Retrograde Ureteral Catheterization Is Not Essential in Percutaneous Nephrolithotomy: A Randomized Controlled Trial

### 1. Research Background Percutaneous nephrolithotomy (PCNL) is currently the first-line treatment for upper urinary tract stones larger than 2 cm. It is minimally invasive and enables rapid recovery, so it has gained patients' approval. When performing PCNL, most urologists first place a ureteral catheter retrogradely into the ureter on the affected side with the patient in the lithotomy position, and then change the patient to the prone position for percutaneous renal puncture and stone extraction. The retrogradely inserted catheter can be used for injecting water or contrast agents in reverse, which facilitates percutaneous renal puncture and also prevents stone fragments from entering the ureter during the lithotripsy process. However, when performing PCNL in the standard prone position, it may sometimes be difficult to place an anterograde internal stent or treat ureteral stones, requiring the patient to be changed back to the lithotomy position again. This entails another round of disinfection and draping, thus increasing the workload of the medical team and prolonging the operation time.

In recent years, with urologists gaining more experience in percutaneous renal puncture and the improvement of the quality of ultrasound images, the application of ultrasound-guided percutaneous renal puncture and fistulization has become increasingly popular, being no less effective than X-ray. Ultrasound-guided percutaneous renal puncture and fistulization does not rely on retrograde pyelography. Even experienced urologists do not need to perform retrograde intubation and water injection to form an "artificial hydronephrosis", which saves the operation time required for the traditional procedure of retrograde intubation in the lithotomy position followed by changing to the prone position, and also avoids the risk of infection caused by the possible increase in renal pelvic pressure during retrograde water injection. However, not placing a retrograde catheter may lead to difficulties in puncturing a non-hydronephrotic kidney. During the PCNL lithotripsy process, if stone fragments enter the ureter and are difficult to manage anterogradely, retrograde ureteroscopic treatment is required again, which is difficult to perform in the traditional simple prone position and requires changing back to the lithotomy position. In fact, retrograde ureteroscopic operations can be carried out in the split-leg prone position, which can meet various requirements for anterograde and retrograde operations during PCNL in a single position. This is the particular advantage of PCNL in the split-leg prone position.

Direct percutaneous renal puncture and stone extraction under ultrasound guidance without retrograde intubation in the split-leg prone position can save the operation time of the traditional procedure of intubation in the lithotomy position followed by changing to the prone position. However, there is a risk of stone fragments entering the ureter during lithotripsy. This can be addressed by retrograde ureteroscopy in the split-leg prone position. In addition, higher technical requirements are imposed on ultrasound-guided percutaneous renal puncture. Whether this technique is feasible still needs to be clinically verified.

• 2. Research Objectives To conduct a single-center, prospective, randomized, controlled study to explore the safety, feasibility, and potential advantages of percutaneous nephrolithotomy without retrograde intubation in the split-leg prone position.
• Primary outcome measures: the first access time
• Secondary outcome measures: (1) Stone-free rate (SFR), defined as the absence of residual stones or the presence of fragments ≤ 2 mm on non-contrast computed tomography (NCCT); (2) Operative time, the duration from percutaneous renal puncture to the final wound closure; (3) Anesthesia time, the duration from the completion of anesthesia induction until the final wound closure; (4) Need for retrograde assistance (retrograde ureteroscopic stone treatment or DJ stent placement,); (5) Complications (according to the Clavien-Dindo classification system); and (6) Costs.
• 3. Research Design
• 3.1 Research nature: A single-center, randomized, controlled trial with a 1:1 two-group parallel design, which is randomized and open-label.
• 3.2 Sample size:The sample size was calculated using the trial size package in R, with the first access time as the primary endpoint. The mean time in our initial pilot study was 11.67 ± 1.9 minutes in the no ureteral catheterization split-leg prone position (NUC-SLP) group, and 10.48 ± 2.6 minutes in the traditional position (TP) group, respectively. It was hypothesized that the NUC-SLP group would be non-inferior to the TP group with respect to the first access time, implying that omitting retrograde ureteral catheterization would not significantly prolong the time to establish the first access. Based on the results of a pilot study and previous literature, the non-inferiority margin was prespecified as 2 minutes.With a two-sided alpha of 0.05 and a statistical power of 80%, these parameters yielded a minimum sample size of 63 patients per group (128 total). Accounting for an estimated 10% dropout rate, 70 patients per group (140 total) were enrolled in the study.
• 3.3 Random grouping and control methods: This study adopts a balanced randomization method to generate a random number table and randomly assign patients to groups. The trial uses a mutual control method. Group 1 is the split-leg prone position without a ureteral catheter group, and group 2 is the traditional group. Specific interventions: 1. The surgical position of group 1 is the split-leg prone position, while that of group 2 is first the lithotomy position and then the prone position; 2. Group 1 does not place a ureteral catheter retrogradely, while group 2 does.
• 4. Research Subjects A total of 140 patients with >2 cm upper urinary tract stones.
• Inclusion criteria: 1. Agree to participate in this RCT; 2. Aged 18 - 70 years; 3. Upper urinary tract stones >2 cm.
• Exclusion criteria:(1)Patients with prior nephrostomy or scheduled for a second-look procedure; (2)Patients with congenital renal anomalies including duplex kidney, ectopic kidney, or horseshoe kidney; (3) Pregnant patients; (4)Those who refused to participate or without complete data.
• Withdrawal criteria for subjects: If purulent fluid is found during intraoperative puncture, a nephrostomy tube will be placed and the operation will be terminated, and the patient will be excluded from the group; patients may also withdraw voluntarily.
• 5. Research Process
• 5.1 Preoperative examinations:
• (1) Laboratory tests: Complete blood count, routine urine test, midstream urine culture, liver and kidney function tests, electrolyte tests, coagulation function tests, and blood-borne disease screening.
• (2) Imaging examinations: Unenhanced CT scan of the urinary system, KUB, chest X-ray, electrocardiogram, and echocardiogram if necessary.
• 5.2 Preoperative preparation:
• For patients with a positive preoperative urine culture, sensitive antibiotics should be selected according to the drug sensitivity test to control the infection for 5 - 7 days. For patients with a negative preoperative urine culture, a single dose of broad-spectrum antibiotics is given prophylactically.
• One day before the operation, eligible patients are enrolled according to the generated random number table and number, and the informed consent form is signed. Patients corresponding to "0" in the random number table are arranged into the study group (group 1) to undergo PCNL without a ureteral catheter in the split-leg prone position; those corresponding to "1" are arranged into the control group (group 2) to undergo PCNL in the traditional position.
• 5.3 Surgical methods:
• All patients receive general anesthesia with endotracheal intubation.
• In the study group, the patient is directly placed in the split-leg prone position. A 10-cm soft pillow is used to elevate the upper abdomen, with the lower edge of the pubic symphysis exceeding the lower edge of the operating table by 5 cm. The patient's legs are spread in a "V" shape. The thigh on the healthy side is abducted as much as possible, while the thigh on the affected side is slightly abducted, making the angle between the two legs approximately 80°. The lumbar back and perineum are disinfected and draped, and a urinary catheter is inserted for open drainage. Ultrasound is used to guide the percutaneous puncture of the target renal calyx, and an 18 - 24 Fr tract is established under the guidance of a guidewire, with a peel-away working sheath placed to complete the tract establishment.
• In the preoperative group, the patient is placed in the lithotomy position. A 5 Fr ureteral catheter is retrogradely inserted into the ureter on the affected side through a cystoscope, along with a 16 Fr Foley catheter. Then the patient is turned to the prone position, with a 10-cm soft pillow elevating the upper abdomen, and the surgical area is disinfected and draped again. Sterile normal saline is injected through the ureteral catheter to create artificial hydronephrosis. Ultrasound is used to guide the percutaneous puncture of the target renal calyx, and retrograde contrast is performed if necessary, combined with X-ray-guided percutaneous puncture. Subsequently, an 18 - 24 Fr tract is established under the guidance of a guidewire, with a peel-away working sheath placed to complete the tract establishment.
• After the tract is established, a nephroscope is inserted through the working sheath of the tract, and pneumatic ballistic or holmium laser lithotripsy is performed under the irrigation of the perfusion pump, with a negative pressure suction sheath used to clean the stone fragments. After lithotripsy, bedside X-ray fluoroscopy is used to check the stone clearance status, and further treatment of residual stones is carried out if necessary. For migrated residual ureteral stones that are difficult to manage anterogradely, retrograde ureteroscopy is performed in the split-leg prone position in the study group, while in the control group, the patient is turned to the lithotomy position, disinfected and draped again, and then retrograde ureteroscopy is carried out. Whether to place an internal stent and a nephrostomy tube is determined according to the surgical situation. If there are no active stone residues, no ureteral obstruction, no significant bleeding in the tract, and no perforation or bleeding in the collecting system, a tubeless approach can be adopted. The operation is completed. All operations are performed by the same urologist.