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10, NO. 3, 1990
Extracorporeal Shock-Wave Lithotripsy of Gallstones with the Adjuvant Use of Cholelitholytic Bile Acids
The introduction of extracorporeal shock-wave lithotripsy (ESWL) as a promising alternative to gallbladder surgery represents a dramatic application of high technology to the treatment of a very common disease. Preliminary studies from the United States and other countries indicate that gallstone ESWL may one day have an impact on the management of cholelithiasis. in the same way that kidney stone ESWL has revolutionized the management of urolithiasis. The purpose of this review article is to discuss the role of this new technology as it applies to the current and future management of patients with gallstones.
BACKGROUND ESWL originated in Germany. Shock waves were generated in large water baths by electrohydraulic devices to fragment renal calculi. Experiments in animals were published by Chaussy et all in 1980, and human trials began the same year.? By 1988. more than 500.000 patients with kidney stones had been treated by ESWL.j The application of ESWL to gallstones followed soon. Gallstone ESWL studies in animals were first reported in 1983,' and human trials were begun in 1984.5." By 1989, more than 5000 patients with gallstones had been treated worldwide.' Second-generation lithotripters using piezoelectric and electromagnetic technologies were developed and proved less expensive to install and maintain. In addition, they required little or no anesthesia and no immersion of patients in water baths.x-"'
PRINCIPLES AND TECHNOLOGY Extracorporeally generated shock waves are highamplitude pressure waves characterized by a positive pressure pulse of short duration. Within nanoseconds, pressures as high as 1000 bar (atmospheric pressures) can be attained. The behavior of shock waves follows the laws of acoustics. but differs somewhat from that of Frotw rht Di~7ision of' Gastrorntc,rology crt~d N u t r i t i o t ~ . The G r o r g r Wcishington Univrrsity Mrdic.cr1 Cet~tor.Wrrshrngton. D . C .
Reprint requests: Dr. Albert. Division of Gastroenterology and Nutrition. The George Washington Univers~ty Medical Center. Washington. D.C.
sound waves in regard to wave propagation, reflection, and focusing. Although ESWL has been studied for only a few years, various ESWL technologies are now being investigated in a large number of centers around the world,"6. I 1-23 There are principally three technologies that are being used to generate lithotriptic shock waves. All three technologic principles involve the extracorporeal generation of shock waves in a liquid medium. The first technology (Direx, Dornier, Medstone, Northgate, Technomed) features high-voltage spark d i s ~ h a r g e . ~ . ~ . ~ ~ ' ~ . ? " The sudden evaporation of water results in the generation of shock waves that are reflected by an elliptical reflecting cavity into a focus. With the second generation of lithotripters, shock waves are produced by piezoelectric crystals (Diasonics, EDAP, Wolf) or by an electromagnetic membrane (Siemens). The piezoelectric device features a large array of crystals arranged in a semiellipsoid The crystals are simultaneously excited to generate shock waves that are transmitted first through an oil phase and then through a water medium. Due to both the large surface area and the semiellipsoid arrangement of the piezoceramic elements, the shock waves can be focused onto a small, well-defined area. The piezoceramic elements do not need to be frequently replaced, as is the case with the electrode of the spark discharge-based lithotripters. In contrast to the latter type of machines, the piezoelectric devices do not generally require the use of anesthesia, analgesia, or sedation in the patient.".I5.'"" The principal components of the electromagnetic lithotripter consist of a metal membrane and an acoustic lens. Electromagnetically induced vibrations of the metal membrane result in the generation of shock waves. The waves are concentrated by an acoustic lens in a focus into which the gallstone is positioned. All three types of lithotripters are now constructed with a closed water bath, no longer requiring submersion of the patent. Coupling gel facilitates transmission of the shock waves from the treatment head of each device into the body of the patient. The gallstone is targeted using a computerized ultrasonographic guidance system. Common bile duct stones must be targeted fluoroscopically. Since the soft tissues of the body have an acoustic impedance similar to that of water, the shock waves are transmitted virtually unimpeded until encountering airfilled spaces or concretions, such as stones. In the latter
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MICHAEL B. ALBERT, M.D., and HANS FROMM, M.D.
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case, abrupt changes in the acoustic impedance occur, with the consequent development of 1.ear and shear forces and cavitation phenomena shattering the stone. The power of the shock waves generated differs among the lithotripter systems. Higher total shock-wave energies can be generated with the spark discharge than with the piezoelectrically or electromagnetically produced shock .,5.6.13.IX.?1.?4 primarily due to the larger area into which the shock waves are focused. The sharper focus of the piezoelectric machine appears to allow fragmentation to take place at lower pressures than does the larger focus of the spark discharge-based devices and may account for the diffei-ences in anesthesia and analgesia requirements that exist between the technologies.
IN VlTRO EXPERIMENTS In in vitro lithotripsy studies, gallstone characteristics have been identified that favor effective fragmcntation (Table 1). The relative importance of the size, radiographic appearance (plain x-ray, ultrasound, and computed tomography), and chem~calcomposition of the gallstones as determinants of efl'icacy of fragmentation has been studied at our center and by other^.'".'^-?^ Most studies with spark-gap and piezoelectric devices suggest that the size, weight, and volume of the gallstones rather than their radiologic (or ultrasonographic) appearance or chemical compositior~correlate best with the rate of fragmentation by ESWL,. Staritz et on the other hand, using an electromagnetic lithotripter, showed that low density cholesterol stones, as determined by computed tomography, were more difficult to fragment. Using the EDAP LT-01 piezoelectric lithotripter, we have studied the effect in vitro of the frequency and total number of shock waves, as well as other parameters, on gallstone fragmentation in order to maximize the
TABLE 1. Research to Define the Most Effective and Safest Use of ESWL for Gallstones In vitro models Shock-wave parameters Frequency Intensity Total number of shocks Duration o f treatment Targeting Gallstone parameters Size Number Con>position P l a ~ nx-ray Computed tomography Animal experiments Gallbladder wall damage Injury to adjacent organs and tissue Clinical trials Safety and efficacy Number of retreatments and interval between treatments Use of adjuvant oral dissolution agents Stone recurrence rate Cost-effectiveness
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lithotripter settings." Fragmentation time was inversely proportional to the selected frequency of shock-wave delivery. The mean length of time required to fragment small (5 to 6 mm cholesterol) gallstones was 25 minutes at 1.25 Hz, 19 minutes at 10 Hz, and only 5 minutes at 40 Hz. However, we also found that shock-wave efficacy decreased at higher frequencies; despite the shorter time interval, a mean of 13,000 total shocks was required to fragment completely small stones at 40 Hz, compared with 11,000 at 10 Hz, and only 1900 at 1.25 Hz. In another series of experiments, single stones of similar size and compositibn were fragmented after being positioned at different intervals above and lateral to the lithotripter's focal point. Stones did not fragment at a distance of greater than 15 mm above the focal point or greater than 7.5 mm lateral to the focal point. These results suggest that lithotripter settings and accurate gallstone targeting are important determinants of the efficacy of gallstone fragmentation. Clinically, these in vitro studies should aid considerably in patient selection and in maximizing device settings. This may facilitate broadening of the current eligibility criteria to include calcified and multiple stones.?j
ANIMAL STUDIES Adverse effects of ESWL on tissues were first reported in animal experiment^',^*-^^ and later confirmed . ~ . ~ as . ~ well " as only microin clinical s t ~ d i e s . ~ . ~Gross scopically detectable shock-wave lesions appear to result primarily from vascular injury. Renal lesions in dogs are similar to those in humans and include perirenal edema, hemorrhage, hematomas, subcapsular hematomas, and vascular lesions such as focal necrosis of veins with thromboSis,?Y.~1.32.i1.i5.ih
Gallbladder ESWL in animals can cause hemorrhage in the wall of the gallbladder, in the liver, and in the lungs,4.?K.31.3?.3h.37Vascular lesions have been observed in the hepatic veins of dogs subjected to ESWL." These are reminiscent of changes seen with ionizing radiation." Despite the increasing use of ESWL, little is known about the mechanisms by which tissue is injured. Physical impact of shock waves, cavitation phenomena (formation of expanding bubbles and their subsequent collapse), and formation of free radicals are suspected . " , "impact of many pamodes of tissue i n j ~ r ~ . ' ~ . ~ ~The rameters of shock waves and their production, such as physical characteristics of the wave, peak pressures, voltage, frequency, and total number of shocks, as well as number of treatment sessions and length of intervals between repeated treatments, on the efficacy and safety of lithotripsy has not been defined.
PATIENT SELECTION Initial clinical experience with ESWL at our center and by others suggests that proper patient selection is essential if successful fragmentation is to be
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TABLE 2.
Selection Criteria for ESWL of Gallstones
Currri71
Tl7eoretic~trlRtrriorltrle
Symptomatic patients Stone size < 3 cm
Stone number
5
3
Radiolucent stones Functioning gallbladder
Stones > 5 nim
Cost-benefit ratio Shock-wave energy may not reach threshold to fragment larger gallstones Concrements and debris hinder effective fragmentation Inability to dissolve calc~fied fragments with adjuvant bile acids Poor expulsion of fragments and poor concentration of oral dissolution agents in nonfunctioning gallbladder Sufficient resolution with current inline ultrasound
achieved.h.7.2?.10.1'The patient selection criteria for ESWL of gallstones resemble, in several important aspects, those for oral bile acid cholelitholytic therapy (Table 2). Both the experimental nature of the procedure and costeffectiveness considerations restrict the use of ESWL to symptomatic gallstones. Therefore, only patients with a history of biliary pain are presently considered to be eligible for cholelithotripsy. In addition, in most ESWL centers in the United States only radiolucent gallstones in a functioning gallbladder are being treated. The radiolucency of the gallstones is defined by the absence of visible calcifications in the gallbladder region on a roentgenogram of the abdomen. Gallbladder function is defined by the opacification of the gallbladder by an oral cholecystogram. It is also recommended that the gallstones do not exceed 3 cm in diameter. In addition to stone size, the number of stones has been found to influence the success rate of ESWL. The best results are obtained in patients with single stones.h.'".??The efficacy appears to drop significantly if more than three stones are present. Effective lithotripsy becomes more difficult with increasing stone number due to the obscuration of the concrements by the pile of stone fragments and debris produced by the procedure. Future studies may, however, show that improved accuracy and precision of the ultrasonographic targeting of the stones as well as the ability to repeat the ESWL safely in intervals of only a few days will allow effective cholelithotripsy in patients with more than three stones.
Contraindications to ESWL ESWL is contraindicated in patients who have developed acute complications from gallstone disease, such as acute pancreatitis, cholecystitis, or cholangitis (Table 3). Other contraindications relate to the described predictors of a very low success rate of lithotripsy, that is, the presence of a nonfunctioning gallbladder, of very large (more than 3 cm in diameter) stones or of dense calcifications. The procedure may also be contraindicated in patients in whom anatomic variations of the position of the gallbladder or massive obesity make it very
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FROMM TABLE 3.
Contraindications to ESWL of Gallstones
Frequent attacks of b i l ~ a r ycolic (impending cholecystiti\) Complications from gallstones (cholecystitis. pancreatitis, choledocholithiasis, cholangitis) Nonfunctioning gallbladder (by oral cholecy\tography) Very large o r numerous gallstones Calcified gallstones M a s i v e obesity Subcostal location of gallbladder Bleeding disorder or use of anticoagulants Chronic use of aspirin or nonsteroidal anti-inflammatory agents Large hepatic cy\ts in pathway of shock waves Vascular aneurvsms Pacemaker or significant cardiac arrhythmias Pregnancy
difficult to locate the gallbladder and target the gallstone under ultrasound guidance. In order to prevent bleeding or the development of a hematoma during ESWL, patients should have neither disease- nor drug-induced clotting abnormalities. Therefore aspirin and other antiinflammatory agents should be discontinued at least I week prior to the treatment.
EFFICACY European investigators, adhering to the above selection criteria, have reported excellent ESWL results, a 95 to 100% efficacy in patients with single stones and a 67% efficacy in patients with two or three stones within 12 to 18 months after treatment." These results were obtained with all patients receiving adjuvant therapy with an ursodiol (UDCA)-chenodiol (CDCA) combination. The latter was initiated 2 weeks prior to lithotripsy and terminated 2 months after ultrasonographic documentation of complete disappearance of the gallstones. In most patients, clearance of fragments from the gallbladder occurred only after several months of continuous adjuvant bile acid therapy. Preliminary multicenter results in the United States using similar technologies have been less impressive." Results from two large multicenter trials using spark-gap lithotripters were recently reviewed by the Food and Drug Administration. In a randomized controlled trial, using the Dornier MPL 9000 lithotripter, the overall 6month stone-free rate was 22% in the group treated with adjuvant ursodiol and 8% in the group treated with ESWL alone. In the second study, which was uncontrolled, using the Medstone STS lithotripter in conjunction with ursodiol treatment, 26% of the total patients were stone free by 6 months. When only solitary stones up to a size of 20 mm were considered, the stone-free rates at 6 months in patients treated with both lithotripsy and ursodiol were 48% and 35% respectively, in the two studies ." Similarly, in an on-going uncontrolled multicenter study, using a piezoelectric technology (EDAP LT-01) and adjuvant ursodiol treatment, we and coinvestigators have reported overall stone-free rates of 13%, 29%, and
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FIG. 1. Treatment of patient with piezoelectric shock-wave therapy. A: Baseline ultrasound shows solitary 1.5 cm gallstone in lumen of gallbladder. B: Initial fragrr~entat~on of gallstone after 5 minutes of treatment. C: Complete fragmentation to small particles layering on dependent wall of gallbladder following 60 minutes of treatment. D: Complete clearance of fragments 1 month following the procedure on concomitant ursodiol therapy.
38% at 3 , 6. and 9 months.-" Patients with solitary gallstones 20 mm or sn~allerwere free of stones in 52% of the cases by 6 months. In our center, 37 of 60 patients have been followed for 9 rnonths. The rate of stone freedom is 62% overall and 75% in patients with solitary stones 20 nim or less,4' which is similar to the initial European results. Treatment results from one of our first patients are depicted in Figure I. PLI1our patients have been treated on an outpatient basis, and no patient has required any anesthesia, analgesia. or sedation during treatment. There are probably several explanations tor the wide range in treatment results repc~rtedwith the different technologies as well as by ditferent centers using either the same or different devices in part, this can be attributed to differences in operatol experience and patient selection. Most investigators are experiencing a "learning curve," which is charactzristic for the use of this intricate technology. The maximization of the treatrnent parameters and techniques for the different devices is therefore likely to take more timr:. Furthermore, centers selecting only patients with favorable stone characteristics (solitary, srnall in size) will achieve better overall results than those including larger. multiple, and calcified stones.
ADJUVANT BILE ACID TREATMENT Controlled studies are currently being conducted by United States investigators to evaluate the need for oral bile acid dissolution treatment in conjunction with ESWL. A nurnber of previous observations and pathophysiologic considerations suggest that UDCA or a combination of UDCA and CDCA must be given to most patients for a prolonged period of tirne following ESWL in order to achieve optimal treatment results (Table 4). The described postlithotripsy gallstone disappearance rate during continued adjuvant oral bile acid therapy in both the published European studies and the patients treated at our center is. in most cases, consistent with dissolution of the gallstone fragments, rather than spontaneous gallstone clearance from the gallbladder."." It appears possible. if not likely, that, in many instances. the fragments are ejected from the gallbladder after they have dissolved to a small size. In one study, it was observed that two of three patients who did not comply with the adjuvant bile acid therapy showed persistence of the fragments after a prolonged period of follow-up and prompt conglomeration of the stone fragments." In addition, preliminary results from the Dornier United States multicenter trial show a three-fold increase in
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TABLE 4.
Rationale for Adjuvant Bile Acid Treatment
Disappearance rate of residual fragments post ESWL con\istcnt with gradual d~ssolutionprocess in many patients Impaired spontaneous dissolution o f the stone fragments and their expulsion from the gallbladder in presence of cholesterol-supersaturated bile and decreased gallbladder contractility Contractile function of the gallbladder remains impaired until the gallstone residues are completely dissolved. ESWL improves conditions for oral bile acid dissolut~ontreatment Patients not complying w ~ t hadjuvant bile acid therapy may show either persistence or conglomeration of \tone fragments after ESWL Threefold increase in stone disappearance in patients given adjuvant ursodiol (preliminary results from the Dornier randomired United States multicenter trial)
stone disappearance in patients given adjuvant urso-
dial.-" It also appears likely that the combination of cholesterol-supersaturated bile and decreased gallbladder contractility, which characterizes the majority of cholelithiasis conditions, will impair both the spontaneous dissolution of the stone fragments and their expulsion from the gallbladder. Indeed, recent observations by one group of investigators indicate contractile function of the gallbladder to remain impaired until the gallstone residues are completely d i s ~ o l v e d . ~The ' presence of cholesterol-supersaturated bile per se has been shown in animal studies to lead to changes resembling those of chronic cholecystitis.'" It appears therefore that all presently available data, observations, and pathophysiologic considerations support the rationale for the use of adjuvant oral bile acid therapy in gallstone patients after ESWL.IJ However, controlled data must be awaited before final recommendations can be made concerning the efficacy of adjuvant cholelitholytic treatment with bile acids.
SAFETY Laboratory changes caused by gallbladder ESWL in clinical trials are reportedly limited to transient leukocytosis and infrequent hematuria, hemoglobinuria, and elevation of liver enzyme^.'^^.'^'^^' Stephenson et alx described epithelial denudation as well as mural edema and hemorrhages in human gallbladders exposed to ESWL. The two main adverse effects or complications, which have been reported to occur in only I to 2% of the patients, are cholecystitis and pan~reatitis.~.'"'~ Both complications are thought to be the result of fragments obstructing either the cystic or common bile duct. Fortunately, in most cases, the bile duct obstruction appears to be transient, not requiring surgical intervention. In the minority of cases with postlithotripsy pancreatitis, endoscopic papillotomy was carried out to relieve the common bile duct obstruction. Most of the complications were reported to occur within the first weeks after ESWL.
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Transient hematuria and local petechiae or ecchymoses of the skin at the entrance or exit path of the shock waves are relatively minor adverse effects that appear to be more prevalent with the use of spark discharge than with that of piezoelectric lithotripters. Biliary colic has been observed to continue after lithotripsy at a rate that appears to be similar to that occurring before the procedure until the gallbladder is free of stone fragments, 6 . 1 v . 1 1 . 4 ~The experience in our center concerning lithotripsy-related complications is comparable to that reported by the European authors. Except for occasional biliary pain and a case of mild pancreatitis, no significant symptoms or complications have occurred in any of our patients treated thus far. To our knowledge, several complications associated with kidney lithotripsy have not been reported following biliary lithotripsy. These include hypertension," iliac vein t h r o m b ~ s i s , and ~ " retroperitoneal hemorrhage," and may be unique to kidney lithotripsy due to the focusing of shock waves within the renal parenchyma. Further studies are needed to determine whether differences, which, at least presently, exist between the different types of lithotripters as far as size of the focus or power of the shock waves as well as anesthesia or analgesia requirements are concerned, are reflected by differences in risks or adverse effects and complications.
STONE RECURRENCE AFTER ESWL There is limited information on the rate of gallstone recurrence after ESWL. Preliminary data by one group of investigators indicate it to be lower than the approximately 50% recurrence within 5 years, which has been described after successful oral cholelitholytic treatment, 51-51 In contrast to patients treated with oral dissolution agents alone, however, gallstones that recur after ESWL tend to be associated with biliary pain.lJ More data concerning the postlithotripsy recurrence of gallbladder stones are needed both to evaluate its clinical significance and to develop guidelines for its management. In particular, the question of the appropriateness and feasibility of retreatment by ESWL requires studies for each lithotriptic device and technology.
COMMON BlLE DUCT STONES Sauerbruch and colleagues' from Munich first showed that common bile duct stones could be successfully fragmented with ESWL. Recently, these investigators reported a prospective uncontrolled multicenter trial in which 113 patients with symptomatic common bile duct stones were treated with a spark-gap, waterbath lithotripter." Presenting symptoms and complications included jaundice, cholangitis, and biliary pain. Prior attempts at endoscopic mechanical extraction or solvent dissolution of the ductal stones were unsuccessful. In all cases, sphincterotomy had been performed prior to lithotripsy. Most stones were either impacted in
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the common bile duct or too large for basket extraction. After the patient was immersed in the water bath, the bile duct stones were located and positioned into the shockwave focus under fluoroscopic guidance, aided by injection of contrast medium via a nasobiliary or transhepatic catheter. Successful fragmentation was achieved in 9 1 C/o and complete stone clearance in 86% of patients after one or more ESWL sessions. Clearance was facilitated by endoscopic extraction of residual fragments or by instillation of solvents in 73% and 3% of patients, respectively. The remaining patients passed all of the fragments spontaneously. Side effects and complications occurred in 36% of patients and included mild cardiac arrhythmias, mild and transient hemobilia, skin hematomas, microhematuria, and biliary pain. This well-conducted study showed that the treatment of patients with common bile duct stones not amenable to endoscopic extraction or dissolution can be accomplished safely and effectively with ESWL.
ISSUES CONCERNING THE FUTURE OF ESWL A number of issues concerning the future role of ESWL in the management of gallstonr: disease have been raised at the various meetings. hearings. and symposia held worldwide (Table 5). Areas of debate include patient selection, operator training and credentialling, costeffectiveness, and expanded use of the technology. ESWL would seem to be an ideal therapeutic alternative for the patient with concomitant medical problems who is a poor candidate for surgery. However, there is much debate over whether ESWL should be offered to the healthy, young patient with symptomatic gallstones in whom cholecystectomy is safe and provides a permanent cure in most cases. Even more controversial is the idea of prophylactic ESWL in the asymptomatic patient with gallstones. Although only 15 to 20% of these
TABLE 5. Issues That Need to be Addressed to Determine the Future Role of ESWL of Gallstones Patient selection Operator training and credentialling Cost-el'lectiveness Role of ESWL vis-8-vi\ that of other nonsurg~caland surgical a1 ternatives Expanded use ol' the technology Prophylactic u\e In asymptomatic ydlstone patient\ Interaction and responsibility o f d~flerentspecialtie\ in ESWL program Role in treatment of comon bile duct atones S t a n d a r d i ~ a t ~ oofn definition of treatment succes\ Retreatment rate Expansion of inclusion criteria (stone burden, calcification) Treatment of high-risk patients Optimum treatment parameters Recurrence of stones following complete stone disappearance Long-term sequelae
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patients will go on to develop biliary symptoms or complications, early treatment of stones while they are small, few in number, and not causing problems might be costeffective, particularly if the treatments can be shown to be safe, effective, and able to be performed on an outpatient basis. Another area of concern is over who should operate the lithotripter. Most agree that clinical experience in managing patients with gallstone disease as well as a firm background in biliary ultrasound are required. In some centers, such as ours, a gastroenterologist, with special training in biliary ultrasound, performs the procedure. Other centers take a multidisciplinary approach, involving members from the gastroenterology, surgery, and radiology departments. The length of time required for a nonradiologist to learn biliary ultrasound and the number of lithotripsy treatments necessary to assure competence are being evaluated by professional societies, such as the American Gastroenterological Association, the American Association for the Study of Liver Diseases, the American Lithotripsy Society, and the American Society of Gastrointestinal Endoscopists. The issue of cost-effectiveness is complex and must take into account factors such as the overall effectiveness of the procedure, the stone recurrence rate, retreatment rates, and the relative costs of alternative surgical and nonsurgical treatments. Our current impression is that ESWL will be cost effective in selected symptomatic patients with ideal stone characteristics, i.e., small and few in number. The successful application of the procedure for larger and more numerous stones will likely take more time as treatment parameters are optimized and technology (ultrasound images, focusing, higher energies) is improved. A final interesting issue deals with expanding the use of lithotripsy into areas of medical treatments other than gallstone disease. Recently, reports of treating pancreatic stones'" and even gastric outlet obstruction caused by an intraluminal gallstone" have appeared in the literature. The Food and Drug Administration recently addressed these and other issues, and, at the time of this writing, has felt it prudent to withhold market approval for gallstone lithotripsy until these issues are addressed adequately. The information obtained thus far, both in other countries and in the United States, however, suggests that ESWL is here to stay and should, one day, have a large impact on the management of gallstones in selected patients. A~~Xt7o~vlrdgtnmr.The authors would like to acknowledge Dr. Bernard Zook. Professor of Pathology and Director of Animal Research. for his assistance in reviewing the published animal data.
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thesia and water bath: A crit~calresume in the third year of clinical routine. (Abstr.) Gastroenterology 96:A487, 1989. Ell C. Kerzel W. Langer H, et al: Fragmentation of biliary calculi by means of extracorporeally generated piezoelectric shock waves. Dig Dis Sci 34:10061010, 1989. Schachler R , Sauerbruch T. Wosiewit~U, et al: Fragmentation of gallstones using extracorporeal shock waves: An in vitro study. Hepatology X:925-929, 1988. Staritz M, Floth A, Buess G , et al: Extracorporeal shockwaves (ESW) for gallstone fragmentation: First in-vitroexperience with a second generation device working without the conventional water bath. (Abstr.) Gastroenterology 92:1652A, 1987. Delius M. Enders G . Heine G , et al: Biological effects of shock waves: Lung hemorrhage by shock waves in dogspressure dependence. Ultrasound Med Biol 13:6 1-67. 1987. Delius M. Enders G. Xuan Z, et al: B~ologicaleffects of shock waves: Kidney damage by shock waves in dogs-dose dependence. Ultrasound Med Biol 14: 1 17-122. 1988. Delius M. Jordan M. Ei~enhoeferH. et al: Biological efltcts of shock waves: Kidney hemorrhage by shock waves in dogsadministration rate dependence. Ultrasound Med Biol 14:6XY694, 1988. Delius M. Jordan M. Liebich H. Brendel W: Effect of shock waves on the liver and the gallbladder tlssue of dogs. (Abstr.) Gastroenterology 94:94A. 1988. Newman R. Bland K. Gravenstein N. et al: Extracorporeal shock-wave l~thotripsy(ESWL). I I . In vivo canine results of blast path treatment of human gallstones. J Surg Res 44:578588. 1988. Jaeger P. Redha F, Uhlschm~d G. Hauri D: Morphological changes in canine kidneys following extra-corporeal shock wave treatment. Urol Res 16: 161-166. 1988. Drach GW, et al: Report of the United Cooperative Study of Extracorporeal Shock Wave Lithotripsy. J Urol 135: 11271133. 1986. Abrahams C. Lipson S. Ross L: Patholog~cchanges In the k ~ d neys and other organs of dogs undergoing extracorporeal shock wave lithotripsy with a tubless I~thotripter.J Urol 140:391394, 19XX. Chaussy C. Schm~edtE. Jocham D. et al: Extracorporeal Shock Wave Lithotripsy. Technical Concept. Experimental Research. and Clinical Applicat~on. Munchen, S . Karger, 1986. pp 34-14.. Ell C. Kerzel W. Heydcr N, ct al: Piezoelectric lithotripsy of gallstones. Lancet 1: 1 149-1 150, 1987. Morgan T, Laudone V, Heston W, et al: Free radical production by high energy shock waves-comparison with ionizing irradiation. J Urol 1988: 139: 186-189. 1988. Coleman A, Saunders J , Crum L, Dyson M: Acoustic cavitation generated by an extracorporeal shockwave lithotripter. UItrasound Med Biol 13:69-76. 1987. Albert MB. Fromm H: Non-\urgical alternat~vesin the management of gallstones. J Intensive Care Med 4:3-10, 1989. Brink JA. Simeone JF, Mueller PR. et al: Physical characterIstics of gallstones removed at cholecystectomy: Implications for extracorporeal shock-wave lithotripsy. AJR l988:121:927931. 1988. Stern WR: Members of the Ad Hoc Committee on FDA-related matters of the college. Meeting of the Food and Drug Administration Gastroenterology-Urology Device Section Advisory Panel on extracorporeal shock-wave lithotripsy Ibr gallbladder stones. October 19, 1989. Am J Gastroenterol 85:23840, 1990. Albert MB, Fromm H: U.S. multicenter study of the safety and efficacy in treating gallstones with piezoelectric lithotripsy. Gastroenterology 98:A564, 1990. Albert MB, Fromm H, Borstelmann R, Shehan CM, Gicking
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R: Successful outpatient treatment of gallstones with piezoelectric lithotripsy. Ann Int Med (in press). Spengler U , Sackmann M. Sauerbruch T, et al: Gallbladder motility before and after shock-wave lithotripsy. Gastroenterology 96:860-863, 1989. Lee SP, Scott AJ: The evolution of morphologic changes in the gallbladder before stone formation in mice fed a cholesterolcholic acid diet. Am J Pathol 108: 1-8, 1982. Brunner H, Jurkovic K: Dark urine aftzr extracorporeal shock wave lithotripsy. Lancet 2: 1 150. 1987. Greiner L, Wenzel H . Jakobeit C Biliare StosswellenLithotripsy. Fragmentation und Lyse-
10, NO. 3, 1990
Extracorporeal Shock-Wave Lithotripsy of Gallstones with the Adjuvant Use of Cholelitholytic Bile Acids
The introduction of extracorporeal shock-wave lithotripsy (ESWL) as a promising alternative to gallbladder surgery represents a dramatic application of high technology to the treatment of a very common disease. Preliminary studies from the United States and other countries indicate that gallstone ESWL may one day have an impact on the management of cholelithiasis. in the same way that kidney stone ESWL has revolutionized the management of urolithiasis. The purpose of this review article is to discuss the role of this new technology as it applies to the current and future management of patients with gallstones.
BACKGROUND ESWL originated in Germany. Shock waves were generated in large water baths by electrohydraulic devices to fragment renal calculi. Experiments in animals were published by Chaussy et all in 1980, and human trials began the same year.? By 1988. more than 500.000 patients with kidney stones had been treated by ESWL.j The application of ESWL to gallstones followed soon. Gallstone ESWL studies in animals were first reported in 1983,' and human trials were begun in 1984.5." By 1989, more than 5000 patients with gallstones had been treated worldwide.' Second-generation lithotripters using piezoelectric and electromagnetic technologies were developed and proved less expensive to install and maintain. In addition, they required little or no anesthesia and no immersion of patients in water baths.x-"'
PRINCIPLES AND TECHNOLOGY Extracorporeally generated shock waves are highamplitude pressure waves characterized by a positive pressure pulse of short duration. Within nanoseconds, pressures as high as 1000 bar (atmospheric pressures) can be attained. The behavior of shock waves follows the laws of acoustics. but differs somewhat from that of Frotw rht Di~7ision of' Gastrorntc,rology crt~d N u t r i t i o t ~ . The G r o r g r Wcishington Univrrsity Mrdic.cr1 Cet~tor.Wrrshrngton. D . C .
Reprint requests: Dr. Albert. Division of Gastroenterology and Nutrition. The George Washington Univers~ty Medical Center. Washington. D.C.
sound waves in regard to wave propagation, reflection, and focusing. Although ESWL has been studied for only a few years, various ESWL technologies are now being investigated in a large number of centers around the world,"6. I 1-23 There are principally three technologies that are being used to generate lithotriptic shock waves. All three technologic principles involve the extracorporeal generation of shock waves in a liquid medium. The first technology (Direx, Dornier, Medstone, Northgate, Technomed) features high-voltage spark d i s ~ h a r g e . ~ . ~ . ~ ~ ' ~ . ? " The sudden evaporation of water results in the generation of shock waves that are reflected by an elliptical reflecting cavity into a focus. With the second generation of lithotripters, shock waves are produced by piezoelectric crystals (Diasonics, EDAP, Wolf) or by an electromagnetic membrane (Siemens). The piezoelectric device features a large array of crystals arranged in a semiellipsoid The crystals are simultaneously excited to generate shock waves that are transmitted first through an oil phase and then through a water medium. Due to both the large surface area and the semiellipsoid arrangement of the piezoceramic elements, the shock waves can be focused onto a small, well-defined area. The piezoceramic elements do not need to be frequently replaced, as is the case with the electrode of the spark discharge-based lithotripters. In contrast to the latter type of machines, the piezoelectric devices do not generally require the use of anesthesia, analgesia, or sedation in the patient.".I5.'"" The principal components of the electromagnetic lithotripter consist of a metal membrane and an acoustic lens. Electromagnetically induced vibrations of the metal membrane result in the generation of shock waves. The waves are concentrated by an acoustic lens in a focus into which the gallstone is positioned. All three types of lithotripters are now constructed with a closed water bath, no longer requiring submersion of the patent. Coupling gel facilitates transmission of the shock waves from the treatment head of each device into the body of the patient. The gallstone is targeted using a computerized ultrasonographic guidance system. Common bile duct stones must be targeted fluoroscopically. Since the soft tissues of the body have an acoustic impedance similar to that of water, the shock waves are transmitted virtually unimpeded until encountering airfilled spaces or concretions, such as stones. In the latter
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case, abrupt changes in the acoustic impedance occur, with the consequent development of 1.ear and shear forces and cavitation phenomena shattering the stone. The power of the shock waves generated differs among the lithotripter systems. Higher total shock-wave energies can be generated with the spark discharge than with the piezoelectrically or electromagnetically produced shock .,5.6.13.IX.?1.?4 primarily due to the larger area into which the shock waves are focused. The sharper focus of the piezoelectric machine appears to allow fragmentation to take place at lower pressures than does the larger focus of the spark discharge-based devices and may account for the diffei-ences in anesthesia and analgesia requirements that exist between the technologies.
IN VlTRO EXPERIMENTS In in vitro lithotripsy studies, gallstone characteristics have been identified that favor effective fragmcntation (Table 1). The relative importance of the size, radiographic appearance (plain x-ray, ultrasound, and computed tomography), and chem~calcomposition of the gallstones as determinants of efl'icacy of fragmentation has been studied at our center and by other^.'".'^-?^ Most studies with spark-gap and piezoelectric devices suggest that the size, weight, and volume of the gallstones rather than their radiologic (or ultrasonographic) appearance or chemical compositior~correlate best with the rate of fragmentation by ESWL,. Staritz et on the other hand, using an electromagnetic lithotripter, showed that low density cholesterol stones, as determined by computed tomography, were more difficult to fragment. Using the EDAP LT-01 piezoelectric lithotripter, we have studied the effect in vitro of the frequency and total number of shock waves, as well as other parameters, on gallstone fragmentation in order to maximize the
TABLE 1. Research to Define the Most Effective and Safest Use of ESWL for Gallstones In vitro models Shock-wave parameters Frequency Intensity Total number of shocks Duration o f treatment Targeting Gallstone parameters Size Number Con>position P l a ~ nx-ray Computed tomography Animal experiments Gallbladder wall damage Injury to adjacent organs and tissue Clinical trials Safety and efficacy Number of retreatments and interval between treatments Use of adjuvant oral dissolution agents Stone recurrence rate Cost-effectiveness
10, NUMBER 3, 1990
lithotripter settings." Fragmentation time was inversely proportional to the selected frequency of shock-wave delivery. The mean length of time required to fragment small (5 to 6 mm cholesterol) gallstones was 25 minutes at 1.25 Hz, 19 minutes at 10 Hz, and only 5 minutes at 40 Hz. However, we also found that shock-wave efficacy decreased at higher frequencies; despite the shorter time interval, a mean of 13,000 total shocks was required to fragment completely small stones at 40 Hz, compared with 11,000 at 10 Hz, and only 1900 at 1.25 Hz. In another series of experiments, single stones of similar size and compositibn were fragmented after being positioned at different intervals above and lateral to the lithotripter's focal point. Stones did not fragment at a distance of greater than 15 mm above the focal point or greater than 7.5 mm lateral to the focal point. These results suggest that lithotripter settings and accurate gallstone targeting are important determinants of the efficacy of gallstone fragmentation. Clinically, these in vitro studies should aid considerably in patient selection and in maximizing device settings. This may facilitate broadening of the current eligibility criteria to include calcified and multiple stones.?j
ANIMAL STUDIES Adverse effects of ESWL on tissues were first reported in animal experiment^',^*-^^ and later confirmed . ~ . ~ as . ~ well " as only microin clinical s t ~ d i e s . ~ . ~Gross scopically detectable shock-wave lesions appear to result primarily from vascular injury. Renal lesions in dogs are similar to those in humans and include perirenal edema, hemorrhage, hematomas, subcapsular hematomas, and vascular lesions such as focal necrosis of veins with thromboSis,?Y.~1.32.i1.i5.ih
Gallbladder ESWL in animals can cause hemorrhage in the wall of the gallbladder, in the liver, and in the lungs,4.?K.31.3?.3h.37Vascular lesions have been observed in the hepatic veins of dogs subjected to ESWL." These are reminiscent of changes seen with ionizing radiation." Despite the increasing use of ESWL, little is known about the mechanisms by which tissue is injured. Physical impact of shock waves, cavitation phenomena (formation of expanding bubbles and their subsequent collapse), and formation of free radicals are suspected . " , "impact of many pamodes of tissue i n j ~ r ~ . ' ~ . ~ ~The rameters of shock waves and their production, such as physical characteristics of the wave, peak pressures, voltage, frequency, and total number of shocks, as well as number of treatment sessions and length of intervals between repeated treatments, on the efficacy and safety of lithotripsy has not been defined.
PATIENT SELECTION Initial clinical experience with ESWL at our center and by others suggests that proper patient selection is essential if successful fragmentation is to be
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TABLE 2.
Selection Criteria for ESWL of Gallstones
Currri71
Tl7eoretic~trlRtrriorltrle
Symptomatic patients Stone size < 3 cm
Stone number
5
3
Radiolucent stones Functioning gallbladder
Stones > 5 nim
Cost-benefit ratio Shock-wave energy may not reach threshold to fragment larger gallstones Concrements and debris hinder effective fragmentation Inability to dissolve calc~fied fragments with adjuvant bile acids Poor expulsion of fragments and poor concentration of oral dissolution agents in nonfunctioning gallbladder Sufficient resolution with current inline ultrasound
achieved.h.7.2?.10.1'The patient selection criteria for ESWL of gallstones resemble, in several important aspects, those for oral bile acid cholelitholytic therapy (Table 2). Both the experimental nature of the procedure and costeffectiveness considerations restrict the use of ESWL to symptomatic gallstones. Therefore, only patients with a history of biliary pain are presently considered to be eligible for cholelithotripsy. In addition, in most ESWL centers in the United States only radiolucent gallstones in a functioning gallbladder are being treated. The radiolucency of the gallstones is defined by the absence of visible calcifications in the gallbladder region on a roentgenogram of the abdomen. Gallbladder function is defined by the opacification of the gallbladder by an oral cholecystogram. It is also recommended that the gallstones do not exceed 3 cm in diameter. In addition to stone size, the number of stones has been found to influence the success rate of ESWL. The best results are obtained in patients with single stones.h.'".??The efficacy appears to drop significantly if more than three stones are present. Effective lithotripsy becomes more difficult with increasing stone number due to the obscuration of the concrements by the pile of stone fragments and debris produced by the procedure. Future studies may, however, show that improved accuracy and precision of the ultrasonographic targeting of the stones as well as the ability to repeat the ESWL safely in intervals of only a few days will allow effective cholelithotripsy in patients with more than three stones.
Contraindications to ESWL ESWL is contraindicated in patients who have developed acute complications from gallstone disease, such as acute pancreatitis, cholecystitis, or cholangitis (Table 3). Other contraindications relate to the described predictors of a very low success rate of lithotripsy, that is, the presence of a nonfunctioning gallbladder, of very large (more than 3 cm in diameter) stones or of dense calcifications. The procedure may also be contraindicated in patients in whom anatomic variations of the position of the gallbladder or massive obesity make it very
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FROMM TABLE 3.
Contraindications to ESWL of Gallstones
Frequent attacks of b i l ~ a r ycolic (impending cholecystiti\) Complications from gallstones (cholecystitis. pancreatitis, choledocholithiasis, cholangitis) Nonfunctioning gallbladder (by oral cholecy\tography) Very large o r numerous gallstones Calcified gallstones M a s i v e obesity Subcostal location of gallbladder Bleeding disorder or use of anticoagulants Chronic use of aspirin or nonsteroidal anti-inflammatory agents Large hepatic cy\ts in pathway of shock waves Vascular aneurvsms Pacemaker or significant cardiac arrhythmias Pregnancy
difficult to locate the gallbladder and target the gallstone under ultrasound guidance. In order to prevent bleeding or the development of a hematoma during ESWL, patients should have neither disease- nor drug-induced clotting abnormalities. Therefore aspirin and other antiinflammatory agents should be discontinued at least I week prior to the treatment.
EFFICACY European investigators, adhering to the above selection criteria, have reported excellent ESWL results, a 95 to 100% efficacy in patients with single stones and a 67% efficacy in patients with two or three stones within 12 to 18 months after treatment." These results were obtained with all patients receiving adjuvant therapy with an ursodiol (UDCA)-chenodiol (CDCA) combination. The latter was initiated 2 weeks prior to lithotripsy and terminated 2 months after ultrasonographic documentation of complete disappearance of the gallstones. In most patients, clearance of fragments from the gallbladder occurred only after several months of continuous adjuvant bile acid therapy. Preliminary multicenter results in the United States using similar technologies have been less impressive." Results from two large multicenter trials using spark-gap lithotripters were recently reviewed by the Food and Drug Administration. In a randomized controlled trial, using the Dornier MPL 9000 lithotripter, the overall 6month stone-free rate was 22% in the group treated with adjuvant ursodiol and 8% in the group treated with ESWL alone. In the second study, which was uncontrolled, using the Medstone STS lithotripter in conjunction with ursodiol treatment, 26% of the total patients were stone free by 6 months. When only solitary stones up to a size of 20 mm were considered, the stone-free rates at 6 months in patients treated with both lithotripsy and ursodiol were 48% and 35% respectively, in the two studies ." Similarly, in an on-going uncontrolled multicenter study, using a piezoelectric technology (EDAP LT-01) and adjuvant ursodiol treatment, we and coinvestigators have reported overall stone-free rates of 13%, 29%, and
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FIG. 1. Treatment of patient with piezoelectric shock-wave therapy. A: Baseline ultrasound shows solitary 1.5 cm gallstone in lumen of gallbladder. B: Initial fragrr~entat~on of gallstone after 5 minutes of treatment. C: Complete fragmentation to small particles layering on dependent wall of gallbladder following 60 minutes of treatment. D: Complete clearance of fragments 1 month following the procedure on concomitant ursodiol therapy.
38% at 3 , 6. and 9 months.-" Patients with solitary gallstones 20 mm or sn~allerwere free of stones in 52% of the cases by 6 months. In our center, 37 of 60 patients have been followed for 9 rnonths. The rate of stone freedom is 62% overall and 75% in patients with solitary stones 20 nim or less,4' which is similar to the initial European results. Treatment results from one of our first patients are depicted in Figure I. PLI1our patients have been treated on an outpatient basis, and no patient has required any anesthesia, analgesia. or sedation during treatment. There are probably several explanations tor the wide range in treatment results repc~rtedwith the different technologies as well as by ditferent centers using either the same or different devices in part, this can be attributed to differences in operatol experience and patient selection. Most investigators are experiencing a "learning curve," which is charactzristic for the use of this intricate technology. The maximization of the treatrnent parameters and techniques for the different devices is therefore likely to take more timr:. Furthermore, centers selecting only patients with favorable stone characteristics (solitary, srnall in size) will achieve better overall results than those including larger. multiple, and calcified stones.
ADJUVANT BILE ACID TREATMENT Controlled studies are currently being conducted by United States investigators to evaluate the need for oral bile acid dissolution treatment in conjunction with ESWL. A nurnber of previous observations and pathophysiologic considerations suggest that UDCA or a combination of UDCA and CDCA must be given to most patients for a prolonged period of tirne following ESWL in order to achieve optimal treatment results (Table 4). The described postlithotripsy gallstone disappearance rate during continued adjuvant oral bile acid therapy in both the published European studies and the patients treated at our center is. in most cases, consistent with dissolution of the gallstone fragments, rather than spontaneous gallstone clearance from the gallbladder."." It appears possible. if not likely, that, in many instances. the fragments are ejected from the gallbladder after they have dissolved to a small size. In one study, it was observed that two of three patients who did not comply with the adjuvant bile acid therapy showed persistence of the fragments after a prolonged period of follow-up and prompt conglomeration of the stone fragments." In addition, preliminary results from the Dornier United States multicenter trial show a three-fold increase in
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TABLE 4.
Rationale for Adjuvant Bile Acid Treatment
Disappearance rate of residual fragments post ESWL con\istcnt with gradual d~ssolutionprocess in many patients Impaired spontaneous dissolution o f the stone fragments and their expulsion from the gallbladder in presence of cholesterol-supersaturated bile and decreased gallbladder contractility Contractile function of the gallbladder remains impaired until the gallstone residues are completely dissolved. ESWL improves conditions for oral bile acid dissolut~ontreatment Patients not complying w ~ t hadjuvant bile acid therapy may show either persistence or conglomeration of \tone fragments after ESWL Threefold increase in stone disappearance in patients given adjuvant ursodiol (preliminary results from the Dornier randomired United States multicenter trial)
stone disappearance in patients given adjuvant urso-
dial.-" It also appears likely that the combination of cholesterol-supersaturated bile and decreased gallbladder contractility, which characterizes the majority of cholelithiasis conditions, will impair both the spontaneous dissolution of the stone fragments and their expulsion from the gallbladder. Indeed, recent observations by one group of investigators indicate contractile function of the gallbladder to remain impaired until the gallstone residues are completely d i s ~ o l v e d . ~The ' presence of cholesterol-supersaturated bile per se has been shown in animal studies to lead to changes resembling those of chronic cholecystitis.'" It appears therefore that all presently available data, observations, and pathophysiologic considerations support the rationale for the use of adjuvant oral bile acid therapy in gallstone patients after ESWL.IJ However, controlled data must be awaited before final recommendations can be made concerning the efficacy of adjuvant cholelitholytic treatment with bile acids.
SAFETY Laboratory changes caused by gallbladder ESWL in clinical trials are reportedly limited to transient leukocytosis and infrequent hematuria, hemoglobinuria, and elevation of liver enzyme^.'^^.'^'^^' Stephenson et alx described epithelial denudation as well as mural edema and hemorrhages in human gallbladders exposed to ESWL. The two main adverse effects or complications, which have been reported to occur in only I to 2% of the patients, are cholecystitis and pan~reatitis.~.'"'~ Both complications are thought to be the result of fragments obstructing either the cystic or common bile duct. Fortunately, in most cases, the bile duct obstruction appears to be transient, not requiring surgical intervention. In the minority of cases with postlithotripsy pancreatitis, endoscopic papillotomy was carried out to relieve the common bile duct obstruction. Most of the complications were reported to occur within the first weeks after ESWL.
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Transient hematuria and local petechiae or ecchymoses of the skin at the entrance or exit path of the shock waves are relatively minor adverse effects that appear to be more prevalent with the use of spark discharge than with that of piezoelectric lithotripters. Biliary colic has been observed to continue after lithotripsy at a rate that appears to be similar to that occurring before the procedure until the gallbladder is free of stone fragments, 6 . 1 v . 1 1 . 4 ~The experience in our center concerning lithotripsy-related complications is comparable to that reported by the European authors. Except for occasional biliary pain and a case of mild pancreatitis, no significant symptoms or complications have occurred in any of our patients treated thus far. To our knowledge, several complications associated with kidney lithotripsy have not been reported following biliary lithotripsy. These include hypertension," iliac vein t h r o m b ~ s i s , and ~ " retroperitoneal hemorrhage," and may be unique to kidney lithotripsy due to the focusing of shock waves within the renal parenchyma. Further studies are needed to determine whether differences, which, at least presently, exist between the different types of lithotripters as far as size of the focus or power of the shock waves as well as anesthesia or analgesia requirements are concerned, are reflected by differences in risks or adverse effects and complications.
STONE RECURRENCE AFTER ESWL There is limited information on the rate of gallstone recurrence after ESWL. Preliminary data by one group of investigators indicate it to be lower than the approximately 50% recurrence within 5 years, which has been described after successful oral cholelitholytic treatment, 51-51 In contrast to patients treated with oral dissolution agents alone, however, gallstones that recur after ESWL tend to be associated with biliary pain.lJ More data concerning the postlithotripsy recurrence of gallbladder stones are needed both to evaluate its clinical significance and to develop guidelines for its management. In particular, the question of the appropriateness and feasibility of retreatment by ESWL requires studies for each lithotriptic device and technology.
COMMON BlLE DUCT STONES Sauerbruch and colleagues' from Munich first showed that common bile duct stones could be successfully fragmented with ESWL. Recently, these investigators reported a prospective uncontrolled multicenter trial in which 113 patients with symptomatic common bile duct stones were treated with a spark-gap, waterbath lithotripter." Presenting symptoms and complications included jaundice, cholangitis, and biliary pain. Prior attempts at endoscopic mechanical extraction or solvent dissolution of the ductal stones were unsuccessful. In all cases, sphincterotomy had been performed prior to lithotripsy. Most stones were either impacted in
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the common bile duct or too large for basket extraction. After the patient was immersed in the water bath, the bile duct stones were located and positioned into the shockwave focus under fluoroscopic guidance, aided by injection of contrast medium via a nasobiliary or transhepatic catheter. Successful fragmentation was achieved in 9 1 C/o and complete stone clearance in 86% of patients after one or more ESWL sessions. Clearance was facilitated by endoscopic extraction of residual fragments or by instillation of solvents in 73% and 3% of patients, respectively. The remaining patients passed all of the fragments spontaneously. Side effects and complications occurred in 36% of patients and included mild cardiac arrhythmias, mild and transient hemobilia, skin hematomas, microhematuria, and biliary pain. This well-conducted study showed that the treatment of patients with common bile duct stones not amenable to endoscopic extraction or dissolution can be accomplished safely and effectively with ESWL.
ISSUES CONCERNING THE FUTURE OF ESWL A number of issues concerning the future role of ESWL in the management of gallstonr: disease have been raised at the various meetings. hearings. and symposia held worldwide (Table 5). Areas of debate include patient selection, operator training and credentialling, costeffectiveness, and expanded use of the technology. ESWL would seem to be an ideal therapeutic alternative for the patient with concomitant medical problems who is a poor candidate for surgery. However, there is much debate over whether ESWL should be offered to the healthy, young patient with symptomatic gallstones in whom cholecystectomy is safe and provides a permanent cure in most cases. Even more controversial is the idea of prophylactic ESWL in the asymptomatic patient with gallstones. Although only 15 to 20% of these
TABLE 5. Issues That Need to be Addressed to Determine the Future Role of ESWL of Gallstones Patient selection Operator training and credentialling Cost-el'lectiveness Role of ESWL vis-8-vi\ that of other nonsurg~caland surgical a1 ternatives Expanded use ol' the technology Prophylactic u\e In asymptomatic ydlstone patient\ Interaction and responsibility o f d~flerentspecialtie\ in ESWL program Role in treatment of comon bile duct atones S t a n d a r d i ~ a t ~ oofn definition of treatment succes\ Retreatment rate Expansion of inclusion criteria (stone burden, calcification) Treatment of high-risk patients Optimum treatment parameters Recurrence of stones following complete stone disappearance Long-term sequelae
10, NUMBER 3, 1990
patients will go on to develop biliary symptoms or complications, early treatment of stones while they are small, few in number, and not causing problems might be costeffective, particularly if the treatments can be shown to be safe, effective, and able to be performed on an outpatient basis. Another area of concern is over who should operate the lithotripter. Most agree that clinical experience in managing patients with gallstone disease as well as a firm background in biliary ultrasound are required. In some centers, such as ours, a gastroenterologist, with special training in biliary ultrasound, performs the procedure. Other centers take a multidisciplinary approach, involving members from the gastroenterology, surgery, and radiology departments. The length of time required for a nonradiologist to learn biliary ultrasound and the number of lithotripsy treatments necessary to assure competence are being evaluated by professional societies, such as the American Gastroenterological Association, the American Association for the Study of Liver Diseases, the American Lithotripsy Society, and the American Society of Gastrointestinal Endoscopists. The issue of cost-effectiveness is complex and must take into account factors such as the overall effectiveness of the procedure, the stone recurrence rate, retreatment rates, and the relative costs of alternative surgical and nonsurgical treatments. Our current impression is that ESWL will be cost effective in selected symptomatic patients with ideal stone characteristics, i.e., small and few in number. The successful application of the procedure for larger and more numerous stones will likely take more time as treatment parameters are optimized and technology (ultrasound images, focusing, higher energies) is improved. A final interesting issue deals with expanding the use of lithotripsy into areas of medical treatments other than gallstone disease. Recently, reports of treating pancreatic stones'" and even gastric outlet obstruction caused by an intraluminal gallstone" have appeared in the literature. The Food and Drug Administration recently addressed these and other issues, and, at the time of this writing, has felt it prudent to withhold market approval for gallstone lithotripsy until these issues are addressed adequately. The information obtained thus far, both in other countries and in the United States, however, suggests that ESWL is here to stay and should, one day, have a large impact on the management of gallstones in selected patients. A~~Xt7o~vlrdgtnmr.The authors would like to acknowledge Dr. Bernard Zook. Professor of Pathology and Director of Animal Research. for his assistance in reviewing the published animal data.
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2.
Chaussy C , Brendel W, Schmiedt E: Extracorporeally induced destruction of kidney stones by shock waves. Lancet 2:12651268, 1980. Chaussy C. Schmiedt E , Jocham D, et al: First clinical expe-
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