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PubMed1976

Malignant melanoma of the gallbladder: report of three cases and review of the literature.

Three cases of primary melanoma of the gallbladder are described to add to the five reported in the literature. As an organ of endodermal origin, the gallbladder appears to share the melanoblastic potentiality possessed by similarly derived organs, and hence, the development of a melanoma within the gallbladder is not unexpected. Presence of melanocytes within the gallbladder mucosa is absolute proof that the tumor is primary. Whether these cells originate from the neural crest and migrate to the gallbladder, or result from local differentiation from preexisting cells remains to be answered.

Gallbladder Neoplasms↗

PubMed1977

Carcinoma of the gallbladder in a population of Southwestern American Indians.

The clinical and pathological characteristics of gallbladder carcinoma were studied in a group of 56 Southwestern American Indian patients. This is the third most common malignant tumor among American Indian females in a population served by the New Mexico Tumor Registry accounting for 8.5% of specific cancer diagnoses by site. Carcinoma of the gallbladder is relatively more common within the Indian population than among Spanish Americans or Anglos living in this area. This is true for both sexes. No significant differences in average age at diagnosis, ratio of female to male patients, signs and symptoms, stage at diagnosis or survival were detected in comparison with studies pertaining to gallbladder carcinoma in non-Indian populations. A squamous cell carcinoma component was unusually common however, and carcinoma in situ or atypical adenomatous hyperplasia of the mucosa was frequently documented adjacent to invasive carcinoma. Although gall stones were present in tumor containing gallbladders in 93% of cases, elective cholecystectomy for cholelithiasis is probably not a practical means of prevention of this tumor in view of the unusual frequency of cholelithiasis in Indian women. Pharmacological conversion of bile to a non-lithogenic form may deserve consideration as prophylaxis against both cholelithiasis and carcinoma of the gallbladder in this population.

Adenocarcinoma↗

PubMed1995

Risk factors for gallbladder cancer. An international collaborative case-control study.

BACKGROUND: Gallbladder cancer has an unusual geographic and demographic distribution, suggesting many possible etiologies. METHODS: A case-control study was undertaken at four hospitals in La Paz, Bolivia, and at one hospital in Mexico City, Mexico. Eighty-four patients with newly diagnosed, histologically confirmed gallbladder cancer were compared with 126 control subjects without stones and with 264 control subjects with cholelithiasis or choledocholithiasis without cancer. All study subjects underwent abdominal surgery. Study subjects were interviewed regarding demographic characteristics, medical history, family history, diet, and exposure to agents presumed to be risk factors for biliary cancer. RESULTS: Virtually all subjects in Mexico were judged to be mestizos (i.e., persons of mixed ancestry) In contrast, race was a very strong risk factor for gallbladder cancer in Bolivia. Relative to mestizos who spoke neither language, the odds ratio (95% confidence interval [CI]) for cases versus control subjects without stones for those who spoke Aymara well was 15.9 (CI, 1.9-179), whereas it was 1.4 (CI, 0.2-8.2) for those who spoke Quechua well. An increased risk was also noted for elevated maximum body mass index (P = 0.03), family history of gallstones (odds ratio [OR] = 3.6 [CI, 1.3-11.4]), and physician-diagnosed typhoid (OR = 12.7 [CI, 1.5-598]). An increased risk was also seen with elevated maximum body mass index; compared with those with a body mass index less than 24 kg/m2, those with an index of 24-25 kg/m2, 26-28 kg/m2, and greater than 28 kg/m2 had odds ratios of 1.6 (CI, 0.4-7.6), 1.3 (CI, 0.3-5.6), and 2.6 (CI, 0.5-18.6), respectively (asymptotic test for trend, P = 0.03). Finally, a number of associations were noted with certain dietary and cooking habits. CONCLUSIONS: Patients with gallbladder cancer differed from control subjects in race, body mass, physician-diagnosed typhoid, and certain dietary patterns. These findings may provide useful clues to the pathogenesis of gallbladder cancer, but given the number of analyses performed, additional cases need to be studied.

Adult↗

PubMed2000

Trends in incidence and management of gallbladder carcinoma: a population-based study in France.

BACKGROUND: Little is known, at a population level, about the incidence and management of gallbladder carcinoma. The objective of this study was to determine trends in incidence, treatment, stage at diagnosis, and prognosis of gallbladder carcinoma in a well defined population. METHODS: A series of 484 patients diagnosed over a 20-year period (1976-1995) in a French well defined population was used. Incidence rates were calculated by gender, age groups, and 5-year periods. Prognosis was determined using crude and relative survival rates. A multivariate relative survival analysis was performed. RESULTS: Age-standardized incidence rates were 0.8 per 100,000 inhabitants for men and 1.5 per 100,000 inhabitants for women. There were no significant time trends in incidence in both genders. The proportion of cases resected for cure increased from 18. 1% (1976-1980) to 42.4% (1991-1995) (P < 0.001) as well as the proportion of cases limited to the gallbladder wall, respectively from 15.7% to 27.8% (P < 0.001). Relative survival rates were 16.6% at 1 year and 6.2% at 5 years. Age, stage at diagnosis, and period of diagnosis significantly influenced the prognosis of gallbladder carcinoma. The 5-year relative survival rate rose from 2.7% (1976-1985) to 10.2% (1986-1995). The multivariate analysis showed that age and stage at diagnosis were independent prognostic factors. CONCLUSIONS: This study demonstrated that gallbladder carcinoma incidence is stable in France and that substantial advances in its management have been achieved, but there is evidence that further improvements are necessary to increase survival.

Adult↗

PubMed1988

Preduodenal mechanisms in initiating gallbladder emptying in man.

The existence of preduodenal phases of gallbladder emptying in normal volunteers was investigated by evaluating the effect of sham feeding a sandwich (chew and spit) (n = 15), the sight and smell of food followed by sham feeding a cooked meal (n = 15), and gastric distension (intragastric balloon tube) (n = 9) on gallbladder emptying and comparing these responses with those after ingestion of a standard meal (n = 14). A control group given no intestinal stimuli were studied to determine the frequency of spontaneous emptying during fasting (n = 18). 99mTc-EHIDA (2,6 diethylphenylcarbamoylmethyliminodiacetic acid) was used as the biliary tracer. The frequency of gallbladder emptying during fasting was 0.0045/min. Thus, in any 20 min period emptying occurred spontaneously in only about 1 in 11 volunteers. Significant emptying (greater than 5 per cent over 20 min) occurred in 8 out of 15 volunteers after sham feeding a sandwich (P less than 0.001 versus control), in 8 out of 15 volunteers after sham feeding a cooked meal (P = 1.0 versus sandwich sham feed, n.s.), in 6 out of 9 volunteers after gastric distension (P less than 0.001 versus control) and in 14 out of 14 volunteers after meal ingestion. The rate of emptying was significantly greater in the gastric distension and meal ingestion groups compared with other groups (P less than 0.05). However, the emptying rate after sham feeding was not significantly different from spontaneous gallbladder emptying (P greater than 0.05, n.s.). There was no significant difference in time to onset of emptying between the four stimulus groups (P greater than 0.05, n.s.). These results suggest that pre-duodenal stimuli can evoke gallbladder emptying in man, although the precise physiological significance of this phenomenon remains to be established.

Adolescent↗

PubMed1992

Transmitter diversity in ganglion cells of the guinea pig gallbladder: an immunohistochemical study.

Several neurotransmitters have been reported to exist in the ganglionated plexus of the guinea pig gallbladder. These include substance P, neuropeptide Y (NPY), calcitonin gene-related peptide, vasoactive intestinal peptide (VIP), acetylcholine, norepinephrine, serotonin, and dopamine. To determine which neuropeptides are intrinsic to gallbladder ganglia, we performed immunohistochemistry on colchicine-treated preparations. In separate, single-labeled preparations, a majority of neurons contained substance P-, NPY-, or somatostatin-like immunoreactivity. In double-labeled preparations, a large majority of the neurons that contained substance P-like immunoreactivity also contained NPY-like immunoreactivity and somatostatin-like immunoreactivity. Immunoreactivity for VIP was present in a small percentage of the gallbladder neurons which did not contain substance P-like immunoreactivity. Additional experiments were done to test for the presence of other compounds, known to exist in the neurons of the gut. Although immunoreactivity was found in control preparations of small intestine, the ganglionated plexus of the gallbladder lacked immunoreactivity for galanin, dynorphin, enkephalin, gastrin-releasing peptide, or gamma-aminobutyric acid. We conclude that ganglia of the guinea pig gallbladder contain at least two populations of neurons, based on transmitter phenotype. One of these populations appears to contain substance P, NPY, and somatostatin. Another population, which represents a small contingent of the total population of neurons, contains VIP.

Animals↗

PubMed1990

Isolation of a potent cholesterol nucleation-promoting activity from human gallbladder bile: role in the pathogenesis of gallstone disease.

Gallbladder bile contains nucleation-promoting activity that binds to concanavalin A. The activity was found in gallbladder bile from cholesterol gallstone patients but also in gallbladder bile from patients without stones and patients with pigment stones. Bile from patients with multiple cholesterol gallstones contained high concanavalin A-binding nucleation-promoting activity. The activity was much lower in bile samples from pigment stone patients, patients without stones and patients with a solitary cholesterol stone. Serum contained very little activity and no concanavalin A-binding nucleation-promoting activity could be demonstrated in gallbladder mucosa. This suggests that concanavalin A-binding nucleation promoter is produced in the liver or bile duct epithelium. The activity was fully resistant to digestion with pronase but was heat labile and could be destroyed by prolonged incubation with a mixed glycosidase preparation indicating that sugar residues are important for this activity. On a Superose 12 gel permeation column, promoting activity eluted in two major peaks at apparent molecular weights of 150 +/- 30 kD (n = 5) and less than 5 kD respectively. The mobility on the column was not influenced by pronase digestion. The factor with the higher molecular weight could be isolated further by polyacrylamide gel electrophoresis under nondenaturing conditions. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the apparent molecular weight of the glycoprotein was 130 kD. In conclusion, gallbladder bile contains nucleation-promoting activity that binds to concanavalin A. The activity is increased in bile from patients with multiple cholesterol gallstones and could therefore play an important role in the pathogenesis of gallstone disease.

Bile↗

PubMed1996

Membrane-bound carbonic anhydrase IV is expressed in the luminal plasma membrane of the human gallbladder epithelium.

Alkaline hepatic bile is acidified in the gallbladder to prevent calcium precipitation and gallstone formation. Because membrane-bound carbonic anhydrase (CA) isoenzyme IV participates with cytoplasmic CA II in the acidification of urine in the kidney, we studied its expression in different regions of the human biliary tract using immunohistochemical techniques. The enzyme was expressed in the apical plasma membrane of the gallbladder epithelial cells and in the endothelium of the subepithelial capillaries. In the liver, some epithelial cells of the large bile ducts showed positive staining. Its presence in the gallbladder epithelium could be confirmed by Western blotting, which showed a single 35-kd polypeptide band, corresponding in molecular weight to the intact enzyme. The majority of the enzyme was phased to Triton X-114 detergent phase. A small amount of 35-kd polypeptide was also seen in the water phase. Smaller proteolytic fragments of the enzyme were not seen, suggesting that the tissue sample was well preserved. The results show that CA IV is expressed in abundance in the human gallbladder epithelium, where it may participate together with cytoplasmic CA II and ion transporters in acidification of the gallbladder bile via bicarbonate reabsorption.

Blotting, Western↗

PubMed1999

Expression of delta F508 cystic fibrosis transmembrane conductance regulator protein and related chloride transport properties in the gallbladder epithelium from cystic fibrosis patients.

Cystic fibrosis transmembrane conductance regulator (CFTR), the cystic fibrosis (CF) gene product, functions as an adenosine 3', 5'-cyclic monophosphate (cAMP)-regulated chloride channel in the apical membrane of biliary epithelial cells, including gallbladder epithelial cells. It has been shown that triangle upF508, the most common CF mutation, impedes CFTR trafficking to the apical surface of epithelial cells. To elucidate the mechanisms of CF biliary disease, we examined structural features, CFTR expression, and chloride transport properties in gallbladder epithelial cells from nine triangle upF508 homozygous liver transplant recipients. Three CF patients had microgallbladders, characterized by severe histological abnormalities. Microgallbladder epithelial cells displayed aberrant immunolocalization of CFTR and of other normally apical proteins in the lateral domain of their plasma membrane and in their cytoplasm. This pattern was mimicked by chronic cholecystitis in non-CF patients. In the 6 remaining CF patients, CFTR was predominantly apical in the gallbladder epithelium, consistent with the detection of a fully glycosylated form by Western blot. In CF as compared with non-CF gallbladder epithelial cells in primary culture, chloride efflux was lower in response to cAMP and tended to be higher in response to exogenous adenosine 5'-triphosphate (ATP). The CF cells exhibited a residual cAMP-dependent chloride secretion that was inversely correlated with ATP-induced chloride secretion, and almost completely blunted in the cells derived from microgallbladders. Our results suggest that epithelial structural alterations aggravate triangle upF508 CFTR mislocalization in the gallbladder epithelium. The associated decrease in residual cAMP-dependent chloride secretion may contribute to biliary damage despite the up-regulation of alternative chloride transport pathways.

Adolescent↗

PubMed1988

Frequency of gallbladder cancer in Chile, a high-risk area.

We report an autopsy study of gallbladder cancer prevalence in Chile, where the risk of this disease is among the highest reported world-wide. In 14,768 autopsy protocols obtained from 3 university hospitals, 45% of women and 20% of men older than 20 years had gallstone disease (the major known risk factor for gallbladder cancer). The prevalence of gallbladder cancer in Chileans was compared to that found in a Swedish-Czechoslovakian autopsy study previously published. These countries were chosen because of their high frequency of gallstone disease. The comparison was performed by using logistic regression models adjusting for possible differences in the age-sex structure or the true incidence of gallstones in both populations. We found that the most important single risk factor for gallbladder cancer in Chile was gallstone disease, with an estimated effect on the logistic scale meaning that the cancer risk for subjects with gallstones is seven times higher than for those without the disease. Second in importance was the risk for sex, women being 2.8 times higher than for men. The estimated difference in the sex composition and the incidence of gallstones resulted in 17.9% higher odds of cancer in Chile than in Sweden and Czechoslovakia. However, this difference was not significant. This study suggests that the major etiologic factors of gallbladder cancer in Chileans, Swedes and Czechoslovakians are primarily related to gallstone disease.

Adult↗

PubMed1985

Contractility of maternal and fetal gallbladder: an ultrasonic study.

The volumes of the maternal and fetal gallbladder were examined by ultrasound in a fasting condition during the last trimester of pregnancy in 25 cases and then monitored for 180 min after a standard peroral test meal or glucose administration. The ratio of maternal to fetal gallbladder fasting volumes corresponded to the ratio of the weights. A significant decrease in maternal gallbladder size was observed at 30, 60, and 120 min in both groups, but the changes in the volume of the fetal gallbladder were not significant. This latter observation points toward a resting condition and passive role for the gallbladder in the antenatal gastrointestinal physiology of the fetus.

Cholecystokinin↗

PubMed2005

Gallbladder contraction, gastric emptying and antral motility: single visit assessment of upper GI function in untreated celiac disease using echo-planar MRI.

PURPOSE: To assess gallbladder contraction, gastric emptying, and antral motility in untreated celiac patients and healthy controls using a single MRI examination. MATERIALS AND METHODS: Gallbladder emptying, gastric emptying, and antral motility were measured in 15 celiac patients and 15 age/sex-matched healthy controls following a 323-kcal test meal using EPI techniques. Postprandial dyspepsia scores were recorded on a questionnaire. RESULTS: Fasting gallbladder volume (P=0.01) and the volume of bile ejected postprandially (P=0.014) were increased in celiacs. Gastric emptying tended to be slower in celiacs (P=0.142). Three celiac patients with severe postprandial dyspepsia and total villous atrophy had pathologically delayed gastric emptying and increased fasting gallbladder volume. Antral contractions were absent in five out of 14 patients (36%) five minutes after the meal, but in none of 10 volunteers in whom the antrum could be visualized (P=0.128). CONCLUSION: This study shows that using MRI, multiple parameters related to upper gastrointestinal function in celiac disease can be measured in a single noninvasive study, whereas previously three separate visits would have been required. Celiacs have increased fasting gallbladder volumes and tend to have slower gastric emptying.

Adolescent↗

PubMed2003

Cytochrome P-450 expression and lipid peroxidation in gallbladder cancer.

BACKGROUND AND OBJECTIVES: Carcinoma of the gallbladder is the commonest neoplasm of the biliary tract; however, the etiology of this tumor remains unclear. METHODS: A case-control study was carried out comprising 50 patients with gallbladder cancer and 50 patients with cholelithiasis. Cytochrome P-450 estimation was carried out in the gallbladder tissue, and lipid peroxide product melonaldehyde (MDA) was measured in gallbladder bile. Statistical analysis was carried out by Student's t-test, and one-way analysis of variance (ANOVA). The Pearson correlation coefficient was calculated, and linear regression analysis was performed. RESULTS: The mean cytochrome P-450 concentration was significantly higher in patients with carcinoma of the gallbladder than in controls (t = 3.9, P < 0.001; F = 15.2, P = 0.002). Similarly, the mean concentration of melonaldehyde was significantly higher among cancer patients than in patients with gallstones (t = 2.7, P < 0.003; F = 7.37, P = 0.0078). No significant correlation was observed between tissue MDA and cytochrome P-450 levels (Pearson r = 0.1, P = 0.28). CONCLUSIONS: The results of the present study show that the rise in concentration of MDA is independent of the rise in concentration of cytochrome P-450; however, this is statistically insignificant. This could be due to biliary stasis leading to a rise in biliary concentration of melonaldeyde that is disproportionate to its production.

Adult↗

PubMed2005

Intra-arterial chemotherapy with mitomycin C in gallbladder cancer: a follow-up study.

BACKGROUND AND OBJECTIVES: There is only limited and somewhat controversial information available on hepatic artery infusion of cytotoxic agents in gallbladder cancer. We report the results of 5-year follow-up of all gallbladder cancer patients treated with surgery and intra-arterial mitomycin C or mitomycin C alone in our hospital during 15 years. METHODS: Thirty-five patients with gallbladder cancer were treated with superselective intra-arterial chemotherapy (SIAC) with mitomycin C during 1981-1996. Survival was measured from diagnosis, and all patients were followed up until death or the end of January 2002. Cumulative survival rates and median survival times were calculated for all patients, according to response to treatment and staging. The data are presented as 5-year survival. RESULTS: Median survival times after SIAC for all patients, responders, and non-responders were 48, 60+, and 8.5 months, respectively. Overall response rate was 60%. Survival was significantly better for tumors limited to the gallbladder wall, as expected. Drug toxicity occurred in half of the patients, requiring cessation of chemotherapy in 25% of the cases. CONCLUSIONS: The median survival of gallbladder cancer patients treated with surgery and SIAC seems to be significantly better compared to the previously reported outcome of surgical treatment alone. Drug toxicity limits the use of i.a. chemotherapy and requires careful monitoring for early side-effects.

Adenocarcinoma↗

PubMed1986

Polyps of the gallbladder.

One of the unusual problems associated with gallbladder disease is a polyp discovered by either ultrasonography or by oral cholecystogram. We report a recent experience of two cases of polyps of the gallbladder removed by cholecystectomy. The incidence of gallbladder polyps of any type is quite varied in the medical literature. Eighty percent of polyps occur in females, and these occur after the third decade of life. The polyps can either be cholesterol or inflammatory polyps that are not really benign tumors but just reactions of the gallbladder wall. The true mucosal benign lesions are either adenomyomas or papillomas. The adenomyomas and papillomas have malignant potential. There are case reports of carcinoma in situ and cancer arising from these lesions. The treatment for a gallbladder polyp is a cholecystectomy.

Adult↗

PubMed1993

An approach to histologically diagnosed gallbladder carcinoma following cholecystectomy for presumed benign disease.

Five cases of gallbladder adenocarcinoma treated at Surgical Department 2, Maciel Hospital, Montevideo, Uruguay, in a period ranging from 1985 to 1989 and follow-up to date are reported. All cases were first diagnosed by microscopic examination of the gallbladder, which had been removed for presumed benign disease; there were no intramucosal carcinomas, and 60% of the cases were classified as Nevin's stage II (submucosal and muscularis). Based on the pattern of spread (mainly direct hepatic infiltration, as well as venous and lymphatic involvement), our radical surgical treatment of gallbladder carcinoma includes cholecystectomy, extended lymphatic clearance (along the porta hepatis or R1, pre- and retroduodenopancreatic and hepatic artery R2, and celiac axis R3), and medial hepatectomy (segments, IV, V, and VIII according to Couinaud). Simple cholecystectomy is the treatment of choice in mucosal (T1) neoplasms; otherwise, histologically diagnosed gallbladder carcinoma following cholecystectomy for presumed benign disease calls for reoperation to achieve lymph node dissection and hepatic resection. Overall 2- and 3-year survival was 100% and 80%; mean survival was 50 months. Medial hepatectomy was selected according to gallbladder carcinoma patterns of spread and failures, and entails resection of the parenchyma most frequently involved without compromising liver function, in a quick and safe surgical procedure.

Adenocarcinoma↗

PubMed1995

Neural cell adhesion molecule and perineural invasion in gallbladder cancer.

To clarify the role of neural cell adhesion molecule (NCAM) in perineural invasion, NCAM expression was studied by immunohistochemical staining in 26 cases with gallbladder cancer. In gallbladder cancer, the incidence of perineural invasion and that of positive NCAM expression was 42% and 31%, respectively, which are less frequent than those of bile duct cancer in our previous report. Perineural invasion was observed in 88% of the patients with positive expression of NCAM and in 22% of those with negative expression. The former is similar to that of bile duct cancer but the latter is significantly lower. Eighty percent of the cancer cells that invaded the perineural space were positive for NCAM, when the primary tumor was positive for NCAM expression. Therefore, in gallbladder cancer, positive cells in NCAM expression likely invade the perineural spaces. However, the perineural invasion of negative cells in NCAM expression is not likely to occur as compared to bile duct cancer. In conclusion, perineural invasion in gallbladder cancer is not as common as in bile duct cancer, but the role of NCAM in perineural invasion is more important in gallbladder cancer than in bile duct cancer.

Adenocarcinoma↗

PubMed1994

Er:YAG laser ablation of prairie dog gallbladder epithelium for the prevention of gallstones.

We hypothesized that laser ablation of gallbladder epithelium would prevent gallstone formation in prairie dogs. An Er:YAG laser (lambda = 2.94 microns) was used to ablate the gallbladder epithelium of 24 prairie dogs; 20 sham-irradiated and 12 non-operated prairie dogs served as controls. Prairie dogs were sacrificed at time periods of 4 days, 2 weeks, and 8-12 weeks and evaluated for the presence of gallstones and cholesterol crystals. Laser-irradiated gallbladders demonstrated a lower rate of gallstone formation at 8-12 weeks than the sham-irradiated gallbladders (39% vs. 79%: P < .02). Crystal formation, however, was not different between laser-irradiated (88%) and sham-irradiated (100%) animals. The laser-irradiated group had less epithelium than the non-operated group at all time periods (P < or = .002) and compared to the sham-irradiated group at 4 days and 8-12 weeks (P < or = .001). These data suggest that laser ablation of gallbladder epithelium can reduce the rate of gallstone formation although this effect may be temporary.

Aluminum Silicates↗