Extracorporeal shock wave lithotripsy for pancreatic stones

INTRODUCTION — Treatment of human calculi by extracorporeal shock wave lithotripsy (ESWL) was first used in patients for the treatment of kidney stones in 1980 [1]. Subsequently, this technique has been applied to gallstones [2] and pancreatic stones [3]. (See "Overview of nonsurgical management of gallbladder stones".)

The treatment of pancreatic stones using ESWL will be reviewed here. The treatment of chronic pancreatitis, electrohydraulic lithotripsy, and laser lithotripsy are discussed separately. (See "Chronic pancreatitis: Management" and "Electrohydraulic lithotripsy in the treatment of bile and pancreatic duct stones" and "Laser lithotripsy for the treatment of bile duct stones".)

CLINICAL SIGNIFICANCE OF PANCREATIC STONES — Pancreatic duct stones are found in approximately 22 to 60 percent of patients with chronic pancreatitis (CP) [4]. The stones can lead to obstruction of the outflow of pancreatic secretions, causing increased intraductal pressure [5]. Because the pancreas is relatively noncompliant, the rise in intraductal pressure can induce tissue hypertension and ischemia, which may be a major factor causing pain in patients with CP [6]. This hypothesis is supported by the observation that symptoms may improve following pancreatic duct drainage [7,8].

The extraction of pancreatic duct stones has usually been attempted during endoscopic retrograde cholangiopancreatography (ERCP). However, successful stone extraction during ERCP depends upon the size and location of the stones and may not be possible if strictures are present or pancreatic stones have become embedded in the ductal system. As a result, a method of stone disruption prior to endoscopic extraction could be helpful. ESWL leads to the fragmentation of pancreatic stones, which has improved the results of endoscopic therapy and may have additional indications in the treatment of patients with CP [9].

LITHOTRIPTORS — Lithotripsy works by concentrating focused shock waves (SWs) on stones, which causes their disruption. SWs can be generated by three methods:

●Spark discharge (Dornier system)

●Piezoelectric elements (Wolf system)

●Electromagnetic deflection of a metal membrane (Siemens system)

SW generation takes place in degassed water. The SWs are focused either by reflection of the primary wave, arraying of the piezoceramic elements on a hemispherical disk, or by an acoustic lens. SWs are directed into the body via a water cushion or a water basin.

The stones must be localized using radiographic imaging prior to lithotripsy. Application of several hundred to several thousand SWs to the calculus in a focal area results in gradual disintegration of the stone. Disintegration results from the rapidly rising pressures (up to 500 to 1000 bar) within the focal area [10]. (See 'Stone localization' below.)

Other forms of pancreatic stone lithotripsy have been reported in small case series [11,12]. The techniques involve disruption of pancreatic stones by intraductal mechanical, electrohydraulic, or pulsed-dye laser lithotripsy during ERCP. These methods probably offer no advantage over ESWL, which is simple to perform, has high efficacy and has a low complication rate. (See "Electrohydraulic lithotripsy in the treatment of bile and pancreatic duct stones" and "Laser lithotripsy for the treatment of bile duct stones".)

PATIENT SELECTION — The role of extracorporeal shock wave lithotripsy (ESWL) in the management of patients with chronic pancreatitis is evolving. The technique is not widely available, particularly in the United States, and its efficacy compared with other methods of treatment has not been established in randomized controlled trials (see "Chronic pancreatitis: Management"). However, a meta-analysis including a total of 588 patients found that ESWL was effective in relieving main pancreatic duct obstruction and alleviating pain in chronic calcific pancreatitis, most often in combination with endoscopic therapy [13].

ESWL for pancreatic stones is indicated for patients with all of the following:

●Recurrent attacks of pancreatic pain

●Moderate to marked changes due to obstruction in the pancreatic ductal system

●Obstructing ductal stones (calcified or radiolucent)

Almost all stones are amenable to therapy because their biochemical composition consists of 95 percent calcium carbonate on a protein matrix. In our experience, approximately 44 percent of patients with chronic pancreatitis were eligible for ESWL [9].

The technique is optimally suited for patients who have a dilated main pancreatic duct that contains a single stone but has no stricture. However, patients with relatively unfavorable characteristics (such as those with multiple stones, pancreatic duct strictures, or small pseudocysts, or those who continue to drink alcohol) may also benefit from ESWL. (See 'Clinical results' below.)

Contraindications — The procedure is contraindicated in patients who have coagulation disorders, in women who are pregnant, in patients with implanted cardiac pacemakers or defibrillators, and in patients who have bone, calcified aneurysms, or lung tissue in the shock wave path.

METHODS

Stone localization — Adequate visualization of pancreatic and surrounding anatomy is essential prior to extracorporeal shock wave lithotripsy (ESWL). We usually accomplish this by obtaining good quality plain films of the pancreatic area in left and right oblique positions, as well as a magnetic resonance cholangiopancreatography (MRCP) [14]. In centers in which MRCP is unavailable, a computed tomography scan with and without intravenous contrast can also demonstrate pancreatic ductal obstruction related to pancreatic stones.

In the majority of patients, a two-dimensional radiologic targeting system is required during lithotripsy because ultrasound localization of pancreatic stones is insufficiently precise. In one study, for example, the position of the stone was monitored successfully in 14 percent of patients treated with a piezoelectric lithotriptor using only ultrasound for localization [15].

Localization by ultrasound may be better when the main pancreatic duct is dilated [16]. The median stone size and pancreatic duct size was 12 mm in one report that relied exclusively on ultrasound targeting [17]. For very small stones or radiolucent stones, visualization can be improved by instillation of contrast medium through a nasopancreatic catheter.

Sedation — ESWL can be carried out with moderate sedation, epidural anesthesia [18], or general anesthesia. General anesthesia may be particularly helpful in patients undergoing ESWL and therapeutic endoscopic retrograde cholangiopancreatography (ERCP) during the same session. (See "Anesthesia for gastrointestinal endoscopy in adults".)

Antibiotic prophylaxis — Some authorities have recommended antibiotic prophylaxis for ESWL [19-21]. We, however, only use antibiotic prophylaxis before ERCP when there is cholestasis. (See "Antibiotic prophylaxis for gastrointestinal endoscopic procedures".)

Application of shock waves — Most patients are positioned so that the stones are separated from the spine (slight left or right lateral decubitus), with shock waves (SWs) entering the body from the ventral side [9,15,16,19-23]. Some lithotriptor devices require that the SWs enter from the dorsal side [17,24] or obliquely [25].

The SWs should be focused first on the most distally located stone and then on the other calculi proceeding from the head to the tail. This allows drainage of the fragments downwards through the papilla. A total of 3000 to 5000 SWs using the highest possible energy level (0.54 mJ/mm-2) are usually delivered in one treatment session, which lasts approximately 45 to 60 minutes. When ERCP immediately follows the ESWL session, the energy level of the SW is reduced to a maximum level of 0.33 to 0.37 mJ/mm-2 to avoid duodenal edema and erosions, which might impair further endoscopic treatment.

SWs can be triggered by breathing (when the stone is moving out of the focal zone during breathing) and/or by the electrocardiogram (during the refractory period). This is particularly helpful in patients who have a history of cardiac arrhythmias, as premature ventricular contractions can be observed during lithotripsy. In these patients, SWs should be delivered only during the refractory period to avoid possible ventricular arrhythmias.

Repeat ESWL may be required if stones have incompletely disintegrated, which is often the case in patients with large or multiple stones. The reported mean number of treatment sessions required to complete lithotripsy has ranged from 1.3 to 6.0 per patient in most reports [9,15,18,19,22,23,26-28], though one series reported a median of 13 sessions (range 2 to 74) [17].

Need for ERCP — In our experience, therapeutic ERCP is usually required within a few hours of ESWL to remove stone fragments. However, in other centers, successful spontaneous passage of the residual fragmented stones has been reported [21,27,28]. (See 'ESWL monotherapy compared to ESWL combined with endoscopic drainage' below.)

In a series from Japan, 24 of 32 patients (75 percent) with stones in the main pancreatic duct achieved spontaneous stone clearance following ESWL applied once or twice per week [21]. However, the high rates of spontaneous stone clearance seen in this study may be explained by the selection of patients without severe main pancreatic duct strictures (22 out of 32) and with good residual exocrine function (only two patients out of 32 [6 percent] presented with steatorrhea) [21]. Based on the available data, we suggest allowing spontaneous passage of the stone fragments only in patients without an associated tight stricture and with good residual exocrine function.

On the other hand, many authorities advocate that pancreatic sphincterotomy should be performed prior to ESWL to facilitate stone passage [15,17,19,20,22,29]. Pancreatic sphincterotomy is usually performed after biliary sphincterotomy to separate the two orifices. Placement of a nasopancreatic tube with its tip proximal to the unfragmented stone increases the efficacy of ESWL and may permit stone passage when the tube is perfused during the procedure [9,23].

Stone extraction during ERCP can be accomplished with a mini-Dormia basket using the "rotation-perfusion" technique, which consists of sweeping the basket along the main pancreatic duct with a rotary motion while injecting saline solution to flush out fragments [30]; the Fogarty balloon catheter is less efficient than the Dormia basket. A 6-Fr nasopancreatic catheter should be left in place for one or two days and perfused with an isotonic saline solution (one liter every 24 hours) to eliminate stone fragments.

Studies suggested that delaying endoscopic intervention for more than 36 hours after ESWL may be beneficial for some patients. In a study that compared ERCP >36 hours with ERCP <12 hours or between 12 to 36 hours after ESWL in 267 patients with native papilla (ie, no prior ERCP), delaying ERCP >36 hours was associated with higher rates of successful cannulation (91 versus 71 and 82 percent, respectively) and stone clearance (91 versus 76 and 85 percent, respectively) [31].

Additional therapeutic options may be required in patients who have a pancreatic stricture or other complications of chronic pancreatitis such as a pseudocyst or biliary stricture (see "Approach to walled-off pancreatic fluid collections in adults"). In patients with a dominant dorsal duct (complete or incomplete pancreas divisum), pancreatic ductal drainage can be accomplished through the minor papilla. This was required in approximately 20 percent of our patients [9,23].

EFFICACY — Extracorporeal shock wave lithotripsy (ESWL) permits nonsurgical clearance of pancreatic stones much larger than those traditionally amenable to endoscopic procedures [3,9,24,27,32,33]. Increasing experience with this technique has improved its success [30]. In a multivariate analysis of 70 patients with ductal stones who underwent pancreatic sphincterotomy and attempted stone removal, the availability of ESWL was the only independent factor influencing the technical results of endoscopic management [30].

Technical results — Disintegration of a calcified pancreatic stone can be considered successful when one of the following findings is seen on plain films following ESWL:

●A decrease in the radiographic density of the stone

●An increase in the stone surface area

●Heterogeneity of the stone, which appears as powder-like material filling the pancreatic and the surrounding secondary ducts

These changes should be accompanied by relief of ductal obstruction demonstrated by successful deep cannulation of the main pancreatic duct [9]. Using this definition, the success rate of fragmentation has been approximately 74 to 100 percent in most series, regardless of the shock wave system used (table 1) [9,15-19,21-24,26-28,32,34], except in a study that found higher stone fragmentation rates with the electromagnetic system and the electrohydraulic spark gap system compared with the piezoelectric generator [35]. However, the piezoelectric generator was used in a small minority of patients (5 percent), whereas the electromagnetic system used in 61 percent and the electrohydraulic spark gap system in 31 percent. Lower success rates were reported in two studies with a total of 128 patients. ESWL was considered to be technically successful in only 54 and 60 percent of patients, respectively [17,26]. The high technical failure rate in these series was probably related to the exclusive use of ultrasound to localize stones.

In some reports, successful fragmentation and stone clearance has not correlated with the initial size or the number of main pancreatic duct stones [21,22,33]. However, at least three studies showed successful treatment was more frequent in patients with solitary stones [26,28,36]. In one study, stone clearance occurred in 74 percent of those with solitary stones versus 43 percent in those with multiple stones [26]. In another study, complete removal of stones was achieved more frequently in patients with a single stone (73 versus 48 percent for multiple stones) and without a main pancreatic duct stricture (67 versus 44 percent) [28].

Some studies suggest that a lower stone density is associated with higher rates of complete stone removal [36,37]. In a study of 148 patients with pancreatic duct stones, patients with lower density stones (measured by mean value of CT attenuation, using cutoff value 1000.45 Hounsfield units) had a better stone clearance rate compared with patients with higher density stones (69 versus 60 percent) [37].

Most patients studied required endoscopic extraction of fragments after ESWL for complete clearance from the ductal system except, as mentioned above, in one study in which complete clearance of the main pancreatic duct stones was obtained spontaneously in 75 percent of patients [21]. (See 'Need for ERCP' above.)

Decompression of the pancreatic duct is achieved in 70 to 96 percent of the patients treated with ESWL followed by endoscopic ductal drainage procedures [9,16,18,23,24,38]. Furthermore, in a study of 55 patients treated with ESWL followed by ERCP for ductal drainage, pancreatic pseudocysts resolved in 42 patients (76 percent) at one year follow-up. This presumably occurs as a result of reduced ductal pressure due to alleviation of the distal obstruction [9,38].

Clinical results — Studies have shown that ESWL is effective at both relieving pain in patients with chronic pancreatitis and at improving pancreatic exocrine (but not necessarily endocrine) function. However, the variable natural history of chronic pancreatitis complicates the assessment of treatments aimed at relieving symptoms. In one series, for example, 85 percent of 141 patients with chronic calcific pancreatitis obtained pain relief after a median time of 4.5 years, and the rates of pain relief were similar in those who underwent surgery and in those who did not [39].

Pain relief — The radiographic success of ESWL has been associated with clinical improvement. In a meta-analysis of 27 studies with 3189 patients who underwent ESWL for chronic calcific pancreatitis with main pancreatic duct stones >5 mm in size, 53 percent of patients reported no pain during follow-up (95% CI 51-55 percent) and 33 percent of patients reported mild to moderate pain (95% CI 31-36 percent) [40]. In a subsequent meta-analysis of 22 studies including 3868 patients with chronic pancreatitis and pancreatic duct stones who were treated with ESWL, complete relief of pain was reported by 64 percent of patients (95% CI 58-71 percent), while complete ductal clearance was achieved in 70 percent of patients (95% CI 64-76) [41]. Post-procedural pancreatitis and cholangitis occurred in 4.0 and 0.5 percent of patients, respectively. Individual studies have found that complete or partial pain relief following ESWL was achieved in 62 to 95 percent of patients during a mean follow-up ranging from 7 to 77 months [9,15-17,21,23,26,27,29,33,35,42,43].

Immediate relief of or improvement in pain has been associated with successful decompression of the main pancreatic duct (as suggested by decrease in its diameter or stone clearance) [9,17,24,30]. However, complete stone clearance is not required for symptom relief. Following treatment, a considerable number of patients gain weight due to a reduction in postprandial pain attacks, improvement in pancreatic function, or both.

Multiple studies have looked for factors associated with pain relapse, with variable results:

●The number and location of stones, the presence of a stricture, or continued alcohol use did not appear to be associated with recurrent pain in many reports [9,15,29]. This suggests that ESWL can be attempted in patients with these clinical characteristics.

●In a randomized trial, the presence of obstructing calcifications in the head of the pancreas was independently associated with the absence of pain relapse [44].

●In a series with long follow-up (14.4 years), not smoking was associated with fewer hospital admissions for pain treatment, while alcohol use increased the risk for diabetes, steatorrhea, and mortality [45]. Smoking cessation was also associated with improved outcomes in a second study [42].

●Another report found that pain improvement was associated with nonalcoholic chronic pancreatitis [17].

●Independent predictors of pain relapse at long-term follow-up in another report were a high frequency of pain attacks before treatment (more than or at least two pain attacks during the two months before treatment), a long duration of disease before treatment, and the presence of a nonpapillary stenosis of the main pancreatic duct [30]. These findings suggest that ESWL with endoscopic therapy should be performed as early as possible in the course of chronic pancreatitis.

Pancreatic endocrine and exocrine function — Early ductal decompression of the main pancreatic duct may help prevent further fibrosis, which can lead to pancreatic insufficiency. In addition, it may improve pancreatic function in patients who have already developed pancreatic insufficiency.

Studies have shown that pancreatic exocrine function improves more often after treatment than pancreatic endocrine function [9,17,21,27,43]. In those studies, pancreatic endocrine function remained largely unaffected, except in a few patients. In our long-term studies, we have also observed that endoscopic ductal drainage (including ESWL) can delay the development of pancreatic exocrine insufficiency by approximately 10 years compared with the natural history of chronic pancreatitis patients [45]. By contrast, it did not change the development of diabetes in the course of chronic pancreatitis [45].

The appearance of de novo steatorrhea has been associated with a long duration of symptomatic ductal obstruction, whereas the development of de novo diabetes was only related to alcohol use [45]. These findings are supported by another study in which pancreatic exocrine function deteriorated more significantly in the group of patients with initial incomplete stone removal, whereas the frequency of diabetes was higher in patients with alcohol-related pancreatitis and in those who continued drinking [28]. In a study including 507 patients with chronic pancreatitis, early ductal intervention (ie, within three years from onset of symptoms) was associated with a lower risk of developing diabetes compared with no intervention in a subgroup of patients with idiopathic pancreatitis and main duct stones (hazard ratio [HR] 0.39, 95% CI 0.28-0.55) [46]. However, ductal interventions did not have impact on the glycemic status for patients with an established diagnosis of diabetes.

Stone recurrence — In most series, recurrent pain attacks were usually related to stone migration or recurrence, progressive stricturing of the main pancreatic duct, or pancreatic stent obstruction or dislodgement. The majority of these patients could be managed successfully by endoscopy or a combination of endoscopy and ESWL [9,15,23,27,28,33].

●In a representative series, after achieving complete clearance of the main pancreatic duct, stone recurrence was found in 48 percent of patients at a mean follow-up of 7.4 months. The median "stone-free survival time" calculated with the Kaplan-Meier method was 18.5 months [33]. The technical and clinical success rates for treatment of recurrent stones were comparable to those of initial therapy.

●In another series, stone recurrence developed in 22 percent of patients, with a mean time to recurrence of 25 months [27]. The presence of a ductal stricture was associated with stone recurrence (a finding that we have also observed).

●In a long-term study, approximately one-third of patients experienced pain relapses during a mean follow-up period of 77 months [28]. All such patients had intraductal pancreatic stones. Pain relapse occurred significantly more frequently in patients with incomplete removal of stones after the initial therapy (hazard ratio [HR] of 3.7) and in those with a main pancreatic duct stricture (HR of 3.4). Both factors were significant risk factors for pain relapse on multivariate analysis.

ESWL monotherapy compared to ESWL combined with endoscopic drainage — Few studies have directly compared ESWL monotherapy to ESWL combined with endoscopic drainage, but the data available suggest that the results are similar for the two approaches.

A randomized controlled trial compared ESWL alone with ESWL and endoscopic drainage of the main pancreatic duct for treatment of pain in chronic pancreatitis [44]. In 55 patients with uncomplicated calcified chronic pancreatitis, ESWL alone (n = 26) was found to be a safe and effective treatment. No significant differences in the outcome of pancreatic pain were reported when ESWL alone was compared with the combination of endoscopy with ESWL treatment (n = 29). The patients did not undergo ERCP prior to ESWL, so there was no grading of any associated main pancreatic duct stricture(s). However, a similar decrease in the main pancreatic duct diameter was reported one month after treatment.

In another report of 555 patients, ESWL was applied as monotherapy in 57 percent of patients [27]. Although technical or clinical results were not directly compared between patients treated with ESWL alone or with ESWL and endotherapy, spontaneous stone clearance after ESWL alone was obtained in 70 percent of patients. This rate was similar to the overall complete ductal clearance rate of 73 percent for the series as a whole [27]. However, in a similar multicenter Japanese study [35], complete stone clearance after ESWL alone was recorded in 49 percent and in 74 percent for all cases treated by ESWL with or without endotherapy.

Given the above findings, the advantages of treatment with ESWL alone (noninvasiveness, efficiency, innocuousness, and low cost) have to be considered when choosing the initial therapeutic option in selected patients. (See 'Patient selection' above.)

Need for surgery — Pancreatic surgery is required in 1.4 to 20 percent of patients after technical failure of stone disintegration or endoscopic ductal drainage, or for complications of pancreatitis beyond the capability of endoscopic management. Later surgery may also be indicated for definitive biliary drainage (hepaticojejunostomy) or for pancreatic ductal drainage (pancreaticojejunostomy) [45]. (See "Chronic pancreatitis: Management".)

COMPLICATIONS — Severe complications, such as organ damage or acute pancreatitis, are rare following extracorporeal shock wave lithotripsy (ESWL). Overall morbidity is related primarily to the associated endoscopic procedures and is generally easily controlled with medical treatment. No procedural or hospital mortality has been reported in large published series [9,15-18,21,23,24,32,34,35,47], except for one case of fatal acute cholangitis reported in a multicenter study of 555 patients [27].

A prospective study with a total of 634 patients undergoing 1470 ESWL procedures found that major complications of pancreatic ESWL (eg, post-ESWL pancreatitis, bleeding, infection, steinstrasse, and perforation) occurred at an overall rate of 6.7 percent [48]. Steinstrasse was defined as acute stone impaction at the papilla leading to poor pancreatic drainage and upstream dilation of the pancreatic duct. It was reported in 0.4 percent of cases. This very rare complication could require emergency endoscopic retrograde cholangiopancreatography or ESWL. Risk factors for complications were pancreas divisum (odds ratio [OR] 4.4, possibly owing to a narrow minor papilla) and a longer interval between diagnosis of chronic pancreatitis and pancreatic ESWL (OR 1.3). Protective factors were male sex (OR 0.50), diabetes mellitus (OR 0.45), and steatorrhea (OR 0.43). Interestingly, no procedure-related risk factors were identified.

Data have suggested that use of nonsteroidal anti-inflammatory drugs (NSAIDs) resulted in lower risk of post-ESWL pancreatitis. In a trial including 1370 patients with pancreatic stones, the risk of post-ESWL pancreatitis was lower in patients who received rectally administered indomethacin preprocedure compared with placebo (9 versus 12 percent, relative risk 0.71, 95% CI 0.52-0.98) [47].

Other findings related to ESWL that are of unclear clinical significance include:

●In a small series of 13 patients with pancreatic stones treated by ESWL and investigated before and after lithotripsy, there was a transient increase in serum lipase, mild hemolysis, and an isolated increase in serum LDH 5 isoenzyme, suggesting granulocyte damage [49]. All of these effects were without clinical significance and reversed after 24 hours.

●Petechiae are regularly noted on the skin at the area of shock wave penetration.

●Erosions in the gastric antrum, sometimes hemorrhagic, have been observed when endoscopy has been performed immediately following ESWL, but again, without clinical consequences.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Chronic pancreatitis and pancreatic exocrine insufficiency".)

SUMMARY AND RECOMMENDATIONS

●Indications – We suggest extracorporeal shock wave lithotripsy (ESWL) as a first-line approach in patients with painful chronic pancreatitis associated with obstructive ductal stones (calcified or radiolucent), inducing upstream dilatation of the main pancreatic duct, regardless of the etiology of the chronic pancreatitis (Grade 2B). (See 'Patient selection' above.)

●Postprocedure care – As a general rule, stone fragmentation by ESWL is followed by endoscopic ductal drainage using pancreatic sphincterotomy, fragmented stone extraction, and pancreatic stenting in the case of a ductal stricture. However, in selected patients with uncomplicated calcified chronic pancreatitis, ESWL without endoscopic ductal drainage may be an option. (See 'Need for ERCP' above and 'ESWL monotherapy compared to ESWL combined with endoscopic drainage' above.)

●Efficacy – The best fragmentation rates (approximately 90 percent) are obtained when a fluoroscopic targeting system is used to focus on the stones. (See 'Technical results' above.)

After completion of endoscopic pancreatic ductal drainage, definitive pain relief can be expected in approximately two-thirds of patients at long-term follow-up. (See 'Pain relief' above.)

The best clinical results are seen in patients who do not smoke and in patients who receive early treatment in the course of their chronic pancreatitis. (See 'Pain relief' above.)