Cigarette smoking,alcohol use,and gallstone risk in Japanese men

BACKGROUND/AIM: Results of epidemiological studies concerning the association between smoking and alcohol use and gallstone risk are inconsistent. We examined the relation of smoking and alcohol use to gallstone disease in Japanese men. METHODS: We investigated 174 cases having gallstones as determined by ultrasonography, 104 cases of postcholecystectomy state, and 6,906 controls having a normal gallbladder in the consecutive series of 7,637 men aged 48-59 years receiving a retirement health examination at four hospitals of the Self-Defense Forces from 1986 to 1994. Fifty men had been aware of having gallstones. Known gallstones and postcholecystectomy state were combined as known gallstone disease. Smoking and drinking habits were ascertained by a self-administered questionnaire. Statistical adjustment was made for body mass index, glucose tolerance status, Self-Defense Forces rank, hospital, and either cigarette smoking or alcohol use. RESULTS: Cigarette smoking was not measurably associated with either prevalent gallstones or postcholecystectomy state, nor with either newly diagnosed gallstones or known gallstone disease. Alcohol use was related to a significant decrease in the prevalence odds of both gallstones and postcholecystectomy state, and the decrease was slightly more profound for known gallstone disease. CONCLUSIONS: Cigarette smoking is probably unrelated to the gallstone risk, and alcohol consumption seems to confer protection against gallstone formation.     

Prospective Study of Alcohol Consumption Patterns in Relation to Symptomatic Gallstone Disease in Men

Although the association between alcohol intake and gallstone disease has been characterized previously, the relation between alcohol consumption patterns, specific types of alcoholic beverages, and risk for cholelithiasis has not been addressed systematically. These issues were examined prospectively in a cohort of men who were free from symptomatic gallstone disease in 1986 and were followed to 1996. During follow-up, 2.4% of the men reported newly symptomatic gallstones that were diagnosed by ultrasonography or x-ray, or a cholecystectomy. After adjusting for other known or suspected risk factors, an increase in the amount of alcohol consumed was associated with a decreased risk of symptomatic gallstone disease. An increase in frequency of alcohol consumption also was related to decreased risk. Combining the reports of quantity and frequency of alcohol intake, a consumption pattern that reflected frequent intake (5-7 days/week) of any given amount of alcohol was associated with a decreased risk, as compared with nondrinkers. In contrast, infrequent alcohol intake (1-2 days/week) showed no significant association with risk. All alcoholic beverage types were inversely associated with risk of symptomatic gallstone disease, independent of patterns of consumption. These results suggest that frequent, moderate intake of alcohol decreases the risk for symptomatic gallstone disease, in contrast to infrequent or episodic alcohol intake. Recommendations regarding the benefit of moderate quantities of alcohol for gallstone discase should be weighed against the potential health hazards of alcohol consumption.     

Gallstones and Plasma Lipids in a Danish Population

A cross-sectional study of gallstone disease, ascertained by ultrasonography, comprised 4581 men and women of Danish origin, aged 30, 40,50, and 60 years, of whom 3608 (79%) attended the investigation. The prevalence was assessed in relation to plasma concentrations of total cholesterol, high-density-lipoprotein cholesterol, low-density-lipoprotein cholesterol, and triglyceride. In the univariate analysis gallstone disease was significantly associated with high triglyceride and low high-density-lipoprotein cholesterol. No significant association among gallstones and total cholesterol and low-density-lipoprotein cholesterol was seen. In multivariate analyses triglyceride lost its significant association with gallstone disease, whereas total cholesterol became negatively associated with gallstones. This was seen for both the high-density-lipoprotein and the low-density-lipoprotein fraction of cholesterol. The difficulties in analysing present plasma lipid status with gallstone prevalence must be stressed. Looking only at small gallstones, which could represent newly formed stones, a change from a negative to a positive association between gallstone and both low-density-lipoprotein cholesterol and total cholesterol was seen.     

HCV infection is a risk factor for gallstone disease in liver cirrhosis: an Italian epidemiological survey

We assessed the prevalence of gallbladder disease (i.e. gallstones plus cholecystectomy) among patients with liver disease and its association with the severity and aetiology of hepatic injury. Subjects, referred to 79 Italian hospitals, were enrolled in a 6-month period. The independent effect of the severity and aetiology of liver disease on gallstone disease prevalence was assessed by multiple logistic regression analysis. Overall, 4867 subjects tested anti-hepatitis C virus (HCV) positive alone, 839 were hepatitis B virus surface antigen (HBsAg) alone, and 652 had an excessive alcohol intake. The prevalence of gallstone disease was 23.3% in anti-HCV-positive patients, 12.4% in HBsAg positive and 24.2% in subjects reporting excessive alcohol intake, respectively. Gallstone disease prevalence increased by age in each aetiological category. The proportion of patients with gallstone disease who had a cholecystectomy was the highest in HCV+ subjects. After adjusting for the confounding effect of age and body mass index, compared with patients with less severe liver disease, subjects with HCV-related cirrhosis, but not those with alcohol-related cirrhosis, were more likely to have gallstone disease. Subjects with HCV-related cirrhosis (OR 2.13, 95% CI: 1.38-3.26) were more likely to have gallstone disease when compared with those with HBV-related cirrhosis. HCV infection is a risk factor for gallstone disease. In Italy, the high prevalence of HCV infection among cirrhotic patients has important implications, as cholecystectomy in these subjects is associated with high risk of morbidity and mortality.     

Gallstones and plasma lipids in a Danish population

A cross-sectional study of gallstone disease, ascertained by ultrasonography, comprised 4581 men and women of Danish origin, aged 30, 40, 50, and 60 years, of whom 3608 (79%) attended the investigation. The prevalence was assessed in relation to plasma concentrations of total cholesterol, high-density-lipoprotein cholesterol, low-density-lipoprotein cholesterol, and triglyceride. In the univariate analysis gallstone disease was significantly associated with high triglyceride and low high-density-lipoprotein cholesterol. No significant association among gallstones and total cholesterol and low-density-lipoprotein cholesterol was seen. In multivariate analyses triglyceride lost its significant association with gallstone disease, whereas total cholesterol became negatively associated with gallstones. This was seen for both the high-density-lipoprotein and the low-density-lipoprotein fraction of cholesterol. The difficulties in analysing present plasma lipid status with gallstone prevalence must be stressed. Looking only at small gallstones, which could represent newly formed stones, a change from a negative to a positive association between gallstone and both low-density-lipoprotein cholesterol and total cholesterol was seen.     

Prevalence of cholesterol gallstones positively correlates with per capita daily calorie intake

BACKGROUND/AIMS: Gallstone composition has changed over the past decades in East Asian countries with a prominent increase in the prevalence of cholesterol gallstones. This trend is possibly due to the westernization of dietary habits. This study was undertaken to delineate the changing trends in gallstone composition in Japan since the 1920s and to assess dietary influences on gallstone composition. METHODOLOGY: Between 1971 and 1999, 1264 Japanese patients underwent cholecystectomy for gallstone disease in Niigata University Medical Hospital. Gallbladder stones retrieved from each patient were classified into four types by gross inspection of the cut surface and infrared spectroscopy: cholesterol stone, black pigment stone, brown pigment stone, and other stones. The literature was reviewed to find both changing trends in gallstone composition before 1971 and dietary changes since 1950 in Japan. RESULTS: The prevalence of cholesterol gallstones among Japanese patients undergoing cholecystectomy increased steadily until the 1970s and declined thereafter (P<0.001). Among dietary factors, only per capita daily total calorie intake strongly correlated with cholesterol gallstone prevalence (r=0.93, P=0.02). CONCLUSIONS: During the 20th century, the prevalence of cholesterol gallstones in the Japanese population increased steadily until the 1970s declining thereafter. Per capita daily total calorie intake appears to be the predominant dietary factor affecting cholesterol gallstone prevalence.     

Gallstone Prevalence in Relation to Smoking,Alcohol, Coffee Consumption,and Nutrition: The Ulm Gallstone Study

Background: Besides considering well-known risk factors for the development of gallbladder stones, such as age, sex, fecundity, and hereditary predisposition, efforts at prevention have focused increasingly on other factors, such as nicotine, alcohol, and caffeine consumption, as well as general nutrition, which may be modified. Methods: A total of 1116 blood donors were examined between April 1994 and February 1995 in the central blood bank of the German Red Cross in Ulm, Germany. Each subject received a questionnaire and underwent to an upper abdominal ultrasound examination. Results: Gallbladder stone disease (current cholecystolithiasis and history of cholecystectomy) was detected in 5.8% of the men and 6.3% of the women. Neither regularity nor number of daily meals correlated with the frequency of gallstone disease. Vegetarians (n = 48), as a group, were not found to have gallstones. In relation to the consumption of alcohol, tobacco, or caffeine, a slightly higher prevalence of cholecystolithiasis was found only in heavy drinkers of coffee (P= 0.051; odds ratio (OR), 1.083; 95% confidence interval (CI), 0.999, 1.174). Conclusion: Results of the present study do not show a definite relationship between nutritional factors and the consumption of alcohol, tobacco, or caffeine and an increased prevalence of gallbladder stone disease.     

A population study on the prevalence of gallstone disease: the Sirmione Study

The prevalence of gallstone disease (cholelithiasis and previous cholecystectomy for gallstones) in the population of the town of Sirmione, Italy, examined by ultrasonography, was 6.7% in men and 14.6% in women, ranging from 18 to 65 yr of age (overall prevalence = 11%). The prevalence of cholelithiasis in the same age span was 6.9% (4.5% in men and 8.9% in women). Prevalence of cholelithiasis increased with age in both sexes. Twenty-two percent of gallstone subjects suffered from biliary pain vs. 2% of subjects without gallstones. No difference was observed in the frequency of nonspecific symptoms between subjects with and without gallstones. Of the 132 gallstone subjects, 108 (82%) were not aware of having gallstones prior to the study. Prevalence of gallstone disease was found to be higher in obese and hypertriglyceridemic subjects and to increase with the number of pregnancies.     

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.     

Gallstones and colorectal cancer—There is a relationship,but it is hardly due to cholecystectomy

The prevalence of gallstone disease in 145 consecutive patients with colorectal cancer was compared with gallstone prevalence in 4,159 subjects randomly selected from a population. The group of patients had a significantly higher prevalence of gallstone disease than the population (odds ratio = 1.59; 95 percent confidence limits 1.04-2.45), whereas cholecystectomies occurred with equal frequency in the two groups. There was a nonsignificant trend toward more right-sided cancers in patients with gallstones than in patients without. These results, together with available literature, give substantial evidence for an association between gallstones and colorectal cancer, an association which is not due to cholecystectomy being a predisposing factor to colorectal cancer. Sporadic findings of an association between cholecystectomy and colorectal cancer can be explained by the above relationship.     

Gallstones,gallbladder disease,and pancreatitis: cross-sectional and 2-year data from the Swedish Obese Subjects (SOS) and SOS reference studies

OBJECTIVES: Obesity and weight loss have been associated with gallstone disease. There is also an association between gallstones and pancreatitis. We investigated cross-sectional relationships between body mass index (BMI), body fat distribution, and prevalence of gallstones, gallbladder disease, and pancreatitis in men and women. Furthermore, 2-yr incidences of these disorders were examined in relation to changes in weight and body fat distribution after surgical and conventional obesity treatment. METHODS: Self-administered questionnaires were used to assess biliary and pancreatic disease. In the cross-sectional investigation, 6328 obese patients and 1135 randomly selected reference individuals were used. Longitudinally, 1422 operated and 1260 conventionally treated patients were examined. RESULTS: Obese subjects had significantly higher prevalence of cholelithiasis, cholecystitis, cholecystectomies, and pancreatitis as compared with the reference population. In women, BMI and waist-hip ratio (WHR) were independently related to an increased biliary disease prevalence. In men, only BMI was independently associated with biliary disease. Compared with conventional treatment, obesity surgery significantly increased the incidence of cholelithiasis, cholecystitis, and cholecystectomies in men. There was no incidence difference among women. In both genders, weight loss, but not change in WHR, was related to an increased incidence of biliary disease. CONCLUSIONS: This study showed an increased prevalence of gallstones, gallbladder disease, and pancreatitis in the obese. Biliary disease was related to BMI and WHR in women, but only to BMI in men. Weight loss, but not change in WHR, increased the risk of biliary disease in both genders.     

The ultrasound survey of gallstone diseases of patients infected with Clonorchis sinensis in southern Taiwan

Ultrasonography was used to evaluate the relationship between the gallstone diseases and infection with Clonorchis sinensis. One thousand and ninety-one Hakkanese in southern Taiwan were examined in the past 2 years. Among the 947 cases infected with clonorchiasis, 89 cases were found to have gallstone diseases, which included gallbladder stones (85 cases), common bile duct stones (three cases) and one case of intrahepatic duct stone, indicating a prevalence of 8.97, 0.32 and 0.11% respectively. The overall prevalence of gallstones in the infected group was 9.39%. In the other 144 cases without clonorchiasis infection, eight patients were found to have gallstone disease, which included gallbladder stone (six cases) and intrahepatic duct stone (two cases), indicating an incidence of gallstone of 4.16 and 1.39% respectively. The overall prevalence of gallstones in the non-infected group was 5.56%. A comparison between the infected and non-infected groups was made and showed no significant relationship between gallstone disease and clonorchiasis.     

Nonsteroidal antiinflammatory drug use and gallstone disease prevalence: a case-control study

Objectives: Conflicting results on the relationship between gallstone disease and the use of nonsteroidal antiinflammatory drugs (NSAIDs) have been reported, but studies on the effect of NSAID use in populations not selected on the basis of a high risk for gallstone development are still lacking.
Methods: We conducted a case-control study involving 216 patients, regular NSAID users (43 men and 173 women) consecutively admitted to a rheumatology department, suffering from rheumatoid arthritis ( n = 147 ), osteoarthritis ( n = 49 ), and ankylosing spondylitis ( n = 20 ). Two-hundred sixteen patients who were not NSAID users, matched for gender, age, and body mass index, consecutively admitted to a medical department for various medical pathologies, acted as a control group. All patients underwent upper abdomen ultrasonography.
Results: The overall prevalence of gallstones was similar in the two groups: 24.0% in NSAID users (15.7% actual stones and 8.3% previous cholecystectomy) and 21.3% in controls (13.9% gallstones and 7.4% cholecystectomy). The prevalence of gallstone disease was significantly higher in women than in men, and the mean age was higher in gallstone patients than in gallstone-free patients, in both groups. No significant differences in type and duration of arthritis condition, type and dose of NSAID taken, and duration of treatment between gallstone patients and gallstone-free patients were found. On logistic regression analysis only female gender, aging, and family history of gallstone disease were significantly associated with the presence of gallstones, whereas no relationship between NSAID use and gallstone disease was found.
Conclusions: Chronic NSAID ingestion does not seem to prevent gallstones in arthritis patients; in these patients gallstone disease is associated with classic risk factors (female gender and age).     

Pathological Pancreatic Exocrine Function and Duct Morphology in Patients with Cholelithiasis

Most authors claim alcohol consumption to be the only relevant reason for chronic pancreatitis. However, gallstones might cause this disease, as they do cause acute pancreatitis. In this study 91 gallstone patients and 94 age-matched controls were investigated concerning exocrine pancreatic function (fecal elastase-1 concentrations). Furthermore x-rays of 100 consecutive ERCP patients were evaluated for differences concerning pancreatic duct changes between patients with and without evidence of cholelithiasis. Pathological elastase 1 levels were more frequent in gallstone patients (30,8%) as compared to age-matched controls (19%). Symptoms such as upper abdominal pain, bloating, and fat intolerance were reported more often in gallstone patients. In ERCP of gallstone patients (N = 60), 77% were found to have chronic pancreatitis according to the Cambridge classification, while in nongallstone-patients (N = 32) 47% had chronic pancreatitis. In conclusion, according to these data a pathophysiological connection between gallstones and chronic pancreatitis appears to be probable.     

Surgical practice in symptomatic and asymptomatic gallstone disease.

AIMS: To determine the surgical practice in individuals with symptomatic and asymptomatic gallstone disease using a questionnaire survey. METHODS: A questionnaire was sent to 724 patients with gallstone disease. Details of symptoms, duration of illness, nature of treatment including surgery, color of gallstones retrieved and postoperative follow-up particulars were obtained. RESULTS: The study group included 225 (54%) men; there was a rising trend of prevalence of gallstones in men with increasing age (p<0.05). A third of the patients (142 [34%]) were symptomatic. The mean duration of symptoms was 12.1 months. One hundred and ninety seven patients (48%), including 90 asymptomatic ones, underwent cholecystectomy. Most patients (92.5% of those symptomatic and 76.6% of those asymptomatic) underwent cholecystectomy within one year of diagnosis. Eight asymptomatic patients underwent surgery 3 years or more after diagnosis. The predominant color of stones retrieved was black or brown (57%) or mixed (39%). CONCLUSIONS: A majority of patients with gallstone disease had cholecystectomy within one year of diagnosis. Black or brown pigment stones were the dominant types of gallstones.     

Prevalence of gallstones in liver cirrhosis: a sonographic survey

A sonographic prospective study of the prevalence of gallstones was performed in 140 patients with liver cirrhosis and in 140 controls. Gallstones were found more often in cirrhotic patients (29.2%) than in controls (13.6%) (p less than 0.01). Their prevalence increased with age. The ratio of women to men in cirrhotics was the same as in the general population, with a higher prevalence in women. The prevalence of gallstones increased in decompensated liver disease. There was a significantly higher prevalence of both hypersplenism and hemolysis in cirrhosis. No difference was found in gallstone prevalence in relation to cirrhosis etiology. This prospective study confirms, by means of sonography, the high prevalence of cholelithiasis in liver cirrhosis, and extends the previous data about the lithogenic risk factors in this disease.     

Prevalence of gallstone disease in patients with end-stage renal disease treated with hemodialysis in Korea

BACKGROUND/AIMS: Gallstone disease is one of the major causes of morbidity in adults. Hemodialysis has been found to increase the risk of gallstone formation secondary to increased biliary cholesterol and biliary saturation index. However, there is very little data on the prevalence of gallstones in hemodialysis patients. METHODOLOGY: We compared the prevalence of gallstone disease in patients with end-stage renal disease treated with hemodialysis with that of 208 age- and sex-matched controls (non-uremic group). Patients who had chronic liver disease, renal disease, and diabetes were excluded from the control group. RESULTS: In our study, we found a prevalence for gallstone of 18.2% in patients with end-stage renal disease treated with hemodialysis, which was significantly higher than 5.3% in the non-uremic control. Most of our hemodialysis patients had asymptomatic cholecystolithiasis. Hemodialysis patients with cholecystolithiasis were significantly older than patients without gallstones. We did not find a difference in sex and duration of hemodialysis treatment between patients with and without gallstones. CONCLUSIONS: Our results suggest that the prevalence of gallstone disease is higher in patients with end-stage renal disease treated with hemodialysis than in the non-uremic population in Korea.     

Factors influencing the prevalence of gallstones in liver cirrhosis

BACKGROUND AND AIMS: To investigate the prevalence of gallstone disease in Chinese patients with liver cirrhosis and to identify risk factors for cholelithiasis. METHODS: Blood samples were tested and ultrasonographic examination of the upper abdomen was conducted to observe the prevalence of gallstones in 90 compensated cirrhotic patients (Child-Pugh A), 180 decompensated cirrhotic patients (Child-Pugh B, C) and 300 controls. Risk factors for gallstone formation (age, sex, pregnancy, family history) and the characteristics of liver cirrhosis (Child class, inside diameter of portal vein), and gallbladder (wall thickness) were assessed. RESULTS: Gallstones were found more often in cirrhotic patients (23.7%) than in controls (7.33%, P < 0.001). The prevalence of gallstones in decompensated cirrhotic patients was higher than that of the compensated cirrhotic patients (P < 0.001). Advanced age, female sex, family history of gallstones, gallbladder wall thickness 4 mm or greater and inside diameter of portal vein 13 mm or greater were significantly associated with gallstone disease in patients with liver cirrhosis. Multivariate analysis revealed that age (P < 0.001), sex (P = 0.0005) and thickness (4 mm or greater) of the gallbladder wall (P = 0.0064) were independently associated with gallstone disease in such patients. CONCLUSIONS: This study confirms the high prevalence of cholelithiasis in liver cirrhosis. Age and sex are risk factors for gallstones and gallbladder wall thickness could be an additional risk factor for the development of gallstone in patients with liver cirrhosis.     

Long-term effect of magnesium consumption on the risk of symptomatic gallstone disease among men

BACKGROUND: Magnesium deficiency can cause dyslipidemia and insulin hypersecretion, which may facilitate gallstone formation. However, the effect of long-term consumption of magnesium on the risk of gallstone disease is unknown. METHODS: We prospectively studied magnesium consumption and risk of gallstone disease in a cohort of 42,705 U.S. men from 1986 to 2002. Magnesium consumption was assessed using a validated semiquantitative food frequency questionnaire. Newly diagnosed gallstone disease was ascertained biennially. RESULTS: We documented 2,195 incident cases of symptomatic gallstones during 560,810 person-years of follow-up. The age-adjusted relative risks (RRs) for men with total magnesium intake and dietary magnesium, when the highest and lowest quintiles were compared, were 0.67 (95% confidence interval [CI] 0.59-0.77, P for trend <0.0001) and 0.67 (CI 0.59-0.76, P for trend <0.0001), respectively. After adjusting for multiple potential confounding variables, when extreme quintiles were compared, the multivariate RR of total magnesium intake (RR 0.72, CI 0.61-0.86, P for trend = 0.006) and dietary magnesium (RR 0.68, CI 0.57-0.82, P for trend = 0.0006) remained significant with a dose-response relationship. CONCLUSIONS: Our findings suggest a protective role of magnesium consumption in the prevention of symptomatic gallstone disease among men.     

Gallstone disease in an elderly population: the Silea study

BACKGROUND: Little is known on gallbladder emptying and gallstone composition in the elderly. AIMS AND SUBJECTS: Cross-sectional survey on the prevalence of gallstone disease and associated factors, gallstone characteristics and gallbladder emptying in a population aged > or = 60 years. METHODS: Gallstone number and size as well as gallbladder motor function were assessed by ultrasound. Gallstone composition and pattern were evaluated by conventional radiology and computed tomography (CT) based on Hounsfield units (HU). RESULTS: Gallstones were found in 148/1,065 subjects (13.9%), while 136 subjects (12.8%) were cholecystectomized with an overall prevalence of gallstone disease of 26.7% (sex ratio: F > M). Multiple gallstones (62.7%) and small gallstones (52%, diameter < or = 15 mm) were seen; silent gallstones accounted for 93.9% of the total. Only diabetes mellitus in women was significantly associated with cholelithiasis. Gallbladder fasting volumes were larger in gallstone carriers than in controls (P < 0.01); residual and ejection volumes were also significantly greater in gallstone carriers, whereas ejection fractions were similar in the two groups (50.3% +/- 2.4 versus 54.9% +/- 3.0; not significant). Gallstone calcifications were detected in 29/91 gallstone carriers by X-ray and in another 20 by CT (HU > 90). Moreover, 35 gallstone carriers had a score < or = 50 HU and six had attenuation values between 50 and 90 HU. Six gallstone patterns were identified: hypo-isodense, homogeneously dense, rimmed, laminated, core-hyperdense, gas-containing. CONCLUSIONS: In the elderly, the prevalence of gallstone disease is very high, especially in women, but gallstone size, number and pattern and gallbladder emptying do not differ from those reported in the middle-aged gallstone population. Advanced age is associated with a high rate of calcified, probably pigment stones.