Gastro Intestinal

Clinical and Translational Research Team

  • Mr Andrew G Renehan (AGR), Senior Lecturer in Cancer Studies, Hon. Consultant Colorectal Surgeon
  • Miss Sarah T O'Dwyer (STO), Divisional Director, Consultant Colorectal Surgeon
  • Mr Malcolm S Wilson (MSW), Director of Surgery, Consultant Colorectal Surgeon
  • Dr Mark P Saunders (MPS), Consultant in Clinical Oncology
  • Dr Juan Valle (JV), Senior Lecturer in Cancer Studies, Hon. Consultant in Medical Oncology

This group is fully integrated at a clinical service level with the wider pelvic oncology team, and will form a key component of the proposed Academic Surgery Group (led by Professor Noel Clarke) and Tissue Banking (led by Professor Gordon Jayson).

Research themes

There are five research themes:

1. Chemotherapy clinical trials (leads, MPS & JV):

including NCRN sponsored trials, commercial trials, bio-technology studies, and in-house phase I and II trials. There are currently more than 20 GI trials. Over a 3-month period in 2006, we entered 14% of patients into trials. This figure is likely to have increased in 2007. We run pharmaceutically sponsored studies often as chief investigator for the UK (ie: AZ trials). We enter patients into NCRN trials and are the top recruiter for the ACTII trial and have entered more than 150 patients into the GemCap, Espac-3, ABC-01 and 02 trials. We collaborate with the RMH, Beatson and Leeds oncology centres for smaller biotech studies using new and novel antiangiogenic agents and cytokines. Finally we have generated a series of our own studies that have been published (SCOUT, CPT11/Lokich) or adopted by the NCRN (ie: stomach chemoradiotherapy and ABC-01 and 02 studies). The two latest ones have either just started (pancreas RT study) or are awaiting approval by the regulatory bodies (eSCOUT). The MCap study for inoperable pseudomyxoma is the only study of its type in the world.

2. Radiation and hypoxia (lead MPS):

The GI DOG has been collaborating with the NKI in Amsterdam with the running of the only stomach chemoradiotherapy trial available in the UK. The first paper was published last year in the IJROBP and the 2nd paper has just been accepted. We have recently published an article in Clinical Oncology that shows that the "Christie" rectal radiotherapy at a lower dose to a smaller volume of tissue is just as effective as the radiotherapy used widely in Europe. Further to this, we have again collaborated with the NKI and will soon publish another joint paper to show that this treatment also has less long-term side-effects. Another locally derived study has shown that tumours can be made sensitive to chemotherapy under hypoxic conditions. This was published in the Journal of Gene Medicine this year.

3. Clinical studies in surgery (leads STO & MSW):

(i) Radical pelvic surgery - outcome and quality of life: The group have reported on the clinical outcome on over 550 patients with anal cancers including the largest world series on radical salvage surgery (N = 71). A parallel report of the outcome and QoL in 60 patients undergoing total pelvic clearance has been presented. Studies on radiological imaging in this field complement these studies.

(ii) Peritoneal surface tumours: A unique study of the early biological characterisation of pseudomyxoma peritonei has recently been published reflecting the national centre status for the management of this disease since 2003

(iii) Radiation and adhesion-related intra-abdominal morbidity: There has been a long-term interest within the group in the prevention and treatment of intra-abdominal adhesions, and recent studies have characterised and compared the angiogenic properties of omental versus inter-intestinal adhesions.

(iv) Colorectal cancer follow-up: There have been several published papers from the group evaluating the effectiveness and economic aspects of follow-up after curative resection for colorectal cancer. Recent data has assessed the natural history of the development of second primary colorectal tumours in over 300,000 patients. This research links with research themes of late-effects among other groups at the Christie (Prof. John Radford, Dr Susan Davidson & Professor Peter Trainer) and planned survivorship studies in our group.

Tissue and blood banking: From these research activities, there is a well established and clinically characterised bank of tissue for colorectal tumours (N = 150, 60 paired with mucosa); metastatic liver tumours of colorectal origin (N= 45); pseudomyxoma peritonei tumours (N = 45); and serum and plasma on 600 screened patients (various risk levels); integrated and regulated within the Manchester Cancer Research Centre (MCRC)

4. Colorectal cancer prevention and early detection (lead, AGR):

(i) Colorectal cancer and obesity group: Primary prevention of colorectal cancer has become a major research theme in the group in the past 12 months. Recognising the importance of the worldwide obesity epidemic on health problems in general, AGR leads a group focusing on translational research into the role of obesity and colorectal cancer - both risk and impact on treatment. This is a new subgroup fully integrated within Clinical and Experimental Pharmacology (CEP) - (Professor Caroline Dive) formed since January 2007, and based within the Paterson Institute for Cancer Research. This group also links closely with research activity on obesity and disease at the North West Institute for BioHealth Informatics (NIBHI: Dr Iain Buchan)

Research tools range from epidemiology modelling, through in vitro mechanistic studies of the effects of chronic insulin exposure and glucose modulation, to the development of animal models of diet-induced and genetically-driven obesity with cancer predisposition.

AGR is co-lead for the recently launched Cancer Prevention Research Network, a Manchester initiative pulling together multiple disciplines with an aim of developing cutting-edge high-quality cross-disciplinary research proposals

(ii) Early detection of colorectal cancer and high-risk groups: Our group was a centre in the MRC "Flexi-Scope" trial recruiting some 1800 participants from the South Manchester areas. Biomarker research from this trial demonstrated that the measurement of insulin-like growth factors (IGFs) in the circulation has predictive potential for colorectal adenomas. We subsequently refined and quantified the relationship of circulating IGFs and tumour development through systematic review, and published several studies evaluating factors which may impact upon these predictive models through collaboration with the University of Aarhus, Denmark, and the MRC Human Nutrition Unit in Cambridge.

We have published extensively on the natural history of colorectal cancer development in acromegaly, and developed a colonoscopy screening protocol based on this evidence.

An additional level of research in colorectal cancer screening has been the use bio-mathematical modelling, through collaboration with the Fred Hutchinson Cancer Research Centre, Seattle, USA.

5. Systematic review (lead, AGR):

AGR is a member of the editorial board of the Cochrane Colorectal Cancer Group, and is the co-lead for the Systematic Reviews Research and Education Network (SyREN), Manchester (). The group uses this research tool across its clinical and laboratory projects to comprehensively dissect clinical questions and evaluate issues with quantifiable results. Examples include a meta-analysis of follow-up after curative resection for colorectal cancer, and recently, a large BMA sponsored systematic review of body mass index and sex-specific cancer risk at 13 cancer sites. This work is supported through collaborations with the University of Berne, Switzerland (Professor Matthias Egger)

Publications

Links

The TeloVac trial is a Phase 3  clinical trial in non operable, locally advance and metastatic pancreatic cancer. The trial compares a combination of Gemcitabine and Capecitabine therapy with concurrent and sequential chemoimmunotherapy, the trial uses a telomerase vaccine (GV1001). The main objective is to see if the inclusion of the telomerase vaccine (GV1001) will improve survival in comparison with standard Gemcitabine and Capecitabine alone. To achieve the above objective the trial has been designed so  that the patient will be put into three equally weighted arms.