Cholesterol Gallbladder Stones Research Articles

Investigating the potential mechanism and therapeutic effects of SLXG for cholesterol gallstone treatment

BackgroundShugan Lidan Xiaoshi Granules (SLXG) is a traditional Chinese medicine (TCM) formulation frequently employed to prevent and treat cholesterol gallstones. SLXG is formulated based on the Chaihu Shugan Formula found in an ancient Chinese medical book, a traditional remedy in China for centuries, and has demonstrated successful treatment of numerous patients with gallbladder stones. PurposeThis research sought to clarify the therapeutic impact and molecular mechanisms of SLXG and its active components in the treatment of cholesterol gallbladder stones. MethodsThe study employed network pharmacology, UPLC-HRMS transcriptome sequencing, animal model experiments, molecular docking, and Surface Plasmon Resonance (SPR) to explore the molecular mechanisms of SLXG and its relationship with Traditional Chinese Medicines (TCMs) and potential targets. Furthermore, PPI network analysis, along with GO and KEGG enrichment analyses, were performed to explore the potential mechanisms through which SLXG and its active ingredient, naringenin, prevent and treat cholesterol gallstones. The mechanism of action was further elucidated using an animal model for gallbladder stone formation. ResultsThe study employed a network pharmacology and UPLC-HRMS to investigate the active compounds of SLXG for the treatment of cholesterol gallbladder stones, and subsequently constructed a network of therapeutic targets of SLXG. The results from gene enrichment analyses indicated that SLXG targets the metabolic pathway of bile secretion and the cholesterol metabolism pathway in addressing cholesterol gallbladder stones. The molecular docking results confirmed the interaction between the genes enriched in the pathways and the active ingredients in SLXG. Transcriptome sequencing results demonstrated that SLXG exerts its therapeutic effect on gallstones by regulating cholesterol and bile acid synthesis and metabolism. Furthermore, animal model experiments and SPR provided evidence that SLXG and its active ingredient, naringenin, exert therapeutic effects on cholesterol gallbladder stones by targeting the genes HMGCR, SOAT2, and UGT1A1, and influencing substances associated with cholesterol synthesis and metabolism. ConclusionsUsing systematic network pharmacology methods combined with in vivo validation experiments, we uncovered the fundamental pharmacological effects and potential mechanisms of SLXG and its active ingredient, naringenin, in the treatment of cholesterol gallstones. This research underscores the valuable role that traditional remedies can play in addressing medical challenges and suggests a promising direction for further exploration of natural treatments for the disease.

Fast Morphological Gallbladder Changes Triggered by a Hypercholesterolemic Diet

Introduction and aim. Obesity is a worldwide epidemic problem, described as a risk factor for hepatic diseases, such as non-alcoholic fatty liver disease and other pathologies related to development of cholesterol crystals and cholesterol gallbladder stones. It has been reported that cholesterol overload may cause hepatic damage; however, little is known about the effects of an acute hypercholesterolemic diet on the gallbladder. The aim of this manuscript was to evaluate the impact of a cholesterol-rich diet on the gallbladder.Material and methods. The study included ten eight-week-old C57BL6 male mice, which were divided into two study groups and fed different diets for 48 h: a hypercholesterolemic diet and a balanced Chow diet. After 48 h, the mice were analyzed by US with a Siemens Acuson Antares equipment. Mice were subsequently sacrificed to carry out a cholesterol analysis with a Refloton System (Roche), a crystal analysis with a Carl Zeiss microscope with polarized light, and a histological analysis with Hematoxylin-eosin staining.Results. The hypercholesterolemic diet induced an increase in gallbladder size and total cholesterol content in the bile, along with important histological changes.Conclusion. Cholesterol overloads not only trigger hepatic damage, but also affect the gallbladder significantly.

Solubility and solubilizing capabilities of aqueous solutions of Extractum Taraxaci e radix cum herba aqu. siccum in light of selected values of general Hildebrand-Scatchard-Fedors theory of solubility

Summary Introduction: The general Hildebrand-Scatchard theory of solubility supplemented by Fedors’ solubility parameter − δ 1 2 $- \delta ^{{1 \over 2}} $ was used to estimate the real solubility by −log x2 (log of the mole fraction) of phytochemicals contained in Ext. Taraxaci e radix cum herba aqu. siccum. Surface activity of aqueous solution of extracts was determined and quantified – solubilizing capabilities of solutions of cexp. ≥cmc in relation to cholesterol particle size of Ø=1.00 mm, as well as of ketoprofen were defined. Objective: The calculated value −log x2 collated with the polarity of extraction medium εM allows to estimate the optimal solubility of phytochemicals that determine the viscosity of the aqueous extract of dandelion and above all its surface activity and the ability to solubilize lipophilic therapeutic agents (ketoprofen). Methods: Viscosity of water model solutions of dandelion extracts and exhibition solutions after the effective micellar solubilization of cholesterol and ketoprofen was measured using Ubbelohde viscometer in accordance with the Polish Standard. The surface tension of aqueous solutions of extract and exhibition solutions after solubilization of cholesterol and ketoprofen was measured according to the Polish Standard with stalagmometric method. Results: The calculated factual solubility, and mainly the determined and calculated hydrodynamic size mean, that despite the complex structure of the micelle, it solubilizes cholesterol (granulometric grain of diameter Ø=1.00 mm) and ketoprofen (state of technological fragmentation) in equilibrium conditions. Equilibrium solubilization of ketoprofen also occurs in an environment of model gastric juice (0.1 mol HCl). Conclusions: The obtained results indicate that after the administration (and/or dietary supplementation) with Ext. Taraxaci e radix cum herba aqu. siccum, the physiological parameters of gastric juice would not be measured and its presence (phytosurfactant) in the body of the duodenum (bile A) increases abilities of solubilizing lipophilic therapeutic agents and cholesterol accounting for its use in the treatment of liver diseases and cholesterol gall bladder stones.

The flying classroom

Salmonella enterica serovar Typhi can colonize the gallbladder and persist in an asymptomatic carrier state that is frequently associated with the presence of gallstones. We have shown that salmonellae form bile-mediated biofilms on human gallstones and cholesterol-coated surfaces in vitro. Here, we test the hypothesis that biofilms on cholesterol gallbladder stones facilitate typhoid carriage in mice and men. Naturally resistant (Nramp1+/+) mice fed a lithogenic diet developed cholesterol gallstones that supported biofilm formation during persistent serovar Typhimurium infection and, as a result, demonstrated enhanced fecal shedding and enhanced colonization of gallbladder tissue and bile. In typhoid endemic Mexico City, 5% of enrolled cholelithiasis patients carried serovar Typhi, and bacterial biofilms could be visualized on gallstones from these carriers whereas significant biofilms were not detected on gallstones from Escherichia coli infected gallbladders. These findings offer direct evidence that gallstone biofilms occur in humans and mice, which facilitate gallbladder colonization and shedding.

Low phospholipid-associated cholestasis and cholelithiasis

Low phospholipid-associated cholestasis and cholelithiasis (LPAC) is a genetic disorder characterized by cholesterol gallbladder and intrahepatic stones. It is caused by a mutation of the gene ABCB4, which encodes the canalicular protein ABCB4/MDR3, a flippase that plays an essential role in the secretion of phosphatidylcholine into bile. Failure of this protein leads to secretion of bile that is poor in phospholipids and, hence, highly lithogenic, with potent detergent properties. This, in turn, leads to cholangiocyte luminal membrane injury and biliary lesions causing cholestasis. The diagnosis should be suspected when at least two of the following criteria are present: onset of symptoms before the age of 40 years; recurrence of biliary symptoms (biliary colic, jaundice, cholangitis, acute pancreatitis) after cholecystectomy; presence of echogenic foci within the liver indicative of intrahepatic stones or biliary sludge; previous episode(s) of intrahepatic cholestasis of pregnancy; and family history of gallstones in first-degree relatives. Intrahepatic stones can be demonstrated by ultrasonography with color Doppler examination, computed tomography and magnetic resonance imaging with magnetic resonance cholangiography, and the diagnosis confirmed by ABCB4 genotyping. Therapy with ursodeoxycholic acid offers prompt relief of symptoms and usually prevents complications. In some cases, however, surgery may be necessary.

Gallstones play a significant role inSalmonellaspp. gallbladder colonization and carriage

Salmonella enterica serovar Typhi can colonize the gallbladder and persist in an asymptomatic carrier state that is frequently associated with the presence of gallstones. We have shown that salmonellae form bile-mediated biofilms on human gallstones and cholesterol-coated surfaces in vitro. Here, we test the hypothesis that biofilms on cholesterol gallbladder stones facilitate typhoid carriage in mice and men. Naturally resistant (Nramp1(+/+)) mice fed a lithogenic diet developed cholesterol gallstones that supported biofilm formation during persistent serovar Typhimurium infection and, as a result, demonstrated enhanced fecal shedding and enhanced colonization of gallbladder tissue and bile. In typhoid endemic Mexico City, 5% of enrolled cholelithiasis patients carried serovar Typhi, and bacterial biofilms could be visualized on gallstones from these carriers whereas significant biofilms were not detected on gallstones from Escherichia coli infected gallbladders. These findings offer direct evidence that gallstone biofilms occur in humans and mice, which facilitate gallbladder colonization and shedding.

Expression of ABC gene in liver of patients with cholesterol gallbladder stones

胆囊结石多为胆固醇性或以胆固醇为主的混合性结石,胆汁胆固醇过饱和是胆囊结石发生的必要条件,胆固醇过饱和与胆汁胆固醇含量升高及胆盐与磷脂的下降有密切关系.肝细胞胆小管侧膜上有一些转运蛋白,这些蛋白都属ATP结合盒家族。

Detection of bacterial DNA in cholesterol gall stones

Introduction: Recently, bacterial infection has been shown to play an important role in the formation of cholesterol gallbladder stones. This led us to investigate the presence of bacterial structures in cholesterol gallstones by means of bacterial culture and DNA detection. Method: Gallstones were obtained from 31 consecutive patients operated from May 2005 to October 2006 in the department. Culture study was done using standard bacteriological methods. Cholesterol was estimated by spectrophotometry and stones were divided into cholesterol stones (>70% cholesterol) and mixed/pigment stones (<70% cholesterol). DNA for organisms was extracted from the core of the stone and confirmed by agarose gel electrophoresis. Sterile stones were subjected to PCR amplification. Results: Age of patients ranged from 27 to 66 years (mean = 46.58 years); 14/31 stones were pure cholesterol stones (45%), and 17 (55%) were mixed and pigment stones. On culture, 12 stones (39%) were sterile, while 19 (61%) showed presence of viable bacteria; amongst cholesterol stones, 11 out of 14 were sterile (79%), while only 1 (6%) out of 17 pigment and mixed stone was sterile. E.coli was the most common bacterium isolated (42%) followed by Pseudomonas and Salmonella. DNA extraction was positive in all 31 of the stone samples collected (100%). PCR amplification was positive in all the bacteriologically sterile stones. Discussion: All gallstones, including cholesterol stones, revealed bacterial DNA; suggesting that bacterial infection is associated even with cholesterol gallstones.

Mechanism for the transit-induced increase in colonic deoxycholic acid formation in cholesterol cholelithiasis

Background & Aims: Many patients with cholesterol gallbladder stones (GBS) have a high percentage of deoxycholic acid (DCA) in gallbladder bile (all of which are in the conjugated form), probably as a result of prolonged large bowel transit times (LBTT). However, whether the prolonged LBTT increases DCA formation, solubilization, or absorption (or all 3) is not known. Methods: In 40 subjects (20 with GBS; age range, 24–74 years), we measured LBTT using radiopaque markers, and intestinal luminal pH by radiotelemetry. We also measured quantitative anaerobic bacteriology and the activities of 2 bile acid–metabolizing enzymes in fresh cecal aspirates obtained during clinically indicated unprepared colonoscopy, and related these results to the percentage of DCA in fasting serum measured by gas chromatography–mass spectrometry. Results: Compared with controls, GBS patients had longer LBTT (mean 23.1 ± SEM 2.8 h vs. 36.5 ± 3.3 h; P < 0.01); more total (2.7 ± 0.6 × 109 vs. 5.9 ± 1.5 × 109 cfu/mL) and Gram-positive (9.5 ± 3.1 × 108 vs. 18.0 ± 4.1 × 108 cfu/mL; P < 0.05) anaerobes; and greater 7α-dehydroxylating (7α-DH) activity (3.39 ± 0.59 vs. 10.37 ± 1.15 × 10−4 U/mg protein) in the cecal aspirates. They also had higher intracolonic pH values (P < 0.02) and increased percentages of DCA in fasting serum (13.4% ± 1.52% vs. 21.8% ± 2.19%; P < 0.005). Results of univariate and multivariate analyses confirmed that LBTT was critical in determining the percentage of DCA in serum and showed that 7α-DH activity and apparent distal colonic pH were also significant independent variables. Conclusions: Slow colonic transit (more time), increased Gram-positive anaerobes (more bacteria), and greater 7α-DH activity (more enzyme) favor enhanced DCA formation; transit-induced increases in distal colonic luminal pH favor enhanced DCA solubilization/bioavailability; and increases in LBTT (more time) again favor DCA absorption.GASTROENTEROLOGY 2000;119:806-815

Increases in luminal pH promote the absorption of deoxycholic acid from the colon of patients with cholesterol gallbladder stones (GBS)

Increases in luminal pH promote the absorption of deoxycholic acid from the colon of patients with cholesterol gallbladder stones (GBS)

Dissolution of gallbladder stones with methyl tert-butyl ether and stone recurrence: a European survey.

Since there are now several ways to treat symptomatic gallstone disease, one is able to select treatment on the basis of the patient's comfort, the practicability, effectiveness, and side effects of the technique, and the relative costs. In order to assess the present status of contact dissolution with methyl tert-butyl ether with regard to these aspects, the present enquiry reports the data of 21 European hospitals. Eight hundred three patients were selected for contact litholysis of cholesterol gallbladder stones using methyl tert-butyl ether. Percutaneous transhepatic puncture of the gallbladder was performed under x-ray or ultrasound guidance. Dissolution rate, side effects, and treatment times of 268 patients from one single center were compared to those of 535 patients from the other 20 centers. Two hundred sixty-four patients were followed for five years to assess stone recurrence. Physicians were asked how they assessed the expenditure of the method, the discomfort to the patients, and the staffing situation. Patients were asked to indicate their acceptance on an analog scale. Puncture was successful in 761 (94.8%) patients. Prophylactic administration of antibiotics was not necessary. Stones were dissolved in 724 (95.1%) patients. In 315 (43.5%) sludge remained in the gallbladder. The most severe complication was bile leakage, which led 12 (1.6%) patients to have elective cholecystectomy. Toxic injuries due to the ether were not reported. Method-related lethality amounted to 0%, 30-day-lethality to 0.4%. Stone recurrence rate was about 40% in solitary stones and about 70% in multiple stones over five years. Patients with multiple stones developed recurrent stones almost twice as often as those with solitary stones. The probability of stone recurrence in patients with sludge in the gallbladder after catheter removal was not statistically significantly different from those without sludge. Seventy to 90% of the centers found the puncture to be simple and not distressing for patients and the relation between expenditure and therapeutic success to be acceptable. The acceptance of contact litholysis by the patients was excellent. Contact litholysis when applied by an experienced team provides real advantages in the treatment of gallstone disease. The method is technically simple, well accepted by the patients, and can be easily applied in community hospitals. Contact litholysis may be of particular value in patients who are not suitable for anesthesia or surgery.

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.

Molecular genetic evidence of bacterial colonization of cholesterol gallstones

Background/Aims : Cholesterol gallstone formation is believed to be unrelated to the presence of bacteria because attempts to culture potentially causative bacteria from surgically removed cholesterol stones have failed. However, the formation of gallbladder gallstones takes years. Embedded bacteria may be damaged or killed. The aim of this study was to search for bacterial DNA sequences in cholesterol stones with negative bacterial culture. Methods : Bacterial gene fragments were amplified in vitro from DNA extracted from cholesterol gallbladder stones. Comparative 16S ribosomal RNA sequence analysis was used for identification. Results : Gallstones with cholesterol content between 70% to 90% harbored bacterial DNA (16 of 17 patients). No bacterial DNA was found in the gallstones with cholesterol content of >90% (3 patients). Three bacterial groups typical for gallstone colonization were identified. Propionibacteria-related DNA was found in the stones of 9 patients (45%). Enterobacterial type sequences were obtained in 5 patients (25%). A more heterogenous sequence collection was retrieved from 7 patients (35%) and could be assigned to the major bacterial line of gram-positive bacteria with a low DNA guanine and cytosine content. Conclusions : Most cholesterol gallstones harbor bacterial DNA. It is important to determine the actual role of these microorganisms in gallstone formation.

Dissolution of cholesterol gallbladder stones with methyl tert-butyl ether in patients with increased surgical risk.

The safety and efficacy of methyl tert-butyl ether (MTBE) dissolution of cholesterol gallbladder stones were evaluated in 25 patients with increased risk for surgery. Two patients were treated twice. The MTBE was infused and aspirated manually through a percutaneous transhepatic catheter to the gallbladder. The placement of the catheter failed in three patients (11%). In 19 of 24 patients (79%) there was complete dissolution of stones after a mean treatment time of 12.2 h (range, 4.3-19.5 h). In five patients treatment was discontinued before complete dissolution owing to technical problems or side effects. Side effects were nausea, pain, vasovagal reaction, and fever. Fifteen patients were followed up for a mean of 15.7 months after dissolution. Stone recurrence was found in eight patients, five of whom suffered symptomatic relapse. We conclude that dissolution therapy with MTBE is a safe and adequate alternative to surgery in selected high-risk patients.

Cholesterol nucleation time in gallbladder bile of patients with solitary or multiple cholesterol gallstones.

Patients with multiple cholesterol gallbladder stones have been found to be at a higher risk for the recurrence of gallstones after successful nonsurgical treatment than those with a solitary stone. Cholesterol gallstone recurrence, like primary gallstone formation, probably involves a triple defect with supersaturation, abnormally rapid nucleation of cholesterol in bile and altered gallbladder motor function. We investigated whether the increased recurrence rate of patients with multiple stones might be caused by more rapid nucleation. Therefore the time required for cholesterol monohydrate crystals to appear in ultracentrifuged bile of patients with solitary (n = 71) or multiple (n = 42) cholesterol gallstones was determined. The cholesterol nucleation time was significantly (p less than 0.01) longer in the bile from patients with solitary stones (less than 1 to 16 days, median = 2.0 days) than in the bile from patients with multiple stones (less than 1 to 8 days, median = 1.0 days). Moreover, 15 of 71 (21.1%) patients with solitary cholesterol stones but only 1 of 42 (2.4%) patients with multiple cholesterol stones showed a normal (greater than 4 days) nucleation time. However, no difference in the cholesterol saturation index was found between the bile samples from patients with solitary stones and the bile samples from patients with multiple stones (1.55 +/- 0.65 vs. 1.54 +/- 0.59, mean +/- S.D., respectively). The more rapid cholesterol nucleation in gallbladder bile may, therefore, be the major risk factor causing the higher percentage of stone recurrence in patients with multiple cholesterol stones as compared with patients with solitary cholesterol stones.

Contact Dissolution of Cholesterol Gallstones with Organic Solvents

Contact dissolution of cholesterol gallstones with organic solvents is emerging as a rapid, safe, alternative treatment for symptomatic cholesterol gallbladder stones. Placement of a percutaneous transhepatic catheter into the gallbladder is a rapid and safe technique. The availability of safe, effective cholesterol solvents and solvent transfer devices means that cholesterol gallbladder stones can be eliminated rapidly and safely by CDOS, without the risk of general anesthesia or surgical dissection of the gallbladder bed. Patients with single gallstones are better candidates for CDOS than are patients with multiple gallstones because recurrence after dissolution is less common. Contact dissolution may well be judged the treatment of choice by the medical-surgical gallstone management team in some patients.

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 methyl tert-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 metabolite tert-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.

Total biliary protein, mucus glycoproteins, cyclic-AMP, and apolipoproteins in the gallbladder bile of patients with cholesterol stones and stone-free controls.

The concentrations of total protein, mucus glycoprotein, cyclic-AMP, and apolipoproteins A-I, A-II, and B were determined in the gallbladder bile of patients with cholesterol gallbladder stones and in stone-free controls. The total protein content was significantly increased in gallstone patients (2.03 +/- 0.6 versus 1.31 +/- 0.67 mg/ml; p less than 0.05), as was the mucus glycoprotein concentration (380 +/- 88.5 versus 128 +/- 57.2 micrograms/ml; p less than 0.05). The cyclic-AMP concentration in the gallbladder fluid was increased up to 91 +/- 20 pmol/100 microliters in the gallstone subjects, as compared with 46 +/- 26 pmol/100 microliters (p less than 0.01) in stone-free controls. Cyclic-AMP concentrations correlated positively with the glycoprotein content of the bile in cholesterol gallstone patients (r = 0.66; p less than 0.05). The apolipoprotein concentrations were determined by the radial immundiffusion technique. The corresponding values for patients with stones and controls were 7.5 +/- 0.8 versus 3.0 +/- 0.8 for Apo A-I (p less than 0.025), 10.4 +/- 0.6 versus 6.3 +/- 1.3 for Apo A-II (p less than 0.02), and 1.9 +/- 0.5 versus 1.6 +/- 0.2 mg/dl for Apo B (NS), respectively. Biliary proteins probably play an important role in the nucleation process during the pathogenesis of cholesterol gallbladder stones.

Primary “Brown Pigment” Bile Duct Stones

Bile duct stones from 42 patients were morphologically and chemically analysed. The calculi from 27 patients had important primary bile duct stone (PBDS) features, consisting of a general ovoid shape and fragile structure, with alternating light and dark brown pigmented layers on cross-section. Chemically these stones contained low levels of cholesterol, with high levels of bilirubin and calcium. Subsequent infrared spectroscopy analysis showed that calcium bilirubinate and calcium palmitate were the only calcium salts present. Calcium palmitate was prominent in the light brown layers. A morphological and chemical comparison with gallbladder stones showed that bile duct “stasis stones” were similar in morphological and chemical composition to the brown pigment gallbladder calculi. However, they were distinct from most gallbladder stones, indicating that primary bile duct calculi have an aetiology that is different to 90% of gallbladder calculi. Primary bile duct calculi were observed to occur with or without the presence of a gallbladder, and more interestingly, in the bile duct of two patients with cholesterol gallbladder stones. Bile duct bile of patients with primary choledocholithiasis were always moderately to profusely infected and with abundant calcium bilirubinate precipitation. Moreover, this study has shown that PBDS chemical analyses profiles were consistent and correlated well with their defined morphology. Consequently, PBDS may be accurately identified at the time of operation by morphology. An important aetiological factor would appear to be infection, which would seem to promote bile duct bile stasis and eventual stone growth.

Microprocessor-assisted solvent-transfer system for gallstone dissolution: In vitro and in vivo validation

To improve the efficacy, safety, and convenience of contact dissolution of gallbladder stones, a microprocessor-assisted solvent transfer system was developed. The system's two pumps simultaneously infuse and aspirate solvent into and from the gallbladder at a high flow rate through a multilumen catheter. The microprocessor controls the pumps using a closed-feedback loop control algorithm to regulate intragallbladder pressure to prevent solvent escape into the duodenum. Turbulent solvent flow at the catheter end in the gallbladder is designed to induce rapid stone dissolution and to suspend insoluble residue, thus promoting its aspiration. The system's response and gallbladder emptying capacity was 160-fold faster than the natural gallbladder emptying rate. The rate at which gallstones were dissolved by methyl tert-butyl ether using the system was compared with that achieved with a syringe pump. For 6 of 11 pairs of stones that totally dissolved, the mean dissolution time with the system was 10 ± 6 minutes compared with 112 ± 81 minutes for the syringe pump. In the 5 of 11 stone pairs which dissolved incompletely, insoluble residue was completely eliminated by the system in 21 ± 9 minutes but not by the syringe pump even at 360 minutes. When the system was used in gallstone patients, solvent recovery was 99% ± 1%, and the concentration of a nonabsorbable marker did not change, confirming the lack of appreciable absorption of methyl tert-butyl ether. These studies suggest that the microprocessor-assisted solvent transfer system is a device capable of safe, complete, and fully automatic contact dissolution of cholesterol gallbladder stones using methyl tert-butyl ether or similar solvents.