7.5F Mini Flexible Ureteroscope in Retrograde Intrarenal Surgery: Initial Results from a Multicenter Randomized Clinical Trial

Abstract

Objective:

To report the initial results of an randomized clinical trail comparing the safety and efficacy between 7.5F and 9.2F flexible ureteroscope (FUS) in the management of renal calculi <2 cm.

Materials and Methods:

Eighty patients were enrolled and received retrograde intrarenal surgery (RIRS) with a different size FUS. The operation results and complications were compared.

Results:

Two cases in the 7.5F group and four cases in the 9.2F group failed to insert the 12/14F ureteral access sheath (UAS), respectively, and no significant difference (p = 0.396) was noted. However, 10/12F UAS was inserted in the 7.5F group, but not available in the 9.2F group, and thus, the 10/12F UAS inserting rate in the 7.5F group was higher than in the 9.2F group (100% vs 0%, p = 0.014), and the UAS insertion failure rate in 9.2F group was higher than in the 7.5F group (10% vs 0%, p = 0.040). The operation time in 7.5F group was shorter than the 9.2F group (35.60 ± 7.86 vs 41.05 ± 8.14, p = 0.003). Less irrigation was required in 7.5F group (813.93 ± 279.47 mL vs 1504.18 ± 385.31 mL, p = 0.000). The postoperative fever rate in 9.2F group was higher than 7.5F group (20% vs 5%, p = 0.043). There was no significant difference in sepsis (0% vs 2.5%, p = 0.314) between the two groups. No significant difference was noted in hospital stay (0.93 ± 0.49 days vs 1.14 ± 0.64 days, p = 0.099) between the two groups. The final stone-free rate (SFR) in 7.5F group was higher than 9.2F group (95% vs 80%, p = 0.043).

Conclusion:

The latest 7.5F mini FUS was a reliable instrument in RIRS to keep a good visualization with low requirement of irrigation, low postoperative infection complication, and also a high SFR when compared with the conventional 9.2F FUS.

Clinical Trial Registration:

NCT05231577.

Introduction

Retrograde intrarenal surgery (RIRS) has been a well-established procedure for the management of 1 to 2 cm upper urinary tract stones, with a stone-free rate (SFR) of 81.4% to 92.5%.^1,2 However, postoperative complication following RIRS is still troublesome in clinical practice. Fever and systemic inflammatory response syndrome (SIRS) are the most frequently noted infection complications following RIRS, with an incidence up to 17.5%.³ Without an early and effective intervention, urosepsis could progress to septic shock as high as 30% to 40%, and result in a mortality rate of 22%.^4,5

Postoperative infection following endoscopic lithotripsy is probably due to increased intrarenal pressure (IRP) and the subsequent backflow of irrigation with endotoxin and bacteria.⁶ The American Urological Association (AUA) guideline on medical management of kidney stones indicates that maintenance of a low IRP may decrease the risks of hypothermia and fluid overload caused by significant absorption of irrigation fluid.⁷ Thus, the management of intraoperative IRP is crucial.

There are different risk factors influencing IRP during RIRS, such as ureteral access sheath (UAS), irrigation device, and the size of flexible ureteroscope (FUS).^8,9 Theoretically, the larger the gap between the FUS and the UAS, the better is the drainage of the irrigation, and therefore to keep a lower IRP. However, a larger caliber UAS is not always available, typically in patients with ureteral stricture, and thus, only a smaller caliber UAS can be used in these cases. In this presetting, a smaller caliber FUS is expected. Fortunately, a mini FUS of PU3033A (PUSEN, China) is available in clinical practice recently, with a caliber of 7.5F, and therefore, a potential for greater compatibility with different sizes of UAS, and also lower IRP in a normal UAS.

However, there is still a lack of multiple center randomized clinical trial randomized clinical trail (RCT) to evaluate this 7.5F mini FUS, and to prove its effect on the post-RIRS infection complications. In the present study, we would like to report our initial results of an RCT comparing the safety and efficacy between 7.5F and 9.2F FUS in the management of renal calculi <2 cm.

Materials and Methods

Patient enrollment

After approval from the hospital ethics committee, the present RCT was registered in ClinicalTrials.gov, with an ID of NCT05231577. Patients were recruited in the following four centers in China between May 2022 and May 2023: First Affiliated Hospital of Guangzhou Medical University, PLA General Hospital, West China Hospital of Sichuan University, and Second Affiliated Hospital of Zhengzhou University.

Patients were recruited according to these criteria: (1) agreed to receive RIRS; (2) age between 18 and 70 years; and (3) 1 to 2 cm kidney stones. The exclusion criteria were as follows: (1) patients with middle or distal ureteral stones needing semirigid ureteroscopy; (2) patients with abnormal anatomy such as ureteral stricture, ectopic kidney, horseshoe kidney, and duplicate kidney; and (3) patients with a nephrostomy tube.

It was estimated in the pretest that the postoperative fever rate following RIRS with 7.5F FUS was 8.5%, while it was 11.3% in the 9.2F FUS group, respectively. The test level of type-1 error (α) was set as 0.05 and the test power (1 − β) was 0.8. The sample size ratio of the two groups was 1:1 and the cutoff value for superiority test was 0.2. According to the Walters approximation algorithm, the sample size was calculated that n = 33 in each group. Considering the loss in follow-up, the sample size of each group was set to 40, and therefore, a total of 80 patients were required to be enrolled in the present study.

RIRS procedure

Patients with a positive urine culture were treated with sensitive antibiotics according to a drug sensitivity test for 5 to 7 days. Patients with a negative urine culture were given single-dose prophylactic antibiotics before RIRS.¹⁰

One day before the operation, eligible patients were enrolled into the RCT, 20 cases in each center were enrolled. Informed consent was required from all the participants. Randomization was administrated independently in four centers with a random number generator. Randomization was achieved with a ratio of 10:10, either in the PUSEN PU3033A 7.5F FUS group (Group 1) or in the PUSEN PU3022 9.2F FUS group (Group 2).

All RIRS procedures were performed with general anesthesia and in a lithotomy position. After retrograde insertion of a guidewire with hydrophonic coating into the renal collecting system of the affected kidney, a 12/14F UAS (REBORN, China) was inserted into the upper ureter under fluoroscopy guidance. If the 12/14F UAS insertion failed, 10/12F UAS was tried again in 7.5F group, while the Double-J stent was inserted in 9.2F group and second session RIRS was arranged.

Disposable FUS (PUSEN) was advanced into the renal collecting system, and holmium: yttrium-aluminum-garnet (Ho:YAG) laser was used for lithotripsy, 200 μm laser fiber was preferred. The Ho:YAG laser energy setting was 0.5–0.8 J × 20–30 Hz, depending on the stone characteristics and urologists' preference. 2.2F stone basket was used to retrieve stone fragments after lithotripsy. At the end of the procedure, UAS was removed and a 6F Double-J stent was placed.

Operation time was defined as the time from the insertion of guidewire to the completion of Double-J stent placement. Postoperative vital sign and blood test were recorded. Postoperative fever was defined as body temperature ≥38°C. The patient should be further evaluated for organ dysfunction with SOFA score when qSOFA score was of ≥2 points (respiratory rate ≥22 beats per minute, altered state of consciousness, and systolic blood pressure ≤100 mm Hg, each of which counts as 1 point). Sepsis was diagnosed if the SOFA score was ≥2 points.¹¹ SIRS combined with pre- and postoperative white blood cell ratio was noted to identify potential septic shock patients.¹² Complications were assessed and recorded with the Clavien–Dindo classification system.¹³

Final SFR was determined by the NCCT at postoperative 1 month. Stone-free status was classified into the following three grades: Grade A (no stones on CT scan) absolute stone free, Grade B (≤2 mm fragments) relatively stone free, and Grade C (2.1–4 mm fragments) relatively stone free.

Statistical analysis

All the data were analyzed with the IBM Statistical Package for Social Sciences Statistics (SPSS) version 25.0 (IBM SPSS Statistics). Continuous data were recorded as mean ± standard deviation (mean ± SD) and categorical data were recorded as n (%). The baseline data among 4 centers were compared by the Kruskal–Wallis test. Normally distributed data were analyzed with Student's t test, while categorical data were compared with the χ ² test or Fisher's exact test. p < 0.05 was regarded as a significant difference statistically.

Results

Eighty patients were enrolled in the present RCT. High homogeneity of baseline data among the four centers was noted (p > 0.05). The patients' demographic and baseline characteristics are shown in Table 1, there was no significant difference between the two groups (all p > 0.05).

Table 1.

Patient Demographic and Baseline Characteristics

	ALL (N = 80)	Group1 (7.5F) (n = 40)	Group 2 (9.2F) (n = 40)	p
Age (year)	47.36 ± 13.87	45.38 ± 12.81	49.35 ± 14.76	0.202
Sex (M:F)	55:25	30:10	24:16	0.152
Comorbidity, n (%)	27(33.75)	16 (40.0)	11 (27.5)	0.237
BMI (kg/m²)	22.79 ± 2.56	22.57 ± 2.37	23.02 ± 2.75	0.433
Stone laterality (L:R)	44:36	22:18	21:19	0.823
Stone size (cm)	1.35 ± 0.25	1.31 ± 0.23	1.39 ± 0.26	0.177
CT density (HU)	755.74 ± 217.44	733.75 ± 222.20	773.73 ± 213.09	0.369
Pre-WBC (10⁹/L)	7.25 ± 2.62	6.79 ± 2.37	7.71 ± 2.81	0.117
Pre-Hb (g/L)	140.71 ± 16.68	142.33 ± 16.68	139.10 ± 16.73	0.391
Pre-Cr (μmol/L)	92.34 ± 46.32	96.07 ± 55.27	88.59 ± 35.51	0.654
Positive urine culture, n (%)	12 (15.0)	5 (12.5)	7 (17.5)	0.531

Two cases in 7.5F group and four cases in 9.2F group, respectively, failed to insert 12/14F UAS, no significant difference (p = 0.396) was noted. However, 10/12F UAS was inserted in 7.5F group, but not available in 9.2F group, and thus, the 10/12F UAS inserting rate in 7.5F group was higher than in 9.2F group (100% vs 0%, p = 0.0140), and the UAS insertion failure rate in 9.2F group was higher than 7.5F group (10% vs 0%, p = 0.040).

The operation time in 7.5F group was shorter than in the 9.2F group (35.60 ± 7.86 vs 41.05 ± 8.14, p = 0.003). Less irrigation was required in 7.5F group (813.93 ± 279.47 mL vs 1504.18 ± 385.31 mL, p = 0.000). The postoperative fever rate in 9.2F group was higher than in the 7.5F group (20% vs 5%, p = 0.043). There was no significant difference in sepsis (0% vs 2.5%, p = 0.314) between the two groups. No significant difference was noted in hospital stay (0.93 ± 0.49 days vs 1.14 ± 0.64 days, p = 0.099) between the two groups. The final SFR in 7.5F group was higher than in the 9.2F group (95% vs 80%, p = 0.043) (Table 2).

Table 2.

Operation Results and Complications

	ALL (N = 80)	Group 1 (7.5F) (n = 40)	Group 2 (9.2F) (n = 40)	p
Effective insertion of 12/14F UAS, n (%)	74 (92.5)	38 (95)	36 (90)	0.396
10/12F UAS inserting rate, n/N(%)	NA	2/2 (100)	0/4 (0)	0.014
UAS insertion failure, n (%)	4 (5.0)	0 (0)	4 (10.0)	0.040
Operation time (minutes)	38.33 ± 8.42	35.60 ± 7.86	41.05 ± 8.14	0.003
Irrigation volume(mL)	1159.05 ± 482.15	813.93 ± 279.47	1504.18 ± 385.31	0.000
Hb decreased (g/L)	6.21 ± 9.06	6.80 ± 8.48	6.63 ± 9.70	0.687
Hospital stay (days)	1.03 ± 0.58	0.93 ± 0.49	1.14 ± 0.64	0.099
SFR (%)	70 (87.5%)	38 (95%)	32 (80%)	0.043
Grade A (no stone)	42 (60.0%)	22 (57.9%)	20 (62.5%)
Grade B (≤2 mm)	17 (24.3%)	10 (26.3%)	7 (21.9%)
Grade C (2.1–4 mm)	11 (15.7%)	6 (15.8%)	5 (15.6%)
Complications, n (%)
Fever (Grade I)	10 (12.5)	2 (5.0)	8 (20.0)	0.043
Urosepsis (Grade IVb)	1 (1.25)	0 (0)	1 (2.5)	0.314

SFR = stone-free rate; UAS, ureteral access sheath.

Discussion

To the best of our knowledge, the present study was the first prospective multicenter RCT comparing the safety and efficacy of 7.5F vs 9.2F FUS in the management of renal calculi. Exactly, with a smaller caliber, the latest 7.5F mini disposable digital FUS demonstrated well in the present study.

As a natural orifice transluminal endoscopic surgery (NOTES), RIRS was a well-established minimally invasive modality for the management of upper urinary tract stone.² However, postoperative infection complication was the most concerned complication following RIRS.¹⁴ Series of studies have demonstrated that operation time, urinary tract infection, and stone composition (struvite/infection stone) were independent predictors of infectious complications after RIRS.^14,15 In our previous study, stone size, small-caliber UAS, irrigation flow rate, and struvite calculi were identified as independent risk factors of SIRS after RIRS.¹⁶ In terms of the well-known pathogenesis, endotoxin, bacteria colonized in renal pelvis mucous and calculi released during lithotripsy, was the source of the infection complications following endoscopic lithotripsy. High renal pelvic pressure facilitates the backflow of endotoxin and bacteria into the internal circulation system,¹⁵attributing to postoperative infection complications.^15
–17 Thus, to keep a lower renal pelvic pressure and a shorter operation time in RIRS were essential.

UAS could decrease the irrigation pressures transmitted to the renal pelvis and subsequently to the parenchymal by 57% to 75%,¹⁸ constituting the most efficient tool to keep a low IRP.⁸ Physically speaking, renal pelvic pressure during RIRS was mostly influenced by the reflux of irrigation from the gap between UAS and FUS. Undoubtedly, UAS with larger caliber or a small caliber FUS could effectively reduce the internal pressure in RIRS.^19
–21 On the contrary, better reflex of irrigation was provided when the gap between UAS and FUS got larger in the 7.5F group, the dust and bleeding during lithotripsy could scatter and disappear much more quickly, and therefore, to keep a better visualization in 7.5F group, less irrigation was required. Less irrigation and better reflex of irrigation in 7.5F group contributed to a low IRP.

It was verified in the present study that postoperative fever rate in 7.5F group was lower than in the 9.2F group. Even though IRP was not measured in the present study, the fact did demonstrate its superiority in keeping a low IRP during RIRS, and thus, a lower postoperative fever rate.

The last but not least, a smaller caliber FUS can provide a higher compatibility in a different caliber UAS. As known, UAS cannot always be inserted in RIRS since the ureter condition differed.²² The 7.5F mini FUS was known as a unique FUS with smallest caliber to pass 10/12F UAS, however, the conventional 9.2F FUS cannot. The present RCT demonstrated the superiority of 7.5F FUS over 9.2F FUS when 12/14F UAS insertion failed. In this case, the 9.2F group can only accept the reality of failure. On the contrary, better visualization and excellent handling together facilitated high efficiency in lithotripsy in 7.5F group, and therefore, a shorter operation time and a higher SFR were achieved.

There were some limitations in the present study. First, renal pelvic pressure was not measured in RIRS, since no reasonable and effective method was available to measure renal pelvic pressure in RIRS. Second, the sample size in the present RCT was not as large as imagined. Larger sample size RCTs in more centers were required to verify our finding.

Conclusion

The latest 7.5F mini FUS was a reliable instrument in RIRS to keep good visualization with low requirement of irrigation, low postoperative infection complication, and also a high SFR when compared with the conventional 9.2F FUS.

Footnotes

Authors' Contributions

W.Z.: project development, data collection and analysis, and article writing; W.Z.: data collection and analysis; Z.Z.: data collection and analysis; B.L.: data collection and analysis; H.M.: data collection and analysis; C.L.: data collection and analysis; K.W.: project development and data collection and analysis; X.Z.: project development and data collection and analysis; C.X.: project development and data collection and analysis; G.Z.: project development, data analysis, and article writing/editing.

Human Participants and Informed Consent

The present RCT adheres to the World Medical Association Declaration of Helsinki Ethical Principles for Medical Research Involving Human Subjects. The protocol was reviewed and approved by the hospital ethics committee. Informed consent was required from all participants.

Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Author Disclosure Statement

No competing financial interests exist.

Funding Information

No funding was received for this article.

Abbreviations Used

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