91Ö±²¥

Department of Oncology and Metabolism

The surgical research areas of interest within the Department of Oncology and Metabolism relate to the management of breast cancer with a wide study portfolio spanning molecular genetics, health services research, quality of life research, psycho-oncology, the management of the older patient with cancer, qualitative and mixed methods research and population data modelling and health economics. There is also a very active research group looking at angiogenesis and the genetics of breast cancer and a highly active bone biology unit looking at the management of bone metastases both in terms of the molecular mechanisms of metastatic disease progression and its inhibition, but developing clinical trial interventions to enhance oncology outcomes.

The unit has strong links to other units including ScHARR (statistical modelling, health economics analysis) and the Department of Surgery of the 91Ö±²¥ Teaching Hospitals NHS Foundation Trust. The latter is overseen by the research lead, Professor Steve Brown who has a special interest in perianal disease and inflammatory bowel disease.

The unit offers research supervision of PhDs, MDs, Masters degrees and BMedSci projects across a range of subject areas as detailed below.

Clinical research areas

Breast cancer

The unit has a programme of research evaluating various aspects of the diagnosis and treatment of breast cancer in older women. There is increasing recognition that this age group of women have inferior cancer outcomes to younger women. The group has collaborative links with experts across the UK and Europe and are involved in the study of the use of hormone therapy alone in older women with breast cancer (primary endocrine therapy), with particular reference to the treatment’s efficacy and the decision-making process women undergo in deciding whether to have surgery or not.

Decision-making about the choice of primary endocrine therapy or surgery in older women is an important challenge for women with breast cancer and is an active research interest of the group. The unit has UK wide collaborative links with experts in the field of decision science and has published widely in this area leading a large multicentre cluster RCT to evaluate a decision support intervention for older women.

The unit also has an active research programme investigating the physical and psychological outcomes for women at increased familial breast cancer risk as a result of inheritance of BRCA gene mutations.

Endocrine surgery

There are a number of ongoing projects relating to improving clinical outcomes following management of endocrine surgical disease.
Some of the key research themes are:

1. Thyroid cancer epidemiology – reducing over diagnosis and overtreatment
2. Post surgical hypoparathyroidism – developing new techniques in reducing risk and appropriate management
3. Optimal surgical management of primary hyperparathyroidism

The unit is currently involved in translational and early clinical (phase I/II) studies of novel intraoperative devices and exploring new management strategies in thyroid cancer and primary hyperparathyroidism.

The unit actively involves medical students and trainees at different stages of their training in various audits, service evaluation and clinical research projects. It also offers projects for BMedSci, MSc and MD/PhD research programmes.

Students and trainees interested in endocrine surgery research may contact Mr Saba Balasubramanian by email s.p.balasubramanian@sheffield.ac.uk

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Basic science research

Angiogenesis

The major area of basic science research relates to angiogenesis and the tumour microenvironment. Most human solid tumours exist in sub-optimal levels of oxygen and nutrient supply as a result of the fact that they ‘outgrow’ their pre-existing blood supply. Tumours partially compensate for this by inducing the ingrowth of new blood vessels, angiogenesis. This process is vital to the survival and growth of the tumour. The process is highly complex with many regulatory processes and is a new target for anticancer therapies which is highly promising.

The Microcirculation research group is internationally renowned for its work in this field of research and is actively studying the following areas:

• Angiogenesis
• The Coagulation Cascade
• The Endothelial Cell Cytoskeleton as a Therapeutic Target
• Vascular Maturation and Targeting
• Imaging the Tumour Vasculature in the Clinic

Sarcoma molecular genetics

Sarcomas are very rare tumours derived from the structural tissues of the body such as bone, blood vessels or fatty tissue. They are poorly understood in terms of the underlying mechanism of their development. The Unit has an active research programme looking at the underlying genetic abnormalities of sarcomas.

Breast cancer molecular genetics

The Institute for Cancer Studies has an active programme of research looking at the genetic risk factors which influence whether a woman will develop breast cancer, her response to treatment and survival. There are a number of active collaborative projects between the Institute and Academic Unit of Surgical Oncology. The unit has a large database of linked clinical data, tumour and blood samples from women with the disease and is exploring the relationships between novel genetic and epigenetic factors and clinical/pathological variables such as tumour subtype.

General surgery

General surgery is a wide-ranging department with care of upper and lower gastrointestinal problems as well as liver and pancreatic disease. From a research perspective there has been a recent expansion of services on the back of direct surgical directorate support as well as support from the research directorate. There are 10 research active staff with infrastructure support in the form of 2 research coordinators. Currently additional infrastructure requires nurse support through the Clinical Research Faculty but we are hoping to fund a dedicated research nurse in the near future.

We currently have 10 portfolio studies running or in the process of set up. These include HTA funded projects. We therefore have a track record of obtaining grants and running them successfully to completion. Over the last 2 years the department has published over 30 peer reviewed articles including publications in The Lancet.
Some of the key research themes include:

General coloproctology:
1. Pilonidal sinus classification, core outcome sets, consensus and comparative studies on front running procedures.
2. Haemorrhoidal disease network meta-analyses & PRO validation
3. Enhanced cohort analysis using an interrupted time series for investigation of treatment of rectal prolapse
4. Development of decision aid for treatment of large colonic polyps

Inflammatory bowel disease
5. Perianal Crohn’s disease classification and comparative studies on front running procedures
6. Ileocaecal Crohn’s including mixed-method analysis of patient decision making
7. Investigation into novel methods of anastomosis and effect on recurrence in Crohn’s
8. Development of decision aid for patients considering surgery for ulcerative colitis.

Emergency surgery & perioperative care
9. Risk prediction tools, development of an integrated care pathway and PPI work with elderly patients undergoing emergency general surgery.
10. Evaluation of parenteral nutrition in the management of small bowel obstruction.
11. Identification and optimal management of atrial fibrillation in older patients undergoing colonic resection.

Upper GI surgery
12. Gallstone surgery

The department has successfully supervised several higher degrees including at BMedSci, MD and PhD level. Integrated facilities exist for this work to be carried out and there are strong links with the University of 91Ö±²¥ through ScHARR and with other University laboratory facilities. There are also major collaborations with Queen Mary University of London, Birmingham Clinical Trials Unit and Edinburgh University.

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Academic lead

Professor Lynda Wyld l.wyld@sheffield.ac.uk