Pneumovesicum Approach to En-Bloc Laparoscopic Nephroureterectomy with Bladder Cuff Excision for Upper Tract Urothelial Cancer: Midterm Oncological Results

Abstract

Introduction:

We reported the pneumovesicum (PV) approach to lower ureter and bladder cuff excision and closure. We believe that this approach bears the closest resemblance to the laparoscopic skill set of intravesical dissection and suturing. Herein, we report the midterm oncological results of the approach's use in a series of patients with upper tract urothelial cancer.

Materials and Methods:

From July 2004 to May 2010, 10 patients with upper tract urothelial cancer who underwent PV-assisted laparoscopic nephroureterectomy (LNU) were reviewed. Laparoscopic ports were inserted into the bladder via a suprapubic route, and carbon dioxide PV was induced. Laparoscopic dissection of the lower ureter and excision of the bladder cuff were then performed. The bladder defect was securely closed using laparoscopic suturing, and standard LNU followed.

Results:

Nine men and one woman with a mean age of 71.6 years (47–82) underwent the procedure. Six of the patients had renal pelvic tumor, two had upper ureter tumor, one had midureter tumor, and one had synchronous renal pelvis and upper ureter tumor. In terms of final pathology, there were three, two, and five patients with T1, T2, and T3 diseases, respectively. All of the patients had grade 2 (G2) disease, except for two with grade 3 (G3) disease. Over a median follow-up of 46 months (22–67 months), four patients developed superficial bladder tumor recurrence. The bladder and systemic recurrence rates were 40% and 10%, respectively. There was no port site recurrence.

Conclusion:

Based on our midterm follow-up information, it can be concluded that the PV approach to en-bloc bladder cuff excision and LNU for upper tract urothelial cancer provides intermediate oncological results comparable to those of other approaches to en-bloc excision of the bladder cuff.

Introduction

U pper tract transitional-cell carcinoma (TCC) accounts for <5% of all urothelial tumors.¹ In parts of Asia, the incidence is somewhat higher, but the outlook and recurrence rate remain dependent on the original stage and grade of the lesions.^2,3 Since the first reports of laparoscopic nephroureterectomy (LNU) from the Washington University group,⁴ nephrectomy is now performed primarily using the laparoscopic approach. The approach, per se, does not seem to affect the oncological outcome.⁵ Various minimally invasive approaches for handling the distal ureter are available, although many still consider the open approach to be the gold standard.⁶ To date, however, no consensus has been reached on the best approach for handling it. We first described a pneumovesicum (PV) technique for en-bloc bladder cuff and lower ureter resection, followed by LNU (i.e., PV-assisted LNU [PALNU]).⁷ This method has since been adopted by other research teams.⁸ Herein, we report the midterm oncological outcomes of this approach.

Materials and Methods

A retrospective review of patients with upper tract TCC who received PALNU in our center was conducted. The study period was from July 2004 to March 2009. Patients' demographic and operative details and clinical outcomes at the latest follow-up were collected for analysis, with particular attention paid to the development of local and distant recurrences.

During the study period, 10 patients (9 men and 1 woman) were reviewed. Table 1 presents the patients' characteristics. Their mean age was 71.6 years (range: 47–82). Seven tumors occurred in the left side. Six tumors were in the renal pelvis, two in the upper ureter, one in the midureter, and there was one synchronous tumor in the renal pelvis and upper ureter. Three, two, and five patients had T1, T2, and T3 diseases, respectively. Eight had a grade 2 (G2) disease, one had a grade 3 (G3) disease associated with sarcomatoid change, and one a grade 3 (G3) renal pelvis disease associated with a synchronous G3 upper ureteric tumor. One patient had a small (5-mm) incidental renal-cell carcinoma in the kidney specimen. The resection margins for the distal ureter/bladder cuff were all clear.

Table 1.

Characteristics of the Patients

Patient number	Sex	Age at diagnosis	Side	Site	Stage	Grade	Follow-up (months)	Bladder recurrence	Systemic recurrence
1	M	81	Left	Pelvis	T1	2	67	Three superficial	No
2	F	77	Left	Upper ureter	T1	2	64	No	No
3	M	63	Left	Pelvis	T1	2	58	No	No
4	M	79	Right	Pelvis	T3^a	2	56	No	No
5	M	59	Left	Upper ureter	T2	3^b	50	No	No
6	M	47	Left	Pelvis	T3	2	42	One superficial	No
7	M	72	Right	Midureter	T2	2	39	No	No
8	M	79	Left	Pelvis	T3	2	38	No	No
9	M	82	Right	Pelvis	T3	2	22	Three superficial	12 months postop
10	M	77	Left	Pelvis^c	T3	3	28	Six superficial	No

Coexisting 5-mm renal-cell carcinoma.

Invasive urothelial cancer with sarcomatoid changes.

Synchronous tumor at upper ureter T1G3.

postop = postoperatively.

The PALNU technique is briefly described here. Upon induction of general anesthesia, the patient is put in the lithotomy position. After check cystoscopy, the bladder is distended with normal saline. Under cystoscopic guidance, three 5-mm PediPorts (Tyco) are inserted at the suprapubic area in a triangular fashion into the urinary bladder. The bladder is then drained, and carbon dioxide PV is induced with the pressure set at 15 mm Hg. The ipsilateral ureteral orifice is first closed using a 3-0 Polysorb Ski needle with a figure-of-eight stitch to prevent the spillage of tumor cells from the upper tract. This stitch is also used for retraction to facilitate subsequent ureteral dissection. The ureteral orifice, surrounding bladder cuff, and intramural ureter are dissected with monopolar scissors or a hook, and the dissection is extended to the perivesical fat. An additional endoloop is then used to ligate the distal ureter; which also serves as the distal landmark for subsequent laparoscopic ureteral dissection. The bladder defect, which is usually 1 to 2 cm in length, is repaired by a single-layer full-thickness repair. A 16F urethral catheter is inserted, and all ports are removed. The patient is then put in the lateral position, and standard transperitoneal laparoscopic radical nephroureterectomy proceeds. The ureter is traced down to the pelvis until the previously placed endoloop is identified, which signifies the complete mobilization of the ureter. The specimen is then delivered via the port extension.

Perioperative and postoperative events were reviewed. Complications that were coded by the International Classification of Disease (ICD) (World Health Organization [WHO]-ICD 10) were retrieved from the territory-wide computer system. Clinical status was obtained from the medical records, including cystoscopy surveillance results and ongoing studies. We arranged for 3-monthly flexible cystoscopy and cytology. Follow-up imaging is arranged as per grading and staging of the disease. In general, cross-sectional imaging is obtained every 6 to 12 months.

Results

The mean operating time was 7.5 hours, and the associated blood loss was minimal. One patient (patient 1) experienced superior mesenteric artery injury during the subsequent nephrectomy, which required open repair. Otherwise, there was no open conversion or major intraoperative complications.

The average urethral catheter time was 11.8 days. Cystography was performed in selected cases, and none of the patients developed urinary leak. The mean hospital stay was 10.2 days (range: 6–17 days). No major postoperative complications were noted.

The median follow-up period was 46 months (range: 22–67 months). The oncological results are shown in Table 1. Four patients developed superficial bladder tumor recurrence, one of whom developed systemic recurrence. The overall bladder recurrence rate was 40%, and the systemic recurrence rate was 10%. Details of the recurrences are listed in the following text.

Patient 1 had multiple superficial recurrences, with the first episode occurring 9 months after left PALNU, and the tumor was located at the posterior wall of the bladder away from the previous left ureteral orifice scar. Transurethral resection of bladder tumor (TURBT) was performed, and the pathology was Ta grade 2 (TaG2). This patient's two subsequent recurrences were both at the left lateral side wall with a size <5 mm, and both were TaG2.

Patient 6 had one recurrence about 6 months after left PALNU. The recurrent tumor was a 1-cm papillary growth at the left posterolateral side wall away from the ureteral orifice scar. The pathology was TaG2.

Patient 9 harbored T3G2 disease of the right renal pelvis, and he developed multiple rapid bladder recurrences away from previous ureteric orifice scar. The first recurrence was detected during his first surveillance cystoscopy, and multiple tumors (with the largest one being 3 cm) were noticed. A computerized tomogram showed no extravesical recurrence. TURBT was performed, and all tumors were found to be TaG3. Despite intravesical Bacillus Calmette-Guérin (BCG) administration, multiple recurrences were again noticed during the next surveillance cystoscopy. The pathology remained that of TaG3 disease. The third recurrence was small and noticed during the 9-month surveillance cystoscopy after initial PALNU, and the pathology was TaG2. This patient developed multiple lung metastases at 12 months after the initial operation and then underwent systemic chemotherapy (gemcitabine and cisplatin). He died at 22 months after PALNU.

Patient 10 first presented with multiple superficial bladder tumors. TURBT was performed, and all were identified as TaG2. Left ureteroscopy showed papillary tumors at the renal pelvis, and PALNU was performed. He then had four episodes of bladder recurrence, despite adjuvant intravesical mitomycin C and BCG administration. There was no recurrence at the scar of the previous ureteric orifice or the previous port sites. This patient is still surviving 28 months after PALNU, with no evidence of systemic metastasis.

Discussion

LNU was popularized by the Washington University group.⁴ Others have since provided evidence that the convalescence and morbidity profile of LNU are better than those of the open approach.⁹ The longer-term, cancer-specific survival and recurrence rates following LNU have been also shown to be comparable to those of open nephroureterectomy.^10,11 Although the nephrectomy component of the approach is fairly standard, the optimal approach for the excision of the distal ureter and bladder cuff remains debatable.

Many techniques for the management of the distal ureter have been reported. They can be classified as the transurethral, combined transurethral and transvesical, laparoscopic, and robot-assisted approaches (Table 2), and all have certain unique features. The original laparoscopic technique was assisted by the use of a stapler^12,13 or Ligasure (Valleylab; Tycohealthcare).¹⁴ However, the use of either device constitutes a “blind” technique. Stapler use carries the long-term risk of stone formation, whereas ligature use carries a small risk of inadvertent damage to the opposite ureteral orifice. The transurethral resection approach is also commonly used, along with its various modifications. The pluck technique, which is employed in the setting of hand-assisted laparoscopy, is probably the least demanding technically.¹⁵ The main concern, however, is the spillage of urine, both from the upper tract during mobilization and from the bladder defect after the procedure. The sealing of the bladder defect is dependent on Foley drainage.

Table 2.

Reported Techniques for the Management of Distal Ureter, and Local and Systemic Recurrence Rates

Author	Method	Number of patients	Follow-up	Bladder recurrence	Distant recurrence
Shalhav, 2000¹³	Stapler	13	Mean: 24	3 (23%)	4 (31%)
Matin and Gill¹²	Combined cysto-laparoscopy	36	Median: 22	5 (13.9%)	5 (13.9%)
Matin and Gill¹²	Stapler	12	Median: 19	5 (41.7%)	4 (33.3%)
Kurzer et al¹⁵	Transurethral resection, hand-assisted	41	Median: 10 (1–54)	20 (49%)	4 (16%)
Tsivian et al¹⁴	Ligasure	13	Mean: 11.6 (1–23)	2 (15.4%)	Not reported
Agarwal et al¹⁸	Modified pluck	13	Mean: 15.3 (6–24)	5 (45%)	1 (7.7%)
Present study	Pneumovesicum	10	Median: 46	4 (40%)	1 (10%)

Robotic assistance to enhance the secure closure of the bladder defect has been also reported.¹⁶ Obviously, the associated costs of such a technique are a major issue, as the main part of this procedure is ideal for conventional laparoscopic surgery.

The main feature of our transvesical technique is that it entails the secure closure of the ureteral orifice during dissection, as well as that of the bladder defect upon completion. Our technique bears strong resemblance to the standard open transvesical technique, although there are some essential differences between it and the technique initially described by Gill et al¹⁷ with subsequent modifications made by Agarwal et al.¹⁸ For PALNU, the operation is mainly performed with transvesical laparoscopic instruments under carbon dioxide PV. Our use of cystoscopy is limited to examination of the bladder for any synchronous bladder tumor and the provision of visual guidance for port insertion and gas insufflation. The contraindications for this technique are concomitant bladder cancer, small contracted and irradiated bladder, an incompetent urethra that leaks, and an extreme large-sized prostate that distort the position of the distal ureter. In contrast, in the technique reported by Gill et al,¹⁷ the transvesical instruments are mainly used for ureteral stenting and retraction; the dissection is otherwise largely carried out using a resectoscope in an irrigation fluid-filled bladder. The delineation of the dissection plane and range of available instruments in their approach are probably limited compared with our laparoscopic approach.

As with any technique, the main concern is the risk of local recurrence and incomplete resection of the ureteral orifice. A summary of the local and systemic recurrence rates found in the literature is provided in Table 2. The reported bladder recurrence rates range from 13.9% to 50% and the distant recurrence rates from 8.3% to 25%. In the present series, in which the median follow-up period was 46 months, the overall bladder recurrence rate was 40% and the systemic recurrence rate was 10%. All the tumors in the four bladder recurrence cases in our series were superficial. Patients 9 and 10 exhibited multiple bladder tumors during recurrence. The other two patients each had only a solitary recurrence located away from the port sites and ureteral orifice scar. Patient 9 died of liver and lung metastases, but there was no pelvic lymph node metastasis in any of his computed tomography images. Our methods do not seem to increase the risk of port site or ureteral orifice scar recurrence, although a larger series and longer follow-up are needed to confirm our initial observations.

The limitations to the present study include small number of patients treated over a long period of time. The operating time is long and change of position is required. In addition, laparoscopic suturing skill is required in the confined space of the PV, which at times can be difficult to maintain. Interestingly, a total of six surgeons were involved and it appeared that the technique was readily transferable and no major modification was required during the technique. It would be difficult to ascertain how such approach contributes to a reduced hospital stay, as the local healthcare system typically allows patient staying till catheter removal, with minimal added cost for the patient.

However, the key feature of our technique remains the replication of the operating steps in the open approach, including the early closure of the ureteral orifice, the resection of an adequate bladder cuff, and the subsequent closure of the bladder defect under vision. The entire specimen is removed en bloc. In this manner, we minimized the potential for tumor seeding. In addition, we also decreased urine leakage and shortened the recovery period, thus allowing earlier catheter removal. Guzzo et al have further modified our technique by positioning the patient in the modified lateral decubitus position,⁸ which avoids the need for a position change between the two stages of the procedure and allows the performance of nephrectomy prior to distal ureterectomy.

In this initial series of patients, we did not include those with lower ureteral urothelial cancer. There remains some concern about tumor seeding during the initial manipulation of the ureter and suturing. The favorable results reported herein, however, indicate that our technique may be also applicable to any upper tract TCC, as long as the tumor does not extend to the intramural position of the ureter.

Conclusion

PALNU is a technically sound procedure that can be easily adopted by surgeons with laparoscopic skills. Our midterm follow-up suggests that there is no significantly increased risk of local or systemic recurrences.

Footnotes

Disclosure Statement

No competing financial interests exist.

Abbreviations Used

References

Munoz

, Ellison

. Upper tract urothelial neoplasms: Incidence and survival during the last 2 decades. J Urol, 2000; 164:1523–1525.

Pang

, Lim

EKW

, Chong

, Sugiono

, Yip

SKH

, Cheng

CWS

. Prognostic factors for upper tract transitional cell carcinoma: A retrospective review of 66 patients. Asian J Sur, 2008; 31:20–24.

, Li

, Ke

, Wu

, Huang

. The prognostic predictors of primary ureteral transitional cell carcinoma after radical nephroureterectomy. J Urol, 2009; 182:451–458.

McDougall

, Clayman

, Elashry

. Laparoscopic nephroureterectomy for upper tract transitional cell cancer: The Washington University experience. J Urol, 1995; 154:975–979.

Lee

, Yip

SKH

, Tan

, Cheng

. Laparoscopic nephroureterectomy for upper urinary tract transitional cell carcinoma. Scand J Urol Nephrol, 2006; 40:283–288.

Macejko

, Pazona

, Loeb

, Kimm

, Nadler

. Management of distal ureter in laparoscopic nephroureterectomy—a comprehensive review of techniques. Urology, 2008; 72:974–981.

Cheng

, Ng

, Mak

et al. Pneumovesicum method in en-bloc laparoscopic nephroureterectomy with bladder cuff resection for upper-tract urothelial cancer. J Endourol, 2007; 21:359–363.

Guzzo

, Schaeffer

, Allaf

. Laparoscopic radical nephroureterectomy with en-bloc distal ureteral and bladder cuff excision using a single position pneumovesicum method. Urology, 2008; 72:850–852.

Gill

, Sung

, Hobart

et al. Laparoscopic radical nephroureterectomy for upper tract transitional cell carcinoma: The Cleveland Clinic experience. J Urol, 2000; 164:1513–1522.

10.

El Fettouh

, Rassweiler

, Schulze

et al. Laparoscopic radical nephroureterectomy: Results of an international multicenter study. Eur Urol, 2002; 42:447–452.

11.

Bariol

, Stewart

, McNeill

, Tolley

. Oncological control following laparoscopic nephroureterectomy: 7-Year outcome. J Urol, 2004; 172:1805–1808.

12.

Matin

, Gill

. Recurrence and survival following laparoscopic radical nephroureterectomy with various forms of bladder cuff control. J Urol, 2005; 173:395–400.

13.

Shalhav

, Dunn

, Portis

, Elbahnasy

, McDougall

, Clayman

. Laparoscopic nephroureterectomy for upper tract transitional cell cancer: The Washington University experience. J Urol, 2000; 163:1100–1104.

14.

Tsivian

, Benjamin

, Sidi

. A sealed laparoscopic nephroureterectomy: A new technique. Eur Urol, 2007; 52:1015–1019.

15.

Kurzer

, Leveillee

, Bird

. Combining hand assisted laparoscopic nephroureterectomy with cystoscopic circumferential excision of the distal ureter without primary closure of the bladder cuff—is it safe? J Urol, 2006; 175:63–67.

16.

Nanigian

, Smith

, Ellison

. Robot-assisted laparoscopic nephroureterectomy. J Endourol, 2006; 20:463–465.

17.

Gill

, Soble

, Miller

, Sung

. A novel technique for management of the en bloc bladder cuff and distal ureter during laparoscopic nephroureterectomy. J Urol, 1999; 161:430–434.

18.

Agarwal

, Khaira

, Clarke

, Tong

. Modified transurethral technique for the management of distal ureter during laparoscopic assisted nephroureterectomy. Urology, 2008; 71:740–743.