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Penis Allotransplantation in Beagle Dog Hindawi Publishing Corporation BioMed Research International Volume 2016, Article ID 1489204, 7 pages http://dx.doi.org/10.1155/2016/1489204 Research Article Penis Allotransplantation in Beagle Dog Yongbin Zhao, Weilie Hu, Lichao Zhang, Fei Guo, Wei Wang, Bangqi Wang, and Changzheng Zhang Department of Urology, The General Hospital of Guangzhou Military Command, No. 111, Liuhua Road, Guangzhou, Guangdong 510010, China Correspondence should be addressed to Weilie Hu; [email protected] Received 14 September 2015; Revised 30 November 2015; Accepted 10 December 2015 Academic Editor: Gerald Brandacher Copyright © 2016 Yongbin Zhao et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. This is an original research of penis allotransplantation. The paper presents an experiment allogenic penis transplantation model in Beagles, with a focus on recovery of blood supply and changes in tissue architecture. Twenty adult Beagles were allocated to 10 pairs for penile transplantation. After operation, the skin and glans were observed. If adverse symptoms occurred, the transplanted penis was resected and pathologically examined. Frequency of urination, urinary stream, and patency level were recorded 7 days after transplantation. Cystourethrography was performed on Day 10. The transplanted penises were resected on Day 14for pathological examination. The research showed that transplanted penises survived after allotransplantation, and the dogs regained urination ability. Penis autotransplantation in Beagles is feasible. This preliminary study shows a potential for application of this new procedure for penis transplantation in humans. 1. Introduction Although this method could help patients with complete penile defect to regain the ability of standing urination, War injury, trauma, penis tumor surgery, and congenital several issues remain including poor appearance of the glans diseases may be associated with partial or complete penile penis, short penis length (<5.0 cm), and erectile dysfunction defect, which deprives men of the ability of urination while [5–8]. Recently, V-Y advancement flaps from the lower pubic standing and sexual activity. This condition often causes area are being widely used in V-Y plasty to increase the length mental and psychological trauma and induces a heavy emo- of penis [9, 10]. However, this approach also suffers from tional and psychological burden to the patients and their poor appearance of the glans penis, limited penile length, and families. The main treatment methods for penis defects erectile dysfunction. includephalloplastywithfreeflapsorpedicledflaps,penis Therefore, reproductive organ transplantation has been lengthening, and penis reconstruction [1–3]. Ideal treatment suggested as an important alternative treatment for penis should achieve excellent appearance and feeling, ability to defects. In a retrospective study, Lee et al. analyzed animal urinate while standing, and successful sexual intercourse. The studies (including testicle transplantation, ovarian transplan- first case of penis replantation has been performed in 1971 [4], tation, and en bloc vagino-utero-ovarian transplantation) and has been followed by many others. However, replantation performed over the past 25 years and have proposed that is not always possible and reconstruction is then necessary. allogeneic penis transplantation could be applicable in the Resection of the superficial suspensory ligament and near future if approved by ethics committees [11]. One patient about one- to two-thirds of the deep suspensory ligament in China successfully underwent penis allotransplantation in maybeperformedtoincreasethelengthofthepenis,which 2006,butthepenishadtoberesectedbecauseofpsycholog- could increase the length by about 3.2–5.0 cm (mean 4.1 cm) ical issues [12]. and 0.8–1.2 cm, respectively. However, there is a high risk Penises from Brown-Norway rats were transplanted to of injuring the deep dorsal vein, dorsal artery, and nerves. adult Lewis rats (en bloc allogeneic transplantation), and 2 BioMed Research International results showed that immunosuppressors including FK506 Thebilateraldorsalveinsandarteriesandaccompanying could effectively prevent rejection in allogenic penis trans- nerves were carefully isolated and protected under the assis- plantation [13]. Transplantation of single organ including tance of a surgical microscope (magnification: 10x). About kidney, heart, liver, and lung has been widely applied, 2 cm of the vessels and nerves were isolated. Then, a clamp and the technologies involved are well known. Similar to was used to block the vessels, and the tunica intima was limbs, the penis consists of skin, blood vessels, nerves, rinsed using heparin sodium solution to prevent thrombosis. cavernous bodies, albuginea, and urethral mucosa, making The residual cavernous body was ligated with a rubber band, penile transplantation a composite tissue transplantation [14], and the dorsal vessels and nerves were isolated for about and the rejection reactions are usually more serious than 2 cm. A custom-made 12 F silica gel induct catheter was in single organ transplantation [15, 16]. Results from animal inserted through the external urethral orifice into the bladder. studieshaveshownthatpenisautotransplantationshadahigh Absorbable suture (4-0) was used to suture the cavernous success rate; however, allogeneic penis transplantation still body of urethra and albuginea of cavernous body of penis remains a challenge for clinicians [17, 18]. Penis defects do torestorethecontinuityofthepenisandurethralcanal. not endanger the life of the patients but cause profound psy- Continuous suture with two fixed points was performed chological problems that greatly affect the patients’ quality of to anastomose the deep dorsal vein of the penis using 9-0 life. Therefore, penis allotransplantation could be performed damage-free vascular suture. Suture of the dorsal artery of the in selected cases with the appropriate immunosuppressive penis and accompanying nerves was made using 11-0 damage- regimen. free vascular suture. The rubber band was then loosened to The structures of the penis of Beagle dogs are very similar identify any blood leakage of the vascular anastomosis and to to the human penis [19]. In the present study, allogeneic observe the arterial pulse and vein filling. Size-4 thread was penile transplantations using microsurgery were performed used to suture the subcutaneous tissue and size-7 thread was in Beagles to investigate the graft survival and the restoration used to suture the penile skin. The incisions were covered by of urination function, with a focus on recovery of blood sterile gauzes and bound with elastic bandages. supply and changes in tissue architecture. Results could provide evidence for allogeneic penile transplantation in 2.3. Treatments and Observation. Combined immune induc- humans. tion was performed using preoperative FK506 (2 mg) and MMF (250 mg). Methylprednisolone (500 mg) and pantopra- 2. Materials and Methods zole (80 mg) were used intraoperatively. Intravenous dripping of dexamethasone (7.5 mg/kg) was performed for 3 days 2.1. Animals. Twenty Beagles (weight: 15–17 kg, mean 16.8 kg) (once/day) after surgery and then switched to 0.2 mg/kg/d of were provided by Zhaoqing Kangda Experimental Animal muscular injection for immune induction therapy. Mainte- Co., Ltd. The dogs had free access to water and food. The nance immunosuppressive therapy using FK506 (1 mg/kg/d, diameter of the dogs’ penises ranged from 2.2 to 3.0 cm (mean intragastric administration) and MMF (20 mg/kg/d, intra- 2.6 cm). The 20 dogs were allocated to 10 pairs, each pair venous dripping) was also performed. Ampicillin and bicillin consisting of half-brothers in order to reduce immunological were administered to prevent infection. Nutritional therapy issues and to focus on blood supply and changes in tissue and supporting treatment were also performed. architecture. This study was approved by the ethics committee After surgery, the skin and glans were carefully observed of our hospital and was performed according to animal to identify any color change and tissue swelling. The catheter protection rules. was removed on Day 7 after the operation. Frequency of urination, urinary stream, and patency level were recorded. 2.2. Microsurgical Allogeneic Penis Transplantation. Lympho- Cystourethrography was performed on Day 10. The trans- cyte toxicity test [20] had to be negative before surgery. planted penis was resected on Day 14 for pathological Muscular injection of scopolamine (0.3 mg) and phenobar- examination. If the glans was white, if the skin was black, bital sodium (0.1 g) was performed 30 min before surgery if there was obvious tissue swelling or necrosis, or if there to decrease salivary gland secretion to help in perform- was an irreversible acute rejection during the observation ing tracheal intubation and maintain the respiratory tract period, the transplanted penis was resected immediately and unblocked. Heparin sodium (12,500 U) was intravenously pathological examination was performed. After the period of injected to reduce the risk of embolism after surgery. Alter- observation, all dogs were returned to the animal center for nate muscular injection of Su-Mian-Xin II (0.08 mL/kg) and use in studies needing large animals (such as orthopedics or ketamine (5–10 mg/kg)
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