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[Carcinoma of the gallbladder unexpectedly diagnosed after cholecystectomy for lithiasis (author's transl)].

Patients with clinically apparent carcinoma of the gallbladder seldom survive 5 years. This is only seen in about 20% of the patients whose gallbladder carcinoma is unexpectedly first discovered by the pathologist after a routine cholecystectomy for lithiasis. The prognosis of this seldom seen early stage of carcinoma of the gallbladder, which is applicable to only 10-23% of all gallbladder carcinomas, is strongly dependent on the penetration of the tumor in the wall of the gallbladder. Of the patients with a carcinoma infiltrating only the mucosa of the gallbladder, 60% can be cured for 5 years by a simple cholecystectomy, whereas for more advanced cancers this procedure seem to be inadequate. In these stages a relaparotomy should be considered with an addition wedge resection of the liver and a regional lymphadenectomy.

Aged↗

Effect of trimebutine maleate on emptying of stomach and gallbladder and release of gut peptide following a solid meal in man.

We investigated the effect of orally administered trimebutine maleate on gastric and gallbladder emptying and on the release of gut peptide, pancreatic polypeptide (PP), and gastrin in humans for 120 min after ingestion of a solid meal. Gastric emptying was measured by a radionuclide technique. Gallbladder emptying was estimated by real-time ultrasonography. The oral administration of 200 mg of trimebutine maleate significantly shortened the lag time in starting gastric emptying (P < 0.05). Considering gallbladder emptying, trimebutine significantly inhibited the fasting emptying induced by neural reflex. Postprandially, there was a tendency toward an accelerated gallbladder emptying in the early phase. Neither the maximal percentage of gallbladder emptying nor the time of peak gallbladder emptying were affected. Trimebutine significantly blunted the post-prandial PP response in the cephalic and gastric phases, reflecting a vagal-cholinergic activity (P < 0.05). The PP response in the intestinal phase was also blunted. Gastrin release was significantly augmented only during the period of fasting after drug administration (P < 0.05). The major effect of trimebutine maleate appears to be a shortening of the lag time at the start of gastric emptying probably via its anticholinergic activity.

Administration, Oral↗

Fluid secretion by gallbladder mucosa in experimental cholecystitis is influenced by intramural nerves.

The normal fluid absorption across the gallbladder mucosa is, in experimental cholecystitis, changed to an active net fluid secretion. This fluid secretion, studied in anesthetized cats, is not abolished by extrinsic gallbladder denervation and is unaffected by atropine but is strongly reduced by intraarterial tetrodotoxin or intraluminal administration of lidocaine hydrochloride. Intravenous somatostatin or hexamethonium administration also reduce this secretion. Indomethacin, known to abolish this fluid secretion, did not further reduce it when administered after nerve blocking agents in the present study. These data demonstrate that the prostaglandin-induced gallbladder fluid secretion in experimental cholecystitis is influenced by intramural nerves. It is suggested that gallbladder inflammation is associated with prostaglandin-induced activation of intrinsic nerves which may stimulate the epithelial cells to fluid secretion. In the obstructed gallbladder, this secretion causes gallbladder distension by increasing the intraluminal pressure. This mechanism may have a key role in the pathophysiology of acute cholecystitis.

Animals↗

Hyperglycemia modulates gallbladder motility and small intestinal transit time in man.

The aim of the present study was to investigate the effect of acute hyperglycemia on (1) the intestinal phase of gallbladder contraction induced by the intraduodenal administration of emulsified fat, and (2) the small intestinal transit time measured by the lactulose breath hydrogen test. Six healthy volunteers were studied in random order during normoglycemia and hyperglycemia (blood glucose levels 15 mmol/liter). Gallbladder volumes were measured with ultrasonography. Administration of 1 and 2 g/hr of fat resulted in significant reductions in gallbladder volumes from 24 +/- 2 cm3 to 11 +/- 1 cm3 (P < 0.05) and 8 +/- 1 cm3 (P < 0.05), respectively during normoglycemia, and from 24 +/- 2 cm3 to 21 +/- 2 cm3 (P < 0.05) and 16 +/- 2 cm3, respectively (P < 0.05) during hyperglycemia. Compared to normoglycemia, the gallbladder contraction was significantly (P < 0.05) reduced during hyperglycemia. No significant differences in CCK secretion were observed between experiments. Small intestinal transit time during hyperglycemia (101 +/- 12 min) was significantly (P < 0.05) prolonged compared to normoglycemia (57 +/- 12 min). During hyperglycemia, basal PP levels and PP secretion in response to intraduodenal fat were significantly (P < 0.05) reduced compared to normoglycemia. It is concluded that (1) low doses of intraduodenal emulsified fat result in significant gallbladder contraction and CCK secretion, (2) acute hyperglycemia inhibits intraduodenal fat induced gallbladder contraction, (3) acute hyperglycemia does not affect the intraduodenal fat induced CCK secretion, (4) small intestinal transit is significantly prolonged during acute hyperglycemia, and (5) acute hyperglycemia inhibits basal and stimulated plasma PP secretion, suggesting impaired vagal-cholinergic tone during hyperglycemia.

Acute Disease↗

5-hydroxytryptamine 3-receptor antagonist modulates gallbladder emptying and motilin release induced by erythromycin.

In the present study we evaluated the effect of ondansetron (formerly indicated as GR38032F), a potent and selective type-3 5-hydroxytryptamine receptor antagonist, on erythromycin-induced gallbladder emptying and motilin release, as well as gallbladder emptying induced by a regular meal in healthy volunteers. Gallbladder emptying was evaluated by sonography. Ondansetron, at the dose of 0.05 mg/kg, significantly reduced (P < 0.001 by ANOVA) the gallbladder emptying induced by 2 mg/kg/hr erythromycin, but did not increase basal gallbladder volume or inhibit gallbladder emptying induced by a regular meal. Ondansetron also inhibited the motilin release induced by erythromycin (P < 0.001, by ANOVA). These results suggest that serotoninergic mechanisms modulate the effects of erythromycin on the gastrointestinal tract. The exact site of action of ondansetron remains to be identified.

Adult↗

Effect of oral ibuprofen on formation of prostaglandins E and F by human gallbladder muscle and mucosa.

In a randomized double-blind trial, the effect of ibuprofen on the pain produced by gallbladder disease and on gallbladder mucosa and muscle wall tissue PGE and PGF production was evaluated to determine if the pain of cholecystitis and prostaglandin formation were altered by administration of a prostaglandin synthetase inhibitor. To ascertain potential differences in extracellular and intracellular prostaglandin production rates, gallbladder mucosal cells and muscle tissues were maintained in tissue culture medium and then subsequently homogenized. PGE and PGF concentrations were measured in culture medium and homogenates utilizing radioimmunoassay. Gallbladder mucosa and muscle tissue produced nanogram per milligram protein amounts of PGE and PGF. As the histological estimation of the degree of inflammation increased, so also did the production of PGE. Increased inflammation was associated with unchanged PGF levels, resulting in an increased ratio of PGE/PGF with increasing inflammation. Oral ibuprofen administration was effective in decreasing PGE production by gallbladder mucosa and muscle and eliminating the significant correlation between PGE levels and the histologic degree of inflammation found in the placebo-treated patients. Ibuprofen significantly decreased the pain of cholecystitis when compared to placebo-treated patients. However, there was poor correlation between pain relief and changes in PGE production by gallbladder mucosa and muscle. PGE may play a mediator role in inflammation associated with cholecystitis. Prostaglandin synthetase inhibition decreases the pain associated with cholecystitis; however, the absence of correlation with decreased PGE formation suggests that other prostanoids may play an important role in producing the symptoms of cholecystitis.

Administration, Oral↗

Effect of dietary cholesterol and indomethacin on cholelithiasis and gallbladder motility in guinea pig.

This study examines the effects of dietary cholesterol and subcutaneous indomethacin on gallstone formation, gallbladder motility, and bile composition in guinea pigs. Guinea pigs on cholesterol diets developed gallstones which were not primarily composed of cholesterol and were not prevented by indomethacin. Animals receiving cholesterol diets showed significant gallbladder enlargement which was inhibited by indomethacin. Cholesterol did not alter gallbladder pressure-volume relationships or the response to CCK, while indomethacin diminished gallbladder tone. Although cholesterol feeding did not appear to alter smooth muscle contractility in the guinea pig gallbladder, it caused significant gallbladder enlargement by a mechanism which may be dependent on prostaglandins.

Animals↗

Pathogenesis of the "Courvoisier gallbladder".

To investigate the pathophysiological basis of Courvoisier's law, the gallbladder size and pliability were measured in chronic calculous cholecystitis with (7 patients) or without (25 patients) common duct obstruction, in periampullary malignancy (6 patients), and in the normal state (3 patients). The duration and level of jaundice, when present, were correlated to the gallbladder size and ductal pressure as measured at operation. It was found that in vitro the gallbladders were equally pliable in all groups. Therefore, the classical explanation, that stone obstruction of the common duct does not result in dilated gallbladders because of less pliable organs from preexisting fibrosis, does not seem to apply for this series of patients. A markedly higher ductal pressure and a longer history of and deeper jaundice were also found in patients with dilated gallbladders. The data of this study support the alternative explanation that chronically increased ductal pressure is the probable cause of dilated gallbladders seen in malignant obstruction of the common duct.

Ampulla of Vater↗

Oral administration of loxiglumide (CCK antagonist) inhibits postprandial gallbladder contraction without affecting gastric emptying.

The effect of a single oral dose of loxiglumide, a cholecystokinin antagonist, on postprandial gallbladder contraction and on gastric emptying was evaluated in humans. Following a 12-hr fasting period, two tablets of loxiglumide (400 mg each) or placebo was administered on different days, in random order and in a double-blind fashion to 10 healthy volunteers 15 min before the ingestion of a 1050-kcal standard meal. Gallbladder and antral volumes were measured by real-time ultrasonography in basal conditions and at fixed time intervals after the meal. Oral loxiglumide administration was followed by a total inhibition of the gallbladder contraction for 60 min after the end of the meal ingestion. Thereafter, up to the end of the study period, gallbladder volume was larger than that of the placebo study (at 300 min after the meal 2.7 +/- 1.6 ml after placebo and 8.2 +/- 3.5 ml after loxiglumide; P less than 0.008). No difference between placebo and loxiglumide was found in the antral volumes at any time interval (postprandial 63.5 +/- 16.5 ml after placebo and 59.4 +/- 24 ml after loxiglumide; at 300 min after the meal 20.8 +/- 13.3 ml after placebo and 18.9 +/- 9.5 ml after loxiglumide). In conclusion, a single oral dose of loxiglumide at the dose of 800 mg can inhibit postprandial gallbladder contraction without affecting gastric emptying. It would therefore appear that in man endogenous CCK, released after a solid-liquid, caloric, nutrient-balanced meal, plays a major role in the contraction of the gallbladder but does not affect gastric emptying.

Administration, Oral↗

Impact of recent advances in hepatobiliary imaging techniques on the preoperative diagnosis of carcinoma of the gallbladder.

Among 26 patients with gallbladder carcinoma, 11 resected cases were studied retrospectively with respect to the preoperative imaging techniques and the operative procedures employed. Ultrasonography, endoscopic ultrasonography, and computed tomography were valuable in detecting gallbladder carcinoma preoperatively while direct cholangiography and angiography were helpful in designing operative strategy. The ultrasonographic findings were: a polypoid (fungating) mass protruding into the gallbladder lumen in 45%, abnormal thickening of the gallbladder wall in 18%, and a mass in the gallbladder invading adjacent organs in 18% of cases. Approximately 80% was diagnosed preoperatively by ultrasonography. Correct diagnosis was made by computed tomography in 60% of the cases. Endoscopic ultrasonography offered valuable information on the depth of tumor invasion. Direct cholangiography and angiography were useful in assessing the extent of the tumor spread. Recent advances in hepatobiliary imaging techniques, especially ultrasonography and computed tomography, contributed greatly to the detection and evaluation of gallbladder carcinoma at an early and resectable stage.

Adult↗

Primary gallbladder carcinoma: imaging findings in 50 patients with pathologic correlation.

Different diagnostic imaging modalities [contrast cholangiography, ultrasonography, and computed tomography (CT)] in a large group of patients with proven gallbladder carcinoma are reviewed. Noninvasive cross-sectional imaging methods strongly correlated with the different gross pathologic types of gallbladder carcinoma. The most common observed type was a mass replacing the gallbladder (39%). Other types observed either by sonography and/or CT were a focal/diffuse gallbladder wall thickening and the presence of an intraluminal polypoid mass. Despite the improvement in several imaging modalities, most of the preoperatively diagnosed gallbladder carcinomas were in advanced stage (84%). A combined approach using noninvasive diagnostic methods and percutaneous aspirative biopsies may reduce the number of explorative laparotomies in the final diagnosis of gallbladder carcinoma.

Aged↗

Effects of bicarbonate on fluid and electrolyte transport by guinea pig and rabbit gallbladder: stimulation of absorption.

The effect of bicarbonate (HCO3) on fluid absorption by guinea pig gallbladder was investigated in vitro. Stimulation of fluid absorption was concentration dependent resulting in a fourfold increase in transport over the range 1 to 50 mM. Phosphate, Tris, glycodiazine and glutamine buffers failed to substitute for HCO3 in stimulating absorption. Unidirectional 22Na fluxes were measured across short-circuited sheets of guinea pig and rabbit gallbladders mounted in Ussing-type chambers. In both species the net Na flux was unaffected by serosal HCO3 alone but was stimulated by addition of HCO3 to the mucosal bathing solution. Transepithelial electrical potential difference in rabbit gallbladder was about 1.4 mV (lumen positive) when HCO3 was present in the mucosal or in both compartments. This fell to 0.2 mV under HCO3-free conditions or when HCO3 was present only in the serosal solution. The respective values for guinea pig gallbladder were -1.6 and -0.6 mV (lumen negative). HCO3 stimulation of Na absorption by guinea pig gallbladder was abolished by increasing the bathing pH from 7.4 to 7.8, an effect resulting mainly from a reduction in JNams. Tris buffer (25 mM) inhibited HCO3-dependent fluid absorption in this species completely at pH 8.5 and partially at 7.5. These results indicate that HCO3 stimulates gallbladder transport in both species by an action from the mucosal side. This effect cannot be attributed to simple buffering of H+ but may be explained by the participation of HCO3 in the maintenance of intracellular H+ for a Na/H-exchange.

Animals↗

Preduodenal mechanisms compensate completely for absent pancreatic enzymes to stimulate gallbladder after meals.

We studied gallbladder emptying with gamma scintigraphy in nine dogs prepared with chronic pancreatic fistulas, so that pancreatic enzymes could be either completely excluded from the duodenum or supplied in normal amounts. During duodenal perfusion of the fasted dogs with fat emulsions, gallbladder emptying was significantly less rapid when the emulsion contained inactive vs active enzymes, confirming the potency of lipolytic products in the intestine as stimuli of gallbladder emptying. However, after feeding either a 115-g or a 460-g meal, each 18% fat, the gallbladders emptied identically whether or not pancreatic enzymes were excluded from the duodenum. We concluded that while products of pancreatic lipolysis in the small intestine are potent stimuli of gallbladder contraction, preduodenal mechanisms can compensate completely for the absence of pancreatic hydrolysis in stimulating gallbladder emptying after a meal.

Animals↗

Gallbladder emptying, plasma levels of estradiol and progesterone, and cholecystokinin secretion in liver cirrhosis.

Defective gallbladder emptying has been proposed as a possible accessory pathogenetic factor to explain the increased prevalence of gallstones in liver cirrhosis. In this study we have evaluated the fasting volume and the meal-stimulated emptying of the gallbladder, the plasma levels of estradiol and progesterone, and the basal and postprandial secretion of cholecystokinin in Child A cirrhotic patients compared to normal subjects. Basal (42.2 +/- 27 vs 22.8 +/- 8.4 ml) (P < 0.002) and residual (8.4 +/- 8.7 vs 4.6 +/- 3.8 ml) (P < 0.05) gallbladder volumes were higher in cirrhotics but neither the integrated gallbladder response to meal nor the maximal percentage of emptying was significantly different. Circulating estradiol and progesterone was slightly increased in only 1/13 and 5/13 cirrhotics, respectively. In eight cirrhotics and seven normals taken from the overall populations, the secretion of cholecystokinin was also measured. The fasting plasma level of cholecystokinin was higher in the cirrhotics (6.71 +/- 5.08 vs 2.02 +/- 0.46 pmol/liter) (P < 0.01). The meal-stimulated integrated plasma cholecystokinin response also was greater in cirrhotics (438.5 +/- 615 pmol/liter/270 min) than in normals (153 +/- 170.4 pmol/liter/270 min), but this difference was not significant because of the small study population. In spite of a normal kinetics of postprandial emptying, cirrhotic patients show increased fasting gallbladder volume and increased plasma levels of basal and postprandial cholecystokinin. Circulating estradiol and progesterone do not seem to be responsible for the large gallbladder volume found in liver cirrhosis.

Adult↗

Heterotopic gastric mucosa of the gallbladder.

A case of heterotopic gastric mucosa in the fundus of the gallbladder is reported. A 23-year-old man, who had been healthy and asymptomatic, visited our hospital because of abnormal findings in a liver enzyme test given during a routine health screening. Ultrasonography demonstrated a highly echogenic polypoid mass in the fundus of the gallbladder. The gallbladder mass was confirmed by both computed tomography and intravenous cholangiogram. After a 10-month follow up, laparoscopic cholecystectomy was performed. Intraoperative touch smear cytology of this lesion revealed class II cells. The surgical specimen revealed a 15 x 10 x 5 mm polypoid lesion in the fundus, with no gallstones in the gallbladder. Histologically, the polypoid lesion consisted of both fundic type and pyloric type gastric glands located in the mucosa of the gallbladder. In the literature, 42 cases of heterotopic gastric mucosa of the gallbladder have been reported, only 3 of which, including this present case, were found incidentally, with no apparent symptoms.

Adult↗

Effects of cisapride on gallbladder emptying and pancreatic polypeptide and cholecystokinin release in humans.

We investigated the effects of cisapride on gallbladder motility and on the release of pancreatic polypeptide and cholecystokinin in the fasting and postprandial states. Cisapride (7.5 mg) and/or a test meal was administered intraduodenally to seven healthy volunteers with or without atropine pretreatment (0.5 mg, i.m.). In the fasting state, cisapride increased gallbladder volume to 154% of the basal level, and significantly elevated plasma pancreatic polypeptide levels. The effects of cisapride were inhibited by atropine. In the postprandial state, integrated pancreatic polypeptide and cholecystokinin responses were increased by cisapride to 180% and 192%, respectively, of control values. Atropine inhibited the integrated gallbladder and pancreatic polypeptide response to about 60% of the control value, but did not affect the cholecystokinin response. These observations suggest that: (1) fasting gallbladder tone is influenced by cholinergic inhibitory mechanisms, (2) acetylcholine (ACh) is the final mediator for about 40% of the postprandial gallbladder emptying and pancreatic polypeptide response, and (3) coordination between the ACh-independent cholecystokinin response and ACh-dependent pancreatic polypeptide response may be important in the regulation of postprandial gallbladder emptying.

Adult↗

Cholangiographic appearance of multiseptate gallbladder: case report and a review of the literature.

A case of multiseptate gallbladder is described, with a review of the literature. This is the 24th such case report. The patient complained of right upper quadrant pain, colicky in nature. Abdominal ultrasonography showed multiple fine echoes within the gallbladder. On endoscopic retrograde cholangiography, multiple radiolucent lines crossing the gallbladder in various directions were noted within the gallbladder. The gallbladder was crisscrossed by numerous delicate septations and had a honeycomb appearance. These findings suggested multiseptate gallbladder.

Adolescent↗

Early carcinoma of the gallbladder accompanied by hemobilia: report of a case.

The majority of cases of hemobilia are of traumatic or vascular origin; however, we report herein the rare case of a 51-year-old man with early carcinoma of the gallbladder accompanied by hemobilia. He had been diagnosed as having gallbladder polyps during an admission to a local hospital for treatment of cardiac failure. Preoperative evaluation in our hospital suggested that the polypoid lesion was an advanced carcinoma of the gallbladder. Laparotomy revealed that the gallbladder contained blood clots, and a cholecystectomy was performed. Histological examination confirmed the main lesion to be IIb-type early carcinoma of the gallbladder and proved that the blood clots had been misinterpreted as polyps or advanced carcinoma before the operation. The diagnostic approaches and characteristics of hemobilia in the gallbladder are discussed with a review of the literature.

Adenocarcinoma↗