Transhepatic topical dissolution of gallbladder stones with MTBE and EDTA

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, methyltert-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 methyltert-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 methyltert-butyl ether. In the case of isodense stones, the average instillation time of methyltert-butyl ether was 12.3±4.7 hr. There was a statistically significant difference in methyltert-butyl ether instillation time between the both groups (P<0.001), but the total instillation time required for stones with a mean density of more than 50 HU was significantly longer (P<0.0001); consequently, in these patients the incidence of severe complications was higher without reaching statistical significance. Mild complications occurred in 95.2% of patients and severe complications were observed in 16.8% of cases. Posttreatment CT examinations after intravenous application of contrast media revealed gallbladder mural hyperemia followed by edematous swelling of the pericystic tissue layer in 96.3% of patients. Eight of eleven patients (72.7%) with gallbladder sludge revealed gallstone recurrence in the course of a 12-month observation period. In the successfully treated group, only one patient experienced gallstone recurrence (P=0.0066). In principle, the use of bile acid ethylene diaminetetraacetic acid dissolution medium made the dissolution of calcified or pigment stones possible, although the side effects are greater than with cholesterol stones. More effective and safer solvents for these more difficult to dissolve stones should be sought.     

Gallbladder stone recurrence after medical treatment do gallstones recur true to type?

Medical treatments that dissolve or remove gallbladder stones but leave the gallbladder in situ have the disadvantage of gallstone recurrence. Little is known about the composition of recurrent stones or whether they recur true to type. In 21 patients with recurrent stones detected 5–74 months (mean ±sem, 26±4 months) after being rendered stone-free with dissolution therapy (N=15) or percutaneous cholecystolithotomy (N=6), we compared pretreatment and postrecurrence gallstone number, maximum gallstone attenuation scores measured by computed tomography (CT) and, in 13, the dissolvability of the recurrent stones with oral bile acids ± extracorporeal shock-wave lithotripsy. Before treatment, five patients had solitary and 16 had multiple stones but on recurrence, the gallstones differed in number from the primary stones in 10 of the 21 patients. As a result of patient selection, before dissolution, the primary stones were all radiolucent with maximum CT scores of <100 Hounsfield units (HU) (mean 45, range 10–84 HU). On recurrence, the stones were again CT-lucent in 13 of the 15 patients but were CT-dense in the remaining two (118 and 176 HU). Initially, all six patients treated by percutaneous cholecystolithotomy had radio-opaque stones, with a mean CT score of 459 (range 100–969) HU. However, on recurrence, only one had calcified stones (HU 140); the remaining five had CT-lucent stones (16–98 HU,P<0.05). Of the 13 patients whose recurrent, plain x-ray-lucent and CT-lucent stones were treated with oral bile acids ± lithotripsy, 12 (92%) showed evidence of gallstone dissolution. We conclude that gallbladder stones do not recur true to type in up to two thirds of patients. However, irrespective of original gallstone composition, recurrent stones are usually radio- and CT-lucent, presumed cholesterol-rich, and therefore potentially dissolvable with oral bile acids.     

Methyltert-butyl ether in the endoscopic treatment of common bile duct radiolucent stones in elderly patients with nasobiliary tube

Methyltert-butyl ether is an effective dissolution agent for cholesterol stones. The aim of this work was to evaluate the effect of methyltert-butyl ether on radiolucent common bile duct stones in patients in whom endoscopic extraction has failed. From September 1985 to September 1987, 1374 patients underwent endoscopic retrograde cholangiopancreatography in our Liver Unit. An endoscopic sphincterotomy was indicated in 195 patients with common bile duct (CBD) stones because of an age over 65 years and/or surgical contraindications. Endoscopic sphincterotomy was efficient in 187 patients, allowing complete stone removal in association with conventional endoscopic methods and mechanical lithotripsy in 170 patients. Twelve of the 17 patients with failure of conventional endoscopic treatments were either older than 75 years (11 patients; mean age, 86±4.5 years) or exhibited a surgical contraindication. Stones completely obstructed CBD in six patients and had a diameter exceeding 25 mm in the six other patients. These subjects were selected for stone dissolution by methyltert-butyl either (MTBE) according to the following protocol. MTBE was directly infused into CBD through a nasobiliary catheter, twice daily for 4–13 days (mean, seven days). Bile duct opacification, repeated after MTBE treatment, revealed the complete disappearance of CBD stones in one patient, a decrease in stone size in five patients and no change in the six tther patients. MTBE treatment was well tolerated except in three patients who complained from transient abdominal pains and nausea. At the second attempt of endoscopic treatment, CBD stones were found to be softened and easily broken up, allowing a complete clearance in six patients. MTBE treatment failed to improve stone extraction in the five other patients. These results show that, in patients with large radiolucent stones in the CBD, unextractable by conventional endoscopic methods, the direct infusion of MTBE in CBD rarely led to a complete stone dissolution; however, this treatment partially solubilizes stones, enabling their complete endoscopic extraction thereafter in half the patients.A preliminary report of this work was presented at the American Gastroenterological Association, Digestive Disease Week, 1988, New Orleans.     

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.     

Manual and automatic gallstone dissolution with methyltert-butyl ether

The aim of the study was to establish the efficiency of cholesterol gallstone dissolution with methyltert-butyl ether in a large group of patients and to compare the results of patients treated manually by a nurse or using an automatic pump. Gallbladder puncture was successful in 228 patients (99%). After 9 hr, 211 patients (91%) were stone-free; 144 (68%) of them left the hospital on the fourth day. In radiolucent stones not isodense with bile on a CT scan, dissolution rate decreased by 10%, treatment time was prolonged by 40%. Forty-two of the 228 patients were selected for the hand-syringed group, 42 patients, who matched these patients in stone size and number, were treated with an automatic pump (Baxter). Stone burden in matched pairs was comparable. Stones dissolved in 96% of the patients in both groups. Sludge remained in the gallbladder in 52% after manual treatment and 60% after automatic therapy. Side effects were identical in both groups. None of the side effects were pump-related. Automatic therapy reduced the time needed by the nurse to treat each patient by 70%.     

Management of recurrent gallstones

The risk of gallstone recurrence following non-surgical treatment has been overestimated in the past for two reasons: (1) diagnosis of primary gallstone dissolution was based on oral cholecystography; and (2) gallstone recurrence was expressed as a cumulative recurrence rate. Results based on better methodologies for diagnosis of gallstones (ultrasonography) and for calculation of results (life-table analysis) have indicated that gallstones recur in about 50% of patients, and that the risk of recurrence is confined mainly to the first 5 years after dissolution.Pretreatment gallstone characteristics, but not patient characteristics, are important risk factors for gallstone recurrence. Multiple stones are more likely to recur than solitary stones, a phenomenon attributable to the presence of a potent pronucleating factor in the bile of patients with multiple stones. This observation, and the finding that NSAID administration may reduce gallstone recurrence via inhibition of mucin secretion, suggests that the nucleation defect might be a key factor in the pathogenesis of recurrent gallstones.Prophylaxis with low-dose CDCA or UDCA has proven ineffective for preventing gallstone recurrence, although it may reduce it. Since the majority of recurrent gallstones are small when first seen because of regular ultrasonographic follow-up, multiple, radiolucent and in functioning gallbladders, they are amenable to bile acid retreatment, and intermittent bile acid therapy is probably a viable strategy for long-term management of cholesterol cholelithiasis.     

Symptomatic versus silent gallstones

It is unknown whether demography, gallbladder function, or the radiographic appearance of gallstones predispose them to cause symptoms. We investigated these features in a consecutive series of 260 patients with newly diagnosed, uncomplicated gallstone disease, of whom 146 had experienced biliary pain and 114 were asymptomatic. All patients underwent double-dose oral cholecystography and cholecystosonography, and the combined data of these examinations were used to assess gallbladder function and stone number, size, and radiopacity. The gallstones were multiple in 68%, radiolucent in 73%, and in visualized gallbladders in 79% of the 260 patients. The comparison of different variables in patients with and without biliary pain showed that the female gender (P=0.030; odds ratio 1.86), a family history of gallbladder disease (P=0.022; odds ratio 1.89), a nonvisualized gallbladder (P<0.001; odds ratio 3.14), multiple stones (P=0.036; odds ratio 1.89), and those which were small (P=0.009; odds ratio 2.08) or of dissimilar size (P=0.041; odds ratio 1.91) were associated with biliary pain. Women with silent stones had been pregnant more often (P<0.001, difference between means 1) than those with biliary pain. Gallbladder function and the radiologic characteristics of stones were unrelated to age and gender. Estimates of eligibility for nonsurgical therapies among the 146 symptomatic patients were 44% for bile acid therapy, 16% for lithotripsy, and 56% for methyltert-butyl ether. In conclusion, some inherent features of gallstones are associated with biliary pain. Whether they have predictive value of future symptom development in subjects with silent stones can be determined by prospective follow up.     

Gallstone recurrence after successful percutaneous cholecystolithotomy:a 10-year follow-up of 439 cases

BACKGROUND: Stone recurrence is a major problem in the medication of gallstones with gallbladder preservation. The aim of this study was to determine the long-term recurrence rate of gallstones and the clinical outcome after successful percutaneous cholecystolithotomy (PCCL) treatment, and to investigate the possible risk factors for gallstone recurrence. METHODS: After successful PCCL for gallstones, 439 patients were followed up during a 10-year period. The long-term gallstone recurrence rate and clinical outcome were evaluated. Risk factors associated with stone recurrence were identified. RESULTS: Gallstone recurrence was detected in 182 of 439 PCCL patients, giving an overall recurrence rate of 41.46%. The cumulative gallstone recurrence rate for each of the 10 post-operative years was 9.57%, 18.91%, 27.33%, 34.14%, 37.59%, 39.86%, 41.90%, 42.73%, 42.85%, and 43.21%, respectively. Among these recurrent patients, 94 were asymptomatic, 80 suffered from nonspecific upper gastrointestinal symptoms and 8 suffered from abdominal pain or biliary colic. Thirty-eight of the 182 patients were retreated with cholecystectomy. The risk factors for stone recurrence included a family history of gallstones, preference for fatty food, accompanying liver disease, multiple stones and poor gallbladder function pre-PCCL. CONCLUSIONS: In this study, the overall recurrence rate of gallstone was 41.46% during a 10-year period. The highest frequency of gallstone recurrence was during the 5th to 6th postoperative years and then continued to slowly increase. Risk factors for stone recurrence varied.We suggest that the use of PCCL in patients with gallstones should be considered carefully because of stone recurrence.     

Medical dissolution of gallstones

Retained gallstones in the bile ducts account for 60–70% of all the cases of postchole-cystectomy syndromes. A solventd-limonene preparation was injected directly to the biliary system of 200 patients to dissolve or disintegrate the retained gallstones. The outcomes were: retained stones completely disappeared in 96 cases (48%); partial dissolution in 29 (14.5%); chelating agent was also used with partial dissolution in 16 (8%); ineffective in 59 (24.5%). To make this method more effective, several guidelines should be observed including anin vitro trial dissolution test. Cautious observation for possible side effects and frequent hepatic and pancreatic function tests during the treatment with this preparation also should be performed.     

Effect of laser fragmentation of cholesterol and mixed gallstones onin vitro dissolution in methyltert-butyl ether

This study examined cholesterol and mixed gallstone dissolution in vitroby methyltert-butyl ether (MTBE) after gallstone fragmentation. Three morphologically identical gallstones were obtained from 42 patients. One stone from each patient was fragmented with laser energy at a wavelength of 504 nm delivered to the stone surface with a 320-m quartz fiber. Intact and fragmented stones from the same patient were incubated without stirring in MTBE and dissolution was expressed as the percent of initial stone weight remaining after 2 hr. Stone composition did not correlate with the amount of laser energy required for stone fragmentation. Fragmented stones dissolved faster than intact stones in MTBE with 13.97%±0.37% vs 31.0%±0.51% respectively (mean±SEM) of initial stone weight remaining at 2 hr (P<0.0001). Initial stone weight and stone matrix content significantly predicted dissolution of intact (P=0.0033 and P=0.0483, respectively) and fragmented stones (P=0.003 and P=0.0001, respectively) in MTBE. These data suggest that the gallstone matrix may inhibit stone dissolution even after stone fragmentation.Dr. Smith was supported by NIH grant DK39107.A portion of this work appeared in abstract form in Gastroenterology 94:A577, 1988, and was presented at the annual meeting of the American Gastroenterological Association in New Orleans, May 1988.     

Combined treatment of symptomatic gallbladder stones by extracorporeal shock-wave lithotripsy (ESWL) and instillation of methyl,Tert-butyl ether (MTBE)

Twenty-four patients with symptomatic gallbladder stones (12 radiolucent and 12 calcified) were treated by a combined approach of extracorporeal shock-wave lithotripsy (ESWL) and subsequent instillation of methyltert-butyl ether (MTBE). The patients received a mean of 1500±185 shock-wave discharges. The mean instillation time of MTBE was 13±4.2 hr. Treatment was tolerated without major adverse effects. Within a time period of three to five days eight of 12 patients with pure radiolucent stones and four of 12 with calcified stones became stone-free. After a median follow-up of five months (range: one week to 26 months), a total of 11 patients (92%) with radiolucent stones and of eight patients (66%) of those with calcified stones were free of stones, fragments, or debris. These clearence rates appear high when compared with reports on monotherapy with ESWL or MTBE, suggesting a positive effect of a combined approach in selected patients. Two patients exhibited recurrent stones after six and seven months respectively.Supported partly by a grant from the Koerber Foundation.     

Risk factors for the development of gallstone recurrence following medical dissolution. The British-Italian Gallstone Study Group

OBJECTIVE: To assess risk factors for gallstone recurrence following non-surgical treatment. DESIGN: A prospective follow-up of a multicentre cohort of post-dissolution gallstone patients. SETTING: Six gastroenterology units in the UK and Italy. PARTICIPANTS: One hundred and sixty-three patients with confirmed gallstone dissolution following non-surgical therapy (bile acids or lithotripsy plus bile acids), followed up by ultrasound scan and clinical assessment at 6-monthly intervals for up to 6 years (median, 25 months; range, 6-70 months). OUTCOME MEASURES: Subject-related variables (sex, age, height, weight, body mass index), gallstone-related variables (number, diameter, presence of symptoms, months to complete stone clearance), treatment modalities (bile acid therapy, extracorporeal shock wave lithotripsy) and follow-up related variables (weight change, use of non-steroidal anti-inflammatory agents, statins, pregnancies and/or use of oestrogens) were assessed by univariate and multivariate analysis as putative risk factors for gallstone recurrence. RESULTS: Forty-five gallstone recurrences were observed during the follow-up period. Multiple primary gallstones and length of time to achieve gallstone dissolution were the only variables associated with a significant increase in the recurrence rate. Appearance of biliary sludge during follow-up was also significantly related to development of gallstone recurrence. Use of statins or non-steroidal anti-inflammatory agents did not confer protection against recurrence. CONCLUSIONS: Patients with primary single stones are the best candidates for non-surgical treatment of gallstones, because of a low risk of gallstone recurrence. The positive association of recurrence with biliary sludge formation and time to dissolution of primary stones may provide indirect confirmation for the role of impaired gallbladder motility in the pathogenesis of this condition.     

Gallstone dissolution with methyltert-butyl ether in 120 patients—Efficacy and safety

Of 612 patients with cholesterol gallbladder stones, 120 were eligible for percutaneous transhepatic litholysis with methyltert-butyl ether (MTBE). Puncture of the gallbladder was successful in 117/120 (97.5%). In 113/117 (96.6%) the stones dissolved. With solitary stones, treatment lasted for an average of 4 hr, with multiple stones 10 hr. Mean hospitalization was 3.6 days. In 3/117 (2.6%) patients a bile leakage developed; 33% reported mild complaints. After the end of treatment 34% had some residue in the gallbladder; two of these patients developed recurrent stones. MTBE is exhaled, is distributed in fatty tissue, and is excreted renally together with its metabolitetert-butanol. Methanol was found only in traces. Gallbladder histology of six patients showed chronic cholecystitis. Since these findings were independent of treatment time and the interval between treatment end and operation, they are most consistent with stone-related changes rather than caused by MTBE.     

In vitro dissolution of cholesterol gallstones. A study of factors influencing rate and a comparison of solvents

Models of the common bile duct and gallbladder were constructed to study conditions that affect the rate of cholesterol gallstone dissolution by monooctanoin and other potential solvents. In the bile duct model, the rate of monooctanoin infusion was not an important factor in accelerating dissolution time. In contrast, the exclusion of bile from interfering with solvent-stone contact or the enhancement of solvent-stone contact by stirring significantly accelerated stone dissolution. The combination of both bile exclusion and stirring increased the dissolution rate of gallstones by monooctanoin 15-fold. When compared with two other ethers and with monooctanoin, methyl tert-butyl ether was found to be the most potent gallstone solvent. Methyl tert-butyl ether completely dissolved 219-mg cholesterol stones within 60 min. In the gallbladder model, in the absence of stirring both methyl tert-butyl ether and monooctanoin floated on bile, whereas the gallstones sank resulting in minimal stone-solvent contact. To increase the stone-solvent contact, we used a pump to create sufficient turbulence to mix the solvent with bile. Pump stirring of monooctanoin in the presence of bile achieved rates of stone dissolution approaching that of stirred monooctanoin without bile. Stirring of methyl tert-butyl ether and bile, however, did not achieve sufficient solvent-stone contact to appreciably accelerate dissolution in the presence of 50% bile. Stone-solvent contact was a critical factor in determining the rate of gallstone dissolution in both gallbladder and common bile duct models. Efforts to enhance contact include bile exclusion and intraluminal stirring--both of which are clinically applicable. Methyl tert-butyl ether is a potent new cholesterol gallstone solvent with excellent potential for use in humans. Even with this potent agent, however, rapid gallstone dissolution is likely to require removal of most of the bile from the dissolution medium.     

Low early gallstone recurrence rate after successful extracorporeal lithotripsy in patients with solitary stones.

Piezoelectric lithotripsy with the EDAP LT-01 machine combined with adjuvant bile acid therapy results in complete clearance of radiolucent gallstones in selected patients. We assessed stone recurrence rate in 84 patients with complete clearance of stone fragments and followed up at least 12 months after cessation of bile acid therapy (mean 17 months, range 12-33). Fifty-four patients had a solitary stone and 30 multiple stones. Bile acid therapy was continued for 3 months after complete fragment stones clearance which was ascertained by two consecutive ultrasound examinations. Stone recurrence was assessed by ultrasonography at 6 and 12 months, and then at least once a year. Gallstone recurrence occurred in 5 patients (6%) between 9 and 12 months with no further recurrence up to 33 months. The rate of recurrence at one year was 3.7% in patients with a solitary stone and 10% in patients with multiple stones. Only one patient with stone recurrence had recurrent biliary pain. We concluded that early gallstone recurrence rate after successful lithotripsy seems to be low in patients with solitary stones.     

Utility of biliary microscopy for the prediction of the chemical composition of gallstones and the outcome of dissolution therapy with ursodeoxycholic acid

To learn whether microcrystalline solids in bile could predict gallstone composition, the findings determined by polarizing microscopy of gallbladder bile were related to stone type at cholecystectomy in 53 patients. Cholesterol crystals were present in 36 of 39 cholesterol stone bile and absent in 12 of 14 bile from non-cholesterol stones. Fifteen cholesterol stones (eight radiopaque) contained calcium carbonate, and characteristic vaterite microspheroliths were observed in 53% of their bile. In another study, crystals in basal duodenal bile were related to the outcome of gallstone dissolution treatment with ursodeoxycholic acid, 10 mg/kg X day. In 39 patients treated for 1 yr, efficacy (complete gallstone dissolution) was 41% overall and 52% in patients with stones less than or equal to 10 mm in diameter. In connection with the findings of biliary microscopy, efficacy was 93% in 14 patients with cholesterol crystals in bile, and 27% in 11 patients with microspheroliths in bile. Cholecystectomies in 9 patients with dissolution failure revealed 4 cases of non-cholesterol stones and 5 cases (including 3 with on-therapy calcification) of calcium carbonate-rich cholesterol stones with a surface/interior mineral ratio greater than 3. The results confirm that cholesterol crystals in bile are a sensitive measure of cholesterol gallstones. They also show that vaterite microspheroliths in bile indicate the presence of calcium carbonate in gallstones. Both findings suggest that biliary crystals reflect gallstone composition, and it is demonstrated that this information is useful in predicting the success or failure of cholelitholysis with ursodeoxycholic acid. Finally, the data show that radiologically undetectable stone calcification reduces the probability of dissolution, and that the calcified structures appearing in some stones during treatment are composed of calcium carbonate.     

The Relation between Biliary Lipids,Nucleation Time,and Number of Gallbladder Stones after Percutaneous Gallbladder Puncture

Tudyka J, Kratzer W, Maier C, Mason R, Wechsler JG. The relation between biliary lipids, nucleation time, and number of gallbladder stones after percutaneous gallbladder puncture. Scand J Gastroenterol 1994;29:844-848.

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 equals; 120) and multiple (n equals; 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 equals; 0.93; p < 0.01). We found a negative correlation between CSI and TLC (r equals; ? 0.77 for solitary stones and r equals; ? 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.     

Recurrent Gallstone Formation after Successful Extracorporeal Shock-Wave Lithotripsy

Gallstone recurrence was evaluated in 184 patients exhibiting complete stone disappearance after successful extracorporeal shock-wave lithotripsy (ESWL) and concomitant oral bile acid therapy. Follow-up examinations conducted 6–43 months after termination of adjuvant bile acid therapy revealed recurrent calculi in 40/184 (21.7%) patients (27 females, 13 males, p < 0.01; 13 patients with solitary, 27 patients with multiple stones) after a median stone-free period of 11 months (range 1–33 months; mean ± SD, 13 ± 8 months). Therefore, an overall probability of stone recurrence of 11.8% was observed 12 months after complete stone disappearance had been confirmed sonographically and bile salt therapy terminated, and a probability of 25.5% after 24 months. Gallstone reformation occurred in 30/146 (20.5%) patients with initially solitary and 10/38 (26.3%) patients with multiple calculi [not significant (NS)]. Only 3/40 (8%) patients with recurrent calculi reported biliary colic. Sonographic gallbladder contractility values acquired at the time recurrent stones were detected did not show any significant differences, compared with the data obtained in the pretreatment examinations; neither were any differences noted between the patients with gallstone reformation and those who remained stone-free. In 20/33 (61%) patients with recurrent stones who opted for further conservative re-treatment (ESWL and/or oral litholysis), complete stone disappearance was achieved a second time. The recurrence rates achieved within the first 3 yr after successful shock-wave lithotripsy of biliary calculi cover a range similar to the rates noted after dissolution therapy.     

Unconjugated bilirubin in hepatic bile with brown pigment gallstones and cholangitis

To investigate the role of cholangitis in hydrolysis of bilirubin in bile with brown pigment gallstones, bilirubin composition and bacterial growth in hepatic bile with and without cholangitis were studied. The study included 38 brown pigment gallstone cases (28 without cholangitis and 10 with cholangitis). The proportion of unconjugated bilirubin in hepatic bile with cholangitis (16.9±8.5%, mean ± SD) was significantly higher than that without cholangitis (3.7±1.8%, P<0.001. A positive correlation was found between bacterial population with -glucuronidase activity and the proportion of unconjugated bilirubin in bile in cases of brown pigment stones with cholangitis P<0.05) but not in those without cholangitis despite the fact that bacterial species and population are similar regardless of the presence of cholangitis. In cholangitis, pH of bile becomes lower toward the optimal pH of bacterial -glucuronidase. Together the lower concentration of bile acid and the lower pH in bile result in lower solubility of unconjugated bilirubin, promoting its precipitation. Thus occasional bouts of cholangitis may result in periodic deposition of bilirubinate on brown pigment stones with layered structures by inducing cyclic changes of bile composition in situ.     

Sphincter of Oddi Dysfunction After Successful Gallstone Lithotripsy (Postlithotripsy Syndrome) Manometric Data and Results of Endoscopic Sphincterotomy

After successful gallstone lithotripsy, biliarypain recurs in about one third of patients. However,gallstone recurrence can be shown in only 40-60% ofthese patients. Therefore, other causes, such as sphincter of Oddi dysfunction (SOD), may besuspected. Twenty-two consecutive patients withrecurrent biliary pain after successful gallstonelithotripsy without evidence of gallstone recurrence atultrasonography were enrolled. Liver tests were elevated in 13patients and ERC showed a dilated bile duct in nine. All22 patients underwent sphincter of Oddi (SO) manometry,bile sample analysis for microlithiasis, endoscopic sphincterotomy (ES), and bile duct explorationwith a Dormia basket. Thereafter, the patients wereclinically followed at bimonthly intervals. SO manometryrevealed SOD in 15/22 patients. This was more often the case in patients with initiallylarger (>2 cm) or multiple stones than afterlithotripsy for solitary small stones (P < 0.01).Microlithiasis was detected in one patient, anotherpatient had small biliary calculi at bile ductexploration (both without SOD). After ES, 14/15 patientswith biliary SOD but none of the five without SODimproved (median follow-up: two years; P < 0.01). The one patient with CBD stones became symptom-freeafter ES, while the patient with microlithiasis improvedafter additional cholecystectomy only. Overall, ESproved to be the adequate therapy in 15/22 patients (68%, median follow-up: 22 months). Aftergallstone lithotripsy, SOD is found in about two thirdsof patients with recurrent symptoms but withoutgallstone recurrence. In this group CBD stones ormicrolithiasis are rare. Therefore, SOD has to be suspected inthis situation and ES gives favorable results, even whenperformed on a clinical basis only (without SOmanometry).