, Wales and Northern Ireland, their treatment and the outcomes. The CEU has been the host organisation for this registry since April 2005.
National Vascular Registry The National Vascular Registry reports on the process of care and outcomes among patients who undergoing major vascular surgery, including the repair of abdominal aortic aneurysm, and lower limb bypass and amputation. It is run in partnership with the Vascular Society of Great Britain and Ireland.
73 20 years of the RCS Surgical that directly involved patients. During the for ongoing research. Among trainees Research Fellowship Scheme fellowship, almost all respondents had who received their award between 1993 enrolled in a higher degree (MD or PHD) and 2003, over 90% have become The RCS Research Fellowship scheme and the completion rate has been very consultants, and a quarter of respondents was established in 1993 to give medical high. Among those who had a Fellowship are currently in academic posts. trainees an opportunity to undertake in the first 15 years of the Scheme, 91% The RCS Fellowship scheme has played research on a surgical topic. Since then, of responders had successfully obtained a significant role in the funding and between 20 and 30 one-year Fellowships their degree. delivery of surgical research. It needs to have been offered annually, with the The research undertaken during the be remembered that an article in 2008 addition of a small number of two to Fellowships had led to numerous peer- described the UK academic cancer three-year awards that have tended to reviewed publications and conference surgeon as ‘an endangered species’, be awarded jointly with other research presentations, with a typical recipient and in recent years, less than 2% of funding bodies. publishing between two to five peer- the UK’s medical research funding was In 2015, the CEU and Research reviewed articles during their Fellowship awarded to surgery-based projects. Department surveyed the 502 surgeons and presenting three to six times at The positive responses from Fellowship who had received awards between national or international conferences. recipients shows that the value of the The survey respondents supplied Scheme to trainees and how it supports 1993 and 2013, to discover what the information on 527 scientific articles the development of clinicians with the Fellowships had enabled the trainees (limited to a maximum of three citations necessary skills to support medical to achieve and how their career had per respondent), many of which had been research in this country. then developed. published in journals with high impact The Fellowships were typically awarded factors. The three most common journals Teaching to trainees in their late 20s/early 30s. were the British Journal of Surgery The CEU runs a number of courses The majority of those aged under 30 had (38 articles), British Journal of Cancer for surgeons and other health care not started Specialty Training when they (22), and the Journal of Bone and Joint professionals on statistics, clinical began their Fellowship, whereas most Surgery (14). A small number of articles research methods and evidence-based responders aged 32 or over had. had appeared in major international surgery. The courses use a mixture of journals, including Science, the Lancet teaching methods ranging from lectures The survey responders had undertaken and British Medical Journal. to interactive seminars and hands-on a broad array of research topics: 62% computer practicals. Course faculty often of Fellowship recipients had undertaken Respondents were also positive about the includes methodologists recruited from laboratory-based basic research, while Fellowship scheme had facilitated both CEU staff as well as senior clinicians with another 17% had focused their research their clinical and academic career, with a strong interest in research and audit. on new surgical techniques or practice 60% going on to secure further funding
David Cromwell with Anne Jones and Kate Lyons of the Clinical Audit and Effectiveness Dept, Kingston Hospital, who spoke to staff in CEU about how they manage the national clinical audit programme in an acute trust
74 Mathew Parry and Arun Sujenthiran, Research Fellows at the CEU office
Selected publications by CEU 3. Chadwick, G.; Groene, O.; Riley, 6. Loftus IM, Paraskevas KI, Johal A, staff in 2015 and 2016 S.; Hardwick, R.; Crosby, T.; Hoare, Waton S, Heikkila K, Naylor AR, J.; Hanna, G.B.; Greenaway, K.; Cromwell DA. Delays to Surgery 1. Neuburger, J. ; Currie, C. ; Cromwell, D.A.; Gastric Cancers and Procedural Risks Following Wakeman, R. ; Tsang, C. ; Plant, F. ; Missed During Endoscopy in Carotid Endarterectomy in the De Stavola, B. ; Cromwell, D.A. ; England. Clin Gastroenterol Hepatol UK National Vascular Registry. van der Meulen, J. ; The Impact of a (2015) 13(7):1264-1270.e1 Eur J Vasc Endovasc Surg. 2016; National Clinician-led Audit Initiative 52(4):438-443 on Care and Mortality after Hip 4. Walker, K.; Kuryba, A.; Scott, Fracture in England: An External N.; van der Meulen, J. Regional 7. Mennie JC, Mohanna PN, Evaluation using Time Trends in variation in length of hospital stay O’Donoghue JM, Rainsbury R, Non-audit Data. Med Care (2015) after major surgery for colorectal Cromwell DA. The Proportion of 53(8):686-691 cancer European Journal of Cancer Women Who Have a Breast 4 Years Care (2015) 24:19-20 after Breast Cancer Surgery: A 2. Tovikkai, C. ; Charman, S.C. ; Population-Based Cohort Study. 5. Aggarwal A, Cathcart P, Payne Praseedom, R.K. ; Gimson, A.E. ; PLoS One. 2016; 11(5): e0153704 van der Meulen, J. ; Time-varying H, Neal D, Rashbass J, Nossiter impact of comorbidities on mortality J, van der Meulen J. The National 8. Shalhoub J, Cromwell D, Coomer after liver transplantation: a national Prostate Cancer Audit - introducing M, Alderson D. The impact of cohort study using linked clinical a new generation of cancer audit. The Royal College of Surgeons and administrative data. BMJ Open Clin Oncol (R Coll Radiol). 2014 of England research fellowship (2015) 5(5):e006971 Feb;26(2):90-3 scheme. Ann R Coll Surg Engl. 2016 Jul; 98(6):431-5
75 Research in the Faculty of Dental Surgery
By Professor Paul Speight, FDS Research Chair
Throughout our history the Faculty nine recipients of research fellowships Society, British Society of Paediatric of Dental Surgery has been active and 31 small grants have been awarded. Dentistry and British Association for in research into the causes and Two PhD fellowships have also been the Study of Community Dentistry and management of oral and dental awarded in partnership with the the British Society of Periodontology. diseases. In the early days this was Wellcome Trust. Our awards primarily Together we have awarded a number carried out in the College in the support clinical trainees to obtain of grants to help improve the status of Department of Dental Science. This research experience and the fellowships children’s oral health in the UK. This has included seminal and pioneering allow them to take time out of clinical included studies to explore how children research into the development of a training to study towards a PhD. Among and their families can become more caries vaccine, which was carried out our recipients, 15 have now obtained involved in their own care, investigations at Buckston Browne Farm at Downe in senior positions in Universities or the of the outcomes and acceptability of Kent. In 1996, when the College sold NHS and at least three have become orthodontic treatments and studies of the farm the Department closed and professors in their clinical specialties. tissue engineering in the management research was no longer conducted at of facial deformities. Projects supported by the Faculty the College. However, the endowed have covered all areas of oral and Case studies of some of our funds were still available and the dental research including oral cancer, successful Fellows: Faculty decided to use these to promote craniofacial abnormalities, periodontal oral and dental research through the diseases and facial pain. Recently award of grants and fellowships. the Faculty has debated the concerns Since 2008 the Faculty has distributed around the poor oral health of children almost £1.5 million to support research and to this end we have formed across the country. There have been partnerships with the British Orthodontic
Projects supported by the Faculty have covered all areas of oral and dental research including oral cancer, craniofacial abnormalities, periodontal diseases and facial pain.
76 Development of a web-based version of the Children’s Experience of Dental Anxiety Measure for clinical assessment
Annie held a Faculty Fellowship in clinical setting on a tablet device. 2015, whilst she was in her first year as With software engineers, she pilot a substantive consultant in Paediatric tested the eCEDAM with children, Dentistry in Sheffield. As part of her using their opinions and ideas to PhD research Annie had interviewed guide its development. The validity children to explore their experiences and usability of the eCEDAM has of dental anxiety and, with a team of also been evaluated in a randomised experts that included psychologists, trial of 100 children comparing the contributed to the development of a new eCEDAM to conventional paper-based Patient Reported Outcome Measure questionnaires. This important work for childhood dental anxiety called the gives children a voice in their own care, Children’s Experience of Dental Anxiety allows clinicians to properly assess and Measure (CEDAM). The award of the manage dental anxiety in their young Fellowship allowed Annie to take time patients, and will have uses in research out of her consultant role to develop and to evaluate treatment approaches and test an electronic version of the CEDAM to inform the development of similar (eCEDAM), foruse as a web-based measures in other dental specialties. application that children could use in a Annie Morgan – Sheffield
The epigenetics of HPV16- mediated oral & oropharyngeal squamous cell carcinoma
Andrew was awarded the inaugural Institute (NCRI) and the Paul Toller FDS-Wellcome Trust Fellowship in Research Prize on two separate 2010, allowing him to take time out from occasions from the British Association of his higher surgical training in Oral and Oral & Maxillofacial Surgeons (BAOMS). Maxillofacial Surgery. This allowed him Andrew completed his research and to work full time as a Clinical Research was awarded his PhD in 2013 and Fellow at the University of Liverpool has subsequently presented his work and to study for his PhD in molecular at several national and international oncology. His research was focused on conferences and has published widely, oropharyngeal cancer (OPC), and its including six peer-reviewed publications association with human papillomavirus resulting directly from this Fellowship. (HPV). The main aim of his work was to clarify the epigenetic alterations that Andrew also completed his clinical occur in HPV-positive OPC, and the training in 2013, and was awarded the potential mechanisms through which the Gold Medal for his performance in the virus may cause this disease. First, he Intercollegiate FRCS Examination. He evaluated the prevalence of HPV infection is currently a Senior Clinical Lecturer in in OPC and developed valid diagnostic Head & Neck Surgery at the University tests for HPV detection in lesions. of Liverpool and is a Consultant Oral He then undertook an analysis of the and Maxillofacial Surgeon in the epigenetic changes found in HPV-driven internationally renowned Head & Neck cancer samples and cell lines. Unit at Aintree University Hospital. Andrew Schache – Andrew received several prizes during Liverpool his Fellowship, including the Richard Hambro Student Prize Award awarded by the National Cancer Research
77 Case studies of small grants:
Expression analysis of candidate genes regulating successional tooth formation in the human embryo
Ryan was awarded a Faculty small grant GAS1 and RUNX2 are all expressed in 2013. This enabled him to carry out during human tooth development. research in craniofacial science as part The domains of GAS1 and RUNX2 of his Academic Clinical Lectureship. This were consistent with a role influencing work was undertaken following his PhD, the function of the primary lamina, but which he completed at King’s College only GAS1 transcripts were identifiable London in 2012 in tooth wear and dentine in the successional lamina at early stages hypersensitivity. Ryan also had previous of human development. His work was experience in craniofacial science having published in a leading physiology journal studied for an intercalated Bsc during (Olley, RC, Xavier G, Seppala M, Volponi his undergraduate dental degree. He AA, Geoghegan F, Sharpe PT, Cobourne was awarded the UK and Ireland BDA/ MT. (2014) Expression analysis of Denstply student clinician prize. candidate genes regulating successional tooth formation in the human embryo. His faculty-funded research project Frontiers in Physiology 21(5):445). focused on understanding the molecular regulation of human successional As part of his Academic Clinical tooth formation. The primary aim was Lectureship, Ryan also completed Ryan Olley – London to investigate expression analysis of his specialist clinical training in fixed, candidate genes identified in human removable and implant prosthodontics embryos during early embryonic at Kings College London, and has recently development (8-14 weeks). Using been appointed Senior Lecturer and three-dimensional histology and in situ Consultant in Prosthodontics at Dundee hybridisation, he found that SPROUTY2, University and Hospitals.
Innate immune responses in patients with inflammatory bowel diseases
Helen was awarded a small grant in This grant allowed Helen to successfully 2014. This allowed her to develop her gain further grant funding from the post-doctoral research investigating Academy of Medical Sciences to innate immune responses in patients continue her research. Helen has with oral mucosal disease, specifically published her work in peer review inflammatory bowel diseases. The oral journals and presented both nationally cavity is an often forgotten part of the and internationally, all made possible gastrointestinal tract and can be the by this grant from FDS. first site of presentation of disease. Helen is currently a Consultant Senior Using patient blood samples, Helen Lecturer in Oral Surgery at the University characterised patient neutrophil Dental Hospital of Manchester, where function and macrophage cytokine she combines both clinical practice with release profiles, opening up interesting research, plus teaching of undergraduate new avenues of further research on and postgraduate students. this subject. Helen Petersen – Manchester
78 Biological effects of Titanium products on oral epithelial cells
Over the past five years the focus of our Confocal microscopy was used with research group has been to develop complementary X-ray and electron a better understanding of peri-implant microscopy techniques to demonstrate disease. Dental implants are an that oral epithelial cells can take increasingly common treatment modality up (intracellularise) clinically use to replace individual teeth or secure representative Ti products with dentures. However, the development little impact on cell viability. of peri-implant disease (inflammation A variety of genomic and cellular around the implant) can result in implant and molecular biological approaches loss or the need for revision surgeries. were applied to study which biological The pathogenesis of peri-implant pathways were influenced by this disease is poorly understood but oral interaction. Key findings include that microbes which colonise the implant pre-exposure to Ti can subsequently surface and the patient’s immune modify which cytokines are expressed response are known to be involved. by the cells when challenged with a Increasingly however, implant material periodontal microbial pathogens and derivatives characterised as nanoscale the presence of extra-cellular Ti, modified Joanna Batt Titanium (Ti) particles and Ti-biomolecule chemical gradients of cell signalling associations have been additionally molecules (chemokines) which are UNIVERSITY OF BIRMINGHAM implicated as a modulating factor in the essential for the host to mount an CLINICAL LECTURER IN | progression of peri-implant inflammation. adequate inflammatory response. RESTORATIVE DENTISTRY Our group using synchrotron X-ray These findings form part of an increasing MENTOR: measurements were one of the first portfolio of evidence generated by Prof Owen Addison – to characterise this accumulation of the group which support the overall University of Birmingham implant debris and demonstrated that hypothesis that ‘free’ Ti in peri-implant Professor of Applied Biomaterials – Consultant (Hon) in Restorative Dentistry it accumulated in close proximity to tissues can increase the risk of for epithelial cells. Accordingly the objectives progression of peri-implant inflammation. of this project were to model interactions between oral epithelium (adjacent to the implant surface) and Ti implant products.
79 Prizes & Travelling Awards
Travelling Awards Ethicon Foundation Fund • Rahul Kotwal – Australian Institute of Musculo-skeletal Research The College is pleased to be able to The Ethicon Foundation Fund was (AIMS) offer a variety of awards as a result of established by the generosity of Ethicon • Ben Spiegelberg – London Health the generous support of companies and Limited. The Fund provides financial Sciences Centre, Ontario, Canada individuals. These awards give surgeons assistance towards the cost of the • Fateh Ahmad – Memorial Sloan the opportunity to work in an overseas travel to and from a research or training Kettering Cancer Centre & NYU institution to learn more about a particular fellowship, thereby promoting international Langone Medical Centre surgical technique or area. The main goodwill in surgery. Applicants should • Anthony Barabas – Foothills benefit of the travelling awards is that be sufficiently advanced in their training the surgeon who benefits can translate to benefit from such an experience or be Medical Centre, Calgary, Canada the experience and know-how gained within one year of their appointment as Recipients May 2016 during the overseas fellowship to his or consultant surgeon. her own knowledge base, to benefit future • Nadia Ashraf – Sydney Cochlear patients in this country. The committees Recipients May 2015 Implant Centre that decide the recipients of the travelling • Peter Domos – Lyon, at the Clinique • Jemma Bhoday – Toronto, Canada awards always include leading surgeons. Orthopaedic Santy the University • Nikolaos Chatzizacharias - Medical Hospital Centre of Toulouse College of Wisconsin Rex and Jean Lawrie • Andrew Chetwood – Royal Adelaide • Charles Jowett – The Alfred Fellowship and Stefan Hospital, Adelaide Hospital, Melbourne and Anna Galeski Fellowship • Nil De Zoysa – The Princess • Stella Smith – Groote Schuur Alexandra Hospital, Brisbane Each year the families of Rex and Jean Hospital, Cape Town • Jonathan Dunne – Queen Elizabeth Lawrie, and Stefan and Anna Galeski, • Thet Win – Brigham Hospital, Central Hospital, Blantyre, Malawi fund a number of surgeons to undertake Boston • Navin Mani – Memorial Sloan various surgical skills workshops, and • Riaz Agha – University Hospital, Kettering Cancer Centre, New York other such activities, to help improve Brussels • Daniel Marsland – Mater Hospital surgical skills, and thus surgical care, • Rafid Al-Mahfoudh – The Weill Foot and Ankle Unit, Brisbane for people in low and middle income Cornell Brain and Spine Center, • Sid Nagala – Memorial Sloan countries throughout the world. Such New York generosity is deeply appreciated by the Kettering Cancer Center, New York • Siong-Seng Liau – Department of College, the numerous UK surgeons • Graham Sleat – University of British Gastrointestinal Surgery, L’Institut who receive the fellowships’ support Columbia and Vancouver General Mutualiste Montsouris, Paris and most importantly the surgeons who Hospital • Ibrar Majid – International Centre learn various surgical skills in the host • Misha Verkerk – Hearing for Limb Lengthening, Baltimore countries. Of late, these two fellowships Centre, Ivano-Frankivsk, Ukraine have supported surgeons going to Recipients December 2015 Malaysia, Borneo, Mongolia, Ethiopia, Recipients December 2016 • Catherine Bradshaw – Mexico and Guatemala. • Muneer Ahmed – University Red Cross Children’s Hospital, of Tokyo, Japan Recipients up to May 2017 Cape Town • Neil Barua – Institute for • Abigail Vallance • William Lo – Hospital for Sick Neurosciences Montpellier, France • Victoria Twigg Children, Toronto • Jack Broadhurst – • Ellie Edlmann • Charlotte Bendon – O’Brien Institute Catharina Ziekenhuis, • Michelle Wilkinson of Regenerative Surgery, Eindhoven, The Netherlands • Bynvant Sandhu St Vincent’s Hospital, Melbourne • James Brousil – Radboud University • Anna Sharrock • Rebecca Mills – The Children’s Medical Center, Netherlands • Johnny Mathews Hospital at Westmeade, Sydney • Rhiannon Harries • Charlotte Brown – Bishop Caeser • Sherif El-Tawil – Royal North • Naomi Wright Asiili Hospital, Luwero District, Shaw Hospital, Sydney & Sydney • Tom Pinkney Uganda Orthopaedic Research Institute 80 • Thomas Goff – Australian Institute Recipient 2015 2015 Winner of Musculo-skeletal Research • Madji Osman • Hew Torrance ‘Modulating the postgraduate immune response to trauma to fellowship, Sydney Recipient 2016 prevent life-threatening infectious • Thomas Hester – Foothills Medical • Amitava Banerjee complications’ Centre, Calagary, Canada • Christopher Hill – The Hospital for H J Windsor Prize 2015 Runners-up Sick Children, Toronto, Canada The H J Windsor Prize was established • Jason Fleming ‘Metabolism – • Zita Jessop – Royal Melbourne in 1975 with a gift of £2,500 from the a master regulator of cancer Hospital, Australia late Dr H J Windsor KSG CBE FRCS cell behaviour’ • Milap Rughani – Princess Alexandra of Brisbane, Australia. The Prize is • Keval Patel ‘The Potential of Hospital, Brisbane, Australia intended to “assist in the advancement Circulating Nucleic Acids to • Shankar Thiagarajah – Mount Sinai, of surgery by an annual prize or by such Improve Outcomes for Patients Hospital, Toronto, Canada other means as the Council shall from with Urological Cancers’ • Jim Tiernan – Cleveland Clinic, time to time determine” Cleveland, Ohio, USA 2016 Winner • Emily Young – St Paul’s Hospital, Recipients 2015 • Muneer Ahmed ‘Magnetic technique Vancouver, BC, Canada • Rebecca Mills for Breast Cancer Treatment’ Colledge Family • Matthew Sewell 2016 Runners-up Memorial Fellowship Fund Recipient 2016 • Pankaj Chandak ‘Novel strategies The Colledge Memorial Travelling • Michelle Griffin in overcoming barriers in Fellowship was established by Miss transplantation using 3D printing Cecilia Colledge in 1979 in memory of The Rosetrees Trust Prize and ex-vivo normothermic her father, the distinguished surgeon The Rosetrees Trust Prize was (bypass machine) perfusion of Lionel Colledge and her brother Maule established in 2009 and applicants are human kidneys.’ who died in active service during the asked to write an essay to “describe how • Peter Szatmary ‘Rediscovering Second World War. The Fellowship your research project will contribute to inflammation in acute pancreatitis’ was founded to promote and advance improvements in patient care within the the study and knowledge of surgery, in next five years”. particular head and neck surgery, for the benefit of patients. Applicants must be senior trainees or new consultants and plan to a study for a period overseas.
Recipient 2015
• Asit Arora
Recipients 2016
• Mahmoud F Bhutta • Abhijit Ricky Pal • Navin Mani Sir Ratanji Dalal Research Scholarship This research scholarship was founded under the will of Sir Ratanji Dinshaw Dalal. It is awarded jointly by The Royal College of Surgeons of England and the Royal College of Physicians of London. Applications are invited for this research scholarship, which is intended to support a project in either tropical surgery or tropical medicine. The scholarship is tenable for one year and is open to all medical practitioners registered in any part of the Commonwealth. It may be held in any institution in Britain or overseas that is approved by The Royal College of Surgeons of England and the Royal College of Physicians of London.
Galeski winner Michelle Wilkinson in Mongolia with the locals
81 81 Higher Degrees for Intercalated Medical Students
Medical students’ grants are awarded to medical students wishing to undertake an intercalated Bachelor of Science degree related to surgery. Owing to the variation in the ways students are funded or not funded for such degrees, students require additional support in areas such as bench fees, consumables or subsistence. Each award is worth up to £5,000.
Halimat Afolabi Robert Geraghty Toby Murray Oliver Baker Lysander Gourbault Ahmed Shafi Eilidh Bruce Alexandra Griffiths Tittu Thomas Charmilie Chandrakumar Kit Wing Lam Lauren Wallace Rachel Dbeis Choong Ngan Lou Simon Erridge Simon McElligott
82 83 3D printed TPU and collagen incorporated scaffold for the application of wound healing invitro
HALIMAT AFOLABI incorporated in it in order to promote the proliferation of dermal fibroblasts MEDICAL SCHOOL: University College London and endothelial progenitor cells as a model for wound healing. In all I learnt SITE OF WORK: a wide range of skills including 3D Royal Free Hospital, London design and printing, cell culture and immunofluorescent microscopy. I hope I am grateful to have received the RCS to continue doing translational research award as it helped me to participate in in regenerative medicine and I believe laboratory based regenerative medicine, this opportunity provided an excellent which is an area of research I have been foundation for future research. very interested in but have not had the opportunity to pursue. My project was on wound healing, and involved creating a 3D printed patch with collagen gel Cell culture work under a sterile hood
The identification of frailty in colorectal surgical patients
OLIVER BAKER Frailty is the loss of resilience to be able to present it at the international stressors, such as illnesses or surgery, conference of sarcopenia and frailty next MEDICAL SCHOOL: University of Leeds Medical School and is seen among both young and year. We hope this study will form the elderly patients. It is strongly associated basis of future research into frailty and SITE OF WORK: with poor post-operative outcomes but may aid clinicians incorporate frailty into St James University Hospital, Leeds is currently not routinely assessed. In pre-operative assessment. My thanks our pilot study we found considerable are given to the RCS for their generous This award helped me to conduct frailty among adult colorectal surgery grant, without which this research project a research project looking at the patients and the proportion increased wouldn’t be possible. identification of frailty in colorectal among elderly patients. We plan to surgery patients at a university hospital. publish this work and hope that we will
Oliver with his supervisors; Mr Dermot Burke and Thomas Dale-Maclaine, the senior research nurse and members of the pre-assessment team
84 Development and validation of the Robot-Assisted Partial Nephrectomy (RAPN) assessment tool
EILIDH SUMMERS BRUCE from open surgery has implications for patient safety, and this has called for MEDICAL SCHOOL: King’s College London the development of safety-checklists such as this. SITE OF WORK: Guy’s Hospital, London Although based at Guy’s Hospital, I carried out this research in association with a variety of experts on an In receiving the College’s generous international level, and it is with the award, I was presented with the generosity of the RCS that I have opportunity to undertake research in the been able to travel to these centres. field of surgical education as part of my I travelled to Belgium to observe intercalated BSc. I have since graduated RAPN and to Madrid as a conference with a first class honours in anatomy delegate. I am incredibly grateful for from KCL. the support of the RCS. We developed a scoring system to be used in the training and assessment of surgeons undertaking RAPN. In robotics, Eilidh at the EAU 2015 Congress in Madrid, the requirement for a different skills set with the da Vinci Xi Surgical Robot
The role of the primary cilium in the regulation of hedgehog signalling and mechanotransduction in alkaptonuria
CHARMILIE CHANDRAKUMAR MEDICAL SCHOOL: Barts and The London School of Medicine and Dentistry, Queen Mary University of London SITE OF WORK: The School of Engineering and Materials Science Queen Mary, University of London
Alkaptonuria is a rare genetic disorder that causes the destruction of joints, similar to osteoarthritis. Currently, not much is known about the mechanisms of the disease. The research that we conducted was to explore the role of primary cilia, a component of cartilage, that is known to be involved in cell signalling pathways such as mechanotransduction and hedgehog Charmilie with colleagues from the Institute of Bioengineering signalling, which are key pathways in I am extremely grateful to the Royal techniques as well as different aspects of cartilage health. The results of this project College of Surgeons of England for research. This year has further inspired show that these pathways are abnormal in their generosity. I truly appreciate me to pursue a career in academic alkaptonuria, thus, allowing us to further their support, as it has enabled me to surgery. Thank you very much! understand the nature of the disease and learn about an array of experimental opening new avenues in research.
85 The epigenetics of rectal cancer: clinical implications
RACHEL DBEIS It is one of the first studies to identify who would respond better or worse than relevant genes and regulators in rectal others, to specific treatments, leading to MEDICAL SCHOOL: Peninsula College of Medicine and Dentistry, cancer specifically. Future studies can the development of more personalised The University of Exeter Medical School use this information to identify patients and successful treatments.
SITE OF WORK: Royal Devon & Exeter Hospital and The University of Exeter Medical School, Exeter
Rectal cancer is a form of bowel cancer that needs surgery to try to cure it, with or without chemotherapy and radiotherapy. We don’t yet have a way to identify people who will not respond to the combination of treatment and ultimately spare them unnecessary side effects.
There are chemical switches that control the activity of how our genes work, identified in other cancers, like lung cancer. They can tell us how people may respond to treatment.
My project looked at chemical switches in rectal cancer patients. We used new technologies to extract the genes, look at the chemical switches and analyse them. At the INSPIRE National Intercalators’ Conference with best poster prize award
Are synovial plicae of the knee normal anatomical features or a consistent pathology?
ROBERT MICHAEL Synovial plicae around the knee are GERAGHTY poorly investigated and are therefore poorly understood. My project aimed to MEDICAL SCHOOL: identify plicae in cadaveric knees using University of Southampton a novel technique of latex injection and SITE OF WORK: proximodistal dissection rather than the Bristol University Centre for traditional distoproximal approach. After Comparative and Clinical Anatomy identification, plicae were then sampled for histological analysis.
This study has yielded some interesting results. Firstly, plicae are more common than the literature suggests. Secondly, plicae may act in lieu of an anterior joint capsule and thirdly, they may have a role in patellofemoral osteoarthritis. These topics will be covered in forthcoming abstracts and publications.
I would like to thank the College for their generous help this the year, without which I would not have been able to do. The skills I have gained this year in the dissection room and laboratory will help A knee with plicae, which may act towards a future career in both surgery in lieu of an anterior joint capsule and academia. Robert dissecting a knee
86 Exploiting the MT1-MMP/NG2 axis for surgical applications in human and canine sarcoma: a comparative oncology approach
LYSANDER JAMES We also wanted to use these biomarkers In conclusion our research has shown GOURBAULT to detect human and dog sarcoma that MT1-MMP may prove invaluable cells in the blood as they metastasize. in future sarcoma treatments and help MEDICAL SCHOOL: By using flow cytometry we detected guide diagnosis. Newcastle University potential cancer cells in two human SITE OF WORK: sarcoma patients’ blood. Northern Institute of Cancer Research, Newcastle and The Queen’s Veterinary School Hospital, Cambridge
During my intercalated year I investigated sarcomas which are a rare form of cancer with high mortality. MT1-MMP and NG2 are biomarkers known to promote sarcoma metastases. Thanks to the generous support from The Royal College of Surgeons, I was able to investigate whether these biomarkers were linked to patients’ survival. By staining patient tissues we showed that MT1-MMP, but not NG2, is expressed in most human and dog patient biopsies and is linked to how long patients survive. Lysander (far right) with the Cambridge Surgical Discovery Centre Team
Renal ischaemia reperfusion injury; the mitochondrial perspective
ALEXANDRA The RCS award helped finance my My project analysed changes in CAROLINE GRIFFITHS MRes in Transplantation Sciences mitochondrial proteins during investigating the response to ischaemia ischaemia and reperfusion using an MEDICAL SCHOOL: (inadequate blood flow) and reperfusion animal model. We also investigated Newcastle University (restoration of blood flow) in kidney the use of isofluorane, a commonly used SITE OF WORK: transplants, with a focus on mitochondria anaesthetic agent. We found that this Institute of Genetic Medicine, (small energy producing organelles). could prevent the changes that occurred Newcastle Upon Tyne in mitochondria exposed to ischaemia. Mitochondria induce damage during ischaemia and reperfusion, termed I am grateful for the support from the ischaemia-reperfusion injury (IRI), RCS and my supervisors which made through harmful free radical production. this study possible, enabling me to gain Understanding this process could enable valuable research experience and skills the development of targeted treatments that will be useful throughout my career. to prevent IRI to increase the function and survival of transplanted kidneys.
Alex performing in gel activity assays at the Centre for Life
87 To identify the differences in gaze behaviours of junior and expert bariatric surgeons
SIMON ERRIDGE at a national surgical conference and aim to be published in a peer- MEDICAL SCHOOL: Imperial College School of Medicine reviewed publication. SITE OF WORK: This experience was invaluable to my Department of Surgery and Cancer on-going education as it allowed me to at St Mary’s Hospital London gain a new range of skills in research and academia and has reaffirmed my desire to pursue a career in academic surgery. We used a set of eye tracking glasses I would like to thank the Royal College of to distinguish between the dwell times Surgeons for making my project possible of surgeons gaze on different areas and my supervisors Mr Mikael Sodergren of interest. The results from the project and Mr Sanjay Purkayastha. have been submitted for presentation Mr Sanjay Purkayastha, Simon’s co- supervisor, wearing the eye tracking glasses
Using MR optic radiation tractography to predict visual field deficits after epilepsy surgery
KIT WING LAM The average resection plot can be used This model correctly predicted the visual to predict visual outcomes after surgery. outcomes of two patients. Further work is MEDICAL SCHOOL: Cardiff University The hope is that this model can provide being undertaken to validate the model. further support for informed consent. SITE OF WORK: Cardiff University Brain Imaging Centre (CUBRIC)
For some patients with medial temporal lobe epilepsy surgery is a viable option. However, a major complication is visual field defects. This arises due to damage to nerves carrying visual information, known as the optic radiation, in particular, the region called Meyer’s loop.
The grant funded Magnetic Resonance Imaging (MRI) of the patients pre and post-operatively. The MRI technique (tractography) enabled mapping of the nerve bundles in the brain. In doing so, we were able to overlay the pre-operative nerve pathways onto a template resection. The template resection consisted of MRI scans of previous patients; all of whom were operated on by Professor William Gray (Project Supervisor). Kit Lam interpreting an MRI scan in CUBRIC
88 Prosthetic deep venous valves for deep venous reflux
CHOONG NGAN LOU additive manufacturing for testing valve prostheses and conducted a MEDICAL SCHOOL: Imperial College London systematic review on the developmental considerations of prosthetic deep SITE OF WORK: venous valves. We identified gaps in our Imperial College London, Bessemer understanding of the deep venous system Building, South Kensington Campus and in the design and testing of valve prostheses for further focused research. No good treatment currently exists for I am grateful to the College for the award chronic venous insufficiency caused by that has made this possible and would like dysfunctional valves in the deep veins. to thank my supervisors Professor Alun Despite efforts to restore structure and H Davies and Mr Andrew Busuttil for their function to the deep venous system, guidance and support. a suitable valve prosthesis has not been developed.
With the funding provided by the Royal College of Surgeons, we developed two bench-testing setups using
Choong with his supervisor Mr Busuttil
The effects of sonic hedgehog on the proliferation of neural stem and progenitor cells
SIMON MCELLIGOTT I believe the skills that I have gained Therefore I would like to sincerely thank from this experience will provide me the College, and their funding partners, MEDICAL SCHOOL: University of Southampton with a strong foundation to pursue a for their invaluable support. future career in academic surgery. SITE OF WORK: Southampton General Hospital, Southampton, Hampshire
During my intercalation year, the generous award from the Royal College of Surgeons of England enabled me to undertake a Master’s degree in medical science in the Clinical Neurosciences Department at Southampton General Hospital.
The award allowed me to conduct a project that investigated the potential use of neural stem cells as a line of therapy in traumatic brain injury. More specifically, this involved using a range of laboratory techniques to mimic the processes that occur in traumatic brain injury and assess whether a specific molecule, called Sonic Hedgehog, was able to activate and stimulate the proliferation of endogenous neural stem cells. Simon carrying out his research
89 The quantitative definition of the kynurenine pathway
TOBY BENJAMIN JAMES samples using liquid chromatography MURRAY tandem mass spectrometry. The analytical method developed this year MEDICAL SCHOOL: has proven to be extremely sensitive University of Edinburgh Medical School and precise. We have managed SITE OF WORK: to detect, and quantify, each main Queens Medical Research Institute, compound involved in the kynurenine Royal Infirmary of Edinburgh, Edinburgh. Scotland pathway at extremely low concentrations. We have defined the rates of formation The award provided fantastic support for the main compounds, along with during my MScR in Surgery degree identifying their metabolism, distribution at the University of Edinburgh. and excretion parameters. I investigated the flux of tryptophan I am extremely grateful to the College metabolism through the kynurenine for their support, this year has been pathway. This pathway is important in an incredible experience and has the pathogenesis of inflammation and cemented my desire to pursue a multi-organ dysfunction syndrome career in academic surgery. following severe acute pancreatitis. Toby with the Deputy Lab Manager, Mr George Just who assisted with the Our aim was to define the flux of the development of the mass spectrometry pathway pre-clinically, using stable assay. Behind is the liquid chromatography isotope tracers and analysing plasma tandem mass spectrometry system we used
Multi-centre validation of simulation-based ureteroscopy curriculum – prospective study
AHMED MOHAMED ABDEL SHAFI MEDICAL SCHOOL: King’s College London SITE OF WORK: MRC Centre for Transplantation, NIHR Biomedical Research Centre – King’s College London, 5th Floor Tower Wing, Guy’s Hospital, London
This was a year full of opportunity that I used to explore aspects of surgery and start to plan for the future aiming to pursue a career in surgery. I gained skills in basic surgical skills, laparoscopic skills, and virtual simulators. I was also able to spend time at the Royal Veterinary College, for part of my surgical anatomy project, which included comparing the difference between human and animal hearts and their possible use in heart transplant in the future. I had an article based on my BSc project accepted to The Surgeon Journal, ‘The Role of Simulation in Urological Training – A Quantitative Study of Practice and Opinions’, and I am preparing more articles to get published. I am truly grateful for the financial support Ahmed with his supervisor Dr Abdullatif Aydin after being taught different urological that made it all possible. procedures/skills using The URO Mentor virtual reality simulator
90 Development of novel small-molecule inhibitors of Orai1
TITTU THOMAS MEDICAL SCHOOL: University of Leeds SITE OF WORK: Leeds Institute of Cardiovascular and Metabolic Medicine, Leeds
Vascular smooth muscle cell remodelling can lead to cardiovascular diseases including atherosclerosis and vascular aneurysms and the pathological process underpinning remodelling has been previously established; however there is no medication currently targeting remodelling. During my intercalated year I undertook a project aimed at developing novel inhibitors targeting this process. Tittu using the FlexStation to analyse results with Dr Marc Bailey
With the generous support from investigate and develop the multitude I would like to thank the College for the the Royal College of Surgeons, of compounds available. My project grant which made it possible for me to the award was utilised to purchase concluded with identifying three conduct this project and introduce me consumables for tissue culture and compounds with the potential for clinical to the world of novel research. Flexstation experiments, necessary to use in the future.
Development and validation of a cognitive training tool for laparoscopic surgery
LAUREN WALLACE MEDICAL SCHOOL: King’s College London SITE OF WORK: Guy’s Hospital, London
During my intercalated year I undertook a project focused on an exciting new approach to surgical training. Cognitive training, or the use of psychological processes to enhance performance of skilled behaviour, has proven valuable in the disciplines of sports and aviation, and has great potential as a method for training surgical skills.
My dissertation project, supported by the Royal College of Surgeons, sought to design and test a cognitive training tool to teach laparoscopic suturing. Following literature review and expert consultation, Lauren supervising one of the study participants as they carry out a laparoscopic suturing task we produced a unique new tool that Our research demonstrated that cognitive utilised different types of cognitive training can be an effective method for training. Results comparing the developed surgical skills training and paves the way tool to traditional teaching methods were for it to play a greater role in the future of extremely positive, with technical skills surgical education. being considerably improved in those participants using the tool.
91 92 Elective Prize Reports The Elective Prize in surgery is awarded to clinical students at a UK medical school wishing to pursue a career in surgery and planning to undertake their elective attachment in surgery in the developing world. Each award is worth up to £500.
Ernest Chew Caitlin MacLeod Alistair Reed Keiran David Clement Kyung-Hoon Moon Rosa Sun Anna Craig-McQuaide Seneka Nakagawa Patrick Hickland Graeme Downes Daniel Nash Ankur Khajuria Francesco Fiorini Denise Osei-Kuffour Zahra Jaffry Vincent Quan
93 Paediatric trauma and orthopaedics – a Cape Town experience
ERNEST CHEW operation clinics. The most inspirational PREISKEL ELECTIVE moment for me was following up a previously disabled child learning to walk MEDICAL SCHOOL: again after surgery. This has further University College London re-enforced my enthusiasm for the SITE OF WORK: speciality and the lessons learnt will stay Red Cross Children’s Hospital & Maitland with me throughout my career. Cottage Orthopaedic Hospital, Cape Town, South Africa
My elective was an awe-inspiring experience. It strengthened my surgical knowledge pertaining to childhood orthopaedic conditions and gave me a better understanding of how these diseases can drastically affect a child’s quality of life. I was an active team member assisting in many operations, managing patients in the trauma unit Ernest (on the right) assisting in an and being involved in fracture and post A ward round at Maitland Cottage Hospital operation at Red Cross Hospital
The spectrum of paediatric urology presenting to a tertiary centre in a low-income country
KEIRAN DAVID CLEMENT PREISKEL ELECTIVE MEDICAL SCHOOL: University of Aberdeen Medical School SITE OF WORK: Queen Elizabeth Central Hospital, Blantyre, Malawi
I spent my elective within the paediatric surgical department of the Queen Elizabeth Central Hospital (QECH), Blantyre. I scrubbed in on numerous interesting cases including large intra-abdominal tumours and spina bifida repairs. I also completed two departmental audits while there, one on the spectrum of paediatric urology presenting to QECH, and another on the outcomes of children with gastroschisis, a commonly fatal disease. The amount of work being carried out with the lack of resources was staggering, and re-kindled my desire to volunteer in a low-resource setting in the future. I thoroughly recommend Malawi to other students. The outpatient department waiting area in QECH
94 Neurosurgery elective in Recife, Brazil
ANNA CRAIG-MCQUAIDE My neurosurgery elective at Hospital PREISKEL ELECTIVE Pelópidas Silveira, under the supervision of Dr Carolina Martins, was an invaluable MEDICAL SCHOOL: experience. HPS is a new public tertiary Imperial College London hospital providing cardiology, neurology SITE OF WORK: and neurosurgery services to a poor Hospital Pelópidas Silveira (HPS), Recife population and with limited resources. (Pernambuco), Brazil The staff were exemplary and I am indebted to them for all they taught me. This included invasive procedures (central lines, arterial lines, intubation and lumbar puncture). I assisted in theatre on a daily basis with a mixture of cases – elective and emergency, cranial and spinal, and I was given the opportunity to acquire many new surgical skills. It was a fantastic experience and one which confirmed my passion for neurosurgery.
Anna with a post-operative patient and his Anna inserting a ventriculo-peritoneal shunt family whom she assisted with his ten-hour for the first time tumour resection
Trauma care in Johannesburg
GRAEME DOWNES RCS ELECTIVE MEDICAL SCHOOL: Imperial College London SITE OF WORK: Charlotte Maxeke Hospital/Baragwanath Hospital, Johannesburg, South Africa
Simulated gunshot patient The elective student team
It was my aim that during my trip that I I also wished to gain first-hand experience I certainly learnt a great deal about the would get the chance to experience how of treating patients who had suffered treatment of trauma patients and would healthcare is different in Johannesburg traumatic injuries and to get a chance recommend such an elective to any to the UK, due in part to the different to become more familiar with the gold student interested in this area. financial constraints and greater numbers standard ATLS (advanced trauma life of seriously injured patients. support) methodology.
95 Trauma clerkship and outreach township clinics
FRANCESCO FIORINI trauma room of Groote Schuur hospital PREISKEL ELECTIVE in Cape Town. In addition to scrubbing in on various emergency surgeries, MEDICAL SCHOOL: it was an excellent opportunity to start GKT School of Medicine at King’s College London developing some independence in clinical management and refine practical SITE OF WORK: skills – from suturing complicated Groote Schuur Hospital, Cape Town, South Africa wounds to the occasional chest drain. Moreover, volunteering at student-led township clinics offered great insight into Medical electives are our best chance the local public health and social needs. to immerse ourselves in a specialty that This was a truly phenomenal experience, we intend to pursue and everything that which I definitely recommend to fellow Francesco (far right) in the trauma room at comes with it: the people, values, and students and thank the RCS for its Groote Schuur hospital, with some great challenges. I spent mine in the busy generous award. local and elective medical students
Trauma and general surgery in Empangeni, South Africa
KYUNG-HOON MOON PREISKEL ELECTIVE MEDICAL SCHOOL: Imperial College School of Medicine SITE OF WORK: Ngwelezana Hospital, Empangeni, South Africa
For my elective, I travelled to the land of African warriors, Kwa-Zulu Natal in South Africa. I spent six weeks in general surgery at Ngwelezana Hospital. It was an incredible experience with great teachings. I had a lot of theatre time as the second surgeon and learnt that patience at times of stress is an important surgical skill. I also conducted a retrospective study looking at recovery of trauma patients and organised teaching for nurses on resuscitation equipment.
This placement gave me the confidence that I needed before starting my first job and I strongly recommend Ngwelezana for other future trauma surgeons.
Hoon (middle) with the general surgery theatre nurses
Hoon teaching nurses on resuscitation equipment during lunchtime
96 Perspectives of global surgery: Malawi and the World Health Organisation
ZAHRA JAFFRY My elective has been an incredible my time as an intern at the World Health PREISKEL ELECTIVE experience. In Malawi, I had the Organisation. Throughout, I was able to opportunity to see, first-hand, the develop both clinical and academic skills, MEDICAL SCHOOL: problems with access to safe and assisting in theatre and learning about a King’s College London good quality surgical care and how range of orthopaedic conditions as well SITE OF WORK: successful projects such as the Beit as working on projects in global surgery. Beit Cure International Hospital, Cure International Hospital can be. It was life-changing. Blantyre, Malawi and The World Health Organisation, Geneva, Switzerland Efforts in addressing the problem were happening on an even larger scale during
Interns at the World Health Organisation, Geneva, Switzerland Theatres at the Beit Cure International Hospital, Blantyre, Malawi Surgery for children with cardiac disease at the Aswan Heart Centre, Egypt: a medical student’s perspective
CAITLIN SARA MACLEOD tremendously privileged and humbled PREISKEL ELECTIVE I am to have met those that I did at the AHC, witnessing the journeys of patients MEDICAL SCHOOL: and their families from diagnosis to University of Aberdeen treatment and recovery, not to mention SITE OF WORK: the remarkable industry and teamwork Aswan Heart Centre (also known as of the staff. I was also fortunate enough the Magdi Yacoub Heart Foundation), Aswan, Egypt to meet the extraordinary man who has deeply inspired and motivated me: Professor Sir Magdi Yacoub. My elective at the Aswan Heart Centre This opportunity has only affirmed my (AHC) was one of the best experiences desire to become a surgeon, and my of my life. Further to the fantastic determination to add what I can to life, in abundance of learning opportunities in any small way – so I offer my unreserved adult and paediatric cardiology clinics, gratitude to those who helped to make catheterisation lab, on the wards and this exceptional experience a reality. in theatre, what struck me most was the human experience. The AHC is the tertiary referral centre for cardiac conditions, serving all of Egypt and the surrounding area, providing world-class care free of charge to those in need. Parents travel hours or even days, commonly in a cramped, sweltering mini-bus, to reach the AHC, which often Caitlin with staff nurse Amany and a is the only hope to the save the life of The truly phenomenal staff 21-day-old boy following an arterial their child. I cannot fully express how of the Aswan Heart Centre switch operation
97 General surgery in Kingston, Jamaica
SENEKA CHOI NAKAGAWA I carried out my medical elective at the My elective allowed me to see a range RCS ELECTIVE UWI hospital in Jamaica, where I clerked of interesting cases, and gave me a lot patients, attended ward rounds, surgeries of hands-on experience, while making MEDICAL SCHOOL: and clinics. The majority of surgical me appreciate the difficulties faced when University of Nottingham patients were admitted due to road traffic practicing medicine in a developing SITE OF WORK: accidents and abdominal emergencies, country. I thoroughly enjoyed my time in University of the West Indies however a large number were also Jamaica and would highly recommend it (UWI) Hospital, Kingston, Jamaica admitted due to stabbings and shootings. to anyone as an elective destination.
Seneka clerking patients prior Doctors and medical students Seneka worked with to elective surgery Trauma and orthopaedics at Baragwanath Hospital in Johannesburg
DANIEL NASH RCS ELECTIVE MEDICAL SCHOOL: Peninsula College of Medicine and Dentistry SITE OF WORK: Chris Hani Baragwanath Academic Hospital in Johannesburg, South Africa
I undertook my elective in Trauma and Orthopaedics at Chris Hani Baragwanath Academic Hospital in Johannesburg, South Africa. I spent four weeks in trauma and four in the orthopaedic department observing operations, attending ward rounds and clerking patients. In the trauma department there were opportunities to extensively practise clinical skills such as arterial blood taking, cannulation, suturing and more, as well as to become involved with resuscitations. In orthopaedics I saw many conditions that are uncommon in the UK, for example spinal tuberculosis and untreated clubfoot, and was also able to examine a large number of X-rays. Daniel at Baragwanath Hospital
98 Surgical elective in plastic surgery and cleft lip and palate surgery
DENISE OSEI-KUFFOUR It was enlightening to observe and PKK ELECTIVE discuss the similarities and differences in healthcare provision, and I would MEDICAL SCHOOL: thoroughly recommend this elective. Imperial College London SITE OF WORK: Komfo Anokye Teaching Hospital (KATH), Kumasi, Ghana
My elective took place in Kumasi, Ghana in the joint specialities of Plastics and Maxillofacial surgery. There was ample opportunity to observe both specialities whilst attending weekly clinics, ward rounds and theatre. I learnt about the multidisciplinary management of cleft lip and palate in clinic and observed the complex surgery involved. I gained further experience of the breadth of reconstructive work undertaken Plastic surgery ward round at Emergency by plastic surgeons from burns to Denise (centre) assisting in maxillofacial Centre. Denise (centre) with Dr Emmanuel neoplasms to congenital anomalies and theatre with Dr Michael Yelibora (right) Adu (far left), Dr Yaw Asiedu Anokye (left) the humanitarian role of the speciality. and Dr Kofi Bedu-Addo (left) and Dr Robert Sagoe (right)
General surgery in Johannesburg
VINCENT QUAN I travelled to Johannesburg to complete RCS ELECTIVE my medical elective in general surgery, a city famous for its surgical and trauma MEDICAL SCHOOL: training. During my time there I spent time Barts and The London School of Medicine and Dentistry on ward rounds, assisting in theatres and often did 27-hour shifts in the surgical SITE OF WORK: pit where all surgical emergencies are Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa handled. This elective has allowed me to gain a great deal of hands on experience and work in the pit allowed me to broaden my experience beyond that of general surgery. I aim to bring back the confidence that Baragwanath has instilled in me back to the NHS.
The CHBAH Surgical Pit where we saw Middle of the night vascular acutely unwell surgical patients surgical emergency
99 Plastic surgery and trauma in India and general surgery in Zambia
ALISTAIR REED PKK ELECTIVE MEDICAL SCHOOL: The University of Oxford SITE OF WORK: Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India and Monze Mission Hospital, Monze, Zambia
Alistair with surgical colleagues in the Alistair teaching the basics of chest radiography to nursing students at theatre coffee room at PGIMER Monze Missions Hospital
At PGIMER, I immersed myself in At a small mission hospital in Zambia, Overall, my elective was an inspiring, the busy plastic surgery department I took an active role in surgical patient humbling and memorable experience and spending time on the wards, in clinics care. Resources were limited, but working I have made lasting links for the future. and theatres. In the trauma unit I saw without investigations provided a fantastic many cases of severe trauma from road opportunity to develop my clinical skills. traffic and construction-related injuries, which highlighted the urgent assessment and initial care of critically ill patients. An elective in trauma and neurosurgery, Johannesburg
ROSA SUN RCS ELECTIVE MEDICAL SCHOOL: University of Cambridge SITE OF WORK: Chris Hani Baragwanah Hospital, Soweto, Johannesburg, South Africa
I completed an elective in trauma and neurosurgery in the biggest government hospital in Johannesburg. I set out to learn traumatology from the world leading experts, and also wished to witness the variety of exaggerated pathology Africa had to offer. First patient on Sunday morning Johannesburg offered even more than I patients. This was the best two months in could wish for. With a massive caseload, my medical training thus far, and I would I worked day and night shifts assisting in fully recommend to those who are not surgery and resuscitating major trauma faint-hearted.
100 Paediatric orthopaedics
PATRICK HICKLAND MEDICAL SCHOOL: University of British Columbia SITE OF WORK: British Columbia Children’s Hospital
My final year elective in British Columbia Children’s Hospital was extremely rewarding. As an orthopaedic intern, I had newfound responsibilities; lengthy surgeries seemed shorter as I was involved throughout, and clinics more educational because I assessed patients independently. My time on call acutely managing fractures was exciting but also difficult, in discovering non-accidental injuries. Fortunately my supervisors were quick to help, and their tutorials and ad hoc discussions were enlightening. Having chosen this elective due to a similar healthcare system to the UK, I have no doubt that my experience will help me in my future practice as a surgeon. Patrick still smiling at the end of a lengthy scoliosis surgery
Plastic and reconstructive surgery sub-internship
ANKUR KHAJURIA MEDICAL SCHOOL: Harvard Medical School SITE OF WORK: Brigham and Women’s Hospital, Boston, USA
I undertook a Plastic and Reconstructive Surgery sub-internship at Harvard Medical School. Team rounds started at 5.30am every day, followed by assisting in cases in theatre with ample opportunities for wound closure using sutures, and teaching on anatomy/ operative techniques. I also taught anatomy to 3rd year Harvard students. I witnessed exemplary teamwork and operative skills in challenging eight to ten hour procedures and in turn enhanced my knowledge and technical skills. I was also able to establish research collaborations; I am currently leading a project on national guidelines Ankur assisting in a craniofacial case in the Operating Room implementation in the US. I would highly recommend this sub-internship to others interested in Plastic Surgery. 101 Hunterian, Arris & Gale, Arnott, Zachary Cope, Joseph Toynbee & Lionel Colledge Memorial Lectures 2015/16
Hunterian Mr KM John Chan, SCTS, Birmingham, 25th March 2015 Pathophysiology and surgical treatment of functional ischaemic mitral regurgitation
The Lionel Colledge Mr Jonathan Bernstein – BACO Meeting, Liverpool, 8-10th July 2015 Memorial Lecture
Hunterian Mr Richard Shaw, BAOMS ASM, Liverpool, 23rd July 2015 Nature or Nurture? The Epigenetics of Head & Neck Cancer
Hunterian Mr Michael Douek, BASO/RSM, London, 2nd November 2015 Magnetic technique for sentinel node biopsy in cancer surgery
Joseph Toynbee Dr Lloyd Minor – RSM, London, 6th November 2015 Memorial Lecture
Hunterian Mr David Leonard, BAPRAS, Birmingham, 25th November 2015 Transplant Tolerance for Vascularized Composite Allotransplantation through Induction of Stable Hematopoietic Mixed Chimerism in a Clinically-relevant Large Animal Model
Hunterian Dr Ernest Azzopardi BAPRAS, Birmingham, 27th November 2015 Multidrug resistant burn wound infection: establishing the causative profile and novel translatable theranostic strategies
Zachary Cope Mr John Hunt – SARS, RCS London, 6th January 2016 Memorial Lecture
Hunterian Professor Dileep Lobo, SARS, RCS London, 7th January 2016 Experiments in fluid and electrolyte pathophysiology: Effecting change in clinical practice
Arnott Mr Pankaj Chandak, BTS Meeting, Glasgow, 24th February 2016 Living Donor Transplantation - a journey from open to minimally invasive nephrectomy
Arris & Gale Mr Jonathan Hyam, SBNS, Gordon Holmes Prize neuroscience meeting, RSM, London, 28th April 2016 Using Surgery to Identify the Neural Anatomy Governing Cardiovascular and Respiratory Physiology
Hunterian Mr Christopher Gibbons, BOOS annual meeting, Dublin, 20th May 2016 Orthoplastic Reconstruction in Sarcoma Surgery
Hunterian Mr Peter Thompson – BAUS Academic Urology annual meeting, Liverpool, 27th June 2016 The difficulty interpreting endotoxaemia post transrectal prostate biopsy
Hunterian Mr Stephen Price, SBNS, Telford, 21st September 2016 Local Control of Glioblastomas: Lessons from John Hunter and Advanced MR Imaging of the Peritumoural Region
Hunterian Mr John Greenwood, BAPRAS Winter Scientific Meeting, London, 24th November 2016 The Evolution of Acute Burn Management – Retiring The Split Skin Graft
102 Fundraising in focus Make a donation or leave a legacy to Surgical Research
Research at the College relies exclusively Currently we are unable to support 80% of Grants are not restricted to research on voluntary income that has been gifted those applying for research grants due to fellowships and we are delighted to through donations, legacies and grants. lack of funds. If you would like to make discuss opportunities to encourage and We need your help if this work is to a donation or discuss a legacy, please develop the potential of young surgeons continue and flourish. Future innovations contact the College’s Development through education, training and research in surgery will continue to be driven by Office on 0207 869 6086, or by email at by way of travel and educational grants or research and surgical research continues [email protected] annual prizes and awards. to provide significant advances in a wide range of areas.
Funding Partnerships: • Enid Linder Foundation Endowments, restricted • ENT UK • Addenbrooke’s Charitable Trust and legacy funds: • Facial Surgery Research Foundation • Association of Breast Surgery (Saving Faces) • Anderson Reid Fund • Association of Coloproctology • Frances & Augustus Newman • Annie Julia Speight Legacy of Great Britain & Ireland Foundation • Albert Pomfret Legacy • Association of Upper Gastrointestinal • Freemasons Fund for Surgical • Barlow Research Fellowship Surgeons Research • Bernhard Baron Fund of Great Britain & Ireland • Get A Head Charitable Trust • Black Legacy • Ballinger Charitable Trust • George Drexler Foundation • Blond McIndoe Fund • Bowel Disease Research Foundation • Golden Bottle Trust • Buckston Browne Gift • Breast Cancer Now • Henry Lumley Charitable Trust • Burghard Bequest • British Association of Endocrine & • Mary Kinross Charitable Trust • Carol Rummey Legacy Thyroid Surgeons • McKinsey • Cicely Fay Simpson Legacy • British Association of Paediatric • Michael & Anna Wix • Dennis F Clark Legacy Surgeons (BAPS) Charitable Trust • Doris K King Legacy • British Association of Plastic, • Miss N Shotts FDSRCS • Dr Shapurji H Modi Memorial Reconstructive & Aesthetic Surgeons • National Joint Registry ENT Research Fund (BAPRAS) • Orthopaedic Research UK • Edward Lumley Fund • British Association of Surgical • Philip King Charitable Settlement • Eleanor M Heslop Legacy Oncology (BASO) • PKK • Gwendoline Shrimpton Legacy • British Orthopaedic Association • Prostate Cancer UK • Harold Bridges Bequest (BOA) • Reuben Foundation • Harry S Morton Fund • British Society of Endovascular • Rosetrees Charitable Trust • John L Williams Legacy Therapy (BSET) • Sahlgrenska Hospital, Gothenburg • Laming Evans Research Fund • British Society of Surgery • Shears Foundation • Lea Thomas Fund of the Hand • Vascular Surgical Society • Lillian May Coleman Legacy • Cancer Research UK of Great Britain & Ireland • Osman Hill Collection & Research • Colin and Anna Frizzel • Virginia Mason Hospital, Seattle • Parks Visitorship Charitable Trust • Wellington Hospital • Patricia Constance Curry Legacy • Colledge Family Fund • Welton Foundation • Philip & Lydia Cutner Legacies • Dinwoodie Charitable Company • Wyndham Charitable Trust • Renee Recheal Liebesny Legacy • Dunhill Medical Trust • Shirley M Kanaar Legacy • Edwin George Robinson • Sir Arthur Sims Fund Charitable Trust • Sorab (Soli) Jamshed Lam Legacy • Eido Healthcare Limited • Tudor Edwards Fellowship • Vandervell Research Fund
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Picture 16 gallery
International surgical skills Society of Academic and Miscellaneous workshops Research Surgery (SARS) 2017 meeting in Dublin 13 Professor Harold Ellis celebrating his 1 Bill Thomas teaching in Addis Ababa 90th birthday at the College with former Westminster Hospital Nurses 2 Bynvant Sandhu demonstrating suturing in 8 Professor Michael Kerin delivering the John 14 Professor Malcolm Reed and Clare Marx at Addis Ababa Farndon Lecture Brighton Medical School 3 Derek Alderson teaching in Guatemala 9 Professor Monty Mython & Professor 15 Martyn Coomer with the Fulbright Scholars 4 Tom Pinkney teaching in Guatemala Mike Grocott from the Royal College of Harveer Dev and Katherine Gash before they 5 Rhiannon Harries teaching knot tying Anaesthetists went to the States, at a Fulbright Reception in Veracruz 10 Delegates from Belfast at Lancaster House 6 Derek Alderson teaching in Veracruz 11 Professors Dion Morton, Arnie Hill and 16 2015/16 Research Fellows Vanessa Brown, 7 The Faculty in Veracruz Derek Alderson Mohammed Chowdhury, Tom Wiggins & 12 Professor Sir John Temple delivering the Peter Szatmary with the Trustees of the BBA lecture Freemasons’ Research Fund at their annual meeting at the College
105 You can make a diff erence. We need to develop our surgeons through training and research opportunities so that they excel and fulfil their potential and provide the highest standards of patient care.
Future innovations in surgery will continue to be driven by research and surgical research continues to provide signifi cant advances in a wide range of areas.
Research at the College relies almost exclusively on legacies, gifts and donations. We need your help if this work is to continue and fl ourish. Making a will is a signifi cant personal responsibility and the people and causes you remember in your will are a positive recognition of all that is important to you.
We understand that the welfare and concern for your family and friends comes fi rst. Just as a will brings security to those closest to you, a legacy to the Royal College of Surgeons plays a crucial role in maintaining and supporting the improvement of surgical care for patients.
For more information or an informal chat about a legacy to the College, please contact us at fundraising rcseng.ac.uk or call 020 7869 6086.
106
4738 - RCS - Surgical Research Report_AD_AW.indd 1 23/06/2017 17:09 You can make a diff erence. We need to develop our surgeons through training and research opportunities so that they excel and fulfil their potential and provide the highest standards of patient care.
Future innovations in surgery will continue to be driven by research and surgical research continues to provide signifi cant advances in a wide range of areas.
Research at the College relies almost exclusively on legacies, gifts and donations. We need your help if this work is to continue and fl ourish. Making a will is a signifi cant personal responsibility and the people and causes you remember in your will are a positive recognition of all that is important to you.
We understand that the welfare and concern for your family and friends comes fi rst. Just as a will brings security to those closest to you, a legacy to the Royal College of Surgeons plays a crucial role in maintaining and supporting the improvement of surgical care for patients.
For more information or an informal chat about a legacy to the College, please contact us at fundraising rcseng.ac.uk or call 020 7869 6086.
107
4738 - RCS - Surgical Research Report_AD_AW.indd 1 23/06/2017 17:09 For information on donating visit www.rcseng.ac.uk/donate email [email protected] or call 020 7869 6086
To contact the research department email [email protected] or call 020 7869 6614
The Royal College of Surgeons @RCSnews
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