Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03149692 |
| Other study ID # |
N11/07/243 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
November 11, 2011 |
| Est. completion date |
December 11, 2020 |
Study information
| Verified date |
September 2021 |
| Source |
University of Stellenbosch |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
One case of unsuccessful penile transplantation has been reported from China. The patient had
suffered an industrial machine accident and lost his penis to the level of the pubic skin.
Unfortunately the patient's wife insisted at about two weeks post-operatively that the organ
be removed. At the time of surgical removal the penis was viable, except for a degree of
superficial skin necrolysis. This has sparked debate on ethical issues regarding penile
transplantation. South Africa is uniquely positioned in Sub-Saharan Africa and worldwide with
relatively advanced medical services and a high prevalence of ritual circumcision practice
with reports of high morbidity and mortality in the last 20 years. The substantial number of
young men left with a severe penile defect or complete loss of the penis [9] creates a
possible place for penile allograft transplantation as a treatment option.
Description:
Literature review and rationale Ritual circumcision has been practised for centuries in
Africa and other parts of the world. Clinical trials have shown that adult male circumcision,
if performed correctly, could play a role in the prevention of HIV transmission and protect
against invasive penile cancer. The prevalence of ritual circumcision practiced in Eastern
and Southern Africa varies from about 80% in Kenya to about 20% in Uganda and Southern
Africa. The procedure referred to as ritual circumcision is performed in a non-clinical
environment by a traditional circumcisionist with no formal medical training. The main
geographical area for this rite of passage in South Africa is among the Xhosa-speaking people
of the Eastern Cape.
The complications of this procedure may lead to severe genital mutilation with partial or
complete penile loss and may even result in mortality. In a study by Meissner and Buso
conducted in the Eastern Cape from 2001 to 2005 there were 1748 hospital admissions, 107
genital mutilations and 177 deaths caused by ritual circumcision. Septicaemia, pneumonia and
dehydration were the most common causes of death. The extent of genital mutilation varied
from partial loss of the glans or distal penile shaft and urethra, to complete loss of the
penis due to gangrene. Less common complications of ritual circumcision include polyarticular
septic arthritis. The complication rates of ritual circumcision are much higher than those
reported for infant and neonatal circumcision (1-7%) where the complications are mostly minor
and almost never result in penile loss However, in a systematic review of the literature
Wilcken et al found that the acquisition of data from the ritual circumcision studies was
often poor, as only 11 of 1639 articles reviewed were suitable for analysis. Other causes of
penile loss include electrical burns, self-mutilation and shotgun wounds. These aetiologies
are rare in South Africa in contrast to the large numbers of ritual circumcision related
penile amputees.
Figure 2. Loss of penis after a ritual circumcision complication and a ventilated critically
ill patient with a septic penis after ritual circumcision. (Own pictures) The current
treatment for total penile loss is surgical total penile reconstruction (TPR), also called
total phallus reconstruction. The goal of TPR is to create a cosmetically acceptable, sensate
penis, functional urethra that extends up to the distal glans which permits voiding in a
standing position, and providing enough bulk to allow the insertion of a penile prosthesis
for sexual intercourse. In addition, the donor-site should cause minimal morbidity and should
be easy to conceal. The above goals are difficult to obtain in South African state patients,
as penile prostheses are not available due to their high cost (about ZAR 80 000 per
inflatable prosthesis).
The most widely used TPR technique is a radial forearm free flap (RFFF) described by Song et
al in 1982. However the urethrocutaneous fistula rate is up to 40% and the donor site
morbidity around 9%. The tissue flap is taken from the inside of the forearm and the defect
covered with a skin graft. The flap is fashioned into the shape of a penis and a skin tube
created inside to connect to the urethra. This flap may contain radial bone to provide
rigidity and enable sexual function. Radial bone harvesting increases the morbidity of the
donor site, as the forearm becomes very thin distally. The operation takes around 7 - 10
hours to perform. It provides a phallus which is cosmetically acceptable after tattooing the
glans penis, but completely incapable of sexual function without a prosthesis, if bone is not
incorporated. In a series of 15 adult female to male gender reassignment patients, only 7
received prostheses, indicating that not all TPRs are suitable to receive a prosthesis.
An artificial penile prosthesis is expensive and not available to state patients in SA due to
lack of funding. These prostheses can extrude (especially with repeated sexual intercourse)
or become infected. Jarow et al found 21.7% risk of infection if a penile reconstructive
procedure was done with prostheses surgery. Infection of prostheses normally necessitates
removal.
Other less commonly used types of tissue flaps for TPR are:
1. Free osteocutaneous fibula flap described by Sadove et al in 1993 with significant donor
site and urethral complications of strictures (32%) and fistulas (16 %).
2. Free scapular flap described by Rorich et al in 1997, which has been reported in limited
patient numbers.
3. Vertical rectus abdominis flap described by Santi et al in 1988.
4. Suprapubic abdominal wall flap reported by Bettocchi et al in 85 patients who underwent
gender re-assignment, with urethral complications in 75%.
It is clear from the above that free flap TRP has many difficulties. The fact that several
techniques have been described indicates that a single satisfactory operation with acceptable
outcomes does not exist.
Most of the reported series were comprised of patients with gender dysphoria. Men requiring
TPR for penile loss after ritual circumcision differ radically from most cases in the
literature, in that these young men were subjected to a life-threatening event, often under
peer pressure. Apart from the physical disfigurement, there is severe psychosocial
debilitation resulting from the loss of sexual function and fertility. The reality in South
African state hospitals is that the operative time and resources to provide free flap TPR for
these patients is rarely available. If such surgery is performed, it is rarely followed by
prosthesis placement, due to the high cost and the risk of complications such as extrusion
and infection. Consequently, many mutilated young men face a future with severe sexual and
psychosocial problems.
Transplantation of human body structures other than organs such as the heart, liver, pancreas
and kidney is known as composite tissue allotransplantation (CTA) and has been practised for
years in centres with available expertise. In 1998 Dubernard et al transplanted a forearm
harvested from a brain dead man to 48-year old man. By 2009 at least 40 hand transplants had
been performed, with very few immunological rejections and minimal immunosuppressive
treatment in many cases . A possible explanation of this immune tolerance is that a type of
chimerism is achieved, possibly due to the presence of bone marrow in the graft.
Allograft cadaver penis transplantation as treatment for penile loss from ritual circumcision
could have the following benefits:
1. Psychological improvement
2. Cosmetic improvement
3. Sexual function re-established
4. Penile sensation re-established
5. Fertility restored
6. Shorter operation time
The negative factors are the following:
1. Immunosuppressive therapy to prevent organ rejection, which may be long-term
2. Intensive and comprehensive pre-operative counselling of the recipient and his spouse or
partner
3. The necessity for long-term follow-up. One case of penis transplantation has been
described in a man who lost his penis in an industrial machine accident. The donor was a
young brain-dead male whose parents consented to the procedure. The Ethics review board
of the hospital approved the procedure, which took 5 hours to perform. The penis
survived 14 days and was viable, but the wife of the recipient then insisted that the
penis be removed. At the time of amputation the corpora cavernosa and corpus spongiosum
were viable. However, the skin suffered from superficial epidermal necrolysis that was
diagnosed histologically. Venous congestion was evident on the penile skin, but no
mention was made of anastomosis of the superficial dorsal vein of the penis.
Zhang et al debated the ethical issues of penis transplantation and expressed concerns about
the body image expectations of the recipient and the fact that a cadaver would be buried
without a penis. He concluded that good communication with the donor family would be
essential. Dubernard (who performed the first hand transplant) commented on the single penis
transplantation case and stressed that it is experimental but feasible. He expressed concern
that the skin may be highly immunogenic and may be rejected separately from the rest of the
penis. He also said that hand and face transplantation used to be a myth and a dream and has
now turned into a reality.
