“Splitting a liver on a machine perfusion pump had never been done clinically in the USA, until now”
In a pioneering effort at Northwestern Medicine, Dr Satish Nadig (Chief, Division of Organ Transplantation, Northwestern University Feinberg School of Medicine, Chicago, IL, USA) and his team have pushed the boundaries of transplant surgery with the life-saving resection and partial liver transplantation with delayed total hepatectomy (RAPID) procedure. Traditionally, liver transplants have not been performed for patients with metastatic colorectal cancer, but Dr Nadig’s innovative approach – involving splitting the liver using a normothermic machine perfusion pump – offers new hope. In this interview, he discusses the novel and unique case of Barclay Missen and how these developments could reshape treatment options for patients previously considered untreatable.
Q1. Please can you provide a snapshot of Barclay Missen’s story, and the innovative transplant procedure that was performed in 2024.
It’s very interesting and groundbreaking for healthcare in the USA. We typically do not transplant for metastatic disease, but Northwestern is really pushing the boundaries above and below the diaphragm. We have the first and only program to transplant lungs for lung cancer, for example. We also have a long history of transplanting for liver cancer and, more recently, we have started transplanting patients who have colon cancer that has spread to their liver.
When colon cancer spreads to the liver the colon is usually removed and patients undergo chemotherapy that circulates through their whole body. However, the five-year survival rate with chemotherapy alone is about 10%, meaning 90% of patients die within five years. It is really dismal and there are not many good options. In Europe, some groups started performing liver transplants for metastases from colon cancer and found that five-year survival rates could reach 60–80%, significantly better than with chemotherapy alone. Some programs in the USA, including ours, started adopting this approach.
However, there is a major hurdle: the liver transplant allocation system is based on liver function, not on the presence of cancer. These patients’ liver function remains relatively intact, despite their liver being riddled with cancer, so they score low on the transplant list. Not everyone has a living donor available, and historically the United Network for Organ Sharing (UNOS) had not made provisions for patients with colorectal metastases to the liver.
Barclay Mission’s case was unique. He was in his early 50s with two children – a salt-of-the-earth gentleman – and had been diagnosed with colorectal cancer that had metastasized to his liver. His colon had been removed, and parts of his liver had been surgically resected to control the cancer, but disease remained confined to his liver. After a year of unsuccessfully searching for a living donor, and suffering significant side effects from chemotherapy, he was ready to enter hospice care. He articulated this to us clearly – and we could not let him die without trying to help.
Around that time, one of my partners came across a technique developed in Oslo involving the RAPID procedure. In this approach, a small segment of liver from a deceased donor is transplanted into the patient after partial resection of the cancerous liver. That small segment is not initially sufficient to support the body, so it is allowed to grow over two weeks. After that, the remaining cancerous liver is removed.
There were several challenges. We needed to allocate a suitable liver to Barclay, have a liver that could survive long enough on a machine to allow for surgical preparation and have the technical capability to perform the operation. We decided we could make this happen at Northwestern by combining several technologies.
We collaborated with a normothermic machine perfusion company, set up an operating room for two weeks and practiced splitting discarded human livers on the pump. To my knowledge, no one in the USA had ever split livers on a perfusion pump clinically before. Once we demonstrated it was feasible, we paused Barclay’s chemotherapy, confirmed the cancer had not spread and positioned him to receive organ offers.
Because of his low score, he would never have been offered a liver under normal circumstances. However, an organ offer came through for another patient, Kelly Podres, and we approached her to propose using part of the liver for Barclay. Without hesitation, she agreed.
On the day of surgery, the liver arrived on a normothermic machine perfusion pump from a donor after cardiac death. We split the liver on the pump: the larger segment went to Kelly, and simultaneously, we resected half of Barclay’s cancerous liver and implanted the small graft. After two weeks, once it had grown sufficiently, we removed the rest of his diseased liver. Barclay went from preparing for hospice care to being cancer-free for more than five months.
Barclay Missen and Kelly Podres
Q2. This is such an incredible story. Please explain further how the normothermic machine perfusion pump works and the process of splitting the liver.
Splitting livers has been done for decades. In fact, the very first split-liver transplant in the USA was performed for a baby here in Chicago at the University of Chicago in the mid-1990s. We have been splitting livers for smaller patients, often children, for many years. Living donation is also based on splitting the liver.
What we did was unique – we split the liver while it was on a normothermic preservation and assessment technology called TransMedics Organ Care System. The pump keeps blood flowing through the liver outside the body at body temperature. These technologies are relatively new and not yet mainstream, but we are adopting them. We demonstrated that it is feasible to split a liver on a pump – even one from a donor after cardiac death, which traditionally would be considered a marginal organ. The pump revitalizes the organ and allows us to assess its viability by measuring bile production, checking blood flow and taking biopsies. This opens enormous future possibilities – not just for cancer patients, but for any patient desperate for a liver transplant. It also lays the groundwork for future research into growing livers on perfusion pumps, an area still in its infancy but sparked by this clinical case. The normothermic machine perfusion pump connects to the arteries, veins, and bile duct of the liver and circulates blood from the donor in a pulsatile fashion, simulating a heartbeat. This keeps the liver functioning outside the body and allows us to evaluate it before transplantation.
Q3. Is this approach particularly suited to patients with liver metastases from colorectal cancer, or could it also work for liver metastases from other cancers?
It’s particularly suited to patients with colorectal cancer for a few reasons. First, the colon can be removed, and patients can still do well. Second, we have a good understanding of the tumour biology – we can measure tumour-related factors using circulating tumor DNA to monitor the disease. Third, and very importantly, the cancer invading the liver does not typically impair liver function. Since half of the liver remains in place for two weeks while the transplanted segment grows, the remaining liver must continue to support the patient during that time. That is why colorectal metastases are particularly suitable for this approach.
Q4. What is your vision for the CLEAR program?
Northwestern has launched the Colorectal Metastasis to Liver Extraction with Auxiliary Transplant and Delayed Resection (CLEAR) program to help patients like Missen. The initial 80 participants will be enrolled in a clinical trial, with their outcomes serving as the primary endpoint. The eligibility is for patients with colorectal cancer that has metastasized to the liver, but the aim is really to find the ‘Barclay Missions’ of the country – those patients who have no hope, no living donors and no options. We want to offer them hope.
Many oncologists across the country still do not know that we are transplanting for colorectal cancer. So, it is about education and disseminating the word that this is possible. Northwestern must be more than just a direction – it must be a destination for these patients.
Q5. What are the next steps? What future studies are there, and what can we hope to see in the coming years?
We plan to split more livers on the pump – to date, no one else in the USA has done it. We will also initiate research studies focused on growing livers on pumps, building on the early research we have started. Additionally, we want to expand the use of split livers not just for patients with colorectal cancer, but also for other patients with different conditions who are disadvantaged by the current allocation system. This approach could benefit pediatric patients as well.
Disclosure: Satish Nadig has no financial or non-financial conflicts of interest to declare in relation to this video.
Cite: Q&A with Dr Satish Nadig: Novel RAPID technique ‘redefines possibilities’ for colorectal cancer with metastasis to the liver. touchONCOLOGY. May 1st, 2025
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