Stories of service members who have lost limbs or suffered traumatic brain injuries as a result of blast injuries in Afghanistan or Iraq often make headlines, but another devastating consequence of these blasts is rarely discussed.
In 2006, a team of clinicians from Guangzhou General Hospital in China reported the results of the first attempted penis transplant, which was largely unsuccessful (Hu W et al. Eur Urol. 2006;50:851-853).
In that case, a 44-year-old man, whose penis had been lost to a traumatic injury, received a transplanted penis harvested from a 22-year-old brain dead donor. However, the donor penis was removed after 14 days because the patient and his wife could not psychologically accept the penis, in part due to significant posttransplantation swelling (Hu W et al. Eur Urol. 2006;50:1115-1116).
Studies of the blood supply to the penis by researchers at Johns Hopkins have since attributed the poor outcome in the Chinese patient to a failure to reconnect certain blood vessels that have only recently been identified as essential, said Gerald Brandacher, MD, associate professor of surgery and scientific director of the Reconstructive Transplantation Program at the Johns Hopkins School of Medicine.
“We think the failure was a perfusion problem,” Brandacher said.
The first successful penis transplant was performed 8 years later by a team of surgeons led by André van der Merwe, MD, head of the division of urology at Stellenbosch University at Tygerberg Hospital in Cape Town, South Africa.
The 21-year-old man had all of his visible penis amputated as a result of a ritual circumcision gone awry. Ritual circumcisions are a rite of passage for some young South African men, but a lack of training, sterile techniques, and improper wound care often leads to serious complications and even deaths. According to Stellenbosch University, as many as 250 penis amputations may result from botched circumcisions in South Africa annually.
A major barrier to the transplant was finding families willing to donate, in part because of the symbolic importance of the organ and concerns about leaving the deceased family member without a penis. The process of finding a donor took years, noted van der Merwe. Eventually, he and his team offered to reconstruct something that looked like a penis from skin on the donor’s arm to replace the donor’s penis, which assuaged the families’ discomfort.
“It was a major breakthrough for us,” van der Merwe said.
The 9-hour surgery was successful, and the man has since regained sexual function, van der Merwe said. The man has not had any difficulties accepting the new penis; in fact, “[t]his guy just moved on [with his life],” van der Merwe said.
In August, van der Merwe and his colleagues received government permission to continue the penis transplant program. Based on what they’ve learned from the first transplant, van der Merwe believes they will be able to reduce operating time by half.
Wake Forest and Johns Hopkins have been building on the published information, as well as information from van der Merwe and his colleagues, to develop their own protocols.
One of the most difficult aspects of preparing for penile transplants has been weighing the ethics of the procedure—a process that began before the first hand transplants were offered in US hospitals, according to Brandacher.
“Despite the devastating injury, it is not life-saving,” Brandacher explained.
For a non–life-saving transplant, clinicians are in the difficult position of weighing the physical risks of a transplant, including rejection, graft-host disease, and cancers related to immunosuppression, against psychological and quality-of-life benefits, said Craig Klugman, PhD, a bioethicist and chair of the department of health sciences at DePaul University in Chicago.
In the case of penis transplants, the psychological benefit could be considerable because the penis is so central to a man’s identity, Klugman said. For young veterans, who may be in their prime years of dating or building a family, there is also an issue of justice.
“You have a person who sacrificed part of their life for our society,” Klugman said. “That is one reason to go ahead.”
Given the experimental nature of the transplants and the possible risk, both Wake Forest and Johns Hopkins have conducted ethical reviews of their programs, and each has begun a painstaking process of screening and preparing potential transplant recipients.
“It’s just making sure the patients we choose have the highest chance of success,” said Anthony Atala, MD, chair of the department of urology at Wake Forest University School of Medicine.
At Johns Hopkins, only patients who are not candidates for more traditional types of genital reconstruction will be considered, said Brandacher. At both institutions, the patient must be mentally healthy, undergo a psychosocial evaluation to ensure they have good family support, and be fully aware of the need for additional surgeries and lifetime use of immunosuppressive drugs. Partners of the patients are also being involved to ensure everyone has realistic expectations.
“The candidate we are going to move forward with is a model patient,” Burnett said.
Brandacher said in his experience with hand transplants since 2001, most patients immediately incorporate the new hand.
“I’m fairly positive that the patients who seek this type of reconstruction will adapt and accept the graft,” Brandacher said.
Special care also has been given to gaining support from organ procurement organizations and approval from families of donors. Brandacher said he and his colleagues began discussions with organ procurement organizations very early in the process to ensure they don’t scare families away from donation.
“This is a very, very special ask,” Brandacher said. “Approaching a donor family is a sensitive process.”
One thing that has aided the process of procurement for hands is sharing the stories of the potential recipients, with the patients’ permission.
“That really helps families come forward,” Brandacher said.
PREPARATIONS UNDER WAY
Both surgical teams have begun rehearsing both patient and donor surgeries using cadavers for each planned surgery.
“These procedures are highly individualized due to the injury patterns,” Brandacher explained.
During the procedure, key blood vessels, nerves, the urethra, and the corporal bodies of the recipient will be attached to the corresponding donor anatomy using microsurgical techniques used in other types of organ transplants, according to Burnett.
One of the challenges is carefully orchestrating the work of the teams of surgeons and other clinicians during the daylong surgery, Burnett said. After surgery, patients will receive the same care as any other patient who has undergone a microsurgical procedure to ensure proper blood flow to the transplanted organ, Brandacher said. Over time, the patient’s nerves will regrow—at a rate of about an inch a month, helping restore sensation, Brandacher said.
To minimize the need for immunosuppressive drugs, Brandacher and his colleagues will use a protocol originally developed for hand transplants that uses donor-derived bone marrow (Schneeberger S et al. Ann Surg. 2013;257:345-351). After their transplant, patients receive an infusion of the donor’s bone marrow, which results in patients having bone marrow that contains both the donor’s and their own stem cells. This helps promote tolerance to the donor hand and reduces the need for immunosuppression after the transplant. In the current protocol, Brandacher and his colleagues use a single immunosuppressant drug given at low doses.
So far, the regimen has been used in 10 allotransplants for 7 patients and has been successful in all very adherent patients, he said. “We think this is one major step to favor the risk-balance equation [for penis transplants],” Brandacher said.
The team at Johns Hopkins plans to conduct 60 penis transplants and collect detailed information about patient outcomes, including sexual function, to determine if such transplants might be useful for a wider patient population. This could include men who have had penile cancer and those born missing a penis. Transgender individuals have also expressed an interest in the procedure.
“We are thinking about how to move forward [with gender reassignment surgeries]; …that requires more discussions,” Burnett said.
In the future, laboratory-grown penises may provide an alternative to donor penises. Atala’s laboratory has already successfully grown and transplanted rabbit penises (Chen K et al. Proc Natl Acad Sci U S A. 2010;107:3346-3350). After recovery, the animals were able to successfully impregnate females.
Atala, who also directs the Wake Forest Institute for Regenerative Medicine, and his colleagues are growing penile tissue from human cells in the laboratory and conducting the necessary safety testing to gain regulatory approval for a clinical trial in humans.
Laboratory-grown vaginas and urethras have already been successfully transplanted in individuals with urogenital defects (Raya-Rivera A et al. Lancet. 2014;384:329-336; Raya-Rivera A et al. Lancet. 2011;377:1175-1182). In these procedures, a biopsy specimen of vulvar or bladder tissue less than half the size of a postage stamp is taken from the patient, Atala said. The cells are then grown in laboratory incubators that mimic physiological conditions and are used to reconstruct the organ layer by layer, he said.
“The advantage of the engineered penis is you are taking cells from the patient,” Atala said. “It’s easier from a psychological perspective for the patient, and from a medical perspective you don’t need antirejection medication.”
While transplants using laboratory-grown phalluses remain on the horizon, Brandacher said, regenerative medicine is already contributing new information about nerve growth and immunology useful for both donor and laboratory-grown transplants.
For patients, these new options may help restore more than just their sexual function and ability to urinate normally. When van der Merwe asks his patient about the biggest difference in his life after the transplant, he explained, the patient replies, “I am happy again.”