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Gallbladder disease in adolescents, although not uncommon, has been neglected in the literature, which is unfortunate because adolescents possess a unique set of characteristics. Drawing on the relevant available literature, the author outlines our current knowledge about gallbladder disease in adolescents. Particular attention is devoted to gallstone formation, associated medical conditions, and predisposing risk factors.
Previous studies have reported high rates of gallbladder disease and gallbladder cancer among all American Indians. Data from the New Mexico Tumor Registry confirm these findings, specifically showing high rates for New Mexico's American Indians, as well as for the state's Spanish population. This review explores several risk factors, including parity, obesity, age, cholesterol level, and genetic factors. From the available evidence, genetic factors appear to be the most important, with parity a contributing factor.
Gallbladder epithelium is unique among the gastrointestinal cell types because proteins and protein levels in the fluid bathing the luminal side of the cells (bile) are different from and can be compared with those in the fluid bathing the basal side (serum). To help identify cellular changes that occur during the development of gallbladder cancer, we obtained gallbladder tissue, serum, and bile specimens from 20 patients with invasive adenocarcinoma of the gallbladder, three with high-grade dysplasia (carcinoma in situ), six with low-grade dysplasia, 12 with hyperplasia, and 10 with acute or chronic cholecystitis. We obtained serum samples from 40 patients with invasive adenocarcinoma and bile samples from 29 of these patients; serum samples from three with high-grade dysplasia and bile specimens from two of these; serum and bile samples from five with low-grade dysplasia; serum or bile samples from 126 with metaplasia, hyperplasia, or cholecystitis, including serum samples from 121 and bile samples from 110; and serum and bile samples from eight with normal biliary tracts. The study was conducted in Mexico City, Mexico, and La Paz, Bolivia. We performed flow cytometric DNA analysis on gallbladder tissue specimens and measured levels of carcinoembryonic antigen (CEA) and CA 19-9 antigen in the serum and bile specimens. Analysis of the cell cycle compartments by flow cytometry revealed marked variations of the proliferation index for the different disease states (P less than .0001). The proliferation index increased with progression from cholecystitis to invasive adenocarcinoma. Of the bile and serum measurements, only serum CA 19-9 values were correlated with flow cytometry measurements (r = -.49, P = .005). Overall, the serum and bile measurements were in agreement (P less than .01). However, with the exception of the correlations among serum measurements for the patients with invasive adenocarcinoma, most of the correlations could be explained by differences in the disease state. In particular, the progression from normal tissue to invasive adenocarcinoma involved no change in bile CA 19-9 level and only a slight change in bile CEA level but much larger changes in serum CEA and CA 19-9 levels. It appears that the progression from normal tissue to invasive adenocarcinoma results in increased production of these antigens and often in loss of cell polarity as well, i.e., inability to prevent leakage of the antigens into the serum.
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Impaired gallbladder emptying is a recognized sign of acalculous gallbladder disease (AGBD). The emptying function was studied by ultrasonographic monitoring before and after ingestion of fat-containing food in a prospective study comprising 124 patients (136 examinations). In 17 patients the antero-posterior diameter of the gallbladder was unchanged or increased postprandially in addition to the onset of abdominal pain and nausea, signs interpreted as consistent with AGBD. Cholecystectomy, performed in 12 of these individuals, revealed histopathologic changes of different degree in 11 and adhesions of the gallbladder to adjacent organs in 8. The method is simple to perform, cheap, has no side effects and gives a low rate of false positive diagnoses.
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Gallbladder disease is a common source of morbidity in the Mexican American population. Genetic heritage has been proposed as a possible contributor, but evidence for this is limited. Because gallbladder disease has been associated with Native American heritage, genetic admixture may serve as a useful proxy for genetic susceptibility to the disease in epidemiologic studies. The objective of our study was to examine the possibility that gallbladder disease is associated with greater Native American admixture in Mexican Americans. This study used data from the Hispanic Health and Nutrition Examination Survey and was based on 1,145 Mexican Americans who underwent gallbladder ultrasonography and provided usable phenotypic information. We used the GM and KM immunoglobulin antigen system to generate estimates of admixture proportions and compared these for individuals with and without gallbladder disease. Overall, the proportionate genetic contributions from European, Native American, and African ancestries in our sample were 0.575, 0.390, and 0.035, respectively. Admixture proportions did not differ between cases and noncases: Estimates of Native American admixture for the two groups were 0.359 and 0.396, respectively, but confidence intervals for estimates overlapped. This study found no evidence for the hypothesis that greater Native American admixture proportion is associated with higher prevalence of gallbladder disease in Mexican Americans. Reasons for the finding that Native American admixture proportions did not differ between cases and noncases are discussed. Improving our understanding of the measurement, use, and limitations of genetic admixture may increase its usefulness as an epidemiologic tool as well as its potential for contributing to our understanding of disease distributions across populations.
Evaluation of gallbladder diseases by computed tomography (CT) is limited compared with ultrasonographic evaluation. However, CT can bring about excellent information in advanced carcinoma of the gallbladder, severe and complicated cholecystitis, porcelain gallbladder, and indication for dissolution of gallbladder stones. Unique findings are also available in emphysematous cholecystitis, xanthogranulomatous cholecystitis, stones with gas (Mercedez-Benz sign), limy bile, and enhancement in acute cholecystitis. Combined use of CT and ultrasound apparently increase the accuracy of diagnosis in carcinoma and cholecystitis. This article is composed of sections on carcinoma, cholecystitis, stone, bile in the gallbladder, calcification, gas and fat, and miscellaneous topics including polypoid lesions, adenomyomatosis, hydrops, and wall thickening.
The relation between plasma lipids and gallbladder disease was examined by using data collected between 1984 and 1987 from 1,303 Rancho Bernardo, California, women aged 50 years and older. In univariate analyses and after adjustment for age and body mass index, high density lipoprotein cholesterol (HDL cholesterol) and low density lipoprotein cholesterol (LDL cholesterol) were inversely related and triglyceride level was positively related to gallbladder disease. However, using multiple logistic regression, only LDL cholesterol, triglycerides, age, and body mass index were significantly related to a history of gallbladder disease, whereas HDL cholesterol was no longer associated with gallbladder disease. The risk of gallbladder disease increased with greater age, body mass index, and triglyceride level, but decreased with increasing LDL cholesterol level. Total amount of alcohol consumed per week, number of cigarettes smoked per day, and current estrogen use were not significantly associated with gallbladder disease. The relation of HDL cholesterol and LDL cholesterol to the risk of gallbladder disease requires further investigation.
BACKGROUND & AIMS: Gallbladder disease is one of the most common conditions in the United States, but its true prevalence is unknown. A national population-based survey was performed to determine the age, sex, and ethnic distribution of gallbladder disease in the United States. METHODS: The third National Health and Nutrition Examination Survey (NHANES III) conducted gallbladder ultrasonography among a representative U.S. sample of more than 14, 000 persons. The diagnosis of gallbladder disease by detection of gallstones or cholecystectomy was made with excellent reproducibility. RESULTS: An estimated 6.3 million men and 14.2 million women aged 20-74 years had gallbladder disease. Age-standardized prevalence was similar for non-Hispanic white (8. 6%) and Mexican American (8.9%) men, and both were higher than non-Hispanic black men (5.3%). These relationships persisted with multivariate adjustment. Among women, age-adjusted prevalence was highest for Mexican Americans (26.7%) followed by non-Hispanic whites (16.6%) and non-Hispanic blacks (13.9%). Among women, multivariate adjustment reduced the risk of gallbladder disease for both Mexican Americans and non-Hispanic blacks compared with non-Hispanic whites. CONCLUSIONS: More than 20 million persons have gallbladder disease in the United States. Ethnic differences in gallbladder disease prevalence differed according to sex and were only partly explained by known risk factors.
The correlation between gallbladder stones (gallstones) and various gallbladder diseases was examined. The incidence of gallstones was 47.1% in cases of non-neoplastic epithelial polyp, 48.0% in adenoma, and 59.1% in adenocarcinoma. There was no relation between the incidence of gallstones and sex. The incidence of gallstones in cancer cases showed no difference among histological gradings. Non-neoplastic epithelial polyps, adenomas and carcinomas were divided into metaplastic type and non-metaplastic type based on the presence or absence of metaplastic changes. Comparison of the incidence of gallstones showed that cases of metaplastic-type polyp and adenoma had a higher incidence of gallstones than non-metaplastic-type polyp and adenoma. In the cases of cancer, no differences were observed in the incidence of gallstones between metaplastic-type and non-metaplastic-type carcinomas. However, comparison among early carcinomas showed that metaplastic-type carcinoma had a significantly higher incidence of gallstones than the non-metaplastic-type. These results suggest that gallstones may play an important role in the histogenesis of gallbladder diseases of the metaplastic type.
PURPOSE: Prospective studies of gallbladder disease have investigated a limited number of risk factors and have been conducted predominantly in women. Determinants of hospitalized gallbladder disease were examined in a large, population-based cohort of men and women. METHODS: Subjects, aged 45-64 years, were participants in the Atherosclerosis Risk in Communities (ARIC) Study who reported no history of gallbladder disease at baseline (n = 12,773). Incident cases of gallbladder disease were identified through surveillance of hospital discharges between the baseline visit (1987-1989) and 1996. RESULTS: The crude incidence rate of hospitalized gallbladder disease was 3.8 per 1000 person-years. In women, increasing risk was observed for increasing levels of body-mass index and waist-to-hip ratio, whereas in men, increased risk was observed only in the morbidly obese (BMI >or= 35). Fasting serum insulin, low HDL cholesterol, elevated triglycerides, and hormone replacement therapy were all positively associated with gallbladder disease risk. The relative risks associated with having one, two, or three or more components of the "multiple metabolic syndrome" in men were 1.45 (95% CI = 0.9-2.3), 2.17 (1.3-3.6), and 2.34 (1.3-4.3), respectively. CONCLUSIONS: In men, hyperinsulinemia and dyslipidemia may have some role in the etiology of gallbladder disease beyond their association with obesity, whereas in women, increased body size, central adiposity, and hormone replacement therapy may be more important determinants of gallbladder disease.
An inconsistent association has been found between gallbladder disease and diabetes mellitus. We hypothesized that insulin resistance rather than diabetes status may be a primary factor involved in gallstone formation. A total of 5,653 adult participants in the third United States National Health and Nutrition Examination Survey without known diabetes underwent gallbladder ultrasonography and phlebotomy after an overnight fast for measurement of serum insulin, C-peptide, and glucose. Gallbladder disease was defined as ultrasound-documented gallstones or evidence of cholecystectomy. Subjects were characterized as having normal fasting glucose (<110 mg/dL), impaired fasting glucose (110 to <126 mg/dL), or undiagnosed diabetes (>/=126 mg/dL). After controlling for other known gallbladder disease risk factors, among women, undiagnosed diabetes was associated with increased risk of gallbladder disease (prevalence ratio [PR] = 1.91, 95% confidence interval [CI] = 1.29-2. 83); whereas impaired fasting glucose was unassociated. Gallbladder disease risk in women increased with levels of fasting insulin (PR = 1.63, 95% CI = 1.11-2.40) and C-peptide (PR = 2.07, 95% CI = 1.32-3. 25) comparing highest to lowest quintiles. However, the association of gallbladder disease with undiagnosed diabetes was not diminished when the model included fasting insulin (PR = 1.85, 95% CI = 1.24-2. 77). In men, there was a statistically nonsignificant association with undiagnosed diabetes (PR = 2.11, 95% CI = 0.76-5.85), but no association of gallbladder disease with insulin or C-peptide. Among women higher fasting serum insulin levels increased the risk of gallbladder disease, but did not account for the increased risk in persons with diabetes.
Low rates of gallbladder disease among blacks have been reported but not systematically studied. The authors investigated the rate of hospitalization with a diagnosis of gallbladder disease in the follow-up in 1982-1984 of the first National Health and Nutrition Examination Survey, a population-based study conducted across the United States in 1971-1975. Based on hospital discharge diagnoses of gallbladder disease, 368 cases were identified for the period 1971-1984 among 10,551 persons, aged 25-74 years, who denied gallbladder disease at the baseline examination. The crude incidence of gallbladder disease per 1,000 person-years was 2.59 for white men, 1.45 for black men, 4.09 for white women, and 2.35 for black women. Controlling for obesity, parity, ethanol consumption, use of diuretics, use of oral contraceptives, and two indicators of socioeconomic status, the authors found that the hazard rate of hospitalization with gallbladder disease increased with age for white women and decreased for black women. The hazard ratio for black women compared with white women at 30 years of age was 0.71 with a 95% confidence interval of 0.52-0.96, but at age 70, it was 0.18 with a 95% confidence interval of 0.09-0.37. For women, obesity and parity were important risk factors for gallbladder disease (p less than or equal to 0.001), and the use of diuretics was marginally associated (p = 0.08). Black men compared with white men had a hazard rate of gallbladder disease of 0.53 with a 95% confidence interval of 0.24-1.16. For men, increasing age was related to gallbladder disease (p less than 0.001), and obesity was weakly related (p = 0.06). The black/white hazard ratios decreased further when controlling for socioeconomic status, persisted if the study population was limited to those hospitalized during follow-up, and increased slightly for cases with an acute complication of gallbladder disease. Thus, differential access to medical care may not explain the lower rate among blacks.
Thirteen patients with gallbladder disease underwent power Doppler ultrasound (PDUS) before and after microbubble contrast agent injection. Lesion and liver bed vascularity was evaluated. Pathological diagnoses in nine patients were two acute cholecystitis, four chronic inflammation, one adenoma and two adenocarcinoma. Two cases of cancer were included on clinical and radiological findings. Two cases were excluded because no pathologic diagnosis was available. Liver bed hyperemia was noted only in acute cholecystitis. Contrast-enhanced PDUS was superior to nonenhanced PDUS in the demonstration of vascularity of gallbladder diseases. However, contrast-enhanced PDUS has limited value in the differentiation.
The ethnic and geographic distributions of several common chronic diseases show distinct patterns that are consistent with the distribution of genes and genetic admixture. For example, diabetes and gallbladder disease occur most frequently among Amerindians, while those genetically admixed with them (such as Mexican-Americans) have intermediate rates, and lowest rates are found among Whites and Blacks. Because there will be heterogeneity from individual to individual in ancestral affinity within an admixed population, a method is developed for estimating each person's admixture probability. Results confirm that there is substantial heterogeneity of individual admixture among Mexican-Americans in Starr County, Texas, with a mean value indicating that 65% of genes in this population are Caucasian derived and 35% Amerindian derived. The individual estimates are shown to be unrelated to the probability of being diabetic and only marginally related to gallbladder disease, with those having the most Amerindian affinity being at increased risk. These results are a consequence of the independent assortment of loci and indicate that unless the markers employed are related (including linkage) to the disease of interest, the method will have limited utility. Individual admixture estimates will be useful, however, for examining aspects of population structure and will find increased utility for predicting disease and examining disease associations as more and more of the genome is represented by markers, a very probable prospect with the abundance of DNA polymorphism being identified by restriction enzymes.