Antegrade flexible ureteroscopy-assisted percutaneous nephrolithotomy for staghorn calculi: a prospective randomized controlled study

Urolithiasis is a common urological condition worldwide. With the advancements in lithotripsy technology and endourological equipment, various treatment options are available depending on individual patient factors. The primary treatment methods for removing renal calculi include extracorporeal shock wave lithotripsy (SWL), percutaneous nephrolithotomy (PNL), and ureteroscopy (URS) [1]. Due to its safety and effectiveness, PNL has become a standard procedure for treating renal stones > 2 cm [1‐3]. The reported stone-free rate (SFR) for PNL is around 90% [4]. However, when mentioning staghorn calculi, the SFR is generally unsatisfactory, and it is challenging to remove all stones through a single percutaneous renal tract [5‐7]. Patients may require staged surgery and bear the risk of multiple operations and anesthesia. To achieve better stone removal in a single surgery, the surgeon may need to create multiple percutaneous renal tracts, particularly for stones in multiple or parallel calyces. However, the conventional point is that multiple tracts requires specialists with skilled puncture technique and experience in performing accurate percutaneous puncture, otherwise it may lead to greater bleeding and higher complication rates than the single-tract method [8‐10].

With the development of endoscopic surgical technology, endoscopic combined intrarenal surgery (ECIRS) has been introduced as an improvement to eliminate the need for multiple tracts while simultaneously improving the SFR in a single surgery. It has been proven safe and effective for treating large stones, facilitating percutaneous tract, and improving SFR [11]. Several developments have been made in the ECIRS position, including the prone split-leg position (PSL), supine lithotomy position, and Galdakao-Modified Supine Valdivia position (GMSV). In recent years, the ECIRS technique has become widely accepted in clinical practice and is often discussed in clinical research for the staghorn calculi management [12]. However, there are still some concerns that prevent ECIRS from gaining more widespread adoption, because this procedure requires two sets of surgical equipment, namely lithotripsy and endoscopic equipment, and two experienced surgeons. Furthermore, the attendant increased costs are constantly mentioned [12‐14]. There is still no clear indication for ECIRS in the treatment of staghorn calculi. With less equipment and surgeons, the PNL combined with anterograde flexible endoscopy technique can also manage staghorn calculi like ECIRS. Pastore et al. demonstrated that the combined laparoscopic and antegrade flexible cystoscope for management of staghorn calculi was feasible and repeatable [15]. PNL combined with flexible nephroscope has also been reported to improve the SFR for staghorn stones [16, 17]. Compared with flexible cystoscope, flexible ureteroscope has a larger bending angle at the front end and a wider observation range. In recent years, several studies have been carried out on antegrade flexible ureteroscopy-assisted PNL (aPNL) for the treatment of staghorn calculi, but all of them were retrospective studies with small samples or case reports [18, 19]. The existing constraints on reusable flexible ureteroscope assisted PNL include a high initial purchase cost, vulnerabilities, high expenditures for repair, and a risk of cross-infection [20]. However, there have been encouraging reports on the improvement of single-use flexible ureteroscope over the past few years, which could solve these problems. Therefore, we conducted a prospective randomized controlled trial to compare the efficacy and safety of single PNL (sPNL) and aPNL in treating staghorn calculi by one urologist as a supplement to ECIRS.

The European and American Urological Association Guidelines recommend percutaneous nephrolithotomy (PNL) as the first-line treatment for large and complex kidney stones [1, 23]. However, using a single tract for PNL in staghorn calculi has always been challenging due to the higher likelihood of residual stones, despite advances in technology and instrumentation [12].

To achieve an excellent SFR during treatment, several strategies have been proposed in clinical practice. Large et al. [24] demonstrated that secondary procedures were required in 39% of patients treated with single-access PNL for staghorn renal calculi. This process increased the number of anesthesia sessions, costs, and patient discomfort. The location, staghorn status, and size of stones are important factors in determining the percutaneous tract required. Under certain circumstances, multiple percutaneous tracts or increasing the swing amplitude of the rigid ureteroscope may be necessary during PNL. However, these additional tracts and increased swing amplitude can lead to a higher incidence of complications and postoperative discomfort [10, 25, 26]. Wang et al. [9] and Huang et al. [10] reported that patients treated with additional tracts had a higher incidence of comorbidity and a negative impact on renal function without an increase in SFR.

Endoscopic combined intrarenal surgery (ECIRS) was first reported in 2008 [27]. With the introduction of disposable flexible ureteroscopes and lithotripsy equipment, ECIRS has become a revolutionary approach for treating kidney stones due to its higher one-step SFR and lower morbidity compared to PNL alone [12, 28]. Hamamoto et al. [29] evaluated the ECIRS technique in the prone split-leg (PSL) position for the treatment of staghorn calculi and found it to be a safe and effective approach without increasing the number of percutaneous tracts. In addition, Zhao et al. [30] compared the efficacy and safety of ECIRS in the Galdakao-modified supine Valdivia (GMSV) position to PNL and found that ECIRS in the GMSV position had a significantly higher SFR but lower procedure-associated morbidity than the PNL group. This technique combines the advantages of the high efficacy of PNL and the wide exploration angle of flexible ureteroscope. It can be used simultaneously for ureteroscopy and PNL, reduces postural changes after anesthesia, avoids chest and abdomen compression in the prone position, and facilitates intraoperative anesthesia monitoring. Despite the numerous benefits of ECIRS technique, it requires two groups of surgeons and two sets of imaging displays and lithotripsy equipment. In addition, a high degree of cooperation between surgeons is also required to reduce operation time. There is no clear indication for ECIRS in the treatment of staghorn calculi, so how to select patients who are eligible for ECIRS before surgery is a problem that needs to be solved urgently.

Therefore, PNL needs further improvement for higher efficacy, fewer complications, and lower costs. Prior to the application of the ECIRS technique, anterograde flexible cystoscopy or flexible nephroscopy which allowed for the use of thicker laser fibers was performed to improve the SFR of staghorn stones. This surgical approach offers higher lithotripsy efficiency, faster flushing and clearer vision [15‐17]. However, the caliber of the cystoscope and nephroscope makes it difficult to perform anterograde examination of the ureter, which increases the risk of larger stones remaining in the ureter. Moreover, our model experiments in vitro demonstrated that flexible ureteroscope was superior to flexible cystoscope in the observation of various renal calyces, especially the parallel calyces. That is because flexible ureteroscope has larger degree of distal deflection but a smaller distal outer diameter compared to flexible cystoscope. In the past, reusable flexible ureteroscope has been limited by high initial purchase cost, vulnerabilities, and high expenditures for repair. However, the currently used disposable flexible ureteroscope can reduce the risk of cross-infection and equipment maintenance costs, which makes antegrade flexible ureteroscopy-assisted percutaneous nephrolithotomy possible.

Previous studies have suggested that PNL combined with anterograde flexible ureteroscope is a preferred treatment for staghorn calculi, but they were retrospective studies or case reports [18, 19]. Therefore, we conducted the prospective randomized controlled trial to thoroughly investigate the efficiency and safety of aPNL. In our previous research, we found that surgery parameters and clinical outcomes were associated with the number of stone branches. In addition, we observed that staghorn calculi with a stone branch number of five or more were more likely to require multiple tracts and staged PNL, and had lower SFR [21]. The present study data demonstrated that aPNL could improve SFR and reduce the percutaneous tract number with shorter operative time (P < 0.05). The shorter operative time in aPNL might be attributed to the reduced percutaneous tract number. Percutaneous tract was established under ultrasound guidance in our center. After the first tract was established, some patients might experience urine extravasation, which could lower the quality of the image and thus increase the operative time. In addition, in order to access the stones, we sometimes had to increase the swing amplitude of the rigid ureteroscope in sPNL group. This procedure might cause bleeding of the percutaneous tract, subsequently blurring the vision during lithotripsy and prolonging the operative time. aPNL could also reduce the need for staged surgeries, particularly for patients with stone branch numbers of 5 or more. However, there was no statistically significant difference in hemoglobin change and blood transfusion rate despite an increase in the number of tracts in this study. The other perioperative complications between the two groups were also comparable.

A flexible ureteroscope can be used to displace stones that cannot be reached by a rigid ureteroscope into the renal pelvis for treatment, or it can directly break them down. The front end of the disposable ureteral flexible ureteroscope has a larger bending angle, allowing it to assist in the examination and treatment of stones that are not visible by a rigid ureteroscope. This is particularly useful for stones located in the parallel calyces of the puncture channel, which can be broken down by Holmium laser lithotripsy under the flexible ureteroscope, or under the rigid ureteroscope after the stone basket has been displaced to the renal pelvis. This one-stage procedure improves the SFR and shortens the operation time. Using this technique limits the swing amplitude of the rigid ureteroscope and reduces the number and size of tracts required during the procedure. This helps to decrease the risk of parenchymal laceration and increase the overall safety of the operation. In addition, performing anterograde flexible ureteroscopy can maintain low-pressure perfusion of the kidney, which helps to decrease the risk of postoperative infection. After the lithotripsy is completed, the flexible ureteroscope can be used to check and manage any residual stones in the ureter.

The current study has some limitations. First, the present surgical approach cannot completely replace other surgical methods. Second, our findings in the present study were based on a relatively small sample at a single center and further validation in a multicenter study with a large size sample is required. Lastly, the length of the flexible ureteroscope used in the study might influence the surgeon’s lithotripsy experience. To address this limitation, a flexible ureteroscope with a more suitable length should be developed in the future.

aPNL is a promising treatment option for multiple kidney and staghorn stones. It has been found to have a higher SFR and a lower rate of multiple percutaneous tracts, staged surgery, and operative time compared to PNL alone. This is particularly true for patients with a stone branch number of 5 or more. Importantly, aPNL does not increase the incidence of surgical complications.