HCA International Foundation Travelling Fellowship Report

The Toronto Hepato-Pancreato-Biliary (HPB) Surgical Oncology and Multi-organ Transplantation Fellowship: A ‘Finishing School’ for a HPB Surgical Oncologist

Fellowship recipient:

Mr Siong-Seng Liau, MD FRCS (Gen Surg) MRC-Academy of Medical Sciences Tenure-track Clinician Scientist

Honorary Consultant in HPB Surgery Department of Surgery, Addenbrooke’s Hospital, University of Cambridge

Centre location:

HPB Surgical Oncology and Multi-organ Transplantation Unit, Toronto General Hospital, Canada

Mentors:

Prof Steven Gallinger, Chief of HPB Surgical Oncology, Professor of Surgery

Prof Paul Greig, Programme Director of Toronto HPB Fellowship, Professor of Surgery

Duration:

1 year; 1 Jan – 31 Dec 2013

A premier HPB Surgical Oncology fellowship programme

I have now completed the one-year post-CCT Fellowship in Hepatopancreatobiliary (HPB) Surgical Oncology and Multi-organ Transplantation at the Toronto General Hospital and Princess Margaret Comprehensive Cancer Centre, Canada. It was a great privilege to be the first British trainee to be accepted into this prestigious programme. This is probably one of the most technically demanding HPB Surgical Oncology Fellowships in the world. Many graduates of this fellowship programme have taken up leadership positions in major HPB units worldwide. Indeed, I was fortunate to have been given the opportunity to complete this 2-year programme within 1 year. I had the opportunity to work closely with a group of surgical mentors who are each highly-skilled and with so much to offer in terms of surgical teaching and skill impartment. In addition, I worked with a highly-selected group of HPB and Transplant Fellows who came from some of the most prestigious HPB and Transplant units in the world. The volume of caseload was astounding. From the start, it was clear that the focus of this fellowship was on intense operative training to achieve the highest standards. In fact, this was expected by each surgical mentor that fellows were the primary surgeons in each operation from ‘skin-to-skin’, even with the most complex operations. For instance, I performed a liver transplant ‘skin-to-skin’ with the assistance of Prof Paul Greig soon after arriving in the unit, and the patient sailed through the postoperative course! The transplant commitments were onerous, including donor calls covering a large area of Ontario and often, out with the province on private jets arranged by the Ontario Transplant Agency, the Trillium Gift of Life Network. The ethos of the programme emphasises the importance of ‘hybrid’ training (i.e. combined HPB and transplant training) as surgical skills involved in multiorgan transplantation (particularly, liver transplantation) complements and enhances the surgical competence of a HPB surgical oncologist. The in-depth experience in liver transplantation provided a unique training opportunity, as many of the principles of liver transplantation are highly relevant to complex HPB resectional surgeries. Having completed this programme, I cannot agree more with this principle, as one’s confidence builds with training in such complex surgeries, particularly with vascular reconstructions required for major HPB resections. There is no doubt that this year has provided me with an outstanding fellowship experience, with a broad and intense training.

Structure of programme

At an early stage of the fellowship, I already felt that the fellowship programme makes a concerted effort to respect the learning needs of each fellow. A structured fellowship objective list was given at the outset. The programme director (Professor Paul Greig) meets regularly with the fellows to review their progress. My fellowship year consisted of 9 months of combined HPB and transplant experience, followed by 3 months of dedicated HPB Surgical Oncology training under the mentorship of Professor Steven Gallinger. The multidisciplinary experience included participation at Surgical Oncology and Hepatoma Tumour Boards with close interaction with our radiation/medical oncology and interventional radiology colleagues. The HPB Surgical Oncology clinics were run at the Princess Margaret Comprehensive Cancer Centre, often in parallel with Medical and Radiation Oncology which facilitated the close interaction with the Oncology teams to provide a seamless cancer care. There were weekly dedicated fellow teaching sessions delivered by the Transplant service. Of note, the Friday HPB Surgical Oncology Rounds were highly educational with each fellow having to discuss in detail the management of difficult clinical cases. This served to train fellows to think independently, offer alternative surgical approaches, and to discuss the roles of adjuvant and neoadjuvant therapies. I found this a wonderful opportunity to train in reviewing CT and MRI imaging ‘on the fly’ and to appreciate subtle important findings that may affect surgical management. Each fellow is placed on the spot to assess imaging of complex surgical cases and often, the fellow decides the management strategy (with the consensus from the attending staff surgeons). The fellows are trained to efficiently interpret the resectability of complex oncology cases, and are required to think through the balance of issues associated with each surgical approach, and to provide alternative surgical strategies (e.g. two-stage liver resections for bilobar colorectal liver metastases, combined RFA and liver resections, combined liver resections with colonic resection of primary cancer). In addition, there was also extensive discussion on the suitability of patients for surgical oncology trials (e.g. R-CAP trial with neoadjuvant chemotherapy followed by arterial resection for locally advanced pancreatic cancer deemed unresectable upfront). Through this training, I have gained sufficient experience to independently interpret imaging modalities to plan surgical treatment, which will be useful for undertaking the roles of a Consultant HPB surgeon during a HPB MDT in the UK.

Breadth of experience

During the course of the year, I was exposed to over 250 major operative cases. The Toronto HPB Surgical Oncology team attracts some of the most technically-demanding HPB cases from the region of Ontario and Canada as a whole. I learnt to manage an extraordinary array of complex HPB conditions. The service also features experience in laparoscopic assessment and treatment. From the HPB standpoint, many of the cases undertaken are difficult resections requiring major vascular reconstructions which often may be considered out with the technical expertise of smaller units. Further, I was trained in the overall objectives of surgical oncology which focus on combined modality approach (surgical treatment, chemoradiotherapy and novel targeted therapies) to the treatment of HPB cancer patients. This was the most intense surgical/operative experience that I had during my surgical career. As such, my surgical experience completely exceeded my expectation. Not only was I ‘coached’ in complex HPB resections and transplant operations, I was also allowed to teach surgical residents and mentor them through parts of the operations. This, I found useful, in that, I will have acquired the ‘Toronto’ way of surgical teaching; empowering the trainees and guiding them through complex operations through a series of steps (without taking over!).

The unit is also a world-renowned centre for living donor liver transplantation (LDLT), being the largest North American centre for this (a total of over 500 LDLTs performed to date). The quality of surgery required to achieve this status and the good outcome associated with this technically demanding surgery runs parallel with the quality of training within this fellowship. Given that the Toronto HPB Unit is the largest in Canada, the specialist experience I obtained during the year included extended liver resection for Klatskin tumour, repair of bile duct injuries (post lapaparoscopic cholecystectomy referred from elsewhere), pancreatic resections with vascular reconstructions, laparoscopic liver and pancreatic resections, living donor (LD) hepatectomies and LD liver transplants. This extent of major cases undertaken as a fellow will be difficult to replicate in other units in the world. My surgical experience has enhanced my competence to undertake major HPB resections, and the experience from vascular reconstructions gained from multiorgan transplantation (especially liver transplantation) has provided me with the expertise to provide an aggressive approach to HPB malignancies, but being mindful that aggressive surgical resection can only provide a good outcome if we are selective.

Of interest, given that Toronto has a large immigrant population and there is a high prevalence of hepatitis B compared to other Western populations, consequently the caseload for HBV cirrhosis and hepatocellular carcinoma (HCC) is high. As such, I gained extensive experience in managing HCC in the spectrum of patients with varying degrees of liver cirrhosis. The careful tailoring of treatment for such group of patients is crucial to achieve satisfactory outcome. This experience was gained by participating in the weekly hepatoma rounds where the multidisciplinary approach is particularly emphasized.

Importantly, I gained important technical ‘pearls’ from the team of outstanding surgeons. The operative set-up (e.g. placement of retractors, operative planning) to ease resections cannot be underestimated, and I have adopted this in my own consultant practice. Precise conversance with liver anatomy and major hepatectomy techniques can only be gained through extensive caseload experience with a wide spectrum of disease. With this fellowship, I think I have achieved this. I have enhanced my knowledge and skill base, especially in the techniques to major hepatectomies (i.e. spectrum of techniques from using hydrojet liver transection to conventional Kelly clamp technique) and a detailed understanding of the surgical anatomy for segmental resections. Throughout the fellowship, I was exposed to a meticulous approach with elegant techniques of dissection for elucidating hepatic vascular and biliary anatomy. In pancreatic resections, although I have had significant experience Whipple’s pancreaticoduodenectomies prior to starting this fellowship, I gained further technical pearls to fine-tune this complex surgical undertaking.

In summary, I have achieved the following learning objectives within the year:

  • Achieved competency in liver resection including extended liver resection with vascular resection
  • Achieved competency in pancreatic resection including portal vein resection/reconstruction
  • Enhanced skills in minimally-invasive techniques for the diagnosis and management of HPB malignancies (including laparoscopic liver resection and distal pancreatectomy)
  • Exposure and in-depth understanding of the roles of neoadjuvant and adjuvant chemo- and radiotherapy specific to HPB malignancies
  • Achieving skills set required to run surgical oncology trials.

Research training in HPB Surgical Oncology

As an Academic HPB Surgical Oncologist, my translational research interests are focussed on the molecular pathogenesis of pancreatic cancer, with the aim of identifying rational therapy for this disease based on our understanding of the biology. Being affiliated with the Princess Margaret Comprehensive Cancer Centre (one of the largest comprehensive cancer centre in the world), I was able to keep abreast with the latest developments in the treatment of pancreatic cancer. In the last 3 months, I was the HPB Surgical Oncology fellow to Professor Steven Gallinger, who mentored my attachment. During this time, I was able to focus more on the research work, given that the ward work was assisted by a group of competent senior residents. Throughout the year, I was regularly attending the Gallinger Laboratory Meeting, and gave several talks during that time. Professor Gallinger is the Director of the Pancreatic Cancer Translational Initiative at the Ontario Institute of Cancer Research. His laboratory is focussed on identifying high-risk genes that predispose to development of hereditary pancreatic cancer.

As a basic scientist and a surgeon, I was determined to undertake projects which allow me to understand the biology of pancreatic cancer, and at the same time, link the biology to the clinical picture of real patient disease. My research interests in Cambridge involve the development of novel in vivo models with inherited aberrant DNA repair genes (e.g. BRCA2) to recapitulate hereditary and sporadic pancreatic cancer. These mouse models with deficient DNA repair mechanisms display a ‘mutator’ phenotype which may help to explore the wider genetic landscape of pancreatic cancer. Our research strategy of characterising the genetic landscape underpinning pancreatic cancer development will yield rational therapies and new biomarkers for this deadly cancer. These mouse models also allow therapeutic testing of novel agents, paving the way for personalised pancreatic cancer therapy based on tumour mutations. As a continuum of this work, I identified a specific project in Toronto which allows me to understand the link between the biology and clinical feature of patients with BRCA1/2 mutations who develop pancreatic cancer. This project serves to understand the natural history of this unique group of hereditary pancreatic cancer, and to identify if there are any predictors of long term survival. The completed manuscript is entitled ‘Clinico-pathological features and survival outcomes of pancreatic cancers in BRCA1 and BRCA2 mutation carriers: the Ontario experience’.

Further, my ongoing work in Cambridge involves the development of novel PALB2 (partner and localizer of BRCA2 gene) in vivo model of pancreatic cancer. Coincidentally, Professor Steven Gallinger’s group had recently identified a patient with germline mutation in PALB2 gene who developed pancreatic cancer. Having negotiated the ethical approval, I retrieved the samples from the Ontario Biorepository, harvested the DNA from both the germline sample and the pancreatic cancer and these are currently undergoing next-generation whole genome sequencing to allow us to understand the impact of such germline mutation on the genetic landscape of the resulting pancreatic cancer. This work will complement my current research in Cambridge. Given the hectic clinical schedule during the year, I am proud to have completed this research, and they were intended as achievable milestones.

Dividends of fellowship

The unique nature of this fellowship is that it aims to provide well-rounded ‘hybrid’ training for a HPB Surgical Oncologist, combined with in-depth technical training in multi-organ transplantation. This fellowship represents an ideal training position for a surgeon-scientist to achieve excellence in clinical surgery and research. More importantly, the unit has a group of academic surgeons who are outstanding role models. It is exemplary as they are examples of surgeons who are technical experts, and at the same time, remain passionate and productive in academic endeavours. This convinced me that a career as a surgeon-scientist is clearly possible! Through this fellowship, I am privileged to have work for Professors Gallinger, Greig and Grant, whom I can rely on as career mentors, which I will surely benefit from when building a career as a young surgeon-scientist.

This fellowship has laid the foundation for life-long friendships and research collaborations between the Cambridge and Toronto HPB units. This fellowship promoted cross-fertilisation of research ideas and clearly, this will be immensely helpful for my development as an academic surgeon. I am convinced that the exposure gained through this effort has been one that is worthwhile, both to my personal development and in providing me with the impetus to train as an academic HPB surgeon. I have now returned to Cambridge to assume the post of an Academic Consultant HPB Surgeon, funded by the MRC and Academy of Medical Sciences Clinician Scientist Fellowship. I intend to transfer the skills and knowledge learnt to my trainees.

Acknowledgement

I would like to thank the HCA International Foundation for supporting this fellowship.

Grants awarded

  1. Pancreatic Society of Great Britain and Ireland (PSGBI) Pump-priming Grant (Role: PI, HPB basic oncology research).
  2. Royal College of Surgeons of Edinburgh Small Research Grant (Role: PI, HPB basic oncology research).
  3. MRC Centenary Early Career Award (Role: PI, HPB basic oncology research).

Publications – book chapter

  1. S-S.Liau, D.A. Tuveson: Molecular pathology of pancreatic cancer. Chapter in Molecular Oncology: Causes of Cancer and Targets for Treatment, 1st Edition, (Edward Gelmann, Charles Sawyers, and Frank Rauscher III, eds), Cambridge: Cambridge University Press 2014.

Publications – peer reviewed

  1. S-S.Liau, M.S. Qureshi, R. Praseedom, E. Huguet (2013). Molecular pathogenesis of hepatic adenomas and its implications for surgical management. Journal of Gastrointestinal Surgery 2013; 17:1869-82 (2012 Impact factor: 2.361).
  2. S-S.Liau, L. Cassidy, A.R. Venkitaraman (2014). Chromosome instability and carcinogenesis: insights from murine models of human pancreatic cancer associated with BRCA2 inactivation. Molecular Oncology 2014 (in press) (2012 Impact factor: 6.379).
  3. D. Al-Adra, R. Gill, S. Axford, X. Shi, N. Kneteman, S-S.Liau (2014). Treatment of unresectable intrahepatic cholangiocarcinoma with yttrium-90 radioembolisation: a systematic review and pooled analysis. Completed; in submission.
  4. S-S.Liau, E. Whelan, H. Shoushtari, Z. Kanji, S. Holter, S. Cleary, S. Gallinger (2014). Clinico-pathological features of BRCA1/2-associated pancreatic cancers: is this a clinically heterogenous disease? Completed; in submission.

Publications – unindexed

  1. S-S.Liau (2013). Laparoscopic hepatopancreatobiliary fellowship with Professor Brice Gayet at the Institut Mutualiste Montsouris, Paris. ALSGBI Winter Newsletter 2014 (in press)

 

    Mr Siong-Seng Liau with Prof Steven Gallinger at the end of an all-day HPB Surgical Oncology Clinic at the Princess Margaret Comprehensive Cancer Centre
    The Toronto General Hospital HPB Surgical Oncology Team (L-R; Prof Carol-Anne Moulton, Dr Alice Wei, Dr Sean Cleary, Mr Siong-Seng Liau and Prof Steven Gallinger)
    Farewell Dinner at the end of my one-year fellowship (L-R; Prof Paul Greig, Prof David Grant, Dr Pablo Serrano, Mr Siong-Seng Liau, Prof Mark Cattral and Dr Ian McIlvray)
    Prof Paul Greig delivering one of the weekly fellow’s teachings on segmental anatomy of the liver
    Mr Siong-Seng Liau performing a Whipple’s pancreaticoduodenectomy, assisted by Prof Carol-Anne Moulton