Study Type – Therapy (case series) Level of Evidence 4
What’s known on the subject? and What does the study add?
The resection of the distal ureter and its orifice is an oncological principle during radical nephroureterectomy which is based on the fact that it represents a part of the urinary tract exposed to a considerable risk of recurrence. After removal of the proximal part it is hardly possible to image or approach it by endoscopy during follow-up.
Recent publications on survival after nephroureterectomy do not allow the conclusion that removal of distal ureter and bladder cuff are useless. Several techniques of distal ureter removal have been described but they are not equivalent in term of oncological safety.
• The standard treatment of upper urinary tract urothelial carcinomas (UUT-UCs) must obey oncological principles, which consist of a complete en bloc resection of the kidney and the ureter, as well as excision of a bladder cuff to avoid tumour seeding.
• The open technique is the ‘gold standard’ of treatment to which all other techniques developed are necessarily compared, and various surgical procedures have been described.
• The laparoscopic stapling technique maintains a closed system but risks leaving behind the ureteric and bladder cuff segments.
• Transvesical laparoscopic detachment and ligation is a valid approach from an oncological stance but is technically difficult. The major inconvenience of the transurethral resection of the ureteric orifice and intussusception techniques is the potential for tumour seeding.
• Management of the distal ureter via the robot-assisted laparoscopic method is technically feasible, but outcomes from these procedures are still preliminary.
• Therefore, prospective comparative studies with more thorough explorations of these techniques are needed to solve the dilemma of the management of the distal ureter during nephroureterectomy. However, bladder cuff excision should remain the standard of care irrespective of the stage of the disease.
Open nephroureterectomy (ONU) remains the standard surgical treatment for upper urinary tract urothelial carcinoma (UUT-UC) [1,2]. For the distal ureter, it is standard practice to remove the intramural portion and ureteric orifice (UO), as well as the excision of a bladder cuff. Ideally, this is achieved by removal of an en bloc, ‘closed system’, specimen after controlled occlusion of the UO. However, several techniques of ureter and bladder cuff resection have been described. The challenges of all of these techniques are to remove the entire specimen en bloc, without tumour spillage, to conform to stringent oncological principles in the least invasive way possible. The aim of this article is to review the currently available data on the management of the distal ureter during nephroureterectomy.
SURGICAL ACCESS FOR NEPHROURETERECTOMY
ONU can be performed with either one incision, via a transperitoneal approach, or with two incisions via a flank approach combined with a lower abdominal incision for the distal ureter and the bladder cuff .
LAPAROSCOPIC NEPHROURETERECTOMY (LNU)
LNU has become a common treatment for UUT-UC with decreased perioperative morbidity [4,5]. Moreover, the oncological outcomes and survival rates are similar to ONU [4,6,7]. However, several precautionary measures must be taken when operating in a pneumo-peritoneal environment that may favour tumour spillage.
ROBOT-ASSISTED NEPHROURETERECTOMY (RANU)
Nazemi et al. described the robotic approach but with no obvious advantages compared with other methods thus far.
Technique: Open removal of the distal ureter can occur either after a laparoscopic procedure or after an open procedure to dissect the kidney and the ureter. To excise the lower distal ureter, a lower midline, modified Pfannenstiel or Gibson incision can be performed. The lower ureter is clipped, dissected free, and removed in continuity with the bladder cuff. The bladder cuff may be secured extravesically (using a right angle clamp) or via an anterior cystotomy. The en bloc specimen is delivered through the same incision [4,9–11].
Advantages: This approach conforms to the oncological principles previously described and minimizes the risk of tumour spillage [3,12,13]. It also enables the visual confirmation of complete excision and accurate histological examination. Patient repositioning is usually required but not always mandatory.
Disadvantages: The ‘blind’ extravesical clamping may compromise the contralateral UO and does not inevitably guarantee adequate bladder cuff retrieval . An anterior cystotomy is avoided in the presence of synchronous bladder UC because it retains the potential to seed tumour into the extravesical space [2,3,12]. Furthermore, prior pelvic surgery, irradiation, or obesity may render the open procedure more difficult.
Evaluations: Open series are typically used by authors as the standard point of comparison for other techniques, and no authors have reported failures of this method. There are few postoperative complications (e.g. urinoma, urinary infection). The rates of recurrence for bladder tumours are ≈30%[3,4,9–11].
PURE STANDARD LAPAROSCOPIC EXCISION OF THE DISTAL URETER AND THE BLADDER CUFF
Technique: A pure classic laparoscopic excision of the distal ureter and the bladder cuff can also be performed. Hattori et al.  described this technique where the ureter was ligated at the distal site of the tumour. Retracting the ureter cranially, a ‘stay’ suture was placed at an anterior point on the bladder, and the bladder was opened. Incising around the UO, the distal ureter was detached with the bladder cuff. The opened bladder wall was closed with running stitches.
Advantages/disadvantages: While respecting the aforementioned oncological principles, this method is technically difficult to perform.
Evaluations: This method was technically successful in all 10 cases reported, with minimal bleeding and an average operative time of 87 min . The margins of the bladder cuff were all negative, and at a mean follow-up of 19 months revealed there was only 10% bladder tumour recurrence.
Modified technique: Shoma  described a modification for the excision of a bladder mucosal cuff around the ipsilateral ureter. In this procedure, the detrusor muscle was further dissected away from under the bladder mucosa for 1 cm around the UO. Thus, a bladder cuff of mucosal origin only could be retrieved. A purse-string suture was applied at the edge of the dissected mucosa, and the cuff was excised. The mean operative time was 226 min. During a follow-up of 31.5 months, one patient developed recurrence in the renal bed.
LAPAROSCOPIC EXTRAVESICAL STAPLING OF THE DISTAL URETER AND URETERIC UNROOFING [12–16]
Technique: The ureter is clipped early and dissected caudally until it diverges to merge with the detrusor muscle fibres at the vesico-ureteric junction. Gentle traction on the ureter will ‘tent up’ the wall of the bladder at the vesico-ureteric junction, enabling placement of a 12-mm laparoscopic GIA tissue stapler or a large Hem-o-lok clip. A more recent trend describes the stapling of the bladder cuff as the initial step, followed by transurethral resection (TUR) of the ipsilateral UO until the staple line is reached . This method is usually combined with a ureteric unroofing procedure.
The ureteric unroofing technique was described by the Washington University group . It can only be used in transperitoneal LNU and comprises cystoscopic incision of the entire anterior length of the intramural ureter, electrocautery to the cut the edges and floor of the intramural ureter, placement of a 7.5 F occlusion ureteric balloon catheter in the renal pelvis to prevent urine spillage, laparoscopic dissection of the kidney and ipsilateral ureter down to the level of the bladder, and specimen detachment following placement of an Endo-GIA stapler on the bladder cuff.
Advantages: It may help reduce operative duration and facilitates a minimally invasive procedure while maintaining a closed urinary tract, thus, preventing tumour spillage.
Disadvantages: Operating the stapler may prove awkward in the restricted pelvic space. Additionally, an error in judgement might result in either part of the intramural ureter being left behind or inadvertent injury to the contralateral UO. In addition, the stapled margin cannot be assessed histologically, and the staple line can be a source of stone formation.
Contraindications: The presence of mid or lower ureteric and bladder tumours.
Evaluations: A comparison at nearly 4 years after LNU showed an increased positive margin rate and local recurrence rate, and decreased recurrence-free intervals were noted in the laparoscopic-stapled group when compared with the open group . However, none of these results is statistically significant, probably owing to the few patients. Several authors have compared the various methods of distal ureteric excision and reported a higher incidence of positive surgical margins (up to 25%) and local recurrence (up to 15%) in the pure LNU with laparoscopic stapling cohort [20,21].
Modified technique: Tsivian et al.  described a variation on the laparoscopic-stapling technique, using a 10-mm LigaSure Atlas. There were two bladder recurrences distant from the site of surgery but no reports of local recurrence in 13 patients followed for nearly 1 year after surgery.
TRANSVESICAL LAPAROSCOPIC DETACHMENT AND LIGATION TECHNIQUE
Technique: During retroperitoneal LNU, this technique of securing the distal ureter and bladder cuff using transvesically placed laparoscopic ports was described by Gill et al. . In this procedure, a transurethral Collin’s knife incision of the bladder cuff is made after placement of a catheter into the affected ureter. Traction on the incised bladder cuff enables the mobilization of 3–4 cm of distal ureter into the bladder. The entire ureter can then be pulled through in a cephalad fashion after radical nephrectomy and ureteric dissection.
Advantages: The transvesical technique adheres to general oncological principles of complete and controlled en bloc specimen extraction. The ureteric catheter and Endoloop occlude the ureter, thereby reducing urine leakage. Further, an indwelling ureteric catheter can aid identification and mobilization of the ureter during the laparoscopic procedure. Complete retrieval is confirmed by visualization of the Endoloop.
Disadvantages: This may be a difficult technique to master for most urologists, and the operating duration is usually lengthened by 60–90 min [23,24]. Other criticisms of this approach include the potential for irrigation fluid extravasation resulting in dilutional hyponatraemia, the need for patient repositioning, and the possibility of port-site metastases.
Contraindications: The presence of distal ureteric tumour or concomitant bladder tumours, previous pelvic surgery, or irradiation and obesity .
Evaluations: Matin and Gill  reviewed retrospectively the outcomes in 60 patients after LNU, who had either had a laparoscopic stapling (12 patients) or transvesical laparoscopic detachment of the distal ureter (36). After a mean follow-up of 23 months, positive margins were more common in the former group (25% vs 2.8%), as were the rates of bladder recurrences at the ipsilateral UO/scar (41.7% vs 13.9%), retroperitoneal recurrence (8.3% vs 5.6%), and distant metastasis (25% vs 8.3%). None of these differences were statistically significant, and definitive conclusions are difficult to derive from such a small retrospective series.
Modified technique: A similar technique has been described using a pneumovesicum to secure the UO and bladder cuff [25,26]. This approach has several theoretical advantages, including en bloc removal of the entire specimen, excellent visualization in the bladder and minimization of the potential for tumour seeding with early closure of the UO during distal ureteric dissection, and the use of pneumovesicum instead of fluid irrigation. Another advantage of a pneumovesicum approach is that the ports are placed extraperitoneally (similar to a suprapubic tube), and the need for a large transvesical incision is eliminated, which potentially improves recovery times, minimizes bladder spasms and haematuria, and allows for earlier Foley catheter removal. However, there are no data concerning the long-term oncological outcomes of this technique.
THE ORIGINAL TUR OF THE UO TECHNIQUE, I.E. THE ‘PLUCK’ TECHNIQUE
Technique: The original TUR of the UO (TURUO) technique, also known as the ‘pluck’ technique, was originally used during ONU and subsequently adapted for LNU. Patients undergo rigid cystoscopy with aggressive resection of the UO and intramural ureter into the perivesical fat. Once the proximal specimen is mobilized, the previous TUR eases the subsequent bladder cuff excision. In 1998, Keeley and Tolley  first described the use of the pluck technique in LNU, thus making the procedure purely laparoscopic. This involves initial endoscopic resection of the UO. The ureteric lumen is completely coagulated to prevent urinary spillage. NU is then performed using a flank incision, with gentle traction of the ureter.
Disadvantages: One disadvantage of this technique is the increase in procedure duration caused by the need for re-positioning. Notably, the potential for incomplete resection of the intramural ureter exists. Thus, this procedure should be avoided in patients with distal ureteric tumour .
Evaluations: Salvador-Bayarri et al.  compared the results of the pluck technique with those of standard NU and concluded that the pluck technique did not increase the risk of tumour recurrence after NU for upper urinary tract carcinoma.
Pluck Technique modifications
Various modifications on the pluck theme have been described to minimize tumour spillage. A preformed polydioxanone Endoloop can be passed through the cystoscope to ligate and occlude the UO . Mueller et al.  recently described a technique with injection of Tisseel into the ureter after confirming the absence of bladder tumours and introducing an 8 F olive-tipped ureteric catheter into the UO.
Pluck Technique in hand-assisted LNU
Alternatives to endoscopic management of the distal ureter during hand-assisted LNU have been reported [31–34]. Gonzalez et al.  described a technique implementing insertion of a laparoscopic port, followed by introduction of a 24 F nephroscope, allowing endoscopic Collin’s knife incision of the bladder cuff. This is performed subsequent to dissection of the kidney and ureter and after clips have been placed on the lower ureter.
Alternatively, a similar technique may be performed without the need for a bladder port or patient repositioning . Vardi et al.  reported a novel modification to this technique by inserting a flexible cystoscope per urethra and a 5 F electrode (ACMI, Norwalk, Conn, USA) to incise a circumferential 2-cm cuff of bladder around the UO using a cutting and coagulating current. Patient repositioning after the nephrectomy is avoided, and the bladder opening is not closed. There were no pelvic recurrences in their small group of patients after a mean follow-up of 31 months.
None of the endoscopic techniques have been evaluated extensively. There are no randomised trials and no comparative data on outcomes due to the rarity of UUT-UCs.
INTUSSUSCEPTION TECHNIQUE OR URETERIC STRIPPING
Technique: Principles of this technique include initial catheterization of the ureter, using either a ureteric catheter or a stone basket ligation, and division of the ureter as part of the renal mobilization. This is followed by securing the distal ureter to the ureteric catheter/stone basket, transurethral incision of the bladder cuff, and removal of the distal ureter by gentle traction on the catheter via the urethra . The distal ureter intussuscepts into the bladder and can either be removed transurethrally or via a small lower midline incision and anterior cystotomy. Various technical devices, including sutures, vein strippers, balloon catheters, and double ligations, have been described in an attempt to improve ureteric excision of the ureter [36,37].
Disadvantages: The main drawback of this procedure is a failure to guarantee adequate excision of the intramural ureter and bladder cuff, potentially resulting in tumour recurrence.
Contraindications: Because the ureter is transected, it is contraindicated for ureteric tumours and primarily confined to low-grade renal pelvic tumours. Additionally, any cause for pelvic fibrosis, such as previous surgery or irradiation and retroperitoneal fibrosis, may further increase the risk of retention of ureteric remnants.
Evaluations: The stripping and pluck techniques were compared in a systematic review . Whereas there were no reports of local disease recurrence in the stripping group, this technique was associated with a 10% complication rate (including retained ureters and catheter breakage), resulting in an open conversion rate of 9.5–12.5% in patients after difficult extraction. In a comparative study of patients who underwent total NU with transurethral ureteric stripping and patients who underwent the standard two-incision NU, transurethral stripping appears to be associated with significantly greater intravesical tumour recurrence rate .
A robot-assisted laparoscopic approach has also been reported [40,41]. The principal advantage of the robotic approach appears to be that repositioning of the patient from flank to supine and movement of the patient cart are unnecessary. Keeping the patient in the flank position not only shortens the operative duration, but also improves exposure of the distal ureterectomy and closure of the bladder cuff.
All current available options for distal ureter management are presented in Fig. 1.
Each technique of distal ureter management has inherent advantages and disadvantages. However, thus far, no prospective, randomised trials have compared the different approaches. The reported recurrence rates within the bladder after various management techniques of the distal ureter during NU vary considerably from 6.7% to 50%. Additional long-term comparative outcomes are needed to solve the dilemma of the distal ureter.