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Formation and inhibition of lysolecithin in human gallbladder bile.

Homogenized human gallbladder epithelium was incubated at 37 degrees C with 14C-lecithin in diluted gallbladder bile. During the incubation, lecithin was transformed to lysolecithin. The reaction rate was higher at pH 4.5 than at pH 7.0. No degradation of lecithin occurred if the reaction mixture did not contain the homogenate. Lysolecithin was mixed with red blood cells in (a) diluted human gallbladder bile and (b) 0.15 M saline. The surface activity in the different systems was then assessed from the amount of hemoglobin recovered in the red cell pellet after centrifugation. In human bile, 500 mug lysolecithin/ml did not affect the amount of hemoglobin recovered whereas in saline, concentrations exceeding 25-30 mug/ml affected the red blood cells such that no hemoglobin was pelleted by the centrifugation. Lysolecithin was further studied for effect upon lecithin-3H-cholesterol-dicetylphosphate liposomes containing 14C-glucose. The surface activity of lysolecithin was assessed from the distribution of 3H- and 14C-activity after centrifugation. Although 500 mug lysolecithin/ml increased the non-sedimented 14C-activity, 5000 mug lysolecithin/ml was necessary to decrease significantly the amount of sedimented 3H-activity. The results are interpreted such that phospholipase A activity from the gallbladder epithelium, if released into the gallbladder bile, may generate lysolecithin from lecithin. However, the surface activity and, thus, the inflammatory mediating activity of lysolecithin is inhibited by components in the gallbladder bile, possibly lecithin.

Bile↗

Left-sided gallbladder on the basis of a right-sided round ligament.

Left-sided gallbladder, a rare congenital anomaly, is defined as a gallbladder located to the left of the round ligament. A 42 year-old female underwent a cholecystectomy for gallstone disease. At laparotomy, we found that the round ligament was located to the right of its normal position and was continuous with the right anterior branch of the portal vein. Though normally situated, the gallbladder was therefore, on the left side of the anomalously right-sided round ligament, fulfilling the definition of a left-sided gallbladder. This case indicates that a third type of left-sided gallbladder may occur in addition to the other forms: one resulting from a right-sided round ligament, in addition to the "true" left-sided gallbladder and the variety seen in situs inversus.

Adult↗

Heterotopic gastric mucosa in a gallbladder with an anomalous union of the pancreatobiliary duct: a case report.

A 25 year-old woman experienced a sudden onset of epigastralgia with nausea, and consulted our hospital. Because the abdominal pain did not subside with medication, she was hospitalized. On physical examination she had a slight tenderness of the right upper abdominal quadrant. Laboratory studies disclosed increases in the serum alkaline phosphatase, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and serum amylase levels. Abdominal ultrasonography, computed tomography, and endoscopic retrograde cholangiopancreatography revealed choledocholithiasis and a pancreatic duct which originated from the common bile duct. A common bile duct stone was removed with a basket catheter after an endoscopic sphincterotomy was performed. Since an anomalous union of a pancreatobiliary duct is a high risk factor of gallbladder cancer, laparoscopic cholecystectomy was perfomed. The post-operative course was uneventful and she was discharged on the twentieth post-operative day. In a microscopical examination of the resected specimen, a pyloric type gastric mucosa was clearly evident in the submucosa, while the remaining gallbladder demonstrated chronic cholecystitis. Some cases of heterotopic gastric mucosa in the gallbladder come from metaplasia, and metaplasia is also one of the most important factors in the carcinogenesis of gallbladder cancer. In conclusion, the present case is the first report of gastric mucosa with an anomalous union of the pancreatobiliary duct. Heterotopic gastric mucosa in the gallbladder may be one of the causes of gallbladder cancer, and close attention should, therefore, be paid to any occurrence of heterotopic gastric mucosa in this region.

Adult↗

Staining in the liver surrounding gallbladder fossa on hepatic arteriography caused by increased cystic venous drainage.

In 8 patients with gallbladder disease in whom no extension of the disease to the liver was confirmed by surgery, wedge-shaped (segmental) staining of the liver just adjacent to the gallbladder fossa (gallbladder bed) on hepatic arteriography was seen. This was always accompanied by definite visualization of the cystic veins with the drainage directed to the gallbladder bed and became most dense following the peak of the opacification of the cystic veins. We therefore concluded that the increased cystic venous drainage to the intrahepatic portal vein causes the staining in the nondiseased gallbladder bed on hepatic arteriography.

Angiography↗

Cisapride improves gallbladder contractility and bile lipid composition in an animal model of gallstone disease.

BACKGROUND: The hepatic secretion of supersaturated bile and gallbladder stasis are key events in cholesterol gallstone formation. The therapeutic value of cisapride, a prokinetic agent, was assessed in ground squirrels on a 1% cholesterol diet. METHODS: Biliary lipid secretion was measured directly and bile salt pool size assessed by isotope dilution ([14C]cholic acid). Gallbladder contraction was measured in vitro in response to cholecystokinin (CCK). RESULTS: Cholesterol-fed animals had a combined hepatic secretory defect (a 53% decrease in bile salt secretion and also a 31% increase in cholesterol secretion). Adding cisapride restored bile salt secretion to control levels but did not affect cholesterol secretion. In cholesterol-fed animals, the cholesterol saturation index of gallbladder bile more than doubled and cholesterol crystals developed; cisapride markedly reduced cholesterol saturation, thus preventing crystal formation. Gallbladder contractility, measured in vitro in response to CCK, decreased 23% in animals on the 1% cholesterol diet; cisapride restored the CCK dose-response curve to normal. The bile salt pool as assessed by isotope dilution was similar in all groups. CONCLUSIONS: Thus, lithogenic bile develops in this model because of reduced bile salt secretion and increased cholesterol secretion. Cisapride renders biliary lipid composition towards normal by enhancing gallbladder (and possibly intestinal) motility and cycling of the bile salt pool, thereby increasing bile salt secretion.

Animals↗

Cholecystosonographic evaluation of the prevalence of gallbladder diseases. A university hospital experience.

Ninety-five healthy volunteers and 515 patients with problems other than those of the biliary tract were examined using real-time, gray-scale, B-mode ultrasonography. Eighty-two patients (13.44%) were found to have asymptomatic gallbladder disease: 68 (11.14%) had cholelithiasis, 5 (0.81%) had acalculus cholecystitis, and 2 (0.32%) had polyps. Three cases of carcinoma of the gallbladder were also detected, suggesting that ultrasound examination of the high-risk population in an endemic area should not be confined to the disease concerned but that the gallbladder of such patients should also be screened to pick up asymptomatic gallbladder disease. Hence ultrasound can be used as a screening modality for the early detection of carcinoma of the gallbladder.

Adult↗

From the archives of the AFIP. Benign tumors and tumorlike lesions of the gallbladder and extrahepatic bile ducts: radiologic-pathologic correlation. Armed Forces Institute of Pathology.

A diverse spectrum of benign tumors and tumorlike lesions arises from the gallbladder and bile ducts, and despite their diversity, these lesions share common embryologic origins and histologic characteristics. Although these lesions are relatively uncommon, their importance lies in their ability to mimic malignant lesions in these locations. Benign neoplasms are derived from the epithelial and nonepithelial structures that compose the normal gallbladder and bile ducts. The epithelium gives rise to adenomas, cystadenomas, and the unusual condition of biliary papillomatosis. Granular cell tumors, neurofibromas, ganglioneuromas, paragangliomas, and leiomyomas are examples of benign tumors that may originate from nonepithelial structures. Tumorlike lesions are more commonly found in the gallbladder and include xanthogranulomatous cholecystitis, adenomyomatous hyperplasia, cholesterol polyps, and heterotopias. In the clinical setting of a patient with nonspecific abdominal complaints or symptoms of biliary obstruction, the discovery of a gallbladder or bile duct polyp or mass, gallbladder wall thickening, or biliary stricture is most often indicative of malignancy. However, the differential diagnosis should include benign tumors and tumorlike lesions. The preoperative determination of a benign lesion may significantly alter therapy and patient prognosis.

Bile Duct Diseases↗

[Immunohistochemical demonstration of pepsinogens I and II in the gallbladder].

The immunohistochemical expression of pepsinogen I (PI) and pepsinogen II (PII) was studied in 103 gallbladder carcinomas, 25 non tumoral gallbladder lesions and 23 gallbladder cancer metastases. PI was positive in 6% of carcinomas and only in 2% of non tumoral contiguous mucosa. PII was positive in 46% of carcinomas and 43% of controls. Metastases were negative for both enzymes. Pyloric gland metaplasia of non tumoral mucosa adjacent to the tumor expressed PII in 68.9% and PI in 3.4% of cases. The same lesion in non tumoral gallbladders was positive for PII in 66.6% of cases, and no case expressed PI. There was no relationship between PI expression and the histological degree of differentiation. Only tumors with serosal or subserosal involvement were positive for PI. PII had a higher expression in early or well differentiated tumors. Tumors with pyloric gland metaplasia in the contiguous non tumoral mucosa expressed PII more frequently. Our results, based on the expression of PI and PII, suggest a relationship between the presence of pyloric gland metaplasia and some types of gallbladder cancer.

Biomarkers, Tumor↗

Gallstone formation and gallbladder bile composition after colectomy in dogs.

A high prevalence of gallstones has been described in patients following colectomy. The aim of this study was to examine whether lithogenicity is attributed to colectomy. In the present study, changes in gallbladder bile composition and the mechanism of gallstone formation after colectomy were examined in dogs. Ten mongrel dogs underwent restorative proctocolectomy. Seven dogs which received sham operations served as controls. Over a 12-week postoperative period, samples of gallbladder bile, formed gallstones and serum were collected and analyzed. In 7 of the 10 (70%) colectomized dogs, gallstones were found in the gallbladder, while the control dogs had no stones. Macroscopically the gallstones were similar to black pigment stones observed in humans. Chemical analysis and Fourier transform-infrared spectroscopy examination revealed that the stones were composed mainly of sodium bilirubinate and proteins, with minor amounts of calcium salts and cholesterol. Significant increases in biliary pH and concentrations of ionized calcium and unconjugated bilirubin were observed in the gallbladder bile of the colectomy group compared with that of the control group. The total bile acid and total bilirubin concentrations were significantly decreased in the colectomy group. Cholesterol crystal nucleation did not occur. The inhibitory effect of gallbladder bile on calcium carbonate precipitation in an in vitro assay system was preserved even after colectomy. In conclusion, proctocolectomy increases the concentration of unconjugated bilirubin in gallbladder bile and induces pigment gallstones which are composed mainly of sodium bilirubinate and proteins since calcium ions and cholesterol are stabilized in dogs.

Animals↗

Sex differences in gallbladder prostaglandin synthesis mediated by acute inflammation.

The influences of sex and acute inflammation on prostaglandin biosynthesis in rabbit gallbladder were examined by radiochromatography. Male rabbit gallbladder microsomes converted small amounts of labelled arachidonate to total prostaglandin synthesis with PGE2, 6-keto PGF1 alpha (stable metabolite of PGI2) and PGF2 alpha as the major products synthesized. Microsomes from the male rabbit gallbladder inflamed by bile duct ligation for 3 days increased total prostaglandin synthesis five-fold with 6-keto PGF1 alpha being the major prostaglandin produced. Female rabbit gallbladder microsomes converted three times more arachidonate to total prostaglandin synthesis than did microsomes from the male rabbit. Bile duct ligation did not alter total prostaglandin biosynthesis in the female rabbit gallbladder, but significantly decreased synthesis of PGE2, thromboxane B2 and PGF2 alpha and increased synthesis of 6-keto PGF1 alpha. These data suggest that although bile duct ligation had different effects on male and female gallbladder total prostaglandin synthesis, 6-keto PGF1 alpha is the major product induced by this stimulus for acute inflammation.

Acute Disease↗

Gallbladder and gastric emptying: relationship to cholecystokininemia in diabetics.

Background: Impaired gastrointestinal and gallbladder motility, as a complication of long-lasting diabetes mellitus, has been ascribed to the possible development of autonomic neuropathy, although the intervention of hormonal factors may not completely be excluded. In this regard, cholecystokinin (CCK), a gut hormone known to regulate pancreatic exocrine secretion, gallbladder contraction, and bowel motility in response to a meal, is impaired in patients with diabetes mellitus. This prompted us to evaluate the relationship between the plasma levels of CCK and gallbladder and gastric emptying in neuropathy-free diabetic patients treated with insulin (group A) or with oral hypoglycemic agents (group B) under basal conditions and in response to a standard test meal. Methods: Plasma CCK was measured by radioimmunoassay. Gastric and gallbladder emptying were evaluated ultrasonographically. Results: Plasma CCK levels were significantly lower in both groups of diabetics than in healthy controls during a fast and in response to a standard meal. However, meal ingestion was able to evoke a pattern of CCK response in both groups of diabetic patients similar to that seen in controls. Fasting gallbladder volume was higher in patients with diabetes than in controls, whereas the percentage of emptying was lower in patients of both groups. Gastric final emptying time was significantly longer in both groups of diabetics than in controls. Conclusion: This study shows that patients with diabetes have lower plasma levels of CCK, which may explain their relatively hypotonic gallbladder and reduced gastric motility.

Journal Article↗

Possibility of Differential Diagnosis of Small Polypoid Lesions in the Gallbladder Using FDG-PET.

Purpose: We discuss three cases of patients with small polypoid lesions of gallbladder in which we successfully differentiated the malignancy or benignity preoperatively using positron emission tomography (PET) scanning with 18F-labelled deoxyglucose (FDG).Methods and Results: The first case involves a 47-year-old woman who had a 15 x 10 mm polypoid lesion of the gallbladder. FDG-PET was performed and revealed no FDG uptake. The histopathological diagnosis was a cholesterol polyp. The second case is a 56-year-old woman who had a 22 x 8 mm polypoid lesion in the neck of the gallbladder and wall-thickening of the fundus. FDG-PET was performed and no FDG uptake was found. The postoperative diagnosis was pseudo-tumorous sludge in the neck and adenomyomatosis of the fundus. The third case is a 77-year-old man who had a 15 x 15 mm polypoid lesion in the gallbladder. PET revealed a focus of FDG uptake at the site of the gallbladder. The histopathologic diagnosis was adenocarcinoma. Focal FDG uptake was the sole indicator of a malignant tumor of the gallbladder.Conclusions: FDG-PET may become one of the most useful tools for the accurate preoperative diagnosis of gallbladder carcinoma.

Journal Article↗

Increased biliary group II phospholipase A2 and altered gallbladder bile in patients with multiple cholesterol stones.

BACKGROUND & AIMS: Multiple cholesterol stones are associated with more biliary complications and show more rapid cholesterol nucleation than solitary stones. Group II phospholipase A2 (PLA2-II) may play a critical role in the process of mucosal inflammation, which in turn may produce pronucleating agents. PLA2-II concentrations in gallbladders and gallbladder bile from patients with different types of gallstone disease were assayed to correlate PLA2-II with alterations in biliary composition. METHODS: PLA2-II protein concentrations were assayed immunoradiometrically using monoclonal antibodies against human splenic PLA2-II. RESULTS: Immunoreactive PLA2-II levels in gallbladder bile were significantly higher in patients with multiple cholesterol stones (68.2 +/- 6.3 ng/dL, mean +/- SEM; n = 24) than in those with solitary stones (24.9 +/- 2.8; n = 20; P < 0.01), those with multiple pigment stones (24.2 +/- 3.7; n = 18; P < 0.01), or control subjects (13.4 +/- 1.7; n = 19; P < 0.01). Increased biliary immunoreactive PLA2-II levels in multiple cholesterol stones were associated with a concomitant increase in the lysophosphatidylcholine to phosphatidylcholine ratio; free arachidonate, protein, and hexosamine concentrations; and gallbladder bile viscosity. The gallbladders showed an increased PLA2-II protein mass and steady-state messenger RNA levels, which was associated with increased prostaglandin E2 levels. CONCLUSIONS: Increased biliary PLA2-II may be of pathogenetic importance in multiple cholesterol stones, probably through potentiating gallbladder mucosal inflammation with associated biliary alterations favoring cholesterol crystal formation.

Adult↗

Ultrasonic gallbladder function in chronic kidney disease: does predialysis, hemodialysis, or CAPD affect it?

BACKGROUND: There are contradictory reports about the prevalence of cholelithiasis in chronic kidney disease (CKD). The pathogenesis of gallstones is associated with the lithogenic changes of bile composition, increased tendency to nucleation, and decreased gallbladder motility. The studies related to these factors can predict the development of cholelithiasis. The aim of this study was to evaluate the ultrasonic gallbladder function in CKD and to compare it in predialysis (PreD), hemodialysis (HD), and continuous ambulatory peritoneal dialysis (CAPD) patients. METHODS: Age, gender, and body mass index matched 49 CKD patients (14 PreD, 19 HD, 16 CAPD), and 17 control individuals were included in the study. Diabetic and cirrhotic patients were not included. Ultrasonic gallbladder volume was evaluated in pre- and postprandial period, and ejection fraction was calculated. We also measured several biochemical parameters (cholesterol, triglyceride, blood urea nitrogen (BUN), creatinine, calcium, Phosphorus, parathormone, albumin, total protein) in blood. RESULTS: Preprandial gallbladder volume in PreD, HD, CAPD, and control groups were 26.7 +/-13.6, 20.8+/-10.4, 23.2+/-14.7, and 26.4+/-14.8 mL, respectively (p > 0.05). Ejection fractions were 54.1 +/- 22.9%, 54.9 +/- 23.9%, 48.6 +/- 15.9%, and 51.8 +/- 19.2% in PreD, HD, CAPD, and control groups, respectively (p > 0.05). Serum triglyceride was higher in PreD patients than control group (207 +/- 144 vs. 110 +/-48 mg/dL) (p<0.05). Serum BUN, Cre, P, and PTH levels were higher in CKD groups than the control group, whereas serum total protein and albumin levels were higher in the control group (p<0.05). Serum Ca was lower in PreD and HD patients than in the controls (p<0.05). CONCLUSIONS: In conclusion, CKD and renal replacement therapy (HD and CAPD) do not affect gallbladder functions, but more studies are needed to evaluate prevalence of gallstones, gallbladder motility, and the composition of bile in CKD.

Adult↗

Laparoscopic cholecystectomy for acute inflammation of the gallbladder.

OBJECTIVE: The aim of this study was to prospectively assess the results of laparoscopic cholecystectomy in patients with acute inflammation of the gallbladder. SUMMARY BACKGROUND DATA: Laparoscopic cholecystectomy has become the standard treatment for symptomatic gallbladder disease. Its role in the surgical treatment of acute cholecystitis has not been defined, although a number of recent reports suggest that there should be few contraindications to an initial laparoscopic approach. METHODS: All patients presenting with symptomatic cholelithiasis from October 1990 until June 1992 were evaluated at laparoscopy with intention of proceeding to a laparoscopic cholecystectomy. The gross appearance of the gallbladder was categorized as acute inflammation, chronic inflammation, or no inflammation. Ninety-eight (23.4%) of 418 patients had acute inflammation of the gallbladder: 55 were edematous, 10 were gangrenous, 15 had a mucocele, and 18 had an empyema. RESULTS: The authors assessed outcome in these patients. The frequency of conversion to an open operation was 33.7% for acute inflammation, 21.7% for chronic inflammation (p < 0.05), and 4% for no inflammation (p < 0.001). The conversion rate was highest for empyema (83.3%) and gangrenous cholecystitis (50%), while the conversion rate for edematous cholecystitis was 21.8% and for acute inflammation with a mucocele it was 7%. The median operation time for successful laparoscopic cholecystectomy for acute inflammation was 105 minutes, which was longer than that with no inflammation (90 minutes). However, the incidence of complications was not different from that for chronic or no inflammation. The median postoperative stay for patients with acute gallbladder inflammation was 2 days for successful laparoscopic cholecystectomy and 7 days for patients converted to an open operation. CONCLUSIONS: Laparoscopic cholecystectomy for acute inflammation of the gallbladder is safe and is associated with a significantly shorter postoperative stay compared to open surgery. A greater number of patients required conversion to open operation compared to those with no obvious inflammation. Conversion to open operation was most frequent for empyema and gangrenous cholecystitis, suggesting that once this diagnosis is made, excessive time should not be spent in laparoscopic trial dissection before converting to an open operation.

Acute Disease↗

Evaluation of the gallbladder by gray scale ultrasonography.

A review of the results of the evaluation of the gallbladder by gray scale ultrasonography in 52 patients is presented. When the gallbladder was successfully identified by ultrasound (46 patients) the detection of stones was 98% accurate. When the gallbladder was not identified (four patients), a contracted gallbladder containing numerous stones was found at operation. The left lateral decubitus position proved very helpful in displaying the gallbladder when it could not be identified in the standard supine position. Ultrasonic evaluation of the gallbladder is of most value in the patients who have had unsuccessful radiographic studies.

Cholelithiasis↗

Relation of gallbladder function and Helicobacter pylori infection to gastric mucosa inflammation in patients with symptomatic cholecystolithiasis.

BACKGROUND: Inflammatory alterations of the gastric mucosa are commonly caused by Helicobacter pylori (Hp) infection in patients with symptomatic gallstone disease. However, the additional pathogenetic role of an impaired gallbladder function leading to an increased alkaline duodenogastric reflux is controversially discussed. AIM: To investigate the relation of gallbladder function and Hp infection to gastric mucosa inflammation in patients with symptomatic gallstones prior to cholecystectomy. PATIENTS: Seventy-three patients with symptomatic gallstones were studied by endoscopy and Hp testing. METHODS: Gastritis classification was performed according to the updated Sydney System and gallbladder function was determined by total lipid concentration of gallbladder bile collected during mainly laparoscopic cholecystectomy. RESULTS: Fifteen patients revealed no, 39 patients mild, and 19 moderate to marked gastritis. No significant differences for bile salts, phospholipids, cholesterol, or total lipids in gallbladder bile were found between these three groups of patients. However, while only 1 out of 54 (<2%) patients with mild or no gastritis was found histologically positive for Hp, this infection could be detected in 14 (74%) out of 19 patients with moderate to marked gastritis. CONCLUSION: Moderate to marked gastric mucosa inflammation in gallstone patients is mainly caused by Hp infection, whereas gallbladder function is not related to the degree of gastritis. Thus, an increased alkaline duodenogastric reflux in gallstone patients seems to be of limited pathophysiological relevance.

Atrophy↗

Gallbladder carcinoma: a retrospective analysis of twenty-two years experience of a single teaching hospital.

BACKGROUND: The purpose of this study was to retrospectively evaluate our experience with gallbladder cancer since the establishment of a tumour registry in our institute. METHODS: Between 1975 and 1998, 23 consecutive patients with gallbladder cancer were identified using the tumour registry database. There were 18 females (78%) and 5 (22%) males. The mean age at diagnosis was 70.6 (range 42-85) years. The diagnosis was achieved either intra-operatively or following the histological analysis of the gallbladder (n = 17), following gallbladder or liver biopsy (n = 4) or at autopsy (n = 2). Presenting symptoms included upper abdominal pain, weight loss, nausea, vomiting, fever, painless jaundice, hepatomegaly, upper abdominal mass, upper abdominal tenderness, and gastrointestinal haemorrhage. RESULTS: Histological examination revealed 20 adenocarcinomas (87%), 2 squamous cell carcinomas (9%) and one spindle cell sarcoma (4%). At presentation, 14 (61%) gallbladder cancers were stage IV, 5 (22%) were stage III and 4 (17%) were stage II. Kaplan Meier analysis revealed a mean survival of 3.2, 7.8 and 8.2 months for stage IV, III, and II disease respectively. Out of 14 patients with stage IV disease, 8 patients received adjuvant chemotherapy and survived for 4.6 months whereas six patients who did not receive adjuvant chemotherapy survived for 1.3 months. This difference was statistically significant (p = 0.04). CONCLUSION: The majority of patients with gallbladder cancer presented with advanced stage disease (stage IV) which carries a dismal prognosis. Patients who received chemotherapy with stage IV disease, however, did better than those who did not, but this is probably a reflection of patient selection.

Journal Article↗