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PubMed1988

Progesterone receptors regulate gallbladder motility.

The increased incidence of gallstones in multiparous women may be related to hormonal effects on the gallbladder and its contractility. The occurrence of estrogen and progesterone receptors were studied in the gallbladders of three groups of female guinea pigs (normals, oophorectomized, and oophorectomized treated with estrogen + progesterone for 14 days). Gallbladder contractile response in vivo to cholecystokinin (CCK) was related to the presence of these receptors. The gallbladders from normal females showed low progesterone and estrogen binding activity (4.9 +/- 2.0 and 2.4 +/- 0.8 fmoles/mg cytosol protein). Oophorectomized females had no detectable progesterone or estrogen receptors, but after treating oophorectomized females for 14 days with estrogen + progesterone, gallbladder concentrations of progesterone receptors increased significantly to 14.7 +/- 5.9 fmoles/mg and estrogen binding activity was minimally detectable at 1.4 +/- 0.8 fmoles/mg. The gallbladder contractile response to CCK was inversely related to the concentration of progesterone receptors in the gallbladder wall. These data suggest that the gallbladder contains progesterone receptors which are susceptible to circulating hormonal conditions and which have a regulatory effect on gallbladder contractility.

Animals↗

PubMed2004

Polypoid lesions of the gallbladder.

BACKGROUND: Polypoid lesions of the gallbladder encompass a wide variety of pathology. Although most of these lesions are benign, some early carcinomas of the gallbladder do present as polypoid lesions. Problems remain in selecting patients with polypoid lesions of the gallbladder for surgery, the operative approach, and the method of follow-up of those deemed not needing surgery. DATA SOURCES: This review was done by Medline search of the English literature by the keywords "polypoid lesions of gallbladder," "gallbladder polyps," "carcinoma of gallbladder," and "benign tumors of gallbladder." CONCLUSIONS: Most small polypoid lesions of the gallbladder are benign and remain static for years. Three- to six-monthly ultrasonography examination is warranted in the initial follow-up period but it is probably unnecessary after 1 or 2 years. Age more than 50 years and size of polyp more than 1 cm are the two most important factors predicting malignancy in polypoid lesions of the gallbladder. Other risk factors include concurrent gallstones, solitary polyp, and symptomatic polyp. Laparoscopic cholecystectomy is the treatment of choice unless the suspicion of malignancy is high, in which case it is advisable to have open exploration, intraoperative frozen section, and preparation for extended resection.

Algorithms↗

PubMed2005

Natriuretic peptides cause relaxation of human and guinea-pig gallbladder muscle through interaction with natriuretic peptide receptor-B.

Atrial natriuretic peptide (ANP) binding sites have been demonstrated in the guinea-pig gallbladder muscle with unclear function. To investigate effects of natriuretic peptides in the gallbladder, we measured relaxation of isolated human and guinea-pig gallbladder strips caused by natriuretic peptides, including C-type natriuretic peptide (CNP), brain natriuretic peptide (BNP) and ANP, as well as des[Gln18, Ser19, Gly20, Leu21, Gly22]ANP(4-23) amide (cANP(4-23)), a selective natriuretic peptide receptor-C (NPR-C) agonist. Results in the human gallbladder were similar to those in the guinea-pig gallbladder. CNP, BNP, ANP and cANP(4-23) alone did not cause contraction or relaxation in resting gallbladder strips. However, in carbachol or endothelin-1-contracted strips, CNP caused moderate, sustained and concentration-dependent relaxation. The relaxation was not affected by tetrodotoxin or atropine in endothelin-1-contracted gallbladder strips and not by tetrodotoxin in carbachol-contracted strips. These indicate a direct effect of CNP on the gallbladder muscle. The relative potencies for natriuretic peptides to cause relaxation were CNP>>BNP> or = ANP. cANP(4-23) did not cause relaxation. These indicate the existence of the natriuretic peptide receptor-B (NPR-B) mediating the relaxation. Taken together, these results demonstrate that natriuretic peptides cause relaxation of human and guinea-pig gallbladder muscle through interaction with the natriuretic peptide receptor-B.

Animals↗

PubMed1999

Excess membrane cholesterol alters human gallbladder muscle contractility and membrane fluidity.

BACKGROUND & AIMS: The relationship between muscle contractility, plasma membrane cholesterol, and fluidity was investigated in human gallbladders with gallstones. METHODS: Isolated gallbladder muscle cells were used to measure contraction. Plasma membranes of gallbladder muscle were purified in a sucrose gradient and measured for cholesterol content and cholesterol/phospholipid mole ratio. Membrane fluidity was determined by using fluorescence polarization and was expressed as the reciprocal of anisotropy. RESULTS: The maximal contraction induced by cholecystokinin octapeptide was significantly less in gallbladders with cholesterol stones than in those with pigment stones. The membrane cholesterol content and cholesterol/phospholipid mole ratio were significantly higher in gallbladders with cholesterol stones than in those with pigment stones. Membrane anisotropy was also higher than in gallbladders with pigment stones, reflecting lower membrane fluidity in gallbladders with cholesterol stones. After muscle cells from cholesterol stone gallbladders were incubated with cholesterol-free liposomes for 4 hours, cholecystokinin octapeptide-induced contraction, membrane cholesterol content and cholesterol/phospholipid ratio, and membrane fluidity returned to normal levels. CONCLUSIONS: Gallbladder muscle from patients with cholesterol stones has increased membrane cholesterol/phospholipid mole ratio and decreased membrane fluidity resulting in impaired muscle contractility. These abnormalities are corrected by removing the excess cholesterol from the plasma membranes.

Cell Membrane↗

PubMed2004

An evaluation of laparoscopic cholecystectomy after selective percutaneous transhepatic gallbladder drainage for acute cholecystitis.

BACKGROUND: The aim of this study was to evaluate the safety and usefulness of laparoscopic cholecystectomy after selective percutaneous transhepatic gallbladder drainage in patients with severe acute cholecystitis and patients with acute cholecystitis and severe comorbid disease. METHODS: According to whether percutaneous transhepatic gallbladder drainage was performed before surgery, 133 patients with acute cholecystitis were divided into a percutaneous transhepatic gallbladder drainage group (n=60) and non-percutaneous-transhepatic-gallbladder-drainage group (n=73). Background factors, safety, and postoperative course were retrospectively evaluated and compared between these two groups. RESULTS: Compared with the non-percutaneous-transhepatic-gallbladder-drainage group, the percutaneous transhepatic gallbladder drainage group was significantly older (p=0.0009), had a higher frequency of comorbid disease (p=0.0252), and a worse American Society of Anesthesiology classification (p=0.0021). In individual statistical tests, body temperature (p=0.0288), white blood cell count (p=0.0175), and C-reactive protein value (p=0.0022) were significantly elevated in the percutaneous transhepatic gallbladder drainage group; however, for frequency of comorbid disease, body temperature, and white blood cell count, significance was removed by correction for multiple testing of data. There was no significant difference in gender distribution, history of upper abdominal surgery, or body mass index between the two groups. The duration of surgery was marginally but significantly longer in the percutaneous transhepatic gallbladder drainage group (p=0.0414; in a single statistical test; however, that significance was removed by correction for the multiple testing of data). Between the two groups, there was no significant difference in blood loss at surgery, frequency of postoperative complications, rate of conversion to open laparotomy, interval until oral feeding was resumed, and length of postoperative hospital stay. CONCLUSIONS: These data suggest that satisfactory outcomes can be achieved with selective pre-operative gallbladder drainage in older and sicker patients with acute cholecystitis.

Acute Disease↗

PubMed2005

Precancerous mucosal changes in the gallbladder of patients with occult pancreatobiliary reflux.

BACKGROUND: Pancreatobiliary reflux can occur even if the pancreaticobiliary junction is normal (occult pancreatobiliary reflux), and it may be associated with gallbladder carcinoma. The aim of the present study was to examine precancerous mucosal changes in the gallbladder from patients with occult pancreatobiliary reflux. METHODS: The mucosa of the gallbladder from 13 patients who underwent cholecystectomy was examined histopathologically. These patients had an anatomically normal pancreatobiliary junction and a biliary amylase concentration greater than 10,000 IU/L. The gallbladder of patients without carcinoma was further examined by using immunohistochemical techniques to detect Ki-67, and the results were compared with those from control patients. RESULTS: Of the 13 patients, 5 (38%) had gallbladder carcinoma and 8 (62%) did not. Of the 8 patients without carcinoma, 4 (50%) had dysplasia accompanied by hyperplasia, and 2 (25%) had hyperplasia alone of the gallbladder mucosa. The Ki-67 labeling index was significantly higher in hyperplastic and dysplastic mucosa than in control gallbladder mucosa (p < 0.0004). CONCLUSIONS: Occult pancreatobiliary reflux could be associated with precancerous mucosal changes in the gallbladder, such as hyperplasia and dysplasia with increased cellular proliferation, and could be a possible risk factor for gallbladder carcinoma.

Aged↗

PubMed1998

Bolus intravenous infusion of amino acids or lipids does not stimulate gallbladder contraction in neonates on total parenteral nutrition.

BACKGROUND/PURPOSE: Stimulation of gallbladder contraction in patients receiving total parenteral nutrition (TPN) may be beneficial in preventing cholestatic jaundice associated with TPN. Bolus intravenous administration of either amino acids or fat promotes gallbladder contraction in normal adult volunteers after a period of starvation. This phenomenon has not been investigated in patients receiving continuous TPN. The aim of this study was to test the hypothesis that bolus intravenous infusion of amino acids or fat produces gallbladder contraction in neonates receiving TPN. METHODS: Twenty-eight studies of gallbladder contraction were performed in 18 neonates receiving continuous TPN (median weight, 2.3 kg; range, 1.3 to 7.3; gestational age, 37 weeks; range, 28 to 40; age, 6.5 days; range, 2 to 180). Different types of experiments were performed: (1) bolus intravenous infusion of amino acid or fat for 60 minutes at twice the normal infusion rate; (2) bolus intravenous infusion of amino acid or fat for 15 minutes at four times the normal infusion rate. Gallbladder volume was measured by real-time ultrasonography by a single investigator. Measurements were made before starting the bolus infusion and every 15 minutes for 1 hour. RESULTS: The volume of the gallbladder before bolus intravenous infusion was not significantly different between experiments (median, 985; range, 603 to 1,802 mm3). These volumes are consistent with an enlarged and atonic gallbladder as previously reported in infants receiving parenteral nutrition. In all experiments there was no significant decrease in gallbladder volume after bolus infusion of either amino acids or fat. CONCLUSIONS: Contrary to their effects in adults, bolus infusions of amino acids or fat did not induce gallbladder contraction in neonates on TPN. This may have been because of lack of starvation in the neonates and/or the effect of continuous glucose infusion.

Amino Acids↗

PubMed1999

The ultrasonographic 'triangular cord' coupled with gallbladder images in the diagnostic prediction of biliary atresia from infantile intrahepatic cholestasis.

PURPOSE: The aim of this study was to evaluate the importance of the ultrasonographic "triangular cord" (TC) coupled with gallbladder images in the diagnostic prediction of biliary atresia (BA) from infantile intrahepatic cholestasis. METHODS: Seventy-nine infants with cholestatic jaundice underwent ultrasound examinations, focusing on the TC and gallbladder images. The TC was defined as visualization of a triangular or bandlike periportal echogenicity (3 mm or greater in thickness), which represents a cone-shaped fibrotic mass cranial to the portal vein in infants with BA. An abnormal gallbladder (nonvisualized or small) was thought to be more suggestive of BA than infantile intrahepatic cholestasis. RESULTS: Among 25 infants with BA, 21 showed TC, whereas 4 had no TC. Fifty-three of 54 infants with infantile intrahepatic cholestasis had no TC, showing a diagnostic accuracy of 94% with 84% sensitivity and 98% specificity. As for positive predictive value in the diagnosis of BA by the TC coupled with gallbladder images, it was 100% when a positive TC was coupled with an abnormal gallbladder and 88% when a positive TC was coupled with a normal gallbladder. It decreased to 25% when a negative TC was coupled with an abnormal gallbladder. CONCLUSIONS: The TC appears to be a very specific and definite ultrasonographic finding in the early diagnosis of BA. Positive TC regardless of gallbladder images is highly suggestive of BA, showing a 95% positive predictive value, but BA cannot be ruled out when negative TC is coupled with an abnormal gallbladder, requiring further diagnostic modalities such as liver needle biopsy or hepatobiliary scintigraphy.

Bile Ducts, Extrahepatic↗

PubMed1999

Lipid solubilization in human gallbladder versus hepatic biles.

BACKGROUND/AIMS: Cholesterol crystallizes more rapidly in gallbladder than in hepatic biles, supposedly due to formation of cholesterol-supersaturated vesicles in concentrated gallbladder biles because of preferential micellization of phospholipids compared to cholesterol. We therefore aimed to compare lipid solubilization in hepatic and gallbladder biles. METHODS: Mixed micellar and vesicular phases were separated from hepatic and associated gallbladder biles of seven cholesterol gallstone patients by using state-of-the-art gel filtration with bile salts at intermixed micellar/intervesicular compositions and concentrations in the eluant. RESULTS: Vesicles were found in 6 out of 7 hepatic biles, but only in 2 of the corresponding gallbladder biles. Both percentage (7.8+/-5.1 vs. 36.3+/-7.6%; p = 0.01) and amount (0.9+/-0.2 vs. 1.7+/-0.3 mM; p = 0.06) of vesicular cholesterol were lower in gallbladder biles. Similar results were found for vesicular phospholipids (1.3+/-0.8 vs. 11.6+/-6.0%; p = 0.05; and 0.3+/-0.1 vs. 1.1+/-0.5 mM; p = 0.07). The vesicular cholesterol/ phospholipid ratio was 1.7+/-0.5 in hepatic bile but 4.3 and 1.8 in the 2 gallbladder biles which contained vesicles. Mixed micelles in gallbladder biles had a higher cholesterol saturation index than mixed micelles in hepatic biles (1.43+/-0.11 vs. 1.15+/-0.07; p = 0.02). CONCLUSIONS: Concentration of bile in the gallbladder leads to decreased vesicular lipid contents. The finding of supersaturated mixed micelles in the absence of vesicles in a significant number of patients points to the possibility of non-vesicular modes of crystallization.

Bile Ducts↗

PubMed1998

Transforming growth factor alpha immunoreactivity in human gallbladder and extrahepatic biliary tract tumours.

AIMS: Transforming growth factor alpha (TGF-alpha), a protein structurally similar to epidermal growth factor (EGF), is implicated in the development of many human tumours. This study examines the expression of TGF-alpha in gallbladder and extrahepatic biliary tract tumours in which EGFR expression has been previously shown to be important. METHODS: A monoclonal antibody to the TGF-alpha protein was used to investigate the immunohistochemical expression of TGF-alpha in carcinoma of the gallbladder (n = 13), common bile duct (CBD) (n = 6) and ampulla of Vater (n = 8). Tissues from cases of chronic cholecystitis (n = 11), gallbladder dysplasia (n = 3) and adenoma (n = 1), and ampullary carcinoma in situ (CIS) (n = 3) were used as non-malignant controls. These cases were previously studied for EGFR expression. RESULTS: TGF-alpha overexpression, defined as intense immunoreactivity in more than two-thirds of cells immunostained for TGF-alpha, was present in most gallbladder carcinomas (n = 10; 77%) but with no significant differences in expression between different tumour grades. None of the cases of gallbladder dysplasia or chronic cholecystitis had strong TGF-alpha expression and this was significantly different from the carcinomas (P = 0.013 and P = 0.0001, respectively; chi 2 test), although a few cases of chronic cholecystitis showed weak (n = 4), moderate (n = 6) or no (n = 1) immunoreactivity. A few ampullary carcinomas (n = 2; 25%) and CIS (n = 1; 33%), and half of the CBD carcinomas (50%) had strong TGF-alpha immunoreactivity. There was correlation between TGF-alpha and EGFR immunoreactivity in the tumour cases (r = 0.70, r2 = 0.49, P = 0.0001; simple regression analysis), although the rate of EGFR immunoreactivity in CBD and ampullary carcinomas was somewhat higher than that of TGF-alpha. However, no statistically significant correlation between TGF-alpha expression with patient survival or tumour recurrence (r = 0.11, r2 = 0.012, P = 0.65; simple regression analysis) was found. CONCLUSIONS: Increased TGF-alpha expression occurs more frequently in gallbladder carcinoma than in gallbladder dysplasia, chronic cholecystitis, CBD or ampullary tumour, with no specific relationship to tumour grade, suggesting that TGF-alpha overexpression occurs early in the development of gallbladder cancers, and that biliary tract cancers have a different molecular origin. Correlation was found between TGF-alpha and EFGR expression in gallbladder and biliary tract tumours.

Adenocarcinoma↗

PubMedDate not supplied

Number and size of stones in patients with asymptomatic and symptomatic gallstones and gallbladder carcinoma: a prospective study of 592 cases.

The development of gallbladder carcinoma has been correlated with the presence of a single large gallstone in two retrospective studies. The objective of the present study was to determine the number and size of gallstones in patients with gallbladder carcinoma compared to asymptomatic and symptomatic female patients with gallstones. The following three groups of patients were included in this prospective trial: (A) 78 asymptomatic patients with gallstones; (B) 365 symptomatic patients with gallstones; and (C) 149 patients with gallbladder carcinoma. At the end of the operation, the resected gallbladder was opened and the number of stones counted. The maximum size of the stones was determined using calipers. Patients with gallbladder carcinoma were significantly older than patients in the other two groups (P <0.001). In the group with asymptomatic gallstones, there were significantly more patients with one single stone, whereas in the group with gallbladder carcinoma there were significantly more patients with multiple stones (more than 11; P <0.01). Patients with gallbladder carcinoma had significantly larger stones, regardless of the number of stones present (P <0.001). We postulate that the increase in the number and size of the stones among patients with gallbladder carcinoma could simply be an effect of aging or it could be a reflection of the long-term presence of stones in the gallbladder rather than some particular chemical or physical influence.

Adult↗

PubMed2001

Effect of somatostatin on postprandial gallbladder relaxation.

Although the inhibitory effect of somatostatin (SST) on gallbladder contraction is well known, the influence of SST on gallbladder motility during the late postprandial or relaxation phase has not been studied. We therefore investigated the effect of SST on gallbladder relaxation and gut hormone release during the late postprandial phase. Eight healthy volunteers participated in two experiments performed in random order during continuous infusion of either SST or saline (placebo) starting 2 h after meal ingestion. At regular intervals, gallbladder volumes were measured (ultrasonography) and blood samples were taken for determination of plasma cholecystokinin (CCK), pancreatic polypeptide (PP), peptide YY (PYY) and neurotensin levels (radioimmunoassay). Postprandial gallbladder contraction was similar in both experiments: 68 +/- 4% vs. 66 +/- 4%. During SST infusion, postprandial gallbladder contraction was significantly (P<0.01) reduced (2874 +/- 813% *240 min) compared with saline (9391 +/- 1595% *240 min). Plasma CCK, PP, PYY and neurotensin levels were in the same range in the early postprandial phase but were significantly reduced during SST infusion compared with placebo (late postprandial phase). Plasma levels of CCK correlated with gallbladder volumes during both the contraction and relaxation phase (r=0.68, P=0.01 and r=0.61, P=0.008, respectively). SST enhances gallbladder relaxation and reduces hormone secretion in the late postprandial phase. The results point to an association between CCK and gallbladder volume not only during the postprandial contraction phase but also during the relaxation phase.

Adult↗

PubMed2002

Effects of motilin on human interdigestive gastrointestinal and gallbladder motility, and involvement of 5HT3 receptors.

A plasma motilin peak and a partial gallbladder emptying precede the antral phase III of the migrating motor complex (MMC). To clarify the causal relationship between these factors, we aimed to study the role of motilin in interdigestive gastrointestinal and gallbladder motility simultaneously. In addition, involvement of 5HT3 receptors in the action of motilin was studied. Eight fasting, healthy male volunteers received 13Leu-motilin or 0.9% NaCl i.v. for 30 min, in randomized order on two separate occasions, from 30 min after phase III. Seven of the eight subjects also received the 5HT3 receptor antagonist ondansetron in addition to motilin, on a third occasion. Antroduodenal motility, gallbladder volumes and plasma motilin were measured. The interval between the start of infusion and phase III was 95.0 (57.6-155.7) min for saline, 28.7 (21.0-33.2) min for motilin, and 39.3 (30.7-100.5) min for motilin + ondansetron (P < 0.05). Gallbladder volume decreased by one-third from 10 min after both motilin and motilin + ondansetron infusion (P < 0.05), and returned to baseline with duodenal passage of phase III. In two of the seven subjects phase III was absent after motilin + ondansetron, although gallbladder volume decreased and only refilled during a later spontaneous phase III. We conclude that motilin induces both partial gallbladder emptying and antral phase III. Indeed, although gallbladder emptying clearly precedes antral phase III, ondansetron only prevented phase III in some cases and had no effect on gallbladder emptying. Passage of phase III in the duodenum makes an important contribution to gallbladder refilling.

Adult↗

PubMed2002

Expression of scavenger receptor class B type I in gallbladder columnar epithelium.

BACKGROUND: The lipid content of bile may be modified by the gallbladder epithelium. Recent studies indicate that cholesterol can be absorbed from bile and that this can be enhanced by apolipoprotein (apo) A-I. SR-BI is a multifunctional receptor capable of binding a wide array of native or modified lipoproteins, phospholipid or bile acid micelles. As apo A-I is a ligand for scavenger receptor class B type I (SR-BI) we have characterized the expression of this receptor in murine gallbladder. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR), immunoblotting and immunohistochemistry were used to study SR-BI expression in murine gallbladders. SR-BI expression was also used to examine gallbladders from high-fat-fed wild-type and apo B-100 transgenic mice. RESULTS: SR-BI and SR-BII mRNA are expressed in gallbladder. SR-BI immunoreactivity was localized to the columnar epithelium of the gallbladder. Immunoreactive SR-BI in gallbladder had an estimated molecular weight of 57 kDa, in contrast to the expected 82 kDa. Deglycosylation experiments indicated that the size difference between the two forms of the receptor is due to post-translational modification. Fat feeding of apo B transgenic mice resulted in gallstone formation but had no effect on the abundance of SR-BI. CONCLUSIONS: Gallbladder epithelial cells express SR-BI. This opens the possibility that SR-BI may influence the modification of bile in the gallbladder.

Animals↗

PubMed2001

Laparoscopic cholecystectomy and unsuspected gallbladder cancer.

Gallbladder cancer is a relatively uncommon malignancy. Its presentation is similar to that of gallstone disease and sometimes with non-specific symptoms. Laparoscopic cholecystectomy has become the method of choice for removing the gallbladder in most benign conditions. Occasionally, unsuspected gallbladder carcinoma is encountered in association with laparoscopic cholecystectomy. Overall gallbladder cancers have a poor prognosis, despite surgery or adjuvant therapies. However, in selected cases, a favourable outcome can be expected and the less favourable predicted outcome can be improved. Management of patients with gallbladder cancer in different situations is discussed: gallbladder cancer noted post-operatively on final pathology, gallbladder cancer noted after removal of the gallbladder and opening of the specimen at the time of surgery, difficulty encountered at the time of dissection and resultant suspicion of gallbladder cancer, and diagnosis of extensive disease at initial placement of the laparoscope.

Cholecystectomy, Laparoscopic↗

PubMed2002

Opioid agonists inhibit excitatory neurotransmission in ganglia and at the neuromuscular junction in Guinea pig gallbladder.

BACKGROUND & AIMS: Opiates administered therapeutically could have an inhibitory effect on the neuromuscular axis of the gallbladder, and thus contribute to biliary stasis and acalculous cholecystitis. METHODS: Intracellular recordings were made from gallbladder neurons and smooth muscle, and tension measurements were made from muscle strips. Opioid receptor-specific agonists tested: delta, DPDPE; kappa, U-50488H; and mu, DAMGO. RESULTS: Opioid agonists had no effect on gallbladder neurons or smooth muscle. Each of the opioid agonists potently suppressed the fast excitatory synaptic input to gallbladder neurons, in a concentration-dependent manner with half-maximal effective concentration values of about 1 pmol/L. Also, each agonist caused a concentration-dependent reduction in the amplitude of the neurogenic contractile response (half-maximal effective concentration values: DPDPE, 189 pmol/L; U-50488H, 472 pmol/L; and DAMGO, 112 pmol/L). These ganglionic and neuromuscular effects were attenuated by the highly selective opioid-receptor antagonist, naloxone. Opioid-receptor activation also inhibited the presynaptic facilitory effect of cholecystokinin in gallbladder ganglia. Immunohistochemistry with opioid receptor-specific antisera revealed immunostaining for all 3 receptor subtypes in nerve bundles and neuronal cell bodies within the gallbladder, whereas opiate-immunoreactive nerve fibers are sparse in the gallbladder. CONCLUSIONS: These results show that opiates can cause presynaptic inhibition of excitatory neurotransmission at 2 sites within the wall of the gallbladder: vagal preganglionic terminals in ganglia and neuromuscular nerve terminals. These findings support the concept that opiates can contribute to gallbladder stasis by inhibiting ganglionic activity and neurogenic contractions.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1990

Percutaneous transhepatic gallstone dissolution with methyl tert-butyl ether in complicated stone diagnosis and gallbladder anomalies.

In a total of 117 successfully punctured patients with gallbladder stones that were to be treated with methyl tert-butyl ether, 11 showed shell-like structured concrements on the CT scan. In 2 patients, pigment stones and very old concrements were suspected. In these 13 patients solitary stones dissolved in 2.9 hours, multiple stones in 10.8 hours, which corresponds to the treatment time of the total group. In 4 patients we diagnosed cholesterol stones, but dissolution was very slow, suggesting that the stones were covered with pigment. In 21 patients we found marked gallbladder anomalies, such as extreme septation, two-chamber gallbladders, gallbladder diverticula with a wedged stone, or gallbladders in which the fundus was positioned cranially. In these patients puncture time was prolonged by 25%. However, since in all patients the stones dissolved in the same time as in the total group (solitary stones; 3.1 hours: multiple stones: 10.4 hours) and since in 33% there was also sludge in the gallbladder, shape variants of the gallbladder obviously have no influence on the stone type. Whether they induce recurrent stones more often than normal gallbladders cannot be assessed at present. Shape variants of the gallbladder and layered stones on CT scan, however, do not represent a contraindication to MTBE therapy.

Cholecystography↗

PubMed1995

Clear cell carcinomas of the gallbladder and extrahepatic bile ducts.

Although clear cell carcinomas have been described in numerous anatomic sites, their occurrence in the gallbladder and extrahepatic bile ducts (EHBD) is practically unknown. We report 10 such cases. Seven arose in the gallbladder and three in the EHBD; all patients with gallbladder tumors were females with cholelithiasis whose ages ranged from 56 to 68 years. Patients with EHBD tumors were younger (38 and 40 years of age) and had extrahepatic biliary obstruction and abdominal pain. Two patients with gallbladder carcinomas had elevated serum carcinoembryonic antigen (CEA) levels, and another without hepatic involvement had markedly elevated circulating levels of alpha-fetoprotein (AFP). Histologically, nine tumors were adenocarcinomas and one was a squamous cell carcinoma. Seven adenocarcinomas consisted of cords, sheets, nests, papillae, and trabeculae of clear cells with well-defined cytoplasmic borders. Two were composed predominantly of glands and papillary structures. The cells contained PAS-positive diastase-labile granules and were cytokeratin- and EMA-positive and immunoreactive for erythropoiesis-associated antigen. One gallbladder tumor contained areas of hepatoid differentiation, a feature described in gallbladder neoplasms only once before. These areas were AFP-positive and immunoreactive for CEA. By electron microscopy, they showed hepatoid differentiation with formation of bile canaliculi. In two gallbladder tumors, neoplastic cells contained subnuclear vacuoles reminiscent of early secretory endometrium. Foci of conventional adenocarcinoma or mucinous carcinoma were recognized in all nine tumors. The squamous cell carcinoma showed only foci of squamous differentiation with keratinization. The clear cells of this neoplasm had a trabecular and solid growth pattern. These clear cell neoplasms of the gallbladder and EHBD must be differentiated from metastatic renal cell carcinoma, based upon the presence of areas of conventional adenocarcinoma or foci of squamous differentiation since results of special stains and immunohistochemistry are similar in both neoplasms. One of the patients with EHBD carcinoma is alive and symptom-free 6 years following right hepatic lobectomy. Five patients with gallbladder tumors had direct extension into the liver and died with metastases. Two are living with metastases.

Adenocarcinoma, Clear Cell↗