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Postoperative local recurrence affects 20-30% of patients with rectal cancer. Between 1993 and 2013, University of Leeds researchers identified the importance of pathology studies to show a disease-free margin around the excised tumour and how to predict this margin routinely and accurately using simple histopathology and preoperative MRI.
We also used photography in the pathological assessment of the quality of surgery and were instrumental in the adoption of modern techniques by professional organisations around the world.
Following adoption of our techniques in England and Scotland, local recurrence has halved with 10% better survival and cost savings of £60 million. Our methods have also become the gold standard in the treatment of rectal cancer patients around the world.
Impact: Health and welfare; a UK clinical trial of uterine artery embolisation (UAE), with five-year follow-up, defined the risk- and cost-benefit of UAE versus surgery.
Significance: The trial informed guidelines/recommendations internationally and changed clinical practice. Women worldwide can now make an informed choice about their treatment; economic factors have been quantitated.
Beneficiaries: Uterine fibroid patients, the NHS, healthcare providers.
Attribution: G. Murray, UoE, developed and delivered innovative trial methodology; clinical aspects led by University of Glasgow.
Reach: UK guidelines; worldwide (Australia, USA, Europe) effect on clinical practice that will impact up to 25% of women.
Colorectal cancer is a common disease, which frequently causes death or morbidity, either because of failure to control the primary tumour or failure to prevent distant metastases. Leeds researchers have devised new treatment approaches using chemotherapy and radiotherapy and tested them in large randomised controlled trials which have led to major changes in clinical practice in the management of rectal cancer and advanced colorectal cancer (aCRC), driving clinical decision-making and improving outcomes for patients. This includes better-evidenced treatment for elderly patients and patient stratification on the basis of molecular biomarkers.
Severe Limb Ischaemia (SLI), in which there is reduced blood flow to the leg(s), is the commonest cause worldwide of gangrene and limb loss. The BASIL trial, led by Professor Andrew Bradbury at the University of Birmingham, was the first (and remains the only) randomised controlled trial to investigate whether surgical bypass or endovascular (`keyhole') treatment is best at relieving symptoms and preventing amputation and/or death in patients with SLI. The outcomes of the study have been of worldwide interest, and the recommendations put forward by the team have been endorsed by a number of high profile clinical organisations. These findings are also nowincorporated within a series of national and international guidelines on SLI.
Research at Cardiff University is underpinning the abandonment of the 100-year-old surgical practice of removing all axillary lymph nodes in cases of breast cancer. Such surgery frequently caused arm lymphoedema, loss of arm mobility and lymphatic system damage. Cardiff led the seminal ALMANAC trial which showed that full node clearance was unnecessary if a biopsy of the first draining `sentinel' node was cancer-free. Cardiff then spearheaded the impact on practice through a training and awareness programme for surgeons, primarily in the UK, but also in China, India, Brazil and Turkey. By 2010 these efforts had established the Sentinel Lymph Node Biopsy (SLNB) procedure as standard in the UK, while the study was also cited in USA guidelines. The main beneficiaries of the impact are the 50-75% of breast cancer patients who now enjoy lower levels of pain, shoulder disability and arm lymphoedema. Healthcare providers also benefit financially from a reduced need for extensive surgery.
Researchers at the MRC Clinical Trials Unit conducted a systematic review and meta-analysis of individual patient data on neoadjuvant chemotherapy for invasive bladder cancer. This work has been cited as evidence in 19 national and international clinical practice guidelines from 2008 to 2013. In most cases, the guidelines citing this review substantiate their clinical recommendations by directly quoting the review content.
Before 2010, there was no accepted standard treatment for patients with advanced biliary tract cancer. The ABC02 trial showed that the combination of two drugs (gemcitabine and cisplatin) significantly improves survival, with acceptable side effects. Consequently, national and international guidelines have been revised to recommend this regimen as a standard of care. Furthermore, in ongoing trials of novel therapies, gemcitabine/cisplatin has become the comparator group, and the aim is to improve survival above what this can already achieve.
Bowel cancer is the third most frequently diagnosed cancer worldwide. University of Glasgow researchers have established Xeloda (an oral 5-fluorouracil precursor) and XELOX (a chemotherapeutic regimen combining Xeloda with oxaliplatin) as highly effective, targeted therapies for patients with bowel cancer. Since 2008, European regulatory approval of these therapies has been incorporated into major international clinical guidelines. The research has transformed patient care by improving the treatment experience, with more convenient dosing schedules and fewer side effects compared with previous chemotherapy procedures. Xeloda and XELOX have transformed chemotherapy for bowel cancer and decreased therapeutic costs, potentially saving around £4,762 (Xeloda) and £947 (XELOX) per patient for the NHS.
Work led by researchers at UCL has had a national and international impact on the way that patients with symptoms suggestive of colorectal cancer are investigated. Specifically, investigation of the role of CT colonography (a relatively novel and non-invasive method of investigating the large bowel using an X-ray scanner) has led to this examination replacing the standard alternative of barium enema in the UK National Bowel Cancer Screening Programme and for symptomatic patients in the NHS. The research has also led to easing of pressure on over-subscribed endoscopy services in the NHS because patients can be safely diverted towards CT colonography as an alternative.
The University of Oxford's International Subarachnoid Aneurysm Trial (ISAT) changed clinical practice worldwide by showing that endovascular coiling is a more effective and safer treatment than neurosurgery following subarachnoid haemorrhage, with fewer complications and improved quality of life. Subarachnoid haemorrhages account for 1 in 14 strokes and are caused by bleeding in and around the brain; approximately 85% occur when cerebral aneurysms rupture. ISAT was the first trial to compare neurosurgery, or neuroradiological endovascular coiling in patients with ruptured cerebral aneurysms causing acute subarachnoid haemorrhage.