Interviewed by Katarina Zorcic, Jenny Kang, and Ashwin Sritharan
Could you briefly introduce yourself to our audience and tell us a little bit about what you do?
Dr. Cypel: I am the surgical director of the Ajmera Transplant Centre and I am a thoracic surgeon and lung transplant surgeon. My daily life [revolves around] doing lung transplants and surgeries for cancer and other problems, but, from an administrative standpoint, [my role] is more of a surgical director of the group.
What inspired you to enter that field and do a lot of work with lung transplantation?
Dr. Cypel: Surgery was an area [that I] was very interested [in] from the beginning of medical school. My preferred classes were anatomy, and amongst the anatomy areas, I felt [that] the chest was the most beautiful one. [My] interest in surgery comes from [having the ability to] resolve a problem in a very immediate fashion, so I wasn’t as attracted [to] some of the clinical work [where] you have to give medications to see effects five years from now. And for lung transplants, that’s even more important because you have someone who is gasping for air and in a matter of 6 to 8 hours you change that person’s life. When you give [them] new lungs, they can breathe again and [you] improve their quality of life. This immediate result, combined with the physiology and anatomy of the chest, brought me [to be] more interested in this area.
On the note of being able to help people who are in need of lung transplants, could you talk about some of the barriers that can hinder the viability of double lung transplants?
Dr. Cypel: One of the major obstacles is related to the availability of donor organs. If you don’t have enough donors, then you have a big list of patients in need but you can’t help all of them. [Another obstacle] is the [mere] complexity of lung transplantation. [Recipients] can have a lot of complications related to immunosuppression and infections. The lung is the organ that has the highest rate of infection and rejection. One of the major reasons for that is because the lung is the only organ that is exposed to the [external] environment, so it’s much more susceptible to viral infections and stimulation of the immune system.
Touching on donor availability, could you further talk about Ex Vivo lung perfusion and its impact on the size of the donor pool for lung transplantation?
Dr. Cypel: Most of the lungs [about 80%] that we [receive] from donors cannot be used because they have injuries which are related to the process when someone dies [such as inflammation and blood clots]. Ex Vivo is a technique to try to treat those injuries after removing the organ from the donor because it’s very difficult to treat [them] in the donor. Once you take the organ out, the normal way [to] preserve the organ is cold preservation, but when [organs] are cold, the cells are non-functioning so you can’t give treatment. Ex Vivo brings the lungs back to life in a normal physiological condition, providing oxygen and nutrients. [Then], you can add specific treatments [such as] antibiotics, anti-inflammatory medications, and anticoagulants only to the organ you’re treating. Just [using] Ex Vivo, we have doubled the number of transplants we do here [at the UHN] — we had about [a] 100% increase from 2011 to 2019. We used to do 85-100 [transplants] and now we’re doing 200 lung transplants.
How have you directly seen impacts, either from the invention of Ex Vivo or from the lack of donors, impact your own practices?
Dr. Cypel: [Ex Vivo] has also increased the ability to preserve organs for longer — instead of 6 hours of preservation, we have gone up to 18 hours of preservation. [Additionally] there are a lot of donors that we wouldn’t [have] used in the past; donors with sudden infections like Hepatitis C [as well as] the use of these donors after cardiac death. [These] are basically donors that have withdrawal of life sustaining care in the ICU because they don’t have the chance of a meaningful recovery. [Therefore] when they do arrest, we take the organs and use [them] for transplants — this is about 30-40% of our donors these days.
Do you see us going in a certain direction in the future that could help us increase the number of donors further?
Dr. Cypel: There [are] a lot of donors that we still don’t use — I think there’s still a lot of potential for that. In the future, we [need to see] how we can improve not only the number of donors, but actually change these organs in a way that the recipients of these organs won’t develop complications. [Almost] every complication of a transplantation is related to the fact that [recipients] need to receive immunosuppressive medications. If we [could] change the organ before the transplant in a way that the recipient wouldn’t see it as foreign, we could use much less immunosuppression. We have been working on some of these strategies with genetic modification of the organ during Ex Vivo to decrease the antigen expression, for example. We have also done some studies, such as removing the ABO blood type from the organ, so it becomes like a universal organ and you don’t need to potentially match anymore on [the basis of] blood type. I think that will open a lot of opportunities as well as increase fairness of organ allocation. [Finally] we are treating some of the viral infections in donor organs that cause major problems in the recipient later on.
In your experience, to what extent has COVID-19 impacted the need for increased organ donors?
Dr. Cypel: Because people that need transplants from COVID-19 [require] lung transplants, it has increased the demand for lung transplants. [However] I wouldn’t say as much in Canada as it has been in the US, for example. I just saw in the news this weekend that one in ten lung transplants performed in the US are now performed for COVID-19. [At the UHN] we do have ICU patients in need of lung transplants because of COVID-19. I don’t think the demand has been huge for us here [in Canada], unlike other countries that COVID-19 has completely overrun. The one issue with COVID-19 is our number of overall donors has decreased. [This could be due to] ICUs being full with COVID-19 patients and not having the resources to manage organ donors.
What are some specific challenges that you think are faced when you have to procure an organ from a donor who has experienced cardiac death compared to a living donor?
Dr. Cypel: There are two major categories of donors: cadaveric donors and live donors. There are then two types of cadaveric donors: brain death donors and cardiac death donors. All organs are functioning normally [in brain death donors] except the brain. The surgical teams go and take the organs from that person. Cardiac death is a little bit different because the person is not brain dead yet, but has significant injuries [so] there is very little chance or no chance of recovery. The ICU team withdraws life support and that person’s heart will stop when you disconnect them from the ventilator, for example. If you look at the main differences between cadaveric donors and live donors, then there are very different challenges. [For] live donations you need a compatible donor, oftentimes it is a family member. This is mostly used for liver and kidney transplants; we don’t do live donation for lung transplants. They do this [live lung donations] in Japan, however, so it’s possible to do it. Usually the organs from live donors are healthier. Cadaveric donors are someone that was sick, and then [the organ is] in the hospital for several days, so [it accumulates] more infections.
You mentioned that they do living lung donations in Japan. Are there any particular reasons for this difference between Japan and Canada or North America in general?
Dr. Cypel: [In Japan] they take a part of the lung [from] a family member and then part of a lung [from] another family member. Then, [they] transplant these two parts into a recipient. The reason they do that in Japan is mostly because they don’t have many cadaveric donors, mainly from a cultural perspective [since] the concept of brain death isn’t very well accepted. That’s one of the reasons why the organ donation rates in Japan are very low.
Do you see live donations potentially coming to Canada?
Dr. Cypel: Yes, I think there is a place for live donors for [the] kidney and liver. UHN is the largest place in North America for live transplants for kidneys and livers. For lungs, there may be an opportunity for pediatric transplants; you could take a part of the lung from a [parent] or relative [since] it’s usually a good fit from an adult to a kid to take part of the lung. We don’t have a lot of pediatric donors, so that’s one potential use that we could do in Canada.
There was a lung transplant that was recently delivered by drone for the first time at the UHN. Could you explain the rationale and significance behind this delivery, along with what it implies for the future?
Dr. Cypel: Yes, that was a proof of concept project. In the future we [might] not need to send teams in and planes to carry organs. [For example], let’s say you have a donor in Ottawa. There will be a surgical team in Ottawa that can retrieve the organs for us. If the intended recipient is here [in Toronto], they [can] put the organs in these special boxes in a drone, which delivers [them] to the hospital. This would increase a lot of efficiencies in the logistics of transportation, be cost efficient, improve quality of life and safety. These drones could also bring organs to organ repair facilities that we developed [where] the organ is treated immediately, and then the drone can take the organ back [to the hospital].