Penile transplant: Procedure raises technical, ethical issues

National Report-A 64-year-old man who underwent the first genitourinary vascularized composite allograft (penile) transplant in the U.S. has a new future. “I’m going to walk out of here complete,” Thomas Manning told the press in May after surgeons at Massachusetts General Hospital attached the penis of a deceased donor to him.  

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While the 15-hour procedure is now behind him, the hard work for teams of urologists, plastic surgeons, and organ donation facilitators has only just begun. It’s not just a matter of perfecting the procedure, which has only been successfully performed twice in the world. The teams also must determine who’s eligible for the procedure. Already, policies differ. And they must find spouses and parents who are willing to allow the removal of their deceased loved one’s penis.

Here are the answers to frequently asked questions about the technical, financial, and ethical issues surrounding penile transplantation surgery.

Where was the first successful procedure performed?

The first reported penis transplant was performed in China in 2006. But the patient had it removed, reportedly because his wife rejected it.

In 2014, surgeons in South Africa successfully attached a penis from a deceased donor to a man who’d had his penis amputated after gangrene set in following a ritual circumcision.

“This patient really had nothing left,” said Andre van der Merwe, MD, head of urology at Cape Town’s Stellenbosch University, in a presentation at the 2016 AUA annual meeting in San Diego.

He told the audience that African men who’ve lost penile function face major challenges. “These people are ostracized and severely discriminated against in their own society. They cannot have kids, and they are essentially seen as dead by community leaders.”

In this case, surgeons could have tried to reconstruct the penis by taking tissue from the forearm or thigh, he says, but this is not ideal for men who make their living from manual labor.

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The patient had intercourse at 5 weeks after the procedure, contrary to the advice of his doctors, Dr. van der Merwe says. Still, the patient is “happy and sexually active” with normal erections and ejaculations, he says.

Next: How is the Massachusetts patient doing?

How is the Massachusetts patient doing?

“We are delighted with the progress of our first recipient,” said one of his surgeons, Dicken S.C. Ko, BSc, MD, director of the Massachusetts General Hospital Urology Regional Program and associate professor of surgery at Harvard Medical School, Boston.

According to Dr. Ko, the patient was doing well as of late July. “He had an episode of rejection, as anticipated, and was treated without any complication,” Dr. Ko said. Sexual function is not anticipated for several months, but voiding function returned normally after a catheter was removed at 3 months, he said.

Next: Who's eligible for a penile transplant?

Who’s eligible for a penis transplant?

At Massachusetts General, eligible patients have lost their genitalia and associated tissues due to cancer or trauma, says Dr. Ko. Manning, the hospital’s first penile transplantation patient, suffered from penile cancer, which affects about 2,000 U.S. men annually and is a major cause of penectomy.

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Dr. BurnettJohns Hopkins University in Baltimore, in contrast, is focusing its program on injured military veterans, says Arthur L. Burnett II, MD, MBA, professor of urology and director of the Basic Science Laboratory in Neurourology at Johns Hopkins Medical Institutions. On the military side, statistics suggest that more than 1,300 men suffered from genitourinary injuries while serving in Iraq or Afghanistan from 2001 to 2013. Many of the victims lost all or part of their penises.

Johns Hopkins is not working with cancer patients at this time. “We’ve had candidates along those lines, but they hadn’t seemed to us to be the right candidates for the initial attempts,” Dr. Burnett told Urology Times. “Concerns include the risk of a cancer recurrence and the use of an immunosuppressant in those who have had or have cancer.”

In contrast, the military patients are young, “and they’re coming back with lost limbs and much of life to meet,” said Dr. Burnett. The penis “is very much of who they are and what they understand themselves to be,” he said.

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Johns Hopkins plans to improve penile transplants over 60 procedures in military veterans over the next several years. “There are so many hurdles,” he said. “Keep in mind that the kind of reconstructions that we’re talking about here may comprise portions of abdominal wall. We’re talking about the whole front of someone’s pelvis.”

Next: What are the unique technical challenges of these procedures?

What are the unique technical challenges of these procedures?

The Massachusetts General procedure took 15 hours and required the services of 13 surgeons: seven attendings and six fellows and residents. More than 30 people made up the caregiving team, including anesthesiologists, nurses, physician assistants, scrub nurses, circulators, and organ bank workers.

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According to Dr. Ko, these are the first procedures of their kind to require transplantation of skin pedicles-flaps of grafted skin that are still connected to the body-to ensure that the tissue and skin in the penile shaft is viable. The procedures also require revascularization of arteries and connectivity of nerves, he says. (See illustration showing perfusion territories of penile arteries.)

“The biggest challenge is every case because every case has a different anatomy and a different extent of what is missing from trauma, burns, cancers, or combat,” Dr. Ko said.

Next: What role do urologists play on transplant teams?

What role do urologists play on transplant teams?

Dr. Ko“Urologists are an integral part of the team” at Massachusetts General, Dr. Ko said. “In particular, as a urologist and a transplant surgeon, I have the anatomical experience, reconstructive expertise, and transplant immunology knowledge to help implement such a program.”

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He says his urologic team also includes an oncologist and a sexual medicine expert to assist with evaluations before and after the transplant.

Dr. Burnett said urologists “play the role of making sure that urologic components of the reconstruction are met.” While plastic surgeons may know about reconnecting fine nerve vessels and making sure the skin is reconnected in the most attractive way, “We’re going to know the greatest detail on how the urethra is reconstructed and how corporeal bodies need to be properly reattached,” he said.

What are the benchmarks for a successful transplant?

Dr. Ko says the objectives are natural appearance, urologic voiding function, and potential restoration of sexual function.

What is the risk of rejection?

“Rejection is anticipated in about 15%-18% in the first year,” Dr. Ko said. “The first episode usually occurs in the first month as with other vascularized composite allografts [involving multiple structures such as nerves and blood vessels]. It is comparable to the hand and the face, but the characteristics will be different from solid organs.”

Next: Will sexual function be restored?

Will sexual function be restored?

According to Dr. Burnett, some patients do have erectile function in the stump of the penis, and the procedure could provide the structure for a full erection. In other cases, a penile implant may be required.

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It’s too early, however, to know how the Boston patient will fare. “When sexual function is restored, the patient will know, and it won’t be a mystery,” Dr. Ko said. “We are cautiously optimistic that the function will be restored. However, we do not anticipate this to return for many months after the transplant.”

What about reproductive function?

The patient who underwent the South Africa procedure was able to father a child naturally, although the baby reportedly was stillborn.

In the Massachusetts General case, Dr. Ko says the surgical team did not aim to restore reproductive function, although the patient still has testes. “We did not alter the recipient’s own reproductive anatomy,” he said. “There were no reproductive tissues that were anatomically transplanted from the donor.”

Could the patient reproduce? It’s possible, Dr. Ko says, but not probable due to “numerous physiological and social factors in play,” such as potential age-related infertility.

Could testicles also be transplanted?

Some men, of course, have injured or missing testicles. But Dr. Burnett says there are no plans to transplant these organs, even though he believes it’s technically possible to do so.

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“From a societal perspective, I can’t imagine how we’d do that,” he said. “Passing genes from one person to the next is a huge loaded subject.”

Next: How much do these procedures cost?

How much do these procedures cost?

Dr. Ko declined to provide a specific figure for the May procedure, saying the expenses are still being calculated.

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However, The New York Times quoted a fellow surgeon as saying the procedure runs from $50,000 to $75,000. According to the newspaper, both Massachusetts General and Johns Hopkins are paying for the procedures.

As for insurance coverage, Dr. Ko cautioned that insurers typically don’t cover clinical experimental procedures.

Can penises be procured from donors just like other organs?

No. Under U.S. law, specific consent is required for donations of organs like hands, faces, and penises. Simply signing an ordinary donor card is not enough.

Dr. Klassen“It’s clearly a very sensitive topic, not something that most families were expecting,” David Klassen, MD, chief medical officer of United Network for Organ Sharing, told Urology Times. “There’s probably going to be some concern and potential reluctance of donor families to agree to this.”

Indeed, “we face huge issues” regarding donors, Dr. Burnett said, and challenges lurk on multiple fronts.

For one, he says, it’s a challenge to approach a possible donor’s next of kin and ask if their loved one’s penis can be donated. “You’re asking to take their genitalia, and that can be a tough call,” he said.

The next of kin of the donor in South Africa, in fact, insisted that a phallus be created on the dead man’s body to replace the one transplanted into the living man, Dr. van der Merwe said.

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The intermediaries who work with families of potential donors are another challenge, Dr. Burnett says, since their buy-in is needed for a donation to occur. “They can shut down a family right away.”

Next: Are organ procurement centers willing to seek donor penises?

Are organ procurement centers willing to seek donor penises?

Massachusetts General worked with the New England Organ Bank. In Maryland, the Living Legacy Foundation is waiting to identify a donor who can serve as a subject for research at Johns Hopkins. “This will allow us to fine-tune the intricacies of the recovery on a donor case before the actual transplant occurs,” said Charlie Alexander, president and CEO of the foundation.

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Centers in Los Angeles and the Seattle region say they aren’t working to procure these organs. However, “I am unaware of programs not being willing to recover these grafts,” Alexander said. “There are very few transplant centers performing the transplant today. So logistically, it may not currently be necessary for some organ procurement organizations to recover the tissue due to no local transplant programs performing the surgery.”

What are the bioethical issues regarding these procedures?

Dr. AgichThe bioethical issues surrounding penis transplant center on whether they are in the best interest of the patient, according to bioethicist George J. Agich, PhD.

“What are the risks or burdens that the patient wanting the transplant may not appreciate and may not want?” asked Dr. Agich, professor of philosophy (emeritus) at Bowling Green State University in Bowling Green, OH and co-director of the International Conferences on Clinical Ethics & Consultation.

Richard Huxtable, PhD, professor of medical ethics and law and director of the Center for Ethics in Medicine at the University of Bristol in the U.K., has concerns about the need to take immunosuppressant drugs. “Thinking of the public interest, one might wonder whether we should be subjecting potential recipients to such risks,” he said. “Is the patient really the recipient or, instead, society at large, given its apparent fixation on beauty and occasional intolerance of difference?”

Are patients seeking gender reassignment surgery potential candidates for a transplant?

For now, Johns Hopkins is focusing only on members of the military who have suffered trauma to the penis. As for gender reassignment, he says penis transplants in biological women would be a challenge because of the lack of a male pelvis with the appropriate internal structures that attach to the penis. Other potential candidates for a transplant may include those with birth defects and ambiguous genitalia, Dr. Burnett says.

At Massachusetts General, Dr. Ko said, “There are a lot of anatomic challenges there that are still far from the clinical translational stage of any program. The plan in our program is initially limited to those patients who have had devastating loss of genitals due to cancer and trauma.”

Should urologists refer appropriate patients to clinics that offer penis transplantation?

Dr. Huxtable“Urologists may be the most direct advocates for this procedure and the most direct conveyors of patients,” Dr. Burnett said. “Hopefully, they could be the ones who can help bring forward the message that this is an important and very meaningful approach.”

At Massachusetts General, Dr. Ko said, “We are happy to evaluate patients that have had devastating loss of genitalia. But we do not have an open clinical program for enrollment, as this is still strictly an experimental procedure.”

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