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The incidence of gallbladder stones and gallbladder function in beta-thalassemic children.

PURPOSE: To determine gallbladder motor function and gallstone prevalence in beta-thalassemic children. Abnormalities in gallbladder function or bile acid metabolism may contribute to gallstone formation in these patients. MATERIAL AND METHODS: In 17 beta-thalassemic patients and 12 normal healthy children with similar age, sex and weight, gallbladder size was measured using real-time US, and volume was calculated using the ellipsoid method. RESULTS: In the beta-thalassemic patients, cholelithiasis was present in 2 patients (11.8%). Sludge, which can be a predisposing factor for cholelithiasis and cholecystitis when it persists, was detected in 5 patients (29.4%). One of the patients had both cholelithiasis and sludge. Compared with the control group, beta-thalassemic children had larger fasting volume, residual volume, and smaller contraction index. CONCLUSION: Beta-thalassemic patients have enlarged gallbladders that retain an increased residual volume of bile. Gallbladder enlargement, bile stasis, and impaired emptying of sludge may be important events in the pathogenesis of pigment gallstones in beta-thalassemic patients.

Adolescent↗

The human gallbladder increases cholesterol solubility in bile by differential lipid absorption: a study using a new in vitro model of isolated intra-arterially perfused gallbladder.

In this study, we first developed and validated a new in vitro isolated, intra-arterially perfused, gallbladder model and then applied the method to investigate the absorption of biliary lipids by the gallbladder wall and the effect of this process on the composition of human bile. Oxygenated and glucose-added buffer was perfused through the cystic artery to maintain organ viability. A standard pooled natural bile, radiolabeled with H3-cholesterol and C14-palmitoyl-linoleoyl-phosphatidylcholine, was instilled in the lumen via a cystic duct catheter. Changes in bile volume and lipid concentrations were monitored at time intervals to evaluate the disappearance of lipids from bile caused by gallbladder absorptive function. Organ viability was demonstrated by stable lactate dehydrogenase (LDH) organ release and oxygen consumption throughout the experiments. In the pig, disappearance rates of lipids from bile were similar in vitro and in vivo, demonstrating the validity of the isolated in vitro model for functional studies. By applying our in vitro isolated preparation to the human gallbladder, we found that 23% of cholesterol and 32% of phosphatidylcholine, but only 9% of bile salts, disappeared from bile in 5 hours. As a consequence, at the end of the experiments, cholesterol (P < .05) and phospholipid (P < .05) molar percentages were significantly reduced, while the bile salt (P < .05) molar percentage was significantly increased with respect to values at the beginning of the studies. Our findings are of pathophysiological relevance and support the concept that the human gallbladder modifies the relative composition of biliary lipids in such a way as to increase cholesterol solubility in bile.

Absorption↗

Asymptomatic metachronous metastatic renal cell adenocarcinoma to the gallbladder. Report of a case and guidelines for evaluation of intraluminal polypoid gallbladder masses.

A case of asymptomatic metachronous metastatic unilateral renal cell adenocarcinoma to the gallbladder detected five years after resection of the primary renal neoplasm is reported here. The lesion was diagnosed by contrast enhancement of a gallbladder mass on abdominal computerized tomography scan and by color Doppler sonographic study of the gallbladder, both of which demonstrated the vascular supply to the intraluminal gallbladder mass. The biological behavior of renal cell adenocarcinoma is reviewed. Guidelines for the evaluation of intraluminal gallbladder masses are suggested.

Aged↗

Large cholesterol polyp of the gallbladder mimicking gallbladder carcinoma.

Gallbladder tumors larger than 10 mm in diameter have a high incidence of malignancy. We report an extremely rare case of a large cholesterol polyp of the gallbladder mimicking gallbladder carcinoma. Ultrasonography and computed tomography showed a larger papillary mass in the fundus of the gallbladder with a maximum diameter of about 30 mm, the largest gallbladder polyp ever reported to our knowledge.

Carcinoma↗

Laparoscopic treatment of gallbladder duplication. A plea for removal of both gallbladders.

BACKGROUND: Gallbladder duplication is a rare congenital condition, which can now be detected preoperatively by imaging studies. METHODS: We report a case of duplicated gallbladder with symptomatic unilobar gallstones. Appropriate biliary workup (ultrasound, oral cholecystography, and intravenous cholangiography) allowed a correct preoperative diagnosis. RESULTS: Laparoscopic treatment included selective removal of the diseased accessory gallbladder. However, postoperative acute cholecystitis and symptomatic gallstone occurred in the remaining main gallbladder, and laparoscopic reintervention was required 27 months later. CONCLUSIONS: This case illustrates the need for complete removal of both gallbladders during initial surgery. Precise intraoperative recognition of vascular and biliary anatomy-including abnormalities-is highlighted to avoid mistakes during surgery.

Adult↗

The honeycomb gallbladder: a new category of acquired pseudo-multiseptate gallbladder.

We report two cases of honeycomb gallbladder as a new category of acquired pseudo-multiseptate gallbladder associated with chronic cholecystitis with stones. The two patients were elderly women without any abdominal symptoms or abnormality of laboratory data. On the imaging examinations, a hyperechoic collection with acoustic shadowing on the inferior surface of the liver was typically observed on ultrasonography, with multiloculated gallbladder being observed on computed tomography. Macroscopic findings of the cut plane of the gallbladder showed a characteristic appearance, with thin pseudo-septations arising from the wall and bridging the lumen from side to side, with a honeycomb appearance, including small stones. Microscopic findings suggest that these septational structures could have developed over a chronic inflammatory course after acute obstruction of the cystic duct. Cholecystectomy should be the choice of treatment for honeycomb gallbladder from the viewpoint of clinical management.

Aged↗

Microsatellite instability in gallbladder carcinoma: two independent genetic pathways of gallbladder carcinogenesis.

Although the genetic basis for gallbladder carcinogenesis has not been clarified, considerable evidence has shown that genetic alterations play an important role in the development and progression of human cancers. In this study, we analyzed 30 gallbladder carcinomas to investigate the role of genetic alterations in their tumorigenesis, and to study correlations with their clinicopathological features. Tissue samples were obtained from 30 patients with gallbladder carcinoma (11 men and 19 women; mean age, 62 years; age range, 38-80 years). Genomic DNAs were extracted from fresh tumor tissue. We examined loss of heterozygosity (LOH) in the p53, APC, DCC, RB, and NM23-H1 gene regions by polymerase chain reaction (PCR)-LOH assay using an automated fluorescent DNA sequencer employing four microsatellite markers (p53, APC, DCC, NM23-H1). Five additional microsatellite markers were used for the determination of microsatellite instability (MSI). LOH was found at p53 in 9 of 15 informative cases (60%), at DCC in 10 of 22 (45%), at APC in 5 of 15 (33%), at RB in 1 of 8 (13%), and at NM23-H1 in 1 of 15 (7%). MSI was observed in 5 of 30 cases (17%) in at least one chromosomal loci of these nine microsatellite markers. None of the patients with MSI-positive tumors showed lymph node metastasis, and there was an inverse correlation between MSI and the presence of LOH in gallbladder carcinoma. These results suggest that there are two independent genetic pathways in gallbladder carcinogenesis; that is, an MSI pathway and an LOH pathway.

Adult↗

PHI-like immunoreactivity in the gallbladder and in vitro effect of porcine PHI on smooth muscle of the gallbladder.

The occurrence and distribution of PHI-like immunoreactivity in the guinea pig gallbladder has been analysed by radioimmunoassay and immunocytochemistry. Chromatography of gallbladder extracts by gel permeation and high-performance liquid chromatography revealed that guinea pig PHI-like immunoreactivity is of a similar size to that of porcine PHI but may differ in its amino acid sequence. Immunocytochemistry showed PHI-immunoreactivity to be localised to nerves found predominantly in the ganglionated plexus and the mucosal plexus of the gallbladder. Pure natural porcine PHI induced a dose-dependent relaxation of the isolated guinea pig gallbladder muscle which was not blocked by antagonists to acetylcholine, catecholamines, histamine, and 5-hydroxytryptamine. PHI may thus be one of the local factors involved in controlling gallbladder function.

Animals↗

Pathophysiology of tumor progression in human gallbladder: flow cytometry, CEA, and CA 19-9 levels in bile and serum in different stages of gallbladder disease.

Gallbladder epithelium is unique among the gastrointestinal cell types because proteins and protein levels in the fluid bathing the luminal side of the cells (bile) are different from and can be compared with those in the fluid bathing the basal side (serum). To help identify cellular changes that occur during the development of gallbladder cancer, we obtained gallbladder tissue, serum, and bile specimens from 20 patients with invasive adenocarcinoma of the gallbladder, three with high-grade dysplasia (carcinoma in situ), six with low-grade dysplasia, 12 with hyperplasia, and 10 with acute or chronic cholecystitis. We obtained serum samples from 40 patients with invasive adenocarcinoma and bile samples from 29 of these patients; serum samples from three with high-grade dysplasia and bile specimens from two of these; serum and bile samples from five with low-grade dysplasia; serum or bile samples from 126 with metaplasia, hyperplasia, or cholecystitis, including serum samples from 121 and bile samples from 110; and serum and bile samples from eight with normal biliary tracts. The study was conducted in Mexico City, Mexico, and La Paz, Bolivia. We performed flow cytometric DNA analysis on gallbladder tissue specimens and measured levels of carcinoembryonic antigen (CEA) and CA 19-9 antigen in the serum and bile specimens. Analysis of the cell cycle compartments by flow cytometry revealed marked variations of the proliferation index for the different disease states (P less than .0001). The proliferation index increased with progression from cholecystitis to invasive adenocarcinoma. Of the bile and serum measurements, only serum CA 19-9 values were correlated with flow cytometry measurements (r = -.49, P = .005). Overall, the serum and bile measurements were in agreement (P less than .01). However, with the exception of the correlations among serum measurements for the patients with invasive adenocarcinoma, most of the correlations could be explained by differences in the disease state. In particular, the progression from normal tissue to invasive adenocarcinoma involved no change in bile CA 19-9 level and only a slight change in bile CEA level but much larger changes in serum CEA and CA 19-9 levels. It appears that the progression from normal tissue to invasive adenocarcinoma results in increased production of these antigens and often in loss of cell polarity as well, i.e., inability to prevent leakage of the antigens into the serum.

Antigens, Tumor-Associated, Carbohydrate↗

Ultrasonic visualization of the non-opacified gallbladder: response of the normal and obstructed canine gallbladder to C8CCK.

In vitro studies of a simulated gallbladder show that B-scan ultrasonography is as reliable as radiography in measuring changes in volume of the organ. The width or planimetric area of the sonogram correlates with the change in balloon volume and with similar radiographic measurements. In vivo measurements of the normal canine gallbladder stimulated by a carefully prescribed infusion of C8CCK in the dose range of 2.2 to 5.5 ng/kg/min over an 8 to 10 minute interval, showed a clearly defined decrease in gallbladder width. In ligation and division of the common bile duct no change in gallbladder size was demonstrated. We conclude that sonography alone can be used to measure a change in gallbladder size to better differentiate complete obstruction of the common bile duct from medical causes in the jaundiced patient.

Animals↗

Emptying the gallbladder prior to intravenous cholangiography: effect on gallbladder visualization.

Experiments were done to test the hypothesis that emptying the gallbladder prior to intravenous cholangiography (IVC) would result in earler and better opacification of the gallbladder. Five dogs were studied on two separate days in a crossover experiment. Each dog had a standard IVC (15-minute infusion of meglumine iodipamide) 2.5 cc/kg of following a 14-16-hour fasting period. On one of the days, 0.3 mcg/kg of Ceruletide was intramuscularly administered to each dog 30 to 45 minutes prior to the iodipamide infusion. Films obtained at the end of infusion and at 20, 40, 60, and 90 minutes were evaluated independently by three radiologists. The results indicate that pretreatment with Ceruletide produces a significant (p less than 0.05) improvement in the quality of gallbladder opacification during the first 90 minutes following iodipamide infusion. We conclude that earlier and better opacification of the gallbladder during IVC can be obtained by prior emptying of the gallbladder with a cholecystokinetic agent.

Animals↗

PGE2 hyperpolarizes gallbladder neurons and inhibits synaptic potentials in gallbladder ganglia.

Gallbladder prostaglandin E2 (PGE2) levels are significantly elevated in pathophysiological conditions, resulting in changes in gallbladder motility or secretion that may involve actions of the prostanoid in intramural ganglia. This study was undertaken to examine the effects of PGE2 on neurons of the intramural ganglia of the guinea pig gallbladder. Application of PGE2 by microejection or superfusion elicited a complex triphasic change in the resting membrane potential (RMP). For example, application of PGE2 by microejection (100 microM) resulted in a brief hyperpolarization (mean duration 11.1 +/- 1.3 s), followed by a mid-phase repolarization toward or above RMP (mean duration 50.7 +/- 8.1 s), and finally a long-lasting hyperpolarization (mean duration 157.3 +/- 36.7 s). Associated with these PGE2-evoked alterations in RMP were changes in input resistance measured via injection of hyperpolarizing current pulses. An examination of the action potential afterhyperpolarization (AHP) during the PGE2-evoked response revealed an attenuation of both the amplitude and duration of the AHP. However, only a slight increase in excitability of gallbladder neurons in the presence of PGE2 was evident in response to depolarizing current pulses, and PGE2 did not cause the cells to fire spontaneous action potentials. Application of PGE2 reduced the amplitudes of both fast and slow excitatory synaptic potentials. These results suggest that increased prostaglandin production may decrease ganglionic output and therefore contribute to gallbladder stasis.

Animals↗

Hepatic versus gallbladder bile composition: in vivo transport physiology of the gallbladder in rainbow trout.

Ion and water transport across the teleost Oncorhynchus mykiss gallbladder were studied in vivo by comparing flow and composition of hepatic bile, collected by chronic catheter, to volume and composition of terminally collected gallbladder bile. Differences in composition were comparable with those of other vertebrates, whereas bile flow (75 microl. kg(-1). h(-1)) was below values reported for endothermic vertebrates. The gallbladder concentrates bile acids five- to sevenfold and exhibits higher net Cl(-) than Na(+) transport in vivo, in contrast to the 1:1 transport ratio from gallbladders under saline/saline conditions. Transepithelial potential (TEP) in the presence of bile, at the apical surface, was -13 mV (bile side negative) but +1.5 mV in the presence of saline. Bile acid in the apical saline reversed the TEP, presumably by a Donnan effect. We propose that ion transport across the gallbladder in vivo involves backflux of Na(+) from blood to bile resulting in higher net Cl(-) than Na(+) flux. This Na(+) backflux is driven by a bile side negative TEP and low Na(+) activity in bile due to the complexing effects of bile acids.

Animals↗

The effects of morphine and enkephaline on gallbladder function in experimental cholecystitis. Inhibition of inflammatory gallbladder secretion.

Administration of morphine or its derivatives is the traditional way to treat biliary pain. Despite the common use of morphine and its analogues in patients with cholecystitis and biliary pain, their effects on the function of the inflamed gallbladder are not known. In the present study it is demonstrated that morphine usually contracts the normal gallbladder but does not influence the fluid transport across the mucosa. In experimental cholecystitis morphine and enkephaline do not further contract the gallbladder but, by specific opioid receptors, reduce the inflammatory fluid secretion by the mucosa. In case of obstruction of the gallbladder, fluid secretion by the mucosa will distend its wall and induce biliary pain. It is suggested that the pain-relieving effect of morphine in cholecystitis and attacks of biliary pain is mediated not only by a central analgesic effect but also by an influence on the function of the inflamed gallbladder.

Animals↗

Cyclin D1 overexpression is a critical event in gallbladder carcinogenesis and independently predicts decreased survival for patients with gallbladder carcinoma.

This study was designed to test the hypothesis that cyclin D1 overexpression is involved in the multistep process of gallbladder carcinogenesis and can be used to predict poor prognosis for patients with gallbladder carcinoma (GBC). Cyclin D1 expression was examined immunohistochemically in a series of specimens, including 8 normal epithelia, 8 benign adenomyoma lesions, 6 precancerous adenomas, and 37 carcinomas of the gallbladder. Four of the 6 (67%) adenomas and 15 of the 37 (41%) adenocarcinomas demonstrated cyclin D1 overexpression (>5% nuclear staining), whereas all normal epithelia and adenomyoma lesions were negative for cyclin D1. Kaplan-Meier curves showed that cyclin D1 overexpression was significantly related to decreased overall survival (P < 0.05) in patients with GBCs. The Cox proportional hazards model identified cyclin D1 overexpression as an independent prognostic marker for death (P = 0.024; risk ratio, 4.2; 95% confidence interval, 1.2-14.7). To test whether cyclin D1 overexpression is a critical event in gallbladder neoplasms, cyclin-dependent kinase inhibitor p27Kip1 was introduced to ascertain how cyclin D1 affects clinical outcomes. Subsequently, neoplasms were divided into three groups on the basis of the combination of cyclin D1 expression and p27Kip1 status, which had been determined previously. Group 1 showed no abnormality in either cyclin D1 or p27Kip1 expression. Group 2 showed aberrant expression of one of the two proteins, whereas group 3 showed concurrent abnormalities in both proteins. Results indicated that overall survival was greatest in group 1, followed by a significant decrease in group 2 and a more precipitous decrease in group 3. In conclusion, cyclin D1 overexpression is an early event in gallbladder carcinogenesis and independently predicts decreased survival for patients with GBC.

Aged↗

Chemical sclerosis of the gallbladder. An experimental study in pigs of the effect of absolute ethanol and polidocanol on gallbladder epithelium.

Chemical ablation of the gallbladder with absolute ethanol and polidocanol 3% was attempted in 23 and 10 pigs, respectively, after open transhepatic cholecystostomy. Absolute ethanol caused complete necrosis of the gallbladder epithelium in 10 pigs and partial necrosis with focally present gallbladder epithelium in 9. An intact epithelium was observed in 4 pigs but it was not possible to determine whether this epithelium was the original one, not affected by the ethanol, or regenerated after previous damage. Gallbladders with hemorrhage and hydrops were frequently encountered. Gallbladders treated with polidocanol all had an intact epithelium.

Animals↗

[Gallbladder contraction and microscopi observation of the gallbladder wall in gallstone patients].

On the basis of oral cholecystography (OCG), we selected gallstone patients for nontoperative intervention. Their gallbladder function was considered as normal when gallbladder contracted over 50%-75% after a fat meal at 1 hour. We collected 99 gallstone patients and 19 normal controls; gallbladder function was normal in 77 patients and poor in 22. After a fat meal gallbladder volumes were calculated by B ultrasonography. The results showed that both fasting and residual volume in patients with so-called normal contraction were significantly greater than that in the controls (P < 0.001), though the contraction rate was not different. The combination of gallbladder contraction rate measurement and residual volume calculation by ultrasonography was superior over traditional OCG.

Adult↗

Eosinophilic dysplasia of the gallbladder: a hitherto undescribed variant identified in association with a "porcelain" gallbladder.

Non-mass forming, neoplastic intraepithelial proliferations (dysplasia) represent the most well-accepted precursor lesions to gallbladder adenocarcinomas. They are typically small, localized, grossly unrecognizable lesions that have been identified in the epithelium adjacent to up to 79% of gallbladder adenocarcinomas. Morphologic variants that have been reported include flat, micropapillary, papillary and cribriform. We have recently encountered a morphologically distinctive, previously unreported lesion to which we have applied the designation eosinophilic dysplasia. This lesion was identified in a gallbladder with diffuse mural fibrosis and calcification (porcelain gallbladder). The dysplastic focus was confined to one tissue section, and was comprised of a localized true papilla [i.e with a fibrovascular core], measuring approximately 1.2 mm in greatest dimension and an adjacent, flat, 7-cell epithelial segment. These foci were lined by cells displaying significant nuclear enlargement [1.5-4 times the adjacent benign cells], nuclear pleomorphism, occasional multinucleation, hyperchromasia and nuclear membrane irregularities. Nucleoli were present but inconspicuous. These cells also showed voluminous eosinophilic to granular cytoplasm, such that the overall nuclear-to-cytoplasmic ratio was generally not increased. The cells displayed diffuse and marked nuclear immunoreactivity for p53, and approximately 70% of the cells showed nuclear positivity for Ki-67. The cells were also positive for cytokeratin 7 and were entirely negative for carcinoembryonic antigen (CEA) and chromogranin A. The cells of the adjacent normal epithelium were positive for cytokeratin 7 and CEA, negative for p53 and chromogranin A and showed a Ki-67 labeling index of <10%. Marked overexpression of the p53 protein as well as its high proliferative index are strong arguments in favor of the dysplastic nature of this lesion. However, further studies are required to elucidate its true clinical significance and to determine whether or not its association with a porcelain gallbladder, as noted herein, is entirely fortuitous. However, such studies can only be performed with an increased recognition by practitioners of this distinctive variant.

Journal Article↗