Direct Dissolution of Gallstones with Methyl tert-Butyl Ether by Endoscopic Cannulation of the Gallbladder

Methyl tert -butyl ether (MTBE) rapidly and effectively dissolves cholesterol gallbladder stones. Due to the invasive nature of transhepatic catheterization, we studied the safety and efficacy of MTBE stone dissolution, delivered by endoscopic, retrograde cannulation of the gallbladder. Extracorporeal shock-wave lithotripsy (ESWL) was employed in patients with multiple stones, to increase contact surface area and facilitate dissolution. We successfully cannulated the gallbladder in 13/17 patients (76.5%) attempted, with no associated complications. After cannulation, MTBE lysis was then conducted on all patients, and 10/13 patients (77%) cannulated were either stone-free at completion, or had only residual gallbladder sludge. Predissolution ESWL successfully fragmented stones in 6/7 patients (86%) in which it was attempted. Both ESWL and MTBE were well tolerated by all patients. Endoscopic retrograde cannulation of the gallbladder and MTBE dissolution is a promising alternative for the treatment of gallbladder stones in patients who will not receive surgery.     

Incidence, natural history, and risk factors for biliary sludge and stones during pregnancy

Gallstones are strongly associated with higher parity in women. This study prospectively assessed the incidence, natural history, and risk factors for biliary sludge and stones during pregnancy and the postpartum in 3,254 women at an army medical center. Women with a prior cholecystectomy or with stones at their first study ultrasound were excluded. Gallbladder ultrasound and subject questionnaires were obtained in each trimester and at 4 to 6 weeks postpartum. Serum glucose, lipids, insulin, leptin, estradiol, and progesterone were measured at 26 to 28 weeks' gestation. A nested case-control study was done to examine the effects of serum leptin and insulin on incident gallbladder disease. At least two study ultrasounds were available for 3,254 women. Sludge or stones had been found on at least one study ultrasound in 5.1% by the second trimester, 7.9% by the third trimester, and 10.2% by 4 to 6 weeks postpartum. Regression of sludge and stones was common, such that overall 4.2% had new sludge or stones on the postpartum ultrasound. Twenty-eight women (0.8%) underwent cholecystectomy within the first year postpartum. Prepregnancy body mass index was a strong predictor of incident gallbladder disease (P < .001). Serum leptin was independently associated with gallbladder disease (odds ratio per 1 ng/dL increase, 1.05; 95% CI, 1.01, 1.11), even after adjusting for body mass index. In conclusion, incident gallbladder sludge and stones are common in pregnancy and the postpartum, and cholecystectomy is frequently done within the first year postpartum. Prepregnancy obesity and serum leptin are strong risk factors for pregnancy-associated gallbladder disease.     

Postdissolution gallstone recurrence

The intuitive assumption that gallstones will rapidly recur in all patients is clearly incorrect. At least 50% of patients do not develop stones within three to five years of complete dissolution, and the risk may decrease after the first two or three years. This is not so surprising when one considers the complexity of the pathogenic process. Bile must be sufficiently supersaturated with cholesterol, an imbalance in nucleating and antinucleating factors must occur, at least transiently, and, for some patients, a defect in gallbladder emptying may be necessary. Occasionally, pathogenic mechanisms that had been present, eg, estrogens, obesity, or medications such as clofibrate, may no longer be active. The best method to reduce the risk of recurrence is to reverse one or more of the essential pathogenic mechanisms. Desaturating bile in cholesterol by oral therapy with a bile acid such as ursodiol should be effective. A search for other safe, effective, and cost-effective approaches persists, eg, for novel bile acids resistant to bacterial degradation and for various dietary regimens. Alteration of cholesterol nucleation with nonsteroidal antiinflammatory agents is also under investigation. In addition, enhancement of gallbladder emptying is an interesting approach that is worth studying. If stones do recur, the course of action is not always clear. Recurrent stones are usually “silent,” and we do not usually treat asymptomatic stones. These small cholesterol stones are temptingly easy to dissolve, however. At least in those patients whose level of surgical risk would be high if symptoms developed, prophylactic dissolution therapy may be desirable.     

Cancer risk in different types of gallstones (author's transl)

Among 22,868 autopsied adults were 7,411 cases with cholelithiasis or cholecystectomy. In the cancerous gallbladders pigment-stones, pure crystalline cholesterol stones and lobulates stones were seldom found but multiple faceted stones and solitary combined stones are more frequent. If the partial volume of gallstones increased, there were more cases with cholecystitis or later carcinoma. Nevertheless in males with all forms of gallstones, carcinoma of the lung, the stomach, the colon and rectum and the prostatic gland were more frequent then carcinoma of the gallbladder. Only in female with multiple faceted stones and solitary combined stones, carcinoma of the gallbladder was the most frequent cancer. The "St?rfeld" of the gallbladder with stones is more important for the localisation of a later carcinoma in female then for men. If the gallbladder with stones should be resected in good time, the patient is protected of the risk of cancer of gallbladder, but the percentage of all cancers among inoperated cases with gallstones is not higher than among cases with previons cholecystectomy. Instead of carcinoma of the gallbladder other cancers develop after cholecystectomy.     

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.     

Role of endoscopic evaluation in idiopathic pancreatitis: a systematic review

In approximately 20% of patients with acute pancreatitis, a cause is not established by history, physical examination, routine laboratory testing, and abdominal imaging. For those with a single unexplained attack, the role of invasive evaluation with endoscopic retrograde cholangiopancreatography is unsettled but has been generally limited to those patients with suspected bile duct stones or malignancy. Recent studies suggest that microlithiasis is causative in up to 75% of patients with an unexplained attack and gallbladder in situ, whereas sphincter of Oddi dysfunction is most prevalent in those with recurrent attacks who have previously undergone cholecystectomy. EUS has been shown to be highly accurate for the identification of gallbladder sludge, common bile duct stones, and pancreatic diseases. Given this apparent diagnostic utility, an EUS-based strategy may be a reasonable approach to evaluate patients with a single idiopathic attack. ERCP and sphincter of Oddi manometry should generally be reserved for patients with multiple unexplained attacks and negative EUS results, especially for those patients who have previously undergone cholecystectomy.     

Gallstone disease: Epidemiology, pathogenesis, and classification of biliary stones (common bile duct and intrahepatic)

Gallstones are common in Western countries and Japan. Most gallstones are found in the gallbladder, but they sometimes pass through the cystic duct into extrahepatic and/or intrahepatic bile ducts to become bile-duct stones, causing conditions known as choledocholithiasis and hepatolithiasis. Some 10-15% of gallstone patients concomitantly suffer from bile-duct stones. Bile-duct stones can also be formed in the absence of gallbladder stones, and such primary bile-duct stones are more common in East Asian countries than in the Western world. Thus pathogenesis of primary and secondary bile-duct stones is unlikely to be similar. Furthermore, the gallbladder stones are primarily cholesterol or black-pigment stones, whereas most bile-duct stones are brown-pigment stones (calcium bilirubin stones). Thus, epidemiology, pathogenesis and classification of biliary stones are very likely to differ according to stone location (intrahepatic and/or extrahepatic bile duct).     

Approach of suspected common bile duct stones: endoscopic ultrasonography

Recent studies have shown that endoscopic ultrasonography (EUS) is the most sensitive method for diagnosing choledocholithiasis. High sensitivities of more than 95% have been reported by several authors. Imaging the extrahepatic bile ducts and the gallbladder and searching for biliary stones are easy tasks for EUS. EUS has the advantages over ERCP to be less invasive (complication rate similar to diagnostic upper GI endoscopy) and to be able to detect small stones and sludge that can easily be masked by contrast medium during ERCP. In comparison with magnetic resonance imaging (MRI), EUS has the advantage to be close to the investigated areas and to allow the detection of very small stones or sludge, even in non dilated bile ducts. Technical limitations of biliary imaging by EUS are few: upper GI stenosis, previous gastrectomy or Billroth II resection. Imaging can be obscured by the presence of air (previous sphincterotomy or surgical bypass), surgical clips calcifying pancreatitis or a duodenal diverticulum. Main indications of EUS include the detection of choledocholithiasis in patients with a low and intermediate probability of presence of stones, in idiopathic acute pancreatitis, in mild and moderate pancreatitis after normal transabdominal ultrasonography, in pregnant women, in intensive care patients, in the diagnosis of gallbladder lithiasis or sludge, and also when MRI is contraindicated (claustrophobia and metallic implants) or fails to provide a diagnosis or is not available. Screening of choledocholithiasis with EUS has also been proposed in patients scheduled for laparoscopic cholecystectomy, but this is not common practice in Belgium.     

Gallstone disease. Management of common bile-duct stones and associated gallbladder stones: Surgical aspects

For many years, open exploration of the common bile duct has been the treatment of choice for patients with common bile-duct stones. During recent decades endoscopic sphincterotomy has gained wide acceptance as an effective and less invasive alternative. After sphincterotomy, subsequent (laparoscopic) cholecystectomy is warranted in patients with gallbladder stones. This chapter will discuss whether sphincterotomy should be performed prior to, during or after cholecystectomy, and will also address the question of whether single-stage treatment by laparoscopic cholecystectomy and laparoscopic bile-duct exploration is in fact preferable. The rate of recurrent choledocholithiasis after endoscopic biliary sphincterotomy can reach more than 20%. This review focuses on the risk factors--delayed bile-duct clearance and bactobilia--that may lead to recurrent primary bile-duct stone formation. Underlying altered bile composition (relative phospholipid deficiency) should be recognised in a subgroup of patients. Identification of these risk factors may significantly affect treatment policy.     

Black pigment gallstones with cholesterol gallstones in the same gallbladder

We studied 1312 consecutive patients who underwent surgery for gallstones in the biliary tract at one university hospital in Siena, Italy, with a systematic classification of gallstones found within the gallbladder. Of these patients, 1226 were found to have gallbladder stones; 94 of these had black pigment gallstones. Of these, 13 patients were found to have black pigment gallstones and cholesterol gallstones within their gallbladder. They all had multiple black pigment gallstones, usually very small (all <6 mm diameter), in association with larger cholesterol stones in the gallbladder lumen. The cholesterol gallstones were single in seven cases, double in two cases, and multiple in four cases. All 13 of these patients with black pigment stones in association with cholesterol stones had histologic evidence of either adenomyomatosis or Rokitansky-Aschoff sinuses in the gallbladder wall. In nine of the 13 patients, the black pigment stones were located both in the gallbladder lumen and in close association with the gallbladder wall (in areas of adenomyomatosis or in Rokitanski-Aschoff sinuses). In the other four patients, the stones were found in close association with the gallbladder wall alone and not freely mobile within the gallbladder lumen. It is concluded that cholesterol stones and black pigment stones may be found in the same gallbladder. This association is infrequent with an incidence of 13 of 1226 (1.06%) in our series. There appears to be some relationship between the formation of the black pigment stones and the presence of adenomyomatosis or Rokitanski-Aschoff sinuses. However, the pathogenesis of these two compositionally distinctly different types of stones within the same gallbladder is not understood and deserves further study.     

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.     

The management of bile duct stones.

Bile duct stones are almost always associated with gallbladder stones and coexist with gallbladder stones in approximately 10% of patients. The frequency of coexisting bile duct stones increases with advancing age. In patients with stones in both the gallbladder and bile duct, therapeutic options for the latter include laparoscopic or open exploration of the bile duct, and pre-operative and post-operative endoscopic sphincterotomy and stone extraction. Endoscopic sphincterotomy remains the treatment of choice for bile duct stones after cholecystectomy. However, management algorithms in individual institutions will be influenced by surgical and endoscopic expertise and by other factors such as overall costs. After surgical or endoscopic removal of bile duct stones, estimates of the lifetime risk of recurrent stones range from 5%-20%. Increased life expectancy and the apparent absence of simple preventative measures indicate that the burden of bile duct stones on health expenditure is likely to increase in many countries.     

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.     

Treatment of gallstones with piezoelectric lithotripsy and oral bile acids. A multicenter study

The efficacy of the combination of piezoelectric lithotripsy and oral bile acids in the treatment of gallbladder stones was assessed. Three hundred and sixty-three patients with symptomatic radiolucent gallstones in functioning gallbladder were treated in five medical centers using the same protocol with the EDAP LT 01 lithotripter. No anesthesia, analgesia or sedation was used. After one session of lithotripsy, fragmentation was observed in 89% of the patients, and satisfactory fragmentation (fragments less than or equal to 5 mm) in 29%. The satisfactory fragmentation rate was higher in patients with solitary stones less than or equal to 20 mm than in patients with solitary stones 21-35 mm or multiple stones (p less than 0.001). After multiple sessions (mean 1.6 session/patient, range 1-5) the overall rate of satisfactory fragmentation was 50%. After 12 months on oral bile acid therapy, complete clearance of the gallbladder was observed in 69% of patients with solitary stones less than or equal to 20 mm, 25% of patients with solitary stones 21-35 mm and 37% of patients with multiple stones. No complication was observed during the lithotripsy. During follow-up under bile acid therapy, there were five complications (1.4%): four patients had acute cholecystitis and one had mild, self-limited pancreatitis. We conclude that piezoelectric lithotripsy with the EDAP lithotripter is a safe and effective treatment which can be performed in outpatients. Satisfactory fragmentation and rapid disappearance of stones are obtained mainly in patients with solitary stones less than or equal to 20 mm.     

Endoscopic retrograde cannulation of the gallbladder: direct dissolution of gallstones

Percutaneous transhepatic catheterization of the gallbladder for dissolution of cholesterol stones by instillation of methyl tert-butyl ether (MTBE) is an invasive therapeutic procedure. The only non-invasive alternative available to now, endoscopic retrograde cannulation of the cystic duct, was difficult because of the cystic duct's tortuosity and spiral valves. We therefore developed a catheter system which, using conventional duodenoscopes during a routine endoscopic retrograde cholangiography (ERC) procedure, permits reliable and safe catheterization of the gallbladder without the need for endoscopic sphincterotomy. In 18 of 22 patients (82%) we were able to place a cysto-nasal catheter, and in 14 patients MTBE dissolution therapy was then performed. Eight patients (57%) were completely free of stones after treatment; the other six (43%) had residual debris. In 4 of 22 patients (18%) cannulation attempts failed, in 3 patients due to cystic duct blockage by a calculus. Endoscopic retrograde cannulation of the gallbladder (ERCG) represents a promising alternative to the invasive percutaneous transhepatic catheterization procedure.     

Apolipoprotein E genotype and the risk of gallbladder disease in pregnancy

The E4 allele of apolipoprotein E (apoE4) has previously been associated with symptomatic gallstone disease. The aim of this study was to determine if apoE4 is associated with the development of gallbladder sludge and/or stones during pregnancy. We conducted a nested case-control study based on an ongoing cohort study of gallbladder disease in pregnancy. Women in this study receive gallbladder ultrasounds in each trimester of pregnancy. Cases (n = 52) were defined as women with incident gallbladder sludge or stones diagnosed at the third trimester ultrasound. Controls (n = 104) were defined as women without gallbladder sludge or stones on any of 3 study ultrasounds. ApoE genotyping was performed from stored white blood cell pellets. Data were analyzed by stratified analysis and multivariate logistic regression. Cases and controls were similar in baseline characteristics. Forty-two women had sludge, 6 had gallstones, and 4 had both sludge and stones. After adjusting for risk factors such as age, parity, and body mass index, the odds ratio (OR) for the association between heterozygosity or homozygosity for the apoE4 allele and incident gallbladder sludge or stones was 0.91 (95% confidence interval [CI], 0.41-2.02). Further adjustment for family medical history and serum lipid levels did not substantially change these results (OR, 0.73; 95% CI, 0.29-1.82). In conclusion, apoE4 appears to have little or no overall association with the development of new gallbladder sludge or stones in pregnancy. However, an effect could not be ruled out in certain subgroups, such as blacks or women who are homozygous for apoE4.     

胆石病微创外科治疗发展现状

胆囊结石的发病率呈逐年上升趋势,胆管结石的发病率逐年下降,随着腔镜微创外科技术的发展,胆石病的治疗实现了微创化。胆囊疾病包括急诊均可采用腹腔镜手术治愈,近年来出现的单孔技术更加完善了胆囊切除的微创化,胆囊结石合并胆管结石目前多采用三镜联合技术,其理想目标应为两种疾病通过三镜技术的优化组合一次性治愈,避免留置T管,保留括约肌功能,缩短住院时间,降低医疗费用。     

Juxtapapillary duodenal diverticula: association with biliary stone disease

In order to explore the relationship between duodenal diverticula and biliary stone disease, we reviewed 2231 endoscopic retrograde cholangio-pancreatography procedures. We found at least one juxtapapillary diverticulum per 239 patients (10.8%). The occurrence of duodenal diverticula increases with age. Patients with duodenal diverticula were older, had more gallbladder stones, more common bile duct stones, had undergone cholecystectomy more frequently, and experienced more frequently common bile duct stone recurrence after cholecystectomy. We thus confirm an association between the presence of diverticula of the second part of the duodenum, and biliary stone pathology, including gallbladder stones, common bile duct stones, and recurrent stones after cholecystectomy. We discuss the aetiopathogeny of this affection.     

Biliary lithotripsy with a new electromagnetic shock wave source

During a two-year study period 170 consecutive patients with gallbladder stones, suitable for lithotripsy, were treated with a new electromagnetic lithotriptor (Modulith) and oral bile acids; 142 patients were treated as outpatients. Sufficient fragmentation were obtained in 94% when 2112±137 shocks in 211 sessions with an energy setting of 17.8±0.8 kV were administered. Only 4/170 patients needed transient analgesia. Overall, side effects were transient and mild, but three patients developed biliary pancreatitis, which was treated by endoscopic sphincterotomy in two of them. A total of 67/100 patients were free of stones after one year. Subgroup analysis showed that 80% of the patients (stone diameter 5–20 mm), 64% (20–30 mm) and 65% (multiple stones), respectively, can expected to be free of stones after 12 months. In addition, 25 patients with large, endoscopically not extractable common bile duct stones were treated by lithotripsy with the Modulith. After endoscopic placement of a nasobiliary tube, stone targeting was possible by ultrasonography in 14 patients and by fluoroscopy in another 11 cases. In 23 of the 25 patients (92%) stone clearance by endoscopy was achieved after application of 2516±565 shocks with an energy preset of 18 kV. One patient refused further endoscopic procedures after successful fragmentation and another required local stone dissolution therapy. Side effects occurred more frequently (P<0.05) after lithotripsy of bile duct stones than of gallbladder stones, but they were without major clinical relevance. The new lithotriptor Modulith thus enables safe and highly effective lithotripsy of gallbladder calculi on an outpatient basis. Moreover, the device also allows successful lithotripsy of bile duct stones.