Noncalcified Stones Research Articles

Dual-layer spectral detector computed tomography versus magnetic resonance cholangiopancreatography for biliary stones.

Dual-layer spectral detector computed tomography (DLCT) can detect noncalcified biliary stones. The diagnostic ability of DLCT for detecting biliary stones may be comparable to that of magnetic resonance cholangiopancreatography (MRCP). This study seeks to compare the diagnostic ability for biliary stones between these two imaging modalities. This retrospective study included 102 cases with a diagnosis of biliary stones including gallstones (n = 66) and common bile duct (CBD) stones (n = 25) or spontaneously passing CBD stones (n = 11). The reference standard used was operative findings, endoscopic retrograde cholangiopancreatography or follow-up over 6 months. In DLCT, 120-kVp images, 40-keV virtual monoenergetic images and material decomposition images were created. We compared the diagnostic ability of DLCT and MRCP for biliary stones using the McNemar's test. The sensitivity and specificity of DLCT versus MRCP for biliary stones were 91.2% versus 95.6% and 90.9% versus 90.9%. Thus, the sensitivity and specificity were not significantly different (P = 0.25 and P = 1.0). Although in small stones (<9 mm) the sensitivity of calcified stones was not different between DLCT and MRCP (100% versus 92.5%), the sensitivity of noncalcified stones in DLCT was lower than that in MRCP (38.5% versus 100%). The diagnostic ability of biliary stones in DLCT appears comparable to that of MRCP in overall cases. However, detecting noncalcified stones less than 9 mm in size is limited in DLCT.

Making the invisible visible: improving conspicuity of noncalcified gallstones using dual-energy CT.

To determine whether virtual monochromatic imaging (VMI) increases detectability of noncalcified gallstones on dual-energy CT (DECT) compared with conventional CT imaging. This retrospective IRB-approved, HIPAA-compliant study included consecutive patients who underwent DECT of the abdomen in the Emergency Department during a 30-month period (July 1, 2013-December 31, 2015), with a comparison US or MR within 1-year. 51 patients (36F, 15M; mean age 52 years) fulfilled the inclusion criteria. All DECT were acquired on a dual-source 128×2 slice scanner using either 80/Sn140 or 100/Sn140kVp pairs. Source images at high and low kVp were used for DE post-processing with VMI. Within 3 mm reconstructed images, regions of interest of 0.5cm2 were placed on noncalcified gallstones and bile to record hounsfield units (HU) at VMI energy levels ranging between 40 and 190keV. Noncalcified gallstones uniformly demonstrated lowest HU at 40keV and increase at higher keV; the HU of bile varied at higher keV. Few of the noncalcified stones are visible at 70keV (simulating a conventional 120kVp scan), with measured contrast (bile-stone HU difference) <10 HU in 78%, 10-20 HU in 20%, and >20 HU in 2%. Contrast was maximal at 40keV, where 100% demonstrated >20 HU difference from surrounding bile, 75% >44 HU difference, and 50% >60 HU difference. A paired t test demonstrated a significant difference (p<0.0001) between this stone-bile contrast at 40 vs. 70keV and 70 vs. 190keV. Low keV virtual monochromatic imaging increased conspicuity of noncalcified gallstones, improving their detectability.

Treatment of gallstones by extracorporeal shock wave lithotripsy

Extracorporeal shock wave lithotripsy (ESWL) has been used since 1985 in a variety of countries for the treatment of gallstones in selected patients (1–14). Clinical use has been routine in western Europe for a decade (15). The limited experience in the United States has been investigational, through tests of the Medstone STS lithotripter (Medstone International, Aliso Viejo, CA) (2, 10, 11), EDAP LT01 lithotripter (EDAP Technomed, Boston, MA) (5), and Dornier lithotripter (Dornier Medical Systems, Munich, Germany) (6). ESWL of cholesterol gallstones with adjuvant bile acid dissolution therapy accelerates stone disappearance; ESWL shatters the stone into small fragments that can be dissolved more quickly. Analysis of stone fragments in the feces of patients who underwent ESWL showed that 3-mm fragments can pass into the intestine without causing symptoms (16). In September, 2000 the Food and Drug Administration approved, subject to a postapproval study, the first lithotripter for gallstone application in the United States, the Medstone STS. Treatment, which comprises lithotripsy treatments of up to 2000 24-kV shocks and administration of ursodiol, is indicated in symptomatic adult patients for whom surgical removal of the gallbladder is medically contraindicated and in symptomatic high-risk patients who have actively refused surgery. Patients must have functioning gallbladders and solitary, radiolucent, noncalcified stones from 4 to 20 mm in maximum diameter. Ursodiol is a naturally occurring bile acid that dissolves gallstones of cholesterol origin. Lithotripters vary with respect to shock wave generation, focusing, and targeting. The Medstone STS, which has been commercially available for the treatment of kidney stones in the United States since 1988, generates a spark-gap shock wave in a water column. The shock wave pulse travels with little attenuation through the water column and soft tissues of the body. When it hits the anterior surface of the gallstone throughout the posterior surface, the changes in acoustic impedance lead to the liberation of compressive and tensile forces, resulting in fragmentation of the stone. Other devices use this electrohydraulic approach or piezoelectric crystals or electromagnetic membranes to generate the shock waves. The multicenter, prospective, postapproval randomized trial of the Medstone STS lithotripter in gallstone therapy is directed toward confirmation of efficacy and collection of additional data supporting safety in routine clinical practice. The selected patients will be treated in the prone position, using i.v. propofol analgesia, and on an outpatient basis. Efficacy of ESWL will be defined as the percentage of patients with stone-free gallbladders according to abdominal ultrasound after 3, 6, and 12 months. Findings will be compared with the results of ursodiol monotherapy.

Treatment of gallstones by extracorporeal shock wave lithotripsy.

Extracorporeal shock wave lithotripsy (ESWL) has been used since 1985 in a variety of countries for the treatment of gallstones in selected patients (1–14). Clinical use has been routine in western Europe for a decade (15). The limited experience in the United States has been investigational, through tests of the Medstone STS lithotripter (Medstone International, Aliso Viejo, CA) (2, 10, 11), EDAP LT01 lithotripter (EDAP Technomed, Boston, MA) (5), and Dornier lithotripter (Dornier Medical Systems, Munich, Germany) (6). ESWL of cholesterol gallstones with adjuvant bile acid dissolution therapy accelerates stone disappearance; ESWL shatters the stone into small fragments that can be dissolved more quickly. Analysis of stone fragments in the feces of patients who underwent ESWL showed that 3-mm fragments can pass into the intestine without causing symptoms (16). In September, 2000 the Food and Drug Administration approved, subject to a postapproval study, the first lithotripter for gallstone application in the United States, the Medstone STS. Treatment, which comprises lithotripsy treatments of up to 2000 24-kV shocks and administration of ursodiol, is indicated in symptomatic adult patients for whom surgical removal of the gallbladder is medically contraindicated and in symptomatic high-risk patients who have actively refused surgery. Patients must have functioning gallbladders and solitary, radiolucent, noncalcified stones from 4 to 20 mm in maximum diameter. Ursodiol is a naturally occurring bile acid that dissolves gallstones of cholesterol origin. Lithotripters vary with respect to shock wave generation, focusing, and targeting. The Medstone STS, which has been commercially available for the treatment of kidney stones in the United States since 1988, generates a spark-gap shock wave in a water column. The shock wave pulse travels with little attenuation through the water column and soft tissues of the body. When it hits the anterior surface of the gallstone throughout the posterior surface, the changes in acoustic impedance lead to the liberation of compressive and tensile forces, resulting in fragmentation of the stone. Other devices use this electrohydraulic approach or piezoelectric crystals or electromagnetic membranes to generate the shock waves. The multicenter, prospective, postapproval randomized trial of the Medstone STS lithotripter in gallstone therapy is directed toward confirmation of efficacy and collection of additional data supporting safety in routine clinical practice. The selected patients will be treated in the prone position, using i.v. propofol analgesia, and on an outpatient basis. Efficacy of ESWL will be defined as the percentage of patients with stone-free gallbladders according to abdominal ultrasound after 3, 6, and 12 months. Findings will be compared with the results of ursodiol monotherapy.

Pulverisation of calcified and non-calcified gall bladder stones: extracorporeal shock wave lithotripsy used alone.

Using a modified electromagnetic lithotripter (Siemens), extracorporeal shock wave lithotripsy (ESWL) was performed in 260 patients with gall bladder stones. Exclusion criteria for treatment were a non-functioning gall bladder, subcostal gall bladder location, and multiple stones occupying more than three quarters of the gall bladder volume. Stone pulverisation was the end point of ESWL. The number of shock wave discharges and sessions was not limited. Pulverisation was achieved in 250 patients (96.1%) after a median of three ESWL sessions (range 1-21). The number of sessions required depended upon stone composition and burden. More than three sessions were required in 60.2% of patients with calcified stones compared with 35.9% of patients with non-calcified stones (p < 0.001). 65.8% of patients with stones measuring more than 30 mm in total diameter required more than three sessions compared with 42.9% of patients with a stone burden less than 30 mm (p < 0.01). At 18-24 (8-12) months follow up, stone clearance was achieved in 94.3% (80.4%) of patients with non-calcified stones, compared with 89.5% (76.8%) in patients with calcified stones and in 75% (71.4%) of patients with a total stone diameter more than 30 mm compared with 95.7% (80.4%) for patients with a total stone diameter less than 30 mm (p < 0.05). ESWL related complications (gross haematuria) occurred in three patients. Thirty six (13.8%) patients experienced biliary colic; four had cholecystectomy, and five endoscopic papillotomy because of common bile duct obstruction. Stone recurrence was seen in 5.3% of patients over a follow up period of up to two years (median 16.6 months).

Bile composition, microspheroliths, antinucleating activity, and gallstone calcification

This study examined if abnormalities in bile composition and antinucleating activity are associated with gallstone calcification. Nineteen controls without gallbladder disease and 42 patients with cholesterol stones were studied. Bile was obtained at surgery and analyzed for pH and Pco2, ionized calcium, and total calcium. The pH and carbonate concentrations of gallbladder bile were significantly higher in patients with calcified stones than in patients with noncalcified stones and in controls, resulting in significantly higher levels of the ion product in patients with calcified gallstones. Microspheroliths of calcium carbonate, seen on microscopic examination of bile, predicted stone calcification with a sensitivity of 86%, a specificity of 86%, and a predictive value of 86%. Bile from control subjects completely inhibited precipitation of calcium carbonate from a supersaturated solution, whereas bile from subjects with calcified and non-calcified gallstones did not. It is concluded that gallstone calcification is related to elevated bile pH and carbonate concentrations, resulting in an elevated ion production of calcium carbonate in gallbladder bile. In addition, bile from subjects with calcified and noncalcified gallstones lacks antinucleating activity for calcium carbonate.

Shock wave lithotripsy of gallstones: results and 12-month follow-up in 174 patients.

At the authors' institution, as part of the on-going Dornier National Biliary Lithotripsy Study, 174 patients with gallstones were randomly assigned to receive either ursodeoxycholic acid (UDCA) or placebo for 6 months after undergoing extracorporeal shock wave lithotripsy (ESWL). Six weeks after ESWL, 40 (23%) patients were re-treated for gallstone fragments larger than 5 mm in diameter. No significant difference in the UDCA- and placebo-treated patients was noted. The overall 6- and 12-month stone-free rates for all patients with initially noncalcified stones were as follows: UDCA patients, 31% and 36%, respectively, and placebo patients, 21% and 23%, respectively (P less than .05). In patients with a single, noncalcified gallstone that was at most 20 mm in diameter, the 12-month stone-free rates were as follows: UDCA patients, 60%, and placebo patients, 33% (P less than .01). Patients with noncalcified stones that were 11-20 mm in diameter who were treated with UDCA had a higher rate of stone clearance than placebo patients. At 6 months, the authors' previous study demonstrated no significant difference in the two groups of patients. However, the stone-free rate at 12 months was noted to be significantly higher for patients with a single, noncalcified stone that was at most 20 mm in diameter begun on UDCA than for all other groups of patients.

Extracorporeal shock wave lithotripsy of gallstones: results and 6-month follow-up in 141 patients.

A study of biliary shock wave lithotripsy of gallstones sponsored by Dornier Medical Systems, Munich, began in the United States in May 1988 to evaluate the efficacy and safety of extracorporeal shock wave lithotripsy (ESWL) and the need for adjunctive therapy with ursodeoxycholic acid (UDCA). One hundred forty-one symptomatic patients with one to three gallstones 5-30 mm in diameter were randomized to treatment. One week before ESWL, patients were given either UDCA or placebo. This treatment was continued for 6 months. All patients underwent follow-up at predetermined intervals. According to the protocol, re-treatment for fragments larger than 5 mm in diameter could be performed only at 6 weeks; 26 (18%) of the 141 patients were retreated. At 6 months, the stone-free rates for single stones were as follows: patients with noncalcified stones receiving UDCA, 29%; patients with noncalcified stones receiving placebo, 24%; and patients with partially calcified stones receiving either UDCA or placebo, 6%. No significant difference was noted between the UDCA and placebo groups. At 6 months, the stone-free rates in patients with single, noncalcified stones 20 mm or less in diameter were 40% (UDCA) and 32% (placebo), which is superior to rates for those with solitary, noncalcified gallstones 21-30 mm in diameter and those with two or three stones.

Computed tomography evaluation of radiolucent gallstones in vivo

Computed tomography facilitates an in vivo classification of gallstones and can aid in the identification of calcifications that escape detection with conventional radiologic procedures. Of patients with radiolucent stones, 54.8% exhibited calcifications either in the form of discrete rims (41.9%) or at the center of the stone (12.9%). Densities of the noncalcified areas of partially calcified stones averaged 40.68 +/- 6.8 Hounsfield units (HU), which was not significantly higher than the average of 31.85 +/- 3.19 HU for noncalcified stones. Calcified regions showed significantly higher densities (240.0 +/- 28.6 HU, p less than 0.001, x +/- SEM). Of the identified stones, 16.1% showed densities greater than 50 HU. These were primarily bilirubin stones, which cannot yet be treated successfully with conservative therapeutic modalities.

Non-surgical options for the management of gallstone disease: an overview

The modalities for the non-surgical treatment of gallstones include oral dissolution by bile salts, local dissolution by methyl-tert-butyl-ether (MTBE), extracorporeal shockwave lithotripsy (ESWL) and percutaneous gallstone clearance. The results of oral bile salt therapy for cholesterol stones have been disappointing, and the only indication for this treatment is after ESWL. The high efficacy initially reported for MTBE has not been confirmed by subsequent experience in other centres: this therapy is toxic and best confined to specialized centres. ESWL, though effective in noncalcified stones, has limited overall applicability (approx. 15%) and is frequently followed by recurrence despite maintenance therapy with oral bile salts. Percutaneous gallstone clearance (radiologic or laparoscopic) has been superseded by laparoscopic cholecystectomy. This offers definitive treatment in a single session and has significant advantages over open cholecystectomy in terms of short hospital stay and accelerated recovery with early return to work or full activity. Destruction of the gallbladder by sclerosant agents (chemical cholecystectomy) requires further experimental evaluation before its introduction to clinical practice.

Gallstone dissolution in methyl tert-butyl ether after mechanical fragmentation: in vitro study.

Twenty sets of three gallstones matched for weight and appearance were selected from 20 surgically resected human gallbladders to test the effect of intracorporeal mechanical fragmentation on gallstone dissolution with methyl tert-butyl ether in vitro. One stone from each set was fragmented by a mechanical lithotriptor and then treated with methyl tert-butyl ether, and one was used as control and was treated intact. The third stone was analyzed for its density pattern on CT and biochemically for its cholesterol and calcium content. On the basis of CT appearance, the stones were classified as noncalcified, partially calcified, or heavily calcified. Mechanical fragmentation reduced dissolution time by 25-69% (mean +/- SD, 44 +/- 16%) for the noncalcified stones and by 20-42% (mean +/- SD, 30 +/- 8%) for the partially calcified stones. No significant reduction was observed for the heavily calcified stones. The degree of reduction was inversely related to maximal stone density (r = -.72) and was independent of its pattern of calcification. This study shows that mechanical fragmentation is effective in accelerating gallstone chemolysis by methyl tert-butyl ether for noncalcified and partially calcified but not for heavily calcified stones.

Gallstone fragmentation with contact electrohydraulic lithotripsy: in vitro study of physical and technical factors.

To identify physical and technical factors that have an effect on fragmentation, the authors performed in vitro contact electrohydraulic lithotripsy (EHL) on gallstones 10 mm or larger in size. Of 122 gallstones, 113 (93%) could be fragmented with 1-46 pulses from a 3-F electrode (average, 10 pulses). Only 12 of the 113 stones could be fragmented with a single spark. Of the nine stones that did not fragment with 50 pulses from a 3-F electrode, four were larger than 30 mm in diameter, and five were seen at radiography to be heavily calcified; all of these stones were fragmented with five or fewer pulses from a 9-F electrode. Stone capture in a wire basket facilitated fragmentation of gallstones of all sizes, but particularly those stones 15 mm or larger. Contact EHL could be performed as well in a 1:1 dilute diatrizoate irrigating solution as in 1:6 normal saline. A significantly greater number of pulses was required to fragment gallstones 15 mm in diameter or larger compared with stones smaller than 15 mm (P less than .01). In addition, stones 15 mm or smaller had a greater tendency to fragment into "gravel" (ie, fragments measuring 2 mm or less), while EHL of stones larger than 15 mm produced larger, discrete fragments of approximately equal size (P less than .05). EHL of heavily calcified gallstones required a significantly greater number of pulses than EHL of less calcified or noncalcified stones (P less than .002).

Extracorporeal shock wave lithotripsy of gallstones: Objectives, current limitations, and preliminary in vitro and in vivo observations

Surgical removal of gallstones is performed about 500 000 times per year in the United States. Although the usual cost ranges from $5000 to more than $10 000 per patient, the operative mortality is less than 1% for otherwise healthy persons. Nonsurgical dissolution of gallstones is often possible, but many gallstones contain calcium compounds that slow or prevent dissolution using the direct content cholesterol solvent, methyl tertbutyl ether (MTBE). Extracorporeal shock wave lithotripsy (ESL) has potential clinical utility for facilitating dissolution and possibly allowing spontaneous or induced passage of small fragments via the bile ducts and intestines. Obstacles to be overcome include predictable fragmentation of multiple stones up to 3 cm in diameter so that all particles are small enough to be rapidly dissolved or pass safely through the bile ducts (⩽ 3 mm). This must be achieved using biologically tolerable shock wave dosages without requiring general anesthesia within one or two treatment sessions. Acute and chronic safety, patient acceptance, and cost must be competitive with surgical treatment. Initial experience suggests that only solitary noncalcified stones (10% of patients with stones) have a high probability of success using ESL plus oral bile acid dissolution therapy. Improving ESL technology and direct contact fragment dissolution using MTBE should increase the clinical utility of shock wave lithotripsy of gallstones.