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An immunohistochemical study of the expression of adhesion molecules in gallbladder lesions.

We investigated the expression of 10 adhesion molecules (alpha-catenin, beta-catenin, gamma-catenin, CD44, CD44v6, ICAM-1, CD56, CEA, E-cadherin, and CD99) in 46 gallbladder carcinomas, 14 adenomas, 15 low-grade dysplasias, nine intestinal metaplasias, and 20 samples of normal gallbladder epithelium by immunohistochemistry. The expression of adhesion molecules was altered in gallbladder carcinomas and adenomas. In gallbladder carcinomas, increased expression of ICAM-1, CEA, and CD44v6 was observed, together with decreased expression of alpha/beta/gamma-catenin and CD99. In adenomas, aberrant expression of CD44v6 and CD56, as well as reduced expression of alpha/beta/gamma- and E-cadherins, was noted. Expression of alpha/beta/gamma-catenin was reduced in low-grade dysplasia, whereas there was no change in the expression of these adhesion molecules in metaplasia. Expression of ICAM-1, CD99, E-cadherin, and CD56 was correlated with clinical stage. In addition a correlation was noted between expression of ICAM-1 and E-cadherin and lymph node metastasis (p<0.05). These results suggest that altered expression of these adhesion molecules is involved in the progression and metastasis of gallbladder carcinomas.

Adenoma↗

Ultrasonographic evaluation of gallbladder function in patients with Schistosoma mansoni infection.

Gallbladder function was studied in 22 patients with portal hypertension due to advanced Schistosoma mansoni infection and in 17 healthy adults. The fasting volume of the gallbladder was significantly less in patients than in controls. The gallbladder wall was grossly thickened in the study group. There was a significant difference between the patients and controls in the reduction of gallbladder volume following a fatty meal. Although the portal vein diameter and the splenic volume were significantly larger in study patients, no significant correlation could be detected between the reduction in volume or wall thickness of the gallbladder and any of the relevant sonographic features of schistosomiasis-induced portal hypertension.

Gallbladder↗

Differences in cholecystokinin release and gallbladder contraction between emulsified and nonemulsified long-chain triglycerides.

BACKGROUND: Fat is a potent stimulus of cholecystokinin (CCK) release. Apart from lipolysis, fatty acid chain length, and saturation, emulsification may also determine the magnitude of CCK release. METHODS: We have studied the effect of emulsification of soybean oil on CCK and pancreatic polypeptide (PP) release (radioimmunoassay [RIA]) and gallbladder motility (ultrasonography). Six healthy subjects were studied on three separate occasions in random order during (1) intraduodenal administration of emulsified long-chain triglycerides (LCT) (6 mmol/h for 120 minutes); (2) equimolar amounts of nonemulsified LCT with addition of emulsifier; and (3) saline with emulsifier (control). RESULTS: Intraduodenal administration of both nonemulsified LCT and emulsified LCT induced significant (p < .05) increases in plasma CCK and PP levels and reductions in gallbladder volume. However, compared with nonemulsified LCT, emulsified LCT resulted in a readier and significantly stronger CCK release (212+/-62 pmol/L per 120 minutes vs 36+/-7 pmol/L per 120 minutes; p < .05); PP release (2034+/-461 pmol/L per 120 minutes vs 671+/-106 pmol/L per 120 minutes; p < .05); and gallbladder contraction (77%+/-2% vs 41%+/-7%; p < .05). No significant alterations were observed in plasma CCK or PP levels and gallbladder volume during administration of saline with emulsifier. CONCLUSIONS: Intraduodenal administration of a low-dose emulsified LCT more potently stimulates CCK and PP release and gallbladder contraction in comparison to equimolar amounts of nonemulsified LCT. These findings point to an important role for solubilization of LCT in determining the magnitude of CCK release from the intestine.

Adolescent↗

Retrobulbar metastasis from gallbladder carcinoma after laparoscopic cholecystectomy. A case report.

Extra-abdominal metastases from gallbladder cancer are very rare; the sites outside the abdomen most frequently affected are the skin, bone and central nervous system. In the literature, only one case of orbital metastasis from gallbladder cancer has been reported, in a patient previously treated by open cholecystectomy. We report the case of a 53-year-old woman who underwent a laparoscopic cholecystectomy for symptomatic gallbladder stones. Postoperative histological examination revealed an unsuspected gallbladder adenocarcinoma. One month later she came to our observation after having developed diplopia and ophthalmic pain due to an orbital metastasis. We decided not to perform a surgical second look because of the already rapid dissemination of the malignant tumor. The few cases of uncommon gallbladder cancer metastases after laparoscopic cholecystectomy described in the literature are discussed, as well as the possible role of laparoscopy in the dissemination and localized seeding of malignant cells.

Adenocarcinoma↗

Cavernous hemangioma of the gallbladder. Case report and review of the literature.

UNLABELLED: Hemangiomas are common benign tumors; they frequently occur in the liver but very rarely in the gallbladder, with only seven cases reported in the scientific literature to date. We here report an additional patient, a 49-year-old white woman presenting with an echogenic lesion of the gallbladder that was incidentally discovered. Cholecystectomy was performed after computed tomography had revealed a gallbladder neoplasm; pathological examination showed the mass to be a cavernous hemangioma. No postoperative complications occurred and the patient is alive and free of recurrence five years after the operation. We present a review of the literature on this topic with special emphasis on the diagnostic and therapeutic challenges these lesions may entail. Hemangiomas of the gallbladder may have extremely variable presentations (from non-specific abdominal pain to acute syndromes resembling cholangitis or choledocholithiasis) and can mimic different lesions (liver tumors, sarcoma). Only surgical exploration can provide a correct diagnosis. Excision is indicated as these lesions may grow to huge sizes, compress adjacent structures or bleed. CONCLUSIONS: Gallbladder hemangiomas are uncommon benign tumors. A preoperative diagnosis is difficult to make. Surgical excision is mandatory both in reaching a final diagnosis and in preventing bleeding or compression of vital structures.

Female↗

Ultrasound diagnosis of metastatic melanoma of the gallbladder.

The abdominal ultrasound examinations of 464 patients with malignant melanoma performed over a 3 year period were reviewed. 23 (5.2%) had soft tissue material attached to the gallbladder wall and projecting into the lumen. Four of these were polyps of less than 1 cm which were thought to be benign, while the remaining 19 had abnormalities likely to be metastatic melanoma. Upper abdominal ultrasound examinations are frequently requested for staging purposes in patients with thick high grade malignant melanoma or clinical suspicion of metastases. Ultrasound clearly identifies the gallbladder and biliary tree in the vast majority of patients and is generally regarded as the imaging modality of choice for suspected gallbladder pathology. As autopsy studies have confirmed the incidence of gallbladder metastases from malignant melanoma to be 15-20%, a careful review of the gallbladder is advocated when abdominal ultrasound examinations are performed on patients with malignant melanoma.

Aged↗

Prophylactic cholecystectomy with gastric bypass operation: incidence of gallbladder disease.

BACKGROUND: Morbid obesity is one of the major risk factors for gallbladder disease, and this risk is even greater following rapid weight loss. Because of this, prophylactic cholecystectomy has been offered to our patients undergoing the transected silastic ring vertical Roux-en-Y gastric bypass (TSRVRYGBP). A study was undertaken to determine the incidence of pathologic gallbladders in patients undergoing this prophylactic cholecystectomy. METHOD: The records of all patients who underwent TSRVRYGBP from June 1999 through December 2000 were reviewed. Pathologic findings of the gallbladder were documented as cholelithiasis, cholecystitis, cholesterolosis, polyps or normal. RESULTS: 761 patients underwent the operation. 178 patients (23%) had cholecystectomy before the surgery. 154 (20%) had gallstones documented by ultrasound and had cholecystectomy at the time of the surgery. 324 of the 429 patients with negative preoperative findings by ultrasound had pathologic evidence of gallbladder disease. CONCLUSION: Because of the high incidence of gallbladder disease even with negative preoperative findings in morbidly obese patients and the lack of significant morbidity with cholecystectomy in experienced hands, routine cholecystectomy at the time of the weight loss operation is justified.

Adult↗

An immunohistochemical study of the expression of cell-cycle-regulated proteins p53, cyclin D1, RB, p27, Ki67 and MSH2 in gallbladder carcinoma and its precursor lesions.

Gallbladder carcinomas are rare but highly lethal neoplasms. We examined the expression of five cell-cycle-related molecules (p53, RB, cyclin D1, p27, Ki-67), and MSH2, in 46 carcinomas, 14 adenomas, 15 low-grade dysplasias, 9 intestinal metaplasias and 20 normal gallbladder epithelia. The expression of these molecules was altered in gallbladder carcinomas and adenomas. In gallbladder carcinomas we observed increased expression of p53, cyclin D1, Ki-67, and MSH2 together with decreased expression of RB and p27 protein. Aberrant expression of cyclin D1 and reduced expression of RB were noted in adenomas, and expression of cyclin D1 was elevated in low-grade dysplasias. However, there was no change in the levels of these cell-cycle molecules in metaplasia. Expression of p53, p27, Ki-67, and MSH2 was correlated with clinical stage (P<0.05) and there was also a correlation between the expression of Ki-67 and MSH-2 and patient age (P<0.05). These results suggest that altered expression of cell-cycle molecules p53, cyclin D1, RB, p27, and of MSH-2 is involved in the progression of gallbladder carcinomas.

Aged↗

[A photo-optical observation of gallbladder motility in dogs (author's transl)].

A photo-optical observation of gallbladder motility was made with a cholangiography on 38 mongrel dogs. The whole area, the sectional length were calculated from the series of roentgenograms, and compared the control value (100) before caerulein administration with the values (percentage of the control value) after caerulein administration. The results obtained are as follows. 1. Preparatory experiments indicated that lateral view is most suitable and intravenous administration of caerulein is more effective. Duration of X-ray discharge was decided as every 1 minute for initial 30 minutes after caerulein administration and every 5 minutes for following 60 minutes. 2. On experiments performed on the above-mentioned condition, there were two types of gallbladder motility. A typical type (12 cases): The length of fundus had most close correlation with the change of the gallbladder area, next was body and neck had less close correlation. The longitudinal length had more less close correlation than the sectional transverse length. An atypical type (8 cases): The longitudinal length had more close correlation with the change of the gallbladder area than the sectional transverse length. 3. By analysing the mean values of a typical type, the gallbladder area (y) could be expressed by the sectional length (x) as follows: neck: y=1.68x -- 68.1 body: y=1.81x-80.0 fundus: y=1.48x-45.4 longitudinal: y=1.83x-88.9

Animals↗

Clinical and ultrasonographical findings in patients with multiseptate gallbladder.

Multiseptate gallbladder is one of the rare congenital malformations of the gallbladder. We present clinical and ultrasonographic findings in seven patients with multiseptate gallbladder. One of them had nausea and right upper quadrant pain, three had recurrent abdominal pain, while the remaining three patients had no symptoms, physical finding and laboratory abnormality which could be attributable to the biliary system. In patients with multiseptate gallbladder, disturbed motility of the gallbladder may be an etiopathogenetic factor for stasis of bile flow and in turn for development of cholelithiasis, cholecystitis and right upper quadrant pain.

Adolescent↗

Drug-induced gallbladder disease. Incidence, aetiology and management.

A great variety of drugs is reported to induce gallbladder disease by various pathogenetic mechanisms. Early epidemiological studies indicated a doubled risk of gallbladder disease in women taking oral contraceptives. More recent studies, however, have failed to confirm those findings; these conflicting results might be explained by the different methods used to define gallbladder disease. It was shown that the lithogenic index of the bile is increased during intake of oral contraceptives. Estrogens cause hypersecretion of cholesterol in bile, due to increase in lipoprotein uptake by the hepatocyte. Progesterone inhibits acyl coenzyme A-cholesterol acyl transferase (ACAT) activity, causing delayed conversion of cholesterol to cholesterol esters. Of the lipid lowering drugs, only clofibrate has been shown to increase the risk for gallstone formation. The other fibric acid derivatives have similar properties, but clinical experience is not as extensive. They seem to be inhibitors of the ACAT enzyme system, thereby rendering bile more lithogenic. Conflicting epidemiological data exist regarding the induction of acute cholecystitis by thiazide diuretics. Ceftriaxone, a third-generation cephalosporin, is reported to induce biliary sludge in 25 to 45% of patients, an effect which is reversible after discontinuing the drug. The sludge is occasionally a clinical problem. It was clearly demonstrated that this sludge is caused by precipitation of the calcium salt of ceftriaxone excreted in the bile. Long term use of octreotide is complicated by gallstone formation in approximately 50% of patients after 1 year of therapy, due to gallbladder stasis. Hepatic artery infusion chemotherapy by implanted pump is shown to be associated with a very high risk of chemically induced cholecystitis. Prophylactic cholecystectomy at the time of pump implantation is therefore advocated. Some drugs, such as erythromcyin or ampicillin, are reported to cause hypersensitivity-induced cholecystitis. Furthermore, there are reports on the influence of cyclosporin, dapsone, anticoagulant treatment, and narcotic and anticholinergic medication in causing gallbladder disease.

Adult↗

Effects of selective vagal stimulation on the gallbladder and sphincter of Oddi and peripheral vagal routes mediating bile evacuative responses induced by hypothalamic stimulation.

Peripheral routes of the vagus nerves to the biliary system were studied in anesthetized dogs using various selective vagal stimulation. Efferent stimulation of the gastric, hepatic, or celiac vagal branch as well as the cervical or thoracic vagal trunk induced gallbladder and Oddi's sphincter contractions, but those induced by hepatic vagal stimulation were rather small. The contraction responses in the gallbladder and sphincter of Oddi induced by thoracic vagal stimulation were greatly reduced after an external ligation around the pyloric sphincter. After administration of sympathetic blockers and atropine, vagally-induced gallbladder contractions were completely abolished and slight relaxation was seen in some animals. On the other hand, relaxation or transient relaxation followed by enhanced contractions was elicited in the sphincter of Oddi by vagal stimulation after atropine and sympathetic blockers. The relaxation response in the gallbladder after atropine and sympathetic blockers was abolished and that in the sphincter of Oddi was greatly reduced after the ligation around the pyloric sphincter. Stimulation of a ventral part of the anterior hypothalamic area induced gallbladder contraction and simultaneous relaxation of the sphincter of Oddi. These responses were completely abolished by the ligation around the pyloric sphincter in six dogs, while a slight relaxation response in the sphincter of Oddi remained in two dogs. These results suggest that the vagal fibers passing across the pyloric sphincter region are important for regulation of canine biliary motility and that extragastric vagal routes play a minor role in the nervous control of canine bile evacuation.

Animals↗

Sonography and computed tomography in the diagnosis of carcinoma of the gallbladder.

The computed tomographic and sonographic findings of 26 patients with gallbladder carcinoma were reviewed, and the problems and pitfalls encountered with these imaging techniques are discussed. The most common finding, a mass filling or replacing the gallbladder, was seen in 42% of the patients. A mass protruding into the gallbladder was seen in 23%, and diffuse asymmetric thickening of the gallbladder wall in 15%. Recommendations are made to avoid some of the diagnostic problems encountered. With careful and meticulous technique early carcinoma of the gallbladder may be detected with greater frequency by cross-sectional imaging techniques.

Aged↗

Gallbladder contractility in patients with spinal cord injuries: a sonographic investigation.

Approximately 30% of all patients who have spinal cord injuries have gastrointestinal symptoms. One cause is gallstone disease; indeed the literature suggests that gallstones are more common in patients with spinal cord injuries because these patients have impaired contractility of the gallbladder with a reduced ejection fraction. To test this hypothesis, we obtained gallbladder sonograms in 30 patients with spinal cord injuries (16 quadriplegics and 14 paraplegics) and in 32 uninjured age-matched control subjects. Four patients and four asymptomatic control subjects had gallstones and were excluded. The remaining 26 patients and 28 control subjects fasted for 12 hr. Longitudinal and transverse sonograms of the gallbladder were made immediately before the ingestion of 25 g of fat, and at 10, 20, 30, 45, and 60 min thereafter. Gallbladder volumes were measured by using the ellipsoid method. Resting and residual volumes and the emptying times were determined and the ejection fractions were calculated. The ejection fractions were significantly lower (p = .003) in the patients than in the control subjects because the resting volumes were lower than in the control subjects (p = .013). However, the emptying times and residual volumes were the same in the two groups. We conclude that gallbladder contractility is normal in patients with spinal cord injuries and that the lower ejection fraction found in such patients is due to a smaller resting volume.

Adult↗

MUC5AC, a gel-forming mucin accumulating in gallstone disease, is overproduced via an epidermal growth factor receptor pathway in the human gallbladder.

Despite evidence that mucin overproduction is critical in the pathogenesis of gallstones, the mechanisms triggering mucin production in gallstone disease are unknown. Here, we tested the potential implication of an inflammation-dependent epidermal growth factor receptor (EGF-R) pathway in the regulation of gallbladder mucin synthesis. In gallbladder tissue sections from subjects with cholesterol gallstones, mucus accumulation was associated with neutrophil infiltration and with increased expressions of EGF-R and of tumor necrosis factor-alpha (TNF-alpha). In primary cultures of human gallbladder epithelial cells, TNF-alpha induced EGF-R overexpression. In the presence of TNF-alpha, EGF-R ligands (either EGF or transforming growth factor-alpha) caused significant increases in MUC5AC mRNA and protein production, whereas expression of the other gallbladder mucins MUC1, MUC3, and MUC5B was unchanged. In addition, on gallbladder tissue sections from subjects with gallstones, increased MUC5AC immunoreactivity was detected in the epithelium and within mucus gel in the lumen. Studies in primary cultures demonstrated that MUC5AC up-regulation induced by the combination of TNF-alpha with EGF-R ligands was completely blunted by inhibitors of EGF-R tyrosine kinase and mitogen-activated protein/extracellular signal-related kinase kinase. In conclusion, an inflammation-dependent EGF-R cascade causes overproduction of the gel-forming mucin MUC5AC, which accumulates in cholesterol gallstone disease. The ability to interrupt this cascade is of potential interest in the prevention of cholesterol gallstones.

Cells, Cultured↗

Duodenal obstruction caused by malposition of the gallbladder in a heifer.

A heifer with clinical findings suggesting obstruction of the proximal portion of the intestine was admitted for diagnostic evaluation. Ultrasonographic examination of the abdomen failed to locate the gallbladder in its normal anatomic position. Exploratory laparotomy and manual examination of the proximal portion of the intestine revealed obstruction of the duodenum caused by abnormal positioning of the gallbladder. The obstruction was relieved by replacing the gallbladder to its normal position; however, relapse occurred within 2 days. To resolve and prevent the recurrence of the obstruction without compromising gallbladder function, a novel surgical technique to provide fixation of the gallbladder to the liver was performed. The heifer recovered rapidly, proceeded to develop normally during the following year, and became pregnant.

Animals↗

A comparison of glucagon, gastric inhibitory peptide, and secretin on gallbladder function, formation of bile, and pancreatic secretion in the cat.

The effects of glucagon, gastric inhibitory peptide (GIP), and secretin on the concentrating mechanism and the motility in the feline gallbladder have been studied in vivo. A technique by which the gallbladder in situ was perfused by an electrolyte solution made possible a simultaneous study of the motility and of the net transport of water and electrolytes across the gallbladder wall. Secretin (0.6 microgram per kg/h) was found to abolish the net absorption of water, Na+, and HCO3- and strongly reduce the net absorption of K+ and Cl-, whereas neither glucagon (1--20 microgram per kg/h) nor GIP (1--30 microgram per kg/h) was found to significantly influence the concentrating function of the gallbladder. The motility of the gallbladder was not influenced by the peptides. The formation of bile and pancreatic secretion was not changed by glucagon or GIP, whereas secretin had a potent effect.

Animals↗

Gallbladder and duodenal bacterial flora after papillotomy in rabbits.

Gallbladder and duodenal bacteria were studied in New Zealand white rabbits 1 and 4 weeks after papillotomy. The gallbladder bile was sterile in all animals before papillotomy. One and 4 weeks after papillotomy growth of both aerobic and anaerobic bacteria was found in the gallbladder bile in five of eight test animals and in none of the control rabbits. The number of bacteria in the duodenum increased in rabbits that developed growth of bacteria in the gallbladder bile after papillotomy. In the test rabbits that did not develop bacteria in the gallbladder bile and in the control group no changes in duodenal bacteria were observed.

Animals↗