Cabrini Monash University Department of

Cabrini Monash University Department of Surgery, The Fröhlich West Chair of Surgery

Head: Professor Paul McMurrick

Safety in Surgery through research: The cornerstone of all our research is the colorectal neoplasia database allowing us to carry out a large number of clinical research projects. For example, research projects investigate which patients are at most risk of developing complications after surgery, which patients might have a recurrence of their cancer, and how we can improve cancer care for improved patient outcomes.

Head of Department - Fröhlich West Chair of Surgery Professor Paul McMurrick

Consulting Surgeons Mr Stephen Bell, Colorectal surgeon, Senior Lecturer Mr Peter Carne, Colorectal surgeon, Senior Lecturer Mr Martin Chin, Colorectal surgeon and Director of Colorectal Fellowship Program Mr Chip Farmer, Colorectal surgeon, Senior Lecturer Emeritus Professor Adrian Polglase Mr Pravin Ranchod, Colorectal surgeon, Lecturer Mr Paul Simpson, Colorectal surgeon Mr Raymond Yap, Colorectal and Academic surgeon, Research Fellow Dr Evan Williams, Colorectal Fellow Dr Gemma Solon, Colorectal Fellow

Senior Research Fellows Dr Simon Wilkins Dr Rebekah Engel Dr Christine Koulis

Database Manager Karen Oliva

PhD Students Stephen Bell, Monash University Sara Hlavca, Monash University

Honours Student Claudia Corrente

In conjunction with clinical governance at Cabrini Hospital, we have a quarterly quality assurance loop to ensure that not only are the overall results for the treatment of bowel cancer at Cabrini at an international standard but also that the individual outcomes of every surgeon are scrutinised and reported.

Personalised medicine tissue platform

Through our three main collaborative projects with Monash University, namely organoids, tissue microarray and the new tissue-slice assay, we are able to match individual tumour responses to drug treatments, gene expression, and immune responses in the laboratory to clinical data in the colorectal neoplasia database on patient outcomes and the success of their treatment. When combined, these three major projects will have the potential to personalise treatment for each bowel cancer patient in the future.

Highlights

1. Colorectal Cancer organoid program Our program is developing a high throughput screening platform to test known and

novel compounds with anti-cancer properties on patientderived tumour organoids. Organoids are “mini-organs” that can be grown in a laboratory dish, recapitulating the features of the tissue from which they are derived. This project aims to not only determine the likelihood of a patient responding to treatment before they receive it in the clinic, but to create a platform for testing novel compounds that may have efficacy for the treatment of CRC.

Grant award: • Eirene Lucas Foundation ‘Anti-cancer compound library resource for drug discovery’ (2019-2020) $10,000 Engel, R (CI) McMurrick, P (CI) • Cabrini Foundation Research Grant ‘Personalising cancer medicine: the development of a high throughput drug screening platform using patientderived colorectal cancer organoids’ (2020-2021) $30,000 Engel, R (CI) McMurrick, P (CI)

Presentation at a national conference: Engel, R 'Organoids as a model for colorectal cancer: the first 50 patient lines' ASSCR - AGCTS - ISCT ANZ 2019 Joint Scientific Meeting, Brisbane, 13th-15th November 2019

Significant Publication: Engel, R et al., (2020) Patient-derived colorectal cancer organoids upregulate revival stem cell marker genes following chemotherapeutic treatment. J Clin Med. 9, 128

2. New Team Member Mr Raymond Yap re-joined Cabrini after a fellowship at AdventHealth Orlando, under world leaders in advanced minimally invasive surgery, Professor John Monson and Professor Matthew Albert. Mr Yap, previously clinical colorectal fellow in 2015, has now been appointed to coordinate research projects. Mr Yap will be able to provide our research fellows with a clinical eye to their research and together the team strives to break new ground in combating bowel cancer through research.

3. Peri-operative care Oversewing staple lines and the relationship to anastomotic complications in colorectal cancer

RESEACHERS: BAQAR A, WILKINS S, OLIVA K, MCMURRICK P

During bowel cancer surgery an anastomosis can be formed with a surgical stapler or hand sewn. This project aims to examine whether oversewing staple lines reduces postsurgical complications for patients.

Podium Presentation and award at an national conference: Wilkins S (2019) The post-operative effect of oversewing stapled anastomoses in colorectal cancer surgery. AGITG Annual Scientific Meeting 21-23rd August 2019 Adelaide, Australia Best Fast Forward Presentation

Publication: Baqar, A et al., (2020) The post-operative impact of oversewing stapled anastomoses in colorectal surgery: A retrospective Australian cohort study. International Journal of Surgery Open 24:91-95.

Our Research

Highlighted project: The Colon Cancer Tissue Microarray Project Personalised medicine allows a tailored approach to medical treatment based on each patient’s specific biology and relies on scientifically developed correlations between responses to treatment and specific biomarkers. The colon cancer tissue microarray project aims to personalise treatment for colon cancer patients by creating a valuable resource to understand each patient’s biology. We create tissue microarrays, comprising of tumour and normal tissue taken from the patient at the time of surgery, and correlate between specific biomarkers of interest and patient outcomes through proteomics. We are on target to complete over 1000 patients with up to five years follow-up by the end of 2020. The results from this study will provide important novel prognostic and predictive information that may identify factors that can influence chemotherapy choice, leading to more personalised streamlining of therapy to each individual patient, as well as identifying new protein targets that could form the basis of targeted therapies.

Highlighted project: The prognostic implications of primary tumour location on recurrence and patient outcomes in early-stage colorectal cancer There is significant interest in identifying markers of indicators to predict outcomes including tumour recurrence and patient survival from colorectal cancer. This project aims to examine the implications of tumour location in early colorectal cancer on recurrence and outcomes. This project shows that overall and cancer-specific survival is worse in those patients with right-sided tumours. A paper from this project is under review at the journal Diseases of the Colon and Rectum. This project also won best MPCCC cancer poster award at last year’s Cabrini Research Week: Oliva K, Bell S, Wilkins S, McMurrick P (2019) Influence of primary site on metastatic distribution and survival of early-stage colorectal cancer.

Selected other projects: Screening and prevention • Comparison of outcomes of colorectal cancer depending on patients within the screening ages

Perioperative care • The impact of double stapled anastomosis in restorative colorectal cancer surgery

Patient outcomes • Factors affecting the short- and long-term outcomes from colorectal cancer surgery in older patients • Patient reported outcome measures • Preoperative glycated haemoglobin and insulin treatment: Risk factors for patients with type 2 diabetes undergoing colorectal cancer surgery • Outcomes after colorectal cancer surgery in patients with Stage IV disease

Collaborative research projects • Defining the T cell-suppressive mechanisms and phenotypic identity of cancer-associated fibroblasts

Mr Raymond Yap

COLORECTAL AND ACADEMIC SURGEON, RESEARCH FELLOW

(After and) Before Cabrini Between his time as the Cabrini research fellow and his appointment as a colorectal and academic surgeon both at Cabrini Hospital and Institute, Mr Raymond Yap has completed the Australian and New Zealand Sub-specialty colorectal training over two years at the Prince of Wales, Sydney and St Vincent’s, Melbourne. After this, he decided to pursue an advanced minimally invasive colorectal fellowship at AdventHealth in Orlando, Florida, the largest hospital by bed count in the USA, with around 2000 beds, four intensive care units and a multitude of operating theatres. The colorectal program was led by Professor John Monson, an internationally renowned academic surgeon as well as Dr Matthew Albert, who invented the Transanal Minimially Invasive Surgery (TAMIS) platform used throughout the world today. The ability to tap into these resources and knowledge was an enlightening experience that allowed Raymond to explore the limits of minimally invasive surgery. There was a strong emphasis on research, and its place within the clinical and cultural milieu of surgery within the USA. There were opportunities to meet many visiting professors, each famous in their own right in the field of colorectal surgery.

In the midst of this activity, he completed a Masters in Surgical Education through the University of Melbourne, focusing on the use of virtual reality simulation in the training of colonoscopy. This allows great insight into the place of simulation in procedural training, and broader exposure to many theoretical and practical concepts that exist in medical education. He was the fellow representative on the Colorectal Surgical Society of Australia and New Zealand’s governing council and an executive member of the Section Committee for Colon and Rectal Surgery for the Royal Australasian College of Surgeons.

Research Interests During his time at Cabrini, he developed a keen interest in surgical outcomes research. He has continued along this path and looks forward to continuing to pursue this at Cabrini. The unique position that Cabrini holds, being the originator of both the minimum and extended datasets of the Bi-National colorectal cancer audit, combined with the volume of colorectal cancer surgery conducted at Cabrini, allows for a fruitful ground for this kind of research. Although currently on hold due to COVID-19, he is interested in medical education research. Raymond hopes that with restrictions slowly lifting, there will be opportunities to conduct further research with Associate Professor David Brewster and the clinical school into how education might be better evaluated and performed.

Future Focus Raymond is a strong believer that Cabrini, as a healthcare leader, needs to continue to develop a strong academic profile. He looks forward to integrating more deeply with the Department of Surgery and Professor Paul McMurrick to increase our research output even further. He is also interested in increasing our links with the Monash Partners Consortium, to further collaboration between sites both for patient recruitment and patient trials. Raymond is eager to see the future of the Cabrini Institute under the leadership of Professor Gary Richardson OAM, and the development of the future Cabrini Cancer Institute.