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Research Professor Andrew G Renehan PhD FRCS FRCS(GenSurg)

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1 Research Professor Andrew G Renehan PhD FRCS FRCS(GenSurg)
Peritoneal Tumour Service Patient Day Christie 21st September 2016 Research Professor Andrew G Renehan PhD FRCS FRCS(GenSurg) Colorectal & Peritoneal Oncology Centre, The Christie NHS Foundation Trust; Division of Molecular & Clinical Cancer Sciences, School of Medical Sciences, University of Manchester; Manchester Academic Health Science Centre

2 Research framework Pseudomyxoma peritonei (PMP) Appendiceal cancers
Peritoneal metastases from colorectal cancer Appendiceal tumours

3 Complications & mortality: cyto +HIPEC for PMP
No. of pts Complications (%) Mortality (%) Washington 501 40 2 Amsterdam 103 54 3 Winston-Salem 110 38 - Regensburg 28 36 7 Milan 33 Lyon 27 44 Vancouver 11 56 18 Sydney 50 48 4 Manchester (2009) 118 9 Yan et al. Systematic review …… cyto + HIPEC .. PMP Ann Surg Oncol 2007

4 Manchester update analysis
Jan 2013 to Jun 2015 Prospective; monitored 3 monthly N: 1105 major complex/major/ intermediate 304 major peritoneal operations Grant Punnett Lee Malcomson

5 Manchester results: complications
Complication grade Totals (N: 304) Grade 0 180 (59) Grade 1 24 (8) Grade 2 63 (21) Grade 3 29 (9.5) Grade 4 6 (2) Grade 5 2 (0.7) App Tumour (N:230) PMCR (N:74) 140 40 19 5 47 16 20 (9) 9 (12) 3 (1) 3 (4) 1 (0.4) 1 (1) 12.5% 10.4% 17.6%

6 UK & Ire. Peritoneal Tumour Services
Reference treatment centres (appendiceal & PMCR) Hampshire Hospitals NHS FT The Christie NHS FT Other treatment centres (PMCR only) Mater Misericordiae University Hospital, Dublin Ninewells Hospital and Medical School, Dundee Good Hope Hospital, Birmingham

7 Study Aim IDEAL Framework
To develop a robust and reproducible framework in which to undertake a phase III trial in patients with PMCR suitable for CRS with or without HIPEC IDEAL Framework As CRS with HIPEC is a complex multi‐component intervention, we propose to address this agenda using the principles of the IDEAL framework Idea Development Exploration Assessment Long-term Study

8 PMP: laboratory research
Andrew Renehan Darren Roberts Peter Stern

9 PMP: laboratory research
Bowel cancer >50% Tumour PMP < 5% Tumour PMP cells Mucin

10 Laser Capture Microscopy
Diseased Epithelium Normal Epithelium

11 PMP: lab findings (1)

12 PMP: lab findings (2)

13 HIPEC Oxaliplatin 0.14 0.22 0.37 0.61 1.0 50 100 Clinical dose range

14 Future studies Cell line ‘high-through’ drug screens in PMP
Determine key driver genes in PMP Characterise colorectal cancer with peritoneal metastases

15 Summary Prospective outcome analyses Trials (multi-step process)
Laboratory research

16 Acknowledgements The patients
The Christie Colorectal & Peritoneal Oncology team O’Dwyer Wilson Selvasekar Fulford Aziz Minicozzi Deshpande Kochhar Mullin Saunders Braun Mullamitha Chakrabarty Christie data team Morrison Punnett Crichton Fernandez de-Silva Halstead Butler Brown Tyrell Secretaries MDT coordinators Anaesthetists Theatre staff Perfusionists CCU staff Ward staff University of Manchester Emsley (statistics & methodology) Science laboratory Stern Roberts Brognard Bowel Disease Research Foundation The patients


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