Urologic surgeons Inderbir Gill, MD, and Nima Nassiri, MD, investigators with Keck Medicine of the University of Southern California in Los Angeles, have launched a clinical trial to perform the world’s first bladder transplant in a live patient. Renal & Urology News interviewed Dr Nassiri to learn more about this history-making trial.
How many patients do you plan to enroll in your trial?
Dr Nassiri: We’re starting with just 1 patient. The procedure has never been done before, and we want to make sure that the inaugural patient does well for several months after surgery to make sure it is safe and feasible. Pending a successful outcome, our trial aims to enroll 5 patients for bladder transplantation. The bladders will be recovered from brain-dead deceased donors, much the same way as kidneys and other solid organs are recovered.
Who are the intended transplant recipients?
Dr Nassiri: The subset of eligible patients is highly selective. There are 3 categories of potential patients. Broadly speaking, the ideal first patient will be someone who is on immunosuppression or in whom immunosuppression is imminent who has terminal bladder pathology that requires cystectomy. De novo immunosuppression cannot be started in the cancer setting, so this limits the patient population.
Kidneys and other solid organs have been transplanted for decades. Why is it only now that bladder transplantation is being studied?
Dr Nassiri: The vascular anatomy of the deep pelvis area is complicated and the procedure is technically complex. Furthermore, a unique collaboration and experience between urology and transplant surgery needs to be established. I think urologists used to be more involved in transplantation, but over the years, the transplant experience within urology has waned. This is a detriment because it’s an excellent surgical experience, especially for trainees. Perhaps the time is ripe for urologists to re-familiarize themselves with some aspects of transplantation, especially as more and more disease processes are managed non-operatively.
What preclinical research preceded the trial’s launch?
Dr Nassiri: Over the course of nearly 3 years, we have transitioned gradually, in step-wise fashion, from animal models, then to a pulsatile perfused cadaver model and, ultimately, to brain-dead but heart-beating deceased human research donors whose hearts were kept beating during the procedure.
What technical challenges, if any, have you encountered?
Dr Nassiri: The recovery of the vascularized composite bladder allograft is certainly the most challenging component. We recovered the bladder through both open and robotic approaches, and we found the robotic approach to be instrumental in facilitating the meticulous vascular dissection in the deep pelvis. With the open procedure, we had some challenges with bleeding and poor visualization and the vascular complexity way down in the deep pelvis. This is a space that we as urologists do not normally operate in, even during a cystectomy, and developing the surgical technique took some time. Ultimately, we were able to decrease the operative time for bladder allograft recovery from 10 hours initially to just under 4.
We recovered the vascularized composite allograft—the bladder with all of its blood vessels intact—and then we prepared that specimen on the back table so there was only 1 arterial inflow and 1 venous outflow. Then we took that allograft and put it back in the body. We wanted to see if the vascular integrity would remain intact and sustained. In one of the donors, we were able to sustain them for 12 hours after the surgery. We then went back in and evaluated the perfusion of the allograft and it looked great.
Lastly, from a logistic standpoint, the coordination of care it takes in order to perform this on a heart-beating brain-dead research donor is tremendous and takes a village to organize. It took over a year and a half to complete the studies in the brain-dead heart-beating human research donors. The organ procurement organization, OneLegacy, was instrumental in facilitating these studies.
Are there any important considerations regarding cold and warm ischemia times?
Dr Nassiri: With any kind of transplant of a solid organ, you want to limit the warm ischemia time as much as possible. We performed intravesical cooling, and we have also tried infusing ice-cold normal saline into vessels before we ligate them in order to cool the bladder down to minimize the warm ischemia time. Cold ischemia time does affect other organs, such as the kidneys, but this is generally seen beyond 12 hours of cold ischemia. Our cold ischemia times have been around 1 hour. That’s a very short cold ischemia time compared to other organs. It is unclear what the impact of this short cold ischemia time would be on the bladder.
What would be the advantages for patients?
Dr Nassiri: The primary advantage is to avoid the potential complications that can happen with urinary diversion using bowel. The gold standard for urinary reconstruction remains the use of some segment of bowel to reconstruct the bladder. However, this predisposes patients to complications, which we have all seen at some point. You can have metabolic derangements, infectious complications, leaks that can be highly morbid and sometimes fatal. These are not small things, especially in an immunosuppressed population.