Gallstone recurrence after successful dissolution therapy.

After successful dissolution therapy of cholesterol gallbladder stones bile again becomes supersaturated and recurrent gallstones may develop. Three different postdissolution treatments [500 mg ursodeoxycholic acid (UDCA) per day (N = 14, group I), 100 mg aspirin per day (N = 14, group II) and diet (N = 15, group III) versus a control group (no treatment, N = 15, group IV) aimed at preventing recurrence of gallstones were investigated in a prospective, randomized study in 58 gallstone patients (33 female, 25 male) after complete stone clearance. Bile samples (prior to dissolution therapy and at stone recurrence) were investigated for biliary cholesterol (C), phospholipids (PL), total bile acid concentration (BA), cholesterol saturation index (CSI), total lipid concentration (TLC), total biliary protein concentration (TP), and nucleation time (NT). In group IV multiple gallstones tended to recur more often than solitary stones (66.7% vs 16.7%) whereas in groups I-III only solitary stones recurred. Recurrent gallbladder stones were detectable in 10 patients (eight patients in group IV and one each in groups I and II, respectively) within one year after dissolution and in two patients (one each in groups III and IV, respectively) after 15 months. Furthermore, the probability of stone recurrence was significantly higher in untreated patients as compared to treated patients. In nine (group IV) of 12 patients with recurrent stones NT, C, CSI, PL, BA, TLC, TP, and bile acid spectrum remained nearly unchanged as compared to their pretreatment values, whereas in three (groups I-III) of 12 cases a decrease in C, CSI, and TP was observed during therapy. However, in each of these three patients, initial and after-treatment TP was significantly higher and NT shorter as compared to groups I-IV. Furthermore, in these cases (N = 3) NT was prolonged, whereas no significant changes were found in PL, BA, TLC, and bile acid spectrum. Recurrence of gallstones, which seems to occur more likely in patients with multiple stones as compared to solitary stones, will happen in the early stage after stone clearance, again causing biliary pain. UDCA, aspirin or diet will reduce the probability for recurrent stones after complete gallstone dissolution.

Combined bile acid therapy is more effective on biliary lipids and dissolution rates than monotherapy after gallstone lithotripsy.

BACKGROUND: Accurate sampling of gallbladder bile for biliary analysis is essential for determining any potential difference between combined bile acid therapy and monotherapy in gallstone patients. METHODS: In 104 gallstone patients undergoing extracorporeal shock wave lithotripsy with following bile acid therapy [either chenodeoxycholic acid (500 mg/day) and ursodeoxycholic acid (500 mg/day), group I (n = 53), or ursodeoxycholic acid alone (1000 mg/day), group II (n = 51)], bile samples, obtained by direct fine needle puncture of the gallbladder, were investigated for biliary lipids, total biliary protein concentration, and nucleation time before and after 12 months of bile acid therapy. RESULTS: Initially, a negative correlation was found between nucleation time and number of gallstones and between total biliary protein concentration and nucleation time (r = -0.52 and r = -0.49 in group I vs r = -0.56 and r = -0.51 in group II, p < 0.01 in each group). The correlation between total biliary protein concentration and nucleation time was also found after 12 months of bile acid treatment (r = -0.54 in group I vs r = -0.47 in group II, p < 0.01 in each group). In group I, the decrease in cholesterol saturation index, biliary cholesterol, cholic acid, deoxycholic acid, and total protein concentration was more pronounced than in group II (p < 0.01). The same effect was found concerning the prolongation of nucleation time (p < 0.01). Furthermore, dissolution rates were higher in group I compared with group II (80.4 vs 69.0%, p < 0.01). CONCLUSION: In gallstone patients, combined therapy with urso- and chenodeoxycholic acid is superior to either ursodeoxycholic acid alone or biliary parameters in bile samples obtained by direct fine needle puncture of the gallbladder.

Solitary versus multiple gallstones: the importance of total biliary protein concentration and other factors.

BACKGROUND: Nucleating and antinucleating factors play an important role in the pathogenesis of cholesterol crystal nucleation. PATIENTS AND METHODS: In 88 gallstone patients (59 female, 29 male) bile was examined for total biliary protein and glycoprotein concentration, nucleation time and cholesterol saturation index. Gallstone density was measured by in vivo computed tomography. RESULTS: Total biliary protein concentration was positively correlated with the number of gallstones (r = 0.84, p < 0.01) and higher in radiologically detectable isodense gallstones as compared to non-isodense stones (p < 0.01). A negative correlation between total biliary protein concentration, glycoprotein concentration and nucleation time was observed (r = -0.45, p < 0.01 and r = -0.49, p < 0.05). Nucleation time was significantly shorter in the case of multiple versus solitary stones (2.6 +/- 1.3 versus 8.5 +/- 3.0 days, p < 0.01). Cholesterol saturation index and biliary cholesterol concentration were similar in both cases, however a negative correlation between cholesterol saturation index and stone density (r = -0.79, p < 0.01) was found. No correlation was found between cholesterol saturation index and nucleation time (r = -0.04, p > 0.1), independent of gallstone number. None of the examined parameters was related to sex, age, weight or gallbladder function. CONCLUSIONS: Multiple gallbladder stones seem to be associated with shorter nucleation time and higher biliary concentrations of total protein and glycoprotein than solitary stones.

Diagnostic value of fine-needle puncture of the gallbladder: side effects, safety, and prognostic value.

Bile sampling without the risk of contamination by pancreatic and duodenal secretions and avoiding unpredictable influences of general anesthesia during biliary surgery on biliary analytics are feasible with percutaneous puncture of the gallbladder. In 207 patients with gallstones, gallbladder puncture was performed under local anesthesia with a 22-gauge spinal needle under continuous real-time ultrasound guidance. Bile samples were investigated for biliary lipids and nucleation time. Complete aspiration of gallbladder bile could be achieved in all patients without complications such as bleeding, bile leak, or inflammation. Of these patients, 11.6% reported mild abdominal problems, 3.4% required analgetics, and in 1.0% biliary colics were observed. Elective cholecystectomy was performed in 1 patient. Of the bile samples, 10.1% were contaminated with bactobilia. Biliary lipids, cholesterol saturation index (CSI), total lipid concentration (TLC), and bacteriological contamination were independent of gallstone number, whereas patients with solitary gallbladder stones exhibited a significantly longer nucleation time (NT) in comparison with those with multiple stones. In patients with gallstones, fine-needle puncture of the gallbladder represents an important diagnostic procedure and can be performed within minutes without major side effects if performed by an experienced sonographer.

The relation between biliary lipids, nucleation time, and number of gallbladder stones after percutaneous gallbladder puncture.

BACKGROUND: Biliary lipids and nucleation time are increasingly of importance in the understanding of the cholesterol nucleation process in gallstone patients. METHODS: Biliary lipids, total lipid concentration (TLC), cholesterol saturation index (CSI) and nucleation time (NT) were studied in 221 bile samples from patients with solitary (n = 120) and multiple (n = 101) gallbladder stones. RESULTS: Biliary cholesterol concentration and CSI did not differ between patients with solitary or multiple stones; however, it was positively correlated with the CSI (r = 0.93; p < 0.01). We found a negative correlation between CSI and TLC (r = -0.77 for solitary stones and r = -0.79 for multiple stones; p < 0.01). Furthermore, levels of total bile acids and phospholipids were similar in cases with solitary and multiple gallbladder stones. TLC did not correlate with single or multiple stones, whereas NT was determined to be negatively correlated with the number of gallstones (r = -0.39; p < 0.01). Patients with solitary stones had a significantly (p < 0.01) longer NT than those with multiple gallbladder stones (7.5 +/- 4.2 days versus 2.3 +/- 1.5 days). CONCLUSIONS: Our findings suggest that there exists a nucleation-promoting activity, which seems to be more pronounced in patients with multiple gallbladder stones than in those with solitary stones, indicating a major risk factor for the higher recurrence rate seen in these patients.

The effect of ursodeoxycholic acid on nucleation time in patients with solitary or multiple gallbladder stones.

OBJECTIVE: The objective of this study was to determine the effect of ursodeoxycholic acid (UDCA), 1000 mg/day, on nucleation time and cholesterol saturation index (CSI) in human gallbladder bile. METHODS AND RESULTS: In 48 patients with cholesterol gallbladder stones undergoing extracorporeal shockwave lithotripsy, bile samples exhibited a significant longer median nucleation time in the case of solitary stones (7.9 +/- 5.1 days) than in patients with multiple stones (1.7 +/- 1.0 days; p < 0.0001). Stone number and nucleation time were correlated inversely (r = -0.79). UDCA led to a significant prolongation of nucleation time (solitary stones 17.9 +/- 5.8 days, multiple stones 18.0 +/- 5.7 days; p < 0.01) with a concomitant disappearance of cholesterol liquid crystals and cholesterol monohydrate crystals in gallbladder bile. Initially, there was no difference in the CSI between patients with solitary stones or multiple gallbladder stones (1.4 +/- 0.3 vs. 1.4 +/- 0.4, respectively). UDCA caused a significant decrease in CSI by 64.3% (p < 0.01). CONCLUSIONS: We conclude that UDCA prolongs the nucleation time by decreasing the cholesterol saturation index, as well as by diminishing cholesterol liquid crystals and cholesterol monohydrate crystals in gallbladder bile from patients with cholesterol gallstones. Second, recurrent stones essentially occur in patients with multiple cholesterol gallstones, reflected by a concomitant short nucleation time.

Gallbladder sludge: spontaneous course and incidence of complications in patients without stones.

Although the ultrasonic detection of gallbladder sludge is relatively frequent, its clinical importance remains unclear, partly because of the paucity of reliable investigations regarding its natural course in patients without stones. In a retrospective study we investigated the course and clinical significance of gallbladder sludge in patients without stones or other identified gallbladder abnormalities. The diagnosis of gallbladder sludge was made by ultrasound scan in 286 (1.7%) of 17,021 patients. The mean follow-up period for these patients was 20.3 +/- 11.5 mo. Of this group 56 patients were without both stones and sludge at the initial examination, and gallbladder sludge developed after a mean observation period of 11.2 +/- 10.6 mo. Within 2.0 +/- 3.5 mo after sludge detection, 40 (71.4%) patients were free of sludge and showed normal gallbladder findings. Gallbladder stones without sludge persistence developed in five patients (8.9%) within 2.5 +/- 0.6 mo after diagnosis of sludge, and gallstones with persistence of sludge developed in two other patients (3.6%) after 6.1 and 30.7 mo, respectively. In no cases did the stones become clinically symptomatic in the course of the follow-up period. Acute acalculous cholecystitis developed in four patients (7.1%) from 6.5 to 37.5 mo after the first examination. In five patients, sludge persisted after a mean 22.3 +/- 13.5 mo of follow-up. Although our data show that gallbladder sludge disappeared spontaneously within a relatively short time in 71.4% of patients, gallbladder sludge must be considered an important pathologic entity because gallbladder stones or complications such as acute cholecystitis occurred in 19.6% of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Does adequate patient selection reduce the risk of gallstone recurrence after successful extracorporeal shockwave lithotripsy?

To determine the risk of gallbladder stone recurrence in these patients, 58 of the first consecutive 61 patients with solitary stones achieving complete stone clearance after ESWL and adjuvant bile acid therapy were included in a prospective study. All patients were observed for at least 12 months following discontinuation of oral bile acids. Twenty-one patients fulfilled our postulated ideal criteria (solitary radiolucent stones between 10-20 mm initial diameter, initial stone density < 50 HU, gallbladder ejection fraction > 70%). The remaining patients (n = 37) fulfilled the criteria of the Munich study group. In patients fulfilling our ideal criteria, stone recurrence was not observed in any patient, while in those fulfilling solely the criteria of the Munich group, five instances of stone recurrence were observed (13.5% [n = 37], p < 0.1). Initial stone count is only one factor influencing the probability of gallstone recurrence following ESWL and discontinuation of oral bile acids. Our data suggest that factors such as low initial stone density at gallbladder CT and good gallbladder function not only accelerate initial stone clearance but also reduce the risk of stone recurrence after ESWL once oral bile acids have been discontinued.

Transhepatic topical dissolution of gallbladder stones with MTBE and EDTA. Results, side effects, and correlation with CT imaging.

Forty-two patients with symptomatic gallstones (28 women, 14 men, mean age 49.8 +/- 13.2 years) were recruited for contact dissolution therapy. Pretreatment CT scans of the gallbladder were obtained in every patient under standard conditions. For contact dissolution treatment of heterogeneous gallstones or gallstones with attenuation values of more than 50 Hounsfield units, methyl tert-butyl ether and bile acid ethylene diaminetetraacetic acid were used in alternating administration at time intervals and durations adapted to the individual tolerance of the patients. In the case of gallstones with mean attenuation values under 50 Hounsfield units, the dissolution therapy was performed with methyl tert-butyl ether alone. In 12 (28.6%) patients a complete dissolution of gallbladder stones could be achieved; 11 patients (26.2%) revealed gallbladder sludge but no radiologically or sonographically visualized residual stone debris. The remaining 19 (45.2%) patients had residual gallstone debris. Shell fragments in three of five rimmed gallstones, seven of eight laminated gallstones, and all densely calcified stones were refractory to contact dissolution therapy. Dissolution rates correlated well with mean attenuation values, whereas no significant correlation was found between stone number and dissolution rates or between stone diameter and dissolution rates respectively. The mean instillation time required for stones with a mean density of more than 50 HU was 17.7 +/- 11.5 hr of bile acid ethylene diaminetetraacetic acid and 5.8 +/- 3.2 hr of methyl tert-butyl ether. In the case of isodense stones, the average instillation time of methyl tert-butyl ether was 12.3 +/- 4.7 hr.(ABSTRACT TRUNCATED AT 250 WORDS)

[Extracorporeal shockwave therapy in endoscopic therapy-refractory gallstones]. / Extrakorporale Stosswellentherapie bei endoskopisch therapierefraktären Gallengangskonkrementen.

Extracorporeal shock-wave lithotripsy (ESWL) was undertaken in 36 patients (12 men, 24 women; mean age 70.9 +/- 2.4 years) with extra- or intrahepatic bile duct stones which could not be removed endoscopically. Stone fragmentation was successful in 32 patients with stones in the choledochal duct and in one with stones in the left hepatic duct. Fragmentation failed in two patients with stones in the left hepatic duct and one with stones in the cystic duct. 26 of the 36 patients were free of stone after spontaneous passage (n = 3) or after endoscopic removal of the residual concrements (n = 23). Complications occurred in only five patients during or after ESWL (cardiac arrhythmias, respiratory failure, pancreatitis, cholangitis).--These data point to ESWL being clearly preferable to surgical intervention in bile duct stones refractory to endoscopic treatment, especially in the elderly with an increased perioperative risk.

Structured reporting of medical findings: evaluation of a system in gastroenterology.

A system using structured reporting of findings was developed for the preparation of medical reports and for clinical documentation purposes in upper abdominal sonography, and evaluated in the course of routine use. The evaluation focussed on the following parameters: completeness and correctness of the entered data, the proportion of free text, the validity and objectivity of the documentation, user acceptance, and time required. The completeness in the case of two clinically relevant parameters could be compared with an already existing database containing freely dictated reports. The results confirmed the hypothesis that, for the description of results of a technical examination, structured data reporting is a viable alternative to free-text dictation. For the application evaluated, there is even evidence of the superiority of a structured approach. The system can be put to use in related areas of application.

Increased gallbladder residual volume in nonresponders to extracorporeal shock wave lithotripsy of gallbladder stones.

In a prospective study of 63 patients, we purposed to determine whether gallbladder contractility or gallbladder volume before biliary lithotripsy are predictors of fragment disappearance. Percentage gallbladder contraction was calculated from the fractional difference in the sonographically measured gallbladder volume after a standard fatty meal. Statistical analysis showed no significant differences in gallbladder contractility between the fragment-free group and the residual-fragment group before (77.2 +/- 12.7% vs. 71.9 +/- 19.3%; p = 0.1044) biliary lithotripsy and after the termination of adjuvant cholelitholysis therapy (76.4 +/- 12.9% vs. 72.2 +/- 17.1%; p = 0.1341). Before treatment, there was no significant difference in fasting gallbladder volume in either group (29.9 +/- 15.4 ml vs. 36.6 +/- 18.8; p = 0.0682), but postprandial gallbladder volume was greater in nonresponders (10.4 +/- 9.4 ml vs. 6.5 +/- 3.8; p = 0.0164). After termination of the therapy, both the fasting gallbladder volume (41.2 +/- 24.2 ml vs. 29.8 +/- 10.3 ml; p = 0.0093) and the postprandial gallbladder volume (11.9 +/- 11.7 ml vs. 7.3 +/- 5.3 ml; p = 0.0267) were greater in the residual-fragment group. The increase of the fasting gallbladder volume in the residual-fragment group was statistically not significant. Our results indicate that the increased residual volume is a significant cause of therapeutic failure in nonresponders.

[Extracorporeal shock wave lithotripsy in patients with bile duct calculi]. / Extrakorporale Stosswellenlithotripsie bei Patienten mit Gallengangsteinen.

21 patients with choledocholithiasis, in whom methods such as endoscopy or mechanical lithotripsy were unsuccessful, extracorporeal shock wave lithotripsy was performed. Fragmentation could be achieved in 90%, complete stone clearance after endoscopic stone extraction occurred in 76%. Extracorporeal shock wave lithotripsy has proven highly effective with a low complication rate and zero lethality. Therefore, its role in the management of gall stone disease in the elderly patient at high perioperative risk cannot be overemphasized.

The relationship between serum lipids, nucleation time, and biliary lipids in patients with gallstones.

The relationship between biliary lipids, cholesterol saturation index, nucleation time, and serum lipids was studied in a group of 45 gallstone patients (10 male, 35 female; age 50.1 +/- 14.5 years). Bile was obtained by direct fine-needle puncture of the gallbladder under local anesthesia and sonographic monitoring. No significant correlation between the serum lipids and either the cholesterol saturation index or total biliary cholesterol levels was observed. We found a positive correlation between the nucleation time and serum triglycerides content (r = 0.45, p = 0.0018) and a negative correlation between nucleation time and biliary cholesterol level (r = -0.38, p = 0.009). The fatty acids derived from the triglycerides are primarily resynthesized to phospholipids in the liver. When the supply of free fatty acids exhausts the metabolic capacity of the liver as, for example, in fat-rich diets, triglycerides accumulate in the liver cells and may possibly by excreted in the bile. Free fatty acids stimulate mucin hypersecretion in the gallbladder. This mucosal hypersecretion has been assigned a significant role in the formation of gallbladder stones. We also found a positive correlation between the total biliary bile acids and serum high density lipoprotein (HDL)-cholesterol in patients with a rapid nucleation time (r = 0.50, p = 0.0128). This supports the findings of other researchers, which suggests that HDL-cholesterol is devoted primarily to bile acid synthesis. In patients with a short nucleation time, the cholesterol saturation index, total lipid concentration, biliary cholesterol, mean age, and biliary bile acids were statistically different in comparison with patients with a prolonged nucleation time.