Clinical Application of One-Position Complete Retroperitoneoscopic Nephroureterectomy

Objective: To explore the surgical method and the clinical e�cacy of complete retroperitoneal laparoscopic radical resection of upper tract urothelial carcinoma (UTUC). Methods: A retrospective analysis of 83 patients with upper urothelial carcinoma from January 2016 to December 2019 in the A�liated Hospital of Xuzhou Medical University was conducted. Among them, 40 patients underwent one-position complete retroperitoneoscopic nephroureterectomy (CRNU) and 43 patients underwent traditional retroperitoneoscopic nephroureterectomy (TRNU). Compare the differences in clinical data, perioperative parameters and postoperative follow-up results of patients with the two surgical methods. CTU and ureteroscopy were used to diagnose. Results: A total of 43 patients (35 males and 8 females) with TRNU were enrolled in this study. Forty patients (31 males and 9 females) received CRNU. The CRNU group had signi�cantly shorter average operation time (105.83±5.80 min versus 147.28 ± 17.58 min) and lower visual pain score (P=0,024). No signi�cant difference was found in age, BMI, T stage, complication, change of albumin and hemoglobin, postoperative hospital stays and tumor recurrence (P>0.05). Conclusion: one-position complete retroperitoneoscopic nephroureterectomy is safe and feasible. The curative effect is a�rmative. It has the conspicuous advantages in minimally invasive, no posture change, less postoperative pain, less interference with abdominal organ and shorter operation time, which could particularly reduce the workload of operating room nurses without any additional postoperative complications.


Background
Upper tract urothelial carcinoma (UTUC) is a relatively rare urological malignant tumor, accounting for 5%-6% of upper urinary tract tumors [1]. In recent years, retroperitoneal laparoscopy nephroureterectomy has been used progressively as a minimally invasive treatment substituted for open surgery in China [2], the standard resection limitation of which generally includes the total nephroureterectomy with excision of bladder cuff [3]. However, prevalently, patient's posture should be changed from side-lying position to horizontal position during this surgery after kidney and upper ureter dissociated, in order for the resection of distal ureter and bladder near ureteral ori ce. Although transperitoneal approach could also accomplish this laparoscopic procedure without posture changes in western countries, pneumoperitoneum interferences on abdominal organs re ecting in abdominal pain, abdominal distension, bacterial translocation and abdominal cavity implantation metastasis has been paid more great attentions in recent study. In this study, we attempt to suggest the complete retroperitoneal laparoscopic radical resection in patients with UTUC. On the basis of mature retroperitoneal laparoscopy procedures, researching domestic experience and lessons, from January 2016 to December 2019, 83 patients in our hospital treated for UTUC underwent one-position complete retroperitoneoscopic nephroureterectomy. It brings satisfactory outcomes in terms of short operating time, minimal tissue dissections. The corresponding procedure and results have been summarized as follows. All patients received general anesthesia, and catheterization was completed after general anesthesia. The patients were placed on 90°the lateral decubitus position. The waist bridge was heightened adequately so as to ensure the patient's waist fully extended. A 10 mm skin incision (Port A) was made at 2 cm above the superior iliac spine. Vascular forceps were used to bluntly separate the muscles along the outer edge of the psoas muscle to reach the extraperitoneal. The retroperitoneal dilator fully expanded the peritoneum to form a cavity. A 12 mm trocar was inserted into the incision and carbon dioxide was continuously injected to maintain the pneumoperitoneum pressure at approximately 12-15 mmHg (1 mmHg = 0.133 kPa). A 5mm trocar was placed at the intersection of the anterior axillary line under the 12 ribs (Port B), and a 12mm trocar was placed at the intersection of the posterior axillary line under the 12 ribs (Port C). The fourth trocar (Port D) was symmetrical with Port A along anterior axillary line and formed an isosceles triangle with Port B so as to facilitate the operation of surgeon (Fig. 1). The positions of the four ports were shown in the Fig. 5. The extraperitoneal fat was removed using an ultrasonic scalpel. The boundary between the peritoneal re ex and the perirenal fascia was exposed. The anatomical landmarks such as the psoas muscle, the perirenal fascia and the peritoneal regurgitation were identi ed. The perirenal fascia was dissected from the dorsal side of the kidney with an ultrasonic knife and separated. In the renal fat sac, the front and back of the kidney were bluntly separated, and the kidney was free. The ureter was separated to the bifurcation of the level iliac vessels and was clamped with Hem-o-lok in the upper ureter to avoid the spread of cancer cells (Fig. 2). Separated up the ureter along the ureter to the renal pelvis, found the renal pedicle, and freed the renal pedicle. Renal artery was clamped with Hem-o-lok at the distance from renal. At least two hem-o-lok was used to clamped at proximal end of renal artery. Renal vein and genital vein at branch of renal vein were separated, clamped with hem-o-lok and cut them. Keep the ipsilateral adrenal gland intact. Check the surgical area to ensure that there is no active bleeding. Efforts continued to detach from the distal end of the ureter. The surgeon exchanged positions with the assistant and placed the monitor on the foot side. Laparoscope was inserted from Port B as an observation port. Ports A and D were used as manipulative ports to separate the ureter and remove the bladder cuff. The ureter and part of the bladder wall were lifted. Multiple Hem-olock clips were used for bladder sleeve resection. The incision in the bladder was sutured with absorbable sutures (Fig. 3). The intact gross specimen of the renal ureter ( Fig. 4) was removed from the 12 mm trocar under the enlarged costal margin and the end of the ureter and the resection of the bladder were examined to ensure its integrity. After the bleeding was stopped and the retroperitoneal drainage tube was placed, the incision was sutured.

1.2.2Traditional retroperitoneoscopic nephroureterectomy (TRNU)
The patients were placed on the lateral decubitus position. Trocar used a conventional retroperitoneal three-hole layout. The affected kidney was removed following the classic radical nephrectomy procedure.
The patient was changed to a supine position, disinfected and toweled again. The oblique incision of the left lower abdomen was made about 10 cm long. Separate the extraperitoneal and remove the affected kidney, continue to separate the ureter and the bladder cuff. The bladder cuff was completely removed and the bladder incision was closed.

Observation Index
All patients' preoperative information was collected, such as gender, age, BMI, right or left side, comorbidities. The perioperative indicators include operation time, bleeding volume, postoperative hospital stay, visual pain score, and postoperative complications.

Statistical analysis
Normally distributed continuous variables were expressed as mean ± standard deviation, and continuous variables that do not conform to the normal distribution were expressed as medians (P25, P75). Continuous variables with normal distribution were analyzed by t test, and continuous variables with skew distribution were tested with Mann-Whitney U. Chi-square test or Fisher exact test was used to analyze categorical variables.

Results
A total of 43 patients (35 males and 8 females) with TRNU were enrolled in this study. Forty patients (31 males and 9 females) received CRNU. The average age of the TRNU group was 69 (51, 79) years, and the average age of the CRNU group was 68.03 ± 9.56 years, with no statistically signi cant difference (P = 0.425). Importantly, there were no signi cant difference in T stage, location, BMI or the side of tumor (P > 0.05) between the two groups. Moreover, the complications of two groups had no signi cant difference (P = 0.346), such as hypertension, diabetes. Overall, there were no signi cant difference was found in the baseline characteristics between the TRNU and CRNU groups. Notably, the operation time of CRNU (147.28 ± 17.58 mins) was signi cantly lower than that of TRNU group (105.83 ± 5.80 mins, P < 0.01). The change of serum albumin before and after the operation re ects the trauma of the patient to a certain extent. However, no signi cant difference was found in the change in serum albumin between the two surgical methods (P = 0.841). Similarly, the changes in hemoglobin and postoperative hospital stay were not signi cantly different (P = 0.789, P = 0.431, respectively). To evaluate the pain caused by surgery, we compared the visual pain scores of two groups and found that the CRNU pain score was signi cantly lower than the TRNU (P = 0.024). Median follow-up time was 10(6, 18) months in the TRNU group and 9(4, 17.5) months in the CRNU group (P = 0.632). There was no signi cant difference in tumor recurrence between TRNU group and CRNU group.

Discussion
UTUC accounts for about 5% of urothelial carcinoma [4], with the characteristics of high recurrence and multi-center occurrence. With the advancement of laparoscopic techniques and the accumulation of operative experience, laparoscopic total nephroureterectomy with excision of bladder cuff have been applicable to a growing number of pelvic ureteral cancer patients in many centers since it was successfully performed by Clayman et al in 1991 [5,6]. Recently, laparoscopic nephroureterectomy has replaced open surgery as standard surgical treatment for upper urinary tract epithelial carcinoma because of the less intraoperative bleeding, minimal invasion, quicker recovery and shorter postoperative hospital stay [7][8][9][10][11].
At present there are many surgical approaches for laparoscopic nephroureterectomy. The most common method was the Bishoff method [12], that is, laparoscopic renal and upper ureter resection in the upper abdomen, and lower ureter and partial bladder incision in the lower abdomen. But this procedure is not completely done under the laparoscopy. In 1999, Gill et al [13,14] reported a complicated laparoscopic radical resection of renal pelvic ureteral cancer. The ureteral bladder wall was rstly treated with lithotomy position, and then supine position was performed through the renal and abdominal ureteral resection surgery. In this operation, two 5 mm cannulas were inserted into the bladder by puncturing the lower abdomen into the bladder, and another surgeon completed ureteral intubation by transurethral insertion of cystoscope. Under the help of grasping forceps of bladder, the inner segment of ureteral bladder wall was cut about 3-4 cm. Then the lasso was placed at the distal end of the free ureteral wall and tightened. Then the electrotomy was continued to remove the entire ureteral wall from the bladder. Ligation of the lasso effectively prevents the leakage of urine in the upper urinary tract, but it could not prevent the leakage of urine containing tumor cells in the bladder, so it still remains the risk of tumor spread. In response to the problem of leaking urine in the bladder and ureteral stump, McDougall et al. [15] proposed a solution: using a linear cutting occluder to perform a sleeve-like resection of the bladder tissue around the ureteral opening. At the same time, the stump was sealed to avoid the urine leakage and prevent the spread of tumor as possible. This report examined the effects of 10 patients and found no tumor spread after surgery. Chandhoke et al[16] followed up for 3-9 months in patients undergoing bladder-sleeve resection with a straight-lined closure. No resection of bladder staples and formation of stones were found after cystoscopy.
A total of 43 patients (35 males and 8 females) with TRNU were enrolled in this study. Forty patients (31 males and 9 females) received CRNU. The CRNU group had signi cantly shorter average operation time (105.83 ± 5.80 min versus 147.28 ± 17.58 min) and visual pain score (P = 0.024). No signi cant difference was found in age, BMI, T stage, complication, change of albumin and hemoglobin, postoperative hospital stays and tumor recurrence (P > 0.05). Surgical trauma will put the patient in a state of emergency, and elevated glucocorticoids will cause protein breakdown. The change of serum albumin before and after the operation re ects the trauma of the patient to a certain extent [17]. There was no signi cant difference in the impact of surgical trauma between the two groups. In addition, we cannot accurately estimate the amount of intraoperative bleeding, so we used the change between preoperative hemoglobin and the rst day of postoperative hemoglobin to estimate the amount of bleeding, which was more accurate.
Similarly, there was no signi cant difference was found between TRNU group and CRNU group.
Accordingly, in this study, based on the traditional retroperitoneal laparoscopic radical nephrectomy, a modi ed four-hole method complete retroperitoneal laparoscopic radical nephrectomy for pelvic and ureteral cancer was performed. After radical nephrectomy and upper ureter dissection, we added the fourth Trocar in the ventral of the sight Trocar which had been located over the iliac crest at the same level. Then, the lens was relocated from the dorsal subcostal Trocar towards the pelvic cavity, and the distal ureter was continued dissociating downward to the bladder wall. Afterwards, multiple Hem-o-lock clips were used for the bladder sleeve resection and absorbable titanium clips were used for clipping the distal bladder incision.
At present, there rarely have reports of the application about complete retroperitoneal laparoscopic radical resection of renal pelvis and ureteral carcinoma. The technique we introduced has the following advantages: 1) Through the establishment of retroperitoneal approach, the anatomical landmark is easy to identify with clear visual eld; 2) The application of absorbable clips of the bladder incision reduces the possibility of postoperative bladder calculus; 3) Four-hole operation is bene cial to adjust the operating eld to the best; 4) The entire surgical procedure without the need of posture changes, shortening the time of operation and reducing potential safety risks during the movement of patients; 5) On the basis of the retroperitoneal laparoscopic nephrectomy, no additional surgical instrument or special equipment should be added so that there has not been a rise in cost.
Through this study, we have some enlightenments as follows: 1) After nding the upper part of the ureter, Hem-o-lock should be used to clamp the distal ureter in order for blocking the implantation metastasis caused by the in ux of proximal urine containing cancer cells; 2) Specimen bag should be used for removing the excision to decrease the occurrence of implantation metastasis to abdominal incision after complete resection; 3) Operation area should be washed repeatedly with warm sterilized water at about 42℃ to destroy the potential escaped cancer cells; 4) Although we do not recommend this new surgical technique in lower ureteral cancer because of the relatively di cult exposure of distal ureter, we are trying to resect the lower ureter and partial bladder rst before the dissociate of kidney and upper ureter. The feasibility and the effect on prognosis are still in observation.
In summary, one-position complete retroperitoneoscopic nephroureterectomy for the treatment of UTUC has its advantage in no posture change, less postoperative pain score, minimally invasive and shorter operation time without any postoperative complications such as bladder calculi, higher local recurrence and vesical implantation metastasis probability of cancer.

Declarations Funding
The study received no funding Compliance with ethical standards This manuscript was approved by the Medical College Committee of the A liated Hospital of Xuzhou Medical University and the patient has signed the informed consent.

Consent for publication
Not applicable

Con ict of interest
The authors declare that they have no con ict of interest.

Availability of data and materials
The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

Authors' contributions
Yongshuang Xiao collected data about patients with upper urothelial cancer. Tan Chen and Qinghui Li performed data analysis and were the main contributors to writing manuscripts. Rumin Wen reviewed the manuscript. Shuofeng Li was the designer of this study. The nal manuscript read and approved by all authors.