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Gallbladder enhancement following angiography: a normal CT finding.

The authors reviewed computed tomography (CT) studies that had been preceded within 2 days by angiography. Twenty-one patients were selected who showed no laboratory evidence of liver or renal disease. Eighteen patients received greater than 37 g of iodine at angiography. Eight of these underwent CT within 2 h of angiography and showed enhancement of the gallbladder wall, nine underwent CT 15 to 48 h after angiography and showed enhancement of the gallbladder contents, and one had no gallbladder enhancement. Three patients received less than 22 g of iodine at angiography and none had gallbladder enhancement on CT. The necessity of differentiating normal gallbladder enhancement from pathology on CT is stressed. In addition, the physiologic mechanisms responsible for gallbladder enhancement are presented, and the relationship of our findings to the total body opacification effect and to infusion tomography of the gallbladder is discussed.

Angiography↗

Cholesterol crystal morphology in acalculous gallbladder disease.

BACKGROUND: Biliary crystal morphology is best described in patients with gallbladder stones, but most patients undergoing bile collection for microscopy have a clinical diagnosis of acalculous gallbladder disease. We investigated the morphology of biliary crystals in such patients. STUDY: Bile was obtained for polarizing microscopy from fresh cholecystectomy specimens of patients with a clinical diagnosis of acalculous or calculous gallbladder disease. Slides for microscopy were prepared by touch contact with bile in freshly opened gallbladder specimens, and following aspiration of gallbladder bile through a 5-French cannula. RESULTS: Bile was examined from five patients with a clinical diagnosis of acalculous gallbladder disease and five patients with known gallstones. Needle-like cholesterol crystals predominated in most patients without gallstones, whereas plate-like and dot-like crystals were more common in patients with gallstones. All three crystal types were seen in most patients. Crystal morphology was not affected by aspiration of bile through a 5-French cannula. CONCLUSIONS: Birefringent needles and dots should be recognized as cholesterol crystals during bile microscopy. These crystal morphologies may predominate in some patients with a clinical diagnosis of acalculous gallbladder disease.

Adult↗

The effects of acute exercise on gallbladder function in an adult female population.

It has been suggested that aerobic exercise influences gallstone disease pathogenesis through its effects on gallbladder motility. The purpose of the present investigation was to examine the effects of acute aerobic exercise on gallbladder emptying. Gallbladder function was evaluated, via cholescintigraphy, in 12 healthy females after undergoing two experimental trials [i.e., postprandial (P) and exercise + postprandial (E + P))]. In the E + P trial, 60 min after injection of 99mTc disofenin, subjects exercised for 30 min at 65.3 +/- 0.9%, (mean +/- SEM) of VO2 peak on a recumbent leg ergometer, and then ingested 8 oz of a liquid meal to promote gallbladder emptying. In the P trial the meal was administered at the same time relative to the E + P trial; however, for the 30 min prior to meal ingestion subjects remained in a resting supine position. Postprandial gallbladder ejection fraction (EF) was nonsignificantly higher in the E + P trial (49.4 +/- 5.1%) than in the P trial (46.6 +/- 6.7%). Results of this study also indicated that during a fasted state the gallbladder undergoes significant periods of spontaneous emptying both at rest EF = 25 +/- 5.6% (P < 0.02) and during exercise EF = 17 +/- 4.3% (P < 0.01). In conclusion, the results of this study indicate that 30 min of aerobic exercise at 65% of VO2 peak does not effect gallbladder motility in a healthy, premenopausal, female population.

Adult↗

Gallbladder filling and post-ceruletide emptying in prairie dogs and rabbits.

The filling and emptying characteristics of the gallbladder in prairie dogs and rabbits were studied to assess the importance of the residual bile in the pathogenesis of gallstones. In prairie dogs under ketamine/xylazine anesthesia, a significantly larger fraction (p = 0.001) of hepatic bile entered the gallbladder (87 +/- 8%) than the intestine during fasting and very little bile emptied (0-3% ejection fraction) following ceruletide infusion. In rabbits under similar anesthesia, only a small fraction of hepatic bile entered the gallbladder (4 +/- 2%) during fasting, and the gallbladder emptied almost completely (85% ejection fraction) following ceruletide infusion. The resultant higher residual bile in the prairie dog gallbladder and lower residual bile in the rabbit gallbladder may explain why gallstones form so readily in prairie dogs but not in rabbits when fed a lithogenic diet. These similarities and differences in gallbladder function must be taken into account when considering any animal as a model for gallstone formation.

Animals↗

Patients with gallstones develop gallbladder cancer at an earlier age.

Significant proportions of Indian patients with gallbladder cancer are young. Multiple risk factors for gallbladder cancer are recognized among Indian patients. The effect of these risk factors on the age of development of gallbladder cancer is not known. We conducted a study to determine the influence of risk factors on the age at diagnosis of patients with gallbladder cancer and to assess the interactions between these risk factors. Patients with gallbladder cancer from two tertiary care institutions during the period 1994-2001 were prospectively studied. An ultrasound examination was done to look for the presence of gallstones. The influence of gender, gallstones, socio-economic status, smoking, residence in rural areas and in the Gangetic belt on the age at presentation was analysed using univariate analysis, logistic and linear regression analyses. The mean age of the 121 patients studied was 55+/-11.7 (SD) years. There were 51 (42%) patients aged less than 50 years. The younger patients (age < or =50 years) were more likely to have gallstones (88 versus 66%; P=0.008) and to have come from a lower socio-economic background (88 versus 71%; P=0.02) in comparison with older patients. However, there was no effect of the other risk factors. The independent determinants for younger age of patients with gallbladder cancer on logistic regression analysis were gallstones [odds ratio (OR) 4, 95% confidence interval (CI) 1.5-11; P=0.006] and lower socio-economic status (OR 3.1, 95% CI 1.1-8.6; P=0.03). On linear regression analysis, age at presentation was lowered by 5.6 years if there were associated gallstones. The mean age of patients with these two risk factors was significantly lower than that of those with one risk factor or no risk factor (52+/-12 years versus 57+/-11 years versus 61+/-9 years; P=0.007). In conclusion, the presence of gallstones and lower socio-economic status were both independently associated with a younger age at diagnosis of gallbladder cancer and their effect was additive.

Adult↗

Gallbladder cancer with a low junction of the cystic duct or an anomalous pancreaticobiliary junction.

OBJECTIVE: To evaluate conditions similar to those of carcinogenesis of the gallbladder between the gallbladder with a low junction of the cystic duct (LJCD) and an anomalous pancreaticobiliary junction (APBJ). DESIGN: Retrospective and clinicopathological analysis of patients with gallbladder carcinoma. SETTING: First Department of Surgery, Kansai Medical University. PATIENTS: Examination of 47 patients (7 men and 40 women; average age: 67.8 years) with gallbladder carcinoma revealed 7 patients (14.9%; 1 man and 6 women; average age: 67.8 years) with LJCD and 6 patients (12.8%; 6 women; average age: 60.3 years) with APBJ. METHODS: Clinical findings in both groups were compared with those of the 34 patients who remained after exclusion of the data of the above 7 patients with LJCD and 6 patients with APBJ. The data of the three groups were examined by the chi 2 test at the 5% level of significance. RESULTS: Most of the gallbladder cancer patients with LJCD or APBJ had gallstones. The biliary amylase levels determined in the gallbladder of patients with LJCD or APBJ were remarkably high. CONCLUSION: The results indicate that patients with LJCD or APBJ are more likely to develop carcinoma of the gallbladder. The factors responsible for carcinogenesis may be alteration of the bile content due to reflux of pancreatic enzymes through the LJCD or APBJ, and mechanical irritation due to gallstones. Therefore, these pathological conditions in patients with LJCD are similar to those experienced in patients with APBJ.

Aged↗

Dose-dependent stimulation of gallbladder contraction by intravenous erythromycin in man.

We have previously shown that a single oral dose of 500 mg erythromycin causes gallbladder contraction. The effect of intravenous erythromycin on antroduodenal motility is dose-dependent; < 3 mg/kg body weight stimulates propagated contractions in a fashion similar to motilin while doses > 7 mg/kg cause giant non-propagated antral contractions not seen with motilin. Using ultrasound, we have examined the effect of differing doses of intravenous erythromycin on gallbladder motility in man. Erythromycin (1 mg/kg) caused fasting gallbladder contraction to 52% of basal gallbladder volume (P < 0.001), and increased gallbladder emptying following a liquid meal (maximal percentage emptied 75 +/- 6.8% vs. 58 +/- 9.0% following saline, P < 0.05). Erythromycin (7 mg/kg) however, had no effect on gallbladder fasting or post-prandial motor activity. We conclude that the effect of erythromycin on gallbladder motility is dose-dependent, with higher doses having no effect. It is possible that at higher doses erythromycin stimulates other receptors in addition to the motilin receptor, and that the combined effect is different to the stimulation of the motilin receptor alone.

Adult↗

Gallbladder Na+/H+ exchange activity is up-regulated prior to cholesterol crystal formation.

BACKGROUND: Gallbladder Na+ and H2O absorption are increased prior to gallstone formation and may promote cholesterol nucleation. Na+/H+ exchange (NHE) isoforms NHE2 and NHE3 are involved in gallbladder Na+ transport in prairie dogs. We examined whether increased gallbladder Na+ absorption observed during early gallstone formation is the result of NHE up-regulation. MATERIALS AND METHODS: Native gallbladder and primary cultures of gallbladder epithelial cells (GBECs) harvested from prairie dogs fed nonlithogenic (CON) or 1.2% cholesterol diet for varying lengths of time to induce cholesterol-saturated bile (PreCRYS), cholesterol crystals (CRYS), or gallstones (GS) were used. NHE activity was assessed by measuring dimethylamiloride-inhibitable 22Na+ uptake under H+ gradient in primary GBECs. HOE-694 was used to determine NHE2 and NHE3 contributions. NHE protein and mRNA expression were examined by Western and Northern blots, respectively. RESULTS: Gallbladder total NHE activity was 25.1 +/- 1.3 nmol mg protein(-1) min(-1) in the control and increased during gallstone formation peaking at the PreCRYS stage (98.4 +/- 3.9 nmol mg protein(-1) min(-1)). There was a shift in NHE activity from NHE2 to NHE3 as the animals progressed from no stones through the PreCRYS and CRYS stages to gallstones. The increase in NHE activity was partly caused by an increased Vmax without any change in K(Na)m. Both NHE2 and NHE3 protein increased moderately during the PreCRYS stage without increases in mRNA expression. CONCLUSIONS: Increased gallbladder Na+ absorption observed prior to crystal formation is in part caused by an increase NHE activity which is not fully accounted for by an increase in NHE proteins and mRNA levels but may be explained by enhanced localization in the membranes and/or altered regulation of NHE.

Absorption↗

Gallbladder motility in sheep: effects of cholecystokinin and related peptides.

Gallbladder motility was recorded as tonic and small amplitude (rhythmic) contractions in conscious sheep fitted with miniaturized strain-gauge force transducers located in the corpus and fundus. Nichrome wire electrodes were chronically implanted in the gastroduodenal area. Both tonic and superimposed rhythmic gallbladder contractions were increased during feeding. They decreased during the periodic phases of antroduodenal quiescence. The excitatory effects on gallbladder and antroduodenal motility were mimicked by pilocarpine and blocked by atropine. Cholecystokinin (CCK-OP) and caerulein elicited motor responses of the gallbladder in a dose-related manner without antroduodenal stimulation. In contrast, pentagastrin induced gallbladder motor responses with concomitant stimulation of the antroduodenal area. The results suggest that feeding may act to trigger gallbladder motor activity through a mechanism related to the increased antroduodenal activity. Direct effects of CCK-OP and caerulein confirm that gallbladder motor function is also mediated through specific receptor sites.

Animals↗

Gallbladder cancer and liver transplantation.

Gallbladder cancer is the fifth most common malignancy of the gastrointestinal tract. Gallbladder cancer is found incidentally at the time of cholecystectomy in 0.35% of patients. Two previous isolated case reports of incidentally found gallbladder cancer in hepatectomy specimens following liver transplantation (LT) showed no adverse outcomes. We reviewed the outcome of four patients. Three patients had end-stage liver disease secondary to primary sclerosing cholangitis and one patient had cryptogenic cirrhosis. Gallbladder cancer was removed at cholecystectomy in one patient 11 months prior to transplant. One patient had suspected gallbladder cancer prior to LT by ultrasound and CT imaging, as well as a rising CA 19-9. The other two patients had incidentally identified gallbladder cancer. Median follow-up was 30 months. There has been no evidence of recurrence and patient survival was 100%. Early gallbladder cancer is not a contraindication for LT, however further follow-up is needed.

Contraindications↗

Ultrasonographic evidence of association of polyps and stones with gallbladder cancer.

OBJECTIVE: The purpose of this study was to evaluate the level of gallbladder cancer risk associated with polyps and stones of the gallbladder by ultrasound examinations. METHODS: We investigated abdominal ultrasonographic findings for gallstones and polyps of the gallbladder and the relationship of these findings to malignancy in 194,767 asymptomatic participants in health screening examinations. RESULTS: Gallstones were detected in 7,985 participants (4.1%), at a prevalence of 5.3% in male and 4.5% in female participants. The prevalence was highest in the participants' seventh decade, followed by the sixth and the fifth decades, in both male and female participants. Polyps were found in 10,926 (5.6%), at a prevalence of 6.9% in the male and 4.5% in the female participants. In the male participants, prevalence was highest in the fourth decade, followed by the third and the fifth decades, whereas in the female participants it was highest in the fifth decade, followed by the fourth and third. High prevalence of polyps > or = 10 mm in diameter was found in the fifth to seventh decades in both sexes. Nineteen participants (0.01%) were diagnosed as having gallbladder cancer, and many of them were in the sixth or seventh decade in both sexes. Patients with stones showed a higher prevalence of gallbladder cancer. This difference was shown to be statistically significant by age-adjusted analysis (p < 0.01). The age distribution of the participants with polyps > or = 10 mm in diameter was correlated with that of patients diagnosed with gallbladder cancer. Furthermore, polyp incidence was significantly related to cancer by statistical analysis (p < 0.01). CONCLUSION: These results suggest an association between gallstone or polyp of the gallbladder and increased risk of malignancy, implying that an etiological association may also exist.

Adult↗

Gallbladder hypocontractility in infantile colic.

We evaluated gallbladder contractility in 58 colicky infants and 57 age-matched controls. Gallbladder size was measured before and 1 h after feeding and the contraction index of the gallbladder was calculated. The results showed decreased contractility of the gallbladder in colicky infants: mean contraction index in colicky infants was 56% (95% confidence interval, 49-63%) and in controls 67% (61-73%). No difference was found in the fasting size of the gallbladder. Postprandial contraction was decreased in colicky infants examined in the evening (n = 14) compared with those examined in the morning (n = 44). Decreased contraction of the gallbladder was found in those colicky infants who presented colicky cry compared with colicky infants without symptoms at the time of examination. No structural abnormalities were found in the general abdominal survey. In conclusion, infants with colic have hypocontractility of the gallbladder. This indicates abnormal biliary tract physiology in association with infantile colic.

Case-Control Studies↗

The influence of morphine, loperamide and naloxone on gallbladder response to prostaglandin E2 in the anaesthetized cat.

In experimental cholecystitis there is a net fluid secretion into the gallbladder lumen and an increased release of prostaglandins. Indomethacin and opiates are known to inhibit this mucosal fluid secretion. Intraluminal or intra-arterial administration of prostaglandin E2 reduces basal gallbladder fluid absorption or induces a net fluid secretion to the lumen and also contracts the normal gallbladder. The use of a continuous perfusion technique in anaesthetized cats in this study shows that the effects of prostaglandin E2 on gallbladder function are blocked by intravenous morphine and loperamide. Naloxone does not affect the gallbladder responses to PGE2 administration. As a mechanism of action it is suggested that opiates inhibit secretory and contractile nerves that are activated by prostaglandins in the gallbladder wall. The findings suggest that the pain relieving effects of opiates in cholecystitis and biliary pain partly are due to blocking of the effects by prostaglandins on gallbladder function.

Animals↗

Release of immunoreactive vasoactive intestinal peptide (VIP) from the gallbladder in response to vagal stimulation.

Immunoreactive VIP was detected in the gallbladder lumen and in the arterial blood and venous effluent from the gallbladder in fasting cats. During perfusion of the gallbladder in vivo there was a constant basal intraluminal secretion of VIP. The VIP concentration in the luminal effluent exceeded that in plasma supporting the notion that there was a release from the gallbladder tissue. The rate of secretion was significantly increased during efferent electrical stimulation of the peripheral cut end of the cervical vagal nerves, after blockade with atropine. A similar increase in concentration of VIP was seen in the venous effluent from the gallbladder. The results suggest a local release of VIP from intrinsic neurons within the gallbladder wall. This release is increased in response to activation of non-cholinergic fibres in the vagus nerves, suggesting a role for VIP in regulation of gallbladder functions.

Animals↗

Intraluminal prostaglandin E2 affects gallbladder function by activation of intramural nerves in the anaesthetized cat.

Gallbladder mucosal net fluid transport and motility were measured in vivo by a continuous perfusion technique in the anaesthetized cat. Prostaglandin E2, administered to the perfused gallbladder lumen, caused a contraction decreasing gallbladder volume capacity, and induced a secretory response by the mucosa. These effects by prostaglandin E2 were abolished by the nerve-blocking agent tetrodotoxin (administered close intraarterially) and somatostatin (administered intravenously), but not by intravenous hexamethonium. Atropine (administered intravenously) reduced the order of magnitude of the gallbladder contraction in response to prostaglandin E2 but did not affect the secretory response by the mucosa. Neither of these drugs significantly affected gallbladder volume capacity or mucosal fluid transport during basal conditions. Tetrodotoxin did not abolish the gallbladder responses to intravenous cholecystokinin or vasoactive intestinal peptide, peptides known to act directly upon smooth muscle and epithelial cell receptors, respectively. It is suggested that prostaglandin E2 affects gallbladder function in vivo mainly by activation of postganglionic non-cholinergic intramural nerve cells.

Animals↗

Aberrant maspin expression in gallbladder epithelium is associated with intestinal metaplasia in patients with cholelithiasis.

OBJECTIVE: Aberrant expression of maspin protein related to DNA hypomethylation in the promoter region is frequently observed in gallbladder carcinomas, whereas the non-tumorous gallbladder epithelium is maspin negative. We investigated maspin expression in non-tumorous gallbladder epithelium in patients with cholelithiasis. METHODS: An immunohistochemical study of maspin expression was performed in 69 patients with cholelithiasis and 30 patients with gastric cancer without cholelithiasis. RESULTS: Immunoreactivity for maspin was observed in focal and patchy regions of the gallbladder epithelium. Positive immunoreactivity for maspin was significantly associated with the presence of intestinal metaplasia in patients with cholelithiasis (p<0.05). CONCLUSION: The high incidence of aberrant maspin expression in both intestinal metaplasia and carcinoma of the gallbladder supports the assumption that intestinal metaplasia of the gallbladder may predispose to gallbladder carcinoma.

Adult↗

Ablation of the cystic duct and gallbladder: clinical observations.

The cystic duct and gallbladder were ablated in eight patients with acute gallbladder disease who had been treated with minicholecystostomy instead of cholecystectomy because of multiple risk factors. First, endoluminal transcatheter radio-frequency electrocoagulation of the cystic duct was performed under fluoroscopic control, which resulted in complete occlusion in all eight patients. Next, the mucosa of the isolated gallbladder was sclerosed with 95% ethanol and 3% sodium tetradecyl sulfate in one to four sessions; no analgesics were required. The gallbladder volumes of all patients, estimated by means of ultrasound, were 1.5-22 cm3 (average, less than 10 cm3) after a mean follow-up period of 5 months. One patient died of a cerebrovascular accident 15 months after sclerotherapy. In all surviving patients, the gallbladder fistulas are dry and obliterated. These early clinical data indicate that electrocoagulation permits reliable, safe obliteration of the human cystic duct. The authors believe that sclerotherapy of the isolated gallbladder is feasible without toxic effects but that their treatment needs adjustment to achieve complete ablation of the gallbladder mucosa in a shorter period and in all patients.

Aged↗

Identification of key residues that cause differential gallbladder response to PACAP and VIP in the guinea pig.

Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) have opposite actions on the gallbladder; PACAP induces contraction, whereas VIP induces relaxation. Here, we have attempted to identify key residues responsible for their interactions with PACAP (PAC1) and VIP (VPAC) receptors in the guinea pig gallbladder. We synthesized PACAP-27/VIP hybrid peptides and compared their actions on isolated guinea pig gallbladder smooth muscle strips using isotonic transducers. [Ala4]- and [Val5]PACAP-27 were more potent than PACAP-27 in stimulating the gallbladder. In contrast, [Ala4, Val5]- and [Ala4, Val5, Asn9]PACAP-27 induced relaxation similarly to VIP. [Asn9]-, [Thr11]-, or [Leu13]PACAP-27 had 20-70% contractile activity of PACAP-27, whereas [Asn24,Ser25,Ile26]PACAP-27 showed no change in the activity. All VIP analogs, including [Gly4,Ile5,Ser9]VIP, induced relaxation. In the presence of a PAC1 receptor antagonist, PACAP(6-38), the contractile response to PACAP-27 was inhibited and relaxation became evident. RT-PCR analysis revealed abundant expressions of PAC1 receptor, "hop" splice variant, and VPAC1 and VPAC2 receptor mRNAs in the guinea pig gallbladder. In conclusion, PACAP-27 induces contraction of the gallbladder via PAC1/hop receptors. Gly4 and Ile5 are the key NH2-terminal residues of PACAP-27 that distinguish PAC1/hop receptors from VPAC1/VPAC2 receptors. However, both the NH2-terminal and alpha-helical regions of PACAP-27 are required for initiating gallbladder contraction.

Animals↗