ORIGINAL ARTICLE: Clinical Endoscopy
Extracorporeal shock wave lithotripsy for difficult common bile duct stones: a comparison between 2 different lithotripters in a large cohort of patients Paolo Cecinato, MD,1 Lorenzo Fuccio, MD,1 Francesco Azzaroli, MD,1 Andrea Lisotti, MD,1 Loredana Correale, PhD,2 Cesare Hassan, MD,3 Federica Buonfiglioli, MD,1 Giulio Cariani, MD,1 Giuseppe Mazzella, MD,1 Franco Bazzoli, MD,1 Rosangela Muratori, MD1 Bologna, Turin, Rome, Italy
Background: Extracorporeal shock wave lithotripsy (ESWL) for difficult common bile duct (CBD) stones is a safe and effective treatment strategy allowing for bile duct clearance in approximately 90% of patients with a low incidence of mild adverse events. Objective: To compare the CBD clearance rates achieved after ESWL performed with 2 different lithotripters (Siemens Lithostar Plus and Storz Modulith SLX-F2) in a large cohort of patients with difficult CBD stones. Design: A retrospective analysis of a prospectively collected database. Setting: Tertiary care center. Patients: All of the consecutive patients who underwent ESWL because of difficult CBD stones between 1990 and 2012 were considered suitable for inclusion. Interventions: ESWL with Lithostar Plus or with Modulith SLX-F2. Main Outcome Measurements: CBD clearance. Results: Three hundred ninety-two patients with difficult CBD stones were treated; 199 patients were treated with the Lithostar Plus and 193 patients with the Modulith SLX-F2. CBD clearance was achieved in 349 patients (89.0%) with no significant difference between the patients treated with Lithostar Plus and those treated with Modulith SLX-F2 (90.5% vs 87.6%; P Z .45). Patients treated with Modulith SLX-F2 underwent a significantly lower number of ESWL sessions (3 [range, 2 to 4] vs 3 [range, 2 to 4]; P Z .0015), had a lower incidence of ESWLrelated adverse events (5.2% vs 13.6%; P Z .009), and never required opioid analgesia (P ! .001). Limitations: Retrospective design. Conclusions: The Modulith SLX-F2 allows the same clearance rate as the Lithostar Plus but has a significantly lower incidence of adverse events and requires fewer ESWL sessions. (Gastrointest Endosc 2015;81:402-9.)
Common bile duct (CBD) stones are routinely managed using ERCP with endoscopic sphincterotomy, followed by stone extraction using balloon catheterization or a Dormia basket.1-6 The main reasons for unsuccessful endoscopic
clearance of CBD stones are size (O15-mm diameter), the shape and number of stones, location proximal to a narrow duct, impacted stones, or difficult anatomy of the biliary tree.7,8 In difficult cases, alternative techniques can
Abbreviations: CBD, common bile duct; ESWL, extracorporeal shock wave lithotripsy.
Currrent affiliations: Gastroenterology Unit, Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy (1), Im3D Medical Imaging Lab, Turin, Italy (2), Department of Gastroenterology and Digestive Endoscopy, Nuovo Regina Margherita Hospital, Rome, Italy (3).
DISCLOSURE: All authors disclosed no financial relationships relevant to this publication. Copyright ª 2015 by the American Society for Gastrointestinal Endoscopy 0016-5107/$36.00 http://dx.doi.org/10.1016/j.gie.2014.04.059
Reprint requests: Rosangela Muratori, MD, Gastroenterology Unit, Department of Medical and Surgical Sciences, S. Orsola-Malpighi University Hospital, 40138 Bologna, Italy.
Received September 6, 2013. Accepted April 29, 2014.
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be used to avoid surgery. Alternative treatments include mechanical lithotripsy, large balloon dilation with or without sphincterotomy,6,9 electrohydraulic and laser lithotripsy, biliary stenting, and extracorporeal shock wave lithotripsy (ESWL).6,10,11 ESWL uses electrohydraulic or electromagnetic energy to fragment CBD calculi. In 1989, the first case series of biliary stone clearance achieved with ESWL was reported.12 The first lithotripter models (ie, Dornier HM3; Dornier Medtech, Wessling, Germany) used electrohydraulic energy and required general anesthesia, with the patient placed in a prone position, and water immersion. High clearance rates were reported, but the model was abandoned once other models were available. Several technical improvements were implemented, such as the use of different principles of shock wave generation (ie, electromagnetic coils in combination with an acoustic lens or spherically aligned piezoelectric elements), a larger aperture to ameliorate the focus size, a water cushion instead of water immersion, and the possibility of using US as a localization system. Between 1990 and 1992, several models were commercialized (ie, Modulith SL 20 by Storz Medical AG [Tägerwillen, Switzerland] and Lithostar Plus by Siemens Co [Erlagen, Germany]) with a wider range of energy (peak pressure), a larger aperture of the focusing system, and the integration of the shock wave source. In recent years, newer models (ie, Modulith SLX-F2 by Storz Medical AG, Compact Delta by Dornier Medtech [Wessling, Germany]) with additional improvements have been proposed. The fluoroscopic localization system has been improved by a high-quality digitized x-ray imaging system mounted on an adjustable C-arm with a preferably isocentrically integrated shock wave; this is called “in-line fluoroscopy,” which can provide several advantages over craniocaudal projections in minimizing localization errors because of the respiratory movement and provides a lateral projection. These newer models have the advantage of higher shock wave focal pressure and a different focus size system (ie, dual in Modulith SLX-F2 or triple in Richard Wolf Piezolith 3000; Richard Wolf, Knittlingen, Germany), which enables the operator to adapt the shock wave parameters for specific anatomic conditions and different stone positions.13 To date, almost all published studies comparing different models of lithotripters have focused on the clearance rates of urologic stones, and studies comparing the efficacy of different lithotripters in the management of biliary stones are lacking.14-24 The aim of our study was to compare the CBD clearance rates achieved after ESWL performed with 2 different models of electromagnetic lithotripters in a large cohort of patients with difficult CBD stones.
ESWL for difficult CBD stones
underwent ESWL for bile duct stones at S. OrsolaMalpighi Hospital (Bologna, Italy) between October 1990 and December 2012 were considered. Only patients with difficult CBD stones, which were defined as stones that cannot be extracted by ERCP with sphincterotomy, Dormia basket, and/or balloon catheter, were included in the analysis. Patients with only intrahepatic stones or patients without previous endoscopic attempts of stone extraction were excluded (Fig. 1). For all patients, the following data were collected: age, gender, number and size of the stones (in the case of multiple stones, the size of the biggest stone was recorded), number of ESWL sessions performed, number of shock waves administered per session, type of targeting used, number of ERCPs required to achieve CBD clearance, clinical outcome, stone fragmentation achievement, type of anesthesia, sedation or analgesia administered during and after the procedure, and the adverse events related to the procedure. All patients provided written informed consent for the ESWL procedure. This retrospective study was approved by our Institutional Review Board and by the Ethics Committee.
Outcomes The primary outcome of the study was CBD clearance, which was evaluated by imaging techniques (radiology and US). The secondary outcomes were the stone fragmentation rate, the number of ESWL sessions, the number of shock waves administered in each session and total hits per patient, the number of endoscopic sessions (ERCPs) required to achieve bile duct clearance, the incidence of adverse events, and the need for sedation or postprocedural analgesia.
ESWL procedure
This study was a retrospective analysis of a prospectively collected database. All consecutive patients who
From October 1990 to April 2005 all procedures were performed using a Lithostar Plus (Siemens Co), whereas from May 2005 to December 2012, all procedures were performed using a Modulith SLX- F2 (Storz Medical AG). The Lithostar Plus is an electromagnetic lithotripter with an ellipsoid aperture of 125 mm, a focal distance of 14 cm, a focal zone of 12 130 to 13 146 mm, and a focal pressure of 15 to 70 MPa.25 The Modulith SLX-F2 is a mobile lithotripter with an electromagnetic cylindrical source. The dual-focus system of this model allows the focal size (precise focus: 6 28 mm, 2.5 to 150 MPa; extended focus: 9 50 mm, 2.5 to 90 MPa) to be adapted to specific anatomic conditions. The shock wave field can be adjusted for various stone sizes and positions. In addition, the location system, with the combination of “in-line fluoroscopy” and “in-line US,” allows for maximum targeting accuracy.26 In our experience, considering the anatomic morphology of the CBD, precise focus was always used. Both lithotripters offered
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METHODS
ESWL for difficult CBD stones
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Figure 1. Study flowchart. ESWL, extracorporeal shock wave lithotripsy.
the possibility of targeting stones with fluoroscopy or US. Stone targeting was performed using an injection of contrast medium via a nasobiliary drainage tube, which was previously placed during an ERCP procedure or with US guidance. All stone sizes throughout the study were measured during the ERCP procedures, correcting for geometric magnification using the tip of the endoscope as the reference for adjusting the measurements. The patients fasted for at least 12 hours before the ESWL treatment and were monitored with pulse oximetry during the procedure. A continuous electrocardiogram was performed in the patients with known cardiac disease or arrhythmias. During the ESWL session, the patients typically maintained a prone position. Routine laboratory tests were performed 6 and 24 hours after the procedure. The time interval between multiple ESWL sessions was at least 24 hours. Only patients with cholangitis and patients with associated intrahepatic stones were treated with antibiotic therapy. Analgesia with opioids (pethidine and fentanyl) and nonsteroidal anti-inflammatory drugs (ketorolac) and sedation with benzodiazepines (midazolam) were used as needed during the procedures. None of the patients received general or epidural anesthesia. Pregnancy and severe irreversible coagulopathy were considered absolute contraindications. Liver cirrhosis, portal hypertension, history or presence of cardiac arrhythmia, pancreatitis, thrombosis, abdominal aortic aneurysm, renal failure, giant liver hemangioma, gut or lung interposition, and voluminous abdominal fluid cysts were considered relative contraindications. 404 GASTROINTESTINAL ENDOSCOPY Volume 81, No. 2 : 2015
Definitions Difficult CBD stones were defined as stones that could not be extracted by ERCP with sphincterotomy, Dormia basket, and/or balloon catheter. Stone fragmentation was defined as the rupture of stones because of ESWL treatment, as fluoroscopically documented. CBD clearance was defined as complete stone removal after ESWL sessions, with or without the need for endoscopic stone extraction, as documented by imaging techniques. Spontaneous bile duct clearance was defined as complete stone removal after ESWL sessions without the need for stone extraction, as documented by imaging techniques. Patients who did not achieve CBD clearance after ESWL and endoscopic extraction attempts were considered treatment failures.
Statistical analysis The categorical variables were summarized in terms of the numbers and percentages and were compared using the 2-sided Fisher exact test or the c2 test as appropriate. Continuous data were tested for normal distribution using the Kolmogorov-Smirnov test. Normally distributed variables were presented, when appropriate, as the mean standard deviation and were compared using a t test or presented as the median and interquartile range, and the Mann-Whitney test was used. A logistic regression analysis was used to evaluate the factors affecting the outcome of ESWL. A 2-sided value of P ! .05 was considered significant. Statistical analyses were performed using the MedCalc package v.11.5 for Windows (MedCalc, Ostend, Belgium). www.giejournal.org
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ESWL for difficult CBD stones
TABLE 1. Patient and CBD stone characteristics
Characteristics
Total (n [ 392)
Lithostar Plus (n [ 199)
Modulith SLX-F2 (n [ 193)
P
Age, y, median (IQR)
76 (69-82)
76 (72-82)
76 (66-82)
.09
Single
163 (41.6%)
91 (45.7%)
72 (37.3%)
.11
Multiple
229 (58.4%)
108 (54.3%)
121 (62.7%)
.11
2.0 (1.5-2.5)
2.0 (1.7-2.5)
2.0 (1.5-2.5)
.25
!2 cm
258 (65.8%)
131 (65.8%)
127 (65.8%)
.92
!3 cm
362 (92.3%)
186 (93.5%)
176 (91.2%)
.45
R3 cm
30 (7.7%)
13 (6.5%)
17 (8.8%)
.45
21 (5.4%)
6 (3.0%)
15 (7.7%)
.04
Number of stones
Stone diameter, median (IQR)
Concomitant intrahepatic stones CBD, Common bile duct; IQR, interquartile range.
RESULTS Patients Between 1990 and 2012, 416 patients underwent ESWL at S. Orsola-Malpighi Hospital (Bologna, Italy). Of these patients, 392 (180 men; median age 76; interquartile range, 69 to 82) were included in the study after applying the selection criteria. Nine patients were excluded because they had only intrahepatic stones, and 15 patients were excluded because endoscopic removal was not attempted before ESWL. Of these cases, the targeting was performed without a nasobiliary tube but with US guidance in 3 cases, with percutaneous transhepatic cholangiogram in 9 cases, and with a Kehr tube in 3 cases. One hundred ninety-nine patients underwent ESWL using the Lithostar Plus, and 193 patients underwent ESWL using the Modulith SLX-F2. A single stone was reported in 163 patients (41.6%), and 229 patients (58.4%) had multiple biliary stones. The median diameter of the stones was 2.0 cm (interquartile range, 1.5 to 2.5). No differences according to the age, gender, or type of CBD stones were detected between the 2 treatment groups. The baseline characteristics of the entire study population and according to the lithotripter used for ESWL are reported in Table 1.
after ESWL and 324 (92.8%) needed 1 or more ERCPs to achieve bile duct clearance (Table 2). The median number of ERCPs after lithotripsy was 1 (interquartile range, 1 to 1). The clearance rates between the treatment groups (Lithostar Plus vs Modulith SLX-F2) were not significantly different (90.5% vs 87.6%; P Z .45). Forty-three patients (11%) were considered treatment failures; in 21 patients (5.4%) a surgical approach was necessary, 12 patients (3.1%) were treated with biliary stenting because they were unfit for surgery, and 10 patients (2.5%) suspended treatment because of a lack of compliance or tolerance, and they refused any other treatments. The multivariate analysis did not identify any factors influencing the CBD clearance. Age, gender, single or multiple stones, stone diameter, number of ESWL sessions, number of shock waves administered, and type of lithotripter used were not independently related to the CBD clearance.
ESWL sessions
CBD clearance was achieved in 349 patients (89.0%). Of these patients, 25 (7.2%) obtained spontaneous clearance
A total of 1290 ESWL sessions was performed in 392 patients. Of the study population, 48 patients (12.2%) required 1 session, 85 patients (21.7%) required 2 sessions, 103 patients (26.3%) required 3 sessions, and 81 patients (20.7%) required 4 sessions. Seventy-five patients (19.1%) required 5 or more ESWL sessions. A median of 3500 shocks (range, 2918 to 4000) was administered in each ESWL session; a median of 10,350 shock waves (range, 6500 to 14,950) was administered per patient. The comparisons between the 2 study groups are shown in Table 3. Patients treated with the Modulith SLX-F2 underwent significantly fewer ESWL sessions (3 [range, 2 to 4] vs 3 [range, 2 to 4]; P Z .0015) and required a lower number of total shock waves (9437 [range, 6075 to 12,650] vs 11,000 [range, 6770 to
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Stone fragmentation rate Stone fragmentation (Fig. 2) was achieved in 378 patients (96.4%) but not in 14 patients (3.6%). No differences were observed between the Lithostar Plus and the Modulith SLX-F2 treatment groups (95.5% vs 97.4%; P Z .42).
CBD clearance
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Figure 2. Multiple difficult CBD before (a) and after (b) ESWL sessions. Complete fragmentation of the stones was achieved. CBD, common bile duct; ESWL, extracorporeal shock wave lithotripsy.
TABLE 2. Outcomes
Outcome
Total (n [ 392)
Lithostar Plus (n [ 199)
Modulith SLX-F2 (n [ 193)
P
Stone fragmentation rate
378 (96.4%)
190 (95.5%)
188 (97.4%)
.42
CBD clearance
349 (89.0%)
180 (90.5%)
169 (87.6%)
.45
25 (7.2%)
8 (4.4%)
17 (10.1%)
.06
324 (92.8%)
172 (95.6%)
152 (89.9%)
.06
43 (11.0%)
19 (9.5%)
24 (12.4%)
.42
Surgery
21 (5.4%)
12 (6.0%)
9 (4.7%)
.65
Stenting
12 (3.1%)
2 (1.0%)
10 (5.2%)
.035
Discontinued
10 (2.5%)
5 (2.5%)
5 (2.6%)
.79
1 (1-1)
1 (1-1)
1 (1-1)
Opioid
70 (17.8%)
70 (35.2%)
0
!.0001
NSAIDs
21 (5.3%)
12 (6.0%)
9 (4.7%)
.84
2 (.5%)
0
2 (1.0%)
.43
37 (9.4%)
27 (13.6%)
10 (5.2%)
.009
Spontaneous After ERCP Treatment failure
No. post-ESWL ERCP (IQR) Medication
Benzodiazepine Side effects ESWL-related adverse events
CBD, Common bile duct; ESWL, extracorporeal shock wave lithotripsy; NSAIDs, nonsteroidal anti-inflammatory drugs.
15,500]; P Z .03). Patients treated with the Modulith SLXF2 received a lower number of shock waves per session compared with the patients treated with the Lithostar Plus, but the difference was not statistically significant: 3416 (range, 2937 to 3800) versus 3540 (range, 2737 to 4000) (P Z .062). The details regarding the ESWL procedures of the patients who achieved CBD clearance are summarized in Table 4. The mean number of sessions required to achieve CBD clearance was 3 (range, 2 to 4). Patients who achieved
CBD clearance and were treated with the Modulith SLX-F2 needed a significantly lower number of ESWL sessions (3 [range, 2 to 4] vs 3 [range, 2 to 4]; P Z .0004). Of the entire study population, independent of the type of lithotripter used, the percentage of CBD clearance after a single ESWL session was 11.7% (41 of 349 patients), and it increased to 34.1% (119/349) and 61.6% (215/349) after 2 and 3 sessions, respectively. The CBD clearance rate achieved with %3 ESWL sessions was 51.7% (93/180) when patients were treated with the Lithostar Plus, and
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ESWL for difficult CBD stones
TABLE 3. ESWL procedure details Total (n [ 392)
Lithostar Plus (n [ 199)
Modulith SLX-F2 (n [ 193)
P
3 (2-4)
3 (2-4)
3 (2-4)
.0015
1
48 (12.2%)
27 (13.6%)
21 (10.9%)
2
85 (21.7%)
27 (13.6%)
58 (30.0%)
3
103 (26.3%)
47 (23.6%)
56 (29.0%)
4
81 (20.7%)
51 (25.6%)
30 (15.5%)
5þ
75 (19.1%)
47 (23.6%)
28 (14.6%)
3500 (2918-4000)
3540 (2737-4000)
3416 (2937-3800)
.062
10,350 (6500-14,950)
11,000 (6770-15,500)
9437 (6075-12,650)
.03
Total (n [ 349)
Lithostar Plus (n [ 180)
Modulith SLX-F2 (n [ 169)
P
3 (2-4)
3 (2-4)
3 (2-4)
.0004
1
41 (11.7%)
24 (13.3%)
17 (10.1%)
2
78 (22.3%)
23 (12.8%)
55 (32.5%)
3
96 (27.5%)
46 (25.6%)
50 (29.6%)
4
76 (21.8%)
47 (26.1%)
29 (17.2%)
5þ
58 (16.7%)
40 (22.2%)
18 (10.6%)
3500 (2908-4000)
3600 (2774-4000)
3360 (2925-3808)
.03
10,000 (6500-14,500)
11,000 (7000-15,500)
9000 (6000-12,312)
.08
ESWL No. of sessions, median (IQR)
No. of shock waves (per session), median (IQR) No. of total shock waves (per patientt), median (IQR)
ESWL, Extracorporeal shock wave lithotripsy; IQR, interquartile range.
TABLE 4. ESWL procedure details of patients who achieved CBD clearance
ESWL No. of sessions, median (IQR)
No. of shock waves (per session), median (IQR) No. of total shock waves (per patient), median (IQR)
ESWL, Extracorporeal shock wave lithotripsy; CBD, common bile duct; IQR, interquartile range.
the clearance rate significantly increased to 72.2% (122/169) when the Modulith SLX-F2 was used (P Z .0001).
The ESWL-related adverse events are reported in Table 2. Thirty-seven patients (9.4%) experienced side effects. Of these patients, 27 (13.6%) were treated with the Lithostar Plus and 10 (5.2%) with the Modulith SLX-F2.
In the Lithostar Plus group, 3 patients reported vomiting, 9 patients had transient palpitations because of benign symptomatic premature ventricular complexes, and 13 patients had bradycardia, which spontaneously resolved after temporary treatment suspension in 11 patients but deferral of the ESWL session was needed in 2 cases. One case of hemobilia and 1 case of lower GI bleeding were reported in the Lithostar Plus group; neither patient required a blood transfusion or specific treatments. In the Modulith SLX-F2 group, 10 patients (5.2%) reported mild, self-limiting ESWL-related adverse events (6 cases of periprocedural nausea and 4 cases of asymptomatic bradycardia, which resolved after treatment suspension). The comparison between the 2 groups demonstrated a significantly lower incidence of ESWLrelated adverse events in the Modulith SLX-F2 group (5.2% vs 13.6%; P Z .009).
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Anesthesia, analgesia, and sedation Of the entire study population, no patients received anesthesia (general nor epidural). Seventy patients (17.8%) needed an opioid injection, 21 patients (5.3%) needed nonsteroidal anti-inflammatory drugs, and 2 patients (.5%) were sedated with benzodiazepines. Opioid analgesia was not required in any patients treated with the Modulith SLX-F2 (P ! .0001). The details are provided in Table 2.
Adverse events
ESWL for difficult CBD stones
DISCUSSION Our study, which involved the largest cohort of patients ever reported, demonstrated that ESWL can achieve clearance of difficult CBD stones in approximately 90% of cases and has a low rate of adverse events (9.4%), which were mostly minor, self-limiting adverse events. The main finding of our study was that using the Modulith SLX-F2 for ESWL allowed for the clearance of difficult CBD stones at the same rate as the Lithostar Plus, but the Modulith SLX-F2 had significantly lower numbers of ESWL sessions and total shock waves. The incidence of ESWL-related adverse events was significantly lower in patients who underwent ESWL with the Modulith SLX-F2 compared with patients treated with the Lithostar Plus. The different outcomes observed could be ascribed to several different technical characteristics of the 2 lithotripters. The smaller focus size of the “precise focus” and “inline fluoroscopy” of the Modulith SLX-F2 allow for better centering and for adaptations to difficult anatomic conditions (ie, obesity, postural pain) and to respiratory movements. These advantages lead to less dissipation of the shock waves and less damage to surrounding tissues and could explain the significantly lower incidence of adverse events and the better tolerability observed. The Modulith SLX-F2 administers a higher focal pressure (150 vs 70 MPa), which with a smaller focal area (6 28 mm vs 13 146 mm) could account for the significantly lower number of sessions and shock waves needed to achieve complete fragmentation of the CBD stones. Although a cost analysis was beyond the aim of our study, the use of the Modulith SLX-F2 should reduce the management cost of patients with difficult CBD stones because of the significant overall reduction in the number of sessions needed to achieve CBD clearance. Similar to our study, one of the largest prospective, noncomparative studies achieved a clearance rate of 84.4% in 283 patients with difficult CBD stones using a Dornier machine (Compact Delta; Dornier Medtech), with a mean of 2.8 sessions per patient; mostly mild and self-limiting adverse events were reported in 15.9% of patients.23 The low number of sessions required to achieve CBD clearance and the high adverse event rate reported by Tandan et al23 might be because of the use of epidural anesthesia during the ESWL sessions. ESWL is generally a safe and well-tolerated procedure, but serious adverse events, such as necrotizing pancreatitis, cholangitis, perirenal hematoma, bowel perforation, splenic rupture, and death, have been described.10,27,28 In our series, we showed that the implementation of technical improvements (ie, location system and focusing) achieved with the latest generation of lithotripters further reduced the incidence of adverse events, particularly the incidence of serious adverse events.
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Our study had several limitations. Though it was based on a prospectively collected database, our study design was retrospective. The most obvious potential study flaw is the historical bias; we tested the bias by comparing the first 30 patients treated with each lithotripter with the last 30 patients. The comparison did not show any significant differences, and we could exclude any learning curve effect on the final outcome (CBD clearance with Lithostar Plus: first 30 cases vs last 30 cases: 90% vs 96%, respectively [P Z .67]; CBD clearance with Modulith SLX-F2: first 30 cases vs last 30 cases: 80% vs 90%, respectively [P Z .47]). The introduction of new techniques for stone extraction, such as large balloon dilation, during the course of the study might be an additional confounding factor, but in our division, all patients with difficult bile duct stones are routinely managed with the placement of a nasobiliary tube and ESWL. Alternative methods, such as mechanical lithotripsy and large balloon dilation, are considered only in patients in whom the placement of a nasobiliary tube is not feasible, is contraindicated, or is not tolerated. The study was not powered to detect rare severe adverse events, so no conclusions can be drawn regarding this issue. ESWL for difficult CBD stones is a safe and effective treatment strategy that allows for bile duct clearance in approximately 90% of patients and has a low incidence of mild adverse events. The Modulith SLX-F2 had the same clearance rate as the Lithostar Plus, but the Modulith SLX-F2 has a significantly lower incidence of side effects and requires fewer ESWL sessions.
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10. Williams EJ, Green J, Beckingham I, et al. Guidelines on the management of common bile duct stones (CBDS). Gut 2008;57:1004-21. 11. Binmoeller KF, Brückner M, Thonke F, et al. Treatment of difficult bile duct stones using mechanical, electrohydraulic and extracorporeal shock wave lithotripsy. Endoscopy 1993;25:201-6. 12. Sauerbruch T, Stern M. Fragmentation of bile duct stones by extracorporeal shock waves. A new approach to biliary calculi after failure of routine endoscopic measures. Gastroenterology 1989;96:146-52. 13. Rassweiler JJ, Tailly GG, Chaussy C. Progress in lithotripter technology. EAU Update Ser 2005;3:17-36. 14. den Toom R, Nijs HG, van Blankenstein M, et al. Extracorporeal shock wave treatment of common bile duct stones: experience with two different lithotriptors at a single institution. Br J Surg 1991;78:809-13. 15. Testoni PA, Lella F, Masci E, et al. Combined endoscopic and extracorporeal shock-wave treatment in difficult bile duct stones: early and long-term results. Ital J Gastroenterol 1994;26:294-8. 16. Adamek HE, Maier M, Jakobs R, et al. Management of retained bile duct stones: a prospective open trial comparing extracorporeal and intracorporeal lithotripsy. Gastrointest Endosc 1996;44:40-7. 17. Meyenberger C, Meierhofer U, Michel-Harder C, et al. Long-term follow-up after treatment of common bile duct stones by extracorporeal shock-wave lithotripsy. Endoscopy 1996;28:411-7. 18. Jakobs R, Adamek HE, Maier M, et al. Fluoroscopically guided laser lithotripsy versus extracorporeal shock wave lithotripsy for retained bile duct stones: a prospective randomised study. Gut 1997;40:678-82. 19. Neuhaus H, Zillinger C, Born P, et al. Randomized study of intracorporeal laser lithotripsy versus extracorporeal shock-wave lithotripsy for difficult bile duct stones. Gastrointest Endosc 1998;47:327-34.
20. Ellis RD, Jenkins AP, Thompson RP, et al. Clearance of refractory bile duct stones with extracorporeal shockwave lithotripsy. Gut 2000;47: 728-31. 21. Sackmann M, Holl J, Sauter GH, et al. Extracorporeal shock wave lithotripsy for clearance of bile duct stones resistant to endoscopic extraction. Gastrointest Endosc 2001;53:27-32. 22. Conigliaro R, Camellini L, Zuliani CG, et al. Clearance of irretrievable bile duct and pancreatic duct stones by extracorporeal shockwave lithotripsy, using a transportable device: effectiveness and medium-term results. J Clin Gastroenterol 2006;40:213-9. 23. Tandan M, Reddy DN, Santosh D, et al. Extracorporeal shock wave lithotripsy of large difficult common bile duct stones: efficacy and analysis of factors that favor stone fragmentation. J Gastroenterol Hepatol 2009;24:1370-4. 24. Muratori R, Azzaroli F, Buonfiglioli F, et al. ESWL for difficult bile duct stones: a 15-year single centre experience. World J Gastroenterol 2010;16:4159-63. 25. Folberth W. A universal lithotripter for interdisciplinary use: the Siemens “Lithostar Plus.” Scand J Urol Nephrol 1989;122(suppl):86-94. 26. De Sio M, Autorino R, Quarto G, et al. A new transportable shockwave lithotripsy machine for managing urinary stones: a singlecentre experience with a dual-focus lithotripter. BJU Int 2007;100: 1137-41. 27. Karakayali F, Sevmis¸ S, Ayvaz I, et al. Acute necrotizing pancreatitis as a rare complication of extracorporeal shock wave lithotripsy. Int J Urol 2006;13:613-5. 28. Leifsson BG, Borgström A, Ahlgren G. Splenic rupture following ESWL for a pancreatic duct calculus. Dig Surg 2001;18:229-30.
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Extracorporeal shock wave lithotripsy for difficult common bile duct stones: a comparison between 2 different lithotripters in a large cohort of patients Paolo Cecinato, MD,1 Lorenzo Fuccio, MD,1 Francesco Azzaroli, MD,1 Andrea Lisotti, MD,1 Loredana Correale, PhD,2 Cesare Hassan, MD,3 Federica Buonfiglioli, MD,1 Giulio Cariani, MD,1 Giuseppe Mazzella, MD,1 Franco Bazzoli, MD,1 Rosangela Muratori, MD1 Bologna, Turin, Rome, Italy
Background: Extracorporeal shock wave lithotripsy (ESWL) for difficult common bile duct (CBD) stones is a safe and effective treatment strategy allowing for bile duct clearance in approximately 90% of patients with a low incidence of mild adverse events. Objective: To compare the CBD clearance rates achieved after ESWL performed with 2 different lithotripters (Siemens Lithostar Plus and Storz Modulith SLX-F2) in a large cohort of patients with difficult CBD stones. Design: A retrospective analysis of a prospectively collected database. Setting: Tertiary care center. Patients: All of the consecutive patients who underwent ESWL because of difficult CBD stones between 1990 and 2012 were considered suitable for inclusion. Interventions: ESWL with Lithostar Plus or with Modulith SLX-F2. Main Outcome Measurements: CBD clearance. Results: Three hundred ninety-two patients with difficult CBD stones were treated; 199 patients were treated with the Lithostar Plus and 193 patients with the Modulith SLX-F2. CBD clearance was achieved in 349 patients (89.0%) with no significant difference between the patients treated with Lithostar Plus and those treated with Modulith SLX-F2 (90.5% vs 87.6%; P Z .45). Patients treated with Modulith SLX-F2 underwent a significantly lower number of ESWL sessions (3 [range, 2 to 4] vs 3 [range, 2 to 4]; P Z .0015), had a lower incidence of ESWLrelated adverse events (5.2% vs 13.6%; P Z .009), and never required opioid analgesia (P ! .001). Limitations: Retrospective design. Conclusions: The Modulith SLX-F2 allows the same clearance rate as the Lithostar Plus but has a significantly lower incidence of adverse events and requires fewer ESWL sessions. (Gastrointest Endosc 2015;81:402-9.)
Common bile duct (CBD) stones are routinely managed using ERCP with endoscopic sphincterotomy, followed by stone extraction using balloon catheterization or a Dormia basket.1-6 The main reasons for unsuccessful endoscopic
clearance of CBD stones are size (O15-mm diameter), the shape and number of stones, location proximal to a narrow duct, impacted stones, or difficult anatomy of the biliary tree.7,8 In difficult cases, alternative techniques can
Abbreviations: CBD, common bile duct; ESWL, extracorporeal shock wave lithotripsy.
Currrent affiliations: Gastroenterology Unit, Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy (1), Im3D Medical Imaging Lab, Turin, Italy (2), Department of Gastroenterology and Digestive Endoscopy, Nuovo Regina Margherita Hospital, Rome, Italy (3).
DISCLOSURE: All authors disclosed no financial relationships relevant to this publication. Copyright ª 2015 by the American Society for Gastrointestinal Endoscopy 0016-5107/$36.00 http://dx.doi.org/10.1016/j.gie.2014.04.059
Reprint requests: Rosangela Muratori, MD, Gastroenterology Unit, Department of Medical and Surgical Sciences, S. Orsola-Malpighi University Hospital, 40138 Bologna, Italy.
Received September 6, 2013. Accepted April 29, 2014.
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be used to avoid surgery. Alternative treatments include mechanical lithotripsy, large balloon dilation with or without sphincterotomy,6,9 electrohydraulic and laser lithotripsy, biliary stenting, and extracorporeal shock wave lithotripsy (ESWL).6,10,11 ESWL uses electrohydraulic or electromagnetic energy to fragment CBD calculi. In 1989, the first case series of biliary stone clearance achieved with ESWL was reported.12 The first lithotripter models (ie, Dornier HM3; Dornier Medtech, Wessling, Germany) used electrohydraulic energy and required general anesthesia, with the patient placed in a prone position, and water immersion. High clearance rates were reported, but the model was abandoned once other models were available. Several technical improvements were implemented, such as the use of different principles of shock wave generation (ie, electromagnetic coils in combination with an acoustic lens or spherically aligned piezoelectric elements), a larger aperture to ameliorate the focus size, a water cushion instead of water immersion, and the possibility of using US as a localization system. Between 1990 and 1992, several models were commercialized (ie, Modulith SL 20 by Storz Medical AG [Tägerwillen, Switzerland] and Lithostar Plus by Siemens Co [Erlagen, Germany]) with a wider range of energy (peak pressure), a larger aperture of the focusing system, and the integration of the shock wave source. In recent years, newer models (ie, Modulith SLX-F2 by Storz Medical AG, Compact Delta by Dornier Medtech [Wessling, Germany]) with additional improvements have been proposed. The fluoroscopic localization system has been improved by a high-quality digitized x-ray imaging system mounted on an adjustable C-arm with a preferably isocentrically integrated shock wave; this is called “in-line fluoroscopy,” which can provide several advantages over craniocaudal projections in minimizing localization errors because of the respiratory movement and provides a lateral projection. These newer models have the advantage of higher shock wave focal pressure and a different focus size system (ie, dual in Modulith SLX-F2 or triple in Richard Wolf Piezolith 3000; Richard Wolf, Knittlingen, Germany), which enables the operator to adapt the shock wave parameters for specific anatomic conditions and different stone positions.13 To date, almost all published studies comparing different models of lithotripters have focused on the clearance rates of urologic stones, and studies comparing the efficacy of different lithotripters in the management of biliary stones are lacking.14-24 The aim of our study was to compare the CBD clearance rates achieved after ESWL performed with 2 different models of electromagnetic lithotripters in a large cohort of patients with difficult CBD stones.
ESWL for difficult CBD stones
underwent ESWL for bile duct stones at S. OrsolaMalpighi Hospital (Bologna, Italy) between October 1990 and December 2012 were considered. Only patients with difficult CBD stones, which were defined as stones that cannot be extracted by ERCP with sphincterotomy, Dormia basket, and/or balloon catheter, were included in the analysis. Patients with only intrahepatic stones or patients without previous endoscopic attempts of stone extraction were excluded (Fig. 1). For all patients, the following data were collected: age, gender, number and size of the stones (in the case of multiple stones, the size of the biggest stone was recorded), number of ESWL sessions performed, number of shock waves administered per session, type of targeting used, number of ERCPs required to achieve CBD clearance, clinical outcome, stone fragmentation achievement, type of anesthesia, sedation or analgesia administered during and after the procedure, and the adverse events related to the procedure. All patients provided written informed consent for the ESWL procedure. This retrospective study was approved by our Institutional Review Board and by the Ethics Committee.
Outcomes The primary outcome of the study was CBD clearance, which was evaluated by imaging techniques (radiology and US). The secondary outcomes were the stone fragmentation rate, the number of ESWL sessions, the number of shock waves administered in each session and total hits per patient, the number of endoscopic sessions (ERCPs) required to achieve bile duct clearance, the incidence of adverse events, and the need for sedation or postprocedural analgesia.
ESWL procedure
This study was a retrospective analysis of a prospectively collected database. All consecutive patients who
From October 1990 to April 2005 all procedures were performed using a Lithostar Plus (Siemens Co), whereas from May 2005 to December 2012, all procedures were performed using a Modulith SLX- F2 (Storz Medical AG). The Lithostar Plus is an electromagnetic lithotripter with an ellipsoid aperture of 125 mm, a focal distance of 14 cm, a focal zone of 12 130 to 13 146 mm, and a focal pressure of 15 to 70 MPa.25 The Modulith SLX-F2 is a mobile lithotripter with an electromagnetic cylindrical source. The dual-focus system of this model allows the focal size (precise focus: 6 28 mm, 2.5 to 150 MPa; extended focus: 9 50 mm, 2.5 to 90 MPa) to be adapted to specific anatomic conditions. The shock wave field can be adjusted for various stone sizes and positions. In addition, the location system, with the combination of “in-line fluoroscopy” and “in-line US,” allows for maximum targeting accuracy.26 In our experience, considering the anatomic morphology of the CBD, precise focus was always used. Both lithotripters offered
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METHODS
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Figure 1. Study flowchart. ESWL, extracorporeal shock wave lithotripsy.
the possibility of targeting stones with fluoroscopy or US. Stone targeting was performed using an injection of contrast medium via a nasobiliary drainage tube, which was previously placed during an ERCP procedure or with US guidance. All stone sizes throughout the study were measured during the ERCP procedures, correcting for geometric magnification using the tip of the endoscope as the reference for adjusting the measurements. The patients fasted for at least 12 hours before the ESWL treatment and were monitored with pulse oximetry during the procedure. A continuous electrocardiogram was performed in the patients with known cardiac disease or arrhythmias. During the ESWL session, the patients typically maintained a prone position. Routine laboratory tests were performed 6 and 24 hours after the procedure. The time interval between multiple ESWL sessions was at least 24 hours. Only patients with cholangitis and patients with associated intrahepatic stones were treated with antibiotic therapy. Analgesia with opioids (pethidine and fentanyl) and nonsteroidal anti-inflammatory drugs (ketorolac) and sedation with benzodiazepines (midazolam) were used as needed during the procedures. None of the patients received general or epidural anesthesia. Pregnancy and severe irreversible coagulopathy were considered absolute contraindications. Liver cirrhosis, portal hypertension, history or presence of cardiac arrhythmia, pancreatitis, thrombosis, abdominal aortic aneurysm, renal failure, giant liver hemangioma, gut or lung interposition, and voluminous abdominal fluid cysts were considered relative contraindications. 404 GASTROINTESTINAL ENDOSCOPY Volume 81, No. 2 : 2015
Definitions Difficult CBD stones were defined as stones that could not be extracted by ERCP with sphincterotomy, Dormia basket, and/or balloon catheter. Stone fragmentation was defined as the rupture of stones because of ESWL treatment, as fluoroscopically documented. CBD clearance was defined as complete stone removal after ESWL sessions, with or without the need for endoscopic stone extraction, as documented by imaging techniques. Spontaneous bile duct clearance was defined as complete stone removal after ESWL sessions without the need for stone extraction, as documented by imaging techniques. Patients who did not achieve CBD clearance after ESWL and endoscopic extraction attempts were considered treatment failures.
Statistical analysis The categorical variables were summarized in terms of the numbers and percentages and were compared using the 2-sided Fisher exact test or the c2 test as appropriate. Continuous data were tested for normal distribution using the Kolmogorov-Smirnov test. Normally distributed variables were presented, when appropriate, as the mean standard deviation and were compared using a t test or presented as the median and interquartile range, and the Mann-Whitney test was used. A logistic regression analysis was used to evaluate the factors affecting the outcome of ESWL. A 2-sided value of P ! .05 was considered significant. Statistical analyses were performed using the MedCalc package v.11.5 for Windows (MedCalc, Ostend, Belgium). www.giejournal.org
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ESWL for difficult CBD stones
TABLE 1. Patient and CBD stone characteristics
Characteristics
Total (n [ 392)
Lithostar Plus (n [ 199)
Modulith SLX-F2 (n [ 193)
P
Age, y, median (IQR)
76 (69-82)
76 (72-82)
76 (66-82)
.09
Single
163 (41.6%)
91 (45.7%)
72 (37.3%)
.11
Multiple
229 (58.4%)
108 (54.3%)
121 (62.7%)
.11
2.0 (1.5-2.5)
2.0 (1.7-2.5)
2.0 (1.5-2.5)
.25
!2 cm
258 (65.8%)
131 (65.8%)
127 (65.8%)
.92
!3 cm
362 (92.3%)
186 (93.5%)
176 (91.2%)
.45
R3 cm
30 (7.7%)
13 (6.5%)
17 (8.8%)
.45
21 (5.4%)
6 (3.0%)
15 (7.7%)
.04
Number of stones
Stone diameter, median (IQR)
Concomitant intrahepatic stones CBD, Common bile duct; IQR, interquartile range.
RESULTS Patients Between 1990 and 2012, 416 patients underwent ESWL at S. Orsola-Malpighi Hospital (Bologna, Italy). Of these patients, 392 (180 men; median age 76; interquartile range, 69 to 82) were included in the study after applying the selection criteria. Nine patients were excluded because they had only intrahepatic stones, and 15 patients were excluded because endoscopic removal was not attempted before ESWL. Of these cases, the targeting was performed without a nasobiliary tube but with US guidance in 3 cases, with percutaneous transhepatic cholangiogram in 9 cases, and with a Kehr tube in 3 cases. One hundred ninety-nine patients underwent ESWL using the Lithostar Plus, and 193 patients underwent ESWL using the Modulith SLX-F2. A single stone was reported in 163 patients (41.6%), and 229 patients (58.4%) had multiple biliary stones. The median diameter of the stones was 2.0 cm (interquartile range, 1.5 to 2.5). No differences according to the age, gender, or type of CBD stones were detected between the 2 treatment groups. The baseline characteristics of the entire study population and according to the lithotripter used for ESWL are reported in Table 1.
after ESWL and 324 (92.8%) needed 1 or more ERCPs to achieve bile duct clearance (Table 2). The median number of ERCPs after lithotripsy was 1 (interquartile range, 1 to 1). The clearance rates between the treatment groups (Lithostar Plus vs Modulith SLX-F2) were not significantly different (90.5% vs 87.6%; P Z .45). Forty-three patients (11%) were considered treatment failures; in 21 patients (5.4%) a surgical approach was necessary, 12 patients (3.1%) were treated with biliary stenting because they were unfit for surgery, and 10 patients (2.5%) suspended treatment because of a lack of compliance or tolerance, and they refused any other treatments. The multivariate analysis did not identify any factors influencing the CBD clearance. Age, gender, single or multiple stones, stone diameter, number of ESWL sessions, number of shock waves administered, and type of lithotripter used were not independently related to the CBD clearance.
ESWL sessions
CBD clearance was achieved in 349 patients (89.0%). Of these patients, 25 (7.2%) obtained spontaneous clearance
A total of 1290 ESWL sessions was performed in 392 patients. Of the study population, 48 patients (12.2%) required 1 session, 85 patients (21.7%) required 2 sessions, 103 patients (26.3%) required 3 sessions, and 81 patients (20.7%) required 4 sessions. Seventy-five patients (19.1%) required 5 or more ESWL sessions. A median of 3500 shocks (range, 2918 to 4000) was administered in each ESWL session; a median of 10,350 shock waves (range, 6500 to 14,950) was administered per patient. The comparisons between the 2 study groups are shown in Table 3. Patients treated with the Modulith SLX-F2 underwent significantly fewer ESWL sessions (3 [range, 2 to 4] vs 3 [range, 2 to 4]; P Z .0015) and required a lower number of total shock waves (9437 [range, 6075 to 12,650] vs 11,000 [range, 6770 to
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Stone fragmentation rate Stone fragmentation (Fig. 2) was achieved in 378 patients (96.4%) but not in 14 patients (3.6%). No differences were observed between the Lithostar Plus and the Modulith SLX-F2 treatment groups (95.5% vs 97.4%; P Z .42).
CBD clearance
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Figure 2. Multiple difficult CBD before (a) and after (b) ESWL sessions. Complete fragmentation of the stones was achieved. CBD, common bile duct; ESWL, extracorporeal shock wave lithotripsy.
TABLE 2. Outcomes
Outcome
Total (n [ 392)
Lithostar Plus (n [ 199)
Modulith SLX-F2 (n [ 193)
P
Stone fragmentation rate
378 (96.4%)
190 (95.5%)
188 (97.4%)
.42
CBD clearance
349 (89.0%)
180 (90.5%)
169 (87.6%)
.45
25 (7.2%)
8 (4.4%)
17 (10.1%)
.06
324 (92.8%)
172 (95.6%)
152 (89.9%)
.06
43 (11.0%)
19 (9.5%)
24 (12.4%)
.42
Surgery
21 (5.4%)
12 (6.0%)
9 (4.7%)
.65
Stenting
12 (3.1%)
2 (1.0%)
10 (5.2%)
.035
Discontinued
10 (2.5%)
5 (2.5%)
5 (2.6%)
.79
1 (1-1)
1 (1-1)
1 (1-1)
Opioid
70 (17.8%)
70 (35.2%)
0
!.0001
NSAIDs
21 (5.3%)
12 (6.0%)
9 (4.7%)
.84
2 (.5%)
0
2 (1.0%)
.43
37 (9.4%)
27 (13.6%)
10 (5.2%)
.009
Spontaneous After ERCP Treatment failure
No. post-ESWL ERCP (IQR) Medication
Benzodiazepine Side effects ESWL-related adverse events
CBD, Common bile duct; ESWL, extracorporeal shock wave lithotripsy; NSAIDs, nonsteroidal anti-inflammatory drugs.
15,500]; P Z .03). Patients treated with the Modulith SLXF2 received a lower number of shock waves per session compared with the patients treated with the Lithostar Plus, but the difference was not statistically significant: 3416 (range, 2937 to 3800) versus 3540 (range, 2737 to 4000) (P Z .062). The details regarding the ESWL procedures of the patients who achieved CBD clearance are summarized in Table 4. The mean number of sessions required to achieve CBD clearance was 3 (range, 2 to 4). Patients who achieved
CBD clearance and were treated with the Modulith SLX-F2 needed a significantly lower number of ESWL sessions (3 [range, 2 to 4] vs 3 [range, 2 to 4]; P Z .0004). Of the entire study population, independent of the type of lithotripter used, the percentage of CBD clearance after a single ESWL session was 11.7% (41 of 349 patients), and it increased to 34.1% (119/349) and 61.6% (215/349) after 2 and 3 sessions, respectively. The CBD clearance rate achieved with %3 ESWL sessions was 51.7% (93/180) when patients were treated with the Lithostar Plus, and
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ESWL for difficult CBD stones
TABLE 3. ESWL procedure details Total (n [ 392)
Lithostar Plus (n [ 199)
Modulith SLX-F2 (n [ 193)
P
3 (2-4)
3 (2-4)
3 (2-4)
.0015
1
48 (12.2%)
27 (13.6%)
21 (10.9%)
2
85 (21.7%)
27 (13.6%)
58 (30.0%)
3
103 (26.3%)
47 (23.6%)
56 (29.0%)
4
81 (20.7%)
51 (25.6%)
30 (15.5%)
5þ
75 (19.1%)
47 (23.6%)
28 (14.6%)
3500 (2918-4000)
3540 (2737-4000)
3416 (2937-3800)
.062
10,350 (6500-14,950)
11,000 (6770-15,500)
9437 (6075-12,650)
.03
Total (n [ 349)
Lithostar Plus (n [ 180)
Modulith SLX-F2 (n [ 169)
P
3 (2-4)
3 (2-4)
3 (2-4)
.0004
1
41 (11.7%)
24 (13.3%)
17 (10.1%)
2
78 (22.3%)
23 (12.8%)
55 (32.5%)
3
96 (27.5%)
46 (25.6%)
50 (29.6%)
4
76 (21.8%)
47 (26.1%)
29 (17.2%)
5þ
58 (16.7%)
40 (22.2%)
18 (10.6%)
3500 (2908-4000)
3600 (2774-4000)
3360 (2925-3808)
.03
10,000 (6500-14,500)
11,000 (7000-15,500)
9000 (6000-12,312)
.08
ESWL No. of sessions, median (IQR)
No. of shock waves (per session), median (IQR) No. of total shock waves (per patientt), median (IQR)
ESWL, Extracorporeal shock wave lithotripsy; IQR, interquartile range.
TABLE 4. ESWL procedure details of patients who achieved CBD clearance
ESWL No. of sessions, median (IQR)
No. of shock waves (per session), median (IQR) No. of total shock waves (per patient), median (IQR)
ESWL, Extracorporeal shock wave lithotripsy; CBD, common bile duct; IQR, interquartile range.
the clearance rate significantly increased to 72.2% (122/169) when the Modulith SLX-F2 was used (P Z .0001).
The ESWL-related adverse events are reported in Table 2. Thirty-seven patients (9.4%) experienced side effects. Of these patients, 27 (13.6%) were treated with the Lithostar Plus and 10 (5.2%) with the Modulith SLX-F2.
In the Lithostar Plus group, 3 patients reported vomiting, 9 patients had transient palpitations because of benign symptomatic premature ventricular complexes, and 13 patients had bradycardia, which spontaneously resolved after temporary treatment suspension in 11 patients but deferral of the ESWL session was needed in 2 cases. One case of hemobilia and 1 case of lower GI bleeding were reported in the Lithostar Plus group; neither patient required a blood transfusion or specific treatments. In the Modulith SLX-F2 group, 10 patients (5.2%) reported mild, self-limiting ESWL-related adverse events (6 cases of periprocedural nausea and 4 cases of asymptomatic bradycardia, which resolved after treatment suspension). The comparison between the 2 groups demonstrated a significantly lower incidence of ESWLrelated adverse events in the Modulith SLX-F2 group (5.2% vs 13.6%; P Z .009).
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Anesthesia, analgesia, and sedation Of the entire study population, no patients received anesthesia (general nor epidural). Seventy patients (17.8%) needed an opioid injection, 21 patients (5.3%) needed nonsteroidal anti-inflammatory drugs, and 2 patients (.5%) were sedated with benzodiazepines. Opioid analgesia was not required in any patients treated with the Modulith SLX-F2 (P ! .0001). The details are provided in Table 2.
Adverse events
ESWL for difficult CBD stones
DISCUSSION Our study, which involved the largest cohort of patients ever reported, demonstrated that ESWL can achieve clearance of difficult CBD stones in approximately 90% of cases and has a low rate of adverse events (9.4%), which were mostly minor, self-limiting adverse events. The main finding of our study was that using the Modulith SLX-F2 for ESWL allowed for the clearance of difficult CBD stones at the same rate as the Lithostar Plus, but the Modulith SLX-F2 had significantly lower numbers of ESWL sessions and total shock waves. The incidence of ESWL-related adverse events was significantly lower in patients who underwent ESWL with the Modulith SLX-F2 compared with patients treated with the Lithostar Plus. The different outcomes observed could be ascribed to several different technical characteristics of the 2 lithotripters. The smaller focus size of the “precise focus” and “inline fluoroscopy” of the Modulith SLX-F2 allow for better centering and for adaptations to difficult anatomic conditions (ie, obesity, postural pain) and to respiratory movements. These advantages lead to less dissipation of the shock waves and less damage to surrounding tissues and could explain the significantly lower incidence of adverse events and the better tolerability observed. The Modulith SLX-F2 administers a higher focal pressure (150 vs 70 MPa), which with a smaller focal area (6 28 mm vs 13 146 mm) could account for the significantly lower number of sessions and shock waves needed to achieve complete fragmentation of the CBD stones. Although a cost analysis was beyond the aim of our study, the use of the Modulith SLX-F2 should reduce the management cost of patients with difficult CBD stones because of the significant overall reduction in the number of sessions needed to achieve CBD clearance. Similar to our study, one of the largest prospective, noncomparative studies achieved a clearance rate of 84.4% in 283 patients with difficult CBD stones using a Dornier machine (Compact Delta; Dornier Medtech), with a mean of 2.8 sessions per patient; mostly mild and self-limiting adverse events were reported in 15.9% of patients.23 The low number of sessions required to achieve CBD clearance and the high adverse event rate reported by Tandan et al23 might be because of the use of epidural anesthesia during the ESWL sessions. ESWL is generally a safe and well-tolerated procedure, but serious adverse events, such as necrotizing pancreatitis, cholangitis, perirenal hematoma, bowel perforation, splenic rupture, and death, have been described.10,27,28 In our series, we showed that the implementation of technical improvements (ie, location system and focusing) achieved with the latest generation of lithotripters further reduced the incidence of adverse events, particularly the incidence of serious adverse events.
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Our study had several limitations. Though it was based on a prospectively collected database, our study design was retrospective. The most obvious potential study flaw is the historical bias; we tested the bias by comparing the first 30 patients treated with each lithotripter with the last 30 patients. The comparison did not show any significant differences, and we could exclude any learning curve effect on the final outcome (CBD clearance with Lithostar Plus: first 30 cases vs last 30 cases: 90% vs 96%, respectively [P Z .67]; CBD clearance with Modulith SLX-F2: first 30 cases vs last 30 cases: 80% vs 90%, respectively [P Z .47]). The introduction of new techniques for stone extraction, such as large balloon dilation, during the course of the study might be an additional confounding factor, but in our division, all patients with difficult bile duct stones are routinely managed with the placement of a nasobiliary tube and ESWL. Alternative methods, such as mechanical lithotripsy and large balloon dilation, are considered only in patients in whom the placement of a nasobiliary tube is not feasible, is contraindicated, or is not tolerated. The study was not powered to detect rare severe adverse events, so no conclusions can be drawn regarding this issue. ESWL for difficult CBD stones is a safe and effective treatment strategy that allows for bile duct clearance in approximately 90% of patients and has a low incidence of mild adverse events. The Modulith SLX-F2 had the same clearance rate as the Lithostar Plus, but the Modulith SLX-F2 has a significantly lower incidence of side effects and requires fewer ESWL sessions.
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Cecinato et al
ESWL for difficult CBD stones
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