Anorectal Transplantation in Human Cadavers: Mock
Anorectal Allotransplantation
Jun Araki1*, Yuji Nishizawa2, Tomoyuki Sato3, Munekazu Naito4, Keiichi Akita5, Kensuke Tashiro1, Takuya
Iida1, Isao Koshima1
1 Department of Plastic Surgery, University of Tokyo, Tokyo, Japan, 2 Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University,
Kagawa, Japan, 3 Saitama Shinkaibashi Clinic, Saitama, Japan, 4 Department of Anatomy, Tokyo Medical University, Tokyo, Japan, 5 Department of Clinical
Anatomy, Tokyo Medical and Dental University, Tokyo, Japan
Abstract
Background: Anorectal transplantation is a method for patients who have lost their anorectal function or suffer from
congenital anorectal dysfunction to recover this function, and this has been investigated in experimental animal
models using pigs, dogs, and rats. In this study, we performed an examination of anorectal transplantation in human
cadavers to investigate whether this procedure could be performed in patients.
Methods: A 77-year-old woman cadaver 1 was used as the donor and a 98-year-old woman cadaver 2 was used as
the recipient. Initially, abdominoperineal excision of the anus and rectum (the Miles’ operation) was performed on the
recipient. Next, an anorectal graft containing the pudendal nerve (PN), pudendal artery (PA), pudendal vein (PV),
inferior mesenteric artery (IMA), and inferior mesenteric vein (IMV) was harvested from the donor. The donor graft
was transplanted into the recipient by intestinal anastomosis and microneurovascular anastomoses orthotopically.
Results: The diameters of the PN (right/left), IMA, and IMV were 2.5 mm/2.5 mm, 2.0 mm, and 1.5 mm, respectively,
in cadaver 1, and 2.0 mm/2.0 mm, 2.0 mm, and 2.0 mm, respectively, in cadaver 2. The length of the PN, PA, PV,
IMA, and IMV in the graft was sufficient to allow proper anastomosis.
Conclusion: This preliminary study indicated that human anorectal transplantation was possible anatomically and
technically. We anticipate our study will aid in the potential future application of this procedure to human patients.
Citation: Araki J, Nishizawa Y, Sato T, Naito M, Akita K, et al. (2013) Anorectal Transplantation in Human Cadavers: Mock Anorectal Allotransplantation.
PLoS ONE 8(7): e68977. doi:10.1371/journal.pone.0068977
Editor: Michael Zimmerman, University of Colorado School of Medicine, United States of America
Received March 27, 2013; Accepted June 3, 2013; Published July 11, 2013
Copyright: © 2013 Araki et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was supported by grants from Kawano Masanori Memorial Foundation for Promotion of Pediatrics and JSPS KAKENHI Grant Number
24-5321. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
* E-mail: arakij-pla@h.u-tokyo.ac.jp
Introduction
condition and potential cure [3]. To avoid colostomies, various
anal reconstructions have been performed and many
alternative therapies have been examined and developed
[4–6]; however, no alternative options have been able to solve
this critical issue until now.
Anorectal transplantation is a supreme method for patients
who have lost their anorectal function or suffer from congenital
anorectal dysfunction to recover this function, and this has
been investigated in experimental animal models [7–12].
Experimental anorectal transplantation was first attempted at
St. Mark’s Hospital, UK, in 2000 [7]. In that study, the
anorectum from female pigs was transplanted into male pigs
without immunosuppression and successful inferior mesenteric
artery (IMA), inferior mesenteric vein (IMV), and pudendal
nerve (PN) anastomoses were achieved. Since then, similar
experimental studies have been reported using rat [8–10],
swine [11], and canine models [12]. However, no reports
Anal function is often lost due to resections of rectal or
perianal cancer, congenital anal dysfunctions, such as anal
atresia or Hirschsprung’s disease, intractable anal fistulas of
inflammatory bowel diseases, such as seen in Crohn’s disease
or ulcerative colitis, and other severe incontinences, such as
seen after accidental trauma or perineal laceration from
childbirth. In addition, current treatments for severe fecal
incontinence are often complex and have unsatisfactory results
[1]. Colostomies have served as effective surgery for various
anorectal dysfunctions and play an important role in allowing
excretion in patients. However, it must be noted that these
patients suffer greatly from stresses caused by their stoma.
Patients have reported decreased sexual activity and fertility at
the time of survey due to colectomy, especially for females [2],
and occasionally prepared for death rather than accepted their
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Anorectal Allotransplantation in Human Cadavers
mesorectum down to the pelvic floor to the top of the anal
canal, and the mesorectum was mobilized from the levator
muscles. The perineal part of the operation was then
performed from below in the prone position, with excision of the
anal canal including the surrounding skin, ischiorectal fat, and
the upper portions of the levator muscles. The anal canal was
circumferentially dissected outside of the external anal
sphincter muscle. Pudendal nerves (PNs), pudendal arteries
(PAs), and pudendal veins (PVs) ran bilaterally along the inside
of the ischial tuberosity and reached the external anal sphincter
muscle. The posterior wall of the anal segment was separated
from the anterior surface of the coccygeal muscle. The levator
ani muscle was transected at the lateral and posterior wall, and
the anterior wall was detached behind the vagina. The rectum
was separated with mesentery at the lower part. The IMA, IMV,
PAs, PVs, and PNs were clipped and cut. Finally, the anal
segment was resected.
currently exist in the literature examining the possibility of
anorectal transplantation in humans. Recently, laparoscopic
surgery of the rectum (e.g., intersphincteric resection) has
allowed the surgical anatomy of the pelvis to be clearer than
open surgery [13,14], and pelvic anatomy in cadaver studies
has improved because of advances in techniques for anorectal
surgery [15,16]. These anatomical understandings may cause
secure reconstruction of the pelvic floor. The aim of this study
was to examine whether anorectal transplantation was possible
in patients by performing mock anorectal transplantation in
human cadavers.
Methods
Information on Cadavers
The cadavers used in this study were donated to the
Department of Anatomy, Tokyo Medical and Dental University,
Tokyo, Japan. Before they died, they made documents of
agreement of donation of the body and those of agreement of
use for the clinical studies. The format of the document is
within expectation of the Japanese law “Act on Body Donation
for Medical and Dental Education”.
A 77-year-old woman who died from right renal cancer was
used as a donor. A 98-year-old woman who died of natural
causes was used as the recipient. Neither of the women had
any past surgical history in their buttocks, colons, rectums, and
anuses. All cadavers had been embalmed using the method
described by Thiel [17,18]. Thiel cadavers are embalmed in a
water-based solution of salts for fixation, boric acid for
disinfection, glycol, chlorocresol and ethanol, and a very small
amount of formaldehyde. This precipitation leads to
homogenization of the tissue. The physiologic texture of the
tissue is maintained by further effects of precipitation and
linking caused by the embalming solution. The skin is life-like,
joints are fully flexible, and ultrasound imaging of nerves and
needle guidance is realistic.
Technique of Donor Anorectal Graft Harvesting
One cadaver served as the donor of the anorectal
transplantation (deceased donor). Surgery proceeded from the
anterior abdominal incision to the perineal incision. In the
abdomen, the surgeon followed the plane outside the
mesorectum down to the pelvic floor to the top of the anal
canal, and the mesorectum was mobilized from the levator
muscles. Next, the gluteal incision was performed in a prone
position. The neurovascular bundle, including the PN and
pudendal artery (PA) and vein (PV), ran through the pudendal
canal, and this was divided and marked (Figure 1-A). The
dissection of the deeper layer reached into the pelvis and
pelvic floor muscles were identified (Figure 1-B) and cut. Next,
the perineal part of the operation was performed from below in
the prone position, with excision of the anal canal including the
surrounding skin, ischiorectal fat, and the upper portions of the
levator muscles. The anal canal was circumferentially
dissected outside of the external anal sphincter muscle into the
pelvis. After clipping and cutting of the IMA, IMV, PNs, PAs,
and PVs, the anorectal graft was finally harvested (Figure 1-C).
Mock Anorectal Transplantation in Human Cadavers
Two colorectal surgeons, one plastic surgeon, and one
anatomist performed the mock anorectal transplantation
together. Initially, abdominoperineal excision (Miles’ operation)
was performed on the recipient. Next, an anorectal graft was
harvested from the donor, and then the donor graft was
transplanted into the recipient.
Technique of Donor Anorectal Graft Transplantation
into the Recipient’s Anorectal Defect
After anorectal graft harvest, the created defect in the
recipient consisted of the anorectal defect (Figure 2-A). The
harvested anorectal graft was transferred from the donor to the
recipient and the sequence of the graft inset was as follows.
The inset of the donor graft started with reconstruction of the
pelvic floor region in the supine position. The pelvic floor
muscles and ligaments were strongly sutured to prevent
descent of the graft. Next, the proximal end of the recipient
intestine was anastomosed to the distal end of the donor
intestine using the Albert-Lambert method. Next, the branches
of the IMV and IMA were anastomosed end-to-end with
interrupted sutures (8-0 nylon, Johnson & Johnson, Tokyo,
Japan) outside of the abdominal cavity (Figure 2-B). Then, the
anorectal graft was orthotopically repositioned and the
abdomen was closed. Next, in the prone position, the
recipient’s circumanal incision was extended to the buttock,
and the PNs were bilaterally identified under the gluteus
Results
Technique of Recipient Abdominoperineal Excision
(Miles’ operation)
The other cadaver served as the recipient of the anorectal
transplants (mock transplants). To mimic the clinical situation,
an abdominoperineal excision (the Miles’ operation) was
performed. Briefly, the procedure was performed through two
incisions, one in the abdomen and one through the region
between the anus and the genitals. Surgery proceeded from
the anterior abdominal incision to the perineal incision. In the
abdomen, the surgeon followed the plane outside the
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Anorectal Allotransplantation in Human Cadavers
Figure 1. Donor anorectal graft harvesting. (A) Right pudendal nerves (PN) and pudendal artery (PA) and vein (PV) were
separated by the blue (PN) and red (PA and PV) vessel loop. (B) Pelvic floor muscles were identified and cut. (C) The anorectal
graft was harvested.
doi: 10.1371/journal.pone.0068977.g001
method allowing for reconstruction of anal function, which is
advantageous over other methods. This is the first report
describing mock anorectal transplantation in a human cadaver.
Since two human cadavers were fixed by the Thiel method, the
flexibility of the joints was well preserved and it was easy to
take the appropriate positions for the operation.
In this study, the IMA, IMV, PNs, PAs, and PVs were
obviously detected in both the donor and recipient cadavers
(Figure 1-A, B Figure 2-C). The length and diameter of the IMA,
IMV, PNs, PAs, and PVs were sufficient to allow anastomoses
without tension. Our previous experiment in dogs revealed that
the anastomoses of PNs, PAs, and PVs had an important role
in the success of anorectal transplantation [12]. A previous
study in humans described the length of the PNs passing out
below the sacrotuberous ligament as being varied from 21 to
44 mm (median, 29.5 mm) [19]. The diameter of the PAs in our
human cadaver was thinner than the previously reported
human data (2.7 ± 0.4 mm at right and 2.7 ± 0.5 mm at left)
[20]. This could be because in cadavers, vessels are collapsed
and lack elasticity and turgor, and nerves are easily dried
during dissection [21]. These data indicated that the
anastomoses of the IMA, IMV, PNs, PAs, and PVs were
technically possible in human anorectal transplantation. In
addition, the levator ani muscle could be strongly sutured to the
pelvic wall to avoid graft ptosis. In this initial study, the warm
ischemia time was about one hour from vessel clamps of the
IMA and IMV to de-clamp of them after anastomoses. We
anticipate that it will also be about one hour in clinical practice
and the cold ischemia time including perfusion and transport
maximus muscle. The neural branches suspected to be
proceeding to the anal sphincter muscle were anastomosed to
the graft’s PNs with epineural sutures (Figure 2-C). Finally, the
skin incisions were closed and the inset of the flap was
completed (Figure 2-D).
Operative Duration and Diameters of Nerves and
Vessels
The duration of the surgical procedure was approximately
seven hours: three hours for donor anorectal graft harvesting,
two hours for the recipient abdominoperineal excision, and two
hours for transplantation into the defect. The diameters of the
PN (right/left), IMA, and IMV were 2.5 mm/2.5 mm, 2.0 mm,
and 1.5 mm, respectively, in cadaver 1, and 2.0 mm/2.0 mm,
2.0 mm, and 2.0 mm, respectively, in cadaver 2. A summary of
the data from the cadavers is presented in Table 1.
Discussion
Anorectal function is constituted in a composite manner by
various structures such as the rectum, anal canal, levator ani,
and anal sphincter muscle, which is innervated by PNs. The
muscular transfer of the gracilis [4] or the gluteus maximus
muscles [5] and the implantation of an artificial sphincter [6]
have previously been performed to recover anal function.
However, none of these procedures are considered ‘gold
standard’ techniques due to the complex nature of anorectal
functions. Anorectal transplantation seems to be a supreme
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Anorectal Allotransplantation in Human Cadavers
Figure 2. Donor anorectal graft transplantation into the recipient’s anorectal defect. (A) Recipient anorectal defect (blue
arrow) after abdominoperineal excision (Miles’ operation). (B) The IMA, IMV, and intestine of the donor graft were anastomosed to
those of the recipient outside of the abdominal cavity. (C) The branches of the pudendal nerve (PN) were anastomosed to the graft’s
PNs with epineural sutures. (D) The skin incisions were closed and the inset of the flap was completed.
doi: 10.1371/journal.pone.0068977.g002
will take in total ischemia time. The warm/cold ischemia time in
intestinal transplantation is about 40 minutes/ 7 hours [22]. The
ischemia times of other composite tissue allografts were 5 h 10
min (cold) in hand [23], 2 h and 40 min in face [24], and 10
hours (cold) in larynx [25]. These times will fit within the range
of acceptable ischemia time for anorectal transplantation. As a
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result, we performed mock anorectal transplantation from a
deceased donor into a recipient after abdominoperineal
excision.
The clinical application of anorectal transplantation is not
only limited to anal dysfunction resultant from postabdominoperineal excision, but also that caused by anal
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Anorectal Allotransplantation in Human Cadavers
required to control transplant infection and rejection. To confirm
these, it is necessary to perform long-term observations after
anorectal allotransplantation in experimental animals such as
dogs or monkeys. It has been thought that anorectal
transplantation is practically difficult in the clinical setting.
However, considering recent advances in operational
techniques
and
transplantation
medicine,
anorectal
transplantation may follow the success of other vascularized
composite allotransplants in humans, including those of the
limb [24], face [25], larynx [26], and uterus [29]. The ethics of
non-life-saving organ transplants involves an assessment of a
possible gain in the quality of life for the recipient relative to the
risks of the procedure and the follow-up interventions
necessary for maintaining organ function [30].
Table 1. Case summary and surgical parameters in human
cadavers.
Cadaver 1
Cadaver 2
Age at death
77
98
Sex
Female
Female
Model
Donor
Recipient
Cause of death
Right renal cancer Natural cause
Time for donor arorectal graft harvesting
3h
-
Time for recipient abdominoperineal excision -
2h
Diameter of pudendal nerve (right/left)
2.5 mm/2.5 mm
2.0 mm/2.0 mm
Diameter of inferior mesenteric artery
2.0 mm
2.0 mm
Diameter of inferior mesenteric vein
1.5 mm
2.0 mm
Acknowledgements
atresia, Hirschsprung’s disease, intractable anal fistulas, or
trauma [26]. And still farther, it may be accompanied en bloc
colon and small bowel transplantation [27]. Therefore, it is
necessary to develop appropriate transplantation and
reconstruction methods for various defects. Evidently, the
postoperative anorectal function must also be examined in
detail. It is well known that the PVs provide the majority
sensations and functions of the anorectum [28]. In our
preliminary study using dogs, anorectal function recovery could
be observed at six months after re-anastomoses of the PVs
(data not shown). And also, the use of immunosuppressants is
We thank Ayako Sato, Ayumi Sakai, Nobuko Yonezawa, and
Paola Fiorito for their technical assistance.
Author Contributions
Conceived and designed the experiments: JA YN. Performed
the experiments: JA YN TS MN. Analyzed the data: JA YN TS
MN KA. Contributed reagents/materials/analysis tools: KA KT
TI IK. Wrote the manuscript: JA YN MN KA.
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