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PubMedDate not supplied

E-cadherin and beta-catenin expression in normal, inflamed and cancerous gallbladder tissue.

BACKGROUND: Changes of the E-cadherin/beta-catenin complex during cell-cell interactions result in the loss of cell adhesion and may account for the ability of cancer cells to metastasize. Gallbladder carcinoma (GBC) can develop during chronic inflammation from normal tissue. The aim of this study was to investigate the expression of E-cadherin and beta-catenin in normal gallbladder mucosa, inflamed gallbladder tissue and GBC. MATERIALS AND METHODS: Tissue from 10 GBC, 10 chronic cholecystitis and 10 healthy gallbladders were used to evaluate the expression of E-cadherin and beta-catenin by immunohistochemistry. RESULTS: The beta-catenin membranous expression decreased between cholecystitis and malignant tissue, as well as between normal epithelium and carcinoma. The E-cadherin membranous expression was reduced in normal gallbladder epithelia compared to carcinoma and also from inflammation to GBC. The cytoplasmatic beta-catenin expression did not show any significant difference. Cytoplasmatic E-cadherin was significantly different from normal gallbladders to carcinomas and between normal tissue and inflammation. No significant difference of the nuclear P-catenin expression could be observed. E-cadherin was not detected intra-nuclear in any tissue. CONCLUSION: Significant differences of E-cadherin and beta-catenin were detected between normal, inflamed and cancerous tissues. These changes of the protein expressions and the associated loss of adhesive mechanisms might lead to a cancerous pathway in GBC.

Cadherins↗

PubMed1991

Effects of age and gender on fat-induced gallbladder contraction and gastric emptying of a caloric liquid meal: a sonographic study.

In this study, the gastric emptying of a liquid fatty meal and the consecutive gallbladder contraction were simultaneously measured by ultrasound in four different age- and sex-related groups of normal subjects: group A, 15 women less than 50 yr (premenopausal); group B, 15 women greater than 50 yr (postmenopausal); group C, 15 men less than 50 yr; and group D, 15 men greater than 50 yr. Apart from a significantly delayed gastric emptying in the premenopausal women, no significant differences in the postprandial relative gallbladder emptying rates were observed between the four study groups. Ninety-five percent of all study subjects had a gallbladder volume reduction of more than 50% after a liquid fatty meal. It is therefore concluded, that 1) endogenous or contraceptive female sex hormones may have a delaying effect on gastric emptying of caloric liquids in the premenopausal state, 2) aging or gender do not significantly influence the fat-induced gallbladder contraction in man, and 3) a 50% residual volume of the gallbladder after a fatty meal should be considered as the upper limit of normal gallbladder contractility (95 percentile of a normal collective).

Adult↗

PubMed1986

Endocrine cells and lysozyme immunoreactivity in the gallbladder.

A total of 89 gallbladders with various conditions were examined histologically and immunohistochemically to detect various kinds of metaplastic changes. The gallbladder mucosa of the fetus and normal gallbladder showed no metaplastic changes. In 32 cases of chronic cholecystitis, metaplastic changes, such as mucous gland metaplasia (23 cases), Paneth's cells (six cases), and goblet cells (four cases) were observed. All cases containing Paneth's cells or goblet cells showed simultaneous lysozyme immunoreactivity and also contained argyrophilic cells. Among 23 cases with mucous gland metaplasia, 15 cases showed lysozyme immunoreactivity, eight contained argyrophilic cells, and 16 showed lysozyme immunoreactivity and/or argyrophilic reaction. The other seven cases showed only mucous gland metaplasia without endocrine cells or lysozyme immunoreactivity. These results suggest that the presence of lysozyme and/or endocrine cells is a conventional marker of gastrointestinal metaplasia of the gallbladder mucosa. Using these markers, 14 (28.6%) of 49 cases of adenocarcinoma of the gallbladder contained endocrine cells; 18 (36.7%) showed lysozyme immunoreactivity; and 25 (51.0%) contained at least one marker of endocrine cells or lysozyme immunoreactivity. These results suggest that at least half of adenocarcinomas of the gallbladder might be derived from metaplastic changes.

Adenocarcinoma↗

PubMed1988

[Surgical therapy of gallbladder cancer].

Because of the normally far advanced tumor stages of carcinomas of the gallbladder, the resection rate in the literature varies from 10 to 30 percent. Our own curative resection rate was 19% in a series of 89 patients between 1969 and 1985 first treated in our hospital. The palliative resection rate was 29%, in 10% we performed a palliative operation and in 36% an explorative laparotomy. The curative resected gallbladder carcinomas were mainly stage I and II tumors, incidentally found at operation or histopathological examination. Has the gallbladder carcinoma invaded perimuscular connective tissue, an extended operation with resection of the segments IVb and V of the liver and lymphnode dissection must be recommended. Stage III and IV carcinomas of the gallbladder with infiltration of the liver can be curatively operated organ-saving in using en-bloc resection of the gallbladder with the adjacent segments IVb and V, or IVb and VI and with lymphnode dissection of the hepatoduodenal ligament. The observed five-year-survival rate (Cutler and Ederer) including lethality of the curative resected carcinoma of the gallbladder is 56.3 +/- 25.2%.

Gallbladder↗

PubMed1987

[Determining the size of the gallbladder with ultrasound--methods and results].

By ultrasound undistorted two-dimensional pictures of gallbladder sections can be obtained. Determinations of size are performed either from one or from several well defined sonographic images. Studies of gallbladder contraction require at least 2 exposures: usually pictures of the "largest longitudinal section" are taken in the fasting state and 30 min after a stimulus (meal, hormones); for evaluation images are measured and compared. Estimations of gallbladder volume require at least 2 sonographic pictures of the gallbladder. We performed measurements in 250 patients. In most cases fasting volumes were between 10 and 25 ml and between 33 and 40 ml. There was a positive correlation with age and with body weight. Patients with cholelithiasis had larger gallbladder volumes than healthy controls. In 10 persons evacuation and filling of gallbladder after a meal was followed by serial measurements: maximal contraction was found between 20 and 45 min; original volumes were then reached after 180 min.

Bile↗

PubMed1983

The incidence of bacteria in gallbladder bile at acute and elective cholecystectomy.

Aerobic and anaerobic bacterial cultivation was carried out on gallbladder bile collected from all patients operated on with cholecystectomy during a 10-month period. Acute cholecystectomy was performed on 34 patients because of acute cholecystitis. Elective cholecystectomy was performed on 177 patients because of non-acute gallbladder pathology. Bacteria were found in gallbladder bile in 16.4% of patients with non-acute cholecystopathy compared to 58.8% of patients with acute cholecystitis (p less than 0.001). An increased incidence of pathogenic bacteria was observed in the acute compared to the elective cholecystectomy material. The acute inflammatory process, its severity and the age of the patient seemed to be important factors which could be related to the increased occurrence of bacteria in the gallbladder bile. A higher incidence of postoperative morbidity and infectious complications was found in patients with pathogenic bacteria in gallbladder bile than in patients with no growth of bacteria or opportunistic bacteria in gallbladder bile.

Acute Disease↗

PubMed1984

[Adrenergic and cholinergic innervation of the normal human gallbladder and in various diseases].

As demonstrate investigations of the human gallbladder neural elements, normal (15 persons), after cholecystectomy resulted from dyskinesia (9 cases), diseases of the gallbladder cervix (28 cases), chronic (263 cases) and acute (16 cases) cholecystitis, using Falk--Hillarp--Govyrin, Karnovsky--Roots, Bielshowsky--Gros methods and incubation in 2% glyoxylin acid solution, a rich adrenergic and cholinergic innervation has been demonstrated in the organ studied at the states mentioned and their connection with the pathomorphological changes in the gallbladder wall. The analysis of 2,428 cases of chronic and acute cholecystitis has been performed in order to compare the clinical signs with changes in the central nervous system and the neural elements of the gallbladders removed. The importance of the gallbladder neural elements in the development of dyskinesia, diseases of the gallbladder cervix and chronic cholecystitis is mentioned.

Adrenergic Fibers↗

PubMed1994

[Ultrasonographic evaluation of gallbladder and gastric emptying after ingestion of water with various saline compositions].

OBJECTIVE: Evaluation of gallbladder and gastric emptying after ingestion of a saline enriched water ("Acqua Santa" di Chianciano) in comparison with a commercial oligomineral water. STUDY DESIGN: A 40-minute blind prospective study. LOCATION: The study was performed at the Terme of Chianciano (Siena) for subjects of group A and at the Institute of Clinica Medica Generale and Terapia Medica of the University of Bologna for subjects of group B. PATIENTS OR PARTICIPANTS: Two groups of healthy subjects were studied. Each group consisted of 12 subjects without gallbladder disease. EXPERIMENTAL PROTOCOL: Fasting subjects of group A ingested alternatively, for two consecutive mornings, 400 ml of the saline enriched water at the natural temperature of 33 degrees C or 400 ml of oligomineral water warmed to the same temperature. Subjects of group B ingested the same waters at 18 degrees C. METHODS: Gastric and gallbladder emptying were evaluated, after ingestion of the different waters, by means of ultrasonography. RESULTS: In both groups gallbladder emptying was significantly higher after ingestion of the saline enriched water. On the other hand gastric emptying was similar with both waters. CONCLUSIONS: This study demonstrated that saline enriched water determines a greater emptying of the gallbladder in comparison with an oligomineral water. This effects is not related to gastric emptying but rather it is due to a higher concentration of saline components and thus to their possible effect on gallbladder motility.

Adult↗

PubMed1993

Abnormal gallbladder function in patients with irritable bowel syndrome.

Abnormalities of the autonomic nervous system function and cholecystokinin release have been described in patients with irritable bowel syndrome. Because the autonomic nervous system and cholecystokinin have an important role in the normal functioning of the gallbladder, we studied gallbladder contraction in response to a meal, using real time ultrasonography in irritable bowel syndrome patients (n = 20) and healthy controls (n = 15). The following parameters were studied: 1) fasting gallbladder volume, 2) residual volume after maximal contraction and at the end of 2 h, 3) maximum percent of gallbladder emptied, and 4) the time taken for maximal contraction. Fasting gallbladder volume (26.21 +/- 1.81 ml vs 15.21 +/- 1.63 ml, p < 0.001), and residual volume after maximal contraction (14.2 +/- 1.69 ml vs. 5.86 +/- 0.98 ml, p < 0.001) and at the end of 2 h (18.81 +/- 1.73 ml vs. 11.65 +/- 1.45 ml, p < 0.01) were significantly higher in the patient group, compared with controls. The maximum emptying was less (49.55 +/- 2.75% vs. 63.98 +/- 4.55%, p < 0.01) and the time taken for maximal contraction (59.25 +/- 3.8 min vs. 42.33 +/- 2.04 min, p < 0.001) was longer in the patient group than in the controls. Based on these observations, we conclude that patients with irritable bowel syndrome have significant abnormalities of gallbladder motor function.

Adolescent↗

PubMed1996

Selective blockade of cholecystokinin type B receptors with L-365,260 does not impair gallbladder contraction in normal humans.

OBJECTIVES: To evaluate the effect of selective blockade of type B cholecystokinin receptors on gall bladder contraction in normal humans and to compare methods for quantitative analysis of gall bladder contraction. METHODS: L-365,260, a novel, nonpeptide cholecystokinin antagonist shown to be selective for type B cholecystokinin receptors, was administered every 6 h over a 5-7 day period. Plasma levels of L-365,260 were determined by high pressure liquid chromatography. Gallbladder contraction after a standardized fatty meal was measured by ultrasonography, and results were calculated by ellipsoid or sum of cylinders methods. RESULTS: L-365,260 levels were comparable to levels in earlier studies demonstrating inhibition of pentagastrin-stimulated acid secretion in normal subjects and blockade of anxiogenic effects of cholecystokinin injections in patients with panic disorder. Regardless of the method used for estimating gallbladder size, none of the L-365,260 doses studied inhibited gallbladder contraction. Gallbladder size was most consistently estimated by the ellipsoid method using measurements normalized to individual values for minimum and maximum gallbladder dimensions. CONCLUSIONS: Multiple oral doses of L-365,260 do not alter ultrasonographically assessed gallbladder contraction at doses shown to be clinically effective in earlier studies. Despite being more difficult to implement, the sum of cylinders method for estimating gall bladder size offers no advantage over the ellipsoid method.

Adult↗

PubMed1996

Ultrasonic evaluation of gallbladder emptying with ceruletide.

In order to develop a practical and reproducible method to assess gallbladder function, gallbladder emptying was studied by ultrasound in 27 gallstone patients after i.m. administration of ceruletide (0.3 micrograms/kg), and the procedure was compared to oral cholecystography with fatty meal. Maximal percent gallbladder contraction was reached in all patients 30 min after ceruletide. Maximal percent contractions were 47.5 +/- 27.7 during ultrasound with ceruletide and 33.9 +/- 16.3 during oral cholecystography with fatty meal (p = 0.03). A significant linear relationship was found between the results obtained with the two different procedures (r = 0.57; p = 0.002). Serial ultrasound determinations of gallbladder emptying were performed in 16 patients. Day-to-day variation was below 20% in 11 subjects, and it ranged between 20 and 40% in 5 subjects. Minor side effects were observed in 9 patients. Ultrasound determination of gallbladder emptying after ceruletide appears to be a practical and reliable method to assess gallbladder function.

Adult↗

PubMed1996

Diagnosis of gallbladder carcinoma with color Doppler ultrasonography.

A 65-yr-old woman was referred to our department for evaluation of a gallbladder lesion detected at another institution, where she was diagnosed with chronic cholecystitis. Conventional ultrasonography revealed that the gallbladder lumen was filled with debris-like components, and the gallbladder wall was mildly thickened. Color Doppler ultrasonography revealed color signals in both the lesion and the gallbladder wall. These signals showed a high-speed pulsatile wave, and one of the visualized signals revealed a high-resistance index (1.0) on fast Fourier transform analysis. These findings were highly suggestive of malignancy. Surgery was performed, and histological examination of the resected specimen revealed carcinoma of the gallbladder. We conclude that color Doppler ultrasonography can be useful in the diagnosis of tumefactive gallbladder lesions.

Adenocarcinoma↗

PubMedDate not supplied

[Ultrasonographic assessment of gallbladder motility in obese subjects].

The reduction in gallbladder motility could play an important role in the pathogenesis of cholesterinic lithiasis by favouring the precipitation of cholesterol crystals, especially in obese subjects who, as is well known, present a greater biliary secretion of cholesterol. In the present study we evaluated, by ultrasonography, the emptying capacity of gallbladder following a liquid meal in 20 obese subjects (BMI 37.8 +/- 11.8 kg/m2) and in 20 control subjects (BMI 23.2 +/- 1.7 kg/m2). The base and residual volume of the gallbladder, expressed in ml, were significantly higher in the obese group than in the controls: 30.7 +/- 11.8 vs 22.0 +/- 6.7 (t = 2.88 p < 0.001) and 14.6 +/- 7.14 vs 10.2 +/- 4.7 (t = 2.14 p < 0.04), respectively. However, there was no significant difference between the percentages of gallbladder emptying in the two study groups, although in the obese subjects the minimum volume was reached at the 60th minute, while in the controls it occurred at 40 minutes. Our data, in agreement with most reports in the literature, indicate that the volume of the gallbladder is greater in obese subjects and they do not present an intrinsic defect in gallbladder contractility; therefore this condition can be excluded from the risk factors of biliary lithiasis in obese subjects.

Adult↗

PubMed1996

Effect of gallbladder contraction induced cholagogia on the pharmacokinetic profile of a sustained-release theophylline formulation.

Bile excretion might change the physiological milieu of the duodenum resulting in enhanced absorption of a drug due to increased solubilisation. This possible influence of bile salts following stimulation of gallbladder emptying via the release of cholecystokinin on the pharmacokinetics of a sustained-release theophylline (CAS 58-55-9) preparation (Bronchoretard) was evaluated in this study. An open, randomised 3-way cross-over study in 12 healthy, non-smoking volunteers was selected to prove or reject this hypothesis. All subjects received 500 mg of the sustained-release theophylline formulation under two different cholagogia stimulating test conditions and under a fasting reference condition. A standard breakfast and i.m. application of cholecystokinin enabled modulation of bile flow; a moderate and extreme contraction of the gallbladder could be induced after a standard breakfast and after i.m. application of cholecystokinin, respectively. Following a standard breakfast, gallbladder volumes were approximately halved (50.6%) compared to the baseline volume after 79 min. Injection of 0.3 micrograms/kg body weight cholecystokinin resulted in quick and complete gallbladder evacuation (94.6%) 36 min after the application of this cholagogue stimulus. Gallbladder volumes remained approximately constant under fasting conditions. This manipulation of bile flow did not influence concentration/time profiles of the sustained-release theophylline preparation compared to the fasting condition. Even almost complete evacuation of the gallbladder after application of cholecystokinin did not modify concentration/time profiles of theophylline in a relevant way. An unintentional rapid release of theophylline could be excluded for this sustained-release formulation for all three treatments, as not a single case of dose-dumping was observed. Furthermore, in vitro dissolution investigations using surfactants are neither predictive of food effects nor bile influence on in vivo absorption at least for the sustained-release formulation tested.

Adult↗

PubMed1997

Morphine augmentation increases gallbladder visualization in patients pretreated with cholecystokinin.

UNLABELLED: The purpose of this study was to determine if a combination of cholecystokinin (CCK) pretreatment followed by morphine augmentation improved the detection of cystic duct patency compared with CCK pretreatment only. METHODS: One hundred fifty-five patients with suspected acute cholecystitis had scintigraphy performed with 185-481 MBq (5-13 mCi) 99mTc-mebrofenin adjusted to the patients' total bilirubin levels. All patients were pretreated with 0.02 microgram/kg sincalide injected intravenously over 3-5 min. Sequential imaging was performed until gallbladder activity was identified or up to 90 min postinjection of mebrofenin. If no gallbladder was identified, a second dose of mebrofenin was given as necessary to have tracer in the biliary system. Then, 0.04 mg/kg intravenous morphine sulfate was administered, followed by imaging for up to 30 min or until gallbladder visualization. RESULTS: Twenty-eight percent (43/155) of the patients pretreated with CCK had nonvisualization of the gallbladder at 90 min postinjection of radiotracer. After intravenous morphine, the gallbladder was identified in 42% (18/43) of these patients (p = 0.0001). CONCLUSION: Hepatobiliary imaging with CCK pretreatment and imaging for 90 min was insufficient to identify all patent cystic ducts. Morphine augmentation significantly increased the frequency of gallbladder visualization in patients pretreated with CCK.

Acute Disease↗

PubMedDate not supplied

Staging of carcinoma of the gallbladder--an ultrasonographic evaluation.

BACKGROUND/AIMS: Preoperative staging of carcinoma of the gallbladder is important in choosing the most appropriate treatment modality. Ultrasonography is commonly used for the diagnosis of carcinoma of the gallbladder, but its role in staging of the disease has not been adequately evaluated. The aim of this study was to prospectively evaluate the role of ultrasonography performed by a single operator in the staging of carcinoma of the gallbladder. METHODOLOGY: Twenty-six patients with carcinoma of the gallbladder were evaluated in this study. Ultrasonographic staging was done by a single senior radiologist and compared with surgical staging using the AJCC TNM staging system. A retrospective evaluation was done of 122 operated patients with carcinoma of the gallbladder, and the findings were compared to the results of the prospective study. RESULTS: In the prospective study, the overall accuracy of ultrasonogaphy in correctly staging the disease was 38% (10/26). Only 1 patient was overstaged, while the majority of patients were understaged (15) due to missed distant metastasis (10) and missed advanced local infiltration (5). The sensitivity in detecting liver infiltration was 50%; lymph node metastasis, 50%; and liver metastasis, 8%. In the retrospective study, the similar detection rates were 27%, 25% and 10%, respectively. CONCLUSION: Real time ultrasonography has been found to have inherent limitations in staging carcinoma of the gallbladder. Its accuracy, though improved in a prospective study, is inadequate in staging the disease accurately. More accurate imaging modalities are therefore required to accurately stage the disease preoperatively, so as to avoid unnecessary laparotomies.

Female↗

PubMed1997

Free radical reactions in the gallbladder.

The changes in the composition of bile can lead to the process of it's crystallization in the gallbladder. In bile model it was shown that inflammation with the generation of reactive oxygen metabolites may induce and influence the cholesterol monohydrate crystal formation within supersaturated bile. The aim of this study was to investigate the ability to detect traces of reactive oxygen metabolites, thiobarbituric acid reactive compounds and dien, in order to compare cholesterol and bilirubin contents in bile and serum during different conditions of inflammation in the gallbladder's wall. In every bile sample a reference to free radical reaction was found. There was an increase in MDA during higher degree of inflammation in the gallbladder, but no alteration in the dien content was observed. In case of common bile duct stones the bilirubin in the serum and in the gallbladder was parallelly high, but in other cases there were no significant correlation. In an occluded gallbladder with hydrops the content of protein was significantly higher in 85% of the cholesterol stones. As a conclusion, free radical reactions in the wall of gallbladder as well as in bile can induce gallstone formation. Further studies are needed to clarify the time which is sufficient to change the composition of bile and the degree of inflammation which lead to the onset of stone formation.

Bile↗

PubMed2003

Strategies for surgical treatment of gallbladder carcinoma based on information available before resection.

HYPOTHESIS: Precise preoperative staging for gallbladder carcinoma is difficult, despite recent advances in hepatobiliary imaging. However, the most accurate preoperative staging may be possible by integrating preoperative key data. OBJECTIVE: To establish useful strategies for the surgical treatment of gallbladder cancer based on information available before resection. DESIGN: Retrospective review. SETTING: University hospital and tertiary referral cancer center. PATIENTS AND METHODS: From January 1, 1978, through March 31, 2001, 152 patients with gallbladder cancer underwent surgical resection with curative intent. Preoperative diagnoses of the T factor (image-T) and N factor (image-N) in the TNM classification were determined by evaluating all findings of diagnostic imaging, including ultrasonography, enhanced computed tomography, endoscopic ultrasonography, and angiography. The distribution of lymph node metastasis and prognostic factors were also analyzed. RESULTS: The overall diagnostic accuracy for image-T was 52.6% (95% confidence interval, 44.7%-60.6%) and was lower in patients with pT1 and pT2 disease (37.2% and 33.9%, respectively). However, image-T was a significant predictor of lymph node metastasis and patient outcome. Preoperative staging for N was more difficult, with only 24.5% (95% confidence interval, 12.4%-36.5%) of the node-positive patients being correctly diagnosed. An analysis of harvested lymph nodes showed that the cystic, pericholedochal, and posterosuperior peripancreatic nodes were the most prevalent sites of metastasis, and these were considered key nodes for the lymphatic spread of gallbladder cancer. By combining data on image-T and positivity of these key nodes, more accurate TNM staging was possible. Although an extended lymph node dissection provided significantly better survival in patients with pN2 disease, there was no survival advantage to more radical operations, including bile duct resection or pancreaticoduodenectomy. CONCLUSIONS: Although precise preoperative TNM staging for gallbladder carcinoma was difficult, the most accurate staging before resection was possible by integrating image-T classification and data from the intraoperative histopathologic examination of key lymph nodes. Based on this staging, we propose algorithms for the surgical treatment of gallbladder carcinoma.

Adult↗