Extracorporeal gallstone lithotripsy

Extracorporeal By William

Gallstone Lithotripsy E. Torres and lgor Laufer

HE FIRST HUMAN extracorporeal shockwave lithotripsy (ESWL) for gallstones was performed in 1986 by the physicians at the Khnikum Grosshadern in Munich, Germany.’ In 1988, Sackmann et al* published encouraging gallstone ESWL results on their first 175 patients. In the same year, the United States biliary ESWL experience began. To date, 10 lithotripter manufacturers have started biliary ESWL trials in the United States at over 80 clinical sites. Worldwide, approximately 20,000 patients have biliary lithotripsy with many investigators publishing their ESWL results on patients with symptomatic gallstone.‘-’

T

LITHOTRIPTER

SYSTEMS

The biliary ESWL clinical trials in the United States use one of three shock-wave generation techniques: electromagnetic shock waves (Siemens, Iselin, NJ; Storz, Culver City, CA), electrostatic spark discharge (Direx, Sunnyvale, CA; Dornier, Marietta, GA; Medstone, Cosa Mesa, CA; Northgate, Arlington Heights, IL; Technomed, Danvers, MA), and pulsed piezoelectric shock generation (EDAP, Westford, MA; Wolf, Rosemont, IL; Diasonics, Milpitas, CA). These second generation lithotripters require no water bath and use ultrasonography as the primary imaging method. They will be capable of performing both renal and biliary ESWL treatments. GALLSTONE

EXTRACORPOREAL SHOCK-WAVE LITHOTRIPSY STUDIES

At this time, the Food and Drug Administration (FDA) has not given premarket approval to

Seminars

PATIENT SELECTION

The selection criteria differ for each device and protocol. In general, the gallstone ESWL protocols specify the following: (1) symptomatic gallstones, (2) the number of stones, (3) the size of stones, (4) limited or no calcification, and (5) patency of the cystic duct. In addition, most protocols require evidence of gallbladder contractility in response to a fatty meal or intravenous cholecystokinin. The general exclusion criteria are listed in Table 1. All patients must fit into anesthesia risk assignment class (ASA) I-III. IMAGING THE GALLSTONE

PATIENT

Ultrasonography Versus Oral Cholecystography

Although ultrasonography is clearly the most sensitive method for detecting small stones, the oral cholecystogram (OCG) appears to be more reliable for determining the size and number of stones. Also, visualization of the gallbladder on OCG provides proof of cystic duct patency. For these reasons, most protocols include a pretreatment OCG along with sonography.

FRAGMENTATION

There are two approaches to the fragmentation of gallstones; the first uses a relatively low number of high-energy shockwaveswith intravenous sedation but needs the fewest number of treatments. The second uses a much higher number of shock waves of lower energy in association with multiple treatments. Little or no intravenous sedation or analgesia is required. AMERICAN

gallstone lithotripsy devices. Therefore, all treatments are performed under investigational protocols. All protocols are evaluating the safety and efficacy of gallstone lithotripsy; in addition, some protocols are evaluating the need for oral bile acid treatment with ursodeoxycholic acid in conjunction with ESWL.

in Roentgenology, Vol XXVI, No 3 (July), 1991: pp 267-274

ABBREVIATIONS ESWL, extracorporea1 shock-wave lithotripsy; OCG, oral cholecystogram; UDCA, ursodeoxycholic acid

From the Stone Treatment Center, Crawford Long Hospital of Emory Universify, Atlanta, GA; and the Biliay Lithottipsy Unit, Hospital of the lJniversi@ of Pennsylvania. Philadelphia, PA. Address reprint requests to William E. Torres, MD. The Stone Treatment Center, Crawford Long Hospital of Emory University 550 Peachtree St, NE, Atlanta. GA 3036.5. Copyright 0 1991 by W B. Saunders Company 0037-198X/91/2603-0012$5.OOlO

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268 Table 1. United

States Exclusion

Criteria

Clinically relevant defective coagulation Pregnancy Cardiac pacemaker or arrhythmia Known common bile duct stones Calcified stone Hepatic cyst, hemangioma, vascular aneurysm or lung in shock-wave path Any indication for the existence of a pigment stone

GALLSTONE FRAGMENTATION DURING EXTRACORPOREAL SHOCK-WAVE LITHOTRIPSY

The ESWL treatment has two componentsfragmentation and fragment clearance (Fig 1). The efficiency of fragmentation is determined by factors such as targeting, stone burden, and shock-wave energy.

Fig 1. Fragmel ntation and fragment clearance. (A) A salitary stone, before ESWL. (B) On day r 1 following ESWL, a cloud of small fra lgments is seen indieating excellent fl .agmentation.

GALLSTONE

ESWL

Targeting Patient positioning. In most patients, the gallbladder can be easily identified in both the supine and prone positions. In some patients, the gallbladder is difficult to locate in either position because of interference from bowel debris or gas or because of obesity. The vast majority of ESWL procedures are performed in the prone position. When prone, the gallbladder moves anteriorly allowing most gallstones to be easily localized, positioned into the focal zone, and treated. In some prone patients, however. the gallstones “bounce” with the shock waves resulting in a decreased amount of energy applied to the stone. It has been suggested that performing supine treatments would allow the gallstones to be “trapped” against the gallbladder wall by the incoming shock wave, thus reducing motion during fragmentation.’ Gallstone Localization Ultrasonography, the imaging procedure of choice during biliary ESWL, can easily localize the gallbladder and gallstone(s). With ultrasonography, continuous monitoring of the fragmentation process is possible-an important aspect of the procedure. Accurate targeting of the gallstone is necessary to minimize striking adjacent structures with the shock waves.

Fig 1. (Cont’d). (C) At 6 weeks, all fragments have been cleared from the gallbladder.

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Two ultrasound transducers are present on many currently available lithotripters to target gallstones or gallstone fragments-an in-line and an out-of-line transducer; many manufacturers have both, although all have at least an out-of-line system available. With both systems, the fragmentation process can be continually monitored; however, direct visualization of the fragmentation process is possible only with the in-line system. Both systemsare desirable on an ultrasound-dependent lithotripter. Gallstone Fragmentation As gallstone fragmentation proceeds, the swirling fragments produce a “cloud of dust” appearance (Fig 2). This generally indicates that good fragmentation is being achieved. However, the cloud of dust may obscure larger fragments that do not become apparent until the following day after the dust has settled. Therefore, we call this the “Stealth Bomber Effect” because the cloud of dust renders the larger fragments invisible to “radar”-ultrasound. During lithotripsy, a gallstone fragment line is formed. The shock waves are distributed over the fragment line in an attempt to further decrease the size of the individual pieces. Gallstone fragments tend to congregate in the most dependent aspect of the gallbladder (Fig 3);

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AND LAUFER

Fig 2. The cloud of dust appearance after fragmentation of a solitary gallstone.

smaller fragments will filter through the larger and become the most dependent, whereas the larger fragments settle on top of the heap of rubble.’ This has been termed the “Rocky Beach Phenomenon.” The remaining shock waves should be concentrated in the layer of large fragments. Gallstone Fragmentation and Stone Burden

Fig 3. The rocky beach phenomenon. An OCG at 6 months following ESWL shows residual fragments within the gallbladder. The largest fragments rest on top of the dust and smaller fragments.

Several factors are thought to affect gallstone fragmentation including gallstone number, size, composition, and volume. Schachler et al” found that routine radiological factors (ie, gallstone radiolucency or CT density) are not predictive of the degree of fragmentation; stone diameter and stone volume are the major factors that limit successful disintegration of human gallstones. Clinical data’.’ have shown that the best results are achieved in patients with single noncalcified gallstones 120 mm using current parameters. When ESWL is performed on patients with large stones or multiple stones, in vitro studies” have shown that increased shockwave energy, ie, increased numbers of shock waves at a higher kilovolt, will have to be administered compared with patients with single gallstones, I20 mm. In general, all gallstones can be fragmented with ESWL; however, the clearance rate for

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ESWL

271

patients with calcified or partially calcified gallstone stones is significantly less than for radiolucent gallstones.2~6~7~‘2 Fragment Clearance

The time to stone clearance is related to a variety of factors with stone volume being the most important. In an attempt to reduce the stone clearance time, physicians performing ESWL now attempt to pulverize rather than fragment gallstones. In vivo work by the group at the Grosshadern Klinikum has shown that the smaller the fragments postlithotripsy, the sooner the patient becomes stone free.’ Role of Oral Bile Acids

Most investigators in the United States use an oral chemolytic agent, ursodeoxycholic acid, as part of the treatment protocol.‘-’ After fragmentation, the surface area available to the chemolytic agent is increased. In vitro work by Schachler’” has suggested that the 2-mm fragment size postlithotripsy would be ideal for rapid dissolution with chemolytic agents. Other investigators13 have demonstrated good gallstone clearance rates without the use of a chemolytic agent; this is presumably due to the small fragment size achieved with high energy and, at times, multiple treatments. Follow-up After Extracorporeal Shock- Wave Lithotripsy

Follow-up studies are performed to document the efficiency of fragmentation, the clearance of small fragments, and the shrinkage and eventual clearance of larger fragments. In most protocols, fragments less than 5 mm call for additional treatments. A diagnostic problem can be produced by the aggregation of small fragments into a larger clump that can resemble a large fragment. We have advocated the use of a rollover maneuver (Fig 4) to disperse these clumps to avoid unnecessary retreatments.14 CLINICAL RESULTS

Initial European Results

The first large biliary ESWL patient study was reported by Sackmann et al2in 1988 and has become the de facto gold standard; this study

reported the results of 184 ESWL treatments in 175 patients and was performed using a modified water bath lithotripter, the Dornier HM3, and general anesthesia. All patients in this study received a combination of chemolytic agents, chenodeoxycholic and ursodeoxycholic acid (UDCA). Patients received anesthesia by a variety of routes: intravenous sedation, 56%; epidural anesthesia, 22%; general anesthesia, 21%; and no anesthesia, 1%. Complete disappearance of fragments was observed in 30% of patients within 2 months of the procedure, 48% at 2 to 4 months, 63% at 4 to 8 months, 78% at 8 to 12 months, and 91% at 12 to 18 months. The dissolution rate was highest (95%) for patients with a solitary stone 120 mm diameter. Nine patients in the study required a second treatment (allowed only at 6 weeks) to produce fragments 15 mm. Adverse events were few: cutaneous petechiae in 14%, biliary colic in 35% until free of stones, and mild pancreatitis in two patients. United States Trials Dornier

National

Biliary

Lithottipsy

Study.

The data6from this study were presented in the intent-to-treat form of analysis that requires that all patients screened and randomized be included in the results. Patients randomized but not treated and patients not returning for follow-up are assumed to be treatment failures. Using the intent-to-treat form of analysis, at 6 months 22% of patients taking UDCA and 8% of patients on placebo were stone-free. If one excludes the patients with calcified stones and those not returning for follow-up, the stone-free rate increases to 32% for patients on UDCA and 18% for patients taking placebo. If the data are further stratified to evaluate a target group of I 20 mm noncalcified solitary gallstones, the stone-free rate increases to 43% for patients on UDCA and remains at 18% for patients on placebo. The patients who had ESWL with UDCA had a higher stone-free rate than those receiving ESWL with placebo. In addition, the trend of increasing successwith UDCA after ESWL suggests that continued treatment with UDCA beyond 6 months would produce further success. The patients with 120 mm radiolucent, noncalcified gallstones on UDCA had the high-

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Fig 4. The rollover maneuver. (A) Six weeks following ESWL, residual fragments are observed within the gallbladder. Some of these fragments appear quite large. (6) Following the rollover maneuver, the fragment clumps disperse showing only small residual fragments.

est stone-free rate at 6 months-a rate significantly higher than the B-month clearance for UDCA alone. United Statesand European Differences The stone-free rates in the other United States studies are, in general, lower than those

in the initial German study.627,15,16 The study by Sackmann et al2 was not published using the intent-to-treat form of analysis and used a modified water bath machine (Dornier HM3) with general anesthesia. When the transition to the second generation nonwater lithotripter occurred, it was assumed that the treatment

GALLSTONE ESWL

273

parameters, ie, energy levels, used on the original lithotripter were readily transferrable to the newer lithotripter; this later proved to be an incorrect assumption. The physician in Europe has more flexibility in changing treatment parameters than in the United States. Recent data from the group at the Grosshadern Klinikum in Munich’ using increased shock-wave energy (ie, increased number of shock waves at a higher kilovoltage) showed a better fragmentation rate and an increased stone clearance at 6 months than data obtained when treatment parameters similar to the US Dormer protocol were used. Similar high clearance rates have also been recently reported in US studies.” GALLSTONE

RECURRENCE

Gallstone fragments present after ESWL may act as a nidus for new stone formation. Studies published after gallstone dissolution with oral bile acids have shown gallstone recurrence to be approximately 10% per year with a maximum of 40% to 50% at 5 yearsl’; however, only 50% of patients with recurrent gallstones after oral bile acid therapy become symptomatic.” In a study on patients post-ESWL, Sackmann et al*” found that early gallstone recurrence after successful lithotripsy occurred in 9% of patients within the first year. The estimated stone recurrence (actuarial analysis) up to 3 years was 11% (-+4%) at 1.5 years with no

further increase up to 3 years. Sackmann, in this article, suggested that the recurrence rate may be lower in patients with single as opposed to multiple gallstones; a stone-free interval of about 9 months after cessation of oral bile acids may have a predictive value for the absence of future stone recurrence. A variety of options for preventing recurrence are being explored. Prolonged oral bile acid therapy, nonsteroidal, antiinflammatory agents, cholesterol-lowering agents, and gallbladder ablation are all under active investigation as potential methods to prevent or treat recurrence.‘l CONCLUSION

Biliary lithotripsy is a safe procedure and in carefully selected patients has a stone clearance rate significantly higher than the use of UDCA alone. This procedure is still in its infancy as compared with other long-established methods of gallstone therapy. As our knowledge of the procedure grows, the efficacy of the procedure will no doubt increase. It seems clear that, at least in patients with solitary radiolucent stones I 20 mm, ESWL is a viable alternative to all current methods of treatment including laparoscopic cholecystectomy. Its ultimate role in the treatment of patients with multiple, larger, and calcified stones remains to be established by future clinical and experimental studies.

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17. Albert MB, Fromm H, Borstelmann R, et al: Successful outpatient treatment of gallstones with piezoelectric lithotripsy. Ann Intern Med 113:164-166,199O 18. Lanzini A, Jazrawi RP, Kupfer RM, et al: Gallstone recurrence after medical dissolution-an over estimated threat? J Hepatol3:241-246, 1986 19. Ruppin DC, Dowling RH: Is recurrence inevitable after gallstone dissolution by bile acid therapy? Lancet 1:181-R%,1982 20. Sackmann M, Ippisch E, Sauerbruch T, et al: Early gallstone recurrence rate after successful shock wave therapy. Gastroenterology 98:392-396,1990 21. Barkun ANG, Ponchon T: Extracorporeal biliary lithotripsy: Review of experimental studies and a clinical update. Ann Intern Med 112:126-137,199O