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PubMed1990

Acoustic artifacts and reverberation shadows in gallbladder sonograms: their cause and clinical implications.

From among more than 7000 sonographic examinations of the gallbladder performed over a period of 2 years, different types of acoustic artifacts were observed in 42 patients. Artifacts originated in the gallbladder wall in 37 cases and within the lumen in 5 cases. Eighteen patients had symptoms related to the hepatobiliary area. Twenty-four patients were fully asymptomatic although cholelithiasis was demonstrated in 8. In 21 cases (50%) some type of gallbladder pathology was associated with the presence of acoustic artifacts. Thirteen patients were cholecystectomized and the associated gallbladder pathology consisted of cholelithiasis (N = 5), cholesterolosis (N = 2), adenomyomatosis (N = 2), emphysematous cholecystitis (N = 2), and acute cholecystitis (N = 2). In 3 of these patients a sonographic/pathologic correlation was established. Only 5 of the 18 symptomatic patients presented acoustic artifacts in an otherwise normal gallbladder. Recognition of those pathological conditions favorable to the appearance of artifacts and reverberation shadows is extremely useful for differentiating merely clinically irrelevant anomalies from those that require prompt management.

Acoustics↗

PubMed1996

Effect of a cholecystokinin receptor antagonist (loxiglumide) on gallbladder contractile function in guinea pigs.

We evaluated the effect of the specific cholecystokinin (CCK) receptor antagonist, loxiglumide, on gallbladder contractile function in guinea pigs. Five mg/kg body weight (BW) of loxiglumide was administered orally to guinea pigs once a day for 3 days. We then investigated gallbladder contractile function and plasma CCK concentrations in the guinea pigs. Maximal gallbladder pressure induced by cerulein was significantly depressed on the 1st and 3rd days following loxiglumide administration. On the 1st day, the plasma CCK concentration was significantly increased compared with that of the control group during fasting and 15 min after the administration of an intraduodenal test meal. These results suggest that the disturbed gallbladder contraction is due to the competitive inhibition of CCK by loxiglumide. Gallbladder contractile function in guinea pigs is depressed by loxiglumide; however, this effect is reversible after short-term loxiglumide administration.

Animals↗

PubMedDate not supplied

Impaired gallbladder function in spinal cord injury on quantitative Tc-99m DISIDA cholescintigraphy.

BACKGROUND: Patients with spinal cord injury (SCI) have increased prevalences of gallstones and acute acalculous cholecystitis. A possible explanation for the increased prevalence of gallstone disease in SCI patients is decreased gallbladder motility causing gallbladder stasis, a known risk factor for gallstone disease. We investigated gallbladder function in SCI. METHODS: Twenty-five normal control subjects and 50 SCI patients were included in this study. Gallbladder function was measured by technium 99m-labeled imino-diacetic acid analogue (Tc-99m DISIDA) cholescintigraphy and represented by the filling fraction (FF) and the ejection fraction (EF). The SCI patients were assigned to subgroups: old versus young, female versus male, high- versus low-level injury, and long versus short injury duration. RESULTS: Forty-two percent of SCI patients had abnormal FFs and 54% of SCI patients had abnormal EFs. Significantly decreased FF and EF values were found in SCI patients, especially in those who were female and had high-level injuries. CONCLUSION: With the use of quantitative Tc-99m DISIDA cholescintigraphy, we found that SCI can significantly impair gallbladder function.

Adult↗

PubMed2005

Long-term survival of patients with gallbladder cancer detected during or after laparoscopic cholecystectomy.

Little evidence is available regarding long-term survival of patients with gallbladder cancer that is discovered at the time of laparoscopic cholecystectomy (LC). Therefore the present study was performed to evaluate long-term outcomes of this disease. Of 1546 patients who underwent LC for benign gallbladder disease between January 1992 and January 2002, 8 patients (0.5%) had cancers that were found during or after LC. The median follow-up period was 55 months (range: 36-142 months). The gallbladder was resected without perforation in all cases. During surgery there was a suspicion of malignancy in 6 of 8 cases. Frozen section analysis showed that 2 had TNM stage Tis tumors, 2 had T1a tumors, and 2 had T2 tumors. Two patients with T2 tumors were immediately converted to extended cholecystectomy. The final pathology revealed another 2 tumors, and demonstrated that 3 patients had Tis tumors, 3 had T1a tumors, and 2 had T2N0M0 tumors. None of the patients underwent additional surgery. All patients survived with no evidence of recurrence during the median follow-up of 55 months. In conclusion, before and during LC, we have not overlooked T2 or more advanced tumor, which requires additional procedures for curative resection. This might result in good survival. We consider that an intensive preoperative work-up and meticulous inspection of the opened gallbladder should be mandatory to detect gallbladder cancer in patients who undergo LC. At present, this is not routinely practiced.

Adult↗

PubMed2004

Four-dimensional volume contrast ultrasound imaging of the gallbladder compared with tissue harmonic imaging: preliminary experience.

Comparison of volume contrast US imaging with tissue harmonic imaging for the evaluation of gallbladder lesions and determination of the adequate slice thickness in volume contrast US imaging were performed. Forty-one patients who had gallbladder lesions (polyps in 26, stones in 12, and sludge in 3) were enrolled in our study. A Voluson 730 Expert US scanner was used throughout. Volume contrast US imaging with slice thicknesses of 3, 5, 10 and 15 mm and tissue harmonic imaging of the gallbladder were obtained. Two abdominal radiologists reviewed the masked images and graded by consensus these images using a five-point scale [from grade 1, (best), to grade 5, (worst)], based on the sharpness of the anterior gallbladder wall, internal artifact, lesion conspicuity and acoustic shadowing from stone. Volume contrast US imaging with thin slice thicknesses (3 or 5 mm) was judged superior to both tissue harmonic imaging and with thick slice thicknesses (10 or 15 mm), with respect to the sharpness of the anterior wall and lesion conspicuity ( P<0.001). In terms of internal artifact, volume contrast imaging with thin slice thicknesses was significantly superior to both tissue harmonic imaging and volume contrast imaging with a 15 mm thickness ( P<0.001) and was judged to be marginally better than with a 10 mm thickness ( p>0.01). With regard to acoustic shadowing, volume contrast imaging with thin slice thicknesses was also significantly better than with thick slice thicknesses ( P<0.01), and it was also marginally better than tissue harmonic imaging ( P>0.01). Volume contrast US imaging with thin slice thicknesses provides a better image quality with fewer artifacts than three other types of images for the evaluation of gallbladder diseases.

Adult↗

PubMed1996

The movement of mucosal cells of the gallbladder within the peritoneal cavity during laparoscopic cholecystectomy.

BACKGROUND: Tumor dissemination to trocar sites following the removal of a gallbladder malignancy by laparoscopic cholecystectomy is well documented. The mode of transfer of malignant cells to those sites remains unclear. METHODS: The appearance and movement of gallbladder mucosal cells within the peritoneal cavity during laparoscopic cholecystectomy was prospectively studied in 15 patients. The appearance of cells on laparoscopic instruments, laparoscopic working ports, and also within a 5-microm polycarbonate filter, filtering exhaust carbon dioxide and attached to one of the main working ports, was noted. RESULTS: Four out of 15 gallbladders were perforated during cholecystectomy. Operative choledochography was performed in 11 of the 15 cases. Glandular cells were found on instruments at the end of the procedure in six cases. Cells were also found in two of the 15 polycarbonate filters and on the laparoscopic ports in two of the 15 cases. CONCLUSION: These findings suggest that cellular contamination of the peritoneal cavity is frequent during laparoscopic cholecystectomy. This may occur when the gallbladder wall is macroscopically breached or when operative choledochography is performed, or by microperforation due to the application of crushing laparoscopic graspers to the gallbladder wall. Glandular cells adhere to instruments in 40% of the operative procedures and may be the main source of dissemination of malignant cells through the peritoneal cavity.

Cholecystectomy, Laparoscopic↗

PubMed1999

Cellular kinetics and gene mutations in gallbladder mucosa with an anomalous junction of pancreaticobiliary duct.

Anomalous junction of the pancreaticobiliary duct (AJPBD) is thought to be an important risk factor for gallbladder carcinoma in Japan. We have reported the characteristic pathology, cellular kinetics, and gene mutations to clarify the mechanism of carcinogenesis in gallbladder mucosa with AJPBD. A comprehensive review of the literature was undertaken, with referencing of major articles on the subject. A sequence of hyperplastic changes, with a corresponding increase in cellular kinetics with progression through dysplasia to carcinoma is important in carcinogenesis of gallbladder mucosa with AJPBD. p53 mutations may contribute to the transition from premalignancy to malignancy in the early stage of carcinogenesis of the gallbladder mucosa, regardless of the presence of AJPBD. The specific mutation of GGT-to-GAT in codon 12 of K-ras may play an important role in carcinogenesis of gallbladder mucosa with AJPBD.

Adenocarcinoma↗

PubMed1992

VIP inhibits CCK-induced gallbladder contraction involving a beta-adrenoceptor mediated pathway in the rainbow trout, Oncorhynchus mykiss, in vivo.

The effects of VIP on CCK-induced contractions of the gallbladder were studied in the rainbow trout, Oncorhynchus mykiss, in vivo. Gallbladder pressures were measured via a catheter inserted into the gallbladder, and drugs were injected through a catheter in the dorsal aorta. CCK-induced contractions of the gallbladder wall were reduced in a dose-dependent manner by VIP. The effect of VIP was inhibited by the beta-adrenergic antagonist sotalol, indicating an adrenergic link in the VIP inhibition of the CCK-induced contraction. It is suggested that activation of VIP nerves could facilitate postprandial filling/refilling of the gallbladder despite the increased plasma levels of CCK during this period.

Animals↗

PubMed1993

Promotion of gallbladder emptying by intravenous aminoacids.

Patients receiving total intravenous nutrition have inert gallbladders; gallbladder sludge and gallstones often develop, but are preventable if gallbladder emptying can be improved. We measured the effect of giving rapid intravenous infusions of aminoacid solutions in eight normal subjects. Four regimens were tested (250 mL over 30 min, 250 mL over 10 min, 125 mL over 5 min, and 50 mL over 5 min). Gallbladder emptying, as measured by ultrasound and cholecystokinin release, depended on both the amount and the rate of aminoacid infusion. Rapid infusion of 125 mL of an aminoacid mixture (Synthamin 14 without electrolytes) over 5 min (2.1 g per min) produced a 64% reduction in gallbladder volume within 30 min, whereas a 50 mL infusion over 5 min produced only a 22% reduction. Intermittent rapid infusion of small amounts of aminoacids may prevent gallstones in patients receiving intravenous nutrition.

Adult↗

PubMed1992

Real-time ultrasonography as a noninvasive tool for the examination of canine gallbladder emptying: a validation study.

An ultrasonographic measurement of the gallbladder volume based on an ellipsoid approximation of the gallbladder shape was validated in vivo in the dog. The mean difference between the ultrasonographically determined and the true gallbladder volumes amounted to 2.0 +/- 1.6 cm3 (mean +/- SD), whereas the regression line computed for the ultrasonographically measured versus true gallbladder volumes was y = 0.892x + 3.0, r = 0.955, p much less than 0.001. The ultrasonographic method enabled a noninvasive, repetitive measurement of either a meal- or caerulein-induced gallbladder emptying in the dog.

Animals↗

PubMed2005

Progesterone inhibits gallbladder motility through multiple signaling pathways.

Progesterone (P) has an inhibitory effect on the contractility of gastrointestinal smooth muscle, including the gallbladder. Since P levels are elevated during pregnancy, a biliary stasis may develop during pregnancy that is characterized by an increase in the fasting and residual volumes and by a decrease in emptying capacity. This study investigates the effect of P and two metabolites on contraction in guinea pig gallbladder strips. P induced a concentration-dependent relaxation in guinea pig gallbladder strips precontracted with cholecystokinin octapeptide (CCK). Pretreatment of gallbladder strips with P (50 microM) also reduced the amount of CCK-induced tension. Nifedipine (1 microM) produced a similar effect. Pretreatment of the strips with PKA inhibitor 14--22 amide myristolated (180 nM) or the PKG inhibitor KT5823 (1.2 microM) either separately or in combination significantly reduced the amount of P-induced relaxation. Rp-cAMPs (0.1mM) or H-89 (10 microM) separately or in combination significantly reduced the P-effect; however, the combination of agents produced the largest reduction. Genistein (1 microM), an inhibitor of protein tyrosine kinases, significantly (p<0.01) reduced the amount of P-induced relaxation. The use of strontium in the Kreb's solution as a substitute for Ca(2+) significantly (p<0.01) reduced the amount of CCK-induced tension. Pretreatment of the strips with 2-APB (26 microM), an inhibitor of IP(3,) induced Ca(2+) release, produced a significant (p<0.01) reduction in P-induced relaxation. We conclude that P inhibits gallbladder motility rapidly by nongenomic actions of the hormone. Several pathways that include tyrosine kinase and PKA/cAMP activity may mediate this effect.

17-alpha-Hydroxyprogesterone↗

PubMed2002

Fragile histidine triad gene abnormalities in the pathogenesis of gallbladder carcinoma.

There is limited information about the molecular changes involved in the pathogenesis of gallbladder carcinoma (GBC). Our recent allelotyping analyses have indicated that chromosome 3p loss of heterozygosity (LOH), including the fragile histidine triad (FHIT) candidate tumor-suppressor gene locus at 3p14.2, is frequently detected in this neoplasm. To investigate the role of the FHIT abnormalities in the multistage sequential development of GBC, 33 formalin-fixed paraffin-embedded invasive GBC specimens and 76 accompanying histologically normal (n = 43) and dysplastic (n = 33) epithelia were examined by immunostaining for expression of Fhit protein. Allele loss at the FHIT gene locus (3p14.2) was studied in all GBCs and in a subset of accompanying gallbladder epithelia by polymerase chain reaction-based LOH analysis, using three 3p14.2 microsatellite markers. In addition, histologically normal epithelium from chronic cholecystitis (n = 19) and dysplasia (n = 13) from gallbladder specimens without cancer were examined for immunostaining and LOH. There was a progressive increase in both the frequency of loss of Fhit expression and LOH at FHIT with increasing severity of histopathological changes. FHIT abnormalities were occasionally demonstrated in histologically normal gallbladder epithelium. Dysplastic foci demonstrated frequent reduction or absence of Fhit immunostaining (38 to 55%) and FHIT allelic loss (33 to 46%). In invasive tumors, these abnormalities were even higher, with 79% reduction or absence of Fhit immunostaining and 76% FHIT allele loss. A high correlation (70%) was observed between Fhit immunostaining abnormalities and allele loss in GBC specimens (P < 0.05). Although a high frequency of FHIT locus breakpoints were detected in both invasive and dysplastic gallbladder specimens, no intronic homozygous deletions on FHIT were detected in GBCs. FHIT gene abnormalities are nearly universal in GBC and these changes are detected early in the sequential development of this neoplasm. Our findings indicate that the FHIT gene is one of the chromosome 3p putative tumor suppressor genes involved in the pathogenesis of this highly malignant neoplasm.

Acid Anhydride Hydrolases↗

PubMed1990

Cholecystectomy provides long-term symptom relief in patients with acalculous gallbladders.

Elective cholecystectomy was performed in 60 patients with biliary colic and acalculous gallbladders during a 5-year period. Gallbladder wall disease was significantly more common (p less than 0.01) in patients with acalculous gallbladders than in a similar symptomatic group with calculous gallbladders. Thirty-four of 43 patients (77%) available for long-term follow-up reported complete symptom relief after cholecystectomy. Preoperative ultrasonography, biliary scintigraphy, oral cholecystography, upper gastrointestinal series, and pathologic features of the gallbladder were equivocal in predicting long-term symptom relief. In patients with acalculous biliary colic, the best predictor of complete symptom relief is an adequate history of true biliary colic.

Adult↗

PubMed1998

Hepatic Helicobacter species identified in bile and gallbladder tissue from Chileans with chronic cholecystitis.

BACKGROUND & AIMS: Cancer of the gallbladder is the number one cause of cancer mortality in Chilean women. Incidence rates for this tumor vary widely on a worldwide basis, being approximately 30 times higher in high-risk than in low-risk populations, suggesting that environmental factors such as infectious microorganisms, carcinogens, and nutrition play a role in its pathogenesis. Because several Helicobacter sp. colonize the livers of animals and induce hepatitis, the aim of this study was to determine whether Helicobacter infection was associated with cholecystitis in humans. METHODS: Bile or resected gallbladder tissue from 46 Chileans with chronic cholecystitis undergoing cholecystectomy were cultured for Helicobacter sp. and subjected to polymerase chain reaction (PCR) analysis using Helicobacter-specific 16S ribosomal RNA primers. RESULTS: Recovery of Helicobacter sp. from frozen specimens was unsuccessful. However, by PCR analysis, 13 of 23 bile samples and 9 of 23 gallbladder tissues were positive for Helicobacter. Eight of the Helicobacter-specific PCR amplicons were sequenced and subjected to phylogenetic analysis. Five sequences represented strains of H. bilis, two strains of "Flexispira rappini" (ATCC 49317), and one strain of H. pullorum. CONCLUSIONS: These data support an association of bile-resistant Helicobacter sp. with gallbladder disease. Further studies are needed to ascertain whether similar Helicobacter sp. play a causative role in the development of gallbladder cancer.

Adult↗

PubMed1999

Mechanisms of gallbladder hypomotility in pregnant guinea pigs.

BACKGROUND & AIMS: Gallbladder muscle contraction becomes impaired during pregnancy. This study was designed to investigate the mechanisms of gallbladder hypomotility induced by pregnancy in guinea pigs. METHODS: Gallbladder muscle cells were obtained by enzymatic digestion. Cell contraction was expressed as percent shortening of initial control cell length. RESULTS: Contraction induced by cholecystokinin (CCK)-8 or guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) was reduced in muscle cells from pregnant guinea pigs. The response to KCl or D-myo-inositol 1,4, 5-trisphosphate was not different between controls and pregnant animals. These findings suggest that impaired contraction in pregnancy might be caused by defective G protein activation. The function and content of G proteins were examined by using [35S]GTPgammaS binding and G protein subunit quantitation. In female controls, CCK-8 at 1 micromol/L caused increased [35S]GTPgammaS binding to Galphai3 but not to Galphaq/11, Galphai1-2, or Galphas. GTPgammaS binding to Galphai3 induced by CCK-8 was reduced in gallbladder muscle from pregnant guinea pigs. Measurements of basal G proteins showed that the content of Galphai3 was significantly lower and the Galphas content was higher in muscles from pregnant guinea pigs than in controls. CONCLUSIONS: Pregnancy may cause down-regulation of contractile G proteins such as Galphai3 and up-regulation of Galphas that mediates relaxation, resulting in impaired gallbladder muscle contraction.

Animals↗

PubMed2004

Pathologic changes in the non-carcinomatous epithelium of the gallbladder in patients with a relatively long common channel.

BACKGROUND: Except for pancreaticobiliary maljunction, the relationship between a relatively long common channel and gallbladder carcinoma is unknown. METHODS: For purposes of this study, a high confluence of pancreaticobiliary ducts was defined as a common channel that is 6 mm or greater in length, together with occlusion of the communication between the pancreatic and bile ducts during sphincter contraction. Pancreaticobiliary maljunction and high confluence of the pancreaticobiliary ducts were detected in 69 (2.1%) and 54 (1.6%), respectively, of 3300 consecutive patients who underwent ERCP. Proliferation activity and genetic alteration were examined in the non-carcinomatous epithelium of the gallbladder in patients with these two radiographic findings at ERCP. RESULTS: The Ki-67 labeling index in the epithelium in cases of a high confluence of the pancreaticobiliary ducts and pancreaticobiliary maljunction without biliary dilatation was significantly greater than that in cases of gallbladder carcinoma without these anomalies (p < 0.01). Overexpression of p53 and K-ras mutations were detected in, respectively, 22.2% and 27.8% of cases of a high confluence of pancreaticobiliary ducts. CONCLUSIONS: A relatively long common channel may be an important risk factor for the development of gallbladder carcinoma. Vigilance for the development of gallbladder carcinoma is indicated in patients with a relatively long common channel, in addition to those with pancreaticobiliary maljunction.

Bile Ducts↗

PubMed2003

Measurements of gallbladder motor function by ultrasonography: towards standardization.

As real-time ultrasonography is a cheap, noninvasive, relatively easy, validated and reproducible technique, it can be repeated over time to document time-related changes of gallbladder motor function. Ultimately, functional ultrasonography estimates gallbladder shape and volume in fasting state and in response to a test meal (liquid or mixed solid-liquid, provided there is sufficient fat content) or exogenous stimulus (e.g., i.v. cholecystokinin or ceruletide). Although functional ultrasonography of the gallbladder has been mainly used for research purposes in specific referral centres, its simplicity makes such a technique appealing in the clinical setting to assess gallbladder motor function in both health and disease. Indications include the study of healthy subjects and of patients during pathophysiologically relevant conditions; in particular when subjects are at risk for gallbladder stasis and gallstone disease or during gallstone disease when a decision concerning medical dissolution therapy is required.

Cholecystolithiasis↗

PubMed1998

Gallbladder motility and gallstone formation in obese patients following very low calorie diets. Use it (fat) to lose it (well).

OBJECTIVE: Dieting obese subjects are at risk of developing gallstones. A gallbladder motor dysfunction could have a pathogenetic role. The principal aim of this study was to evaluate the long term effects of two very low calorie diets differing in fat content on gallbladder emptying and gallstone formation in obese subjects. DESIGN AND SUBJECTS: Gallbladder emptying in response to meals (breakfast, lunch and dinner) in two different diet regimens (3.0 vs 12.2 g of fat/d) was evaluated by ultrasonography in 32 gallstone-free obese patients on different days, before and during (at 45 d intervals) one or two 6-month weight reduction diets (for the first three months: 2.24 MJ (535.2 kcal), 3.0 g fat/d vs 2.415 MJ (577.0 kcal), 12.2 g fat/d; for the second three months, the same low calorie diet of 4.194 MJ (1002 kcal)/d for both groups). In 10 subjects, bile analysis was also performed. RESULTS: Twenty-two (69%) subjects concluded the study, eleven in each group, and a significant weight loss was achieved by all subjects. Gallstones (asymptomatic) developed in 6/11 (54.5%) (P < 0.01) of subjects following the lower fat diet, but in none with the higher fat regimen. In the dieters during the first three months (very low calorie phase) the higher fat meals always induced a significantly greater gallbladder emptying than the lower fat meals. The cholesterol saturation index initially increased significantly and then decreased, without difference between the two groups. CONCLUSION: In the obese during rapid weight loss from a very low calorie diet, a relatively high fat intake could prevent gallstone formation, probably by maintaining an adequate gallbladder emptying, which could counterbalance lithogenic mechanisms acting during weight loss.

Adolescent↗