Surgical techniques and oncological outcomes of pure transperitoneal laparoscopic radical nephroureterectomy for upper urinary tract urothelial carcinoma

Introduction

Upper urinary tract urothelial carcinomas (UTUCs) are uncommon and account for only 5–10% of urothelial carcinomas (1). Open radical nephroureterectomy (RNU) with bladder cuff excision is the standard treatment for UTUC, regardless of tumor location (2). With the advancements in surgical instruments and laparoscopic techniques, laparoscopic RNU is also safe if conducted by experienced hands. There is a tendency toward equivalent clinical outcomes after laparoscopic or open surgery (3,4). Even after RNU, recurrence in the bladder occurs in 22–47% of UTUC patients (5), compared with 2–6% in the contralateral upper tract (6). Five-year cancer-specific survival (CSS) rates are only 50–80% (7,8).

At present, laparoscopic radical nephroureterectomy (LSRNU) is performed by laparoscopic nephrectomy and the management of the distal ureter by open excision or transurethral resection. The conventional laparoscopic approach includes changing the position, disinfection, and draping once again. We innovatively adopted a pure laparoscopic procedure with a single position (9) of the RNU with bladder cuff excision. This approach is minimally invasive, avoids unnecessary operations, reduces infection risk and shortens the learning curve and operative time (10,11). We conducted this study to identify the oncological outcomes, including overall survival (OS) and CSS, of pure transperitoneal LSRNU for UTUC. We present this article in accordance with the STROBE reporting checklist (available at https://tau.amegroups.com/article/view/10.21037/tau-22-653/rc).

Methods

Clinical materials

Between July 2010 and December 2020, 115 patients were admitted to the hospital with the diagnosis of UTUC treated with pure LSRNU by one surgeon. Lymph node dissection was conducted when lymph node metastasis was suspected in the preoperative evaluation or enlarged lymph nodes were found during surgery. Demographic and perioperative data as well as follow-up data were retrospectively collected. Patients were assessed with preoperative imaging studies with chest X-ray, urinary ultrasound and computed tomography urography (CTU) routinely applied. None of these patients had concomitant bladder tumors. Tumors were pathologically staged based on the 2009 Tumor-Node-Metastasis (TNM) classification of malignant tumors, and pathological grades were determined according to the 1973 World Health Organization (WHO) classifications. This study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Ethics Committee of Peking University First Hospital (No. 2021130). Because of the retrospective nature of the research, the requirement for informed consent was waived.

Surgical techniques and procedures

Under general anesthesia, the patient was placed in the 45°–60° lateral position with the lesion side up (taking the left as an example). Access was achieved on the left midclavicular line at the subcostal margin using a Veress needle, and the abdominal ports were placed (Figure 1A). The pneumoperitoneum pressure was maintained at 14 mmHg. A 12-mm trocar for the camera was placed 3 cm above the umbilicus, and the other 12-mm trocar was placed 3 cm below the umbilicus at the outer border of the left rectus abdominis. Then, another 12-mm trocar at the reverse McBurney point, as the main trocar, was placed by the surgeon. A 5-mm trocar was placed along the Veress needle. If the lesion was on the right, the trocar was placed symmetrically. An additional 5-mm trocar for retraction of the liver was necessarily placed inferior to the xiphoid at the midline.

Figure 1 Description of pure transperitoneal LSRNU for UTUC. (A) Operative position and trocar distribution. (B) The distal ureter. (C) A bulldog clamp (5.8 cm long, 1.8 cm wide and 0.3 cm thick. The closing force is approximately 9 Newtons). (D) A bulldog clamp was placed at the bottom of the tent-shaped structure. (E) Bladder closure was performed in a two-layer running manner using a barbed suture. LSRNU, laparoscopic radical nephroureterectomy; UTUC, upper urinary tract urothelial carcinoma.

After mobilization of the colon, the renal pedicle was located through the gonadal veins and ureter. The renal hilum was fully dissociated, clipped and dissected with endovascular gastrointestinal anastomosis (Endo-GIA), and the gonadal veins were dissected at the same time. Radical nephrectomy was performed by fully dissociating the affected kidney and retaining the ipsilateral adrenal gland. An additional 12-mm trocar was placed in the midline of the lower abdomen to dissect the distal ureter and bladder wall without position changes. The ureter was clipped distal to the tumor site by Hem-o-lock to avoid tumor seeding. The ureter was further dissected carefully over the iliac vessels down to the detrusor muscle fibers of the ureterovesical junction (Figure 1B). An intramural ureter and tent-shaped bladder cuff were formed with retraction of the bladder wall. A special laparoscopic bulldog clamp was innovatively used by our center (12) (Figure 1C), which was placed at the bottom of the tent-shaped structure in case of urine spillage (Figure 1D). Once the intramural ureter was separated from the surrounding detrusor muscle and down to the bladder mucosa, the intramural ureter and tent-shaped bladder mucosal cuff could be detected by retraction in the superior and lateral directions. A bladder cuff was incised, and closure was performed in a two-layer running manner using a barbed suture (Figure 1E). After finishing the suture, the bulldog clamp was removed. Finally, the dissected specimen was extracted en bloc.

Postoperative management and follow-up

After the operation, patients received the urethral Foley catheter and pelvic drain. The urethral Foley catheter was removed within 1 week. The pelvic drain was usually removed when the output was <50 mL after the operation. Scheduled follow-up occurred every three months for a year and every 6 months during the next 3 years after surgery by a telephone interview or outpatient visit. Routine blood and urine tests, urine cytology, cystoscopy, and physical examination were performed at each visit. Imaging evaluations, including computed tomography (CT) or magnetic resonance imaging (MRI), were performed every 6 months for the first 5 years and then annually thereafter.

Statistical analysis

Statistical analysis was performed with SPSS software (IBM Corporation, Armonk, NY, USA, version 25.0). Categorical variables are shown as frequencies. Parametric variables are shown as the mean ± standard deviation (SD). OS and CSS were estimated by the Kaplan-Meier method.

Results

The pathological characteristics of the patients are shown in Table 1. A total of 115 patients were included in this cohort study (58 males and 57 females). The mean age of the patients was 68.9 (range, 35–88) years. The mean body mass index (BMI) was 24.6 kg/m², and the mean American Society of Anesthesiologists (ASA) score was 2.2 (range, 1–4). Pathologic analysis showed that 65 (56.5%) of patients were G2 and 50 (43.5%) were G3. Staging revealed 52 (45.2%) patients with pTis-1, 38 (33.0%) with pT2, 24 (20.9%) with pT3, and 1 (0.9%) with pT4. There were more ureteral tumors (50.4%) than renal pelvis tumors (40.9%), and both accounted for 8.7%. Eighteen (15.7%) patients came with multifocal tumors. Seven patients (6.1%) had positive lymph nodes, and one patient was found to have positive surgical margins. The surgical and oncological results are described in detail in Table 2. All surgeries were effectively completed, and no case required open conversion. The mean operative time was 145.69 minutes. The mean estimated blood loss was 56.61 mL. The mean drainage time was 3.46 days. The mean liquid diet time was 1.32 [1–4] days, and the ambulation time was 1.50 [1–5] days. The mean hospital stay was 5.78 days. According to the Clavien-Dindo (C-D) classification system, two patients experienced a postoperative complication. One patient showed symptoms of urine leakage (C-D II), but the phenomenon disappeared completely though the use of antibiotics and unobstructed draining. The other patient experienced postoperative intestinal obstruction (C-D III) and was treated by laparoscopic enterolysis. The mean length of postoperative hospital stay was 5.78 days.

The mean follow-up duration was 54.5 months. Among 115 patients, 13 patients were lost to follow-up, 27 patients died, and 20 died due to the tumor. Six patients experienced local recurrence, and seventeen patients exhibited distant metastasis. Recurrence in the bladder was 16.0% (15/94), compared with 4.6% (4/87) in the contralateral upper tract. The 5-year OS and CSS rates were 78.9% and 81.4%, respectively (Figure 2). At the follow-up, cystoscopy (usually 3 months after surgery) showed that the affected side of the ureteral orifice disappeared (Figure 3).

Figure 2 Estimated Kaplan-Meier overall survival and cancer-specific survival curve.

Figure 3 Postoperative cystoscopy showed that the ureteral orifice disappeared.

Discussion

UTUC is a malignant tumor of the urologic system with a relatively low incidence and poor prognosis. In terms of the surgical approach, open RNU with bladder cuff excision is the gold standard treatment. However, with the advancement of surgical instruments and the development of laparoscopic techniques, laparoscopic RNU, as a more minimally invasive surgical approach, is gradually becoming the mainstream for UTUC in experienced hands and can achieve similar oncological outcomes compared with open surgery (3,13).

The Veress and Hasson technique is now the most widely used laparoscopic entry technique for the method of establishing pneumoperitoneum in laparoscopy (14). The choice mainly depends on the surgeon’s habits and preferences. Our previous related study showed that Veress puncture is safe in urologic laparoscopy (15). Therefore, the Veress technique is commonly used in our center. The traditional laparoscopic approach is performed with at least three trocar incisions and one large incision. Many surgeons hesitate to use laparoscopic procedures for the distal ureter because the pelvic ureterovesical junction is deep, which subsequently converts to open bladder cuff excision with at least an 8 cm incision. Therefore, the traditional laparoscopic approach still causes significant surgical trauma. To pursue more minimally invasive surgery, these procedures can be achieved with one incision just for removing specimens when pure LSRNU emerges (16).

The essential procedure of RNU is the management of the bladder cuff. Several techniques have been deemed to simplify the resection of the distal ureter, including the pluck technique, intussusception, stripping, and transurethral resection of the intramural ureter. Although each technique has its strengths and weaknesses, until now none of these techniques has been convincingly shown to be equal to complete bladder cuff excision (6,17). Additionally, the extravesical stapling technique is a pure laparoscopic approach which requires a shorter operative time and keeps the urinary system closed to avoid tumor spread. Meanwhile, studies have shown higher incidences of positive surgical margins and local recurrence compared to other techniques of bladder cuff excision (18,19). Therefore, it is necessary to optimize this pure laparoscopic technique to reduce surgical trauma and improve oncological outcomes.

Our technique is an innovative modification of pure LSRNU that highlights its advantages. First, the custom-made laparoscopic bulldog clamp helps the surgeon finish the en bloc removal of the complete distal ureter and bladder cuff, similar to the open technique, without opening the urinary tract to prevent tumor spillage. This conforms to the oncological principle because a sufficient bladder cuff is guaranteed by the approach (12). Second, by adding a trocar at the midline of the lower abdomen, surgeons are able to gain sufficient vision and perform precise bladder cuff excision with the patient remaining in the same position. The bulldog clamp accompanied by suturing rather than Endo-GIA with staples could prevent bladder stones to a certain extent. Finally, this technique is not only a more minimally invasive incision in the lower abdomen but also avoids unnecessary operations and in theory reduces the risk of infection without changing the position, disinfection or draping once again.

Several studies have demonstrated that a single dose of intravesical chemotherapy 2–10 days after surgery reduces bladder tumor recurrence (20,21). Therefore, a single dose of intravesical chemotherapy was administered postoperatively. For the oncological outcomes, the Kaplan-Meier analyses showed that the 5-year OS and CSS of pure transperitoneal LSRNU were 78.9% and 81.4%, respectively. This study has relatively better outcomes than some traditional LSRUN approaches (22,23). It has been reported that recurrence in the bladder occurs in 22–47% of UTUC patients (24), compared with 2–6% in the contralateral upper tract (6). Recurrence in the bladder was observed in 16.0% of cases, as compared with 4.6% in the contralateral upper tract in our study. Six patients had local recurrence, including in the renal fossa, ipsilateral retroperitoneal lymph nodes and ureteral stump. Seventeen patients had distant metastasis and the site was most often bone, followed by abdominal cavity, lung and multiple lymph nodes. Kim et al. (23) also reported a similar location of recurrence and metastasis after RNU. However, our surgical method further achieved a lower incidence of progression. As a novel technique, its safety and efficacy were demonstrated by an average follow-up of 54.5 months. Excellent oncological outcomes are achieved by our techniques. This is the largest study with the longest follow-up study among pure LSRNU methods without patient repositioning for UTUC.

Invasive (T3/T4 and N+) UTUC is controversial for minimally invasive RNU or open approaches (25). Although several studies have been conducted to compare the oncologic outcomes of LSRNU and the open approach in patients with UTUC, the findings have been conflicting, and there is no accepted conclusion regarding to which surgical approach technique is more beneficial for patients with UTUC (26). Based on the center’s experience, LSRNU is safe when performed by experienced hands adhering to strict oncological principles to avoid tumor spread and implantation metastasis.

In addition, several authors have described pure robot-assisted RNU with good clinical outcomes (27). If our technique could be adopted in robot-assisted surgery, it might decrease the difficulty of intracorporeal suturing. However, the high cost restricts the availability of robots in China.

There were several limitations in our study. First, the retrospective study was performed in a single medical center in China, which may cause a potential selection bias. A larger number of series and more extended follow-up periods are needed to confirm these results and acquire further evidence about the clinical effects of pure transperitoneal LSRNU for UTUC. We are optimistic that this initial report can serve as a foundation for developing optimal treatment for UTUC.

Conclusions

Pure transperitoneal LSRNU is an effective treatment for UTUC, with no change in body position to complete resection in the distal ureter and bladder wall section. It not only conforms to oncological principles but is also simple, safe, and feasible. Therefore, this technique offers considerable clinical practice value and is worth popularizing and utilizing. More trials and longer follow-up are needed for further confirmation.

Acknowledgments

Funding: None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tau.amegroups.com/article/view/10.21037/tau-22-653/rc

Data Sharing Statement: Available at https://tau.amegroups.com/article/view/10.21037/tau-22-653/dss

Peer Review File: Available at https://tau.amegroups.com/article/view/10.21037/tau-22-653/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-22-653/coif). XL serves as an unpaid editorial board member of Translational Andrology and Urology. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are 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. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Ethics Committee of Peking University First Hospital (No. 2021130) and individual consent for this retrospective analysis was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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