Genetic predisposition to gallbladder stones

Geographic and ethnic differences in gallstone prevalence rates and familial clustering of cholelithiasis imply that genetic factors influence the risk of gallstone formation. Recently, twin, family, and linkage studies confirmed a genetic predisposition to the development of symptomatic gallstones. In rare instances, mutations in single genes confer a substantial risk for the formation of gallstones. However, in the majority of cases gallstones might develop as a result of lithogenic polymorphisms in several genes and their interactions with multiple environmental factors, rendering gallstones generally a complex genetic disorder. Some of the rare monogenic forms of cholelithiasis were unraveled but the lithogenic genes that increase the susceptibility to cholelithiasis in the majority of gallstone carriers remain elusive. Identification of these lithogenic genes will provide novel means of risk assessment, strategies for prevention, and targets for nonsurgical management of cholelithiasis, which currently is one of the most expensive digestive disorders.     

Bile acid dissolution therapy of gallbladder stones

Oral cholelitholytic bile acid therapy has become established treatment for selected patients with cholesterol gallstones. The treatment finds its clinical application both alone and in combination with ESWL. UDCA alone or, less commonly, a combination of this bile acid with CDCA is used. Optimal results can be expected only in carefully selected patients. Bile acid dissolution therapy is most successful in patients with radiolucent gallstones which are ≤0.5 cm in diameter or are shown by OCG to be floating. Dissolution is seldom seen when the stones are > 1 cm in size. Cholelitholytic treatment in combination with ESWL yields optimal results in single radiolucent gallstones which are not greater than 2 cm. ESWL thus makes it possible to use medical treatment effectively in single 1–2-cm gallstones when bile acids alone would not be successful. Bile acid treatment is extremely safe, especially if UDCA is given without the addition of CDCA.     

Percutaneous transhepatic dissolution of gallbladder stones.

The method of percutaneous transhepatic dissolution with methyl tert-butyl ether (MTBE) has been used at the Zagreb Clinical Hospital Department of Medicine since 1989. From December 1989 until December 1991, 69 patients, 51 (74%) females and 18 (26%) males, with symptomatic and cholesterol gallbladder stones were hospitalised at the Department. All patients preferred percutaneous transhepatic dissolution to surgical treatment of gallbladder stones. The gallbladder was successfully punctured and the catheter placed into the gallbladder lumen in 63 (91%) patients, whereas complete dissolution was achieved in 59 (85.5%) patients. In 21 (33.9%) of these 59 patients, after completed dissolution computer-processed roentgenograms and ultrasonic scan of the gallbladder revealed residual particles of debris sized up to 2 mm. Six patients in whom puncture, i.e. the placement of the catheter into the lumen was unsuccessful, were electively operated on the following day without any complications. The mean duration of hospitalisation for 63 patients was 4.5 days.     

Management of common bile-duct stones and associated gallbladder stones: surgical aspects

In most countries, endoscopic sphincterotomy is the first-choice treatment for common bile-duct stones. In patients with residual gallbladder stones, laparoscopic cholecystectomy is the next step. The optimal timing of laparoscopic cholecystectomy after endoscopic sphincterotomy remains to be determined. An alternative approach of combined cholecystocholedocholithiasis consists of laparoscopic cholecystectomy together with laparoscopic stone removal. The advantage of this ‘single-stage’ therapy appears to be limited to patients with stones that can be removed transcystically. This approach is successful in about half of the patients. Laparoscopic common bile-duct exploration is technically more demanding, more time-consuming, and associated with increased postoperative morbidity. If transcystic removal is not possible, a postoperative ERCP with endoscopic sphincterotomy is a good option. Intraoperative ERCP and endoscopic sphincterotomy are also feasible, but require specific organisational efforts.Recurrence of choledocholithiasis after ES is reported in a considerable number of patients (6–21%), resulting from de novo primary stone formation or recurrent secondary migration from the gallbladder. Primary choledocholithiasis is associated with bactobilia and delayed bile-duct clearance, indicated by CBD dilation. Endoscopic reintervention is safe and usually easy to perform. Surgery should be reserved for intractable cases. In selected patients, an underlying lithogenic bile composition (low-phospholipid-associated cholelithiasis) should be identified, and preventive medical treatment with UDCA could be considered.

• in patients with combined cholecystocholedocholithiasis, endoscopic sphincterotomy should be followed by elective laparoscopic cholecystectomy, even in the elderly; however, a ‘wait-and-see’ policy does not lead to higher mortality, and therefore expectant management can be advocated in case of significant contraindications to surgery

• laparoscopic cholecystectomy combined with laparoscopic stone removal offers a one-stage treatment of patients with combined cholecystocholedocholithiasis. Laparoscopic transcystic duct clearance is associated with low morbidity and short hospital stay. In contrast, laparoscopic common bile-duct exploration remains a procedure with increased risk of biliary complications and prolonged hospital stay. In case of stones that cannot be removed transcystically, it may be wise to perform an intraoperative or early postoperative ERCP

• performing an endoscopic sphincterotomy during laparoscopic cholecystectomy using a ‘rendezvous’ procedure may be beneficial in selected patients (especially in case of earlier failed ERCP)

• laparoscopic cholecystectomy after endoscopic sphincterotomy is associated with increased conversion rates to open procedure compared to laparoscopic cholecystectomy for uncomplicated gallstones; laparoscopic cholecystectomy planned early after endoscopic sphincterotomy may reduce this risk

• morphological or functional bile-duct defects, indicated by a dilated CBD, may lead to bactobilia and biliary stasis, thus promoting primary stone formation

• in a subgroup of patients with recurrent bile-duct stones, an MDR3 gene mutation must be considered, resulting in low-phospholipid-associated cholelithiasis. These patients are characterised by early onset of symptoms, recurrence after cholecystectomy, hyperechogenic foci in the liver, and often a history of intrahepatic cholestasis of pregnancy. Ursodeoxycholic acid is beneficial in these patients

• the optimal timing or ERCP in patients scheduled for laparoscopic cholecystectomy (before, during, or after the operation) still needs to be defined.

• further data are needed to determine potentially increased incidence of conversion and postoperative complications for laparoscopic cholecystectomy after endoscopic sphincterotomy compared to laparoscopic cholecystectomy for uncomplicated gallstones

Incidence of gallbladder stones in renal transplant recipients]

BACKGROUND/AIMS: Gallbladder stone is one of the major cause of morbidity in adults. Renal transplantation has been found to increase the risk of gallbladder stone formation. The real incidence of gallbladder stones in renal transplant recipients is not exactly known. We performed this study to identify the risk factors for cholecystolithiasis. METHODS: We compared the prevalence of gallbladder stone in 222 renal transplantation patients with that in 222 age and sex matched controls. Patients who had chronic liver disease, renal disease, and diabetes were excluded from the control group. RESULTS: In our study, the incidence of gallbladder stones is 8.6% (19/222 patients) in renal transplantation patients, which was significantly higher than 3.60% (8/222 control) in the control group (p=0.029). In the most of our renal transplantation patients, cholecystolithiasis was asymptomatic. We did not find a difference in age, sex, duration after transplantation, causes of renal failure, resistance index between patients with and without gallbladder stones in renal transplantation patients. CONCLUSIONS: Our results suggest that the incidence of gallbladder stones is higher in renal transplant recipients than non-transplant population in Korea. Further studies will be needed to focus the factors contributing to the gallbladder stone formation after renal transplantation, especially in regard to immunosuppressive drugs.     

Reversibility of central neuronal changes in patients recovering from gallbladder stones or acute cholecystitis

INTRODUCTION Cholecystectomy in patients with gallstone disease usua relieves the symptoms. However, it has repeatedly be demonstrated that 5%-10% of the patients still suff from severe pain, and even more patients (25%-40% have milder symptoms[1,2]. The …     

Long-term recurrence of gallbladder stones after shock-wave lithotripsy

The whole body retention of radioactive cyanocobalamin, coenzyme B₁₂, methylcobalamin, and hydroxocobalamin was measured by whole body monitoring after oral doses of 1, 5 and 25 μg. At each dose level there were significant differences between the values for whole body retention of the different cobalamins.     

Alternative treatment for gallbladder stones in portal venous thrombosis

BACKGROUND/AIMS: Cholecystectomy for treatment of gallbladder stones in patients with portal vein thrombosis can be a hazardous procedure. Dissection into an area of thin-walled collateral vessels can trigger troublesome bleeding and consequent blood coagulation disorders. METHODOLOGY: In order to avoid dissection, cholecysto-jejunostomy was used as the treatment of choice in three patients with symptomatic gallbladder stones and portal vein thrombosis. RESULTS: Surgical procedure was uneventful, blood or plasma transfusions were not required either at surgery or afterwards. Pre- and postoperative hematocrit evaluations showed no difference, as well as liver function tests. The procedure was well tolerated and patients were discharged from day 5 to 7. Follow-up ranged from 2 to 3 years, no biliary complications were found during this period. CONCLUSIONS: Choleysto-jejunostomy is a safe procedure and can be used as an effective treatment of symptomatic gallbladder stones in patients with portal vein thrombosis.     

Detection of Helicobacter pylori by polymerase reaction in bile samples from gallbladder and bile stones

Some papers report helicobacter pylori existence in bile from surgical specimens obtained during gallbladder or bile ducts surgery. The aim of this work was search by PCR, H. Pylori presence in bile specimens from patients suffering of gallbladder stones or by bile ducts stones. Bile samples were obtained by gallbladder punction during cholecystectomy in 26 patients, 19 of them with gallbladder stones and 7 also with gallbladder stones and bile duct stones. Age ranged from 22-69 years old, median 49.6 years old. Samples were sent to specialized biomolecular laboratory to perform PCR techniques. Two of 26 patients (7.6%) had positive reaction for the presence of DNA of H. Pylori in bile samples. Our research suggest that DNA of H. Pylori can be founded in bile samples patients with gallbladders and duct stones in Argentina.     

Gallstone disease: Symptoms and diagnosis of gallbladder stones

The clinical aspects and the diagnostic features of gallstone disease are described. The natural history of silent gallstones is overviewed, and the risk of developing symptoms and complications is also discussed. The importance of colicky pain as a specific gallstone symptom is highlighted, and the role of both laboratory tests and diagnostic investigations for differential diagnosis is discussed. Finally, we describe the diagnostic features of gallbladder stone disease, including indications, sensitivity, specificity, and limitations of different test investigations under special circumstances.     

Effect of extracorporeal shock-wave lithotripsy on gallbladder emptying in patients with solitary and multiple gallbladder stones

In a prospective study, we investigated the effect of extracorporeal shock-wave lithotripsy (ESWL) on gallbladder contractility and on fasting and residual gallbladder volume in patients with solitary and multiple gallbladder stones with stone densities<100 Hounsfield units (HU) and adequate gallbladder function. Twenty-five patients (seven males and 18 females, mean age 48.5±11.7 years) treated with ESWL were assigned to either group I, consisting of 13 patients with solitary stones<20 mm diameter, or group II, including patients with two to three stones and maximum stone diameter of 30 mm. ESWL was performed with the MPL 9000 lithotripter. Gallbladder ejection fraction was determined using the method of Dodds after a 12-hr fast and following application of a standard stimulative meal. Gallbladder volume was measured by ultrasound over 90 min at 10-min intervals before ESWL, then at 1, 30, 120, and 210 days after ESWL. At 24 hr after ESWL, residual gallbladder volume increased in group I from 7.4 ml to 13.9 ml (P=0.0567) and in group II from 6.5 ml to 20.2 ml (P=0.0076). Thereafter, residual volumes returned to pre-ESWL levels. In group II, post-ESWL fasting volumes were significantly increased over initial values at all time intervals. Correspondingly, only at 24 hr after ESWL, ejection fractions decreased from 73.1% to 64.9% in group I and from 76.5% to 62.7% in group II. No statistically significant differences in gallbladder contractility between the two groups were observed at any point of the follow-up period. ESWL exerts a no more than transient effect on gallbladder motility, regardless of stone count prior to ESWL. We postulate that changes in residual gallbladder volume and reductions in ejection fraction may be due to transitory disturbances in the gallbladder epithelium and resultant gallbladder wall edema.     

Dissolution of calcified cholesterol stones and of brown and black pigment stones of the gallbladder

The influence of different solvents on cholesterol and pigment stones was investigated in vitro. Stone analysis was performed chemically, with infrared spectroscopy (IRS), scanning electron microscopy, energy-dispersive X-microanalysis (EDXA) and wave-length-dispersive X-microanalysis (WDXA). Each set of stones came from one source: eight human calcified cholesterol stones (CHS), eight fragments of bovine radiopaque Ca-bilirubinate stones (BBIL), and two complete BBIL. CHS and BBIL fragments were treated with (1) a buffered, alkaline 1% ethylenediamine tetraacetate solution (BA-EDTA; pH 9.5); (2) with BA-EDTA and monooctanoin preparation (GMOC) alternately; (3) with GMOC alone, and (4) with methyl-tert-butyl ether (MTBE). The complete BBIL were treated with BA-EDTA and MTBE. Furthermore, two human black pigment stones (BPS) were incubated in BA-EDTA. Calcified cholesterol stones are not dissolved by GMOC alone, nor by alternating treatment with BA-EDTA. They are dissolved by MTBE. MTBE is unsuitable for complete Ca-bilirubinate stones but MTBE, GMOC and GMOC/BA-EDTA alternately disaggregate stone fragments. This means that stone fragments behave differently from complete Ca-bilirubinate stones, which is important for further in vitro investigations. Ca-bilirubinate and black pigment stones are disaggregated in BA-EDTA. These results were confirmed with six CHS, 12 BBIL and 12 BPS from 5 further patients, incubated in the most eligible solvent for any individual stone type.     

Decreased postprandial gallbladder emptying in patients with black pigment stones

AIM： To analyze gallbladder contractility in patients with black pigment stones （BPSs） and to compare this with patients with cholesterol stones （CSs） and healthy volunteers.
METHODS： The pattern of bile evacuation from the gallbladder was quantified by computer cholescintigraphy in 28 normal subjects, 22 patients with CSs and 14 with BPSs. The parameters of gallbladder contractility included ejection period （EP）, ejection fraction （EF） and ejection rate （ER）.
RESULTS： A significantly shorter EP was observed in patients with BPSs in comparison to those with CSs （t = 2.4, P 〈 0.05）. EF in BPS patients significantly decreased in comparison to that in CS and normal subjects （t = 6.4, P 〈 0.0001; t = 2.1, P 〈 0.05）. EF in CS patients also significantly decreased in comparison to that in normal subjects （t = -3.0, P 〈 0.005）. Consequently, ER in patients with BPSs and CSs was significantly smaller than that in normal subjects （t = 3.1, P 〈 0.005; t = -3.5, P 〈 0.001）. Moreover, in cases where postprandial reflux of a radioisotope into the common hepatic duct from the gallbladder was observed, EF and ER of either CS or BPS patients showed a significant reduction.
CONCLUSION： Bile evacuation from the gallbladder is reduced in patients with BPSs, in comparison to those with CSs and to healthy volunteers. Bile stagnation due to impaired gallbladder kinetics seems to be one of the predisposing factors for the development of BPSs.