Abstract
A ureteral stricture is a rather rare urological event defined as a narrowing of the ureter causing a functional obstruction and renal failure, if left untreated. The aim of this review article is to summarize and discuss current knowledge on the incidence, pathogenesis, management, and follow up of proximal, mid, and distal ureteral strictures.
Introduction
A
Open repair is considered the gold standard approach, yet it may involve significant morbidity, complications, and prolonged hospitalization with possible increased costs. However, minimally invasive procedures, such as laparoscopic and robot-assisted approaches, are emerging as equally effective and promising techniques with decreased morbidity.
The aim of our review was to summarize current knowledge on the incidence, pathogenesis, risk factors, and management of ureteral strictures.
Evidence Acquisition
A systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. 2 Published studies were identified through the PubMed, Embase, Web of Science, Cochrane, and Scopus databases using the following search terms: ureteral stricture or ureteral stenosis or ureteral obstruction combined with the terms incidence or epidemiology or pathogenesis or ureteroscopic surgery or ureteral dilatation or endoureterotomy or ureteral stent or ureteral reconstruction or ureteral reimplantation or laser surgery or laparoscopic surgery or robotic surgery, on 18 January 2014. The studies were limited to humans and the English language. The authors independently performed abstract followed by full-text screening and excluded articles referring only to congenital causes, fistulas, and case reports. The primary outcome was to report incidence, risk factors, and pathogenesis of ureteral strictures along with all of the techniques described in the literature in their management. Secondary outcomes were the success and complications of the described surgical techniques. Success criteria were absence of symptoms and radiological verification of ureteral patency.
Incidence
Benign ureteral strictures can develop due to congenital or secondary causes after open or endoscopic surgical procedures, stones, trauma, radiotherapy, endometriosis, infections, abdominal aortic aneurysm, retroperitoneal fibrosis, or idiopathically. 3 Excluding the congenital ureteral strictures, which are commonly located at the ureteropelvic junction and will not be presented in this review, more than 70% are benign and iatrogenic strictures. 4 In this category, we also include strictures developed by renal transplantation and urinary diversion (ureteroenteric strictures). Another 20% of ureteral strictures are characterized as idiopathic (Table 1).
Bold indicates specific categories of causes.
Incidence of iatrogenic ureteral injuries fluctuates between 0.3% and 1.5%. 5 By far, pelvic surgery accounts for 82% of all iatrogenic ureteral injuries, from which 73% are of gynecologic origin. 6 Fourteen percent were general surgical procedures, and another 14% were urological. 7 Endoscopic approaches exhibit the highest incidence of benign ureteral strictures (58%). Retroperitoneal and pelvic lymph node dissections are the open urological operations that are most commonly responsible for ureteral injuries.
Ureteral injury in gynecologic surgery ranges between 0.5% and 1.5%. The ureter is more commonly injured during an abdominal hysterectomy (2.2%); while in laparoscopic and vaginal hysterectomy, rates are 1.3% and 0.03%, respectively. 8,9 It should be noted that this type of complication has a 91-fold risk for litigation in Canada compared with other complications, if not managed early or intraoperatively. 10 Risk factors for ureteral injury during gynecological procedures are pelvic malignancy, radicality of the operation, previous irradiation, endometriosis, and congenital anomalies of the urinary tract. 11
Till the introduction of the rigid ureteroscope, ureteral injury induced by a urologic procedure was a rare entity. The incidence of ureteric strictures is 1% after ureteroscopy. 12 One-third of traumatic injuries and the majority of operative injuries occur in the distal ureter. 13
Malignant causes can originate from primary ureteral pathology or extrinsic compression of the ureter from adjacent tumors. Direct infiltration is most often caused by carcinomas of the bladder, prostate, cervix, ovary, endometrium, rectum, and sigmoid colon and they usually involve the distal ureter. Moreover, radiotherapy for pelvic malignancies may lead to a distal ureteral stricture due to ischemic fibrosis. 14 Radiation-induced strictures have an incidence of approximately 2% to 3% with 0.15% added risk per year for 25 years or more postradiation. 15
Ureteroenteric strictures after urinary diversion with the use of ileum range between 1.4% and 15%, while a refluxing anastomosis exhibits a lower incidence compared with the nonrefluxing techniques. 16 Strictures are more common in the left ureter compared with the right ureter due to the transposition of the ureter under the sigmoid colon, which requires additional dissection of the left ureter itself.
Ureteral stricture is the most frequent urological adverse event after a kidney transplantation. As published, their incidence ranges from 3% to 8%. 17 Regarding the stricture location, 73%, 12%, and 15% occur at the distal, mid, and proximal ureter, respectively. 18
Ureteral endometriosis accounts for approximately 1%, among all women with endometriosis. 19 Distal ureteral strictures and especially strictures of the ureterovesical junction are encountered in about 9% of patients suffering from tuberculosis of the genitourinary tract. 20 Prolonged (>2 months) ureteral calculi impaction was associated with a rate of approximately 24% incidence of ureteral strictures at 7 months. 21
Pathogenesis
Shortly after ureteral occlusion, it has been shown in experimental models that the affected kidney exhibits changes in hydrostatic forces and increased oxidative stress. Hydronephrosis induces a cataract of events, having as a hallmark the increased production of TGF-β1 >20-fold. Inflammation, fibrosis, atrophy, and nephron loss are sequelae of the increased expression of TGF-β1. 22
Benign ureteral strictures are classified as ischemic or nonischemic. Wolf et al. 4,23 defined a stricture as ischemic, when it is caused by open surgery or radiation; while the stricture is nonischemic, if it is associated with lithiasis or a congenital defect. Ischemic strictures usually lead to fibrotic scars. However, we should be cautious when using the term ischemic stricture, as no accurate definition exists for this condition.
Iatrogenic injuries during gynecological surgery are frequently associated with the internal iliac artery or its branches, thus jeopardizing the blood supply to the distal ureter. 13 Iatrogenic causes include direct mechanical trauma (ligation, obstruction, laceration, transection, and pin-point coagulation), relative ischemia from large-caliber surgical instruments, and thermal injury. The ureter is more frequently injured in the level of its crossing with the uterine artery. 24 It should be highlighted that iatrogenic ureteral injuries are missed intraoperatively in approximately 33% to 87% of the cases; thus, a high index of suspicion is required by the surgeon involved. 13
Proximal location of a calculus and the use of an intracorporeal lithotripsy device such as an electrohydraulic lithotripter may result in a higher incidence of postoperative strictures, probably due to iatrogenic trauma. 25 Strictures may result from a mucosal inflammatory process after injury to the urothelium. Periureteral fibrosis can be a sequelae of infected urinary extravasation. 26
The causative factor of ureteroenteric strictures is distal ureteral ischemia; in such cases, the distal ureteral neovascularization that arises from the ileum can be ineffective. In addition, the ischemia may be secondary to transposition of the left ureter under the sigmoid mesentery, periureteral urine leak and fibrosis, and the recurrence of tumor. 27
Ureteral obstructions after a kidney transplantation have various causes. Early stenosis tends to be a result of mechanical causes, such as kinks, edema, blood clots, or restrictive submucosal tunnel, whereas late stenosis is provoked by generalized or focal fibrosis resulting from ischemia or rejection. 28 The distal third and the ureterovesical junction are the most frequently affected parts of the ureter in such cases; it seems that ischemia resulting from surgical problems during harvesting or from a high dose of immunosuppression is a major etiological factor. 29 Breda et al. 30 have suggested that stricture formation also depends on the way the graft is harvested, advocating that preservation of the gonadal vein of the graft is protective.
Diagnosis
Appropriate imaging can be crucial when planning and treating a ureteral stricture. Computerized urography or magnetic resonance imaging is excellent in this regard. Diuretic nuclear renography with radiolabeled mercaptoacetyl glycine is utilized to document baseline differential renal function and confirm obstruction. Intraoperative retrograde pyelography is often performed and can help delineate complicated anatomy. In patients with an indwelling percutaneous nephrostomy, antegrade evaluation of the ureter is useful. Very recently, an intraureteral injection of indocyanine green under near-infrared light during robot-assisted operations has been shown to detect the stricture effectively, but it is still under evaluation. 31
Management
The guiding surgical principle during ureteral reconstruction is creation of a tension-free, watertight anastomosis that is adequately spatulated, with a good remaining blood supply and using absorbable, fine sutures. 32 Treatment success is directly associated with the location, the type, and the length of each ureteral stricture among other patient parameters (Tables 4 and 5). Table 2 summarizes all current approaches available, while Table 3 shows our comprehensive review of each approach and their success rates.
Bold indicates comparative study.
weighted averages.
Holmium-YAG=holmium yttrium aluminum garnet.
NA=not applicable
GFR=glomerular filtration rate.
Open techniques
Unlike distal ureteral obstruction, which can be usually reconstructed by straightforward ureteral re-implantation with a psoas hitch, proximal ureteral reconstruction necessitates more advanced surgical maneuvers, such as boari bladder flap, transureteroureterostomy, ileal transposition, or renal autotransplantation. All available techniques are limited by the length of the ureteral stricture itself. It is advocated that strictures of approximately 2 to 3 cm are better treated with end-to-end uretero-ureteral anastomosis, 4 to 5 cm distal strictures are ideal for ureteroneocystostomy, while longer strictures are managed with psoas hitch (6–10 cm) and/or Boari flap (12–15 cm). Refluxing versus antirefluxing procedures in adults have shown similar results in terms of renal function or risk of stricture formation. 33
Boari flap has the advantage that it uses only normal urinary tract, does not jeopardize the ipsilateral renovascular system or contralateral ureter, and can be done in patients with decreased renal function, stone, or bowel disease. De novo postoperative voiding symptoms are rare.
Downward nephropexy is usually performed with or without a psoas hitch or a Boari flap for strictures of the proximal ureter measuring about 5 to 8 cm. Mauck et al. 34 concluded that in 27 patients and after a mean follow up of 11.4 months, the Boari flap with or without a downward nephropexy had similar success rates, when comparing proximal and distal ureteral strictures. This was the largest study regarding downward nephropexy for upper ureteral reconstruction.
Renal autotransplantation is rarely performed for complex ureteral strictures and should be kept as the last reserve when all previously mentioned modalities are not possible or contraindicated. Perioperative renal loss can be a detrimental complication, and it is of paramount importance that a highly experienced renal transplant team should be involved in the procedure. Finally, the use of ileal interposition graft is contraindicated in patients with bowel disease, previous abdominal irradiation, and poor renal function (GFR<50 mL/min). 32
Endoscopic procedures
Endoureterotomy
Endoureterotomy was first described by Kramolowsky et al., 35 who reported that management of ureteroenteric strictures using balloon dilation alone produced poor long-term results. It is the procedure of choice for the initial treatment of benign strictures. Endoureterotomy can be performed via a percutaneous approach, by means of a retrograde access, or using a combined approach. The success rates of endoureterotomy have been reported to be between 53% and 82% for benign ureteric strictures by use of electrocautery and/or cold-knife incision. 4 The same authors have also reported their results with the simultaneous injection of triamcinolone with improved, but not adequately validated results. 4 Several studies have suggested that endoureterotomy achieves superior results when it is applied to strictures in the terminal portions of the ureter (i.e., distal or proximal), in nonischemic strictures, and in short strictures. In contrast, an open approach may be advantageous compared with an endoscopic treatment in cases of strictures measuring more than 2 cm, as well as in strictures caused by radiation or ischemia. Ipsilateral renal function has also been identified as an important predictor of outcome. 36 Repeat endoureterotomy has a high likelihood of success if radiologic improvement is noted after the initial procedure.
Most authors agree with the need for stenting after endoureterotomy. The rationale for the use of stents after ureteral dilation or incision is to promote ureteral healing, prevent extravasation of urine, and avoid re-stricturing. However, when left in situ for prolonged periods, stents may cause inflammation, which prevents adequate healing or promotes the formation of hyperplastic muscle or scar tissue. The ideal duration for stenting is still undetermined. In addition, there is no consensus as to what size of ureteral stent provides the optimal conditions for maintaining ureteral patency. A retrospective report suggested that benign ureteral strictures of any length benefited from the use of a stent 12F or larger, yet other studies of endopyelotomy showed that smaller stents (6F–8F) provide results similar to those of a larger caliber (7F/14F). 37,38
In cases of ureteroenteric strictures, the endoscopic approaches seem to be inferior to open surgery in series with comparable follow up. 39 After endoureterotomy, a stent is usually left in place for 2 to 6 weeks. Success rates with cold knife incision were around 60% on long-term follow up. 40 Electrocautery incision and laser endoureterotomy have shown success rates of 57% to 71% and 50% to 89%, respectively. 41,42
A limitation that should be considered when evaluating the results of the endoscopic management is the diversity seen in published studies due to differences in stricture characteristics, variability in endouteterotomy technique, timing of stent removal, and stent size.
Ureteral dilatation
Balloon dilatation of ureteric strictures in an antegrade or retrograde fashion has been an alternative treatment modality since 1983. 43 The efficacy of balloon dilation for benign ureteral strictures is in the range of 48% to 82%. 44 Several authors report higher success rates of balloon dilation when managing strictures shorter than 2 cm and those that are nonischemic. 45
The Acucise™ device (Applied Medical) was developed in the early 1990s to combine both ureteral dilation and incision. 46 Knowles et al. 47 reported a 90% patency rate in 10 patients with benign distal strictures using cautery wire balloon incision at 36 months of follow up.
Balloon dilatation was the first endourological form of management for ureteroenteric strictures. The technique involves placement of the balloon over a guidewire under fluoroscopic guidance in order to appreciate location and length of the stricture; then, the balloon is inflated in controlled high pressure in order to dilate the stenotic area; finally, a ureteral stent is placed for 1 to 8 weeks. Success rates of 13%–80% were initially reported, while more recent series described complete failure of balloon dilation at a longer follow up. 48,49 Patency rates of 30% to 87% are reported for Acucise cutting balloon catheter. 50 However, the device should not be used for strictures crossing the iliac vessels, as there is a risk for injury in neighboring anatomical structures, such as the bowel or the vessels themselves due to lack of visual control.
Ureteral stents
The goal of metal stents is to provide long-lasting ureteric patency without the need for frequent stent changes and the added morbidity to the patient. 51
The thermo-expandable Memokath® 051 (Engineers & Doctors A/S) stent is the most commonly used metal stent. It is fabricated by a nickel-titanium composite, tends not to encrustate, but may display distal and proximal mucosal hyperplasia that can be responsible for obstruction. Azizi et al. 52 prospectively assessed the effectiveness and tolerance of the Memokath® stent in 16 patients previously treated with standard stenting. The Memokath stent was not placed in two patients due to technical issues, while one stent was removed on postoperative day one. Stent durability lasted for 13 months. Eight stents (40%) remained functional. Postoperative complications included six migrations (30%) and four stent obstructions (20%). Agrawal et al. 53 reported the largest series with 74 Memokath stents placed in 55 patients. After a mean follow up of 16 months, 52 patients had a successful outcome. Immediate complications included urinary extravasation, poor thermo-expansion, and equipment failure, while late complications were migration, encrustation, and fungal infections. However, the cost of this stent is a concern that might be compensated, as frequent stent placements will no longer be necessary.
Several other metallic ureteral stents have been presented, such as the Resonance®, the Allium®, and the Uventa® stents. 54 –56 Their role seems to be mostly palliative in a patient with a short life expectancy; they should be avoided otherwise. They are contraindicated as a treatment for benign disease. Patency rates of these stents have been published in low-powered studies with a follow up of less than 24 months. 54 –56 Stent failure can occur due to recurrent urinary tract infections, progressive renal insufficiency, pain, and stent migration.
Laparoscopic procedures
Laparoscopy has earned its place in ureteral reconstructive surgery, offering the proven advantages of the minimally invasive approach, such as reduced analgesia, quicker recovery, and less blood loss. Laparoscopic procedures for ureteral strictures were first performed in 1994, and they have been associated with success rates equivalent to those reported for open repairs. 57
The laparoscopic approach has shown excellent efficacy, by being successful in more than 90% of the cases, but all the studies were under-powered and retrospective. There are only two comparative studies, comparing the laparoscopic approach with the open one. Simmons et al. have recently reported that laparoscopic treatments for benign ureteral strictures were equivalent in terms of success rates, but superior in blood loss and hospitalization. 58 Rassweiler et al. 57 have also compared the laparoscopic psoas hitch with or without Boari flap with open ureteroneocystostomy. Laparoscopy was better than open procedures in blood loss, need for analgesia, length of stay, and patient ambulation, but had longer operative times (228 vs. 187 minutes). The feasibility of creating an antireflux mechanism laparoscopically has been well demonstrated by both Rassweiler et al. 57 and Simmons et al., 59 although the latter noted that its use is limited in patients with adequate ureteral length. Successful results using this technique have also been reported in the literature for repairing ureteral defects in tuberculosis, trauma, malignancy, and iatrogenic injuries. 60,61
Robotic surgery
The da Vinci Surgical System™ (Intuitive Surgical) has revolutionized reconstructive surgery in urology, providing excellent vision and precise maneuverability.
Very few and under-powered studies are available. To date, there is only one comparative study by Kozinn et al., 62 who presented the results of 24 consecutive mid/distal ureteral reimplantations for benign ureteral strictures. Estimated blood loss (30.6 vs. 327.5 mL, p=0.001) and length of stay (2.4 vs. 5.1 days, p=0.01) were significantly reduced in favor of the robotic group. No recurrent stricture was observed at a median follow up of 30 and 24 months in the open and robotic groups, respectively.
It is considered that robot-assisted procedures are superior in operative times for suturing, perioperative complications, and functional outcomes compared with conventional laparoscopic approaches. However, no safe conclusions can be drawn, as a high level of evidence is lacking.
Ureteral Strictures in Renal Transplants
The most frequently encountered urological complication after a renal transplant procedure is ureteral obstruction. Ureteral obstructions are categorized into early (<3 months) and late (>3 months).
Early obstructions usually respond to percutaneous approaches, such as nephrostomy, retrograde stenting, or dilatation, while late obstructions tend to recur because of the peri-ureteric fibrotic tissue. Percutaneous management can be very successful, achieving improvement of the renal graft function from 58% to 95%, and it has low short- and long-term complication rates. 63 In a follow up of 23 months, Schwartz et al. 64 reported that balloon cautery endoureterotomy had a 63% success rate in kidney transplants with ureteral strictures, despite previous failure of balloon dilation and stenting. Acucise was described as a useful therapeutic modality for uncomplicated short-distance ureteral stenosis after renal transplantation, while longer strictures were not treated successfully with this technique, due to higher complication rates. 65 However, the Acucise technique has the downside of uncontrolled incision in the stenotic area, which might result in harming adjacent structures. Gdor et al. 66 advocated that Ho:YAG laser endoureterotomy should be the initial treatment option in renal transplants with ureteral strictures measuring approximately10 mm.
To summarize, when endourology fails to treat ureteral strictures in kidney transplants, open reconstruction prevails as the gold standard. 67
Aytekin et al. 68 presented the results from 19 patients with transplanted kidney suffering from ureteral stenosis, causing obstruction. They were divided into early (n=9) and late (n=10) groups. The majority of the patients were treated percutaneously by nephroureterostomy, balloon dilatation, and Double-J stent insertion. The clinical success was 100% for the early and 90% for the late obstruction group, respectively, indicating that the timing of the obstruction did not affect the outcome.
Azhar et al. 69 reported the results of subcutaneous pyelovesical bypass graft as a salvage treatment in patients with refractory ureteral strictures. At a follow up of 19 months, seven out of eight renal grafts have preserved satisfactory glomerular filtration rate (GFR), without evidence of obstruction or infection. A similar technique was used by Muller et al. in seven patients with 7 years of mean follow up and good results, but with 47% of infection of the prosthesis. 70 Bach et al. 71 recorded an 87% success rate of the Memokath™ stent in six cases with ureterovesical and two pelviureteral strictures after renal transplantation and a follow up of 4 years.
Malignant Ureteral Obstruction
Due to the limited survival of patients with advanced malignancies, minimal invasive procedures are preferred instead of extensive surgical reconstruction. Radiation-induced ureteral strictures or strictures caused by malignant external compression or infiltration respond poorly to endoureterotomy. A success rate of retrograde stenting for malignant obstruction has been reported between 75% and 84%. 72 Silicone stents in malignant settings have shown reduced effectiveness. They are often misplaced, require regular replacement, and exhibit encrustation and migration. Moreover, patients with permanent ureteral stenting after radiation therapy may develop uretero-iliac fistula, which can be responsible for acute bleeding after a replacement procedure. In case of failure, patients require a percutaneous nephrostomy or an antegrade stent as a palliative treatment. A palliative procedure used to avoid nephrostomy and improve quality of life has been presented by Desgrandchamps et al. 73 and more recently by others, 74 using a subcutaneous nephrovesical bypass, which eliminates the presence of nephrostomy.
Metallic stents were used in order to overcome the prementioned limitations. Liatsikos et al. 75 recently evaluated the mid-term effectiveness (8.5 months of follow up) of the Resonance stent used in 25 patients with malignant ureteral obstruction. The technical success rate was 100%, and all stents remained patent during the follow up.
Eandi and collegues 76 described robot-assisted ureteroneocystostomy in four patients who had distal ureteral transitional cell carcinoma (TCC). With a median follow up of 30.5 months, only one patient who had carcinoma in situ on final pathology underwent adjuvant therapy for cancer recurrence. Hemal et al. 77 reported that in five patients with a median follow up of 10 months, robotic distal ureterectomy and bladder-cuff excision with ureteroneocystostomy for ureteral TCC was performed without complication or recurrence. However, feasible, long-term follow up is needed for establishing the value of this approach in TCC.
Innovative Techniques
Recent case series have featured innovative alternatives to reconstruct ureteral strictures, such as buccal mucosal or autologous vein grafts and cell-seeded biodegradable polymer scaffolds. 78,79 Further data are needed before these innovations will come into clinical practice.
Conclusions
Nowadays, endourological procedures represent the first choice of treatment for ureteral strictures. Literature corroborates that the methods described earlier are inferior to open surgery; however, minimally invasive approaches are often the initial option because of their reduced complication rates, reduced operative time, shorter length of stay, and decreased cost compared with an open reconstruction. Although laparoscopic and robotic approaches for ureteral reconstruction are still in their infancy and high-powered studies are lacking, they seem to be promising.
Footnotes
Disclosure Statement
No competing financial interests exist.