Liver transplantation for cancer is evolving, offering new opportunities for selected patients diagnosed with Neuroendocrine Cancer and other malignancies – in terms of improvements in survival and possibly even quality of life.
In the UK and Ireland, a pilot programme has been established, focussing on the feasibility and usefulness of liver transplantation in a select group of people who have developed liver metastases from a Neuroendocrine Tumour primary.
Neuroendocrine Cancer is divided into 2 key types:
- Neuroendocrine Tumours (NETs): characterised by a well-differentiated appearance, but a range of activity, with growth and cell replication ranging from slow to rapid: Grades 1-3.
- Neuroendocrine Carcinomas (NECs): characterised by a poorly-differentiated appearance, either small or large cell, with a rapid growth and cell replication rate, Grade 3.
The programme was developed on the background of prior UK and Ireland experience and emerging global evidence, that has allowed the identification of a small sub-group of patients with Neuroendocrine Tumours, who may benefit from liver transplantation.
It is hoped that the programme will advance optimal care for this sub-group and spur a greater understanding of Neuroendocrine Tumours: generating further research into the development, diagnosis, and treatment of these malignancies, resulting in better outcomes for all Neuroendocrine Cancer patients.
Liver transplantation: a brief history
It is now 60 years since Starzl and his colleagues, in the U.S., performed the first human liver transplant: unfortunately, with poor outcomes – the first 5 patients died within a month of surgery.
Despite advances in surgical technique there was limited understanding of organ preservation and immunology: a limited understanding of why the body appeared to reject the transplanted organ.
Around the same time, in the UK, a surgeon in Cambridge, Roy Calne, was undertaking research into understanding the reasons for organ rejection and looking at how this could be overcome. From his initial use of antilymphocyte serum to his work in developing the first antirejection drug, he devised a regimen for suppressing the immune system in transplant recipients – that is still in use today.
In 1968, Calne, alongside his hepatology colleague Roger Williams, started the first UK and Europe wide Liver Transplant program and reported five successful cases.
- By 1970, almost 60 liver transplants had been performed in the United States (by Starzl) and 28 in the UK (by Calne).
- In 1979 Cyclosporine was first used (Calne, UK)
- By 1989 Starzl reported a continuous series of nearly 1200 liver transplants- with a 1 yr survival of 73% and 5 yr survival of 64% and in 1990, he reports the successful use of Tacrolimus in patients who had experienced rejection despite the use of accepted immunosuppressant medication.
Currently, in the UK, nearly 1000 liver transplants are performed every year, with a 1- and 5-year survival of 92% and 80%, respectively.
What is liver transplantation?
Liver transplantation is an operation to remove a damaged or diseased liver and replace it with a healthy one. The medical name for the procedure is orthotopic liver transplant (OLT).
Most livers used in liver transplantation come from people who have just died: these are Donors after Brainstem Death (DBD) or Donors after Circulatory Death (DCD).
Sometimes a healthy living person, usually a blood relative, will donate part of his or her liver. This type of donor is called a living-related donor. Non-relative donation is living- altruistic donation.
Adults (recipients) typically receive the entire liver* from a deceased donor or part of a liver from a living (related or altruistic) donor.
*However, surgeons may split a deceased donor’s liver into two parts: the larger part may go to an adult, and the smaller part may go to a smaller adult or child.
In the UK, of the almost 1,000 liver transplants performed every year – more than 80% use livers from deceased donors.
Despite these numbers, we, in the UK, have one of the highest rates of refusal for organ donation – with up to 40% of families declining to donate: this means that even if an individual was on the Organ Donation Register (ODR), families can and do override that person’s registered intention to donate their organs after their death.
This makes donated organs a scarce resource – not only is transplantation highly regulated, but there is also a duty of care that underpins the whole process: to ensure that such a gift is used where greatest benefit might be achieved: respecting the wishes of the donor, the impact on their family, as well as careful consideration around the implications and consequences for the recipient.
Read Chrissie’s experience here
Further information on Liver Transplantation can be read online or downloaded free from the British Liver Trust
Further information related to Organ Donation and Transplantation can be found here
Liver Transplantation and Neuroendocrine Tumours
There have undoubtedly been medical advances in both transplantation and Neuroendocrine Tumours over the last 60 years, but to truly move forward, it is also important to review processes and patient cases. Historically, from data available, liver transplantation for Neuroendocrine Tumour related liver metastases (NETLM) generated poor to barely reasonable overall and tumour-free survival outcomes in earlier case series.
It is therefore unsurprising that in the UK, liver transplantation for NETLM was halted.
But who was being transplanted? what stage/status was their NET? and why or what were they transplanted for?
Changes occur over time, and learning from experience:
past and current, helps to expand knowledge.
Reviewing earlier UK experience in liver transplantation for NETLM, it is evident that transplantation was primarily performed as a palliative procedure: a ‘rescue’ intervention rather than surgery with intent to cure. Learning from this data – as well as incorporating evidence from global transplant experience (where transplantation has continued to be undertaken and developed) it is possible to identify a small number of people diagnosed with liver metastases from a (pancreatic or gut-based) NET primary, who may truly benefit, in terms of disease-free and overall survival, alongside potential improvements in quality of life.
Evidence-based, strict criteria have been established and accepted by UK regulatory bodies, to support a UK and Ireland wide pilot programme for liver transplantation.
UKINETs Bitesize guidance on this programme is available here
Further information on the evidence supporting this guidance is available here
Please note that liver transplantation for NETLM can only go ahead if the primary and any associated lymph nodes have been completely removed – and that this is checked and confirmed.
It is not a guaranteed cure, and neither is it without considerable risk.
For many with NETLM, currently available treatments, such as surgery, interventional radiology/endoscopy, radionuclide therapy, chemotherapy and/or medical management such as SSAs (Lanreotide or Octreotide) or novel/trial therapies will offer the best treatment(s) for them.
Thank you to Tahir Shah and his Neuroendocrine Cancer & Liver Transplantation colleagues, across the UK and Ireland, for driving this programme through to fruition – and sharing your expertise and knowledge.
You can hear Dr Tahir Shah’s discussion with our CEO Catherine Bouvier, on this topic, here
Further information and resources:
British Liver Trust: www.britishlivertrust.org.uk
Helpline: 0800 652 7330 (Monday to Friday – 9:00am to 3:00pm)
Neuroendocrine Cancer UK: www.neuroendocrinecancer.org.uk
Helpline: 0800 434 6476 (Tuesday to Thursday – 10am to 4pm)
NET Patient Network (Ireland): www.netpatientnetwork.ie
Email: help@netpatientnetwork.ie
NHS Blood and Transplant liver transplant resources:
www.nhsbt.nhs.uk/organ-transplantation/liver
HSE Organ donation and transplant Ireland: www.hse.ie
Human Tissue Authority: https://www.hta.gov.uk
Neuroendocrine Cancer Centres of Excellence in UK and Ireland is available from the ENETs website: www.enets.org
UK Liver Transplant Centres is available from the Organ Donation and Transplant website: www.odt.nhs.uk
Ireland – National Liver Transplant Centre is at St Vincents University Hospital in Dublin: www.stvincents.ie