EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Key words : Bladder flap technique, Intestinal segment diversions, Renal transplant

Surgical and urologic complications after kidney transplant negatively impact patient and graft outcomes.^1-3 Multiple risk factors for urologic complications have been identified,^4-11 with evidence for routine stenting and a standardized ureterovesical anastomotic technique as ways to help mitigate these complications.^11,12 Transplant ureteric stricture (TUS), the most common complication, when managed by an open approach, has a higher success rate and translates into better long-term graft survival.^1,13 The most commonly performed open treatments are ureteric reimplantation (UN) and uretero-ureterostomy (UU) or pyelo-ureterostomy (PU) to the ipsilateral native ureter.¹³

The use of endourological or minimally invasive approaches should ideally be reserved for nonsurgical candidates or patients with distal, short (<1-2 cm), nonischemic strictures. However, under certain circumstances, patients may also express a desire to attempt an endourological intervention. In patients with failed attempts at open repair with UN or UU, multiple attempts at ureteral dilatation, and/or with bladder dysfunction, this poses a significant challenge to the reconstructing surgeon. We present a series of challenging ureteric strictures that were managed successfully by use of bladder flap techniques and intestinal segment interpositions/diversions.

Using the University of Wisconsin Transplant Surgery division database, we conducted a retrospective review of medical records and imaging after approval from the institutional review board committee. Informed consent had been obtained from patients for intraoperative pictures and postoperative imaging. The indication for surgery in all included patients was confirmed ureteral stricture after deceased donor kidney transplant, with reconstruction performed after multiple attempts at endourological intervention and/or failed conventional repairs (UN, UU, PU).

In conventional ureteral reconstruction for TUS, we have historically preferred the UU approach as the primary modality; however, more recently, we have attempted to perform UN when feasible. None of the cases included were amenable to conventional techniques. The choice of technique was based on preoperative imaging, intraoperative findings, and bladder and renal anatomy. In this series of cases, a transplant surgeon with urologic training (TMQ) was the primary surgeon with the inclusion of additional transplant surgeons.

Table 1 provides a summary of patient demographics. In the first case, A 66-year-old male patient with end-stage renal disease (ESRD) secondary to multiple myeloma developed a TUS 8 months posttransplant (patient 1). A percutaneous nephrostomy (PCN) tube was placed, and a short (<2 cm), distal stricture was diagnosed at the ureterovesical anastomosis. He subsequently underwent 2 attempts at balloon dilation and nephroureteral stenting with no success. He was also discovered to have underlying bladder dysfunction presumed to be secondary to the previous cyclophosphamide therapy. He underwent urodynamic testing, which demonstrated a bladder capacity of 130 mL and poor compliance. He underwent a combined bladder augmentation and UU by our transplant team and urology colleagues (14 months after his transplant). This was complicated by intestinal and urinary leakage, and he developed an enterocutaneous and vesicocutaneous fistula, with a recurrent ureteral stricture. Despite all, his fistulas failed to seal, and he remained with a nephrostomy tube. After optimization, he underwent an open cystectomy and ileal conduit (23 cm long) to his transplant ureteropelvic junction (end-to-side ureteral anastomosis on to the ileal segment using 5-0 polydioxanone [PDS]) (Figure 1), with resection of his enterocutaneous fistula.

Another case requiring ileal conduit reconstruction was a 56-year-old male patient with ESRD secondary to hypertension and diabetes mellitus (patient 2). The patient had a past surgical history of radical prostatectomy for prostate cancer with adjuvant radiation therapy for seminal vesicle invasion that was complicated by bladder neck contracture requiring incision and dilatation. He had transplant of a complete duplex kidney with double ureters. Two PCN tubes were placed, demonstrating distal strictures of both ureters 5 months posttransplant. He underwent 2 attempts at dilatation by radiology with no success. A thorough preoperative workup discovered a low-capacity, poorly compliant bladder with evidence of bladder outlet obstruction. An open cystectomy and ileal conduit (20 cm long) to the 2 separate renal moieties were performed. The proximal ureter/ureteropelvic junctions were anastomosed in an end-to-side fashion using 5-0 PDS on the conduit separately (Figure 2).

In a case of transplant ureteropelvic junction obstruction (UPJO) presenting 10 years posttransplant, a 61-year-old morbidly obese, hypertensive female patient with diabetes underwent a PU that was complicated by urinary leakage and subsequent restricture (patient 3). She was initially treated with an indwelling PCN tube; however, after repeated admissions with urinary tract infections (UTIs), a collective decision was made to reattempt reconstruction. A preoperative workup demonstrated a compliant, small-capacity bladder (140 mL). After thorough assessment and consent, and respecting her wishes to maintain continence, ileal ureteral substitution was deemed her best option. She underwent an open ileal ureteral substitution with an 18-cm-long ileal segment in an isoperistaltic fashion through a midline transperitoneal approach. The transplant renal pelvis was sewn end to end to the proximal ileal segment (4-0 PDS), and the distal end of the ileum was sewn end to side on the bladder using 4-0 PDS over a secured 7F 24-cm double J stent (Figure 3).

In another challenging case, a 41-year-old male patient with ESRD secondary to a history of posterior urethral valves and bilateral native nephrectomies had underwent 4 renal transplants (1984, 1989, 2006, and 2015) (patient 4). His fourth functional renal allograft was severely hydronephrotic; upon further workup, it was discovered that the patient had UPJO of that kidney, as evident by the nephrostogram after PCN tube placement and a MAG3 nuclear renal scan weeks after PCN tube placement demonstrating a half-life of 25 minutes. He had previously documented satisfactory bladder urodynamics, and, given his surgical history, his options for reconstruction were limited. On the basis of a preoperative cystogram demonstrating good bladder capacity (600 mL), an open ureteral reconstruction with a bladder Boari flap was planned. A midline laparotomy approach was performed, and the stricture segment was transected. After the bladder was opened, the flap was sewn to the renal pelvis in a single layer tubularized over a 20F red rubber catheter that was replaced with a 7F 160cm double J stent after the renal pelvic anastomosis was completed. The bladder closure was then completed in 2 layers using PDS continuous running sutures (Figure 4).

Patient outcomes and follow-up are listed in Table 1. Although complications were incurred postoperatively in all cases, none were related to technical errors or failure of reconstruction; in addition, no mortality or graft losses occurred. In cases of ileal conduit, the postoperative course of patient 1 was complicated by acute kidney injury. After thorough workup and interrogating the bowel and urinary anastomoses, no leak was identified; however, the patient’s renal biopsy showed recurrence of multiple myeloma. His immunosuppression was lowered, and he underwent treatment with the monoclonal antibody daratumumab. He did not require dialysis during that period. After treatment with daratumumab, his creatinine nadired to 1.68 mg/dL at 8 weeks postsurgery. Unfortunately, he developed neutropenia, sepsis, and bacteremia with infective endocarditis, which was treated with intravenous antibiotics and did not require valve surgery. With respect to his reconstruction, he had his nephrostomy tube capped 2 weeks postsurgery after removal of the single J stent. At 4 weeks, a tube check demonstrated no leakage and was removed. He was subsequently discharged with a creatinine level of 1.56 mg/dL. He did develop 2 UTIs that required hospitalization during year 2 after diversion. However, despite extensive reconstructive surgery, recurrence of his multiple myeloma, and multiple medical complications, he has remained dialysis free 5 years posttransplant and 2.5 years after urinary diversion with a creatinine level ranging from 1.8 to 2.3 mg/dL.

In the second ileal conduit case (patient 2), the postoperative course was complicated by a prolonged ileus that resolved. At 2 weeks postsurgery, a nephrostogram showed brisk flow of contrast into the conduit; therefore, the PCN tubes were capped and the double J stents were removed (Figure 2C). At the 4-week postsurgery follow-up, his nephrostomy tubes were removed. At the 8-month follow-up, patient 2 has remained infection free with a creatinine level ranging from 1.7 to 1.9 mg/dL.

In the case of ileal ureter substitution (patient 3), the postoperative course was complicated by a non-ST elevation myocardial infarction (NSTEMI) requiring invasive angiography. The patient’s nephrostomy tube was capped at 2 weeks postsurgery after demonstration of brisk flow of contrast into the ileal segment. At the 3- and 6-week postsurgery follow-up visits, respectively, she had her nephrostomy tube and double J stent removed. At the 1-year follow-up, patient 3 has remained symptom and infection free with a creatinine level of 1.2 mg/dL.

In the case of Boari flap reconstruction (patient 4), the postoperative course was uncomplicated; the patient’s drain tested negative for creatinine, with removal before discharge. At 2 weeks, his nephrostomy tube was capped and the Foley catheter was removed after a negative cystogram check; at 4 weeks, the double J stent was removed along with the nephrostomy tube, followed by a nephrostograms and cystogram at 6 weeks postsurgery, which demonstrated patency of the Boari flap. The creatinine level of patient 4 has remained stable at baseline (1.3-1.5 mg/dL), with no evidence of hydronephrosis on ultrasonography 2 years after reconstruction.

Transplant ureteric stricture management in the modern era is largely dominated by primary attempts with endourological interventions. This is inherently more appealing, as it is less invasive and less costly and demonstrates lower patient morbidity.^13,14 It is also a preferable approach for poor surgical candidates. Unfortunately, these advantages are at the expense of suboptimal success rates. The most durable and definitive treatment in our opinion remains reoperation and restoration of flow of urine. Congruently, we acknowledge that the open surgical approach carries a higher risk for complications, can result in longer hospital stays, and can have perioperative morbidity and mortality.^14,15

In our experience, the use of advanced open urologic reconstructive techniques in managing TUS after failed endourological attempts is technically challenging; however, it is feasible, safe, and associated with good patient and graft outcomes. We have previously demonstrated in a large cohort of our patients that ureteral strictures had a negative impact on long-term graft survival, and recipients who were initially treated with a minimally invasive approach had shorter kidney graft survival compared with recipients with no ureteral strictures.¹ We admittedly continue to utilize endourological options in nonsurgical candidates and in patients who are candidates and who have a strong desire for a less invasive option at the expense of a higher failure rate. However, we strongly believe surgical repair is superior.

In a systematic review of management of distal TUS, open surgical management had a higher success rate than endourological treatments.¹³ In all cases combined, the open approach for primary treatment had an 85% success rate versus a 64% success rate with the endourological technique. Open approaches included in the analysis were ureteric reimplantation, UU, and a nonspecified group. The most common primary open and endourological treatments were ureteric reimplantation and balloon dilatation, with 82% and 58% success rates. In secondary treatments, UU (success rate of 100%) and dilatation with adjunct procedure (laser, electrocautery, cold knife incision; success rates of 76%) were the most common interventions. For both approaches, UTI was the most common complication. Although the analysis showed a higher complication rate in the endourological intervention group, inherently, this has to be interpreted with caution as open surgery in a previously operated/scarred field, and usually after repeated attempts at dilatation, is undoubtedly not without significant risk. In our series, the cases were composed mainly of proximal or total ureteral involvement. The complication rate was high, and 1 patient (patient 3) developed a NSTEMI and required angiography without need for stenting, However, the mortality rate was 0%.

Multiple risk factors have been identified in the etiology of ureteral strictures, including recipient and donor age, delayed graft function, and arterial multiplicity.^1,16 In most cases, the ureteral stricture occurs within the first year after transplant, and the underlying pathology explaining fibrosis or necrosis of the donor ureter is ischemia, rejection, recurrent infections, and/or BK virus.^17,18 Technical errors, mainly at the heel of the anastomosis, also contribute to ureteral leak/stricture formation. In all of the cases in our series, the ureter in the index transplant operation was managed by performing an extravesical modified Lich-Gregoir ureteroneocystostomy; this has been the standard at our center. Multiple studies have addressed the question of PU versus ureteroneocystostomy (UN) for ureteral anastomosis, and there does not appear to be sufficient evidence for inferiority or superiority of either.²¹ The operative time is longer with a PU and is a more technically demanding operation²²; although not significant, the rate of urinary obstruction was shown to be higher with UN. Using a corner-saving UN anastomosis technique,¹⁹ Haberal and colleagues demonstrated a lower ureteral complication rate.²⁰ This technique allows better visualization of both ureter and bladder mucosae, simplifies suture placement in the posterior walls of the ureter, and provides better identification of the lumen of the ureter during suturing.^19,20 Compared with their previous conventional 4-point extravesicular Lich-Gregoir technique, the authors demonstrated a lower ureteral complication rate without the need for stenting.²⁰

Figure 5 depicts our algorithm for preoperative and operative management of TUSs. A PCN tube is of paramount importance prior to operative intervention; as such, we perform all of our reconstructions with a PCN tube placed before surgery. A preoperative computed tomography or fluoroscopic nephrostogram and cystogram performed simultaneously can help to delineate the collecting system anatomy, the true length of the stricture, the capacity and anatomy of the bladder, and the distance from the healthy ureter to the bladder. The PCN tube is usually kept open to drainage for 1 to 2 weeks after the surgical procedure, followed by clamping, with a favorable nephrostogram result. The double J stent is usually kept in place for 4 weeks, and the bladder catheter is usually removed 3 to 5 days postoperatively. The PCN tube is usually removed last, after the stent has been removed, to ensure that the repair was successful. The midline transperitoneal approach is an attractive approach because of the ability to perform more extensive dissection of the bladder, to preserve peritoneum over the kidney and indwelling nephrostomy tube, to utilize secondary layers (eg, omentum, peritoneal flaps), and to have a safe approach by starting the dissection at the bladder and progressing retrograde. However, our group has had equivalent outcomes with conventional reconstructions (UN, UU) using the Gibson incision approach. The midline approach was necessary when performing ileal conduit, ileal ureter, and Boari flap.

Perhaps the most gratifying outcome after tackling these challenging operative fields with densely scarred tissue is the restoration of the urinary tract and long-term preservation of renal function; hence, certain points merit discussion in this series of nonconventional techniques. First, repeated endourological interventions render the ureteral tissue inflamed and scarred and can convert the diseased segment from a short distal stricture to a pan-ureteral problem, rendering the use of the transplant ureter for reconstruction cumbersome and the conventional techniques (UN, UU) difficult to perform. Long-term outcomes of kidney transplants into urinary diversions are comparable with those in the normal transplant population, although the procedure is associated with an increased complication rate and preexisting comorbidity.^23,24 In a series of 55 cases, graft survival was 73% at 7.8 years²⁵; in another series of 59 cases, graft survival was 90% at 1 year, 63% at 5 years, and 69% at years.²³ The most common complications were UTI and bowel complications related to the ileal conduit. The rate of decline in estimated glomerular filtration rate is confounded by preexisting renal function, age,²⁶ comorbidities, and the effects of diverting urine into a bowel segment and the ensuing reabsorption and metabolic complications. This factor is expected to decline 10% to 20% from baseline at 5 years.²⁷

In the 2 cases of ileal conduit diversion in our series, patient 1 unfortunately had recurrence of multiple myeloma in his graft and had multiple medical complications secondary to treatment of recurrence, further contributing to a decline in renal function. In patient 2, renal function remained stable and without infection, demonstrating a satisfactory outcome. From a technical standpoint, the length of the ileal segment required careful tailoring as the transplant ureteral/renal pelvic tissue was not as mobile, especially in a much-scarred area, as when performing an ileal conduit to native ureters that can be easily manipulated.

Congruently, the use of ileum for native ureteral substitution has been well described, with excellent long-term renal function.^28-30 Similarly, complications include UTIs, bowel-related complications, and metabolic sequela. Of technical importance, the use of ?15 cm of ileum is needed to obtain a unidirectional isoperistaltic segment, an important mechanism for pyelonephritis prevention; neither tapering nor antireflux implantation of the ileal ureter is necessary to preserve renal function.^31-33 In patient 3, a 18-cm ileal segment was used for replacing the ureter, with the proximal end of the ileal segment sewn end-to-end to the renal pelvis to ensure a widely patent anastomosis in an isoperistaltic manner. The use of a pyelovesicostomy and Boari flap/bladder advancement flap has been previously reported with success in a renal autotransplant population.³⁴ In a series of 12 patients, the long-term (mean follow-up of 60 months) renal function remained unchanged, and 1 patient required revision of the Boari flap.³⁴ In addition to the principles of a no more than a 3:1 ratio of flap length to base width and a base of flap no less than 4 cm wide, it is important when tailoring the bladder flap to add an additional 1 to 2 cm to the total measured defect to the base and the length of the flap. This is to account for bladder distension and the ensuing attenuation that occurs after the bladder is decompressed (Figure 6).

We acknowledge the inherent limitations of this single-center small series and the variable length of follow-up; hence, firm inferences cannot be made. We have addressed bias by a standardized preoperative workup and management algorithm and the primary involvement of a transplant surgeon with urologic training (TMQ) in all cases. Most TUS cases at our center have been reconstructed with the UU and UN techniques; however, the challenging cases depicted here do arise, and a strength of this small cohort is the ability to demonstrate the feasibility and success of these reconstructive options.

The trifecta of restoration of the urinary tract, preservation of renal function, and mitigation of complications in transplant ureteral reconstruction is a cumbersome and technically challenging problem. In this series, the utility of advanced urologic reconstructive techniques allowed us to salvage grafts and patient outcomes following multiple attempts at endourological interventions and repeated UTIs with indwelling stents and nephrostomy tubes. Although not without complications, no grafts or patients were lost secondary to surgical repair. We advocate that the community strongly consider operative repair of these ureteral complications and reserve minimally invasive options for nonsurgical candidates, with consideration of a single attempt in patients with early, distal, short (<2 cm), nonischemic (ie, technical error) strictures.

Volume: 19 Issue: 5 May 2021

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