The surgical technique and efficacy of a novel pure retroperitoneoscopic extravesical bladder cuff excision without intraoperative repositioning for upper tract urothelial carcinoma

Abstract

To evaluate the feasibility, effectiveness and therapeutic outcomes of a novel pure retroperitoneoscopic extravesical bladder cuff excision (PREBE) in patients with upper tract urothelial carcinoma (UTUC), a retrospectively comparative study between PREBE and traditional laparoscopic nephroureterectomy (TLNU) was done in a single center. We retrospectively evaluated 72 patients diagnosed with UTUC at our hospital from January 2022 to January 2024. The patients who underwent TLNU (n = 35) and PREBE (n = 37) were consecutively enrolled. The kidney and bladder cuff were retroperitoneoscopically dissected and the bladder was repaired with needle sutures under retroperitoneoscopic in the PREBE group. Demographic, perioperative, and follow-up data were collected and compared between the two groups. Both procedures were performed effectively in 72 patients without converting to open surgery. The PREBE group exhibited shorter mean operative time (P < 0.01), less mean estimated blood loss (EBL) (P < 0.01), shorter median drainage tube removal time, shorter median first postoperative defecation (FPD) time (P < 0.01) and shorter median postoperative hospital stay (P < 0.01). However, there was no statistical difference in postoperative pathological results or in the incidence of intravesical recurrence between the two groups. The mean follow-up time was 13.8 months for the PREBE group and 14.4 months for the TLNU group. The PREBE is a safe and effective treatment for patients with UTUC, avoiding intraoperative patient repositioning while offering better perioperative outcomes to those of traditional techniques.

Introduction

UTUC is a relatively rare cancer, accounting for 5–10% of all urothelial tumors [1]. Radical nephroureterectomy (RNU) remains the gold standard treatment for high-grade disease in the ureter and renal pelvis, and a few low-grade tumours are not amenable to more conservative techniques [2, 3]. Due to the high risk of ipsilateral ureteral recurrence, standard management mandates the complete removal of the ureter, including the distal segment and bladder cuff, regardless of tumour location [4]. Various techniques have been developed, including open resection, transurethral endoscopic resection, and laparoscopic stapling of the bladder cuff. However, there is still no consensus on the optimal approach to managing the distal ureter and bladder cuff [4, 5].

Recent evidence-based medicine research indicates that bladder sleeve resection is an independent factor influencing patient prognosis [6]. Currently, achieving sufficient resection of the bladder cuff, preventing urine extravasation, and suturing the bladder incision simultaneously during minimally invasive surgery poses significant challenges. It is a widely accepted practice to combine retroperitoneoscopic nephrectomy with open distal ureterectomy to facilitate complete resection of the bladder cuff. However, this procedure requires intraoperative repositioning and re-disinfection, which can significantly prolong the operation time and increase the risk of adverse postoperative outcomes. Several studies have indicated the efficacy of the endoscopic gastrointestinal automatic (Endo-GIA) stapler as a viable alternative for reconstructing the distal ureter [7]. However, the effectiveness of Endo-GIA staplers in achieving complete bladder cuff resection remains unverified.

Here, we present a novel technique for the complete resection of the bladder cuff, followed by bladder repair with needle sutures under retroperitoneal laparoscopy without repositioning, balancing the advantages of minimally invasive surgery with the need for complete resection of bladder cuff.

Materials and methods

Patients

From January 2022 to January 2024, a total of 72 patients with UTUC who underwent surgery were consecutively enrolled, and relevant data were collected. Among these patients, thirty-seven received the modified PREBE technique, while thirty-five underwent the traditional approach. We retrospectively analyzed demographic and perioperative data to assess the perioperative and oncological outcomes of our innovative PREBE technique.

Before surgery, each patient underwent computed tomographic urography to precisely locate the tumor. Renal dynamic imaging was also performed to evaluate contralateral renal function. Thoracic and abdominal CT scans were conducted to exclude any potential tumor metastases. The mean follow-up time was 13.8 months for the PREBE group and 14.4 months for the TLNU group.

This study was conducted in accordance with the standards set by the Ethics Committee of the affiliated Yantai Yuhuangding Hospital of Qingdao University. All patients were informed that their clinical data might be used in future scientific research, and informed consent was obtained.

PREBE technique

Patients were positioned in a 90° lateral decubitus position with the affected side up and a slightly raised waist bridge, aligning the umbilicus with the middle joint of the operating table. The operative area was disinfected, and a urethral catheter was inserted. A small incision was made 2 cm below the 12th rib and 2 cm ventral to the posterior axillary line. The peritoneum was carefully pushed inward through the incision, creating an extraperitoneal space via blunt dissection and balloon dilation. A 12 mm trocar was inserted into the incision (port A), and another 12 mm trocar was placed 2 cm ventral to the anterior axillary line at the same level (port B). A 10 mm trocar was inserted 2 cm ventral and 3 cm above the iliac crest on the midaxillary line as a monitor port (port C). The final 5 mm trocar was inserted 2 cm outside the rectus abdominis at the same level as port c (port D). Pneumoperitoneum was established with a pressure of 12 mm Hg. Figure 1 illustrates the patient position and port locations.

Fig. 1.

Trocar distribution and change of operative position A. Port distribution of nephrectomy and management of the upper ureter (take the right side for example) B. Port distribution of management of the distal ureter and bladder-cuff resection

Initially, the surgeon used port A and port B as working trocars. If necessary, port D was utilized to assist the operation (Fig. 1A). After accessing the retroperitoneal space, extraperitoneal fat was cleared to improve intraoperative visibility. The perirenal fascia was incised longitudinally with an ultrasonic scalpel to expose the perirenal fat. Dissection then proceeded along the less vascularized plane of the psoas major and quadratus lumborum muscles. The dissection continued deeply along the psoas major until the renal artery was located, clamped with Hem-o-lok clips, and transected (Fig. 2A). The renal vein was managed similarly (Fig. 2B). The ureter was mobilized at the lower pole of the kidney. To prevent tumor seeding during the procedure and facilitate intravesical implantation and spread, the ureter was clipped using Hem-o-lok clips (Fig. 2C). After ligated the ureteral, the lower pole of the kidney was carefully separated from the psoas major, and the ureter was meticulously dissociated towards the pelvic cavity (Fig. 2D). The ultrasonic scalpel was used to separate the superior pole of the kidney from the adrenal gland along the avascular plane between the perirenal fat and prerenal fascia. The kidney was fully mobilized by expanding and dissecting the anterior pararenal space on the ventral side.

Fig. 2.

Operative view of main surgical steps U ureter, RA renal artery, RV renal vein, B bladder. A. The renal artery has been disposed. B. The renal vein has been disposed. C. The ureter was clamped at the lower pole of the kidney. D. Dissociate the ureter toward the pelvic cavity.E. pull the ureter until it forms an umbrella shape. F. The bladder was sutured with 2–0 barb suture

After completing the kidney and upper ureter dissection, the patient's position was adjusted to a 20° head-down and foot-up orientation. The monitor was then positioned in port b. At this stage, the operation primarily utilized port c and port d trocars (Fig. 1B). The surgeon should position themselves facing the patient's feet. To continue dissecting the ureter towards the pelvic cavity, for female patients the occluded umbilical and uterine arteries were clamped with a Hem-o-lok clip and transected. If necessary, part of the lateral ligament of the bladder could be transected to expand the surgical field. The ureter was then pulled until the bladder formed an umbrella shape, and an anterolateral incision was made on the bulge of this umbrella (Fig. 2E). The intramural ureter was fully dissociated. After clamping the distal ureter, a cuff of the bladder wall was excised along with the distal ureter using an ultrasonic scalpel. Chemotherapeutic drugs were instilled into the bladder 30 min before bladder cuff excision via the urethral catheter to prevent tumor implantation in the bladder. The bladder was then sutured with 2–0 barbed sutures (Fig. 2F). The kidney, ureter, and bladder cuff were placed in a specimen bag and extracted through a small Gibson incision (Fig. 3). The surgical site was thoroughly inspected, and a drainage tube was placed in the retroperitoneum and another in the pelvic cavity. The incision was closed, marking the successful completion of the surgery.

Fig. 3.

Gross specimens of complete resection

We have compiled several essential techniques for this procedure: (1) Position the trocar on the iliac spine 2–3 cm higher than usual and shift it 2–3 cm ventrally to minimize the impact of the pelvis on the instruments. (2) Fully mobilize the peritoneum when inserting the fourth trocar, and if needed, use a syringe needle for puncture positioning to reduce the risk of peritoneal injury. (3) For female patients, transect the obliterated umbilical artery, and uterine artery to create a better retroperitoneal working space. (4) Avoid forceful traction on the ureter; instead, keep it under tension towards the head to prevent ureteral rupture. (5) Pull the ureter until it forms an umbrella shape, then make an anterolateral incision on the bulge of the umbrella. To reduce the risk of contralateral ureteral injury, it is recommended to identify the bilateral ureteral orifices before performing the bladder cuff resection. (6) Retain a small amount of bladder tissue on the side of the incision for traction during the bladder cuff resection to better expose the bladder incision; cut it off entirely after the first stitch is sutured. (7) Protect the contralateral ureteral orifice during bladder incision suturing, and replace the drainage bag with a new one to accurately record urine output after the bladder incision is sutured.

Statistical analysis

Fisher’s exact test or χ² test was utilized to compare categorical variables. Quantitative variables were presented as mean ± standard deviation or median with interquartile range. To test for differences between the two groups, the Student’s t test was used for data with a normal distribution, while the Mann––Whitney U test was employed for data with a non-normal distribution. Statistical significance was determined at P value of < 0.05.

Results

The PREBE and TLNU cohorts had mean follow-up times of 13.8 months and 14.4 months, respectively. Both groups underwent successful surgery without the need for conversion to open surgery or any injury to adjacent tissues. Postoperative pathology reports confirmed urothelial carcinoma with negative surgical margins in all patients. Table 1 presents the perioperative outcomes for each cohort. The demographic data, including age and BMI, were similar between the two groups with no significant differences (P > 0.05). Additionally, there were no statistically significant differences observed between the two groups regarding the side of the lesion and tumor location (P > 0.05).

Table 1.

The perioperative outcomes and postoperative pathological stage of patients

Characteristic	PREBE group (n = 37)	TLNU group (n = 35)	p value
Median age, years (range; IQR)	68 (54–84; 12)	65 (55–87; 15)	0.24
Gender, n (%)
Male	23 (62%)	21 (60%)
Female	14 (38%)	14 (40%)
Mean BMI, kg/m2 (range; ± SD)	23.2 (18.3–28.9; ± 2.0)	23.6 (19.9–27.8; ± 2.1)	0.35
Operative side, n (%)
Left	18 (49%)	19 (54%)
Right	19 (51%)	16 (46%)
Tumor location, n (%)
Pelvis	24 (65%)	21 (60%)
Upper ureter	7 (20%)	9 (26%)
Mid ureter	2 (5%)	3 (9%)
Distal ureter	4 (10%)	2 (6%)
Mean operation time, min (range; ± SD)	120.6 (77–173; ± 22.2)	201.3 (138–268; ± 33.1	< 0.01
Mean EBL, ml (range; ± SD)	64.6 (10–150; ± 37.5)		< 0.01
Median post-op HS, Days (range; IQR)	4 (3–5; 1)	5 (4–7; 2)	< 0.01
Median time of RD, Days (range; IQR)	3 (2–5; 1)	4 (2–5; 2)	< 0.01
Median FPD time, Days (range; IQR)	4 (2–7; 2)	5 (2–11; 2)	< 0.01
No. of patients of follow-up (n)	35	32
Mean follow-up, Month (range; ± SD)	13.8 (6–25; ± 5.1)	14.4 (6–26; ± 5.3)
Pathologic T stage, n (%)			0.31
T1	15 (41%)	13 (37%)	0.98
T2	16 (43%)	15 (43%)
T3	6 (16%)	7 (20%)
Pathologic grade, n (%)
G1	16 (43%)	12 (34%)	0.64
G2	14 (38%)	17 (49%)
G3	7 (19%)	6 (17%)
Bladder recurrence, n (%)	6 (16%)	8 (23%)	0.56

Bold fonts represent statistically significant differences

BMI body mass index, EBL estimated blood loss, post-op HS postoperative hospital stay, DR drainage removal, FPD first postoperative defecation

In terms of surgical outcomes, patients who underwent PREBE had a significantly shorter mean operation time (120.6 ± 22.2 vs. 201.3 ± 33.1 min, P < 0.01) and lower mean EBL (64.6 ± 37.5 vs. 118.6 ± 54.6 ml, P < 0.01) compared to those who underwent TLNU. Postoperatively, the PREBE group also had significantly shorter median drainage tube removal times (3 vs. 4 days, P < 0.01) and median time to first postoperative defecation (4 vs. 5 days, P < 0.01) compared to the TLNU group. Furthermore, patients in the PREBE group had a significantly shorter median postoperative hospital stay (4 vs. 5 days, P < 0.01) than those in the TLNU group.

Pathological examination of the specimens revealed no significant differences between the two groups in terms of pathological T stage and tumor grade (P > 0.05), as shown in Table 1. During the follow-up period, six patients (16%) in the PREBE group and eight patients (23%) in the TLNU group experienced intravesical recurrence, though the difference was not statistically significant (P > 0.05). Notably, no patients in either group developed distant metastasis.

Discussion

Radical nephroureterectomy (RNU) remains the gold standard treatment for high-risk non-metastatic UTUC. A critical component of RNU is bladder cuff excision, as failure to remove the cuff is associated with a significantly poorer prognosis [2, 8, 9]. Recent advancements in laparoscopic techniques and the increasing emphasis on minimally invasive procedures have made laparoscopic surgery the preferred approach for treating UTUC. Numerous studies have shown that laparoscopic RNU can offer oncological outcomes comparable to those of open surgery while minimizing the risk of injury [10–14]. Managing the distal ureter and excising the bladder cuff laparoscopically presents significant challenges for surgeons. At present, distal ureteral management is predominantly carried out through open surgery. Although various approaches have been suggested to enhance distal ureteral management techniques, none have achieved a satisfactory balance between the complete removal of the bladder cuff and the comprehensive suturing of the bladder cuff; there remains no consensus on the optimal method [4, 5].

Laparoscopic nephroureterectomy can be performed using either a transperitoneal or retroperitoneal approach, both of which have been shown to be safe and effective [15]. Some reports suggest that complete transperitoneal laparoscopic nephroureterectomy can be achieved without the need for intraoperative repositioning [16–18]. Although the transperitoneal approach offers better anatomical orientation and a larger operative field, the retroperitoneal approach provides direct access to the kidney without requiring movement of the bowel or intraperitoneal organs which reduces the risk of complications related to those organs and minimizes the impact on bowel function [15, 19]. Kim et al. indicate that the retroperitoneal approach is superior to the transperitoneal approach in managing the progression of UTUC in patients [20]. Additionally, it is particularly advantageous for patients with a history of abdominal surgery. For these reasons, we developed the PREBE technique, which employs a purely retroperitoneal approach. By adhering to our trocar placement strategy and minimizing peritoneal injury, our technique provides sufficient surgical space entirely through a retroperitoneal approach.

Traditional laparoscopic nephroureterectomy combined with open bladder cuff resection requires an intraoperative change in patient position and secondary disinfection, which prolongs the operation time and increases procedural complexity. The open bladder sleeve resection also necessitates a long lower abdominal incision, which can significantly impact the patient’s physical appearance. Furthermore, the complex female pelvic anatomy presents additional challenges for surgeons due to the limited dissection space and the intricate structures of the lower abdominal and pelvic regions. By utilizing the PREBE technique, repositioning and secondary disinfection are avoided, with only the surgeon needing to adjust their position. This reduces the overall operation time and eliminates unnecessary delays. Although a lower abdominal incision may still be required for specimen removal, it is considerably shorter than that required for open bladder sleeve resection.

The management of the distal ureter is widely regarded as the most challenging aspect of laparoscopic nephroureterectomy [5]. While open bladder sleeve resection has traditionally been a reliable method for ensuring oncological control, it requires an additional incision, increasing the incidence of complications [21]. An alternative is endoscopic resection, which uses a cystoscope to excise the ureteral orifice and bladder cuff, allowing for easier removal of the distal ureter [22]. This approach eliminates the need for a lower abdominal incision and reduces operation time. However, it requires a change in the patient’s position from endoscopic lithotomy to supine or lateral during surgery, and there is a risk of spilling urine-containing tumor cells into the retroperitoneum, increasing the risk of extravesical recurrence. Additionally, the possibility of leaving residual ureteral tissue, which can lead to intravesical recurrence, remains a concern [16, 23]. Although modified techniques have been developed to mitigate these risks [24], endoscopic resection does not fully adhere to the tumor-free principle of surgery. The use of an endoscopic gastrointestinal automatic (Endo-GIA) stapler offers another alternative, allowing for total laparoscopic management without a change in position, thereby reducing operation time and the risk of complications [7, 25]. However, the ability of Endo-GIA staplers to ensure complete bladder cuff resection remains unproven, and long-term follow-up studies are needed to assess their efficacy [25, 26]. The potential preservation of urothelium between staples may pose a risk of tumor recurrence, making stapling an unreliable and potentially unsafe method for bladder cuff removal [27]. In summary, compared with endoscopic resection, the PREBE technique reduces the risk of spillage of urine containing tumor cells by pulling the bladder cuff upward. In addition, this technique avoids the potential preservation of urothelium between staples and bladder stones caused by the staples using the Endo-GIA technique.

In contrast, our PREBE technique eliminates the need for patient repositioning, only requiring switching the position of the surgeon and the camera placement port during the operation, and the number of surgical assistants was reduced, making this procedure preferable for both the patient and the operator. The PREBE technique has shorter operative time, less blood loss, and shorter hospital stay, all of which contributed to improved postoperative recovery and postoperative management of patients. During distal ureter management and bladder cuff excision, the ureter is elevated, and the bladder incision is positioned upward to minimize the risk of urine spillage containing tumor cells. The bladder cuff is excised under direct laparoscopic visualization, ensuring complete removal while protecting the contralateral ureter. The bladder incision is then carefully sutured with 2–0 barb suture, meeting critical surgical quality metrics such as en bloc specimen removal, minimized risk of tumor spillage, R0 resection, and a watertight closure that allows for early prophylactic intravesical chemotherapy [5]. In different patient subgroups and hospital settings, the PREBE technique has the potential to replace traditional nephroureterectomy or serve as a complement to existing modified techniques, particularly in elderly, obese, or comorbid patients with higher surgical risks.

The primary challenges of the PREBE technique lie in dissecting the entire ureter within a confined surgical space, achieving complete bladder cuff resection, and performing precise bladder suturing. Surgeons performing this technique must possess solid foundational skills in minimally invasive surgery and a comprehensive understanding of pelvic anatomy. For urologists with proficiency in minimally invasive techniques and familiar with the procedure of nephroureterectomy, the learning curve for this technique is not steep.

The potential survival benefits and therapeutic value of performing lymphadenectomy in surgeries for upper tract urothelial carcinoma remain a subject of debate. The adverse effects of lymphadenectomy must be taken seriously, as it can lead to complications such as bleeding, vascular damage, lymphatic fistula, and even potential mortality [28]. Due to the limited surgical space, these adverse events may occur more frequently when performing the PREBE technique. Additionally, performing lymphadenectomy at the timing of the PREBE technique would bring some negative consequences such as longer operative time and less efficient dissection. Therefore, our study did not perform lymphadenectomy on patients. For patients who indeed require lymphadenectomy, combining neoadjuvant therapy to reduce surgical difficulty or switching to an open approach may be considered. Future improvements in the trocar placement and retroperitoneal space expansion techniques of the PREBE method hold promise for further addressing this issue.

However, several limitations exist in this study. First, lymphadenectomy may appear to be a challenge due to the limited space. However, the curative role and the extent of lymphadenectomy remain a matter of debate. Second, the non-randomized and retrospective nature of the patient collection introduces an inherent selection bias that may lead to bias in the study results. The inability to retrospectively collect important research indicators, such as whether significant urine spillage occurred during surgery, may impact the final study outcomes, a larger sample, longer follow-up time, and further analysis are still needed to minimize bias in the future. Finally, the PREBE technique has not yet been widely adopted, necessitating a considerable level of surgical expertise for its application.

Conclusion

In summary, the PREBE technique for single-position total retroperitoneoscopic nephroureterectomy and bladder cuff excision is a safe, practical, and feasible approach that enhances perioperative outcomes without compromising oncological results. This technique demonstrated superior perioperative outcomes and quicker functional recovery compared to traditional methods. Patients who are candidates for nephroureterectomy should be considered for PREBE as a viable treatment option.

Author contributions

XC: Project development, Data analysis, Manuscript writing GLT: Data analysis, Manuscript editing JNS: Data analysis, Manuscript editing FZ: Data analysis, Manuscript editing WCS: Data analysis, Manuscript editing HWZ: Project development, Supervision, Manuscript editing All authors approved the version to be published and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Funding

This study was supported by the Taishan Scholars Program of Shandong Province (No. tsqn202211379).

Data availability

No datasets were generated or analysed during the current study. The data that support the findings of this study are available from the corresponding author upon reasonable request.

Declarations

Conflict of interest

The authors declare no competing interests. The authors have no competing interests to declare that are relevant to the content of this article.