Original Article
The Effect of Ursodiol on the Efficacy and Safety of Extracorporeal Shock-Wave Lithotripsy of Gallstones — The Dornier National Biliary Lithotripsy Study
N Engl J Med 1990; 323:1239-1245November 1, 1990
- Abstract
- Abstract
Background.
In the treatment of gallstones with extracorporeal shock-wave lithotripsy, the bile acid ursodiol is administered to dissolve the gallstone fragments. We designed our study to determine the value of administering this agent.
Methods.
At 10 centers, 600 symptomatic patients with three or fewer radiolucent gallstones 5 to 30 mm in diameter, as visualized by oral cholecystography, were randomly assigned to receive ursodiol or placebo for six months, starting one week before lithotripsy.
Results.
The stones were fragmented in 97 percent of all patients, and the fragments were ≤5 mm in diameter in 46.8 percent. On the basis of an intention-to-treat analysis of all 600 patients, 21 percent receiving ursodiol and 9 percent receiving placebo (P<0.0001) had gallbladders that were free of stones after six months. Among those with completely radiolucent solitary stones <20 mm in diameter, 35 percent of the patients receiving ursodiol and 18 percent of those receiving placebo (P<0.001) were free of stones after six months. Biliary pain, usually mild, occurred in 73 percent of all patients but in only 13 percent of those who were free of stones after three and six months (P<0.01). There were few adverse events. Only diarrhea occurred with a significantly different frequency in the two groups: 32.6 percent were affected in the ursodiol group, as compared with 24.7 percent in the placebo group (P<0.04). Severe biliary pain occurred in 1.5 percent of all patients, acute cholecystitis in 1.0 percent, and acute pancreatitis in 1.5 percent; endoscopic sphincterotomy was performed in 0.5 percent, and cholecystectomy in 2.5 percent.
Conclusions.
Extracorporeal shock-wave lithotripsy with ursodiol was more effective than lithotripsy alone for the treatment of symptomatic gallstones, and equally safe. Treatment was more effective for solitary than multiple stones, radiolucent than slightly calcified stones, and smaller than larger stones. (N Engl J Med 1990; 323: 1239–45.)
Media in This Article
Figure 1
Cumulative Percentages of All Randomized Patients Receiving Ursodiol or Placebo Who Were Free of Stones at Each Visit after Extracorporeal Shock-Wave Lithotripsy.Figure 2
Percentages of All Randomized Patients with Single (Black Bars) or Multiple (Gray Bars) Stones at Base Line Who Were Free of Stones Six Months after Extracorporeal Shock-Wave Lithotripsy Combined with Ursodiol or Placebo.Article Activity
- Article
EXTRACORPOREAL shock-wave lithotripsy of gallstones was initially performed in vitro1 , 2 and in animals.3 4 5 6 Then, Sauerbruch and his colleagues in Munich,7 , 8 followed by other investigators,9 10 11 12 13 14 reported the use of the method to treat gallstones in humans. In conjunction with extracorporeal shock-wave lithotripsy, the patients received the bile acid ursodiol alone or in combination with chenodiol orally to dissolve the fragments.15 16 17 18 In two recent papers19 , 20 the feasibility of lithotripsy without bile acids was demonstrated. None of the studies, however, have defined the contribution of bile acids to the success of extracorporeal shock-wave lithotripsy. Accordingly, the aim of this study was to determine, in a randomized, controlled trial, the efficacy and and safety oflithotripsy alone as compared with lithotripsy combined with ursodiol treatment.
Methods
Experimental Design
Ten centers participated in the Dornier National Biliary Lithotripsy Study (DNBLS). The study was approved by the institutional review board at each center and was conducted with the informed consent of all patients. Patients were eligible for the study if they had biliary pain; were in American Society of Anesthesiologists Class I, II, or III21; had three or fewer radiolucent stones that were 5 to 30 mm in diameter and had a nidus or rim of calcification less than 3 mm; had had oral cholecystography for visualization of the gallbladder; and could receive shock waves that would avoid lungs, bone, aneurysms, or cysts. Patients were excluded from the study if they were in American Society of Anesthesiologists Class IV or V,21 were pregnant, or had any of the following: a pacemaker; arrhythmias; an allergy to contrast medium; coagulopathy; a known ductal stone or obstruction; acute cholecystitis, cholangitis, or pancreatitis; a known pigment stone; hemolysis; or cirrhosis. The patients at each center were randomly assigned in a double-blind fashion to receive 10 to 12 mg of ursodiol (Ursofalk, 250-mg tablets) per kilogram of body weight daily at bedtime or tablets of placebo identical in appearance. The average (±SD) daily dose of ursodiol was 869±237 mg. The tablets were started one week before extracorporeal shock-wave lithotripsy and were continued for six months after the procedure. The patients' compliance was assessed by pill counts, but this method did not provide adequate data. Masked analyses in the gastrointestinal research laboratory at Cedars—Sinai Medical Center22 confirmed the intended content of 60 randomly selected, coded bottles of tablets.
The patients were admitted to the hospital either the night before extracorporeal shock-wave lithotripsy or the morning of the procedure. Initially, patients were kept in the hospital for two nights after the procedure; during the latter part of the study, the second night was optional. Two to eight weeks before lithotripsy, clinical (history and brief physical examination), laboratory (complete blood count; serum measurements of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, bilirubin, amylase, and lipase; and a test for pregnancy), and abdominal ultrasonographic examinations were conducted. These examinations were all repeated 1 or 2 days after lithotripsy, after 6 weeks (±10 days), and after 3 and 6 months (±3 weeks). Chest films, electrocardiograms, and plain films of the abdomen were obtained only before lithotripsy. Oral cholecystography was performed before lithotripsy and at the six—month visit. If after six weeks stone fragments larger than 5 mm were found in the gallbladder ultrasonographically, the patient was scheduled to undergo lithotripsy a second time. The cholecystograms and ultrasonograms were evaluated blindly at each center by designated radiologists.
Extracorporeal Shock-Wave Lithotripsy
Patients underwent extracorporeal shock-wave lithotripsy with the Dornier MPL 9000 lithotriptor. For the first procedure, 94.6 percent of the patients received analgesia and sedation — usually midazolam with either meperidine or fentanyl; the remaining 5.4 percent received nothing. None received general or epidural anesthesia. The delivery of repetitive shock waves was stopped when no more acoustic shadows of fragments were detected sonographically or when 1500 shock waves — the limit imposed by the DNBLS protocol — had been applied.
Outcomes of the Study
Predetermined criteria and clinical procedures were established to diagnose and manage possible complications of gallstones, ursodiol therapy, and extracorporeal shock-wave lithotripsy.15 , 23 Clinical decisions were to be made at the centers without revealing the treatment to the investigators or patients. The treatment was unmasked in nine cases, however, because of pregnancy in three patients (one receiving ursodiol), hives in two (both of whom were receiving placebo), and other reasons in four (three receiving ursodiol).
The predefined principal outcome for the evaluation of efficacy was the complete disappearance of gallstones from the gallbladder, as determined by ultrasonography after six months ("success"). The predefined principal outcome for the evaluation of safety was the occurrence of serious adverse biliary events. Any failure to complete six months of follow-up was considered a withdrawal from the study. The entire cohort of randomized patients was followed to one of the predefined principal outcomes or until withdrawal.
Statistical Analysis
The sample of 600 patients was determined to yield 95 percent power at an alpha level of 0.05 to detect a difference of 5 percent or more between the efficacy rate of extracorporeal shock-wave lithotripsy with ursodiol and the efficacy rate of lithotripsy alone. With the use of an intention-to-treat strategy for the analysis of efficacy, all randomized patients were included, even if they did not undergo extracorporeal shock-wave lithotripsy or an ultrasonographic examination after the treatment. All P values of less than 0.05 were considered to indicate significance. All statistical tests were two-tailed. Differences in the rates of success and the rates of fragmentation between treatments were compared with a chi-square statistic or an exact test, as appropriate. The effect of covariates on the rates of success was assessed with log linear models (Module 4F in BMDP) and logistic regression (Proc Catmod in SAS). We used t-tests to compare means between treatments. McNemar's test was used to compare the laboratory values at base line with those at each later point. Repeated-measures analysis of variance was used to analyze data on blood pressure over time.
Results
Study Population
The randomization of the first patient occurred in May 1988, and the last patient completed six months of follow-up in September 1989. Of the 600 randomized patients, 296 (49.3 percent) were assigned to receive ursodiol and 304 (50.7 percent) to receive placebo. As few as 13 (2.2 percent) to as many as 133 (22.2 percent) of the 600 patients were randomized at the individual centers. No significant differences between the two treatment groups were found in their base-line demographic or clinical characteristics, except for a slight difference in the percentage of white patients (Table 1Table 1
Demographic and Clinical Data at Base Line.*).Among the 600 randomized patients, 511 (85.2 percent) completed the six-month follow-up and 89 (14.8 percent) withdrew. The reasons for withdrawal, with no significant difference between the ursodiol and placebo groups, were adverse effects (3.0 percent), protocol violations by the centers (3.2 percent), patients' noncompliance with the protocol (2.0 percent), and dropping out (6.0 percent); four patients (0.7 percent) withdrew for other reasons, and three (0.5 percent) died. (Three patients had two reasons for withdrawal.)
Extracorporeal Shock-Wave Lithotripsy
Five hundred sixty-six of the 600 patients (94.3 percent) underwent extracorporeal shock-wave lithotripsy, with no significant difference between the ursodiol and placebo groups. The remaining 34 patients (5.7 percent) did not receive shock waves because the stones could not be visualized (7 patients) or because the patients lost interest and withdrew from the study. These patients are included among the withdrawals described above. Among the 566 patients given extracorporeal shock-wave lithotripsy, with no significant difference between the ursodiol and placebo groups, a mean (±SD) of 1446±187 shocks were delivered at a mean voltage of 18.7±1.7 kV. The second lithotripsy was administered to approximately equal numbers of patients in both groups; 232 of the 566 patients who underwent lithotripsy (41.0 percent) had a second treatment. The application data for the second lithotripsy were similar to those for the first one. Ninety-eight percent of the patients were treated in the prone position.
Efficacy
Stones were fragmented to some degree in 97.0 percent of the patients, as assessed by ultrasonography one day after lithotripsy, with no significant difference between the ursodiol and placebo groups. After the first lithotripsy, the fragments were 5 mm or smaller in diameter on day 1 or 2 in 46.8 percent of the patients, with no significant difference between the ursodiol and placebo groups after either the first or the second procedure. The patients who were free of stones on day 1 or 2 were excluded from these analyses, but their inclusion would have affected the data only slightly. Patients with fragments of indeterminate size were grouped with patients whose stones were not fragmented. The smaller the original diameter (P<0.0001) and volume (P<0.0001) of the stones at base line, the greater the percentage of patients with fragments 5 mm or smaller on day 1 or 2.
Among all 600 patients, a statistically significant difference in the percentage who were free of stones after six months (P<0.0001) was found between those receiving ursodiol (21 percent) and those receiving placebo (9 percent) (Fig. 1Figure 1
Cumulative Percentages of All Randomized Patients Receiving Ursodiol or Placebo Who Were Free of Stones at Each Visit after Extracorporeal Shock-Wave Lithotripsy.). Ursodiol treatment tended to be more successful than placebo at each visit. In addition, the success rate in both groups tended to increase with each visit. The diagnosis of the elimination of all stones on the basis of ultrasonography after six months was confirmed by oral cholecystography in all but two patients (2.2 percent). In contrast (P<0.001), 17.7 percent of the patients who were considered free of stones according to oral cholecystography were considered to have stones according to ultrasonography and were therefore not tabulated as free of stones.The success in eradicating single stones was significantly greater (P<0.001) than that with multiple stones (Fig. 2Figure 2
Percentages of All Randomized Patients with Single (Black Bars) or Multiple (Gray Bars) Stones at Base Line Who Were Free of Stones Six Months after Extracorporeal Shock-Wave Lithotripsy Combined with Ursodiol or Placebo.). Nevertheless, extracorporeal shock-wave lithotripsy plus ursodiol was significantly more effective than lithotripsy alone for both single and multiple stones (P<0.0001). The maximal diameter of the stones at base line also significantly influenced the rate of success (P<0.0001) (Fig. 3Figure 3
Percentages of Randomized Patients Who Were Free of Stones Six Months after Extracorporeal Shock-Wave Lithotripsy Combined with Ursodiol or Placebo, According to the Diameter of the Largest Single Stone at Base Line.). The treatment effect persisted (P<0.0002), although among the relatively few patients with stones 5 to 9.9 mm in diameter, the proportions free of stones after six months were almost identical in the ursodiol (48 percent) and placebo (45 percent) groups.The patients who had smaller stones (P<0.0001) or who weighed less (P<0.03) at base line were likelier to be free of stones after six months. Of the 78 patients with minor calcification of their stones at base line, only 2 were free of stones after six months. Among patients who had solitary stones 5 to 20 mm in diameter and no calcification, 34.9 percent of those receiving ursodiol and 18 percent of those receiving placebo were free of stones after six months (P<0.01). When the data were not tabulated on an intention-to-treat basis and only the patients for whom the status of stones was known were included, the success rate of extracorporeal shock-wave lithotripsy was 39.8 percent with ursodiol and 20.5 percent with placebo after six months for radiolucent solitary stones that were 5 to 20 mm in diameter.
There were statistically significant differences (P<0.04) among the centers in the success of lithotripsy: the rates among patients given ursodiol ranged from 7.1 to 36.4 percent, and among patients given placebo, from 6.5 to 25.3 percent. Statistically significant differences among the centers were found for several demographic and clinical variables; however, of these, only the addition of the volume of stones at base line to the analyses of success after six months caused the differences in success rates among centers to lose statistical significance. This finding suggests that the differences in the success rates among the centers were attributable to differences in the distribution of the volume of stones. Moreover, the centers with the higher percentages of patients who were free of stones after six months appeared to be those whose patients had lower stone volumes at base line.
When the success rates for the first 25 percent of the randomized patients were compared with those for the last 25 percent, no "learning curve" for extracorporeal shock-wave lithotripsy was demonstrated; however, the statistical power to demonstrate this was limited by the small number of patients at some centers. Also, no correlation was found between the number of patients treated and the success rate.
Adverse Events
Of the 566 patients who had extracorporeal shock-wave lithotripsy, 72.8 percent reported at least one episode of biliary pain during the six months of follow-up, with no significant difference between the ursodiol and placebo groups. The pain was usually mild (rather than moderate or severe), however, and did not require narcotics for relief. At each visit, most of those who reported pain (67 to 74 percent) had more than one episode, but the number of episodes per week decreased from 0.76 after six weeks to 0.57 after three months and to 0.37 after six months. Also, the number of patients who reported pain at each visit was lowest among those who were free of stones. For example, for the interval between the three-month and six-month checkups, only 13.3 percent of the patients who were free of stones after three and six months had biliary pain, as compared with 40.1 percent of the patients who still had stones at both visits (P<0.0015).
The most frequent nonbiliary adverse events during the six months after extracorporeal shock-wave lithotripsy were tender abdominal wall (46.3 percent of the patients), nausea (36.0 percent), and diarrhea (28.6 percent). Among these, a statistically significant difference between the ursodiol and placebo groups was found only for the patients with diarrhea (32.6 vs. 24.7 percent, respectively; P<0.04). The tender abdominal wall and nausea usually occurred within two days after lithotripsy. Dyspepsia was reported by 20.1 percent of the patients, with no significant difference between the ursodiol and placebo groups. All these nonbiliary events were usually mild (rather than moderate or severe) and reversible (not present at the next visit).
Among all 600 patients, serious biliary events occurred in 24 (4.0 percent) (Table 2Table 2
Type and Care of Serious Biliary Events among the 600 Randomized Patients.). Acute cholangitis occurred in one of the patients with pancreatitis. Jaundice occurred in one patient with biliary pain and in another with acute pancreatitis. Fifty-two percent of the serious biliary events occurred in the first two months after lithotripsy. Four of the cholecystectomies were performed as emergencies.Other serious nonbiliary adverse events (in one patient each) included death from bronchopneumonia before lithotripsy; respiratory arrest that was promptly reversed, and that was attributed to sedation during lithotripsy; cancer of the jejunum discovered and resected two months after lithotripsy; death from heart failure 4 1/2 months after lithotripsy; and death from myocardial infarction several hours after an elective cholecystectomy.
The efficacy in patients who had solitary radiolucent stones less than 20 mm in diameter at base line was greater than that in the group as a whole (as noted above), but the frequency of any of the adverse events was similar.
Hematologic and Chemical Analyses
During the study, the mean hematocrit and hemoglobin values hardly changed from base line, and there were no significant differences between the ursodiol and placebo groups at any visit. At base line, 16 percent of the patients randomly assigned to receive either ursodiol or placebo had values for alanine aminotransferase above the upper limit of normal (as determined in each center's laboratory). The percentage of patients with such elevations after extracorporeal shock-wave lithotripsy was significantly higher (P<0.007) than the percentage at base line in the placebo group on day 1 (30 percent) and after six months (24 percent) and in the ursodiol group on day 1 (24 percent). Moreover, after lithotripsy the percentage of patients with elevations in alanine aminotransferase was higher in the placebo group than in the ursodiol group at each visit; however, the percentage was significantly higher only at the six-month visit (24 vs. 14 percent, P<0.008). Less than 3 percent of the elevations of alanine aminotransferase were more than three times the upper limit of normal.
The percentage of patients (range, 6.6 to 12 percent) with serum amylase levels above the laboratory's upper limit of normal at each visit did not appear to increase after lithotripsy or to differ between the ursodiol and placebo groups.
Blood Pressure and Hematuria
After six months, the mean blood pressure (124.2±18.6/77.0±11.4 mm Hg) was essentially unchanged from base line, and there was no significant difference between the ursodiol and placebo groups.
Microscopical hematuria was found in 33 percent of the patients, and gross hematuria was reported in 9 percent at some visit after lithotripsy. The percentage of patients with microscopical hematuria (usually only 1+) almost doubled from the base-line value of 8.7 percent on the day after each lithotripsy (P<0.0001 after the first procedure) but declined to base-line values at subsequent visits. Only after six months was a significant difference found between the ursodiol and placebo groups ( 11.9 vs. 6.3 percent, P<0.03). Gross hematuria was reported after the first procedure in 6.1 percent of the patients, after six weeks in 3.5 percent (P<0.004 for the comparison with the value after the first lithotripsy), after the second procedure in 5.6 percent, after three months in 1.9 percent, and after six months in 0.6 percent (P<0.001 for the comparison with the value at the second lithotripsy). (At base line, the patients were not asked whether they had hematuria.) No differences between the ursodiol and placebo groups in the percentage with gross hematuria were apparent at any of the visits.
Discussion
Extracorporeal shock-wave lithotripsy with ursodiol was superior to lithotripsy with placebo in eliminating stones from the gallbladder after six months. Moreover, the trend of progressively increasing success with ursodiol after lithotripsy suggests that continued treatment with ursodiol beyond six months would yield further success.
The percentage of patients free of stones after lithotripsy with ursodiol at six months in the DNBLS was about half that reported by Sauerbruch and colleagues in Munich,8 even if only completely radiolucent stones are considered. This difference in efficacy could be explained in part if the combination of ursodiol and chenodiol used in Munich dissolved the fragments more rapidly than the ursodiol used alone in the DNBLS.18 , 24 , 25 (Ursodiol alone was used in the DNBLS because it was unlikely that the combination would be proposed to the Food and Drug Administration for approval in the United States.) Also, the German investigators used an earlier (water-bath) model of the Dornier lithotriptor and general anesthesia. Subsequently, they obtained comparable results with the MPL 9000 model, which does not require a water bath, without general anesthesia only after they delivered approximately 2kV and 200 shock waves more at each treatment than was given with the MPL 9000 lithotriptor in the DNBLS (Paumgartner G: personal communication). Moreover, no other study of lithotripsy seems to have analyzed data on an intention-to-treat basis.
Treatment with the bile acid was begun one week before lithotripsy, as in previous studies, so that the bile would be well on the way to desaturation by the time of the procedure. The data in this study, in agreement with those of Burnett and colleagues,12 do not support the notion that this brief period of pretreatment with oral bile acid — or even the six weeks of treatment before the second lithotripsy — enhances subsequent fragmentation of stones in the gallbladder.
Extracorporeal shock-wave lithotripsy and ursodiol in combination would be expected to eliminate stones in the gallbladder more rapidly than ursodiol alone because fragmenting the stones with a lithotriptor creates a greater surface area for dissolution by ursodiol.1 In fact, the success of the combined treatment in patients with solitary radiolucent stones 5 to 20 mm in diameter (35 percent of the patients were free of stones) is superior to that reported for ursodiol alone in similar patients after six months (about 15 percent were free of stones) and comparable to that usually reported for ursodiol alone after two years (about 35 percent were free of stones).16 , 17 , 26 27 28 29 30 31
The adverse clinical biliary events were unrelated to treatment with ursodiol. Most were probably due to the migration of stone fragments to the cystic or common bile duct, rather than to the direct effects of shock waves on the liver, gallbladder, or pancreas. The percentage of patients with biliary pain during the six months after lithotripsy in our study was higher than that reported after six months in patients with untreated gallstones32 33 34 35 36 or with gallstones treated with bile acids.15 , 35 After lithotripsy, however, the biliary pain was usually mild. Moreover, the percentage of patients with the more serious biliary events was not higher after lithotripsy. Most patients whose stones were eliminated were also freed from biliary pain; tiny fragments below the sensitivity of detection by ultrasonography probably accounted at least in part for the biliary pain that occurred in patients who were reported to be free of stones.
The elevations in aminotransferase levels were almost always minor. Moreover, ursodiol may have prevented these elevations, whether they were caused directly by hepatic trauma from the lithotripsy or by the migration of stone fragments. Ursodiol has recently been suggested to have salutary effects in chronic hepatic disease.37 Finally, the virtual absence of serious adverse events during the first two days after lithotripsy in the DNBLS suggests that it can be performed as an outpatient procedure.
In conclusion, extracorporeal shock-wave lithotripsy with ursodiol was more effective than lithotripsy alone for the treatment of symptomatic patients with gallstones and was just as safe. Lithotripsy was more effective for solitary than multiple stones, radiolucent than slightly calcified stones, and smaller than larger stones. For each patient, the risks and benefits of combined treatment should be compared with those of observation, ursodiol alone, and cholecystectomy.
We are indebted to Drs. Herbert Falk and David Jacobus of Dr. Falk Pharmaceutical Company for donating the tablets of ursodiol and placebo; to the personnel of Dornier Medical Systems, notably Tom Brooks, William Duffell, Ph.D., Mark Jernigan, and Volker Schoewel, for providing technical and logistical support; to Ms. Patsy Johnson, Cedars-Sinai Medical Center, for providing secretarial and administrative assistance; and to Elkan Halpern, Ph.D., Anne Milne, R.R.A. (senior data manager), Rebecca Weiss (senior statistician), Karen Falkner, Laurie Kinsley, John Lee, Ph.D., Kathleen McCarroll, Ph.D., and Natasha Stecyk at Consulting Statisticians, Inc., for providing the biostatistical support for the study.
Source Information
From the Crawford—Long Hospital of Emory University, Atlanta (W.C., R.C.D., H.V.S., W.E.T.); Cedars—Sinai Medical Center, Los Angeles (L.J.S., G.B., S.L., J.W. Marks); University of Iowa Hospitals and Clinics, Iowa City (J.W. Maher, R.W.S.); Northwestern Memorial Hospital, Chicago (D.L.N., A.N.); Methodist Hospital of Indiana. Indianapolis (A.C.J., L.G.J., D.M.); Hospital of the University of Pennsylvania, Philadelphia (I.L., P.F.M.); Massachusetts General Hospital (R.A.M.) and New England Medical Center (R.B.R., J.G.R.), Boston; Humana Hospital, San Antonio, Tex. (R.L.C., D.C., A.R.); University of Virginia Health Sciences Center, Charlottesville (J.Y.G., R.S.J., R.W.M., D.J.P., B.D.S.); and Johns Hopkins Hospital, Baltimore (P.C., D.R.K., K.D.L., H.A.P., G.S.). Address reprint requests to Dr. Schoenfield at the Division of Gastroenterology, Cedars—Sinai Medical Center, 8700 Beverly Blvd., Suite 7511, Los Angeles, CA 90048.
Appendix
The following personnel also participated in the study: Crawford—Long Hospital of Emory University (Atlanta) — Rendon C. Nelson, M.D., Bruce R. Baumgartner, M.D., Henry Heard (physician's assistant), Gayle Rowland, R.N., Virginia Jones, R.N., Carolyn J. Slatter, Marie Wilhem, and Sue Innes; Cedars—Sinai Medical Center (Los Angeles) — Andrew Hamlin, M.D., Mark Friedman, M.D., John Bray, M.D., and Dennis Sarti, M.D. (radiologists); Lori Goldman, R.N., Leila Ahtola, R.N., and Linda Richardson and Marta Feinstein (secretaries); and Johnny Thomas and George Pierson (lithotripsy technicians); University of Iowa Hospitals and Clinics (Iowa City) — Judy M. Swift, R.N., B.S.N.; Geri Quinn, R.N., B.S.N.; Debra Heitshusen, R.N., B.S.N.; Thomas R. Dean (physician's assistant); Mysti L. Grant, B.S., R.D.M.S.; Deb Troyer, T.T., R.D.M.S.; Deb McMann and Kathy Pyle (secretaries); and Edy Soffer, M.D., Joel V. Weinstock, M.D., and Joseph B. Eisenach, M.D. (gastroenterologists); Northwestern Memorial Hospital (Chicago) — Todd W. Arends, M.D. (surgical research fellow); Robert M. Craig, M.D. (gastroenterologist); Cheryl Ramler, R.N., M.A.; and Peter A. Manzie, Annmarie E. Zawislak, and Mary T. Turro (technicians); Methodist Hospital of Indiana (Indianapolis) — Gonzalo Chua, M.D., John C. Kohne, M.D., Beth Kirk, R.N. (nurse coordinator), April Wilson, B.S. (secretary), Susie Wilzbach, R.N., OPtB.S.N., and Susan Wiland (clinical research nurse); University of Pennsylvania (Philadelphia) — Anthony G. Auteri, M.D., Frank P. Brooks, M.D., William R. Brugge, M.D., Charles Cattano, M.D., Jonathon Israel, M.D, David A. Katzka, M.D., Margaret R. Khouri, M.D., William B. Long, M.D, Christopher O'Brien, M.D, Ann Ouyang, M.D, James C. Reynolds, M.D, Robin D. Rothstein, M.D, Yih-Fu Shiau, M.D., Vijay Gohel, M.D., and Peter Arger, M.D. (radiologists); Angelina Castro, M.D. (anesthesiologist); Ira Fox, M.D. (surgeon); Sharon Dudley, R.N.-C., M.S., C.R.N.P, and Rosemarie Borstelmann, R.N.-C., M.S., C.R.N.P. (nurse practitioners); Frances Wisniewski, R.T. (administrator-technologist); Sandra T. Stein (administrator); and Lynn Degree (secretary); Massachusetts General Hospital and New England Medical Center (Boston) — Peter R. Mueller, M.D., Joseph F. Simeone, M.D., and Sanjay Saini, M.D. (radiologists); William B. Latta, M.D., William R. Kimball, M.D., and J. Bucknam McPeek, M.D. (anesthesiologists); Ryan F. Holbrook, M.D., Leslie W. Ottinger, M.D., and George L. Nardi, M.D. (surgeons); Jacquelyn M. Connors (nurse); and Gail A. Arbuthnot (coordinator); Humana Hospital (San Antonio, Tex.) — Delbert Chumley, M.D., Arthur Rosenthal, M.D., Richard L. Carnovale, M.D.; Betsy Mellin, R.N., B.S.N.; Joni Rider (treatment nurse); Wanda Batch, R.N, S.S.N, C.G.C., C.E.T.N. (data manager); Donna Tolbert (data manager and research specialist); Tom Baran (secretary—patient care assistant); Sylvia Fernandez, R.T. (radiology technician); and Sandy Ticer, R.T., R.D., M.S. (chief ultrasonographer); University of Virginia School of Medicine (Charlottesville) — Patricia Abbitt, M.D.; Janet Dix (physician's assistant); Sarah Fabian, R.N.; Julia Dyer, R.N.; Lawrence Watson (ultrasound technician); and Steve Jones and Doug Shefter (lithotripsy technicians); and Johns Hopkins Hospital (Baltimore) — David Widlus, M.D., and Sally Mitchell, M.D. (radiologists); Anthony Kalloo, M.D. (gastroenterology); Marusia Oleksiuk (program coordinator); Jamie Flickenger, R.N.; William Marasco, M.D. (physician's assistant); and Toby Eagle, Chief, C.R.N.A. (anesthesiologist).
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- Citing Articles (26)
Citing Articles
1
Gustav Paumgartner, Gerd H. Sauter. (2005) Extracorporeal shock wave lithotripsy of gallstones: 20th anniversary of the first treatment. European Journal of Gastroenterology & Hepatology 17:5, 525-527
CrossRef2
Luís Carrilho-Ribeiro, David Serra, António Pinto-Correia, José Velosa, Miguel Carneiro de Moura. (2002) Quality of life after cholecystectomy and after successful lithotripsy for gallbladder stones: a matched-pairs comparison. European Journal of Gastroenterology & Hepatology 14:7, 741-744
CrossRef3
Paul Blomqvist, Håkan Ljung, Erik Nilsson, Anders Ekbom. (2000) Cholecystectomy in Sweden 1989 and 1994. Journal of Clinical Epidemiology 53:11, 1174-1180
CrossRef4
Alan N. Barkun, Jeffrey S. Barkun, John S. Sampalis, Jaime Caro, Gerald M. Fried, Johnathan L. Meakins, Lawrence Joseph, Carl A. Goresky, . (1997) Costs and Effectiveness of Extracorporeal Gallbladder Stone Shock Wave Lithotripsy Versus Laparoscopic Cholecystectomy: A Randomized Clinical Trial. International Journal of Technology Assessment in Health Care 13:04, 589
CrossRef5
Mario Angelico, Andrea Mangiameli, Alessandra Nistri, Leonardo Baiocchi, Mara Sofia, Mario Maina, Mario Di Martino, Adriano Blasi. (1995) N-ethyl-tauroursodeoxycholic acid, a novel deconjugation-resistant bile salt analogue: Effects of acute feeding in the rat. Hepatology 22:3, 887-895
CrossRef6
YUKIHIRO TSUCHIYA, HIDEKI TAKANASHI, KAZUO HANIYA, HIROMI NISHIARAI, SIGERU MIKAMI, YUTAKA NATSUKI, HIROSHI KUNIYUKI, HIROBUMI SAITO, NOBUHIKO SAITO, MASAO OHTO. (1994) An early gallstone clearance following repeat piezoelectric lithotripsy. Journal of Gastroenterology and Hepatology 9:6, 597-603
CrossRef7
G. CHOUDHURI, D. K. AGARWAL, R. V. PHADKE, V. RAMESH, W. HAUSER, A. K. KULSHRESHTHA, T. S. NEGI. (1994) Geographic variations in structure and composition of gallstones and their correlation with brittleness. Journal of Gastroenterology and Hepatology 9:5, 452-456
CrossRef8
Peter W. Plaisier, Koen Brakel, RenéL. van der Hul, Hajo A. Bruining. (1994) Radiographic features of oral cholecystograms of 448 symptomatic gallstone patients: implications for nonsurgical therapy. European Journal of Radiology 18:1, 57-60
CrossRef9
G. CHOUDHURI, D.K. AGARWAL, R.V. PHADKE, V. RAMESH, W. HAUSER, J. KUMAR, T.S. NEGI, A. KULSHRESHTHA. (1994) Brittleness of gallstones to lithotripsy: effect of physicochemical and ultrastructural characteristics. European Journal of Clinical Investigation 24:1, 22-27
CrossRef10
DIETER J. ZIEGENHAGEN, ELMAR ZEHNTER, WOLFGANG KRUIS, CHRISTOPH POHL. (1993) Induced gall-bladder contraction accelerates fragment clearance after extracorporeal shockwave lithotripsy. Journal of Gastroenterology and Hepatology 8:5, 406-409
CrossRef11
David L. Nahrwold. (1993) Gallstone lithotripsy. The American Journal of Surgery 165:4, 431-434
CrossRef12
Johnston, David E.Kaplan, Marshall M.. (1993) Pathogenesis and Treatment of Gallstones. New England Journal of Medicine 328:6, 412-421
Full Text13
Bertram I. Cohen, Shigeo Miki, Erwin H. Mosbach, Nariman Ayyad, Richard J. Stenger, Takahiro Mikami, Michiko Yoshii, Kenji Kihira, Takahiko Hoshita. (1993) Bile Acid Sulfonates Alter Cholesterol Gallstone Incidence in Hamsters. Hepatology 17:1, 103-110
CrossRef14
A. Mark Fendrick, Gérard De Pouvourville, Caterine Bitker, Gilles Pelletier. (1992) Treatment of Symptomatic Cholelithiasis in France: A Decision Analysis Comparing Cholecystectomy and Biliary Lithotripsy. International Journal of Technology Assessment in Health Care 8:01, 166
CrossRef15
R.H. Dowling, S.H. Hussaini, G.M. Murphy, G.M. Besser, J.A.H. Wass. (1992) Gallstones during octreotide therapy. Metabolism 41:9, 22-33
CrossRef16
Steven M. Strasberg, Pierre-Alain Clavien. (1992) Cholecystolithiasis: Lithotherapy for the 1990s. Hepatology 16:3, 820-839
CrossRef17
Michael Sackmann, Juergen Pauletzki, Uelker Aydemir, Joseph Holl, Tilman Sauerbruch, Joerg Hasford, Gustav Paumgartner. (1991) Efficacy and safety of ursodeoxycholic acid for dissolution of gallstone fragments: Comparison with the combination of ursodeoxycholic acid and chenodeoxycholic acid. Hepatology 14:6, 1136-1141
CrossRef18
T. Sauerbruch, G. Paumgartner. (1991) Gallbladder stones: management. The Lancet 338:8775, 1121-1124
CrossRef19
T.V Holohan. (1991) Laparoscopic cholecystectomy. The Lancet 338:8770, 801-803
CrossRef20
(1991) Extracorporeal Shock-Wave Biliary Lithotripsy. New England Journal of Medicine 324:25, 1813-1814
Full Text21
I LAUFER. (1991) A transatlantic view of gallstone lithotripsy. Clinical Radiology 43:5, 295-296
CrossRef22
(1991) Lithotripsy of Gallstones. New England Journal of Medicine 324:15, 1068-1069
Full Text23
J. J. Donald, J. S. Fache, H. J. Burhenne, A. Darzi, F. B. V. Keane. (1991) Gallstone clearance: A randomized study of extracorporeal shock wave lithotripsy and chemical dissolution. British Journal of Surgery 78:4, 506-506
CrossRef24
A. Darzi, F. B. V. Keane, H. J. Burhenne, S. H. Lee. (1991) Gallbladder surgery following cholecystlithotripsy: Suggested guidelines for treatment. British Journal of Surgery 78:4, 506-507
CrossRef25
Jorge J. Gumucio, Peter F. Malet. (1991) Laparoscopic cholecystectomy: What is really known about it?. Hepatology 13:3, 604-605
CrossRef26
Way, Lawrence W., . (1990) Changing Therapy for Gallstone Disease. New England Journal of Medicine 323:18, 1273-1274
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- Letters
