Ureteroscopic Lithotripsy for Renal Stones Using a Sheathless Approach or Using a Flexible and Navigable Ureteral Access Sheath (FANS)

BACKGROUND: Ureteroscopic laserlithotripsy (URS) is the preferred treatment modality for renal stones up to 20 - 25 mm. Continous development recent years with thinner flexible endoscopes, more efficient lasers and auxiliary eqiupment has expanded indications for URS. A few years ago, we performed a randomised clinical trial comparing URS lithotripsy using Holmium:YAG laser and Thulium Fiber Laser (TFL). The results of the study favoured TFL lithotripsy. However, there is no consensus regarding optimal laser settings using TFL. To address this issue, we recently performed another randomised clinical trial comparing URS lithotripsy using low and high TFL settings. In that study, low power laser settings resulted in significantly higher stone free rates and lower complication rates compared to high power lithotripsy. It should be noted that a sheathless approach was used in both groups. The sheathless approach used in this study has been criticised as the newly introduced flexible and navigable ureteral access sheath may improve stone free rates and reduce infectious complications.

However, to date, there are no clinical randomised trials comparing a sheathless approach and URS with FANS using different laser settings for TFL to determine what is optimal regarding the clinical outcomes.

AIMS OF THE STUDY: The primary aim of the study is to compare the stone free rates following URS lithotripsy for renal stones with low power TFL using a sheathless approach and URS with FANS (with low and high power settings). Secondary aims are to compare the results of sheathless- and FANS assisted URS lithotripsy in terms of operative time, laser time, intraoperative and postoperative complications. Following the primary comparison between sheathless and FANS groups, another aim is to compare the outcome of low power and high power URS lithotripsy in the FANS patients with respect to operative time, SFR, laser time, intraoperative and postoperative complications.

STUDY DESIGN: The study is planned as a multicenter prospective randomised clinical trial. All patients ≥ 18 years scheduled to URS lithotripsy for renal stones, 8-25 mm, at the day surgery unit at Haukeland University Hospital (HUH), Akershus University Hospital (AHUH) and The Hospital of Vestfold are invited to be enrolled in the study. After written informed consent, patients are randomised to laser lithotripsy using one of three alternative ureteroscopic approaches: Group 1: Sheathless URS using low power TFL 4 -10 Watts, short pulse mode, Group 2: URS with FANS using low power TFL 4 - 10 Watts, short pulse mode or Group 3: URS with FANS using high power TFL 16 - 24 Watts, short pulse mode.

In total, 225 patients will be included in the study, 75 from each of the three stone centres. Among the 75 patients recruited from each hospital, 25 will be randomised to each of the three randomisation groups.

LASER SETTINGS: The laser settings in the three study groups are standardised and need to be maintained throughout the procedure.

* Group 1 - sheathless low power (4-6W), short pulse: 0.4 - 0.5J at 10 or 20Hz, 0.6 - 0.8J at 10Hz * Group 2 - FANS with low power (4-6W), short pulse: 0.4 - 0.5J at 10 or 20Hz, 0.6 - 0.8J at 10Hz * Group 3 - FANS with high power (16-24W), short pulse: 0.4 - 0.5J at 40Hz, 0.6J at 30 - 40Hz, 0.8J at 20 - 30Hz

Standard start-up settings: Group 1 (sheathless, low power) 0.4J/10Hz (4W), Group 2 (FANS, low power) 0.6J/10Ηz (6W) and Group 3 (FANS, high power) 0.4J/40Hz (16W).

THE URS PROCEDURE: The URS procedure is performed in general anaesthesia and prophylactic antibiotics prior to surgery start will be administered according to the departments' guidelines, either according to urine culture or current local regime.

The procedure starts with flexible URS using the 7.5Fr single use MacroLux CoralView flexible ureteroscope with 6.7Fr wedged tip. Cystoscopy may be performed if considered necessary as well as semirigid ureteroscopy. A safety guide wire can be used at the surgeon's discretion but is routinely omitted during URS at the three hospitals. Balloon dilatation (4-5 mm) is performed on demand. However, multiple dilatations at different levels in the ureter should be avoided. Instead, a JJ-stent should be placed and the patient scheduled for a second procedure. If the patient is scheduled for a second procedure, they keep their allocated treatment group according to the first randomisation. Only the specific MacroLux flexible ureteroscope can be used for the endoscopic lithotripsy.

Room-tempered (23oC), gravitational irrigation fluid at 60 cm height is used throughout the procedure when performing a sheathless approach, and gravitational irrigation at ≥ 100 cm height when FANS are applied.

Patients are allocated to the randomisation group immediately once the entire ureter is inspected and confirmed stone free. Allocation to randomisation group is done by opening the sealed envelope revealing the result of the randomisation. FANS can be placed according to randomisation group only after performing initial endoscopy ensuring no stones are present in the ureter. The size of the FANS must be 9.5/11.5 Ch in the present study in the two FANS groups. However, if placement of a 9.5/11.5 Ch FANS fails an 8.5/10.5 Ch FANS can be attempted. Balloon dilatation can be performed as described above if deemed necessary. If placement of a FANS fails, the patient should still be included in the study but registered as failed access. However, per protocol analyses will be performed as it is of interest to explore the risk of failed placement of the sheaths. If a second procedure is planned, this should be performed according to the initial randomisation allocation group.

The amount of suction applied to the FANS can be adjusted according to the surgeons' discretion. A 150μm sized laser fibre must be used for stone disintegration for all patients across the randomisation groups. The stone is disintegrated using TFL with predefined settings as described below and according to the randomisation group. To make the procedures as similar as possible, the stone should be dusted/disintegrated to as small particles as possible rather than fragmented and retrieved. Only residual particles not suitable for further disintegration can be retrieved at the end of the procedure to render the patient stone free.

A JJ-stent can be placed after the procedure if deemed necessary, and if so, this is removed according to standard routine after 1-2 weeks in the outpatient clinic or by the patients themselves if on a string.

FOLLOW-UP: Follow-up with computed tomography (CT) is performed at 3 months post endoscopically for all patients to assess stone free status and exclude a ureteral stricture in addition to a clinical consultation.

ETHICAL CONSIDERATIONS AND APPROVALS: All patients eligible for inclusion in the study will receive oral and written information. Participation in the study is voluntarily, and the patient can choose to withdraw at any point during the study process. Inclusion in the study will only be done after the consent form is signed. The study is approved by The National Committees for Research Ethics in Norway (REK: 992079). In addition, approval by The Data Protection Authorities at Haukeland University Hospital (e-protocol: 6881)has been obtained.

• Operative time [Time frame: During surgery (approximately 1 hour), registered immediately after surgery]
• Laser activation patterns: active laser time [Time frame: During surgery (approximately 1 hour), registered immediately after surgery]
• Intraoperative complications [Time frame: During surgery (approximately 1 hour), registered immediately after surgery]
• Postoperative complications [Time frame: After surgery until 3 months post endoscopically]