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).     

Cholecystectomy improves long-term success after endoscopic treatment of CBD stones

BACKGROUND/AIMS: The aim was to study prospectively primary endoscopic treatment of CBD stones and further the long-term need for renewed gallstone disease interventions, defined as short- and long-term outcome. METHODOLOGY: Seven years prospective follow-up of 101 consecutive patients with CBD stones who underwent endoscopic treatment with the intent of primarily achieving duct clearance. RESULTS: Many patients underwent several endoscopy sessions before stone clearance was completed in 83%. Eleven patients were treated surgically, 2 patients received a permanent stent, and the remaining 3 became stone free with other means. Complications occurred in 47 patients. During follow-up, 31 patients were readmitted for gallstone disease and 15 of these had recurrent CBD stones. Ten percent (8/78) of patients with the gallbladder in situ had acute cholecystitis during follow-up and late cholecystectomy was carried out in 22%. Risk factors for new gallstone disease were an in situ gallbladder containing stones and previous episodes of CBD stones. CONCLUSIONS: A goal of complete CBD stone clearance with ERC and ES proved to be relatively resource consuming. Subsequent cholecystectomy after duct clearance for CBD should be advised when the gallbladder lodges gallstones, especially in younger patients. Recurrent CBD stones were not influenced by cholecystectomy.     

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.     

不同部位及性质胆石症患者肠黏膜通透性改变的临床分析

目的研究不同部位及性质胆石症患者肠黏膜通透性的改变,并探讨肠屏障功能在胆石形成中的作用。方法选择2011年3月-2013年3月收治的108例胆结石患者,健康对照者20例,按结石部位不同分为4组:健康对照组(A1组)、胆囊结石组(B1组)、胆管结石组(C1组)、胆囊结石合并胆管结石组(D1组);所有入选患者全部行手术治疗,收集胆石进行化学分析,根据结石不同性质分为健康对照组(A2组)、胆固醇结石(B2组)、胆色素结石(C2组)、混合性结石组(D2组)。分别用分光光度法测定各组血浆及回肠末端黏膜组织中D-乳酸浓度、二胺氧化酶(DAO)活性,组间比较采用方差分析和LSD-t检验。结果 (1)不同部位结石患者(A1、B1、C1、D1 4组)之间血浆及肠黏膜组织D-乳酸及DAO活性水平相比较差异无统计学意义(P0.05);(2)术后对胆石进行化学分析,胆固醇结石40例(37.04%)、胆色素结石52例(48.15%),混合性结石16例(14.81%);与A2组及B2组比较,C2组血浆及肠黏膜组织D-乳酸及DAO活性差异有统计学意义(P0.05),与D2组比较,差异无统计学意义(P0.05);B2组与A2、D2组比较,差异无统计学意义(P0.05)。结论胆色素结石患者存在肠黏膜通透性的改变,胆色素结石形成与肠屏障功能损伤有一定的关系,肠屏障功能损伤可能在促进胆色素结石的形成中发挥一定的作用。     

胆囊结石与急性胰腺炎的关系

目的 探讨胆囊结石患者发生急性胰腺炎（AP）的影响因素.方法 选取武汉大学人民医院消化内科收治的诊断为胆囊结石的患者118例,通过影像学检查,测量胆囊大小、胆囊结石大小及数量,判断是否伴有胆总管结石.根据有无并发AP进行分组,比较各相关因素对AP发生率的影响.结果 118例胆囊结石患者中并发AP 61例.74例的胆囊大小正常,其中49例（66.2％）发生AP;44例胆囊增大或缩小,其中12例（27.3％）发生AP.31例为单发结石,其中11例（35.5％）发生AP;87例为多发结石,其中50例（57.5％）发生AP.发生AP的11例单发结石患者,其中8例（72.7％）结石≥10mm;50例多发结石患者中41例（82.0％）结石＜10 mm.19例伴有胆总管结石,其中17例（89.5％）发生AP;99例无胆总管结石,其中44例（44.4％）发生AP.各因素的两组间差异均有统计学意义（Х^2=16.758,P=0.000;Х^2 =4.425,P=0.029;Х^2=13.434,P=0.001;Х^2 =12.994,P=0.000）.结论 急性胆源性胰腺炎的发生与胆囊结石相关,胆囊是否正常、胆囊结石大小及数量、是否伴有胆总管结石均是影响AP发生的相关因素.     

Pathogenesis of cholelithiasis in chronic pancreatitis]

The prevalence and the pathogenesis of gallstones in patients with chronic pancreatitis have never been studied prospectively. The aim of this study was to evaluate prospectively the prevalence of gallstones with ultrasonography and to look for markers of pigment or cholesterol stone formation in gallbladder bile. Ultrasonography was performed in 39 patients and detected gallstones in 7 patients and sludge in 3. Common bile duct and intrahepatic bile duct dilatation were observed in 16 and 13 patients, respectively. Liver biopsies were obtained in 31 patients and cirrhosis was found in 4. There were calcium bilirubinate granules in 7 of the 27 bile samples examined. Cholesterol crystals were not found in any case. The nucleation time (median: 21 days) was higher in patients with chronic pancreatitis than in patients with cholesterol stones (median: 2 days) (P < 0.001) but was not different from nucleation time in patients either free of stones (median: 21 days) or with pigment stones (median: 21 days). The cholesterol saturation index was similar in patients with chronic pancreatitis and in controls. The 2 patients with chronic pancreatitis who underwent cholecystectomy had pigment stones. Calcium bilirubinate granules were more frequent in patients with intrahepatic bile ducts dilatation (P < 0.02). In conclusion, this study demonstrates a high prevalence of cholelithiasis in chronic pancreatitis patients. Pigment stone formation could be favored by cholestasis.     

Hepatitis C virus infection facilitates gallstone formation

BACKGROUND: Bile duct damage and hepatic steatosis are two characteristic histological findings in hepatitis C virus infection; and high prevalence of hepatitis C antibody is noted in patients with cholangiocarcinoma. The purpose of the present study was to examine the relationship between biliary diseases and hepatitis C virus infection. METHODS: Persons who received a general checkup in Chang Gung Memorial Hospital between 2000 and 2002 were included. All of them had hemogram, serum biochemistry, hepatitis B surface antigen, hepatitis C antibody and ultrasonography studies. The prevalence of gallbladder stone, bile duct stone and gallbladder polyp/cholesterolosis were compared in different viral infection groups. RESULTS: Of the 28 486 persons, 22 967 were negative for both hepatitis B surface antigen and hepatitis C antibody (group NBNC), 4152 were hepatitis B surface antigen carriers (broup B), 1195 were positive for hepatitis C antibody (group C), and 172 were positive for both markers. The 379 persons (1.3%) having had cholecystectomy were considered to have gallbladder stone at the time when cholecystectomy was done. Gallbladder stone was found in 6.0% persons of group NBNC, 5.4% in group B and 11.7% in group C. The prevalence of gallbladder stone in group C was found especially high for age groups 31-40 years and 61-70 years. The prevalence of bile duct stone was higher in group C (0.4%) than in group NBNC or B (both 0.1%). Stepwise logistic regression analysis showed that age, liver cirrhosis, body mass index, hepatitis C virus infection and gender were independent factors associated with gallbladder stone. CONCLUSIONS: Hepatitis C virus infection facilitates gallstone formation.     

Trypsin level in gallbladder bile and ductitis and width of the cystic duct

BACKGROUND/AIMS: The change from laparotomy to laparoscopy for cholecystectomy has raised the question of how to manage concomitant bile duct stones. The present-day interest--and controversy--has focused on a transcystic approach reported to be feasible in 66-96% of cases, but without explaining the necessary prerequisite: the widening of the cystic duct. The cystic duct, wide mainly in patients with bile duct stones, has been reported to be highly variable: from strictured to very wide. The present study aims at comparing the trypsin level in the gallbladder bile and the cystic duct morphology and width in patients with and without bile duct stones. METHODOLOGY: A prospective series of 63 gallstone patients, 30 with and 33 without bile duct stones (controls), underwent cholecystectomy and bile duct clearance. The study includes the trypsin level in the gallbladder bile, the width and morphology of the cystic duct, and the size of the gallstones. RESULTS: The patients with bile duct stones had, in contrast to the controls, higher trypsin levels in the gallbladder bile (P < 0.001) and wider cystic ducts (P < 0.001) with more pronounced signs of chronic ductitis. CONCLUSIONS: The obtained results strongly suggest that the increased trypsin level, a sign of reflux of pancreatic juice, caused changes in the cystic duct that facilitate gallstone migration, which also ought to render a transcystic stone extraction feasible.     

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

In this chapter the epidemiology, pathogenesis, and natural history of CBD stones (choledocholithiasis) and intrahepatic stones (hepatolithiasis) have been reviewed. Gallstones are extremely common in Western countries, where the prevalence of bile-duct stones is relatively low. In contrast, primary choledocholithiasis and hepatolithiasis appear to be more frequent in East Asian countries than in Western societies, where bile-duct stones are mostly secondary to gallbladder stones passing through the cystic duct. Primary bile-duct stones are composed predominantly of calcium bilirubinate, namely brown-pigment stones. The pathogenesis of primary bile-duct stones is based upon bile stasis and infection, which are associated with bile-duct strictures, extrahepatic anomalies and biliary parasites. In contrast, secondary stones are considered to originate from gallbladder stones, and are commonly composed of cholesterol. Congenital and acquired risk factors predisposing to bile-duct stones include anatomical anomalies, genetic diseases of bilirubin and cholesterol, bacterial infection, and socio-economic problems. Bile-duct stones typical present with fever, abdominal pain, and jaundice (Charcot's triad), and in severe cases also hypotension and mental confusion (Raynold's pentad) which predicts a poor clinical outcome. Furthermore, silent cholangiocarcinoma develops in 10% of the intrahepatic stone cases even after the removal of stones, and therefore the follow-up of these cases is of clinical importance.     

Association between common bile duct stones and treated hypothyroidism

BACKGROUND/AIMS: The purpose of this study was to investigate the frequency of diagnosed hypothyroidism in patients with common bile duct stones. METHODOLOGY: The common bile duct stone group (Group I) consisted of all the patients who had verified gallstones in the common bile duct in endoscopic retrograde cholangiopancreatography during 1995. The control group (Group II) was matched for age, sex, and hospital admission. These patients did not have diagnosed gallbladder or common duct stones. In both groups there were 86 patients (56 women and 30 men). The median age in these groups was 73 (range: 22-92) years at the time of common bile duct stone diagnosis. Medical records of all patients were reviewed. RESULTS: In Group I the prevalence of previously diagnosed hypothyroidism was 7/86 (8%) compared with 1/86 (1%) in Group II (P = 0.01). Hypothyroidism was previously diagnosed only in the common bile duct stone patients (Group I) of over 60 years of age, where the prevalence was 7/66 (11%). In addition, we studied 36 consecutive gallbladder stone patients (Group III) of over 60 years, who had no evidence of common bile duct stones. Hypothyroidism had been diagnosed in them less frequently (2/36 = 6%) than in the age and hospital admission matched common bile duct stone patients (P = 0.01). Other diagnosed endocrine disorders did not differ between the study groups. CONCLUSIONS: There is a significant association between the common bile duct stones and previously diagnosed hypothyroidism. There stronger association between the common bile duct stones and hypothyroidism compared to gallbladder stones and hypothyroidism suggests a mechanism other than merely the cholesterol metabolism mediated mechanism. The 11% prevalence of previously diagnosed hypothyroidism in the common bile duct stone patients of over 60 years of age suggests all patients with common bile duct stones be screened for current thyroid dysfunction.     

经皮胆道造瘘碎石取石术治疗肝内胆管结石患者疗效分析

目的 探讨经皮胆道造瘘碎石取石术治疗肝内胆管结石患者的疗效,并对影响术后结石复发的因素进行分析。方法 2013年1月~2017年1月我院行经皮胆道造瘘取石治疗肝内胆管结石患者894例,在T管引流术后行经皮胆道造瘘碎石取石术治疗。术后行定期超声检查发现结石复发情况,应用Logistic回归分析影响患者术后结石复发的危险因素。结果 在894例患者中,结石完全取尽者844例（94.4%）;随访期间87例（9.7%）患者结石复发;单因素分析发现复发患者年龄≥60岁、胆结石最大直径≥1 cm、胆结石数目≥10个、存在胆管扩张、黄疸、胆汁细菌培养阳性和结石类型为胆色素结石或混合型结石比例显著高于未复发患者（均P<0.05）,进一步行多因素分析显示,年龄≥60岁、胆结石最大直径≥1 cm和胆结石数目≥10个为影响患者术后结石复发的独立危险因素。结论 经皮胆道造瘘碎石取石术治疗肝内胆管结石患者能取得良好的效果,取石安全有效,结石取尽率高。但对于年龄≥60岁、胆结石最大直径≥1 cm和胆结石数目≥10个有高危结石复发因素者,应密切随访,尽早发现,早期处理。     

Pigment gallstone disease

Black and brown pigment gallstones are morphologically, compositionally, and clinically distinct. Black stones form primarily in the gallbladder in sterile bile and are associated with advanced age, chronic hemolysis, alcoholism, cirrhosis, pancreatitis, and total parenteral nutrition. Brown stones form not only within the gallbladder but also within the intrahepatic and extrahepatic ducts; they are uniformly infected with enteric bacteria and are usually associated with ascending cholangitis. Brown stones are related to juxtapapillary duodenal diverticula and are the predominant type of de novo common bile duct stones. Cholecystectomy is usually curative in black pigment stone disease, whereas stones often recur after cholecystectomy for brown stone disease. The pathogenesis of black stones is probably related to nonbacterial, nonenzymatic hydrolysis of bilirubin conjugates. At the pH of bile, this results in two monohydrogenated bilirubin anions that precipitate with calcium ions. Bilirubin monoconjugates that are increased in several conditions, such as Gilbert's syndrome and chronic hemolysis, may play a pivotal role in black stone formation as a source of unconjugated monohydrogenated bilirubin and as a possible co-precipitant with calcium. The precipitation of calcium carbonate and phosphate is influenced by local gallbladder factors. Brown pigment stones are formed in bile infected with enteric bacteria that elaborate hydrolytic enzymes: beta-glucuronidase, phospholipase A, and conjugated bile acid hydrolase. The resulting anions of bilirubin and fatty acids form insoluble calcium salts. We used nb/nb mice with a chronic hemolytic anemia as a model of hemolysis-induced black stone disease. The presence of 40% bilirubin monoconjugates in mouse gallstones indicated the importance of this moiety in the pathogenesis of black stones. Other data obtained by marrow transplantation experiments in mice revealed the relative importance of genotype versus the hemolytic anemia on determinants such as biliary bile acid composition and mucin secretory glands in the mouse gallbladder neck. Additional physical chemical studies of the interaction of unconjugated bilirubin in model bile solutions will be helpful in further delineating the pathogenesis of both black and brown pigment gallstones.     

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.     

A comparative study of gallstones from children and adults using FTIR spectroscopy and fluorescence microscopy

Background

Cholelithiasis is the gallstone disease (GSD) where stones are formed in the gallbladder. The main function of the gallbladder is to concentrate bile by the absorption of water and sodium. GSD has high prevalence among elderly adults. There are three major types of gallstones found in patients, White, Black and Brown. The major chemical component of white stones is cholesterol. Black and brown stones contain different proportions of cholesterol and bilirubin. The pathogenesis of gallstones is not clearly understood. Analysis of the chemical composition of gallstones using various spectroscopic techniques offers clues to the pathogenesis of gallstones. Recent years has seen an increasing trend in the number of cases involving children. The focus of this study is on the analysis of the chemical composition of gallstones from child and adult patients using spectroscopic methods.

Methods

In this report, we present FTIR spectroscopic studies and fluorescence microscopic analysis of gallstones obtained from 67 adult and 21 child patients. The gallstones were removed during surgical operations at Soroka University Medical Center.

Results

Our results show that black stones from adults and children are rich in bilirubin. Brown stones are composed of varying amounts of bilirubin and cholesterol. Green stones removed from an adult, which is rare, was found to be composed mainly of cholesterol. Our results also indicated that cholesterol and bilirubin could be the risk factors for gallstone formation in adults and children respectively. Fluorescence micrographs showed that the Ca-bilirubinate was present in all stones in different quantities and however, Cu-bilirubinate was present only in the mixed and black stones.

Conclusions

Analysis based on FTIR suggest that the composition of black and brown stones from both children and adults are similar. Various layers of the brown stone from adults differ by having varying quantities of cholesterol and calcium carbonate. Ring patterns observed mainly in the green stone using fluorescence microscopy have relevance to the mechanism of the stone formation. Our preliminary study suggests that bilirubin and cholesterol are the main risk factors of gallstone disease.     

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.     

Gallstones and Clonorchis sinensis infection: A hospital-based case–control study in Korea

Background and Aim:  A high prevalence of intrahepatic stones in some areas of East Asia has been believed to be related with Clonorchis sinensis infection. The authors conducted a hospital-based case–control study to evaluate the role of Clonorchis sinensis infection as a risk factor for the development of gallstones in Korea.
Methods:  The cases of 138 patients with gallstones (intrahepatic 44, gallbladder 67, and extrahepatic 27) and matched controls underwent microscopy for C. sinensis , serological tests for C. sinensis using enzyme-linked immunosorbent assay, radiological examinations, and interviews concerning the history of eating raw freshwater fish. We assessed a relationship of three types of gallstones and variables regarding C. sinensis by using univariate and multivariate statistical analyses.
Results:  Univariate statistical analyses showed that radiological evidence of C. sinensis and recent history of eating raw freshwater fish were related to an increased risk of intrahepatic stones ( P  = 0.0002 and 0.0039, respectively). According to multivariate statistical analyses, radiological evidence of C. sinensis was the only risk factor for intrahepatic stones (odds ratio = 7.835; 95% confidence interval = 1.671–36.724). Any evidence regarding C. sinensis was not related to an increased risk of either gallbladder or extrahepatic stones.
Conclusion:  Radiological evidence of C. sinensis was significantly associated with intrahepatic stones.     

Nonvisualized gallbladder on oral cholecystography: implications for lithotripsy

Currently, most protocols evaluating the efficacy of gallstone lithotripsy require a visualized gallbladder on oral cholecystography (OCG). The primary purpose of the OCG is to establish that the cystic duct is patent. When the gallbladder is visualized on OCG, it can also be used to number and size gallstones accurately. Patients with non-visualization of the gallbladder on OCG are excluded from consideration for lithotripsy. The purpose of this study was to evaluate retrospectively the ultrasonographic findings (i.e., number and sizes of stones in 32 patients with nonvisualization on the OCG). In 11 patients (34%) ultrasound (US) did not detect any stone, and it is presumed that the gallbladder failed to visualize for other reasons. Six patients (19%) had one or two stones and 15 (47%) patients had more than three stones. This suggests that 20% of patients with nonvisualization of the gallbladder on OCG would otherwise be eligible for lithotripsy provided that patency of the cystic duct can be demonstrated by other means, such as computed tomographic (CT) examination with oral biliary contrast or cholescintigraphy.     

Carcinoma of the Gallbladder and Extrahepatic Bile Duct in Autopsy Cases of the Aged, with Special Reference to Its Relationship to Gallstones

To demonstrate correlation between occurrence of carcinoma and that of gallstone of the gallbladder and biliary tract, we reviewed the protocols of gallbladder and extrahepatic biliary duct carcinoma and cholelithiasis of 4,482 cases (male 2,237, female 2,245, mean age 77.7 yr) autopsied at the Department of Pathology, Tokyo Metropolitan Geriatric Hospital, during the 27 yr from 1960 to 1986. Gallbladder carcinoma was found in 94 cases, or 2.1%. The incidence was higher in the female than in the male (male 24, female 70, p less than 0.01). Gallstone of the gallbladder was found in 957 cases or 21.4%. In the male, incidences of gallbladder carcinoma and stone increased with age until the lower half of the ninety, whereas in the female, no such tendency was found after the sixties. Incidence of gallbladder carcinoma was significantly higher in the cases with cholecystolithiasis than in those without stone (p less than 0.01). Furthermore, the incidence of gallbladder stones in the cases with relatively early carcinoma was significantly higher than that of those without carcinoma (p less than 0.01). Cholesterol stones were more common than bilirubinate in the carcinoma patients. These results suggest the importance of cholecystolithiasis, especially that of the cholesterol stones, as a background factor of gallbladder carcinoma. Extrahepatic bile duct carcinomas were present in 33 cases or 0.7% (male 19, female 14, no sex preference). The incidence was significantly higher in the cases with stones than in those without stones of the extrahepatic bile ducts (p less than 0.01). However, the fact that small stones were found in the upstream portions of obstruction of biliary tracts and no stone was found at operations in the 11 operated cases suggested that stones may be secondary to the cancerous growth.     

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.     

Measurement of calcium content of gallstones by computed tomography and the relationship between gallbladder function and calcification of gallstones

To evaluate the relationship between gallbladder function and calcification of gallstones, we studied gallbladder contractility by oral cholecystography, the computed tomography (CT) number of stones for 30 gallstone patients, calcium content of 13 stones operatively extirpated, and the degree of inflammatory change in 13 surgical gallbladder specimens. There was significant correlation between the calcium content and CT numbers of stones, and 1% of the calcium content of gallstone was approximately equal to 40 Hounsfield Units (HU) of the CT number. The calcium content of stones in patients with normal gallbladder contractility was extrapolated to be below 1.5%, while that with poor contractility ranged from 0% to 21%. Additionally there is a possibility that calcium content increases, related to the inflammatory change of gallbladder. Hence our results suggested that measurement of the CT number of stones is useful to evaluate the calcium content of gallstones, and that the gallbladder contractility could be one of the factors to influence calcification of stones.