Gargollo PC, Ahmed ME, Prieto M et al: Feasibility study of vascularized composite urinary bladder allograft transplantation in a cadaver model. J Urol 2021; 206: 115.

The urinary bladder functions to store urine at low pressures and expel urine under voluntary control. Under normal conditions the bladder remains in a state of optimal compliance and contractility, allowing for continence and preservation of renal function. In several different urological conditions, the urinary tract is anatomically or functionally damaged, a situation that can result in bladder decompensation and, consequently, renal failure. Pediatric and adult bladder dysfunction is often associated with a variety of congenital or acquired diseases, including neurogenic bladder (NGB) secondary to spina bifida (SB) or spinal cord injury (SCI), bladder agenesis, posterior urethral valves (PUV), bladder and cloacal exstrophy, severe voiding dysfunction, radiation damage, and bladder or urothelial malignancies.¹ Depending on the condition and severity, the ability of a bladder to fill, store, and empty urine may be significantly affected.

Transmission of back pressure from a dysfunctional bladder may have a deleterious effect on the kidneys, leading to end stage renal disease often necessitating renal transplant. In patients without a native bladder or previously subjected to cystectomy regardless of the etiology (malignancy, radiation cystitis etc) the same concept applies. Thus, a healthy and compliant bladder becomes a particularly crucial element to preserve in patients who undergo renal transplantation in order to avoid graft failure secondary to a dysfunctional or absent bladder.

Finding the ideal bladder substitute in case of dysfunction or absence of the bladder has been a challenge for decades, and experiments to achieve this goal have included organic, synthetic, and even bioengineered materials.² Currently, bladder augmentation or neobladder creation can only be performed by using a segment of the gastrointestinal tract. In these cases a physiologically absorptive tissue (intestine) is placed in continuity with the urinary stream, which is normally lined with a fluid-impermeable epithelium. Therefore, the use of intestinal segments in urinary tract reconstruction has multiple significant limitations, including the need for lifelong intermittent catheterization, metabolic disturbances, bowel dysfunction, urinary tract infections, mucus production, stone formation, rupture of the augmented bowel segment (with significant associated mortality), and even malignant transformation. Furthermore, utility of the bowel is sometimes limited by previous abdominal surgery or radiation therapy. Thus, alternate tissue(s) for achieving comparable clinical outcomes while reducing associated morbidity is desperately needed.

Herein we present a novel protocol to potentially solve a significant clinical problem in renal failure patients who require urinary bladder construction or reconstruction by using an expanded renal-bladder vascularized allograft. A total of 6 fresh frozen cadaver torsos (3 male, and 3 female) were included in our study. Four cadavers were injected under fluoroscopic assistance with a silicone and barium mixture according to established protocols in order to better visualize the vascular anatomy on computerized tomography (CT) scanning as well as during gross dissection.^3,4 Contrast enhanced CT imaging was used to delineate urinary bladder vascular anatomy and variabilities. Bladder vascularity was successfully mapped in 4 cadavers. Contrast enhanced CT as well as gross dissections revealed variability in the distal vascular pedicle to the urinary bladder, but all proximal arterial and distal venous branches entered into the internal iliac vessels (fig. 1). Three-dimensional (3-D) renderings with organ subtraction also proved valuable for mock transplant planning.

Figure 1. Through CT imaging combined with vascular micro-injection and 3-D rendering, we have been able to map blood supply to urinary bladder at extreme detail (A). CT renderings can then be rotated (B), and certain anatomical structures can be added to or subtracted from images to allow for specific steps of surgical procedure (C and D).

Figure 2. Gross and micro-dissection in cadaver model have allowed us to very carefully delineate vascular anatomy and plan subsequent donor harvest and recipient implantation. Seen here is magnified view of iliac vessels on donor’s right side (A) and subsequent vascular pedicles going to urinary bladder (B).

Figure 3. A, 3-D CT reconstruction of urinary bladder vascularity. B-F, simulated transplantation procedure in cadaver model. B, dissection of vascular pedicles in donor. C, bladder harvested on its vascular pedicle (only right pedicle is shown). D, donor common iliac artery is anastomosed to recipient external iliac artery. Same is done with vein. E, completed anastomoses. F, bladder graft to be used as patch or configured into neobladder.

Figure 4. Deceased donor kidney and bladder seen in situ (A). Bladder is harvested on its vascular pedicles (B) and removed from donor (C). Recipient is shown with diseased kidneys and diseased urinary bladder (D). Recipient bladder is opened at dome (E), and donor bladder is configured into patch with its vascular pedicles anastomosed to iliac vessels of recipient (F). Recipient in part G of figure is shown with absent bladder. In this case donor bladder is configured into “neobladder” (H), and Mitrofanoff continent catheterizable conduit is created and brought to recipient’s skin (I).

Two cadavers were used to perform “mock” urinary bladder transplants. A vertical midline transperitoneal incision was made and the bladder with its vascular pedicles was exposed. The bladder was dissected circumferentially and the bladder neck was transected. Vasculature from the internal iliac to the bladder was preserved, including the superior vesical, inferior vesical, and the obturator arteries (fig. 2). The vesical veins, deep dorsal veins, and cavernous veins were likewise preserved. The bladder and its vascular pedicles were removed and perfused in a basin of iced slush. Cooled preservation fluid was flushed through the arterial vasculature. The recipient bladder was prepared for augmentation by creating a clamshell bladder incision. The vascular anastomosis was performed at the internal iliac vessels of the donor and recipient end-to-side (donor → recipient; fig. 3). After anastomosis of the vascular pedicles, the prepared bladder allograft was circumferentially sutured into the native bladder using absorbable sutures in a running fashion. The second bladder transplant was fashioned into a neobladder and brought out to the skin with a continent catheterizable conduit (fig. 4).

Bladder reconstruction or neobladder creation is limited by suitable autologous tissue availability. There are no other relatively fluid impermeable tissues in the human body besides the bladder mucosa, the oral mucosa, and the vaginal mucosa. Although buccal mucosa has been used as a urological tissue substitute (mainly in the urethra), its use in the bladder has been limited. The concept of a bioengineered urinary bladder aimed to address the limitations of a lack of suitable tissue availability and inadequately vascularized tissue substitutes.⁵ The fundamental issue with bioengineered grafts, however, remains the absence of an intrinsic vascular supply, which leads to impaired tissue perfusion, ischemia, and tissue demise.³

Vascular composite allotransplantation (VCA) is a rapidly evolving field providing functional and qualitative restoration of life for several patients. Several VCAs, including limbs, the face, uterus, and more recently penile allografts, have been successfully performed over the last decade. However, there are ethical considerations for recipients of VCA grafts requiring long-term immunosuppression for non-“lifesaving” conditions given the potential complications associated with long-term immunosuppression. Because of this, our current phase 1 clinic trial involves bladder VCA transplant only in patients who are already taking immunosuppressive regimens for a previous renal transplant or in patients who will undergo concomitant renal and bladder allotransplantation.⁴ Furthermore, we realize that all of these bladder patches will be atonic, and thus initial attempts at bladder VCA will involve patients already on clean intermittent catheterization.

Transplantation of a vascularized urinary bladder in order to augment or recreate a nonfunctional or absent bladder has not been attempted. We hypothesize that a VCA of the bladder will provide superior outcomes with a reduced rate of complications and side effects for the properly selected patient, when compared to traditional procedures. Currently a phase 1 clinical trial studying concomitant renal and urinary bladder VCA is in progress at our institution.