Relation between the risk of gallstone pancreatitis and characteristics of gallstone in Korea

BACKGROUND/AIMS: Pancreatitis is a serious complication of patients with gallstones. However, risk factors of gallstone pancreatitis were unpredictable until recently. In Korea, characteristics of gallstones are different from Western countries. The present study was designed to determine differences in the risk of gallstone pancreatitis and characteristics of gallstones in Korean patients. METHODOLOGY: Clinical data were collected on patients undergoing laparoscopic cholecystectomy. The physical characteristics of gallstones recovered at surgery were also recorded. Patients with gallstone pancreatitis were compared with patients who had uncomplicated biliary pain. RESULTS: In a logistic regression model, acute gallstone pancreatitis was associated with a stone diameter of less than 5 mm (odds ratio: 3.3695; P = 0.0352) and with stone number of more than 20 (odds ratio: 3.8686; P = 0.0361). No other variable, including pigment stone, age, and sex, remained statistically significant in the adjusted analysis (P > 0.05). CONCLUSIONS: Patients with at least 1 gallstone smaller than 5 mm in diameter and stone number more than 20 each have a more than 3-fold increased risk of presenting with acute gallstone pancreatitis. The composition of gallstones, especially pigment stones, was not an important risk factor in gallstone pancreatitis in Korean patients with stones having a different composition than those from Western countries.     

Clinical Correlates of Gallstone Composition: Distinguishing Pigment from Cholesterol Stones

Objectives: The prevalence of cholelithiasis has been established in population-based surveys employing ultrasonography, and major risk factors have been identified. However, the clinical and epidemiological features that distinguish patients with pigment gallstones from those with cholesterol stones have received little attention. Methods: We prospectively surveyed 551 patients undergoing cholecystectomy for gallstones at two teaching hospitals. Clinical and epidemiological data were collected during patient interviews and by chart review. Gallstones were collected at surgery; physical measurements were recorded, and stone composition was determined by visual inspection and infrared spectroscopy. Results: Patients with pigment stones were older than patients with cholesterol stones ( p < 0.00001). Almost all patients under age 40 yr old had cholesterol stones, but most patients over 70 had pigment stones. Cirrhosis was strongly associated with pigment gallstones (p < 0.00001), although alcohol consumption was unrelated. Univariate analyses suggested associations of stone composition with male sex, diabetes mellitus, educational attainment, and use of thiazides or oral contraceptives, but these were not significant in a logistic regression that adjusted for age, cirrhosis, and other variables. Patients with pigment cholelithiasis had stones that were generally smaller in diameter and fewer in number than those with cholesterol stones. Canclusions: Compared to patients with cholesterol gallstones, those with pigment stones are older and more likely to have a diagnosis of cirrhosis. In addition, their stones are smaller in size and fewer in number than those from patients with cholesterol cholelithiasis.     

Polarizing microscopy of partially dissolved gallstone powder: A simple technique for studying gallstone composition

Abstract A quick and reliable method for estimating the proportion of constituents of a stone may be useful in determining the prevalence of chemical type of gallstones in different geographic areas or ethnic groups. Chemical and infrared spectroscopy estimation facilities are not commonly available in many parts of the world and visual inspection may not be reliable for scientific purposes. To investigate whether identification of microcrystalline solids in partially dissolved stone powder could accurately predict the chemical nature of the gallstone we undertook a blind study on 40 samples of gallstones and compared our results with those of visual inspection and quantitative infrared spectroscopy. There were 29 cholesterol stones (mean cholesterol 83.4 ± 7.5%), six intermediate cholesterol stones (mean cholesterol 48.0 ± 21.2%) and five pigment stones (mean cholesterol 14.3 ± 4.3%) as determined by quantitative infrared spectroscopy. Microscopic examination of partially dissolved gallstone powder in ethanol correctly identified all 29 cholesterol gallstones (sensitivity 100%, specificity 92%), four of six intermediate cholesterol stones (sensitivity 67%, specificity 100%) and all five pigment stones (sensitivity 100%, specificity 97%). It also detected microspheroliths of calcium carbonate in 14 of 16 calcium carbonate containing gallstones (sensitivity 88%, specificity 100%). The chemical grouping of stones on the basis of microscopic examination was correct in 37 (93%) of 40 samples and was especially useful in identifying 'intermediate' cholesterol stones which cannot be recognized by visual inspection. Thus microscopic examination of powdered gallstones appears to be a simple and reliable method of determining gallstone composition.     

Pigment vs cholesterol cholelithiasis: Comparison of stone and bile composition

This report presents a comparative study of gallstone and gallbladder bile composition from 100 unselected American patients, 23 with pigment and 77 with cholesterol cholelithiasis. Cholesterol stones were predominantly composed of cholesterol, whereas pigment stones were mainly composed of an unidentified residue, bilirubin, and bile salts. The residue in pigment stones was not calcium bilirubinate, which sharply contrasts with the composition of bile pigment calcium stones found in Japanese subjects. Bile composition of the two groups differed in that the cholesterol content of biles surrounding pigment stones was significantly less than that of biles surrounding cholesterol stones. Bilirubin in biles was conjugated, but the pigment extracted from stones was unconjugated bilirubin. This study indicates that (1) pigment stones account for an appreciable percentage of gallstone specimens found at cholecystectomy, and (2) pigment stone formation involves the precipitation of bilirubin, bile salts, and unidentified material which is not calcium bilirubinate.Presented at the meetings of the American Federation of Clinical Research, April 29, 1973, Atlantic City, New Jersey. Supported in part by NIH grant AM 14543. Dr. Trotman is a former NIH trainee under NIH grant AM 05462 and currently a recipient of a Macy Foundation Faculty Fellowship.     

Cholesterol and pigment gallstones in Northern India

Two hundred one consecutive patients with gallstone disease who had undergone cholecystectomy were analyzed to determine the relative frequency of occurrence of cholesterol and pigment gallstones and to identify distinguishing features of the two stone types. Cholesterol stones (CS) formed the majority (94%) of gallstones. There were no distinctive clinical, biochemical, or radiological features of CS or pigment stones (PS). However, CS were found significantly more often than PS (P less than 0.05) in multiparous women leading a sedentary life-style. Although multiplicity of gallstones was somewhat commoner with CS (P less than 0.05) and radiopacity with PS (P less than 0.05) as compared with the other stone type, these differences were certainly not discriminatory between CS and PS.     

Gallstone characteristics in mexican americans and non-hispanic whites

Mexican Americans have an elevated risk of gallstones. Their increased rates may be due to genetic admixture with Native Americans, who have extremely high prevalences of cholelithiasis. Native Americans are believed to have almost exclusively cholesterol stones, whereas only 73% of non-Hispanics are reported to have such stones. Hence we hypothesized that Mexican Americans would have a higher proportion of cholesterol stones than would non-Hispanic whites. We interviewed 398 Mexican Americans and 93 non-Hispanic whites undergoing cholecystectomy and analyzed the composition of their gallstones. Mexican Americans were younger than non-Hispanic whites (P<0.05). However, the age-sex standardized proportion of cholesterol stones was 89.7% in Mexican Americans and 87.2% in non-Hispanic whites. We conclude that Mexican Americans and non-Hispanic whites have gallstones of similar composition. The higher stone prevalence of Mexican Americans may be due to factors that predispose to both cholesterol and pigment stones.     

Biliary lipid,bile acid composition,and dietary correlations in Micmac Indian women

The precursor state for cholesterol gallstone formation is cholesterol-saturated bile. We studied a high-risk group for cholesterol gallstones to determine whether dietary variables affect bile cholesterol. Bile samples were analyzed from 46 Micmac Indian women without gallstones and 13 with gallstones for molar percentage cholesterol (MPC) and bile acid composition. The data were analyzed by multiple regression analysis with MPC as the dependent variable and the dietary variables, obtained from four consecutive-day food records, and biliary bile acid composition as the independent variables. In the 46 women without gallstones, obesity, calorie range/calorie intake, and iron and calcium intake were, in their order of importance, significant factors. In normal weight subjects (ponderal index>12.5) relative obesity was still a significant correlate. Obesity and iron intake were positive correlates while calorie range/calorie intake and calcium intake varied inversely. When the effect of obesity was controlled, these factors were still significant in this group, as they were in the gallstone group. In addition, the duration of overnight fast obtained by history, together with the proportions of deoxycholic and chenodeoxycholic acids in bile were correlates of the biliary molar percentage cholesterol.Presented in part at the Tenth International Congress of Gastroenterology, Budapest, June 1976, and at the Bile Lipid Seminar, American Gastroenterology Association, Given Institute, Aspen, Colorado, August 1977.This project was supported under National Health Research and Development Project Number 603-1008-30, Health and Welfare Canada.     

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.     

Hepatic cholesterol and bile acid synthesis in Japanese patients with cholesterol gallstones

In Japan the composition of gallstones is changing rapidly from the once-predominant brownpigment stones to cholesterol ones. The present work was undertaken to clarify the mechanism of cholesterol supersaturated bile production in Japanese patients with cholesterol gallstones. In 26 non-obese and normolipidemic patients (11 with cholesterol gallstones, 8 with black- or brown-pigment gallstones, 7 without gallstones) a liver biopsy and hepatic bile were surgically obtained under standardized conditions. The cholesterol saturation of hepatic bile was significantly higher in cholesterol gallstone patients than in gallstone-free controls (195 ±10 vs. 146 ±8%, respectively; P < 0.01). The microsomal activities of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme for cholesterol synthesis, cholesterol 7 α-hydroxylase, the rate-limiting enzyme for bile acid synthesis, and 7 α-hydroxy-4-cholesten-3-one 12 α-hydroxylase (12 α-hydroxylase), the rate-limiting enzyme for cholic acid synthesis, were assayed simultaneously in the same subjects. There were positive correlations between HMG-CoA reductase and cholesterol 7 α-hydroxylase activities (Rs = 0.62, P < 0.005), and between cholesterol 7 α-hydroxylase and 12 α-hydroxylase activities (Rs = 0.44, P < 0.05) in all subjects, irrespective of the existence of gallstones. The activities of the three rate-limiting enzymes did not differ significantly among the three groups (cholesterol stone, pigment stone and stone-free). In conclusion, the cholesterol supersaturation of hepatic bile in nonobese and normolipidemic Japanese patients with cholesterol gallstones does not result from an increased hepatic cholesterol synthesis or a decreased bile acid synthesis. This study was supported in part by a Grant-in-Aid for Scientific Research (No. 02454226) from the Ministry of Education, Science and Culture of Japan, and a grant from University of Tsukuba Project Research.     

Composition of pigmented centers of cholesterol gallstones

Most cholesterol gallstones have visually pigmented centers, but it is unclear whether this represents simple co-precipitation of pigment with cholesterol during stone nidation or nidation on a true pigment stone center. To clarify this issue, we selected from among 67 sets of cholesterol gallstones, 12 sets with the most conspicuously pigmented centers. The composition of the centers and the peripheries of these 12 stones was analyzed using infrared spectroscopy and compared with that of 10 black pigment gallstones. The pigmented centers of cholesterol stones contained 80.1 +/- 7.9% (mean +/- S.E.) cholesterol, 6.2 +/- 3.4% calcium bilirubinate (only 4 of the 12 centers had measurable calcium bilirubinate), trace amounts of calcium phosphate and no calcium carbonate or calcium palmitate. The peripheral areas of the cholesterol stones contained 91.6 +/- 2.3% cholesterol and no detectable calcium salts. For comparison, the composition of the centers of 10 black pigment gallstones was 13.5 +/- 2.2% cholesterol, 28.2 +/- 5.3% calcium bilirubinate, 5.5 +/- 2.4% calcium phosphate and 10.6 +/- 5.8% calcium carbonate. The composition of only one cholesterol stone center (15.8% cholesterol, 26.8% calcium bilirubinate) resembled that of a pigment stone, but even this center differed from that of a typical pigment stone in that it contained only a trace amount of calcium phosphate and no calcium carbonate. Thus, the chemical composition of pigmented centers of cholesterol gallstones is quantitatively different from that of black pigment stones, suggesting that cholesterol gallstones do not form on a pigment stone nidus.     

Possible role of a defect in hepatic bilirubin glucuronidation in the initiation of cholesterol gallstones

Abnormally low activity of hepatic bilirubin UDP-glucuronosyltransferase was found in 25% of 81 unselected patients with gallstones, as compared with only 3% in 35 controls. At the time of cholecystectomy, the stones were taken for analysis in 48 of 81 patients, and a bile sample was obtained in 42 of them. Among the stones, 75% were cholesterol stones, 15% pigment stones, and 10% 'intermediate' stones. Low hepatic conjugating activity was not preferentially associated with a given type of stone. No relation was found between the enzymic deficiency and the biliary cholesterol saturation index. A high proportion of biliary bilirubin monoglucuronide (over 40%) was found in four of seven patients with low transferase activity, as was earlier demonstrated in patients with overt Gilbert's syndrome. Raised biliary bilirubin monoglucuronide was also found in three patients, out of 46, who had normal transferase but raised biliary beta-glucuronidase activity. There was no evidence that deficient bilirubin conjugation could be a consequence of gallstones: the activity of another hepatic microsomal enzyme, glucose 6-phosphatase, taken as a reference, was measured in 12 patients and was always normal. Taking into account the very high frequency of a bilirubin centre in the cholesterol stones (87% of the cases in the present series), it is suggested that the increased proportion in poorly soluble biliary bilirubin monoglucuronide, which was associated with defective conjugation, could act as a trigger for gallstone initiation, regardless of the final composition of the stone.     

Gallstones in patients with liver cirrhosis: Incidence,etiology, clinical and therapeutical aspects

Gallstones occur in about one third of the patients having liver cirrhosis. Pigment gallstones are the most frequent type, while cholesterol stones represent about 15% of all stones in cirrhotics. Increased secretion of unconjugated bilirubin, increased hydrolysis of conjugated bilirubin in the bile, reduced secretion of bile acids and phospholipds in bile favor pigment lithogenesis in cirrhotics. Gallbladder hypomotility also contributes to lithogenesis. The most recent data regarding risk factors for gallstones are presented. Gallstone prevalence increases with age, with a ratio male/female higher than in the general population. Chronic alcoholism, viral C cirrhosis, and non-alcoholic fatty liver disease are the underlying liver diseases most often associated with gallstones. Gallstones are often asymptomatic, and discovered incidentally. If asymptomatic, expectant management is recommended, as for asymptomatic gallstones in the general population. However, a closer follow-up of these patients is necessary in order to earlier treat symptoms or complications. For symptomatic stones, laparoscopic cholecystectomy has become the therapy of choice. Child-Pugh class and MELD score are the best predictors of outcome after cholecystectomy. Patients with severe liver disease are at highest surgical risk, therefore gallstone complications should be treated using noninvasive or minimally invasive procedures, until stabilization of the patient condition.     

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.     

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.     

Biliary pronucleating proteins and apolipoprotein E in cholesterol and pigment stone patients

BACKGROUND/AIMS: Although cholesterol gallstone patients exhibit higher biliary cholesterol saturation than pigment stone patients, underlying mechanisms that affect stone type are unknown. We hypothesized that pronucleating proteins, hydrophobic bile salts or apolipoprotein E genotype affect stone type. We therefore compared these putative factors in cholesterol and pigment stone patients.METHODS: In 74 cholesterol and 12 pigment stone patients, bile lipids, various pronucleating proteins, crystallization and apolipoprotein E genotype were determined.RESULTS: Crystallization was enhanced, and cholesterol saturation higher in case of cholesterol stones, without any difference in bile salt composition. Concentrations of mucin (0.91+/-0.08 versus 0.31+/-0.06 mg/ml: P<0.0001), protein, IgM, IgG, IgA, haptoglobin, alpha1-acid glycoprotein and haptoglobin were 2-6-fold higher in cholesterol stone patients. Twenty cholesterol stone pts (27%) but only one pigment stone pt (8%) had at least one epsilon4 allele. There was a significant difference in allele frequencies between both groups (cholesterol stones similar to Dutch population: epsilon2 0.074, epsilon3 0.770, epsilon4 0.156: pigment stones: epsilon2 0.250, epsilon3 0.708, epsilon4 0.042).CONCLUSIONS: Various pronucleating biliary proteins are markedly higher in cholesterol than pigment stone patients. Also, apolipoprotein E genotype differs between cholesterol and pigment stone patients. These factors may affect gallstone type.     

胆总管结石十二指肠镜治疗后复发因素研究

目的 探讨胆总管结石经ERCP治疗后复发的相关因素.方法 选择资料完整经ERCP治疗的胆总管结石患者,共802例,其中297例伴胆囊结石,222例胆囊已切除,283例胆囊无结石,统计复发频度并对复发因素进行单变量和多变量logistic回归分析.结果 802例患者平均随访84.8个月,92例（11.5%）结石复发.胆囊结石,胆总管直径≥1.5 cm,机械碎石及胆管角度≤120°在单因素及多因素分析中均显示为复发因素;胆固醇结石,乳头狭窄或Oddi括约肌功能障碍在多因素分析中为复发因素;胆囊切除,毕Ⅱ式胃大部切除,结石≥1.5 cm及多发结石在单因素分析中为复发因素.结论 ERCP治疗胆总管结石的病例中胆囊结石,胆总管直径≥1.5 cm,机械碎石及胆管角度≤120°可能为主要的复发因素;胆囊切除,毕Ⅱ式胃大部切除,乳头狭窄或Oddi括约肌功能障碍,结石≥1.5 cm,胆固醇结石及多发结石也是复发相关因素.     

Gallstones in obesity and weight loss

The prevalence of cholesterol gallstones is increased in obese persons. The risk is especially high in those with the highest body mass index (relative risk 5-6). Weight loss further increases the risk of gallstones: the prevalence of new gallstones reaches 10-12% after 8-16 weeks of low-calorie diet and more than 30% within 12-18 months after gastric by-pass surgery. About one-third of the stones are symptomatic. The increased prevalence of stones is mostly due to supersaturation of bile with cholesterol, because of an increased synthesis by the liver and secretion into bile. Saturation is further increased during weight loss. It returns toward normal after weight stabilization at a lower level, allowing spontaneous stone dissolution in some cases. Identified risk factors for gallstones during weight loss are a relative loss of weight greater than 24% of initial body weight, a rate of weight loss greater than 1.5 kg per week, a very low calorie diet with no fat, a long overnight fast period and a high serum triglyceride level. Ursodeoxycholic acid decreases cholesterol saturation of bile and gallstone incidence during weight loss. Other preventive measures include a control of weight loss rate, a reduction of the length of overnight fast, and maintenance of a small amount of fat in the diet.     

Macronutrients and insulin resistance in cholesterol gallstone disease

Cholelithiasis is a major source of digestive morbidity worldwide. Cholesterol stones account for the majority of gallstones in the United States and other Western countries. The pathogenesis of cholesterol gallstone disease is multifactorial with key factors including cholesterol supersaturation of bile, altered biliary motility, and nucleation and growth of cholesterol crystals. Increasing evidence suggests that many, but not all, causative factors of cholesterol gallstones are related to insulin resistance which, in association with obesity, has reached an epidemic level worldwide. Experimental studies show that hyperinsulinemia, a key feature of insulin resistance, may cause increased hepatic cholesterol secretion and cholesterol supersaturation of bile and gallbladder dysmotility, and thereby may enhance gallstone formation. Insulin resistance syndrome can be modified by environmental factors, including dietary factors. The impact of diet on insulin sensitivity is mediated by both dietary composition and its energy content. The contribution of specific dietary elements to the prevalence and incidence of cholesterol gallstone disease has been explored in animal and human studies. There is considerable evidence to suggest that different types of fatty acids, independent of the total amount of fat consumption, affect insulin sensitivity and cholesterol gallstone disease differently. The effects of salt intake, consumption of protein and carbohydrates, and alcohol drinking on insulin resistance are controversial. Additional intervention trials and controlled experimental feeding studies are needed to further clarify these relationships and to provide useful prophylactic and therapeutic strategies.     

High vesicular cholesterol and protein in bile are associated with formation of cholesterol but not pigment gallstones

To examine the differentiating parameters between cholesterol and pigment gallstones, we compared the nucleation times, concentrations of biliary lipid and protein, and the distribution of vesicular cholesterol in gallbladder bile of 16 patients with cholesterol, eight patients with black pigment gallstones, and nine gallstone-free control patients. Cholesterol monohydrate crystals were present in the fresh bile of only the cholesterol gallstone group. The nucleation time was significantly faster in the cholesterol stone group (3.3±3.2 days) than in the other two groups (pigment stone: 15.8±6.6, control: 16.9±5.7). The cholesterol saturation indices and the distribution of vesicular cholesterol were significantly higher in the cholesterol gallstone group than those in the other two groups. The total biliary protein concentration was significantly (P<0.01) higher in the cholesterol gallstone group [2.57±1.91 (sd) mg/ml] than that in the black pigment stone group (1.09±0.59). All parameters in patients with black pigment gallstone were essentially similar to the controls. We conclude that the presence of cholesterol crystals, rapid nucleation time, high vesicular cholesterol distribution, elevated cholesterol saturation index, and high protein concentration are associated with cholesterol gallstones but not with black pigment gallstones.     

Pigment vs cholesterol cholelithiasis

Although pigment (calcium bilirubinate) gallstones in Japanese subjects are associated with bacterial infection, the role of infection in Americans with pigment gallstones has not been assessed. Anaerobic and aerobic cultures of gallbladder bile, stone, and wall were obtained at cholecystectomy from nine patients with pigment stones and 25 with cholesterol stones. Among pigment-stone subjects, only 1 of 9 grew organisms in greater than 10⁵ colony-forming units (CFU)/ml or g in gallbladder bile or wall. Likewise, growth greater than 10⁵ CFU/ml or g was present in only 1 of 26 biles and 2 of 26 walls from cholesterol-stone patients.Propionibacterium acnes was found in less than 10⁵ CFU/g or ml in at least 1 specimen from 6 of 9 pigment- and 12 of 26 cholesterol-stone patients. This organism was considered a contaminant because propionic acid concentrations in bile, an index of active bacterial metabolism, were similar in specimens with or without low-titer growth. The concentrations of bile salts, phospholipids, cholesterol, and bilirubin in gall-bladder bile was unaffected by the type of bacteria in low-titer growth. But the lipid concentrations were markedly depressed in two biles with bacterial growth greater than 10⁵ CFU/ml. The molar ratio of bile salts and phospholipids to cholesterol was significantly higher in biles surrounding pigment stones than those surrounding cholesterol stones (P<0.01). We conclude that significant bacterial infection (>10⁵ CFU/ml) is not associated with pigment or cholesterol stones in asymptomatic American subjects at cholecystectomy. These data suggest that pigment-stone formation in the United States is not primarily related to bacterial alteration of bile composition, as the experience with Japanese patients would suggest.Supported by NIH Grant AM-16549 and institutional funds of the Veterans Administration.Presented in part at the 77th Annual Meeting of the American Society for Microbiology, New Orleans, May 8–13, 1977.