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PubMed1978

Calcified ballbladder (porcelain gallbladder).

Calcification of the gallbladder wall, otherwise known as porcelain gallbladder, is a relatively rare disease and is frequently asymptomatic. Symptoms suggestive of biliary disease are often absent in patients with this manifestation. Since the condition is uncommon, it is important to recognize the clinical as well as the roentgenographic characteristics of the disease because of the high frequency (22%) of adenocarcinoma in the porcelain gallbladder. To our knowledge, no pathognomic sign of symptoms of the disease have been reported so far. Of five cases of porcelain gallbladder reported, carcinoma of the gallbladder was discovered in one patient. This disease seems to appear mostly in the sixth decade of life and is more prevalent in women. Diagnosis is made in most cases by a simple flat plate of the abdomen, and workup should include other roentgenographic examinations to exclude calcification of other viscera or the thoracic wall. Surgery should not be delayed even if the patient is asymptomatic since the occurence of carcinoma in porcelain gallbladder is remarkably high.

Adult↗

PubMed1998

Genetic admixture and gallbladder disease in Mexican Americans.

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.

Adult↗

PubMed1996

Early carcinoma of the gallbladder: an elusive disease.

Prognosis of carcinoma of the gallbladder can be improved by diagnosing the disease in the early stages. Records of 14 patients with early (UICC AJCC TNM stages I and II) carcinoma of the gallbladder were analyzed. Clinical presentation in all these patients was like benign biliary disease. Ultrasonography could diagnose carcinoma of the gallbladder in only five patients; in the remaining nine patients, even the ultrasonographic diagnosis was benign biliary disease. All patients were operated; carcinoma of the gallbladder was diagnosed at operation in two more patients, but it was first detected only after histological examination in seven patients. All patients except four had associated gallstones. Preoperative diagnosis of early carcinoma of the gallbladder is difficult. The only way to diagnose early carcinoma of the gallbladder is by early surgical treatment of patients with clinical features of benign biliary disease.

Adult↗

PubMed2000

Carcinoma of the gallbladder: role of sonography in diagnosis and staging.

PURPOSE: In an attempt to define the sonographic characteristics of gallbladder cancer, we retrospectively analyzed the sonographic findings in 203 cases of gallbladder cancer confirmed by cytology or histopathology. Patients and Methods Patients with proven gallbladder cancer presenting to a single surgical unit between 1991 and 1995 were identified through a records search. All patients underwent sonographic examination followed by fine-needle aspiration (FNA), biopsy, or laparotomy for establishing the diagnosis. RESULTS: A mass in the gallbladder and gallbladder wall thickening (> 12 mm) were cardinal sonographic findings of carcinoma. Liver infiltration was correctly identified in all patients who had it. Sonography was highly accurate for detecting mass lesions, gallstones, liver infiltration, metastasis, and ascites. However, visualization of lymph nodes, common bile duct infiltration, and peritoneal dissemination was poor. CONCLUSIONS: Sonography was found to be a good diagnostic tool for carcinoma of the gallbladder; however, its sensitivity was poor for staging nodal spread of the disease.

Adenocarcinoma↗

PubMed2000

K-ras oncogene mutation in cancer and precancerous lesions of the gallbladder.

BACKGROUND AND OBJECTIVES: To determine whether K-ras mutation plays any role in the development and progression of gallbladder cancer, or has any clinical or pathological significance in gallbladder cancer patients, we investigated the presence and incidence of this mutation in the normal mucosa, and precancerous and cancerous lesions of the gallbladder. METHODS: DNA was obtained from normal mucosa, dysplastic mucosa, primary cancer tissues, and metastatic lymph nodes that were identified and microdissected from the paraffin blocks of 20 gallbladder cancer cases. K-ras codon 12 mutations were investigated using a modified two-step polymerase chain reaction and the restriction fragment length polymorphism method, and by direct sequencing with an automated sequencer. RESULTS: K-ras mutations were detected in the tissues of 10 out of the 20 patients. A mutation was present in the dysplastic epithelium associated with the primary carcinoma in 3 out of 12 specimens, in metastatic carcinoma in 1 out of 5 patients, and in primary carcinoma in 8 out of 20 patients. Mutation was found only once in the dysplastic, noncancerous epithelium, and only once in a metastatic tumor although not detectable in the primary cancer. Direct sequencing showed that the mutations were G to C substitutions (GGT-->CGT) at the first site of codon 12, except in two cases (GGT-->TGT). There were no correlations between K-ras mutations and clinicopathological factors. CONCLUSIONS: K-ras mutations were detected in half of the gallbladder cancer cases. We suggest that K-ras mutation may play a role in the development of premalignant lesions or early carcinogenesis in some gallbladder cancers. We were unable to find any evidence that K-ras mutation plays any role in tumor progression or metastasis, or that it has any clinicopathological significance.

Adult↗

PubMed1979

Metastatic melanoma of the gallbladder.

Metastatic involvement of the gallbladder in melanoma is rare, but constitutes the most common metastatic lesion involving this organ. Two cases of metastatic melanoma to the gallbladder with radiographic evidence of gallbladder abnormality prior to surgery are presented. These cases are compared to the nine previously reported cases of metastatic melanoma to the gallbladder with abnormal cholecystograms. All eleven cases presented with signs and symptoms compatible with cholecystitis. Nine of the eleven patients had a previous melanoma primary and most had other extrabiliary metastases. Associated cholelithiasis appeared to be only incidental. In addition, nine reported cases of "primary" biliary melanoma were reviewed. Clinical and pathologic presentations in the latter cases were similar to the former cases with metastases. Seventy-eight percent had extrabiliary sites of metastasis at some time in the course of their disease, tending to refute the impression of "primary" biliary melanoma. Melanoma in the gallbladder is much more likely to have metastasized from a regressed skin primary than to have arisen de novo. The two reported cases and the 18 cases from the literature indicate that the physician must consider gallbladder metastasis in melanoma patients presenting with symptoms compatible with cholecystitis.

Adult↗

PubMed1984

Carcinosarcoma and carcinoma of the gallbladder.

Carcinosarcoma is a tumor-containing malignant epithelial and connective tissue elements. The 18th case of carcinosarcoma of the gallbladder is reported in the context of 17 prior cases from the world literature. The 18-year experience of St. Luke's Hospital with extrahepatic and primary gallbladder cancer is presented to provide perspective on this unusual tumor. The diagnosis of malignant disease of the gallbladder is reviewed with special emphasis on the roles of sonography, computerized tomography, and arteriography. The importance of staging as a guideline to prognosis and therapy of gallbladder cancer is discussed. Carcinosarcoma of the gallbladder behaves clinically like carcinoma and guidelines for surgical and palliative therapy of the more common malignancies of the gallbladder should be followed for carcinosarcoma as well.

Adenocarcinoma↗

PubMed1993

Metaplasia and precursor lesions of gallbladder carcinoma. Frequency, distribution, and probability of detection in routine histologic samples.

BACKGROUND: Gallbladder diseases, especially cholelithiasis, are extremely frequent in Chile, and an increasing frequency of gallbladder carcinoma has been observed during the last decades. Hyperplastic and atypical epithelial lesions of gallbladder epithelium have been considered potential precursors of invasive carcinoma. The current study was designed to study the frequency, distribution, extension, and probability of routine detection of potentially preneoplastic changes of gallbladder epithelium. METHODS: Epithelial changes were histologically studied by mapping gallbladders obtained at elective cholecystectomy for lithiasis in 162 Chilean patients. RESULTS: Antral-type metaplasia was found in 95.1% of the cases, intestinal metaplasia in 58.1%, hyperplasia in 46.9%, dysplasia in 16%, and carcinoma in situ in 2.5%. A significant association of intestinal metaplasia with hyperplasia, intestinal metaplasia with dysplasia, and hyperplasia with dysplasia was found. Hyperplasia and dysplasia were also present in four cases with carcinoma in situ. Mean extension of the lesions (percentages of the sections in which the change was observed) was antral-type metaplasia (62.7%), intestinal metaplasia (25.3%), hyperplasia (24.1%), dysplasia (15.5%), and carcinoma in situ (9.7%). Antral-type and intestinal metaplasia were more extensive and more severe in patients older than 50 years of age. Hyperplasia was more extensive in cases in which it was associated with dysplasia and carcinoma in situ. CONCLUSIONS: The extension of metaplasia seems to depend in part on the age of the patients. The association of intestinal metaplasia with hyperplasia and dysplasia agrees with the findings of other authors that relate metaplasia to gallbladder cancer. The epithelial lesions are focal or partially confluent, thus a single random histologic section will detect less than one third of the hyperplasias, dysplasias, and carcinomas in situ.

Adult↗

PubMed1994

An immunohistochemical study of p53 protein in gallbladder and extrahepatic bile duct/ampullary carcinomas.

BACKGROUND: p53 mutations are known to occur frequently in human cancers, including gallbladder carcinoma. However, there has been no study of p53 expression in extrahepatic bile duct/ampullary carcinoma. Furthermore, gallbladder carcinoma is associated with cholelithiasis, whereas no such association is known for extrahepatic bile duct carcinoma, suggesting that they could arise from different pathogenetic mechanisms. METHODS: Twenty-four gallbladder carcinomas and 35 extrahepatic bile duct/ampullary carcinomas were stained with an anti-human p53 protein monoclonal antibody by the streptavidin-biotin immunoperoxidase method. Both the extent and intensity of p53 protein staining were noted. RESULTS: Ninety-two percent of the gallbladder carcinomas stained for p53 protein compared with only 66% of the extrahepatic bile duct/ampullary carcinomas. The statistical significance was maintained even when the comparison was restricted to strong p53 staining in moderately to poorly differentiated adenocarcinomas (P < 0.05). Of the gallbladder carcinomas, poorly differentiated adenocarcinomas stained more strongly than well to moderately differentiated adenocarcinomas; the converse was true for extrahepatic bile duct/ampullary adenocarcinomas. CONCLUSION: The majority of gallbladder and extrahepatic bile duct/ampullary carcinomas stain for p53 protein. The incidence and pattern of staining is different, however, and supports the contention that these could be different tumors with differing etiologies and pathogenetic mechanisms.

Adenocarcinoma↗

PubMed2001

Chemical coding of intrinsic and extrinsic nerves in the guinea pig gallbladder: distributions of PACAP and orphanin FQ.

The complexity of the neural regulation of the gallbladder is reflected by the variety of neuroactive compounds that are found in the intrinsic and extrinsic nerves of the guinea pig gallbladder. The studies reported here used antisera to test for the presence of gallbladder nerves that are immunoreactive for the neuroactive peptides, pituitary adenylyl activating polypeptide (PACAP), and/or orphanin FQ (OFQ, also known as nociceptin). PACAP immunoreactivity was observed in nerve fibers of the paravascular plexus that were also immunoreactive for calcitonin gene-related peptide. These nerve fibers, which are also immunoreactive for substance P, could be followed into the ganglionated plexus. Within the ganglia, a small proportion of neurons was found to be immunoreactive for PACAP; these neurons were also immunoreactive for vasoactive intestinal peptide and nitric oxide synthase. Immunoreactivity for OFQ was observed in the perivascular plexus in nerve fibers that were also immunoreactive for tyrosine hydroxylase. These nerves were previously shown to be immunoreactive for neuropeptide Y. In the ganglionated plexus, immunoreactivity was observed in all gallbladder neurons, as demonstrated by double staining with antiserum directed against the neuron-specific RNA binding protein, Hu. OFQ immunoreactivity was also present in the small catecholaminergic neurons that are observed in a subset of the ganglia. These results further demonstrate the neurotransmitter diversity of the nerves of the gallbladder, and they provide an incentive for studies of the actions of these compounds in the gallbladder wall.

Animals↗

PubMedDate not supplied

Gallbladder cancer.

Gallbladder cancer has a reputation for being aggressive and incurable. Single institution series, however, have defined successful management strategies in which the extent of resection is based on the stage of the tumor at presentation. Careful ultrasound screening for abnormalities in the gallbladder wall, and CA19-9 serum determination prior to routine cholecystectomy may heighten awareness for cancer in this population. For tumors confined to the muscular layer of the gallbladder a simple cholecystectomy is associated with an almost 100% cure rate. Tumors invading through the muscle wall (Stage II) should be managed with extended cholecystectomy, including resection of hepatic segments IVb and V, and an extensive lymph node dissection of the porta hepatis, posterior pancreaticoduodenal, and interaortocaval lymph nodes. This operation for Stage II gallbladder cancer is associated with a 90% to 100% 3-year survival rate. Simple cholecystectomy fails in the majority of Stage II patients. Patients with Stage III and IV tumors may also benefit from an extended cholecystectomy. Patients with bulky primary tumors without lymph node metastases (T4N0) seem to have a better prognosis than those with distant lymph node metastases, and should be treated aggressively when possible. It is advantageous to perform the appropriate extent of surgery for gallbladder cancer at the initial operation. Heightened awareness of the presence of cancer and the knowledge of appropriate management are important. For patients whose cancer is an incidental finding on pathologic review, re-resection is indicated for all disease except Stage I. This review will discuss the epidemiology, pathology, and staging of gallbladder cancer and describe the appropriate surgical management based on the stage of the cancer.

Adult↗

PubMed2005

Angioarchitecture of the rabbit extrahepatic bile ducts and gallbladder.

The angioarchitecture of extrahepatic bile ducts and gallbladder of the miniature rabbit was studied by scanning electron microscopy (SEM) of vascular corrosion casts. Light microscopy of Masson-stained, paraffin-embedded transverse tissue sections served to attribute cast vascular structures to defined layers of bile ducts and gallbladder. In all segments of the bile tract, a mucosal and a subserosal vascular network was found. In glandular segments, the mucosal network was composed of a meshwork of subepithelial and circumglandular capillaries, which serve the mucosal functions. Differences in the angioarchitectonic patterns existed only in the subserosal networks as hepatic ducts own one supplying arteriole only, while the common bile duct owns a well-defined rete arteriosum subserosum. A well-developed dense subserosus venous plexus was present throughout the bile tract. Vascular patterns of the gallbladder body resembled those of the bile duct, whereby the dense subserous venous plexus was located close to the mucosal capillary network. The subserosal network in the neck of the gallbladder resembled that of the cystic duct. Spatial changes of the mucosal vascular network during volume changes of the gallbladder were documented. Measurements from tissue sections revealed bile tract diameters of 220-400 microm (extrahepatic ducts), 500-650 microm (cystic duct), and 4-6 mm (common bile duct). Data gained from high-powered SEM micrographs of vascular corrosion casts revealed vessel diameters of 200 microm (cystic artery), 90-110 microm (cystic vein), 30-40 microm (feeding arterioles), and 25-110 microm (subserosal venules). Crypt diameters in the filled gallbladder were 300-1,500 mum; those in the contracted organ were 100-600 microm.

Animals↗

PubMed1990

Synthesis of prostaglandins I2 and E2 by the canine gallbladder in vitro: studies using a new incubation chamber.

Using a specially designed incubation chamber, differential synthesis and the response to added arachidonic acid (25 mM) and L-alpha-phosphatidylcholine (LAP; 2 mM) was quantified in gallbladders from male and female dogs. Prostaglandin I2 (PGI2) was the predominant prostanoid synthesized, and tissues from females produced much more PGI2 under basal conditions than did gallbladders harvested from male dogs. Addition of arachidonic acid stimulated PGI2 synthesis by almost 100 per cent. Arachidonate-stimulated mucosal and serosal production of PGI2 were (mean(s.e.m.] comparable, 343(178) and 375(89) pg/cm2/min, respectively. Gallbladders from female animals synthesized significantly more PGI2 than did tissue from males. Indomethacin inhibited PGI2 synthesis in a dose-response manner; at 7 x 10(-5) M, prostanoid synthesis was inhibited by greater than 80 per cent. Arachidonic acid did not stimulate prostaglandin E2 (PGE2) production by gallbladder tissue. LAP similarly stimulated PGI2 biosynthesis, but in contrast to the effect of arachidonic acid, the effect was significantly greater in the serosa than the mucosa, 355(107) and 213(59) pg/cm2/min, respectively. LAP also stimulated PGE2 biosynthesis by the canine gallbladder in a pattern very similar to that of PGI2. Based on the differences in response to the two agents added, we conclude that arachidonic acid and L-alpha-phosphatidylcholine stimulate prostaglandin biosynthesis via independent pathways. We advocate the use of the incubation chamber for the assessment of prostanoid biosynthesis by the gallbladder in vitro.

Animals↗

PubMed1997

Chemical ablation of the gallbladder.

BACKGROUND: Chemical ablation of the gallbladder might avoid the need for surgery in elderly, unfit patients. This study examined the efficacy of various chemicals in destroying gallbladder mucosa. METHODS: Ninety-five per cent ethanol, 3 per cent sodium tetradecyl sulphate (STD), trifluoroacetic acid (TFA) 2 mol/l, tetracycline 50 mg/ml, 30 and 50 per cent phenol, and a mucosal exfoliant solution (compound ethylene diamine tetra-acetic acid) were tested for gallbladder ablation in rabbits. Histology was obtained 8 weeks after exposure to these chemicals. RESULTS: Thirty per cent phenol, tetracycline, TFA and ethanol when used as single agents were moderately effective in causing complete gallbladder mucosal obliteration, 50 per cent phenol caused a macroscopic burn of the entire gallbladder. The mucosal exfoliant solution and STD on their own did not cause mucosal destruction but had significantly enhanced efficacy when combined with 95 per cent ethanol, allowing reliable mucosal destruction with a 5-min contact duration. CONCLUSION: Ninety-five per cent ethanol and STD after pretreatment with a mucosal exfoliant solution may be the combination of choice for in situ gallbladder mucosal ablation.

Animals↗

PubMed2003

Randomized clinical trial of ultrasonic versus electrocautery dissection of the gallbladder in laparoscopic cholecystectomy.

BACKGROUND: Laparoscopic cholecystectomy is frequently complicated by gallbladder perforation and loss of bile or stones into the peritoneal cavity. The aim of this study was to compare the use of ultrasonic dissection and electrocautery with respect to the incidence of gallbladder perforation and intraoperative consequences. METHODS: Between January 1998 and January 2000, 200 patients undergoing elective laparoscopic cholecystectomy were randomized to electrocautery or ultrasonic dissection of the gallbladder. The main outcome measures were gallbladder perforation, operating time and the number of times the lens was cleaned. Univariate and multivariate analyses were performed. RESULTS: The perforation rate differed significantly: 16 per cent for ultrasonic dissection (n = 96) and 50 per cent for electrocautery (n = 103) (P < 0.001). The operating time of the least experienced surgeons, who had performed fewer than ten laparoscopic cholecystectomies, was significantly shorter when ultrasonic dissection was used, compared with electrocautery. The number of times the lens needed to be cleaned was significantly lower when ultrasonic dissection was used in complicated gallbladders (P < 0.035). At logistic regression analysis, the risk of perforation in the electrocautery group was about four times higher (odds ratio 0.26, P < 0.001) than that in the ultrasonic group. When the groups were matched for prognostic factors, including body mass index and surgical experience, the results were similar to those obtained with univariate and multivariate analysis. CONCLUSION: The use of ultrasonic dissection in laparoscopic cholecystectomy reduces the incidence of gallbladder perforation and helps the operation to progress. Less experienced surgeons benefit most from ultrasonic dissection, particularly in complicated intraoperative circumstances.

Adolescent↗

PubMedDate not supplied

Gallbladder glycoprotein secretion in mice with hemolytic anemia and pigment gallstones.

The nb/nb mouse with hereditary hemolytic anemia provides an animal model for the study of pigment gallstone disease. We measured glycoprotein synthesis and secretion in gallbladder neck and fundus of 6-month-old mice without stones, and in 12-month old mice with and without stones in order to determine the effect of age and presence or absence of stones on mucin release. We observed that the gallbladder necks of 12-month-old nb/nb mice with pigment stones secreted more 3H-glucosamine-labeled glycoprotein (68.2 dpm per microgram protein) than did the gallbladder necks of mice without pigment stones (31.1 dpm per microgram protein). When expressed as a percentage of total glycoprotein synthesis in the gallbladder neck, secretion of glycoprotein was 23.4% in 6-month-old hemolytic mice and 28.7% in 12-month-old hemolytic mice without pigment stones. However, in the presence of pigment stones, the percentage of secreted glycoprotein rose to 4.08%, which differed significantly from both 6-month-old (p < 0.02) and 12-month-old mice without stones (p < 0.05). Our results suggest that the presence of gallstones in nb/nb mice was associated with a localized increase in glycoprotein release from gallbladder neck. The mechanism for this increase may be precipitation of pigment-mucin concentrations in the gallbladder neck glands which has been previously described in this animal model.

Aging↗

PubMedDate not supplied

Effects of gallbladder function on human bile: compositional and structural changes.

Water and electrolyte absorption leading to increased intraluminal concentrations of lipids and other solutes comprise the primary physiologic effect of the gallbladder. The dynamics of enterohepatic circulation can lead to confinement of up to 60% of the bile acid pool within the gallbladder during prolonged fasting. This bile acid sequestration markedly reduces both the bile salt secretory rate and total solute concentration in comparison with the nonfasting state producing hepatic bile that is more than normally dilute especially in comparison with gallbladder bile. These conditions favor formation of small low-density vesicles in hepatic bile which are more buoyant than the concentrated biliary micelles found in anatomically dependent regions of the gallbladder. Vesicle formation in hepatic bile may explain the "stratification" phenomenon often noted within the gallbladder. This observation could be accounted for by inhomogeneous mixing of the dissimilar lipid particles, i.e., vesicles and micelles. If vesicles are present and stratified as presumed, the overall cholesterol transporting capability of the total lipid particles, including these regionalized vesicles, would be considerably enhanced. The net effect of this process would lead to an overestimation of the true degree of metastable cholesterol supersaturation for the biliary micellar system within the gallbladder on the incorrect assumption of homogeneous mixing of lipids.

Bile↗

PubMed1994

Artificial bile inhibits bile salt-induced gallbladder glycoprotein release in vitro.

The more hydrophobic bile salts cause rapid release of preformed gallbladder mucin and other glycoproteins by gallbladder explants in vitro, whereas the less hydrophobic bile salts elicit a lesser response. This study was designed to determine (a) whether this short-term effect was matched by a sustained increase in glycoprotein secretion over 24 hr and (b) whether it occurred when bile salts were presented in model biles rather than aqueous solution. Although 3 mmol/L taurodeoxycholate in aqueous solution increased release of preformed gallbladder glycoprotein to 843% of control values after 30 min incubation (p < 0.001), no significant increase was observed after 24 hr. The more prolonged exposure also reduced precursor uptake by 32% (p < 0.05) and inhibited synthesis of new glycoprotein by 24% (p < 0.05). Moreover, the stimulatory effect of taurodeoxycholate on release of gallbladder glycoprotein was much reduced when it was presented in model biles rather than in aqueous solution. Nor was there any difference between the effects of more hydrophobic vs. less hydrophobic bile salts when presented in model biles. Aqueous solutions of the more hydrophobic bile salts induce a rapid release of gallbladder glycoprotein in vitro but do not produce a sustained increase in glycoprotein secretion. Their effect is liable to be prevented in vivo by interaction between bile salts and the other lipids in gallbladder bile.

Animals↗