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PubMed1985

Oral water causes emptying of the human gallbladder through actions of vagal stimuli rather than motilin.

A drink of water was found to cause partial emptying of the human gallbladder in parallel with the release of motilin. The water-induced effect on the gallbladder was abolished by atropine, whereas the release of motilin remained unchanged. Exogenous infusions of porcine motilin aimed at achieving either a physiological or a pharmacological plasma motilin increment were both without effect on gallbladder dynamics as compared with saline infusions. It is concluded that the water-induced gallbladder emptying is vagally dependent. Furthermore, the results suggest that motilin does not cause gallbladder emptying in man.

Adult↗

PubMed1992

Gallbladder function in acromegalic patients taking long-term octreotide: evidence of rebound hypermotility on cessation of treatment.

Octreotide is increasingly being used in the treatment of acromegaly. It effectively suppresses growth hormone secretion but also has inhibitory effects on gastrointestinal regulatory peptides and induces gallbladder paresis, which may predispose to gallstone formation. In nine acromegalic patients receiving long-term octreotide treatment gallbladder emptying, assessed by 99Tc-EHIDA scintigraphy after a standard fatty meal, was significantly impaired (p less than 0.005) when compared with normal healthy control subjects. Asymptomatic gallstone formation occurred in one patient who had the most severely impaired gallbladder emptying. Between 24 and 96 h after cessation of octreotide, in six of seven patients studied, gallbladder emptying had not only recovered but demonstrated significant rebound hypermotility (p less than 0.005). This finding has important implications for the administration of long-term octreotide therapy and suggests that a drug-free period each week may enable evacuation of gallbladder contents and reduce the risk of gallstone formation.

Acromegaly↗

PubMed1995

Cholesterol gallstone formation in man and potential treatments of the gallbladder motility defect.

Cholelithiasis affects 10-15% of the adult population in Western society, and about 75% of gallstones are of cholesterol type. Hepatic hypersecretion of cholesterol with the formation of instable cholesterol-rich vesicles in bile, an imbalance between nucleation-inhibiting and nucleation-promoting proteins with further aggregation of cholesterol crystals in a gallbladder with a motility defect (stasis), all play a role in the pathogenesis of cholesterol gallstones. Experimental animal models suggest that gallstone formation can be prevented by improving gallbladder emptying. Thus, a better understanding of the causes underlying the impaired gallbladder motor function in patients with gallstones might lead to the selection of therapeutic approaches for those individuals who are at increased risk for the formation or recurrence of gallstones. The present article focuses on current concepts and theories on the pathogenesis of cholesterol gallstones with emphasis on the gallbladder motility defect. Several treatment strategies for the correction of gallbladder hypomotility are also discussed.

Adult↗

PubMed1989

Cholecystokinin induced gallbladder contraction is influenced by nicotinic and muscarinic receptors.

Effects of pirenzepine, known as a muscarinic receptor antagonist, on the contraction of dog gallbladder elicited by cholecystokinin (CCK) were examined in comparison with atropine and hexamethonium ones. Intraluminal gallbladder pressure in an in situ anaesthetized dog model was chosen for studying gallbladder motility. The intravenous administration of pirenzepine (0.75 mg/kg b.wt.), atropine (3 mg/kg b.wt.) or hexamethonium (5 mg/kg b.wt.) elicited a marked decrease in the increase of intraluminal gallbladder pressure induced by intravenous bolus injections of CCK (0.25-2 Ivy dog unit/kg b.wt.) and by continuous infusion of CCK (0.025-0.4 Ivy dog unit/kg b.wt./min). It was concluded that CCK induced gallbladder contractions were influenced by both nicotinic and muscarinic receptors.

Animals↗

PubMed2004

Relationship between urokinase-type plasminogen activator receptor and vascular endothelial growth factor expression and metastasis of gallbladder cancer.

AIM: To investigate the relationship of urokinase type plasminogen activator receptor (uPAR) and vascular endothelial growth factor (VEGF) expression with clinical and pathological characteristics of human gallbladder cancer. METHODS: uPAR and VEGF expressions in 68 gallbladder cancer tissues were detected with anti-receptor immunohistochemical stain. RESULTS: Expression rate of uPAR was 57.4% (39/68), and VEGF 51.5% (35/68) in gallbladder cancer tissues. Expression of both uPAR and VEGF was significantly related to metastasis, but not significantly correlated with differentiation stage and size of gallbladder cancer. CONCLUSION: Expression of uPAR and VEGF may be an invasive phenotype of gallbladder cancer and indicator for predicting prognoses, and uPAR expression is significantly correlated with the expression of VEGF.

Biomarkers, Tumor↗

PubMed2004

CT biliary cystoscopy of gallbladder polyps.

AIM: CT virtual endoscopy has been used in the study of various organs of body including the biliary tract, however, CT virtual endoscopy in diagnosis of gallbladder polyps has not yet been reported. This study was to evaluate the diagnostic value of CT virtual endoscopy in polyps of the gallbladder. METHODS: Thirty-two cases of gallbladder polyps were examined by CT virtual endoscopy, ultrasound, CT scan with oral biliary contrast separately and confirmed by operation and pathology. CT biliary cystoscopic findings were analyzed and compared with those of ultrasound and CT scan with oral biliary contrast, and evaluated in comparison with operative and pathologic findings in all cases. RESULTS: The detection rate of gallbladder polyps was 93.8%(90/96), 96.9%(93/96) and 79.2%(76/96) for CT cystoscopy, ultrasound and CT scan with oral contrast, respectively. CT biliary cystoscopy corresponded well with ultrasound as well as pathology in demonstrating the location, size and configuration of polyps. CT endoscopy was superior to ultrasound in viewing the polyps in a more precise way, 3 dimensionally from any angle in space, and showing the surface in details. CT biliary cystoscopy was also superior to CT scan with oral biliary contrast in terms of observation of the base of polyps for the presence of a pedicle, detection rates as well as image quality. The smallest polyp detected by CT biliary cystoscopy was measured 1.5 mm x 2.2 mm x 2.5 mm. CONCLUSION: CT biliary cystoscopy is a non-invasive and accurate technique for diagnosis and management of gallbladder polyps.

Adult↗

PubMed2005

Cyclooxygenase-2 promotes angiogenesis by increasing vascular endothelial growth factor and predicts prognosis in gallbladder carcinoma.

AIM: To investigate the relationships between the expression of cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF) and the degree of vascularization, clinicopathologic feature, survival time of patients with gallbladder carcinomas. METHODS: Sixty-four gallbladder carcinoma specimens were evaluated for COX-2, VEGF expression by immunohistochemical methods. Microvessel counts (MVC) were determined using CD(34). The relationships between COX-2, VEGF expression, CD(34)-stained MVC, clinicopathologic features and survival time were analyzed. The correlations between COX-2 and VEGF expression, CD(34)-stained MVC were also investigated. RESULTS: COX-2, VEGF immunoreactivity were observed in 71.9% (46/64) and 54.7% (35/64) specimens, respectively. The average MVC in 64 cases of gallbladder carcinoma was 57+/-14 per high power vision field. The status of MVC was closely correlated with Nevin staging, tumor differentiation and lymph node metastasis (P<0.01, 0.002, and 0.003, 0.000, respectively). Increased VEGF expression was significantly correlated with tumor differentiation (poorly and moderately>well differentiated, P<0.05, P = 0.016). Clinical stages had no relation with the expression of VEGF (P>0.05, P = 0.612). There was a positive correlation between COX-2 expression and clinical stages. The positive rate of COX-2 was higher in cases of Nevin stages S(4)-S(5) (81.8%) than in those of Nevin stages S(1)-S(3) (50.0%) with a statistical significance (P<0.01, P = 0.009). The expression of COX-2 did not vary with differentiation (P>0.05, P = 0.067). Statistically significant differences were also observed according to lymph node metastasis, COX-2 expression and VEGF expression (P<0.01, 0.000, and 0.001, respectively). There was no relation between VEGF, COX-2 expression, MVC and the age and sex of patients. MVC and VEGF positive rate in the COX-2 positive gallbladder carcinoma tissue was higher than that in the COX-2 negative tissue (P<0.05, 0.000, and 0.032, respectively). Patients with VEGF, COX-2 positive tumors had a significantly shorter survival time than those with negative tumors (P<0.05, 0.004, 0.01, respectively). CONCLUSION: Augmented tumor neovascularization induced by VEGF may be one of the several effects of COX-2 responsible for poor prognosis of human gallbladder carcinoma. COX-2 inhibitor, either in combination therapy with other agents, or for chemoprevention, may be effective via suppression of angiogenesis in this fatal disease.

Adult↗

PubMed2005

Multiseptate gallbladder with anomalous pancreaticobiliary ductal union: a case report.

Multiseptate gallbladder, characterized by the presence of multiple septa dividing the gallbladder lumen, is a very extremely rare congenital anomaly of the gallbladder. On the other hand, anomalous pancreaticobiliary ductal union is also one of the congenital anomalous biliary diseases and thought to be related with choledochal cyst or biliary tract malignancies. In this paper, we describe a unique and first patient of multiseptate gallbladder with anomalous pancreaticobiliary ductal union and a review of the literature. To clarify more characters of the multiseptate gallbladder, examination of a larger patient population will be needed and further studies will be required.

Bile Ducts↗

PubMed2005

Effect of rhubarb on contractile response of gallbladder smooth muscle strips isolated from guinea pigs.

AIM: To investigate the effect of rhubarb on contractile response of isolated gallbladder muscle strips from guinea pigs and its mechanism. METHODS: Guinea pigs were killed to remove the whole gallbladder. Two or three smooth muscle strips (8 mm x 3 mm) were cut along the longitudinal direction. The mucosa on each strip was carefully removed. Each longitudinal muscle strip was suspended in a tissue chamber containing 5 mL Krebs solution (37 degrees), bubbled continuously with 950 mL/L O(2) and 50 mL/L CO(2). The resting tension (g), mean contractile amplitude (mm), and contractile frequency (waves/min) were simultaneously recorded on recorders. After 2-h equilibration, rhubarb (10, 20, 70, 200, 700, 1,000 g/L) was added cumulatively to the tissue chamber in turns every 2 min to observe their effects on gallbladder. Antagonists were given 3 min before administration of rhubarb to investigate the possible mechanism. RESULTS: Rhubarb increased the resting tension (from 0 to 0.40+/-0.02, P<0.001), and decreased the mean contractile amplitude (from 5.22+/-0.71 to 2.73+/-0.41, P<0.001). It also increased the contractile frequency of the gallbladder muscle strips in guinea pigs (from 4.09+/-0.46 to 6.08+/-0.35, P<0.001). The stimulation of rhubarb on the resting tension decreased from 3.98+/-0.22 to 1.58+/-0.12 by atropine (P<0.001), from 3.98+/-0.22 to 2.09+/-0.19 by verapamil (P<0.001) and from 3.98+/-0.22 to 2.67+/-0.43 by phentolamine (P<0.005). But the effect was not inhibited by hexamethonium (P>0.05). In addition, the action of mean amplitude and frequency was not inhibited by the above antagonists. CONCLUSION: Rhubarb can stimulate the motility of isolated gallbladder muscle strips from guinea pigs. The stimulation of rhubarb might be relevant with M receptor, Ca(2+) channel and alpha receptor partly.

Adrenergic alpha-Antagonists↗

PubMed2006

Expression of cyclooxygenase-2 is associated with p53 accumulation in premalignant and malignant gallbladder lesions.

AIM: To examine the relationship between cyclooxygenase-2 (COX-2) overexpression and p53 accumulation in gallbladder carcinoma and its precursor lesions. METHODS: Sixty-eight gallbladder tissue samples comprising 14 cases of normal gallblader epithelium, 27 cases of dysplasia (11 low-grade dyplasia and 16 high-grade dysplasia) and 27 adenocarcinomas were evaluated by immunohistochemistry for COX-2 expression and p53 accumulation. The relationship among COX-2 expression, p53 accumulation and clinicopathological characteristics was analysed. RESULTS: COX-2 was expressed in 14.3% of normal gallbladder epithelium, 70.3% of dysplastic epite hlium, and 59.2% of adenocarcinomas. When divided into low- and high-grade dysplasia, COX-2 was positive in 5 (45.4%) cases of low-grade and 14 (87.5%) of high-grade dysplasia (P = 0.019). Accumulation of p53 was detected in 5 (31.2%) cases of high-grade dysplasia and in 13 (48.1%) of carcinomas. No p53 accumulation was found in normal epithelium or low-grade dysplasia. COX-2 overexpression was observed in 17 of 18 (94.4%) cases with p53-accumulation in comparison with 20 (40.0%) out of 50 cases without p53 accumulation (P < 0.001). CONCLUSION: The significant differences in COX-2 expression among normal epithelium, low-grade dysplasia and high-grade dysplasia suggest that overexpression of COX-2 enzyme is an early event in gallbladder carcinogenensis. Furthermore, since accumulation of p53 correlates with COX-2 expression, COX-2 overexpression observed in gallbladder high-grade dysplasia and carcinoma might be partly due to the dysfunction of p53.

Adenocarcinoma↗

PubMed2006

Effect of Fructus Psoraleae on motility of gallbladder isolated smooth muscle strips from guinea pigs.

AIM: To observe the effect of Fructus Psoraleae on motility of isolated gallbladder muscle strips of guinea pigs and its mechanism. METHODS: Guinea pigs were hit to lose consciousness and the whole gallbladder was removed quickly. Two or three smooth muscle strips (8 mm x 3 mm) were cut along a longitudinal direction. The mucosa was gently removed. Every longitudinal muscle strip was suspended in a tissue chamber which was continuously perfused with 5 mL Krebs solution (37 degrees of C), pH 7.4, and aerated with 950 mL/L O2 and 50 mL/L CO2. The isometric response was recorded with an ink-writing recorder. After 2 h equilibration under 1 g-load, 50 microL Fructus Psoraleae (10, 20, 70, 200, 700, 1000 g/L) was added cumulatively into the tissue chamber in turn every 2 min to observe their effects on gallbladder muscle strips (cumulating final concentration of Fructus Psoraleae was 0.1, 0.3, 1.0, 3.0, 10.0, 20.0 g/L). The antagonists, including 4-DAMP, benzhydramine, hexamethonium, phentolamine, verapamil and idomethine were given 2 min before Fructus Psoraleae respectively to investigate the mechanisms involved. RESULTS: Fructus Psoraleae dose-dependently increased the resting tension (r = 0.992, P < 0.001), decreased the mean contractile amplitude (r = 0.970, P < 0.001) and meanwhile increased the contractile frequency of the gallbladder muscle strip in vitro (r = 0.965, P < 0.001). The exciting action of Fructus Psoraleae on the resting tension could be partially blocked by 4-DAMP (the resting tension decreased from 1.37 +/- 0.41 to 0.70 +/- 0.35, P < 0.001), benzhydramine (from 1.37 +/- 0.41 to 0.45 +/- 0.38, P < 0.001), hexamethonium (from 1.37 +/- 0.41 to 0.94 +/- 0.23, P < 0.05), phentolamine ( from 1.37 +/- 0.41 to 0.89 +/- 0.22, P < 0.01) and verapamil (from 1.37 +/- 0.41 to 0.94 +/- 0.26, P < 0.05). But the above antagonists had no significant effect on the action of Fructus Psoraleae-induced mean contractile amplitude (P > 0.05). Moreover, the increase of the contractile frequency due to Fructus Psoraleae was inhibited by 4-DAMP (decreased from 8.3 +/- 1.2 to 6.8 +/- 0.5, P < 0.01) and hexamethonium (from 8.3 +/- 1.2 to 7.0 +/- 0.9, P < 0.05). Idomethine had no significant effect on the Fructus Psoraleae-induced responses (P > 0.05). CONCLUSION: Fructus Psoraleae enhances the motility of isolated gallbladder muscle strips from guinea pigs, in a dose-dependent manner. The effect of Fructus Psoraleae is partly related to M3, N receptor, alpha receptor, H1 receptor, Ca2+ channel, but not related to prostaglandin.

Animals↗

PubMed2006

A case of Crohn's disease involving the gallbladder.

Crohn's disease is well known to affect any part of the gastrointestinal tract including the oral cavity and anus. Various extraintestinal complications have been reported in Crohn's disease, but extraintestinal involvement characterized by granulomatous lesions is uncommon. Here, we have reported a case about the involvement of the gallbladder in Crohn's disease. A 33-year-old woman was diagnosed having panperitonitis due to intestinal perforation and cholecystitis. The patient was moved to the surgical service for an emergency operation. On the resected specimen, there was a broad longitudinal ulcer at the mesenteric side. The mucosa of the gallbladder was nodular and granular, and the wall was thickened. The surface epithelium of the gallbladder was partially eroded and pyloric gland metaplasia was observed focally. Rokitansky-Aschoff sinuses were also present. From the lamina propria to the subserosal layer, there were several well-formed epithelioid cell granulomas, which were the non-caseating sarcoidal type different from the foreign-body and xanthomatous granulomas. Periodic-acid Schiff and acid fast stains revealed no organism within the granulomas. Lymphoid aggregates were present throughout the gallbladder wall. Sections from the resected ileum showed typical features of the Crohn's disease. When cholecystectomy is performed in a patient with Crohn's disease, the possibility of gallbladder involvement should be carefully examined by histopathological tests.

Adult↗

PubMed2007

An unusual cause of cholecystitis: heterotopic pancreatic tissue in the gallbladder.

Gallbladder localization of heterotopic pancreas (HP) is uncommon and very rarely gives rise to symptoms. Herein we report a case of HP found in the gallbladder neck presented with signs and symptoms of cholecystitis. The patient was a 40-year old male, suffering from epigastric pain, abdominal fullness and fever. On physical examination, the right upper abdomen was tender with a positive Murphy's sign. Ultrasonographic examination showed a hydropic gallbladder without stones and he underwent a cholecystectomy. Pathological examination revealed an intramural nodule (9 mm) in the neck region which is consisted of acini, ducts and islet cells of an aberrant pancreatic tissue. Although HP is encountered rarely in the gallbladder and is found incidentally during pathological studies, this case emphasizes that HP might cause symptoms and present clinically as cholecystitis. For this reason, in patients presenting with symptomatic gallbladder diseases, including cholecystitis without any other pathology, HP should be taken into consideration before it is diagnosed as "idiopathic".

Adult↗

PubMed2007

Gallbladder lymphangioma: a case report and review of the literature.

Lymphangiomas are rare, benign tumors of the lymphatic system, usually present in children aged 5 years and younger. Because they are asymptomatic until the mass enlarges to cause symptoms, most lymphangiomas are diagnosed at adulthood incidentally. We experienced a case of a 60-year-old man diagnosed with a cystic lymphangioma of the gallbladder, which was successfully resected without any complication. Magnetic resonance imaging and magnetic resonance cholangiopancreatography were very helpful for the diagnosis of the cystic lesion around the gallbladder as were ultrasonography and computed tomography scan. These showed a multi-lobulated cystic mass with intact cystic duct and bile duct in the gallbladder fossa. The patient underwent an open cholecystectomy and the histological findings were consistent with a cystic lymphangioma of the gallbladder. We here report the case of cystic lymphangioma of the gallbladder with a review of the literature.

Cholangiopancreatography, Magnetic Resonance↗

PubMed2003

Correlation of P-glycoprotein expression with poor vascularization in human gallbladder carcinomas.

AIM: To investigate the relationship between the expression of P-glycoprotein (P-gp) and the degree of vascularization in gallbladder carcinomas. METHODS: P-gp was stained with streptavidin-peroxidase complex immunohistochemical method in routine paraffin-embedded sections of gallbladder carcinomas. Microvessel counts (MVC) were determined using factor-VIII-related antigens. RESULTS: The average MVC in 32 cases of gallbladder carcinomas was (34 +/- 10)/HP. The value of MVC was closely correlated with Nevin staging and tumor differentiation (P<0.01 and P<0.05). The total expression rate of P-gp was 62.5%. The P-gp expression rate in cases of Nevin staging S1-S3 (78.6%) was higher than that of S4-S5 (50.0%) with no statistical significance. The P-gp expression rate was not correlated with tumor differentiation or pathologic types. The value of MVC in P-gp (+) cases was markedly lower than that in P-gp (-) cases (P<0.01). The positive rate of P-gp was significantly higher in cases of smaller MVC than those of bigger MVC (P<0.05). CONCLUSION: MVC may be used as one of the important parameters to reflect the biological behaviors of gallbladder carcinomas. As a major cause of drug resistance, the overexpression of P-gp is closely correlated with the poor vascularization in gallbladder carcinomas.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2000

CEA immunohistochemical localization is correlated with growth and metastasis of human gallbladder carcinoma.

Carcinoembryonic antigen (CEA) is a good marker of colorectal cancer. Recent studies have demonstrated that CEA may function as a metastatic potentiator by different pathways; i.e., modulation of immune responses, facilitation of intercellular adhesion and cellular migration. However, expression patterns of CEA have not yet been established in human gallbladder carcinomas. In this study, we examined CEA expression in human gallbladder adenocarcinomas and its clinicopathological significance. CEA immunoreactivity was detected not only in the cancer cells (cytoplasmic type: 63.0%, 34/54) but also in the cancer stroma (stromal type: 29.6%, 16/54). According to TNM classification, 75.0% (30/40) of T2-4 gallbladder cancers showed cytoplasmic CEA, while 28.6% (4/14) of the T1 cancers were cytoplasmic CEA-positive (p<0.05). Stromal CEA expression was detected in 40.0% (16/40) and none (0/14) of the T2-4 and T1 cancers, respectively (p<0.05). Lymph node metastasis was frequently found in the cytoplasmic CEA- and stromal CEA-positive gallbladder cancers (44.1% and 62.5%, respectively). These observations suggested that CEA expression plays important roles in cancer cell growth and metastasis of human gallbladder adenocarcinomas.

Adenocarcinoma↗

PubMed2000

DF3 expression in human gallbladder carcinoma: significance for lymphatic invasion.

DF3 (MUC 1) is a member of a family of high molecular weight glycoproteins. Recent studies have demonstrated that DF3 is expressed in tumors of various human organs, and may function as an anti-adhesion molecule that inhibits cell-to-cell adhesion, inducing tumor metastasis. However, expression patterns of DF3 have not yet been established in human gallbladder carcinomas. In this study, we examined DF3 expression in human gallbladder adenocarcinoma and its clinicopathological significance. DF3 immunoreactivity was detected not only in the cancer cells (cytoplasmic type; 50.0%, 27/54) but also in the cancer stroma (stromal type; 46.3%, 25/54). According to TNM classification, 65.0% (26/40) of T2-4 gallbladder cancers showed cytoplasmic DF3, while 7.1% (1/14) of the T1 cancers were cytoplasmic DF3-positive (p<0.001). Stromal DF3 expression was detected in 62.5% (25/40) and none (0/14) of the T2-4 and T1 cancers, respectively (p<0.001). Lymph node metastasis was frequently found in the cytoplasmic DF3- and stromal DF3-positive gallbladder cancers (59.3% and 60.0%, respectively). These observations suggested that DF3 expression plays important roles in cancer cell growth and metastasis of human gallbladder adenocarcinomas.

Adenocarcinoma↗

PubMedDate not supplied

The elevated mRNA content as a potential indicator of precancerous states of the gallbladder mucosa in patients with pancreaticobiliary maljunction.

Pancreaticobiliary maljunction (PBM) patients have a high incidence of cancer in the gallbladder. In the present study, we showed that precancerous lesions in the gallbladder of PBM such as hyperplasia or metaplasia, indicated high concentration of the amount of total mRNA. The mRNA content could be easily measured by our new technique utilizing a GenePlate, which is a poly (dT) oligonucleotide immobilized plastic plate, and Yoyo-1, a fluorescent DNA intercalator. To standardize the mRNA contents, we utilized which was defined as the ratio of total mRNA contents to total nucleic acids in a same sample. The mRNA index of the proliferating cells was significantly higher than that of the resting cells, and the mRNA index of cancer cells, such as gastric cancer, colon cancer, bile duct cancer, and gallbladder cancer also showed significantly higher concentration than that of normal mucosa. In the study of precancerous lesion, PBM, the mRNA index was significantly higher than that of mild cholecystitis but less than that of gallbladder cancer, suggesting that in the gallbladder mucosa of PBM, a precancerous state was able to be diagnosed by the mRNA index.

Animals↗

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