Calcified Gallstones Research Articles

S1759 Management of Bouveret Syndrome: A Case Report

Introduction: Bouveret syndrome is an unusual complication of gallstone disease, causing less than 0.2% of small bowel obstructions. It often requires multidisciplinary approaches for treatment. We present here a unique case report of Bouveret syndrome, managed successfully using Holmium LASER alone. Case Description/Methods: A 74-year-old man presented to our hospital with vomiting, decreased appetite, periumbilical pain and nausea. He denied heartburn, fever, chills or jaundice. His past medical history was significant for cardiomyopathy (EF 35%), atrial fibrillation and ventricular tachycardia with AICD placement. He had been admitted 3 months prior with acute cholecystitis and elevated liver function tests. Due to cardiac comorbidities, he was treated with IV Zosyn, cholecystostomy tube and ERCP with sphincterotomy with improvement and he was discharged. 6 weeks later, a tube check confirmed correct placement of the tube and decompression of the gall bladder. This time, his pain differed from the right upper abdominal pain of prior admission. His tube drainage had reduced considerably in the previous day. Physical examination revealed epigastric and supraumbilical tenderness with no guarding or rebound. The cholecystostomy bag had purulent drainage. WBC count was 11.95 x 10,000/cu.mm; liver enzymes and S. Lipase were normal. CT scan showed a change in the position of a previously seen large gallstone, measuring 3.7 cm in diameter. During the previous admission, it was in the gall bladder neck. At this time, it was occupying the duodenal bulb lumen, indicating development of a cholecystoduodenal fistula, and causing complete obstruction. The surgical team recommended endoscopic treatment due to anticipated friability of the tissue (Figure). Endoscopic evaluation showed complete obstruction of the duodenal bulb by a large smooth stone, not allowing passage of even a guidewire beyond the stone. Lithotripsy was chosen to help relieve the obstruction. 410 micron and 990 micron Holmium LASER probes were used with assistance from Urology, via an antegrade approach from the pylorus through a gastroscope. After 2 sessions of lithotripsy 4 days apart, each breaking through pigmented and calcified stone, the stone passed through the small bowel, relieving the obstruction. Discussion: The patient did not require surgical intervention and has recovered well. This case illustrates the feasibility of Holmium LASER to treat heavily calcified and pigmented gallstones. Holmium LASER should be developed for use in GI Endoscopy.Figure 1.: Gallstone obstructing duodenal bulb; LASER lithotripsy of calcified and pigmented stone; residual ulcer in duodenal bulb after stone passed.

Hey, you forgot something! The Management of Symptomatic Retained Gallstones

• The majority of dropped gallstones remain asymptomatic; symptomatic complications are extremely rare. • Patients usually present weeks to months to years after their surgery with focalized abdominal pain. • Common CT findings include fluid filled collections that contain multiple calcified gallstones. • Dropped gallstones have been found in multiple locations; this is the first report of stone fragments in sputum. • Today, interventional radiologic procedures are the mainstay of treatment over open surgical removal. Retained gallstones are a rare but potentially morbid condition. When symptomatic they can require drainage and prolonged antibiotics. With the increase in laparoscopic cholecystectomies performed, the incidence of retained gallstones has risen. A retrospective chart review was performed at a 650-bed hospital over 15 years and cases of retained gallstones were identified. A comprehensive literature review was conducted regarding the management of symptomatic retained stones. Fourteen patients were identified to have retained gallstones. Six patients became symptomatic and required interventions. Included in our report is the first case of retained stone fragments coughed up in a patient's sputum. Post-cholecystectomy patients presenting with vague complaints or peri‑hepatic abscesses months to years after cholecystectomy, even when there is no evidence of stones on imaging, should be considered for symptomatic retained gallstones. Interventional radiologic procedures have become the mainstay treatment of choice, with surgeons moving away from open drainage.

S1645 Successful and Rapid Correction of Severe Hypertriglyceridemia With Insulin in a Case of Hypertriglyceridemic Pancreatitis

Introduction: Acute pancreatitis (AP) is a common diagnosis with 275,000 yearly admissions, but only 1-7% of cases are due to hypertriglyceridemia. In these cases, it is imperative that elevated triglycerides (TG) are rapidly corrected. Plasmapheresis is known to be the most effective treatment, but there is question whether insulin can be utilized. We present a case of hypertriglyceridemic pancreatitis (HTGP) successfully treated with insulin. Case Description/Methods: 29-year-old obese female with history of hyperlipidemia and diabetes mellitus type II presented with epigastric pain radiating to her back, nausea, and vomiting. The patient had no surgical history and denied history of alcohol use. Vital signs were stable, but the patient was in visible discomfort. Abdominal exam displayed tenderness in the epigastric area with absent rebound and guarding and negative Murphy's. Due to the presence of characteristic pain and a lipase level of 1,159 U/L, the diagnosis of AP was made. Additional labs were significant for a hemoglobin A1c of 10.1 and a TG level of 7,951 mg/dL suggesting the etiology of AP. CBC, CMP, and lactic acid were within normal limits. CT abdomen/pelvis demonstrated an unremarkable pancreas and no calcified gallstones or pericholecystic inflammatory changes but an enlarged liver with diffuse fatty changes. The patient was started on aggressive intravenous fluids. Insulin drip (Regular Insulin 1 Units/mL in NS 100 mL infusion) was initiated to correct TG levels along with fenofibrate 145 mg and omega-3 fatty acid 2,000 mg. The patient's TG levels were trended every 12 hours. Within 48 hours, the patient's TG improved to 371 mg/dL allowing the transition to subcutaneous insulin. Two days following admission, the patient was discharged on an insulin regimen in addition to fenofibrate 145 mg and Vascepa 2g BID for outpatient management and recurrence prevention. Discussion: In cases where TGs are over 5000 mg/dL, plasmapheresis is often used while there are only a few documented cases of insulin use in this setting. However, plasmapheresis has multiple drawbacks including cost, invasiveness, and limited availability. Rapid correction of TGs leads to better clinical outcomes in this uncommon etiology of pancreatitis. Our case demonstrates the effectiveness of insulin in rapidly correcting TG levels within 48 hours and decreasing length of hospitalization. Therefore, our case supports the evolving role of insulin as a safe, readily available, and effective alternative for treatment of HTGP.

Spontaneous cholecystocutaneous fistula as the presenting manifestation of IgG4-related disease

A 79-year-old woman with an unremarkable past medical history presented to the outpatient surgery clinic with a 30-day history of dull abdominal pain. She had noticed a skin orifice in the supraumbilical region discharging a yellowish serous material. Ultrasound showed findings of chronic cholelithiasis. An x-ray fistulogram disclosed a 3.9-inch-long fistulous tract from the skin to the gallbladder (Fig 1) confirming the diagnosis of spontaneous cholecystocutaneous fistula. An abdominal CT showed diffuse and smooth thickening of the gallbladder wall with multiple calcified gallstones.

Biliary microbiota and mucin 4 impact the calcification of cholesterol gallstones

BackgroundCholesterol gallstones account for over 80% of gallstones, and the pathogenesis of gallstone formation involves genetic and environmental factors. However, data on the evolution of cholesterol gallstones with various densities are limited. This study aimed to determine the roles of microbiota and mucins on the formation of calcified cholesterol gallstones in patients with cholelithiasis. MethodsPaired gallbladder tissues and bile specimens were obtained from cholelithiasis patients who were categorized into the isodense group and calcified group according to the density of gallstones. The relative abundance of microbiota in gallbladder tissues was detected. Immunohistochemistry and enzyme-linked immunosorbent assay were performed to detect the expression levels of MUC1, MUC2, MUC3a, MUC3b, MUC4, MUC5ac and MUC5b in gallbladder tissues and bile. The correlation of microbiota abundance with MUC4 expression was evaluated by linear regression. ResultsA total of 23 patients with gallbladder stones were included. The density of gallstones in the isodense group was significantly lower than that of the calcified group (34.20 ± 1.50 vs. 109.40 ± 3.84 HU, P < 0.0001). Compared to the isodense group, the calcified group showed a higher abundance of gram-positive bacteria at the fundus, in the body and neck of gallbladder tissues. The concentrations of MUC1, MUC2, MUC3a, MUC3b, MUC5ac and MUC5b in the epithelial cells of gallbladder tissues showed no difference between the two groups, while the concentrations of MUC4 were significantly higher in the calcified group than that in the isodense group at the fundus (15.49 ± 0.69 vs. 10.23 ± 0.54 ng/mL, P < 0.05), in the body (14.54 ± 0.94 vs. 11.87 ± 0.85 ng/mL, P < 0.05) as well as in the neck (14.77 ± 1.04 vs. 10.85 ± 0.72 ng/mL, P < 0.05) of gallbladder tissues. Moreover, the abundance of bacteria was positively correlated with the expression of MUC4 (r = 0.569, P < 0.05) in the calcified group. ConclusionsThis study showed the potential clinical relevance among biliary microbiota, mucins and calcified gallstones in patients with gallstones. Gram-positive microbiota and MUC4 may be positively associated with the calcification of cholesterol gallstones.

Virtual unenhanced imaging of the liver with third-generation dual-source dual-energy CT and advanced modeled iterative reconstruction

ObjectivesTo compare image quality and diagnostic accuracy for the detection of liver lesions of virtual unenhanced (VU) images based on third-generation dual-source dual- energy computed tomography (DECT) compared to conventional unenhanced (CU) images. MethodsThirty patients underwent triphasic abdominal CT consisting of single-energy CU (120kV, 147 ref.mAs) and dual-energy CT arterial and portal-venous phase acquisitions (100/Sn150kV, 180/90 ref.mAs). VU images were generated from arterial (AVU) and portal venous (PVU) phases. CU, AVU and PVU datasets were reconstructed. Quantitative image quality analysis was performed and two abdominal radiologists independently analyzed all datasets to evaluate image quality and identify liver lesions. Radiation dose was recorded and potential radiation dose reduction was estimated. ResultsImage quality was rated diagnostic in 100% of the VU datasets. The mean subjective image quality of the CU datasets was higher than that of VU images (p<0.0001). No significant difference was observed in the mean attenuation values of the liver parenchyma (p>0.99) and hypoattenuating liver lesions (p≥0.21) between CU, AVU and PVU. However, a significant reduction in the attenuation values of calcified lesions (p<0.0001), metallic clips (p<0.0001) and gallstones (p≤0.047) was observed in the AVU and PVU images compared with CU images. A total of 122 liver lesions were found in 25 patients. VU images were more sensitive than CU images for detection of small hypoattenuating liver lesions (≤1cm). However, CU images were more sensitive than VU for calcified liver lesions. The mean radiation dose reduction achievable by avoiding the unenhanced acquisition was 32.9%±1.1% (p<0.01). ConclusionsThird-generation DSCT VU images of the liver provide diagnostic image quality and improve small (≤1cm) liver lesion detection; however calcified liver lesions can be missed due to complete subtraction.

The hunt for microlithiasis in idiopathic acute recurrent pancreatitis: Should we abandon the search or intensify our efforts?

The hunt for microlithiasis in idiopathic acute recurrent pancreatitis: Should we abandon the search or intensify our efforts?

Extracorporeal shock wave lithotripsy

Until now, radiopaque gallstones have been excluded from extracorporeal shock wave lithotripsy (ESWL), because these stones in vivo are less sensitive to the forces that cause disintegration. In Japan there is a higher percentage of patients with radiopaque gallstones than in Western countries. Our purpose in working with patients in Japan was to warrant extensive indication of ESWL to radiopaque gallstones, especially densely calcified stones. Retrospective analysis of clinical data. Patients were classified by computed tomography (CT) of stones. Group A consisted of 78 patients whose gallstones were densely calcified (CT attenuation values in Hounsfield units (HU), 473 +/- 323). Group B consisted of 22 patients whose stones had a calcified rim (CT attenuation values, 357 +/- 244). Ninety-eight patients received adjuvant dissolution therapy with ursodeoxycholic acid. Other recommendations, such as a glass of milk at night, were not given to the patients. One university hospital and one general hospital. One hundred consecutive Japanese patients with radiopaque stones in contractile gallbladder (CT attenuation values, > 150 HU, 447 +/- 310, mean +/- SD) were the subjects. With respect to the efficacy of ESWL, a degree of calcification for stones and its relationship with the rates of stone fragmentation and disappearance were assessed. Fragmentation to less than 3 mm in stone diameter was the aim, without limit of shock wave discharges and sessions. After ESWL sessions stones were fragmented successfully in 74 of the 100 patients (57 of the 78 patients in Group A, and 17 of the 22 patients in Group B). The mean number of discharges per patient was 10,435 +/- 8,726. The mean number of discharges for successful stone fragmentation of Group A (9,839 +/- 8,187) was not significantly different from that of Group B (11,376 +/- 6,344). One year after lithotripsy, 60 of the 100 patients were free of stones (45 in Group A, and 15 in Group B). It appears that patients with either densely calcified gallstones, or those in whom the stones have a calcified rim, are both suitable candidates for lithotripsy.

Basic studies on the utility of ursodeoxycholic acid derivatives for clinical medicine

The aim of this study was to determine whether the derivatives of ursodeoxycholic acid (UDCA) are useful compounds for clinical medicine. 1-1) A conjugate (5-ASA-UDCA monophosphate) of UDCA monophosphate with 5-aminosalicylic acid (5-ASA) was newly synthesized, and basic studies on this compound were carried out. This compound was efficiently deconjugated by cholylglycine hydrolase (CGH) to release 5-ASA, whereas it was completely resistant to deconjugation by pancreatic and intestinal mucosal enzymes. In animal experiments, the urinary excretion of N-acetyl-5-ASA (Ac-5ASA) was measured for 24 h following the oral administration of 20 mg of 5-ASA-UDCA monophosphate. Control rats excreted 276.3 +/- 89.0 micrograms (mean +/- S.E.) of Ac-5ASA whereas rats with intestinal bacterial overgrowth excreted more (1224.1 +/- 231.5 micrograms; p < 0.01). These basic studies indicate that this compound is likely to offer a simple method for the evaluation of intestinal microorganisms without the use of radioisotopes or expensive, special apparatus. 1-2) The disulphate ester of ursodeoxycholyl-p-aminobenzoic acid (PABA-UDCA) was synthesized and compared with PABA-UDCA for its use in the detection of intestinal bacteria. This compound, PABA-UDCA disulphate, had characters in common with PABA-UDCA in that it was deconjugated by CGH to release free PABA. Further, in rat experiments the urinary excretion of PABA was measured for 6 h after oral administration of 15 mg PABA-UDCA disulphate. Ten control rats excreted 188.2 +/- 13.6 micrograms (mean +/- S.E.) of PABA; 10 rats with an intestinal stagnantloop excreted more (530.1 +/- 30.1 micrograms; p < 0.001): whereas 10 rats in each of three groups pretreated with oral administration of various antibiotics excreted less. PABA-UDCA disulphate is a single pass type substance in the gut and its oral administration test reflects the sum of the activities of bacteria in the small intestine and colon. From the results the obtained PABA-UDCA disulphate was considered a good material to detect intestinal bacteria. 2) A conjugate (Lys-UDCA) of UDCA with L-lysine was newly synthesized. In the incubation experiments with plasma, homogenates of the liver and small intestine, various pancreatic enzymes and CGH, Lys-UDCA was deconjugated by carboxypeptidases B and CGH. In the experiment using rodent everted gut sac, Lys-UDCA was actively absorbed from the terminal ileum. Lys-UDCA was recovered well in the bile after intravenous or intraileal administration of Lys-UDCA in biliary fistula rat. These data suggest that Lys-UDCA is a good prodrug of UDCA for intravenous administration. 3) A novel calcium-chelating agent, N"-ursodeoxycholyl-diethylenetriamine-N,N,N'-triacetic acid (UDCA-DTTA), was synthesized to study its ability to dissolve calcified gallstones. In the presence of the agent, sliced human gallstone with a composition of more than 50% calcium bilirubinate was thoroughly dissolved, indicating that calcium bilirubinate was dissolved from the gallstone. The ability to dissolve calcium was comparable to that of EDTA. However, the laminar structure of the sliced gallstone did not disappear in the presence of EDTA, whereas the structure disappeared in the presence of UDCA-DTTA. These results indicate that UDCA-DTTA is an interesting compound as a parent substance for developing a prodrug for an oral or intravenous agent to dissolve calcium-containing gallstones.

Gasless Laparoscopic Cholecystectomy in a 7-Year-Old Boy with Neurofibromatosis Type I

This report describes a case of a 7-year-old boy with cholelithiasis and neurofibromatosis type 1 (NF1), the association of which has not been described previously, to the author's knowledge. The patient had no other predisposing diseases to the development of cholelithiasis. His multiple small calcified gallstones were asymptomatic. For these asymptomatic stones, less invasive laparoscopic cholecystectomy using an abdominal wall lift method was successfully performed. In this technique, one of the trocars was substituted by a 14-gauge sheath through which needle-sized operating instruments were used. The scar at the needle sheath site disappeared completely soon after surgery. Gasless laparoscopic cholecystectomy using needle-sized instruments achieved a minimally invasive as well as a cosmetically satisfactory result.

Bilirubin inhibits calcium carbonate precipitation in gallbladder bile

Previous studies have shown that human bile contains one or more factors that inhibit the precipitation of calcium carbonate from supersaturated solutions of calcium chloride and sodium bicarbonate. Lower concentrations of this factor have been observed in the gallbladder bile of patients with calcified gallstones. We hypothesized that gallbladder bile contains factors that inhibit calcium carbonate and these factors are present in varying concentrations in normal persons and in patients with cholesterol gallstones with and without calcium carbonate. Gallbladder bile of patients without gallstones (n = 8) and of patients with cholesterol gallstones containing either calcium carbonate (n = 8) or other calcium salts (n = 8) was assayed for calcium carbonate inhibition. Individual components of bile (bilirubin, phospholipid, bile salts, and albumin) were tested in different concentrations in the same assay system. In addition, samples of model bile were tested. An inhibitory factor for calcium carbonate precipitation was present within all human gallbladder bile, irrespective of the absence, presence, or type of gallstones. The addition of a bilirubin-albumin solution to a supersaturated solution of calcium chloride and sodium bicarbonate entirely blocked precipitation of calcium carbonate from solution. In addition, serial dilutions of bilirubin exhibited a linear response between bilirubin concentration and inhibitory effect. Model bile and phospholipid dissolved in sodium taurocholate also exhibited a modest inhibitory effect on calcium carbonate precipitation. We conclude that bilirubin, cholesterol, and phospholipids incrementally interfere with calcium carbonate precipitation in supersaturated solutions through the preferential formation of a soluble calcium complex.

Is defective acidification in gallbladder bile with calcified cholesterol gallstones related to mucus hypersecretion?

Is defective acidification in gallbladder bile with calcified cholesterol gallstones related to mucus hypersecretion?

Percutaneous cholecystolithotomy: risks, benefits, and long-term outcome.

For symptomatic patients with gallbladder stones and a patent cystic duct who wish to retain their 'functioning' gallbladders, percutaneous cholecystolithotomy (PCCL) offers an alternative to open or laparoscopic cholecystectomy. However, there are few data on the risks and benefits of this approach or on the long-term outcome. In 21 patients with symptomatic calcified gallstones, PCCL was successful (gallstone clearance) in 17 (81%). Four to 62 (median, 35) months after clearance 9 of the 17 remained symptom-free and stone-free, whereas 4 developed biliary sludge at 7, 30, 32, and 35 months, 2 of whom subsequently developed gallstones. In four other patients gallstones recurred without evidence of preceding biliary sludge at 9, 16, 19, and 27 months, corresponding to an actuarial gallstone recurrence rate at 36 months of 53.4 +/- SEM 15.1%, and a combined stone/sludge recurrence rate of 63.4 +/- 13.5%. PCCL is moderately effective but, because of the frequency of complications and sludge/stone recurrence, is likely to have only a limited residual role in the era of laparoscopic cholecystectomy.

Changes in serum calcium levels influence biliary calcium levels in humans

Background/Aims: There are few data on the influence of serum calcium on biliary total and ionized calcium levels in humans. The aims of the study were to increase serum calcium levels short-term by intravenous calcium infusion and study the resultant changes in total and ionized calcium concentrations ([CaTOT]and [Ca2+]) in T-tube bile. Methods: Serum and biliary total and ionized calcium concentrations were measured over an 8-hour period in 7 postcholecystectomy patients with T tubes before, during, and after a 4-hour intravenous infusion of 10% calcium gluconate. Results: During the infusion, serum [CaTOT]increased from 2.08 ± 0.14 mmol/L (mean ± SD) to 3.18 ± 0.33 mmol/L, and serum [Ca2+]increased from 1.13 ± 0.13 mmol/L to 1.68 ± 0.13 mmol/L. After a 20–40-minute time lag, there were corresponding increases in biliary [CaTOT]from 1.90 ± 0.45 mmol/L to 2.80 ± 0.52 mmol/L and in biliary [Ca2+]from 0.70 ± 0.11 mmol/ L to 1.19 ± 0.16 mmol/L. When the data were pooled, serum [Ca2+]showed significant correlations with both biliary [CaTOT](n = 128; r = 0.56; P < 0.001) and biliary [Ca2+](n = 128; r = 0.64; P < 0.001). Conclusions: These results support the hypothesis that the biliary tree is freely permeable to calcium ions and that serum calcium level is one determinant of biliary calcium concentration. Our data may also explain the observation that patients with hypercalcemia are reported to have a greater than normal prevalence of calcified gallstones.

High-activity carbonic anhydrase isoenzyme (CA II) in human gallbladder epithelium.

Acidification of bile is one of the factors that prevents calcium precipitation and thereby gallstone formation. Carbonic anhydrase II (CA II) has previously been shown to be one of the key factors in the human alimentary tract that regulates the acid-base balance. We demonstrated CA II expression in the human gallbladder epithelium using immunohistochemical techniques, elucidated the CA II content of the epithelium by digital image analysis of the immunohistochemically stained enzyme in samples from 16 patients undergoing cholecystectomy, and correlated the results with the calcium content of the gallstones. Nine patients had symptomatic gallstone disease and seven an acalculous, histologically normal gallbladder. The patients were classified into two groups on the basis of the calcium content of their gallstones: no gallstones or gallstones containing no calcium (Group 1) and gallstones with 2-87% calcium by weight (Group 2). The immunohistochemical techniques showed distinct epithelial CA II-positive staining in most of the gallbladder samples, but digital image analysis revealed distinct variations in staining intensity among them. The median staining intensity index was significantly higher in Group 1 (0.4463) than in Group 2 (0.2376; p = 0.0262). The results suggest that CA II is abundantly expressed in the normal gallbladder epithelium and that decreased expression may be associated with the formation of calcified gallstones. These findings are relevant to the pathogenesis of gallstone disease.

Dissolution of Calcified Gallstones Part I. Correlation of In Vitro Dissolution Kinetics in Methyl Tert-butyl Ether with Patterns of Calcification by Computed Tomography

The authors evaluated the relationship between stone computed tomography (CT) attenuation patterns and the kinetics of dissolution with methyl tertbutyl ether (MTBE). Single moderately and heavily calcified gallstones from 40 patients were selected from a gallstone library and classified for pattern of calcification by in vitro CT scan (dense, rim, core, and laminated). Each stone was placed in a 10-mL aliquot of MTBE for 24 hours. Stone residue was blotted dry and weighted at 8, 16, and 24 hours. Results were normalized with respect to stone size. Only 1 of 40 (4%) specimens dissolved to particulate matter that was smaller than 2 mm. All (6 of 6) stones that were densely calcified showed virtually no dissolution. The rate of gallstone dissolution varied temporally within the rim, core, and laminated stone categories and was related to the composition of the layer exposed to the solvent at any given time. The success and rate of dissolution may be predicted by the pattern of calcification as determined by computed tomography (CT).

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.

Lithotripsy plus ursodiol is superior to ursodiol alone for cholesterol gallstones

The safety and efficacy of gallbladder extracorporeal shock-wave lithotripsy combined with 600 mg/day ursodiol were examined in 85 patients with radiolucent gallstones, 15 with lightly calcified gallstones, and 12 with radiolucent stones pretreated for ≥2 months with 600 mg/day ursodiol. Results were compared with those of a well-matched lithotripsy-eligible group of 32 subjects treated with ursodiol alone (no lithotripsy). Pretreatment with ursodiol significantly improved while gallstone calcification interfered with fragmentation. Small gallstone size and number also aided fragmentation. Biliary lithotripsy plus ursodiol increased efficacy twofold compared with ursodiol therapy alone (47% vs. 22% of subjects gallstone free; P < 0.02). Gallstones did not disappear in any subject with calcified gallstones (P < 0.001 vs. lithotripsy). Product-limit analysis showed that the efficacy for gallstone dissolution increases in the following order: ursodiol alone, lithotripsy-ursodiol, lithotripsy-ursodiol pretreated with ursodiol (P < 0.02, pairwise). Similar mean gallstone-dissolution rate constants (stone size ÷ time to disappear) of stone fragments and whole gallstones during ursodiol therapy suggest that most fragments disappear by dissolution not expulsion. This finding explains why fragmentation appears to be the key predictor of disappearance and even partial fragmentation accelerates gallstone clearance.

Gallstone fragmentation during biliary lithotripsy: effect of stone composition and structure.

In vitro lithotripsy with the Siemens Lithostar was conducted on 36 radiolucent or minimally calcified gallstones housed in an anthropomorphic phantom. The ease and pattern of fragmentation were correlated with global composition for the entire stone, regional or microcomposition (determined by Fourier-transform infrared spectroscopy), and microstructure (determined by scanning electron microscopy). Stones made up of more than 62% cholesterol required 50% more shock waves to pulverize all fragments to 0.3 cm or less than did stones of less than 62% cholesterol (p less than .01). An inverse relationship was found between the number of shock waves needed for fragmentation and the cholesterol content (r = .77). Although a broad range of fragmentation responses occurred, little variation was seen in the ease of fragmentation within stone families. The majority of stones fractured along radially oriented cholesterol plates, but one third of stones treated showed initial chipping or flaking at the periphery before radial fracture. This type of peripheral erosion most often occurred in stones with peripheral pigment rims. These stones required more shock waves and lagged in pulverization compared with more homogeneous cholesterol stones. The efficiency of fragmentation during biliary lithotripsy correlates with the stones' global cholesterol content. A stone's architecture, as reflected by its regional composition and microstructure, partially predicts the mechanism of fragmentation. These in vitro data may be useful in further refining criteria for selecting patients and understanding the fragmentation process.

Extracorporeal shock wave lithotripsy of calcified gallstones. Work in progress.

Thirty-eight patients with calcific cholecystolithiasis underwent extracorporeal shock wave lithotripsy (ESWL) of the gallbladder on an outpatient basis. Twenty-two (60%) patients had fragments smaller than 3 mm on follow-up ultrasound (US) studies after an average of 13,450 shock waves and four lithotripsy sessions. Nineteen of these 22 patients were followed up for an average of 18 weeks, and only three were found to be free of residual fragments at US. The other three patients were lost to follow-up. Sixteen patients are still undergoing biliary ESWL. Comparison of calcified and noncalcified gallbladder calculi revealed that calcified stones required 50% more shock waves for successful fragmentation, fragments cleared considerably more slowly from the gallbladder, and patients had a higher frequency of acute pancreatitis (5% vs 2%) and transient hematuria (8% vs 3%). Stones with dense homogeneous calcification required significantly fewer shock waves for successful fragmentation than stones with calcific lamination. ESWL can be applied occasionally in patients with calcific cholecystolithiasis if an alternative to surgery is required, but success has been limited.