Reconstructive Transplantation for Penile Restoration

Abstract

Male genitourinary trauma often results in devastating physical and psychological sequellae. Traditional options for autologous reconstruction do not fully restore form and function and are prone to significant complications involving urinary strictures and fistulae as well as prosthesis extrusion; we believe that reconstructive transplantation may provide improved outcomes for select patients. Thus far, penile allotransplantation has been performed twice with mixed results. Prior to more widespread implementation, carefully attention must be directed toward minimizing the benefits and minimizing the risks associated with this procedure. There are also a number of ethical considerations unique to penile transplantation that must be considered. In this article, we review the potential risks, benefits and ethical considerations pertaining to penile transplantation and discuss approaches to optimize outcomes.

The Problem

Male genitourinary (GU) trauma can be physically and psychologically debilitating. Often, and particularly in young men, the inability to urinate while standing or to have sexual intercourse can produce feelings of emasculation, distort social relationships, and profoundly impact individuals' quality-of-life. Participation of the United States Military Services in Operation Iraqi Freedom and Operation Enduring Freedom have resulted in devastating GU injuries to Servicemen caused by increased use of both improvised explosive devices and ground troop deployment.^1,2 Unfortunately, traditional reconstruction techniques do not fully restore the lost form and function of the penis and are prone to significant complications. Therefore we believe that reconstructive transplantation, also known as vascularized composite allotransplantation (VCA), may offer a better alternative for penile restoration. In addition, many of these patients have suffered additional injuries to the perineum or limbs. These injuries to the surrounding tissues are not reconstructed in conventional techniques which are focused on the shaft. Limb injuries and other surgeries may eliminate the door sites needed for these reconstructions. Allotransplantation allows the use of tailored graft tissue for each patient without the need for autologous donor sites.

Reconstructive transplantation is being performed around the world with increasing frequency as an alternative to prostheses and autogenous tissue reconstruction.^3,4 The vast majority of cases have involved upper extremity and face transplantation; however, indications are expanding to include the abdominal wall and lower extremities.^5,6 In select cases, the potential for markedly improved aesthetic and functional outcomes can justify the additional risks associated with immunosuppression and allograft rejection.

Worldwide, 2 cases of penile transplantation have been reported in the literature. The first recipient was a 44 year-old male in China who suffered traumatic amputation at the base of his penis. The graft reportedly survived rejection-free until it was surgically removed 14 d post-transplantation at the request of the patient and his wife due to apparent psychological rejection.^7,8 The second recipient was a 21 year-old male in South Africa who lost his penis secondary to complications from a ritual circumcision. The patient reportedly regained full sexual and urinary function 3.5 months post-transplant,⁹ with reports of his girlfriend being pregnant appearing in the lay press.¹⁰ A recent report of a third transplant being performed in the US has appeared in the press as well although no outcomes have been reported in the literature as of yet.¹¹

The divergent outcomes of the first 2 cases reported can greatly inform future applications of penile transplantation, emphasizing the importance of meticulous preparation by the surgical team and careful patient selection during the candidate screening process.

Limitations of Current Reconstructive Options

When considering penile transplantation as a viable option for patients with severe penile defects, we must carefully examine the existing alternatives and whether sufficient potential for improvement exists to justify the additional risks associated with VCA. Although many options for autologous phalloplastic reconstruction are available,^12-16 none consistently provides all the qualities a neo-phallus should possess: acceptable appearance, a competent urethra, tactile and erogenous sensibility, and sufficient rigidity and durability to allow for penetration during sex.¹⁶ Additional concerns regarding autologous reconstruction include the significant donor site morbidity that results from autogenous tissue harvest or the lack of donor tissue in multilateral amputees such as severely injured military personnel. These considerations may in fact rule out autologous reconstruction for certain patients.

The radial forearm free flap, often considered the gold-standard for total penile reconstruction, is the most widely-used method for phalloplasty accounting for up to 90% of reported cases.¹⁶ While it provides adequate aesthetics and fairly consistent return of erogenous and tactile sensation, even in the most experienced hands it is prone to unacceptably high rates of urinary strictures and fistulas as well as prosthesis-associated complications including extrusion, infection, and malposition. In the largest series of radial forearm free flaps for phalloplasty (n=287), Monstrey et al noted a 44% prosthesis explantation rate due to malpositioning, technical failure, or infection. They also reported a 42% rate of urinary complications, including a 32% rate of neo-urethral stricture and 21% rate of urinary fistula formation. The rates cited in other studies are even more discouraging. ^18,19

Risk-Benefit Ratio

Given the suboptimal outcomes associated with currently available options, we believe penile transplantation has the potential to provide markedly improved results, especially in the multiple amputee with limited donor sites. However, as with all types of VCA, careful consideration must be given to the risk/benefit ratio associated with the procedure. Unlike solid organ transplantation, VCA is not meant to be life-saving, but instead is considered life-enhancing. Therefore, the viability of penile transplantation as a reconstructive option will rely heavily upon its ability to provide meaningfully improved outcomes compared to current reconstructive options while minimizing the additional risks associated with life-long immunosuppression and possible rejection.

Maximizing Benefit

The potential benefits of penile transplantation as compared to current reconstructive options include a more normal appearing phallus, improved erectile function without the need for a prosthesis, durability, improved urethral patency with fewer complications related to fisutulae and strictures, and improved erogenous sensation. To maximize these potential benefits, surgical technique will be of the utmost importance, particularly the approach to allograft revascularization.

Our recent studies have indicated the importance of utilizing multiple vascular pedicles to provide optimal graft perfusion.²⁰ We found that the dorsal arteries are the only source of perfusion to the glans and as such would be required to prevent distal necrosis. These arteries provide ample perfusion to the corpus spongiosum and urethra. Anastomosing the dorsal arteries will likely be important in ensuring urethral perfusion and patency since the small size and high variability of the urethral arteries make them ill-suited for consistent use in transplantation. We also found that the cavernosal arteries principally perfuse the corpora cavernosa; therefore, we anticipate that anastomosing the cavernosal arteries will be important in ensuring optimal erectile function. Lastly, we found that the shaft skin, as well as the surrounding suprapubic, groin, and scrotal skin, were perfused by the external pudendal system arising from the femoral artery. Therefore, in the setting of proximal penile transplantation, utilizing the external pudendal arteries will be important in preventing skin necrosis.²⁰

The surgeons who performed the first penile transplant utilized the dorsal arterial system alone to perfuse the graft, and it was unclear if one or both dorsal arteries were anastomosed. Although they reported adequate perfusion, the published picture of the graft at postoperative day 14 demonstrates significant necrosis and desquamation of the shaft skin, likely due to failure to utilize the external pudendal system.^7,8 Unfortunately the article about the second penile transplant is vague on this point.⁹

Beyond the vascularization approach, there are several other technical considerations that may affect graft function. As with all types of VCA, outcomes following penile transplantation will depend on adequate graft reinnervation. An important goal of penile reconstruction is restoration of erogenous sensation. Experience with penile replantation demonstrates the possibility of return sexual function including erogenous sensation and erectile ability. The coaptation of the dorsal penile nerves using microsurgical technique has been shown to improve outcomes in these patients. Presumably, the erectile function is a result of intact or spontaneous regeneration of the autonomic innervation of the proximal cavernosal bodies as no report of repair of the cavernous nerves is made in the literature.^25-27 Whether this function can return after a prolonged period of time following the initial injury may be anticipated by analysis of the results following autologous penile reconstruction. While these reported outcomes pertaining to sensory return following autologous reconstruction have been positive,^18,22 there is reason to believe that penile transplantation may provide enhanced sensitivity and orgasm potential. Approximation of recipient dorsal nerves to the dorsal nerves within the graft provides a relatively short distance for regenerating axons to travel in comparison with other types of VCA, enabling reinnervation to occur relatively quickly and robustly. Finally, the specialized sensory receptors within a penile allograft would likely be better suited to provide erogenous sensation than those within the skin of a radial forearm flap. Penile allotransplantation patients should experience similar or even superior results to either replanted or conventionally reconstructed patients.

Minimizing Risk

Although clinical results with VCA have been highly encouraging, use of life-long, high-dose, multidrug immunosuppression associated with a profound side-effect profile hampers its broader application. Currently, VCA has no standard, established immunosuppressive regimen; most patients have been treated with a “conventional” triple-drug immunosuppressive strategy largely extrapolated from solid organ transplantation.

The induction of donor-specific tolerance would obviate the need for long-term maintenance immunosuppression after VCA. Great strides have been made in this regard using translational large animal models.²³ However, until these strategies are implemented in the clinical arena, we advocate the use of short-course depletional induction augmented with a donor bone marrow cell infusion followed by low-dose maintenance monotherapy (tacrolimus 4-12 ng/mL) to minimize toxicities of conventional immunosuppression. Our group has successfully implemented such a protocol for upper extremity transplantation with favorable functional and immunologic outcomes.²⁴ We believe this protocol is readily translatable to penile transplantation and will help to minimize the risks associated with the procedure due to immunosuppression.

Ethical Considerations

As with hand and face transplantation when first introduced in 1999 and 2005, respectively, penile transplantation may currently be viewed by some as objectionable. However, penile transplantation shares similar considerations as face transplantation: it involves a part of the body that is uniquely personal in nature and strongly associated with one's sense of self and identity as a male. While severe facial disfigurement has been linked to ‘social death’, severe GU injury and penile amputation can cause similar hardships, including profound disturbance to interpersonal relationships and long-term psychosocial distress.² The psychosocial impact of this injury and transplantation make psychiatric professionals critical members of any penile transplant team.

As with all VCAs, which are now regulated by the United Network for Organ Sharing (UNOS), penile donation should adhere to standard UNOS cadaveric transplant donation practices. Penile donation requests, like those for hand and face, should be handled as “research asks” until established as a standard procedure, and consent should only be obtained by trained organ procurement organization recovery coordinators. Donor families should be approached in a step-wise fashion prioritizing life-saving organs over non-vital tissues. No identifying information about the donor should be revealed without the full consent of the donor family.

Finally, it is important that only the penis and no germline tissue (testes/sperm/gametes) be transplanted. The availability of safe testicular implants and testosterone replacement therapy can address the loss of the testes or concomitant injuries negatively impacting testosterone production. Potential donor families and transplant recipients should be educated about the procedure and provided access to informational materials that clearly distinguish between germline tissues and the tissues involved in penile transplantation to alleviate potential concerns.

Final Statement

In summary, we believe that the physical and psychosocial needs of patients suffering from severe genitourinary injuries and penile loss justify the implementation of penile transplantation for select patients who have failed or are not suitable candidates for autologous reconstruction. Careful anatomic study will maximize the potential benefits afforded by the procedure and the application of immunomodulatory protocols may minimize the associated risks. By addressing these considerations, penile transplantation has the potential to surpass results achievable with conventional reconstruction and restore individual's quality-of-life.

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.