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PubMed1988

Cholecystokinin receptors on gallbladder muscle and pancreatic acinar cells: a comparative study.

To compare receptors for cholecystokinin (CCK) in pancreas and gallbladder, we measured binding of 125I-Bolton-Hunter-labeled CCK-8 (125I-BH-CCK-8) to tissue sections from guinea pig gallbladder and pancreas under identical conditions. In both tissues, binding had similar time-, temperature-, and pH dependence, was reversible, saturable and inhibited only by CCK related peptides or CCK receptor antagonists. Autoradiography localized 125I-BH-CCK-8 binding to the smooth muscle layer in the gallbladder. Binding of 125I-BH-CCK-8 to gallbladder sections was inhibited by various agonists with the following potencies (IC50):CCK-8 (0.4 nM) greater than des(SO3)CCK-8 (0.07 microM) greater than gastrin-17-I (1.7 +/- 0.3 microM) and by various receptor antagonists with the following potencies: L364,718 (1.5 nM) greater than CR 1409 (0.19 microM) greater than asperlicin = CBZ-CCK-(27-32)-NH2 (1 microM) greater than Bt2cGMP (120 microM). Similar potencies were found for the agonists and antagonists for pancreas sections. Inhibition of binding of 125I-BH-CCK-8 by 11 different analogues of proglumide gave similar potencies for both pancreas and gallbladder. The potencies of agonists in stimulating and antagonists in inhibiting CCK-stimulated contraction or amylase release correlated closely with their abilities to inhibit 125I-BH-CCK-8 binding to gallbladder or pancreas sections or acini, respectively. The present results demonstrate and characterize a method that can be used to compare the CCK receptors in guinea pig gallbladder and pancreas under identical conditions. Moreover, this study demonstrates that gallbladder and pancreatic CCK receptors have similar affinities for the various agonists and antagonists tested and, therefore, provides no evidence that they represent different subtypes of CCK receptors that can be distinguished pharmacologically.

Animals↗

PubMed1991

Biliary-hepatic recycling of a xenobiotic: gallbladder absorption of methyl mercury.

The role of the gallbladder in the disposition of methyl mercury was investigated in guinea pig, hamster, and macaque monkey. 203Hg-labeled methyl mercury or inorganic mercury (5 microM) and [14C]inulin were instilled into the in situ guinea pig or hamster gallbladder. After 2 h, only 27.6 +/- 7.0% of the methyl mercury remained in guinea pig gallbladder fluid as compared with 85.0 +/- 3.2% of the inorganic mercury and 90.7 +/- 4.5% of the [14C]-inulin. In the hamster, 42.5 +/- 4.5% of methyl mercury and 95% +/- 0.9% of inorganic mercury remained after 2 h. When the sulfhydryl-containing compounds L-cysteine, glutathione, and bovine serum albumin (20 microM) were added to the test solution, cysteine increased and albumin decreased absorption of methyl mercury. Ligation of guinea pig cystic artery decreased gallbladder fluid absorption from 72.7 +/- 8.6 to 26.5 +/- 9.8% over 2 h but did not alter methyl mercury absorption. Bile was also sampled from gallbladders of four monkeys exposed chronically to CH3HgCl and from three control monkeys. For one of the exposed and one of the control monkeys, bile was also collected from the common hepatic duct. In both methyl mercury-exposed and control monkeys, the concentration of methyl mercury in gallbladder bile was lower than in hepatic bile. In contrast, the concentration of inorganic mercury in gallbladder bile was four to seven times that of hepatic bile, suggesting that methyl mercury but not inorganic mercury was being reabsorbed. To assess the functional significance of methyl mercury reabsorption by the gallbladder, guinea pig cystic ducts were ligated, the animals were given CH3 203HgCl (10 mumol/kg iv), and body burden of 203Hg was measured over 16 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

PubMed1993

Guinea pig gallbladder and pancreas possess identical CCK-A receptor subtypes: receptor cloning and expression.

Cholecystokinin (CCK) receptors mediate pancreatic acinar secretion and gallbladder contraction. Pharmacological and functional studies in pancreas and gallbladder demonstrate a CCK-A receptor subtype in both tissues. However, some pharmacological studies and affinity cross-linking studies of CCK receptors on pancreatic acini and gallbladder suggest that these two tissues possess two different subtypes of the CCK-A receptor. We cloned these receptors in guinea pig using a cDNA clone of the CCK-A receptor from rat pancreas. The guinea pig gallbladder CCK-A receptor was cloned by hybridization screening of a gallbladder cDNA library using a cDNA probe from the rat CCK-A receptor coding region. The guinea pig pancreas CCK-A receptor cDNA was cloned via the polymerase chain reaction using primers corresponding to the guinea pig gallbladder CCK-A receptor 5'- and 3'-noncoding regions. CCK-A receptor clones from guinea pig pancreas and gallbladder had identical nucleotide sequences, which were 80% homologous to the rat CCK-A receptor cDNA sequence. The deduced amino acid sequence from guinea pig CCK-A receptors was 89% homologous to the rat CCK-A receptor sequence. Dose-inhibition binding studies of transiently expressed receptors by CCK agonists and antagonists exhibited a CCK-A receptor pharmacologically similar to the rat CCK-A receptor. These studies indicate that the CCK-A receptors in guinea pig pancreas and gallbladder are identical and do not support previous proposals that they may represent different receptor subtypes.

Amino Acid Sequence↗

PubMed1994

Actions of cholecystokinin and norepinephrine on vagal inputs to ganglion cells in guinea pig gallbladder.

Previous studies have demonstrated that all guinea pig gallbladder neurons receive nicotinic synaptic input and that cholecystokinin (CCK) and norepinephrine have presynaptic facilitory and inhibitory effects, respectively, on these fast synaptic events. The current study was undertaken to determine the sources of the cholinergic terminals that provide nicotinic input to gallbladder neurons. To stimulate potential extrinsic inputs to gallbladder neurons, a stimulating electrode was placed on the nerve bundles that pass along the cystic duct. Stimulation of these nerves elicited fast excitatory postsynaptic potentials (EPSPs) in gallbladder neurons that were sensitive to hexamethonium, facilitated by CCK, and inhibited by norepinephrine. After vagotomy, most neurons (14 of 18) did not exhibit any nicotinic input. However, some neurons (3 of 18) did exhibit fast EPSPs in response to fiber tract stimulation, but not cystic nerve stimulation, indicating that interganglionic communication does exist amongst gallbladder neurons. These results demonstrate that the vagus nerves provide the major nicotinic input to gallbladder neurons. Furthermore, these data suggest that vagal terminals within gallbladder are a site of neurohormonal modulation of gallbladder ganglionic output by CCK, norepinephrine, and possibly other compounds.

Action Potentials↗

PubMed2000

Effect of distension of the gallbladder on plasma renin activity in anesthetized pigs.

BACKGROUND: Gallbladder pathology has been associated with cardiovascular disease. Recently, we showed that gallbladder distension in anesthetized pigs reflexly increased heart rate, arterial pressure, and coronary and renal vascular resistance through efferent sympathetic mechanisms. Renin release is affected by sympathetic output, and angiotensin liberation may result in vasoconstriction. This study was undertaken to determine whether gallbladder distension primarily causes a reflex change in plasma renin activity (PRA) and to assess its influence on observed pressor and coronary responses as well as on regional vascular resistance. METHODS AND RESULTS: In 34 alpha-chloralose-anesthetized pigs, balloons positioned within the gallbladder were distended for 30 minutes with volumes of Ringer's solution equal to those of withdrawn bile. In 19 pigs, gallbladder distension at constant heart rate, arterial pressure, and renal flow increased PRA in the absence of changes in urinary sodium excretion. This increase was abolished by cervical vagotomy, section of renal nerves, or blockade of beta-adrenergic receptors. In another 15 pigs, blockade of angiotensin II receptors significantly attenuated the pressor and coronary, mesenteric, and iliac vasoconstriction responses to gallbladder distension. CONCLUSIONS: The present study showed that innocuous gallbladder distension primarily caused a reflex increase in PRA. This increase, which involved afferent vagal pathways and efferent sympathetic mechanisms related to beta-adrenergic receptors, contributed significantly to the pressor and coronary, mesenteric, and iliac vasoconstriction responses to gallbladder distension.

Animals↗

PubMed1983

Cardiovascular reflexes arising from the gallbladder of the cat. Effects of capsaicin, bradykinin, and distension.

We have studied the cardiovascular responses which can be evoked when the gallbladder is stimulated pharmacologically or mechanically. To determine the potential for reflex cardiovascular activation, we applied capsaicin, a selective thin-fiber agonist, to the serosal surface of the gallbladder. This algesic substance evoked cardiovascular responses which included increases in mean arterial pressure (MAP) by 14%, heart rate (HR) by 3%, left ventricular dP/dt at 40 mm Hg developed pressure (dP/dt DP40) by 14%, and systemic vascular resistance (SVR) by 19%. There were no demonstrable effects on the cardiovascular system when this same substance was applied to the surface of the liver. Bilateral vagotomy at the level of the diaphragm did not alter the responses to capsaicin. Right atrial overdrive pacing did not reduce the positive inotropic effect elicited when the gallbladder was stimulated. Removal of the celiac and superior mesenteric ganglia, or selective denervation of the gallbladder, abolished the cardiovascular responses which were evoked previously. beta-Adrenergic blockade, however, abolished only the reflex chronotropic and intropic responses. Thus, the potential for eliciting reflex cardiovascular alterations by stimulating gallbladder afferents with capsaicin was established. In subsequent studies, stimulating the gallbladder with bradykinin, an endogenous polypeptide, evoked a reflex activation of the cardiovascular system similar to that seen with capsaicin (MAP = 14%; HR = 4%; dP/dt DP40 = 18%; SVR = 14%). These reflex responses were dose dependent, were produced by mucosal as well as serosal application of this substance, and were eliminated by bilateral splanchnic nerve action. In contrast to capsaicin and bradykinin, distension of the gallbladder did not cause any cardiovascular alterations. We conclude that stimulation of gallbladder afferents by the algesic substance capsaicin or by bradykinin, an endogenous substance that under certain conditions may be formed in bile, can induce significant reflex activation of the cardiovascular system.

Adrenergic beta-Antagonists↗

PubMed1983

Gallbladder and small intestinal regulation of biliary lipid secretion during intraduodenal infusion of standard stimuli.

The gallbladder and small intestine are reservoirs for the bile acid pool during its enterohepatic circulation and, as such, may regulate biliary secretion of bile acid. During studies of biliary bile acid secretion, a stimulus to gallbladder contraction is continuously infused into the duodenum. Under these conditions, it is assumed that the gallbladder is tonically contracted and that the rate of bile acid secretion into the duodenum equals the hepatic bile acid secretion rate. However, secretion rates vary by as much as 100%, depending upon which of two standard stimuli is used. Therefore, we studied the role of gallbladder emptying and small intestinal transit in determining biliary lipid secretion rate and composition during infusion of these stimuli in five healthy subjects. Each subject was studied with a liquid formula containing 40% of calories as fat, and with an amino acid solution for 10 h. Bile acid, phospholipid, cholesterol, and markers were measured in duodenal bile and hourly secretion rates were calculated by marker dilution technique. Real-time gallbladder sonographs and serum pancreatic polypeptide levels were obtained every 30 min. Small bowel transit time was estimated levels were obtained every 30 min. Small bowel transit time was estimated by the breath hydrogen response after giving lactulose intraduodenally.During liquid formula infusion, gallbladder emptying was more complete, small intestinal transit was faster, and pancreatic polypeptide levels were higher. Secretion rates of all lipids were greater and molar percent cholesterol was lower. For the combined data from both infusions, the secretory relationships of cholesterol to bile acid, cholesterol to phospholipid, and phospholipid to bile acid were curvilinear. We conclude that more complete gallbladder emptying and faster intestinal transit increase the enterohepatic cycling of bile acids and lower the molar percent cholesterol of bile. Some of the fluctuation observed in biliary lipid secretion rates, especially during amino acid infusion, is due to gallbladder refilling and emptying.

Adult↗

PubMed1995

Ultrasound-guided percutaneous fine needle puncture of the gallbladder for studies of bile composition.

Ultrasound-guided percutaneous fine needle puncture of the gallbladder (PFNP-GB) is invaluable for diagnostic and research purposes, but there are few reports about its safety. We therefore describe the efficacy and side-effects of 43 consecutive gallbladder punctures in 39 patients. PFNP-GB was successful in 40/43 (93%), but failed in three. Bile was completely aspirated in 28 of the 40 (70%) successful procedures. After 36 of the 43 punctures (84%), the patients remained asymptomatic, although on seven occasions (16%) the patients complained of right upper quadrant pain 0.5-12 h after the procedure. In six of these, the pain resolved in 2-24 h, although one developed a leucocytosis (22 x 10(9) 1(-1)). The seventh patient developed pyrexia and signs of generalized peritonism, which settled with conservative therapy. Ultrasonographic abnormalities of the gallbladder wall were seen in five of the seven symptomatic patients, consisting of: (i) an increase in the thickness of the gallbladder wall (n = 5) from less than 2 mm to 4-14 mm; (ii) peri-cholecystic collections (n = 2) measuring 5 and 11 mm in diameter; (iii) an intraluminal mucosal flap (n = 1); (iv) an intraluminal echogenic layer (n = 1); and (v) a 12 cm intraabdominal haematoma in the patient with generalized peritonism. Predictors of pain were: (i) the number of needle "passes" (3.7 +/- 0.8, range 2-8, in patients with pain vs 2.0 +/- 0.2, range 1-6, in pain-free patients, p < 0.02); (ii) the absence of gallbladder stones (p < 0.03); and (iii) incomplete aspiration of bile from the gallbladder (p < 0.02). PFNP-GB is an effective way of sampling fresh gallbladder bile, although there is a 16% risk of inducing pain and/or ultrasonographic changes in the gallbladder.

Adult↗

PubMed1996

Sludge in fetal gallbladder: natural history and neonatal outcome.

Normal and pathological conditions of the fetal gallbladder have been a subject of recent investigation by ultrasonographers. Fetal gallstones are the most common abnormal finding and appear as echogenic foci within the gallbladder. We report a series of five fetuses in whom the gallbladders were filled with sludge which appeared as a pear shape echogenic structure. In the majority of cases, gallbladder sludge mimicked intrahepatic calcification or echogenic bowel. Serial ultrasound examinations of these fetuses revealed good interval growth. The gallbladders remained echogenic and were normal in size in three cases and were moderately enlarged in two. All neonates were born in normal condition with no identifiable malformations. Follow-up was obtained in four infants using abdominal ultrasound. A normal appearing sludge free gallbladder was seen in three neonates at 6 weeks of life and in four infants at 12 weeks. Accurate diagnosis of gallbladder sludge will spare the patient unnecessary work-up and anxiety. The natural history of gallbladder sludge in the fetus is benign in nature and is similar to that of fetal gallstones.

Calcinosis↗

PubMed1992

Studies on the electrical stimulation-induced contractile responses of hamster and mouse gallbladders.

Isolated gallbladders of both hamsters and mice showed a contractile response consisting of initial and secondary contractile responses to electrical stimulation with rectangular pulses (50 volt, 40 Hz) of 6 msec duration for a period of 10 seconds. The duration time of the contractile response was very long. This was because the duration time of the process of the initial contractile response was as short as 5 to 40 seconds, but that of the secondary contractile response was as long as 8 to 15 minutes. Both initial and secondary contractile responses of the gallbladder in both hamsters and mice were little affected by atropine (1 x 10(-6)M, guanethidine (1 x 10(-6) M) and tetrodotoxin (1 x 10(-7) M). In both animals, further, the initial contractile response of the gallbladder was little affected by indomethacin (1 x 10(-5) M) and 5, 8, 11, 14-eicosatetraynoic acid (ETYA) (5 x 10(-6) g/ml), while the amplitude of the secondary contractile response of the gallbladder was significantly reduced by such drugs. From these results, we obtain the following conclusions: 1) In both animals, the intramural nerves of the gallbladder may have no influence on the both initial and secondary contractile responses of the gallbladder. 2) The initial contractile response is probably mediated by a direct effect of the electrical stimulation to the muscle in the wall of the gallbladder, while the secondary contractile response is probably attributable to prostaglandins released from the wall of the gallbladder by a direct effect of the electrical stimulation to the wall.

5,8,11,14-Eicosatetraynoic Acid↗

PubMed1994

Gallbladder varices in portal vein thrombosis.

OBJECTIVE: We performed a prospective study to determine the frequency that gallbladder varices are seen on duplex sonograms of patients with portal vein thrombosis. SUBJECTS AND METHODS: Findings of gallbladder wall varices were sought on duplex Doppler sonograms of 74 patients with portal vein thrombosis. The diagnosis of portal vein obstruction was made on the basis of sonographic or splenoportographic findings. RESULTS: Sonography showed gallbladder varices in 22 (30%) of 74 patients. Varices were defined as anechoic, serpentine areas in the wall of the gallbladder showing venous flow on Doppler imaging. However, no gallbladder varices were detected in six patients who had patent surgical splenorenal shunts. Gallbladder varices did not correlate with the site and extent of portal vein thrombosis, the presence of a spontaneous (natural) splenorenal shunt, or endoscopic obliteration of varices. CONCLUSION: Gallbladder varices are common in patients with portal thrombosis. Awareness of gallbladder varices should increase the surgeon's caution during biliary tract surgery in patients with portal hypertension.

Adolescent↗

PubMed1981

Effects of raised intraluminal pressure on gallbladder function and hepatic bile outflow in the cat.

Gallbladder concentrating function and motility and hepatic bile outflow were studied with a perfusion technique in anesthetized cats. The function of the gallbladder distended by an intraluminal pressure of 50 cm H2) was compared with its function at a pressure within the physiological range. It was found that gallbladder distention reduced the rate of net fluid absorption by 53% compared with controls. This reduction was abolished after intravenous administration of indomethacin, a prostaglandin synthetase inhibitor. At raised intraluminal pressure in the gallbladder a slow, continuous increase in the intraluminal capacity was seen. This rate of volume increase was markedly increased after indomethacin administration. A reduction of the hepatic bile outflow after indomethacin was seen in animals with distended gallbladder but not in controls. A mechanism by which gallbladder distention induces biosynthesis of prostaglandins in the gallbladder wall and thereby influences its function is suggested. The results are discussed in relation to clinical findings in man during acute cholecystitis, a situation in which the intraluminal pressure in the gallbladder usually is markedly elevated.

Animals↗

PubMed1994

Gallbladder volume in patients with common hepatic duct dilatation. An evaluation of Courvoisier's sign using ultrasonography.

To evaluate the usefulness of Courvoisier's sign in ultrasonography, gallbladder size in patients with common hepatic duct dilatation was measured using the ellipsoid method during ultrasonographic examination. During a 6-month period 24 patients with malignant obstructions (6 with carcinoma of the ampulla of Vater, 9 with pancreatic head tumors, 5 with carcinoma of the bile duct, and 4 with malignant lymphadenopathy), 50 patients with calculous obstructions, and a group of 50 normal control patients were examined in this study. Gallbladder volumes were larger in patients with biliary tract dilatation (88.8 +/- 6.8 ml) than in the control group (34.3 +/- 2.8 ml) (p < 0.01). Although the duration and total serum bilirubin level were higher in patients with malignant obstructions, the gallbladder volumes were the same in these two groups (93.0 +/- 11.3 ml versus 86.7 +/- 8.5 ml). A linear relationship was found between gallbladder volume and total serum bilirubin in patients with malignant biliary obstructions (r = 0.6, p < 0.001) and in patients with calculous biliary obstructions without gallbladder stones (r = 0.68, p < 0.001). We hypothesized that the gallbladder volume is irrelevant in differentiating the nature of the biliary tract dilatation and that the gallbladder size is dependent on the degree of biliary obstruction when the gallbladder is not afflicted by fibrosis.

Bilirubin↗

PubMed1995

Inflammation reduces mucosal secretion of hydrogen ions and impairs concentrating function and luminal acidification in feline gallbladder.

BACKGROUND: The gallbladder mucosa normally absorbs fluid and secretes H+ ions. The fluid secretion in inflamed gallbladders is induced by prostaglandins and mediated by intramural vasoactive intestinal peptide (VIP)-ergic nerves. METHODS: The influence of inflammation on gallblader contents due to secretion of H+ into the lumen. In animals with inflamed gallbladder this acid secretion was reduced; there was secretion of HCO3- and no evident acidification of the gallbladder contents. Injection of VIP antiserum or indomethacin restored H+ secretion and inhibited HCO3- and fluid secretion by the inflamed gallbladder mucosa. An impaired acidification of the gallbladder contents due to mucosal inflammation may reduce the solubility of calcium salts in gallbladder bile and increase the risk of their precipitation in the lumen. CONCLUSION: Mucosal inflammation reduces H+ secretion and impairs acidification of the gallbladder contents.

Amiloride↗

PubMed2004

Gallbladder motility in patients with hepatic cirrhosis before and after portal azygous disconnection.

AIM: To determine and compare the effect of vagus nerve on gallbladder motility in patients with hepatic cirrhosis before and after portal azygous disconnection (PAD). METHODS: PAD operation (or Hassab's operation) was performed on 18 patients with portal hypertension, and anterior and posterior vagal trunks were cut. On d 3 before operation and d 10 after operation, (99m)Tc-EHIDA 185 MBq was administered intravenously to the patients, and scintigraphy was performed at 0.25 min/frame. A standard fat meal was administered 30 min after scintigraphy, and dynamic imaging was performed 60 min after the fat meal. Following appearance of the region of interest (ROI) in gallbladder, the time-activity curve of ROI was established. The following seven parameters were used: radioactivity at 30 min after injection of (99m)Tc-EHIDA (RC 30 min), bile emptying fraction (EF), bile emptying period (EP), emptying rate (ER), latent period (LP), latent period radiocounting increment (LI), and latent period radiocounting increment rate (LR). RESULTS: The RC 30 min decreased significantly after operation, compared with that before operation (2 693.6+/- 2 406.9 vs 5 606.8+/-2 625.4, P<0.05). The radiocounting of gallbladder increased gradually during LP. LP after operation was significantly longer than that before operation (13.36+/-5.92 vs 2.24+/-1.48, P<0.01). LI and LR after operation were significantly higher than those before operation (2 861.62+/-028.3 vs 331.21+/-421.02, and 113.42+/-49.52 vs 7.57+/-10.75, respectively, both P<0.01). EP after operation was significantly shorter than that before operation (18.5+/-6.3 vs 24.1+/-6.4, P<0.05). EF and ER after operation were significantly lower than those before operation (13.1+/-5.4 vs 32.3+/-16.3, and 0.7+/-0.3 vs 1.4+/-0.8, respectively, both P<0.01). CONCLUSION: PAD operation is a good clinical model in studying the effect of vagus on gallbladder motility. The gallbladder tension after PAD operation decreases significantly during the interdigestive phase. The latent period of gallbladder contraction prolongs and the motility weakens apparently after a standard fat meal. Human vagus influences the gallbladder motility, and cutting of the nerve inhibits the gallbladder motility.

Azygos Vein↗

PubMed2002

Expression of MMP-2,TIMP-2 protein and the ratio of MMP-2/TIMP-2 in gallbladder carcinoma and their significance.

AIM: To study the correlation between expression of MMP-2, TIMP-2 protein and the ratio of MMP-2/TIMP-2 and clinical-pathological parameters of patients with gallbladder carcinoma. METHODS: Carcinomas (n=45) and polypoid lesions (n=15) of the gallbladder were studied for the expression of MMP-2 and TIMP-2 protein by immunohistochemical avidin-biotin-complex method and image analysis. Clinical-pathological data of patients with gallbladder carcinoma such as histological type, grade of differentiation, level of infiltration, liver invasion and lymph node involvement, etc, were recorded. RESULTS: There was significant difference between the average level (1.123+/-0.108 vs 1.030+/-0.054, P=0.002) of MMP-2, the ratio (1.050+/-0.013 vs 0.937+/-0.078, P=0.003) of MMP-2/TIMP-2 in gallbladder carcinomas and in polypoid lesions of the gallbladder. Significant difference was found between the expression of MMP-2 in early stage and advanced tumors, but there was no correlation between MMP-2 protein expression and histological type, differentiation degree, infiltration level, lymph node involvement or liver invasion. Although no difference was observed between TIMP-2 expression and histological type or differentiation degree, significant difference was found between TIMP-2 expression and different Nevin stage, infiltration level, local lymph node involvement or liver invasion (1.168+/-0.067 vs 1.048+/-0.075, 1.170+/-0.062 vs 1.039+/-0.069, 1.039+/-0.076 vs 1.147+/-0.083, 1.048+/-0.074 vs 1.103+/-0.095, P<0.05). MMP-2/TIMP-2 ratio did not correlate with histological type, grade of differentiation and liver invasion, but significant differences were found between MMP-2/TIMP-2 ratio and different Nevin stage, infiltration level and lymph node involvement in patients with carcinoma of gallbladder. CONCLUSION: TIMP-2 and MMP-2/TIMP-2 ratio could reflect more accurately biological characteristic of gallbladder carcinoma and MMP-2/TIMP-2 ratio might be a new significant marker in early diagnosis, in the judgment of invasion or metastasis and the estimate of prognosis in patients with gallbladder carcinomas.

Adenocarcinoma↗

PubMed2001

Is cholecystectomy necessary after ERCP for bile duct stones in patients with gallbladder in situ?

BACKGROUND: The requirement for subsequent cholecystectomy in patients with gallbladder in situ after endoscopic removal of stones from the common bile duct (CBD) is controversial. The aims of this study were to assess the requirement for subsequent cholecystectomy for gallbladder-related symptoms, and to identify the patients who develop symptoms after the endoscopic removal of CBD stones. METHODS: Of 241 patients with gallbladder in situ following endoscopic removal of stones from the CBD, 146 patients (78 men and 68 women; mean age 69 +/- 13 years, range 20-93) with a follow-up time of more than three months without elective cholecystectomy were enrolled in the study. Fifty-nine patients had gallbladder stones (single stones in 27 and multiple stones in 32) and 87 patients had gallbladder in situ without stones. The time from entry to the occurrences of death or cholecystectomy was evaluated retrospectively. Cox regression analysis was used to evaluate the risk factors associated with these events. RESULTS: The mean duration of follow-up was 24.1 +/- 18.0 months (range 3-70 months). During follow-up, seven patients (4.8%) underwent cholecystectomy, on average 18.4 months after CBD stone removal, as the result of acute cholecystitis in four cases, biliary pain in two cases and acute pancreatitis in one case. Laparoscopic cholecystectomy was performed in four patients and open cholecystectomy in three patients. Post-operative morbidity occurred in two patients, with improvement after conservative management. Nine patients (6.2%) died as the result of unrelated biliary disease. Age, sex, presence of gallbladder stones, multiplicity of gallbladder stones and underlying disease did not correlate with subsequent cholecystectomy by Cox regression analysis. CONCLUSION: Elective cholecystectomy is not warranted in patients with bile duct stones when the common duct can be cleared of stones by endoscopic sphincterotomy. We could not find any clinical predictors of further symptoms or complications arising from the retained gallbladder.

Adult↗

PubMed2005

Papillary carcinomas of the gallbladder: analysis of noninvasive and invasive types.

CONTEXT: Although papillary carcinomas have been recognized as distinct morphologic variants of gallbladder neoplasms, they have been lumped together in a single group despite the recognition of noninvasive and invasive types. As a result, the biologic behavior of each type remains undescribed. OBJECTIVE: To compare the biologic behavior of noninvasive and invasive papillary carcinomas of the gallbladder. DESIGN: The clinical and morphologic features of 16 noninvasive papillary carcinomas (>1 cm) of the gallbladder were analyzed, and their clinical behavior was compared with that of 370 invasive papillary carcinomas recorded in the Survey Epidemiology and End Results (SEER) Program of the National Cancer Institute from 1973 through 2001. The biologic behavior of invasive papillary carcinomas was compared with that of invasive nonpapillary carcinomas of the gallbladder recorded in SEER. Hematoxylin-eosin-stained sections were available for review in the 16 noninvasive papillary carcinomas. The number of slides examined per case varied from 3 to 16, with an average of 7. RESULTS: The 16 patients with noninvasive papillary carcinomas included 11 women and 5 men, aged 34 to 83 years (mean age, 61 years). Thirteen patients had cholelithiasis. Laparoscopic cholecystectomy was performed on 12 patients and open cholecystectomy on 4. The tumors measured from 1.3 to 8.6 cm and were well to moderately differentiated. Fourteen noninvasive papillary carcinomas showed biliary phenotype, and 2 showed intestinal phenotype. Follow-up was obtained in 11 patients; 6 were asymptomatic 5 to 11 years after surgery, 2 were symptom free 9 months to 4 years following cholecystectomy, and 3 died of unrelated causes 2 to 3 years after surgery. Three hundred seventy cases of invasive papillary carcinomas were recorded in SEER. The 10-year relative survival rate for 225 patients with invasive papillary carcinomas confined to the gallbladder wall was 52%, while the 10-year relative survival rate for 83 patients with papillary carcinomas that had spread to the lymph nodes was less than 10%. Of the remaining 62 invasive papillary carcinomas, 58 had distant metastases and 4 were not staged. The 10-year relative survival rate for invasive nonpapillary carcinomas confined to the gallbladder wall was 30%. CONCLUSION: Noninvasive papillary carcinomas of the gallbladder-regardless of size, cell phenotype, and degree of differentiation-do not metastasize, and a simple cholecystectomy appears to be a curative procedure. In contrast, invasive papillary carcinomas do metastasize and are associated with a poor prognosis (10-year relative survival rate for tumors confined to the gallbladder wall was 52%, while the 10-year relative survival rate for tumors with lymph node metastasis was <10%). The separation of papillary carcinomas into noninvasive and invasive types is clinically relevant and therefore fully justified.

Adult↗