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PubMed1995

The frequency and influence of gallbladder varices on gallbladder functions in patients with portal hypertension.

Gallbladder varices have been reported in patients with portal hypertension. The exact frequency and significance of these collaterals in patients with cirrhotic and noncirrhotic portal hypertension is not known. One hundred and two patients with portal hypertension [38 with cirrhosis, 29 with noncirrhotic portal fibrosis (NCPF) and 35 with extrahepatic portal vein obstruction (EHPVO)] and 25 healthy controls were studied. Gallbladder varices were seen at ultrasound as tortuous, dilated vessels in the wall or in the bed of the gallbladder. In 35 patients (19 patients with and 16 without gallbladder varices) and in 10 healthy controls, gallbladder functions were studied by determining fasting volume (FV) and then residual volume (RV) every 10 min over 1 h after giving a liquid meal of 420 k.cal. Ejection fraction (EF) was computed as a percentage by the formula: FV--RV/FV x 100. Twenty four (24%) patients had gallbladder varices: Five (13%) with cirrhosis, seven (24%) with NCPF, and 12 (34%) with EHPVO. FV in EHPVO patients was seen significantly more than in cirrhotics (31.6 +/- 15.4 vs 19.3 +/- 6.0 ml, p < 0.05). The RV and EF were not different in the three groups of patients compared with the controls. The EF was similar in patients with or without gallbladder varices (63.3 +/- 10.2% vs 64.6 +/- 10.4%). Gallbladder varices are often seen in portal hypertension, more often in EHPVO patients, and these collaterals cause some gallbladder stasis but do not impede gallbladder function and hence seem unlikely to contribute to gallstone formation.

Adolescent↗
PubMedDate not supplied

Anatomical limit of extended cholecystectomy for gallbladder carcinoma involving the neck of the gallbladder.

BACKGROUND: Extended cholecystectomy is the common operation for gallbladder carcinoma. When extended cholecystectomy is performed, the liver bed can be generously resected from the fundus to the body of the gallbladder; however, the thickness of the liver parenchyma to be removed is limited to the neck of the gallbladder. There have been few reports providing convincing data with regard to how thick the liver can be anatomically resected by extended cholecystectomy. METHODS: The thickness of the liver tissue actually resected at the time of extended cholecystectomy and that potentially resected by extended cholecystectomy were measured in 24 clinical and 25 autopsy cases, respectively, to assess the anatomical limit of extended cholecystectomy. RESULTS: The mean anatomical distances from the neck of the gallbladder to the right hepatic duct and to the bifurcation of the anterior and posterior branch of the right hepatic duct were only 1.6 and 5.9 mm, respectively. The distance from the gallbladder to the bifurcation of the superior and inferior branch of the right anterior hepatic duct, and to the root of the right anterior inferior hepatic duct were 11.2 mm2, and 12.8 mm3, respectively (123:p < 0.05). The actual width of the liver excised by extended cholecystectomy was 5.2 mm at the neck, 11.7 mm at the body, and 8.1 mm at the fundus of the gallbladder, respectively. These results indicate that the neck of the gallbladder is anatomically close to the hepatic hilum including the right hepatic duct and portal vein. CONCLUSIONS: Surgical strategy for gallbladder carcinoma should be considered to rely not only upon the depth of invasion but also upon the site of gallbladder tumor. When gallbladder carcinoma involves the muscle layer or further at the neck of the organ, more extensive hepatectomy than extended cholecystectomy should be considered.

Adult↗
PubMed1990

Effect of truncal vagotomy on cholecystokinin release, gallbladder contraction, and gallbladder sensitivity to cholecystokinin in humans.

The present study was undertaken to investigate the gastric and intestinal phase of stimulation of postprandial gallbladder contraction and endogenous cholecystokinin secretion in patients with truncal vagotomy and pyloroplasty. Gallbladder emptying, measured by cholescintigraphy, and endogenous cholecystokinin secretion, measured by radioimmunoassay, were studied after both intragastric and intraduodenal administration of corn oil. In addition, the gallbladder responsiveness to cholecystokinin was investigated by infusion of stepwise increasing doses of exogenous cholecystokinin. In the 6 patients with truncal vagotomy, plasma CCK and gallbladder responses to intraduodenal fat were significantly delayed compared to normal subjects. In contrast, the onset of the plasma cholecystokinin increase and gallbladder emptying after intragastric fat was significantly earlier in the vagotomized patients compared with the normal subjects. In the normal subjects, plasma cholecystokinin and gallbladder responses to intragastric fat were significantly lower during the first 25 min after stimulation compared with the results after intraduodenal fat, whereas in the patients with truncal vagotomy and pyloroplasty, no differences in plasma cholecystokinin and gallbladder responses were found according to the site of fat stimulation. The gallbladder-emptying response to exogenous cholecystokinin increased significantly in patients who had undergone truncal vagotomy. It is concluded (a) that truncal vagotomy with pyloroplasty influences the timing but not the magnitude of fat-stimulated gallbladder contraction and endogenous cholecystokinin secretion; and (b) that the sensitivity of the gallbladder to endogenous and exogenous cholecystokinin is significantly increased in patients with truncal vagotomy.

Adult↗
PubMed1988

Age-related changes in gallbladder contractility and gallbladder cholecystokinin receptor population in the guinea pig.

We have examined the effects of aging on guinea pig biliary motility both in vitro and in vivo. The first experiment compared contractile tension of gallbladder strips from young adult (6-12 months old) and 3-year-old guinea pigs in vitro. Contraction of gallbladder strips from the young guinea pigs was twice as forceful and was more sensitive to octapeptide of cholecystokinin (CCK-8) stimulation than the gallbladder strips from the older guinea pigs. The two groups were also studied in vivo by measuring changes in the intraluminal pressure of the gallbladder in response to exogenously administered doses of CCK-8. Young adult guinea pigs were more sensitive to CCK-8 at the lower doses tested and demonstrated gallbladder contractions that were more forceful than that of the old guinea pigs. CCK receptors were measured on gallbladder muscularis membranes from young adult and old guinea pigs. The number of receptors on gallbladder membranes decreased with age: 65.0 +/- 17.7 fmoles/mg protein on membranes from 1 year old; 7.9 +/- 2.0 fmoles/mg protein on membranes from 3 years old. The binding affinity of CCK receptors on gallbladder muscularis membranes for binding to CCK-8 was not significantly different in the two age groups studied. We conclude that age-related decreases in gallbladder responses to CCK-8 may be due to decreased concentrations of CCK receptors on gallbladder muscle cells.

Aging↗
PubMed1989

Effect of a synthetic prostaglandin E1 derivative, misoprostol, on fasted gallbladder volume and on meal-induced gallbladder emptying in man.

The effect of a single oral dose of 400 micrograms of misoprostol versus placebo on the fasted gallbladder volume and on meal-induced gallbladder emptying was assessed in 10 healthy subjects according to a double-blind study protocol. Gallbladder volumes were measured by means of real-time ultrasonography. The fasted gallbladder volume before drug administration was 18.9 +/- 1.1 cm3 on the placebo day, and 18.8 +/- 1.4 cm3 on the misoprostol day. No significant change in the gallbladder volume was observed 30 minutes after drug administration (18.3 +/- 1.3 cm3 placebo vs 20.2 +/- 1.8 cm3 misoprostol). The gallbladder volume 10 min after the test meal was significantly larger after misoprostol (16.9 +/- 1.7 cm3) than after placebo (12.8 +/- 1.6 cm3), p less than 0.02. However, the differences at subsequent time points (i.e. 20, 30, and 40 min after the test meal) proved to be insignificant. An insignificant effect of misoprostol on gallbladder emptying was revealed also by the analysis of the respective gallbladder ejection fractions. We conclude that misoprostol does not have any significant effect on fasted gallbladder volume or on meal-induced gallbladder emptying in humans.

Adult↗
PubMed1991

Effect of nifedipine on interdigestive gallbladder volume and postprandial gallbladder emptying in man.

The effect of two oral doses (10 and 20 mg) of nifedipine versus placebo on the fasted gallbladder volume and on the meal-induced gallbladder emptying was assessed according to a double-blind study protocol in 12 healthy volunteers. Eight subjects underwent three studies (with placebo and with both nifedipine doses), whereas in two subjects the effect of a 10-mg nifedipine dose vs placebo and in two others the effect of a 20-mg nifedipine dose vs placebo was examined. The studies were performed on separate days, and the gallbladder volume was measured by means of real-time ultrasonography. Neither placebo nor 20 mg nifedipine per os elicited any significant change in the fasted gallbladder volume. With 10 mg nifedipine per os a significant increase in the interdigestive gallbladder volume was observed: 22.9 +/- 2.9 cm3 before and 26.2 +/- 3.2 cm3 after the drug receipt (P less than 0.005). A trend towards an inhibition of the postprandial gallbladder emptying was observed with 10 mg nifedipine per os without, however, reaching the level of statistical significance. Following 20 mg nifedipine per os, a marked delay in the meal-stimulated gallbladder emptying occurred, as reflected by a decrease in the gallbladder ejection fraction from 48.1 +/- 4.5% (placebo) to 26.4 +/- 5.0% (nifedipine) (P less than 0.02) at 30 min and from 54.0 +/- 3.6% (placebo) to 33.2 +/- 4.6% (nifedipine) (P less than 0.02) at 40 min after the test meal. We conclude that a therapeutic oral dosage of nifedipine has a significant relaxing effect on the human gallbladder.

Adult↗
PubMed2003

A case of gallbladder carcinoma diagnosed preoperatively by the detection of human telomerase reverse transcriptase mRNA in endoscopically obtained gallbladder bile.

It is difficult to accurately diagnose the nature of polypoid lesions in the gallbladder. To increase diagnostic accuracy, we have developed an endoscopic technique for obtaining gallbladder bile, termed endoscopic transpapillary catheterization into the gallbladder (ETCG). We describe here a case of gallbladder carcinoma diagnosed preoperatively by the detection of human telomerase reverse transcriptase (hTERT) mRNA, a catalytic subunit of telomerase, in gallbladder bile obtained using the ETCG technique. A patient with a polypoid lesion 15 mm in diameter in the gallbladder was admitted to our hospital for further examinations. Gallbladder bile collected by the ETCG technique was evaluated cytologically and also analyzed for telomerase activity and hTERT mRNA. Although the results for cytology and telomerase activity were negative, that for hTERT mRNA was positive. Open surgery was carried out and it was confirmed that the lesion was an adenocarcinoma invading the subserosa. The molecular biological analysis of gallbladder bile collected using the ETCG technique was shown to be effective for diagnosing the nature of the polypoid lesion in the gallbladder.

Adenocarcinoma↗
PubMed2006

Expression of pituitary adenylate cyclase-activating polypeptide 1 and 2 receptor mRNA in gallbladder tissue of patients with gallstone or gallbladder polyps.

AIM: To detect the expression of pituitary adenylate cyclase-activating polypeptide receptor 1 (VPCAP1-R)and VPCAP2-R mRNA in gallbladder tissues of patients with gallstone or gallbladder polyps. METHODS: The expression of VPCAP1-R and VPCAP2-R mRNA in gallbladder tissues was detected in 25 patients with gallstone,8 patients with gallbladder polyps and 7 donors of liver transplantation by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The VPCAP2-R mRNA expression level in the control group (1.09+/-0.58) was lower than that in the gallbladder polyp group (1.64+/-0.56) and the gallstone group (1.55+/-0.45) (P<0.05) while the VPCAP1-R mRNA expression level in the control group (1.15+/-0.23) was not apparently different from that in the gallbladder polyp group (1.28+/-0.56) and the gallstone group (1.27+/-0.38). CONCLUSION: The abnormal expression of VPCAP2-R mRNA in gallbladder tissue may play a role in the formation of gallbladder stone and gallbladder polyps.

Adult↗
PubMedDate not supplied

Bacteriological studies of bile from the gallbladder in patients with carcinoma of the gallbladder, cholelithiasis, common bile duct stones and no gallstones disease.

OBJECTIVE: To compare the presence of bacteria of bile from the gallbladder in control subjects, patients with gallstones, and patients with carcinoma of the gallbladder. DESIGN: Prospective open study. SETTING: University department of surgery. SUBJECTS: 372 patients of whom 36 had no signs of gallbladder disease; 211 underwent cholecystectomy for either symptomatic gallstone disease (n = 165) or acute cholecystitis (n = 46); 67 had common bile duct stones and 58 were operated on for carcinoma of the gallbladder. INTERVENTIONS: Aspiration of bile from the gallbladder. MAIN OUTCOME MEASURES: Prevalence of pathogenic bacteria in bile from the gallbladder and correlations between the presence of bacteria, the presence of cancer, and age. RESULTS: No pathogenic bacteria were grown from the bile of the patients who had no signs of gallstones disease. Among the 165 with symptomatic gallstone disease 52 (32%) had pathogens in their bile, and among the 46 with acute cholecystitis the corresponding figure was 19 (41%) while among patients with common bile duct stones this figure was 39 (58%). Among the 58 patients with carcinoma of the gallbladder the bile grew organism in 47 (81%). Patients over the age of 60 years tended to be more likely to have organism in their bile than patients aged 60 or less, and the difference was significant for symptomatic gallstone disease (p < 0.003). Significant differences were also found between patients with symptomatic gallstone disease and those with carcinoma of the gallbladder in both age groups (p < 0.002 in each case). Most of the organism were aerobic or anaerobic Gram negative species, irrespective of type of disease or age. CONCLUSION: Bacteria may have a role in the development of carcinoma of the gallbladder.

Adult↗
PubMed1994

Gallbladder ejection fraction. Nondiagnostic for sphincter of Oddi dysfunction in patients with intact gallbladders.

Thirty consecutive patients with intact gallbladders and biliary pain were evaluated to determine whether gallbladder ejection fraction could identify sphincter of Oddi dysfunction. The mean gallbladder ejection fraction was 45% in patients with abdominal pain and 72% in normal controls. Gallbladder ejection fractions were then correlated with endoscopically measured sphincter of Oddi pressures in patients with abdominal pain. The mean gallbladder ejection fraction was 41% in 7 patients with elevated sphincter pressures and 46% in 23 patients with normal pressures (P = NS). Thirty-six percent of patients with elevated pressures and 33% of patients with normal pressures had abnormal gallbladder ejection fractions. Gallbladder ejection fraction had a sensitivity of 33%, a specificity of 63%, and a positive predictive value of 25% for detection of elevated pressures. Regression analysis revealed a poor correlation between sphincter pressure and gallbladder ejection fraction (r2 = 0.02). These findings suggest that gallbladder ejection fraction cannot be used to diagnose sphincter of Oddi dysfunction in patients before they undergo cholecystectomy.

Abdominal Pain↗
PubMed1999

Gallbladder adenomas have molecular abnormalities different from those present in gallbladder carcinomas.

Although most gallbladder carcinomas evolve from dysplasia and carcinoma in situ, the role of gallbladder adenomas in the pathogenesis of gallbladder carcinoma is still controversial. A series of molecular changes including loss of heterozygosity (LOH) at 17p (TP53 gene), 13q (RB gene), 18q (DCC gene), and 9p21 (CDKN2a gene) chromosomal regions have been identified in dysplasias, carcinomas in situ, and invasive carcinomas of the gallbladder, whereas mutations in K- and N-ras genes are rare. To determine whether the molecular abnormalities of adenomas are similar to those found in carcinomas, we obtained extracted DNA from precisely microdissected tissue from 16 gallbladder adenomas (14 pyloric and 2 intestinal-type). We determined the presence of mutations in TP53, K- and N-ras genes, and LOH at five chromosomal regions (5q22 APC-MCC region, RB, TP53, DCC and 9p21-CDKN2a). For the TP53 mutation study, single strand conformational polymorphism (SSCP) analysis in exons 4 to 8 were performed. K- and N-ras mutations detection was performed by designed restriction fragment length polymorphism (RFLP) method and sequencing. Only a single LOH (at 5q22) was detected in a gallbladder adenoma of intestinal type. No mutations at the TP53 were detected. Four adenomas (25%) showed K-ras mutations (two in codon 12 and two in codon 61). We conclude that gallbladder adenoma lacks the molecular changes frequently detected in dysplasia, carcinoma in situ, and invasive carcinoma of the gallbladder. Likewise the occurrence of K-ras mutations at codon 12 and 61 in 25% of adenomas strongly suggests that these lesions are not precursors of invasive gallbladder carcinoma.

Adenocarcinoma↗
PubMed1992

Gallbladder mucosal function: studies in absorption and secretion in humans and in dog gallbladder epithelium.

The gallbladder is conventionally regarded as an absorptive organ such that dilute hepatic bile is both stored and concentrated. We studied 35 patients who had recovered from a percutaneous transhepatic gallbladder drainage performed for acute cholecystitis. After an overnight fast, gallbladder bile was dark brown in color and had a wide scatter in the lipid composition. Two hours after a meal, the gallbladder bile was opalescent white in color and had the composition of an extracellular fluid. This phenomenon was uniformly observed in all 35 patients and was also consistently reproducible when five patients were repeatedly studied. We used normal dog gallbladder epithelial cell monolayers grown in culture and examined sodium flux. Control gallbladder cells absorbed sodium. When secretin (0.5-2.5 x 10(-7) M) was added, there was a prompt reversal of sodium flux, resulting in net secretion. We conclude that secretion is a physiological function of the gallbladder mucosa. After feeding, the neural and humoral factors divert stored and newly secreted bile into the duodenum and induce active de novo secretion thus producing a gallbladder bile that is opalescent white with no lipids. Our results also have important implications on the origin of the pathological "white bile," the pathogenesis and treatment of gallbladder sludge, as well as the kinetic analysis of compounds undergoing enterohepatic recirculation.

Absorption↗
PubMed1998

Neural control of the gallbladder: an intracellular study of human gallbladder neurons.

BACKGROUND/AIMS: Gallbladder neurons are important governors of gallbladder function. In animal models, gallbladder ganglia can be regulated both by neural and hormonal inputs. The purpose of this study was to demonstrate the feasibility of obtaining recordings from human gallbladder neurons. METHODS: Human gallbladders (n = 33) were bathed in oxygenated Krebs solution (37 degrees C) containing the vital fluorescent stain 4-Di-2-ASP to localize the ganglia. Cells were characterized using conventional intracellular recording techniques. RESULTS: The mean resting membrane potential of human gallbladder neurons was -51.2 +/- 1.8 mV (n = 11). Depolarizing current pulses elicited only 1-4 spikes regardless of the amplitude or duration of the stimulus. Afterspike hyperpolarizations had a mean duration of 144.5 +/- 19.2 ms (n = 10). Anodal break excitation was not recorded with hyperpolarizing current pulses. Fiber tract stimulation elicited fast excitatory postsynaptic potentials in all neurons tested. CONCLUSION: Intracellular recordings of human gallbladder neurons utilizing 4-Di-2-ASP are thus feasible, but are very problematic due to the density of connective tissue overlying the ganglia. As human and guinea pig gallbladder neurons have similar basic electrical properties, the guinea pig may be an appropriate model for further electrophysiological studies into gallbladder disease.

Action Potentials↗
PubMed1983

Diurnal profile of gallbladder size in diabetic patients: ultrasonographic evaluation of diabetic neurogenic gallbladder.

The diurnal change of gallbladder size was clearly measured with a real time ultrasonography. To visualize the gallbladder, 21 diabetic patients and 11 healthy subjects were scanned right subcostally in the supine position nine times between 8:00 a.m. and 8:00 p.m. Photographs of the images were produced on Polaroid film, and the area of gallbladder was calculated. The diurnal changes of the gallbladder size were expressed as the percentage of the size measured at 8:00 a.m. after an overnight fast. The gallbladder in normal control started contracting immediately after breakfast and reached 57.2 +/- 7.6% at 9:00 a.m. In the diabetic patients with and without autonomic neuropathy the gallbladder contracted to 80.9 +/- 14.5% and 72.4 +/- 14.8%, respectively, at 9:00 a.m. while the nadir of the diurnal profile curve in healthy subjects was 24.5 +/- 3.6% at 3:00 p.m., in the diabetic patients with and without autonomic neuropathy those were 57.7 +/- 6.1% at 6:00 p.m. and 41.3 +/- 8.3% at 8:00 p.m., respectively. This implies that the gallbladder contraction was delayed and poor in diabetic patients. In this paper, the gallbladder tonicity index is proposed, which is useful for the easy evaluation of autonomic state of gallbladder in diabetes mellitus.

Adolescent↗
PubMed2006

Management of cancer gallbladder found as a surprise on a resected gallbladder specimen.

Carcinoma gallbladder is associated with an overall 5-year survival rate reported less than 5% due to late diagnosis. Advent of ultrasound scanning may help in detecting gallbladder polyps and an early gallbladder cancer. Excellent 5-year survival (up to 100%) has been reported for Stage Ia disease and the survival has significantly improved for Stage Ib, II, and III if appropriate re-operation is carried out soon after the incidental detection of gallbladder cancer. Laparoscopic cholecystectomy (LC) is contraindicated in the presence of gallbladder cancer. It is recommended to excise all laparoscopic port sites, at the time of re-operation. Re-operation for Stage II gallbladder cancer is associated with a 90-100% 3-year survival rate. Patients with Stage III and IV tumors also benefit from an extended cholecystectomy. Patients with bulky primary tumors without lymph node metastases (T4N0) seem to have a better prognosis than those with distant lymph node metastases, and should be treated aggressively. It is advantageous to perform the appropriate extent of surgery for gallbladder cancer at the initial operation. Heightened awareness of the presence of cancer and the knowledge of appropriate management are important. For patients whose cancer is an incidental finding on pathologic review, re-resection is indicated for all disease except Stage Ia. Radiotherapy and chemotherapy have not been found effective as an adjuvant or palliative therapy in gallbladder cancer.

Cholecystectomy↗
PubMed1999

[Microbiological study of gallbladder bile in a high risk zone for gallbladder cancer].

BACKGROUND: Gallbladder cancer is frequent in Chile and there is sparse information about the association between this type of cancer and the presence of bacteria in the gallbladder bile. AIM: To determine the presence of aerobic bacteria in gallbladder bile in patients with and without gallbladder cancer. MATERIAL AND METHODS: A microbiological analysis of bile and pathological study was performed in 608 gallbladders, obtained during to cholecystectomies performed to 513 women and 95 men aged 44 years old as a mean. RESULTS: Pathological study showed a chronic cholecystitis in 468 cases (77%), an acute cholecystitis in 140 (33%), cancer in 24 (3.9%) and dysplasia in 5 cases (0.8%). A positive culture was obtained in 22.5% of women and 28.5% of males. Twenty seven percent of women over 30 years old had positive cultures compared with 10% of younger women (p < 0.001). Thirty two percent of acute cholecystitis had positive cultures, compared with 24% of chronic cholecystitis (p = 0.03). E Coli was isolated in 51% of positive cases, Streptococci-Enterococci in 24%, Enterobacter sp in 9%, Klebsiella and Proteus in lower proportions. Salmonella sp was isolated in 4 cases, being all women with chronic cholecystitis. Thirteen of 29 cases with cancer or dysplasia had positive cultures (45%), compared with 25% of patients with inflammatory gallbladder diseases (p = 0.02). Streptococci-Enterococci were isolated in 7 cases and Enterobacter sp in three. CONCLUSIONS: The presence of Salmonella sp in gallbladder bile was not frequent in the studied patients. Its role in the pathogenesis of gallbladder cancer must be reassessed.

Adult↗