Randomized controlled, multicentre clinical trial comparing a dual-probe ultrasonic lithotrite with a single-probe lithotrite for percutaneous nephrolithotomy

Authors


James E. Lingeman, Methodist Hospital Institute for Kidney Stone Disease, 1801 North Senate Boulevard, Suite 220, Indianapolis, IN 46202, USA. e-mail: jlingeman@clarian.org

Abstract

Study Type – Therapy (case series)

Level of Evidence 4

What’s known on the subject? and What does the study add?

Studies have indicated that not all ultrasonic lithotripters are created equal when it comes to efficiency of stone fragmentation and removal. To improve the efficiency of stone fragmentation and removal, combination pneumatic and ultrasonic devices have been developed. This study demonstrates that one available combination device, the Cyberwand, did not decrease the time to removal of the target stone nor did it increase the stone free rate compared to a standard ultrasonic lithotripter.

OBJECTIVES

• To compare the Cyberwand (Gyrus/ACMI, Southborough, MA, USA), a dual-probe ultrasonic lithotrite, with a single-probe ultrasonic lithotrite.

• The Cyberwand incorporates coaxial high- and low-frequency ultrasonic probes that work synergistically.

PATIENTS AND METHODS

• An institutional review board-approved, multicentre, randomized controlled trial to compare the Cyberwand to the Olympus LUS-II (Olympus America, Inc., Melville, NY, USA) single-probe lithotrite was performed.

• Patients undergoing a percutaneous nephrolithotomy (PCNL) with a target stone >2 cm in diameter were eligible for the study.

• The primary outcome was the time to removal of the targeted stone.

RESULTS

• A total of 57 PCNLs were performed after randomization: 25 Cyberwand and 32 LUS-II.

• There was no difference (P > 0.05) observed between the two devices for target stone surface area (Cyberwand 526.6 cm3 vs LUS-II 540.1 cm3), time to clearance of target stone (Cyberwand 15.8 min vs LUS-II 14.2 min) and target stone clearance rate (Cyberwand 61.9 mm2/min vs LUS-II 75.8 mm2/min).

• Of the patients with stone analysis, hard stones (calcium oxalate monohydrate, brushite and cystine) were noted in 14 (56.0%) of the 25 Cyberwand and 18 (62.1%) of the 29 LUS-II patients.

• Fifteen of the 25 (60.0%) Cyberwand and 20 of the 32 (62.5%) LUS-II patients were stone-free after the initial PCNL.

• Those patients not rendered stone-free went on to receive a secondary PCNL.

• Device malfunction occurred in eight of 25(32.0%) Cyberwand and five of 32 (15.6%) LUS II patients.

• Complications were similar in both treatment groups.

CONCLUSION

• No appreciable difference between the dual-probe Cyberwand and the standard ultrasonic Olympus LUS-II lithotrites can be identified.

Abbreviation
PCNL

percutaneous nephrolithotomy

INTRODUCTION

Percutaneous nephrolithotomy (PCNL) allows for the rapid removal of any renal stone, regardless of size or composition. Once percutaneous access is achieved, PCNL relies heavily on intracorporeal lithotripsy to facilitate stone fragmentation and removal. In general, ultrasonic devices are the most commonly used intracorporeal lithotrites during PCNL. Although ultrasonic lithotripters are excellent for simultaneous fragmentation and removal of most urinary calculi, they are somewhat dependant on stone composition because the fragmentation abilities are limited in the setting of hard cystine or calcium oxalate monohydrate stones [1–3]. For such hard stones, pneumatic lithotripters or a holmium laser are often used for fragmentation because these devices readily break stones of any composition [4]. Unfortunately, a major disadvantage of pneumatic lithotrites is that they are incapable of concurrently removing pieces when fragmenting the stones. Rather, manual fragment removal with graspers and basket, or fragmentation/suctioning via an ultrasonic lithotripter, is necessary, which can be a time-consuming process requiring switching between the lithotrite and retrieval devices.

In an attempt to merge the excellent fragmentation abilities of the pneumatic devices, at the same time as maintaining the suction capabilities of the ultrasonic probes, combination devices have been introduced [5–10]. In vitro testing of two combination devices, the Cyberwand (Gyrus/ACMI, Southborough, MA, USA) and the Lithoclast® Ultra (Microvasive, Natick, MA, USA; EMS, Bern, Switzerland) has shown the Cyberwand to be more efficient, with a twofold more rapid stone penetration [10]. Although previous testing has shown excellent clinical results with the Lithoclast Ultra [7], clinical data for the Cyberwand are lacking.

A rigorous and impartial evaluation of intracorporeal lithotripters is of great importance to urologists because each device may have certain unique properties that make it more suitable for particular applications. Thus, despite the promising results obtained in vitro, the present study aimed to evaluate the clinical efficacy of the Cyberwand intracorporeal lithotripter. Through a prospective, multicentre, randomized trial, we compared target stone clearance rates using the Cyberwand with those for the Olympus LUS-II (Olympus America, Inc., Melville, NY, USA) device. In vitro testing has shown the LUS-II device to be the most efficient ultrasonic device on the market, which is why it was chosen for comparison [11].

PATIENTS AND METHODS

The Cyberwand is an intracorporeal lithotripter with a dual-probe ultrasonic design, incorporating coaxial high frequency and low frequency. The two probes are concentric, with a 2.77-mm outer diameter inner probe and a 3.75-mm outer diameter outer probe. The inner probe is fixed to the hand piece and vibrates at 21 000 Hz. The outer probe is free to move in a reciprocating fashion and is pushed outward by a sliding piston (free mass) driven by the vibration energy of the inner probe. The outer probe returns to its starting position by resistance from a coil spring. The outer probe is 1 mm shorter than the inner probe and its maximal excursion is 1 mm, such that it never passes the tip of the inner probe. The Olympus LUS-II is a standard ultrasonic lithotrite with a 3.4-mm outer diameter probe. It has a generator unit that powers a piezoelectric crystal array within an attached hand piece. When the generator is activated, the crystals vibrate at frequencies of up to 27 000 Hz [12]. Both the Cyberwand and LUS-II have hollow probes to allow suction capabilities.

The present study was conducted as a prospective, multicentre, randomized, clinical study comparing the Cyberwand and the Olympus LUS-II intracorporeal lithotripter devices. After individual institutional review board approval was obtained at each location, patients were enrolled at seven sites. Patients aged >18 years undergoing PCNL for renal calculi ≥2 cm in diameter and easily visible on preoperative plain abdominal film of kidney, ureter and bladder or CT scan were considered eligible for the study. Both men and women were eligible; however, women of child-bearing age required a recent negative pregnancy test before undergoing the surgical procedure. Patients were excluded if they had any of the conditions: radiolucent stones; largest stone size <2 cm; pregnancy; inability to provide informed consent; active urinary tract infection; recent shock wave lithotripsy within the last 3 months; or if multiple percutaneous access was anticipated during the PCNL.

All patients had their stone burden evaluated by plain abdominal film of kidney, ureter and bladder or CT scan preoperatively. The targeted stone was outlined using a digital system to assess the stone surface area (measured in mm2). Patients were randomized to treatment with the Olympus LUS-II or the Cyberwand. All randomization occurred at the central study site to minimize systematic error and potential investigator bias.

Operatively, once percutaneous access was established, the time (min) for the clearance of the targeted stone burden was recorded. Clearance rate was calculated by dividing the surface area of the stone burden by the clearance time. Any malfunction of the intracorporeal lithotrite was specifically recorded. Other parameters recorded included the number and location of accesses performed, stone analysis, stone-free rate and complications. Stones were assigned a stone composition based on the most predominant component noted at time of stone analysis. Stone-free rate was defined either by CT scan or secondary nephroscopy within 30 days of initial procedure. Preoperative, intra-operative, and postoperative management of the patient undergoing percutaneous stone removal did not differ from standard of care.

STATISTICAL ANALYSIS

Sample size calculations were initially performed using a two-sided Student’s t-test with a power of 90% and a significance level of α= 0.05. The primary outcome of interest was the clearance time of the targeted stone burden. Mean clearance time using the Olympus LUS-II was reported to be 44 mm2/min by Pietrow et al. [7]. The original sample size calculations were based on the assumption that the Cyberwand would reduce the mean clearance time by 50% and, assuming a common standard deviation of 22 min for the procedure times, 46 total subjects would be needed (i.e. 23 in each group). Outcome comparisons between groups were analyzed with a t-test to compare means, with P < 0.05 considered statistically significant. Interim data analysis indicated that the distribution of stone types was not represented equally among both groups and, because stone composition could affect stone clearance rates, an increase in the sample size was calculated. At interim analysis, two-thirds of the subjects enrolled were found to have hard stones. An increase in the sample size by 50% (70 in total, with 35 in each treatment group) would provide 46 patients with hard stones and a better likelihood of sufficiently equal distribution.

RESULTS

Between July 2006 and May 2008, 57 patients with a target renal calculus ≥2 cm underwent PCNL and stone fragmentation using either the Cyberwand (n= 25) or the LUS-II (n= 32). Enrolment per site is given in Table 1. In the Cyberwand and LUS-II groups, men comprised 56.5% (n= 13) and 62.5% (n= 20) of the cohort, respectively. The mean (range) age at treatment for the Cyberwand group was 54 (36–74) years and was similar to that of 55 (19–75) years for the LUS-II group.

Table 1. Enrollment at participating sites
SiteOriginal Cyberwand probesOlympus LUS-IINew Cyberwand probesTotal per site
Duke 2 1 0 3
Johns Hopkins 0 2 0 2
Methodist10151035
Northwestern 3 3 1 7
Wisconsin 1 2 0 3
Western Ontario 8 8 723
Vancouver 1 1 5 7
 Total per device25322380

There was no difference in stone surface area between the Cyberwand and LUS-II groups, with a mean (range) of 526.6 (189.0–1488.2) mm2 vs 540.1 (111.5–2085.9) mm2, respectively (P= 0.90). Table 2 summarizes the stone composition for each group. Of the patients with an available stone analysis, the presence of ‘hard stones’ (i.e. calcium oxalate monohydrate, brushite and cystine) was similar between the Cyberwand (14/25; 56.0%) and LUS-II (18/29; 62.1%) groups.

Table 2. Summary of stone composition analysis for both the Cyberwand and the Olympus LUS-II patients
CompositionCyberwandLUS-II
n= 25% n= 32%
  1. There was a similar number of ‘hard stones’ (i.e. calcium oxalate monohydrate, brushite and cystine) in each cohort.

Not performed  0 3 9.4
Available for analysis n= 25  n= 29 
 Calcium oxalate13521344.8
 Calcium phosphate624310.3
 Uric acid416620.7
 Cystine0 413.8
 Struvite141 3.4
 Brushite141 3.4
 Triamterene0 1 3.4

Operatively, there was no difference in the total time to remove the target stone between the Cyberwand and LUS-II groups, with a mean (range) of 15.8 (1.19–61) min vs 14.2 (0.53–44.35) min, respectively (P= 0.70). There was also no difference in clearance rates (stone surface area per total stone removal time) between the Cyberwand and LUS-II groups, with a mean (range) of 61.9 (6.1–222.69) mm2/min vs 75.85 (9.16–551.9) mm2/min, respectively (P= 0.51). The operative results are summarized in Fig. 1. In the Cyberwand group, there were eight device malfunctions that temporarily interrupted the surgical procedure, including four clogged probes and four lithotrite malfunctions (broken probes). In the LUS-II cohort, there were three device malfunctions, including one clogged probe, one broken probe and one equipment failure. No intraoperative complications were reported in either treatment group.

Figure 1.

Comparison of stone surface area, time to remove the targeted stone and clearance rate between patients undergoing PCNL with the Cyberwand compared to the LUS-II.

The mean length of patient hospitalization was similar between the Cyberwand (2.72 days) and LUS-II (2.44 days) groups. In the Cyberwand treatment group, 15 (60.0%) patients were stone-free on postoperative CT scan and 10 (40.0%) went on to undergo a secondary PCNL, resulting in a total stone-free rate of 100%. In the LUS-II group, 20 (62.0%) patients were stone-free after the primary procedure and nine (28.0%) went on to undergo a secondary PCNL, resulting in a stone-free rate of 90%. The number of accesses required is presented in Table 3. Postoperative complications were similar in each group and are summarized in Table 4. No patient in either group required a blood transfusion.

Table 3. Number of accesses required during PCNL
AccessOriginal Cyberwand probes (n= 25)Olympus LUS-II (n= 32)
Type  
 Single21 (84%)30 (94%)
 Double3 (12%)2 (6%)
 Triple1 (4%)0
Location  
 Upper pole7 (28%)10 (31%)
 Mid pole5 (20%)2 (6%)
 Lower pole13 (52%)20 (63%)
Table 4. Summary of postoperative complications among patients treated with either the Cyberwand or the LUS-II lithotrites
ComplicationCyberwandLUS-II
n= 25% n= 32%
Fever0 3 9.4
Hydronephrosis0 1 3.1
Ileus140 
Perinephric haematoma140 
Persistent flank pain140 
Pleural effusion283 9.4
Respiratory difficulty141 3.2
Discharged home with nephrostomy tube416721.9

After completion of enrolment, the Cyberwand manufacturer released a new probe with a reinforced design to improve durability. Specifically, the free mass had been modified to limit device malfunction. Data were collected from 23 patients with the new design utilizing the same study parameters as those for the randomized control trial. There were no device malfunctions with the redesigned probe. The results from the initial randomized clinical trial and the new probe are presented in Table 5.

Table 5. Summary of clearance rates and stone free rates for patients treated with either the original or the newer Cyberwand probes or the Olympus LUS-II lithotrite
VariableCyberwandOlympus LUS-IINew Cyberwand probes
(n= 25)(n= 32)(n= 23)
Surface area (mm2)526.61540.14506.38
Clearance time (min) 15.81 14.17 13.62
Clearance rate (mm2/min) 61.90 75.85 39.33
Stone free rate 15 (60%) 20 (62%) 12 (52%)
Secondary procedure 10 (40%)  9 (28%)  7 (30%)

DISCUSSION

For almost 100 years, intracorporeal lithotripsy has been utilized for the removal of bladder calculi in one form or another; however, it was not until the advent of PCNL that this technology evolved for use on renal calculi [13]. Because of the high complication rate noted with electrohydraulic lithotripsy [14] and the inability of laser and pneumatic lithotripsy to concurrently remove stone fragments, most lithotrites that are currently in use are ultrasonic [15]. Although the ultrasonic lithotripters are excellent for simultaneous fragmentation and removal of must urinary calculi, they are not universally successful, especially in the setting of hard stones, such as cystine, calcium oxalate monohydrate [1–3]. The inability of ultrasound to fragment hard calcium phosphate stones may also account for the lower stone-free rates observed with PCNL when brushite stones are treated [16]. To combat the limitations of ultrasonic lithotripsy, at the same time as retaining its suction stone removal capabilities, dual-probe lithotripters have been developed. Although previous studies have shown excellent clinical results with one dual-probe lithotripter, the Lithoclast Ultra [7], in vitro studies have shown that a newer dual-probe device, the Cyberwand, is almost twofold more rapid with respect to stone fragmentation [10]. We therefore attempted to assess the clinical impact of the Cyberwand dual-probe lithotripter compared to a standard ultrasonic device, the Olympus LUS-II.

In our prospective, multicentre comparison, we noted no significant difference in stone clearance rates between the Cyberwand and LUS-II intracorporeal lithotrites. Although the groups were not specifically matched for such variables, there was no significant difference in stone surface area or the percentage of cystine, calcium oxalate monohydrate and brushite stones in either cohort. Both devices were safe because no intraoperative complications occurred and postoperative complications were similar between each treatment group. Stone-free rates after primary and secondary PCNL were similar between each group.

The lack of any difference in stone clearance between the Cyberwand and LUS II stands in marked contrast to the results reported for in vitro studies [10], emphasizing the importance and need for well designed comparative clinical trials. One possible explanation for the lack of difference in stone clearance between the two devices was the tendency for the Cyberwand probe to plug. In addition, the initial production version of the Cyberwand probe had a tendency to malfunction or break, requiring replacement during the procedure. Finally, the design of the Cyberwand probe provides a significantly smaller diameter of the ultrasound wand lumen than the LUS II, which could affect the efficiency of fragment clearance.

The outcomes of the present study provide conflicting results compared to a clinical study that assessed another dual-probe device, the Lithoclast Ultra [7]. In the Lithoclast Ultra study, the dual-probe device was significantly faster than the LUS-II at total stone clearance time (21.1 vs 43.7 min) and stone clearance rate (39.5 vs 16.8 mm2/min). The authors noted a higher complication rate in the LUS-II treatment rate, although the complications could not be directly related to the device and the stone-free rates were similar in each treatment group. A comparison of the Lithoclast Ultra study with our current Cyberwand study shows that the mean stone clearance times for the Cyberwand and Lithoclast Ultra are similar (16.3 vs 21.1 min, respectively), in contrast to previous in vitro studies, suggesting that the Cyberwand was more efficient [10]. However, stone clearance rates appeared to be lower with the Lithoclast Ultra than the Cyberwand (39.5 vs 61.9 mm2/min, respectively) (Fig. 2). The significant difference between the two studies revolves around the performance of the LUS-II device. In the previous Lithoclast Ultra study, the LUS-II was substantially slower at stone removal, requiring a mean of 43 min compared to 13.5 min in the present study [7]. Furthermore, stone clearance rates were markedly slower for the LUS-II in the Lithoclast Ultra study than in the current study (16.8 vs 75.85 mm2/min).

Figure 2.

Comparison of stone surface area, time to remove the targeted stone and clearance rate among patients undergoing PCNL with the Cyberwand, LUS-II or Lithoclast Ultra. Data for the Cyberwand and LUS-II were obtained in the present study. Data for the Lithoclast Ultra were obtained [7].

Certain limitations of the study should be noted. Because this is a multicentre trial, multiple surgeons were involved and thus subtle differences in the PCNL technique existed between sites. Although the protocol gave specific instructions for stone removal, some surgeons may have defined the stone removal time differently between sites. One surgeon may have defined stone removal as the time to remove only the bulk of the stone, whereas another defined it as time to remove all small crystal fragments. Because each site contributed patients in both study cohorts, these differences in interpretation should not have resulted in significant differences in study group comparisons. Additionally, postoperative stone-free status was determined by CT scan, which is the most sensitive tool for assessing complete stone removal, although it also lacks specificity because intraparenchymal calcifications can be misread as residual stones. For this reason, we combined the results obtained from the postoperative CT and secondary PCNL to assess final stone-free status.

Despite the aforementioned limitations, the data reported in the present study offer a rare clinical analysis of currently available devices. They also highlight certain variables that must be controlled in future instrument comparison studies, such as the definition of stone removal time, methods for stone removal, and the definition of stone-free. Subsequent to the initiation of the present study, other powerful intracorporeal lithotrites have been introduced, including the Cook-LMA Stone Breaker (LMA Urology, Gland, Switzerland), which is a pneumatic device, and the Swiss Lithoclast Select (Boston Scientific, Natick, MA, USA), which is a dual-probe device. To provide urologists with an impartial assessment of the capabilities of these products, they should be compared with other currently available devices.

In conclusion, the Cyberwand combined pneumatic/ultrasonic lithotrite is capable of disintegrating and clearing stone material at a rapid rate. There was no increased rate of operative or postoperative complications in the Cyberwand group compared to the standard single-probe. Furthermore, stone-free outcomes were similar after PCNL using the Cyberwand compared to PCNL using a standard ultrasonic device. However, stone clearance rates obtained with the Cyberwand were not superior to those obtained with standard ultrasonic lithotripsy.

ACKNOWLEDGEMENTS

We would like to thank the Gyrus/ACMI and Olympus Companies for supplying the Cyberwand lithotripsy test equipment to each study site.

CONFLICT OF INTEREST

The authors declare the following associations. Mitchell R. Humphreys is a consultant and advisor to Lumenis. Furthermore, Stephen Y. Nakada is a consultant to Cook. John D. Denstedt is a consultant to both Boston Scientific and Cook. Hassan Razvi has worked in scientific studies and trials with Cook, Allergan and Nerites Corp. Ben H. Chew has declared consultancy work with Boston Scientific, whilst James E. Lingerman has acted as a consultant and advisor to Lumenis and has participated in meetings with them. Furthermore, he has worked similarly with Boston Scientific as a consultant and advisor, and has participated in meetings with them. He has also worked on a scientific study /trial for Olympus.

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