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Contact Nanopulse Lithotripsy
*A. V. Gudkov, *V. S. Boshchenko, **V. Y. Afonin

* - State Educational Institution of Higher Professional Education, Siberian State Medical University of the Federal Agency for Health Care and Social Development (SEI HPE SibSMU of Roszdrav), Urology Department, Tomsk
** - Urology Department of the Medical Sanitary Station No. 2, Tomsk

At present, urolithiasis accounts for an average of 34.2% of all urologic diseases in Russia and ranks in second place among them (N. A. Lopatkin, A. G. Pugachyov, O. I. Apolikhin, 2002, N. K. Dzeranov, K. A. Baybarin, A. V. Kazachenko, 2006) [1, 2]. Urolithiasis frequently leads to complications requiring active intervention. During the last decade, more and more stone removals have been carried out using contact endourological methods, which have made it possible to reduce the time of the procedure, the duration of the post-operative period and also to lower perioperative risk compared to extracorporeal shock wave lithotripsy (ESWL) and open lithotomy [3, 4, 5, 6].
The existing types of lithotripters for contact lithotripsy (CL) are divided into the following groups depending on the type of effect on the calculus: mechanical, electrohydraulic, pneumatic, ultrasound and laser [7, 8, 9, 10]. The laser and electrohydraulic methods [7, 9] are considered the most efficient CL methods. In addition, electrohydraulic and laser lithotripters are equipped with thin flexible probes 0.66 to 0.825 mm in diameter [10], which can be insrted through the operating channels of modern flexible endoscopes to disintegrate stones in all sections of the ureter, pelvis and calyces [8, 11]. However, electrohydraulic lithotripsy (EHL) causes complications more often than the other methods because it requires high shock wave intensity and a large number of pulses to effectively disintegrate stones. In 17.6% of cases it results in ureter perforation [5]. Laser lithotripsy (LasL) is safer, but it is more costly and time-consuming [9]. Pneumatic lithotripsy (PNL) is considered "the gold standard" of safety among the other methods of CLT. However, because of the rigid probes that are large in diameter, pneumatic and ultrasound lithotripsy (USL) have limitations when disintegrating stones in proximal sections of urinary tracts [5].
Thus, there is a need to develop and introduce into clinical practice a CL method that would combine a maximum safety profile with a high efficiency of stone disintegration in any section of the urinary system. Laboratory personnel at the Institute of Strength Physics and Materials Science of Tomsk Scientific Centre SB RAS (Siberian Branch of the Russian Academy of Sciences) have developed a method of nanopulse lithotripsy whose main principle involves transmitting an electric pulse of approximately 102...103 nanoseconds directly to the stone [12].
The purpose of the study was to develop a method of contact nanopulse lithotripsy and to assess its efficacy and safety for patients with uroliths in various locations.

Materials and methods
The study involved 146 patients (average age 4816 years, age range 19-88) with stones in the kidneys, ureteropelvic segment (UPS), ureter or bladder, who had signed the informed consent to participate in the study. The patients were hospitalized either as an emergency admission with renal colic (124 patients (85%)) or as a scheduled admission (22 patients (15%))
All patients were divided into 3 groups depending on the location of their stones. The first group included 10 (7%) patients with UPS stones, the second and the biggest one consisted of 124 (85%) patients with ureteral calculi, and the third had 12 (8%) patients with bladder stones. Study inclusion criteria included the presence of:

- ≤6 mm stone in the ureteropelvic segment or in any ureter section, causing recurrent renal colic and a urodynamic abnormality, whilst nots disturbance, having no tendency to having a tendency toward spontaneous passage whilst the patient is in the setting of in the course of stone-eliminating therapy and/or has undergone an unsuccessful attempt at ureteral lithotripsy and/or ESWL (1-2 procedures).
- >6 mm stone in a kidney, the ureteropelvic segment or any ureter section and causing renal colic and a urodynamic abnormality.
- A long-standing ureter stone of any size, causing no renal colic, but worsening the function of a kidney and impairing urodynamics.
- The presence of "steinstrasse" after extracorporeal shock wave lithotripsy.
- A bladder stone of any size without a tendency toward spontaneous passage.
The structure of the study inclusion criteria for the group I and II patients is outlined in Table 1.
The study did not involve patients with the following conditions:
 Stricture of urinary tracts located more distally than the stone.
 Spinal and pelvis disorders preventing patient positioning in a chair.
 Severe overall condition with respect to the primary illness or concomitant diseases, preventing the procedure or anaesthesia frm being carried out.
The clinical course was uncomplicated in 122 (84%) of the patients included in the study, 24 (16%) had complications of urolithiasis (Table 2). Before nanopulse lithotripsy (NPLT), 79 patients underwent the following remedial measures that proved to be ineffective: 66 (45%) were prescribed stone elimination therapy, 4 (3%) - underwent lithoextraction, 5 (3.5%) - extracorporeal shock wave lithotripsy, 2 (1%) - ureteric catheterisation by a ureter catheter, 2 (1%) - ureter stenting. To control renal colic, 67 patients also underwent further antispasmodic therapy prior to NPLT.
The following procedures were performed for all patients: gathering of complaints, anamnesis; physical assessment; complete urinalysis; complete blood count, blood biochemistry panel, blood coagulation system analysis; bacteriological urine test, ultrasound examination of the kidneys, ureters, and bladder in B-mode, excretory urography, and retrograde pyeloureterography according to indications in the case of nonopaque ureteral calculi.
Contact nanopulse lithotripsy was carried out using the Urolit-105M nanopulse lithotripter (Lithotech Medical, Israel and TRS MedLine, Ltd. (Russian Federation)). Probes with tips 5.4 Fr (1.7 mm) in diameter and 650 mm in length were used for fragmentation of stones in the bladder. A probe with a tip 3.6 Fr (1.1 mm) in diameter and 650-1300 mm in length was used to fragment stones in the ureter. A probe with a tip 1.9 Fr (0.6 mm) in diameter and 650-1300 mm in length was used for fragmentation of stones in the upper sections of the ureter and in the kidney.
Patients were prepared for NPLT according to the general procedure of preparation for endoscopic operations. Disintegration was performed under intravenous, spinal or peridural anaesthesia. After the insrtion of a rigid or flexible ureteropyeloscope (7.5-11.5 Fr) and the detection of a stone, a filter was installed or the concrement was caught into a basket in order to prevent the stone or its fragments frm migrating up the ureter. Then, under direct vision, the lithotripter probe was advanced to the stone through the operating channel of the endoscope in order to bring the working end of the probe into direct contact with the stone. Pulse energy value, frequency and number of pulses were set on the device control panel according to the type of the stone and its size. After the working parameters of the device were set, the pulse generation mode was switched on using a pedal, and stone fragmentation was performed. Destruction of the stone occurred due to the formation of an electric pulse inside the stone when the flexible probe made direct contact with it. The nanopulse lithotripsy of a ureteral calculus was finished by insrting a ureteral catheter or a stent for 2-5 days.
After NPLT, the patients were given follow-up monitoring for 1 month. This made it possible to assess the incidence complications and the quality and length of the post-NPLT recovery period. The patients discharged frm the hospital were interviewed by the phone on the 7th, 14th and 30th day following NPLT. If the patients had any complaints, they were invited to undergo a follow-up examination.
The results of the study were processed by means of standard methods of biological and medical statistics using the STATISTICA for Windows program, version 6.0 (StatSoft Inc., USA). The obtained data was represented in the form of average values and their standard deviations - M. Dichotomous and ordinal qualitative data were expressed as frequencies (n) and ratios (%). The certainty of intergroup differences of mean values was assessed by using Student's t-test, and the certainty of changes in the values was assessed by using the paired t-test. Variance analysis was used for multiple intergroup comparison. The certainty of the property distribution difference was assessed by using a goodness-of-fit test 2, 2 with Yates adjustment and Fisher's exact test. Differences of the values were assessed as valid at the level of p0.05 [13].

Results and discussion
Sizes of concrements in groups I and II are presented in Table 3. In group III the average size of stones was 17.8±9.7 mm (frm 12 to 35 mm). The biggest were concrements in the bladder, the smallest - in the distal end of the ureter.
The average duration of a NPLT procedure was 65±38 minutes. In 144 (98%) cases, NPLT was accompanied by lithoextraction. Fragmentation of concrements in the pelvicalyceal system (PCS) required a significantly lower energy in the pulse than that used for ureter and bladder concrement fragmentation (Table 4). This is probably because the PCS stones in our study had a lower degree of hardness. Energy values in the pulse for NPLT in groups II and III were comparable, however the number of pulses necessary for destruction of concrements in the bladder was reliably higher than in the ureter (9657 vs. 2531, p<0.01). Single or paired pulses were used for fragmentation only in the ureter, whilst serial pulses were used in the bladder. A large number of pulses for NPLT and a high frequency of their repetition in group III were caused primarily by the larger size of the concrements in the bladder (Tables 3, 4). We tried to design the optimal parameters of NPLT for an initial impact on stones localized in different sections of urinary tracts. Thus, fragmentation of concrements in the PCS should be carried out using single pulses starting with a pulse energy of 0.45 J. The fragmentation of concrements in the ureter should be carried out by single or paired pulses of 0.45-0.6 J, and fragmentation in the bladder requires the effect of paired or serial pulses of 0.6-0.7 J pulse energy.
The overall efficacy rate of contact nanopulse fragmentation of concrements in patients suffering frm urolithiasis was 96%. In 92.5% of the cases, full destruction of the concrement was achieved during the first NPLT procedure. This was the case in another 3.5% of cases with repeated NPLT, and fragmentation was partial in just 4% of cases. NPLT proved to be technically feasible for all patients with PCS, ureter and bladder stones. Complete lithotripsy was achieved in 100% of cases when the stone was located in the in the PCS, in 91% of cases when it was in the upper third part of the ureter, and in 100% of cases when it was in the middle third. Previously, it was possible to disintegrate concrements of such localization only by means of EHL, LasL, and partially by PNL and extracorporeal shock wave lithotripsy (ESWL) [14, 15]. According to the data of previously published studies, the stone fragmentation rate in cases whr they were proximally located in the ureter and when other CL methods (jint use of PNL+EHL+LasL) and ESWL methods were used was lower than that achieved by us using NPLT (82% for CL, 75% for ESWL and 91% for NPLT) [16, 17, 18]. This made it possible to rate NPLT as a highly effective method of proximal ureter concrement treatment, with an efficacy rate close to that of LasL (according to different authors, LasL efficacy is 88-97%) [11].
The fragmentation rate of distal ureter stones with the use of NPLT was 95%. This is comparable to the cumulative efficacy of all CL methods in the case of similarly located stones (95% efficacy) [19], and it considerably exceeded ESWL efficacy (78%) [20]. This meant that NPLT could be considered an equally effective method (compared to other CL methods) of distal ureteral calculus treatment. Such an assertion also applies to bladder concrements, which we managed to destroy by means of NPLT in 100% of cases.
Having demonstrated the identical efficacy of NPLT and LasL, we decided to compare the number of pulses necessary for the destruction of a stone using both methods of treatment and, correspondingly, the duration of the procedure and anaesthesia. We set out to do this using our own data and the results of recently published LasL studies [21]. According to Lam J. S. et al., who applied LasL to 106 patients with a varied concrement localization in urinary tracts, the stone was destroyed after 200-500 pulses in 20% of cases, after 500-1500 pulses in 75% of cases, and after > 3000 pulses in 5% of patients [21]. In our study, the average number of 307 pulses was enough for destruction of PCS stones, 7148 pulses for upper, 4017 for middle and 815 for lower thirds of the ureter stones correspondingly, 9657 pulses for bladder stones. The number of pulses did not exceed 150 for any of the patients.
However, the clinical efficacy of the new method does not have an independent significance without its clinical safety. Eleven (8.2%) patients with PCS and ureter calculi suffered frm the following intraoperative complications during NPLT: ureter perforation - 4 (3%), migration of concrement to the kidney - 7 (5.2%) patients.
In our study, ureter perforation was recorded in 2 cases in the upper third of the ureter and in 2 cases in the lower third. All the patients had had a complicated clinical course of urolithiasis (ureteritis), location of the stone in the ureter for 6-9 days before NPLT, and stone size greater than 8 mm. This required prolonged fragmentation and the use of a rigid ureteroscope in an area of edematous, loose ureteric wall, which led to its perforation. In these cases, the initiated endoscopic intervention was stopped, and three of the patients underwent open surgery - ureterolithotomy. In the other case, a stent was placed and the NPLT procedure was subsequently repeated, this time successfully.. The incidence rate of ureter perforation could also have been influenced by our modest amount of experience using NPLT at the initial stage of the research, since the last 40 patients involved in the study did not suffer frm perforation of the ureter.
In 7 cases (5.2%), the concrement migrated to the kidney. Migration of the concrement was more characteristic of the patients in which the stone had a high location: in the upper third of the ureter - 5 patients, in the middle third - 1 patient, and in the lower third - 1 patient. The patients with migrated concrements underwent NPLT and were given active follow-up monitoring of the clinical course of the disease.
In our study, 23 (16%) patients were recorded to have episodes of macrohematuria on the day of NPLT, which in all cases was spontaneously arrested within several hours without haemostatic therapy. We evaluate this phenomenon more as a consequence of endoscopic manipulation rather than a NPLT complication.
No intraoperative complications were recorded in the third group of patients.
The following complications were recorded during the early postoperative period: relapse of renal colic - 15 (10.3%) cases, acute pyelonephritis - 2 (1.4%), exacerbation of chronic pyelonephritis - 8 (5.5%), exacerbation of chronic cystitis - 2 (1.4%), acute retention of urine - 1 (0.7%).
Notwithstanding the fact that nanopulse CL in the majority of cases ended with the removal of all visible stone fragments, spontaneous passage of small concrement segments during the postoperative period was documented in 37 (25.3%) cases. In 24 cases, the passage of fragments occurred spontaneously and required no additional intervention. In 15 (10.3% of all patients) cases, the passage of fragments provoked a relapse of renal colic and required the intervention, either ureteroscopy with lithoextraction (in 8 (5.4%) cases) or repeated NPLT of the concrement fragments (in 7 (4.8%) cases) with subsequent stenting of the ureter. No significant differences were revealed in the postoperative period between group I and II with respect to colic recurrence, however there was a tendency for there to be a more frequent recurrence of symptoms in patients who had an initial location of concrements in the PCS and in the upper third of the ureter.
Acute pyelonephritis developed in two patients during the early postoperative period, which required conservative treatment in one case, and urgent, open operative intervention in another case due to the formation of kidney carbuncles. Therapy for 8 patients with exacerbation of chronic pyelonephritis was conducted using standard remedies whilst monitoring the excretory function of the kidney that had undergone the procedure.
An early postoperative complication in group III was exacerbation of chronic cystitis (2 cases (1.4%)), possibly caused by a greater amount of injury to the bladder mucosa due to the large number of pulses used during NPLT and to the duration of procedure because of the initially large size of the concrements (28 mm and 35 mm, respectively). Patients of group III with exacerbation of chronic cystitis underwent antibacterial and anti-inflammatory therapy.
One (0.7%) patient frm group III experienced acute urinary retention because a large stone fragment became wedged in the neck of the urinary bladder. This required repeated urethroscopy and NPLT of the stone fragment.
No follow-up postoperative complications were registered during one year of observation.
The average time of patients' hospitalization in the groups was frm 11.87.6 (group I) to 8.05.2 (group III) days, which is considerably shorter than after carrying out of an open lithotomy [14, 22]. The proportion of urolithiasis patients discharged frm the hospital on the 3rd day after NPLT was 46%, and on the 5th day - another 30% of patients.
1.Contact nanopulse lithotripsy is an effective method of urinary concrement fragmentation in all sections of the urinary tract, bringing positive results in 96% of cases.
2.Fragmentation of concrements in the PCS should be carried out starting with a pulse energy of 0.45 J in single pulses. The fragmentation of concrements in the ureter should be carried out by using single or paired pulses of 0.45-0.6 J, and fragmentation in the bladder requires the effect of paired or serial pulses of 0.6-0.7 J pulse energy.
3.NPLT is a comparatively safe method of treatment, causing intraoperative complications in 8.2% of cases.
4.The risk of intraoperative complications during NPLT increases when the concrements subjected to fragmentation are more than 8 mm in size or are long-standing ureteral concrements complicated by ureteritis.