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PubMed2000

Well-differentiated adenocarcinoma of the gallbladder mimicking minimal deviation adenocarcinoma of the cervix.

We report a case of well-differentiated adenocarcinoma of the gallbladder, histologically mimicking minimal deviation adenocarcinoma (MDA) of the cervix. A 71-year-old Japanese male underwent cholecystectomy because of the suggestion of gallbladder carcinoma. The resected gallbladder showed a localized thickening of the gallbladder wall with a polypoid lesion measuring 12x7 mm in diameter. Microscopically, the polypoid lesion proved to be a well-differentiated adenocarcinoma composed of columnar cells with a clear cytoplasm. In the thickened gallbladder wall, well-formed glands were extensively distributed; they were surrounded by a slightly desmoplastic reaction instead of lamina propria, or were directly in contact with smooth muscle cells. The diagnostic criteria for cervical MDA may be useful in distinguishing well-differentiated adenocarcinoma of the gallbladder from benign conditions, such as Rokitansky-Aschoff sinus and adenomyomatosis. It is remarkable that the tumor cells of the present case expressed gastric type mucin which is characteristic of mucinous type cervical MDA.

Adenocarcinoma↗

PubMed1999

Tumor-host interactions in the gallbladder suppress distal angiogenesis and tumor growth: involvement of transforming growth factor beta1.

Angiogenesis inhibitors produced by a primary tumor can create a systemic anti-angiogenic environment and maintain metastatic tumor cells in a state of dormancy. We show here that the gallbladder microenvironment modulates the production of transforming growth factor (TGF)-beta1, a multifunctional cytokine that functions as an endogenous anti-angiogenic and anti-tumor factor in a cranial window preparation. We found that a wide variety of human gallbladder tumors express TGF-beta1 irrespective of histologic type. We implanted a gel impregnated with basic fibroblast growth factor or Mz-ChA-2 tumor in the cranial windows of mice without tumors or mice with subcutaneous or gallbladder tumors to study angiogenesis and tumor growth at a secondary site. Angiogenesis, leukocyte-endothelial interaction in vessels and tumor growth in the cranial window were substantially inhibited in mice with gallbladder tumors. The concentration of TGF-beta1 in the plasma of mice with gallbladder tumors was 300% higher than that in the plasma of mice without tumors or with subcutaneous tumors. In contrast, there was no difference in the plasma levels of other anti- and pro-angiogenic factors. Treatment with neutralizing antibody against TGF-beta1 reversed both angiogenesis suppression and inhibition of leukocyte rolling induced by gallbladder tumors. TGF-beta1 also inhibited Mz-ChA-2 tumor cell proliferation. Our results indicate that the production of anti-angiogenesis/proliferation factors is regulated by tumor-host interactions.

Angiostatins↗

PubMed1997

p53 tumour suppressor gene protein expression in early and advanced gallbladder carcinoma.

AIMS: Gallbladder carcinoma is one of the most frequent malignant tumours occurring in Chile and the mortality rate in both sexes ranks among one of the highest in the world. Mutation of p53 tumour suppressor gene has been demonstrated in many tumours. Our aim was to determine protein expression of p53 gene in early and advanced gallbladder carcinoma. METHODS AND RESULTS: Protein expression of gene p53 was studied by immunohistochemical means in 191 gallbladder carcinomas (157 primary tumours, 34 metastases) and 25 controls. In 86 out of 191 cases (45%), protein expression of gene p53 was observed. Differences related to sex, age, or race were not observed. All gallbladder controls were negative. Twenty-five per cent of well-differentiated tumours were p53 positive, while moderate or poorly differentiated carcinomas reached 50% (P = 0.04). p53 expression was observed in 23.5% of early carcinomas and in 48.2% of advanced carcinomas (P = 0.01). No differences between primary tumours and metastasis were demonstrated. CONCLUSIONS: Protein expression of p53 tumour suppressor gene is observed in 45% of gallbladder carcinomas. The absence of expression in controls and in normal mucosa adjacent to tumours suggests its utility in differentiating atypical gallbladder epithelia from neoplastic lesions.

Carcinoma↗

PubMed2000

Enhanced cell kinetics, p53 accumulation and high p21WAF1 expression in chronic cholecystitis: comparison with background mucosa of gallbladder carcinomas.

AIMS: Since neoplasia resulting from chronic inflammation has recently attracted increasing attention, we have investigated surgically removed gallbladders to examine the relationship between chronic cholecystitis and carcinogenesis. METHODS AND RESULTS: The mucosa of 108 cholecystectomy specimens without gallbladder cancer and 54 surgically resected gallbladder carcinomas were classified into three groups according to the degree of lymphocytic infiltration, and assessed immunohistochemically for Ki67, p53, p21WAF1 and apoptosis. In gallbladder mucosa without carcinoma, all four parameters tended to increase with the inflammation score (IS). Significantly positive correlations were revealed between Ki67 and p53, Ki67 and p21WAF1, and p53 and p21WAF1. However, in gallbladder carcinoma cases, values of p53 and p21WAF1 for background mucosa were elevated as compared to the mucosa of cholecystitis with low IS, but there was no correlation between their expression and IS, except for Ki67. CONCLUSIONS: Severe chronic cholecystitis is associated with acceleration of epithelial cell turnover, damaged cells being eliminated by apoptosis. The background mucosa of gallbladder carcinomas showed similar cell proliferative activity (Ki67) to that in cholecystitis, with no parallel changes of p53 and p21WAF1 expression, suggesting the possibility of unknown cofactors causing genomic damage.

Adenocarcinoma↗

PubMed2003

Incidental finding of gallbladder carcinoma detected during or after laparoscopic cholecystectomy.

AIM: Carcinoma of the gallbladder is a rare neoplasm with a dismal prognosis. With the increase of cholecystectomies due to the wide acceptance of laparoscopic cholecystectomy, the incidental diagnosis of gallbladder carcinoma is more frequent. We report our experience with gallbladder cancer diagnosed during or after the performance of laparoscopic cholecystectomy. METHODS: We evaluated 11 patients with gallbladder cancer out of 5539 patients who underwent laparoscopic cholecystectomy. Patient clinical and demographic characteristics were reviewed. RESULTS: Intraoperatively in 297 patients there was the suspicion of adenocarcinoma and frozen sections were performed. In four of them the diagnosis of adenocarcinoma was confirmed. In two of them the procedure was converted to open with gallbladder liver bed resection and regional lymph node dissection while the other two were considered inoperable. Of the remaining 5242 patients, seven were diagnosed postoperatively at the pathologic examination. Of these, five patients refused to undergo a repeat operation. We did not observe port site metastasis in any of our patients. Survival was low and ranged from 3-14 months. CONCLUSION: Gallbladder cancer runs a short course, with a poor prognosis. The use of a meticulous laparoscopic technique seems to be important for the diagnosis and the avoidance of early complications of the disease.

Adenocarcinoma↗

PubMed2004

Guanylin regulates chloride secretion in the human gallbladder via the bile fluid.

BACKGROUND & AIMS: The biliary epithelium of bile ducts and gallbladder modifies the composition of primary hepatic bile by absorption and secretion of an electrolyte-rich fluid. The underlying transport mechanisms, however, are still incompletely understood. We investigated the expression, the cellular localization, and the functional role of guanylin, a bioactive intestinal peptide involved in the cystic fibrosis transmembrane conductance regulator (CFTR)-regulated electrolyte/water secretion, in the human gallbladder. METHODS: Peptide-specific antibodies were raised to localize guanylin and its affiliated signaling proteins, i.e., the guanylin receptor, guanylate cyclase C (GC-C), cGMP-dependent protein kinase type II (cGKII), and CFTR in the human gallbladder and cholangiocarcinoma cells (Mz-Cha-1) by RT-PCR, Western blot, and immunocytochemistry. A sensitive ELISA was used to assess the range of guanylin concentration in human bile fluid. The functional role of guanylin was investigated in subconfluent Mz-Cha-1 cell monolayers by isotope efflux experiments. RESULTS: Guanylin and its affiliated signaling proteins are highly expressed in the human gallbladder. Guanylin is localized to secretory epithelial cells of the gallbladder and is present in the bile, whereas GC-C, cGKII, and CFTR are confined exclusively to the apical membrane of the same epithelial cells. Functional studies in Mz-Cha-1 cells identify guanylin as a specific regulator of biliary Cl(-) secretion that very likely is mediated by an intracellular increase of cGMP-concentration. CONCLUSIONS: Based on the present findings and on the functional role of guanylin in other epithelia, it is likely that gallbladder epithelial cells synthesize and release guanylin into the bile to regulate electrolyte secretion by a paracrine/luminocrine signaling pathway.

Bile↗

PubMed2000

[Postoperatively detected gallbladder carcinoma. Follow-up or reoperation?].

BACKGROUND: The prognosis of gallbladder carcinoma is generally poor. The 5-year survival rate amounts to less than 5% in most series due to the high proportion of advanced stages at the time of diagnosis. Early stages are commonly found only with histological work-up after cholecystectomy (CCE). In these cases the question arises whether or not reoperation for completion resection would be indicated. PATIENTS/METHODS: A retrospective analysis examined all patients of the Clinic of Surgery (Charité) in Berlin with gallbladder carcinoma operated on between January 1981 and August 1993. A literature search was carried out using the MEDLINE retrieval system for the key words "gallbladder carcinoma", "surgical therapy", and "reoperation" limited to the period after 1970. RESULTS: The retrospective results of the own clinic and the analysis of the literature review demonstrate significantly higher survival rates after reoperation compared to CCE alone and observation for all cases of gallbladder carcinoma with stages T1b or higher stages. The extended radical CCE can be performed with low morbidity. With preceding laparoscopic CCE the trocar sites have to be completely excised. DISCUSSION: To avoid the situation of postoperative diagnosis of gallbladder carcinoma, the surgeon should intraoperatively during CCE perform a careful macroscopic control of the gallbladder. Suspect findings should be followed intraoperatively by histological examination. Nevertheless, local spread of GBCa and distribution of lymphatic metastases can certainly not be assessed completely after simple CCE. Based on the published results and because of low morbidity reoperation is indicated for most cases of GBCa when diagnosed postoperatively.

Cholecystectomy↗

PubMed1994

[Color Doppler ultrasound of gallbladder varicose veins in children. A rare sign of portal hypertension].

In a retrospective study of 21 children with portal hypertension (P. H.) four patients (19.2%) presented with gallbladder varices as documented by colour-coded Doppler sonography (CCDS) gallbladder varices (GV). Three of four patients with GV had portal vein thrombosis, one patient had cholestatic cirrhosis. Thickening of the gallbladder wall with serpentine anechoic structures was visible in all cases. Blood flow could be documented within the widened veins of the gallbladder wall in 3 of the 4 patients with duplex Doppler US, but in all patients with CCDS. US follow-up studies within 3-5 years were done on 2 patients and showed that GV appeared 2 years after the clinical diagnosis of P. H. With CCDS, varices of the gallbladder wall may be diagnosed readily and differentiated from other diseases associated with thickening of the gallbladder wall.

Adolescent↗

PubMed1994

Percutaneous endoscopic polypectomy of gallbladder polyps.

We report here our preliminary experience with percutaneous endoscopic polypectomy of gallbladder polyps. Five patients with a total of 17 cholesterol polyps (size: 4-6 mm) and one patient with two gallbladder adenomas (size: 5 mm), four of whom were symptomatic and all of whom refused cholecystectomy, underwent a single-stage procedure under epidural anesthesia. All patients had functioning gallbladders, as assessed by oral cholecystography after stimulation. Following a small incision, the gallbladder was pulled out of the abdominal wall, incised, and a cholecystoscope introduced. The polyps were coagulated at their stalk using microwave irradiation (70-80 mA, 9 sec) and removed for histopathological evaluation thereafter. A catheter was left in situ for ten days. Follow-up for a mean of 11.6 months (8-16 months) showed all patients to be symptom-free and without recurrence of polyps on ultrasonography. Gallbladder function was assessed in five cases by meal-stimulated oral cholecystography, and in one by hepato-iminodiacetate acid (HIDA) scan and was found to be well preserved. The preliminary results warrant further evaluation of this method of removing indeterminate gallbladder polyps.

Adult↗

PubMed1988

[Ultrasound scanning of thickening of the gallbladder wall and its diagnostic significance in critical care patients].

In a prospective study including 398 intensive-care patients, we analysed the ultrasonographic relevance of a gallbladder wall thickening. In 24 of 398 (6%) cases a wall thickening was found that could be differentiated into two types of walls. In 20.8% (5/24) the gallbladder wall thickening was an expression of an acute cholecystitis. In further differential diagnosis of a gallbladder wall thickening pathological states with hypoalbuminaemia occupy the prime position. The pathological mechanism has not yet been completely clarified. Hypoalbuminaemia without inflammatory alterations of the organ was found in 37.5% of the cases with gallbladder wall thickening. In 41.6% of the patients the wall thickening had to be taken as a non-specific ultrasonographic sign. On the whole, therefore, gallbladder wall thickening has thus to be valued primarily as non-specific sign. In a few cases only, it implies an autonomous affection of the gallbladder.

Adult↗

PubMed1984

[The size of the gallbladder in acute viral hepatitis].

We investigated sonographically the gallbladders of 22 patients during the course of acute viral hepatitis. The size of the gallbladders in the fasting state varied characteristically. When the illness was at its severest, the gallbladder was slightly filled or empty. Later on in the course of the illness, the volume increased until the gallbladder was tightly filled. The area of the gallbladder was measured repeatedly with the same patient and individually correlated inversely with the values of aminopeptidases, but not in a strictly linear manner. This is in fact an easily detectable, sonographical marker of the clinical development of a severely disturbed liver function. When a gallbladder is seen empty, slack or with an apparently thickened wall in the fasting state, the diagnosis of a parenchymal jaundice may be considered.

Acute Disease↗

PubMed1984

[Cholelitholysis and gallbladder diverticula].

Fifty patients with cholesterol stones in their gallbladder, with few symptoms were treated with the bile acids cheno- or ursodeoxycholic acid. 38 had a "normal" gallbladder, 12 had diverticula of the gallbladder. After the complete dissolution of the stones the bile acid treatment was stopped. The follow-up period lasted up to 7 years. No recurrence was observed in the gallbladder of 18 patients, but 32 developed new stones. With a second bile acid treatment we could dissolve the new stones of 13 patients, up to now without further relapses. After the second bile acid treatment of 9 months and x-ray controls 19 patients (38%) developed insoluble material in their gallbladders, independent of the presence of diverticula. We tried to eliminate calcium sediments with cholecystokinin-like substances. Temporary success was achieved in three of five patients only, and one person only remained free of further relapses. There is no reason to exclude patients with cholesterol stones and diverticula of the gallbladder from litholytic therapy.

Adult↗

PubMed2003

Preoperative diagnosis and staging of gallbladder carcinoma by EUS.

BACKGROUND: EUS has recently been shown to be efficacious for the preoperative assessment of depth of invasion of gallbladder carcinoma. This study assessed the value of EUS for determining T stage (International Union Against Cancer). METHODS: Preoperative EUS findings in 41 patients with gallbladder carcinoma were analyzed retrospectively. EUS images were classified according to the shape of the tumor and the adjacent gallbladder wall structure as follows: type A, pedunculated mass with preserved adjacent wall structures; type B, sessile and/or broad-based mass with a preserved outer hyperechoic layer of the gallbladder wall; type C, sessile and/or broad-based mass with a narrowed outer hyperechoic layer; type D, sessile and/or broad-based mass with a disrupted outer hyperechoic layer. EUS and histopathologic findings were compared, including the depth of invasion of the tumor in the resection specimen. RESULTS: The 4 categories of EUS images of gallbladder carcinoma correlated with the histologic depth of invasion and T stage. Accuracies for the EUS classification as type A corresponding to pTis, type B to pT1, type C to pT2, and type D to pT3-4 were, respectively, 100%, 75.6%, 85.3%, and 92.7%. CONCLUSIONS: Preoperative EUS imaging accurately depicts T stage of gallbladder carcinoma and allows for effective therapeutic decision making.

Adult↗

PubMed2003

Metastatic carcinoma of the gallbladder after a renal cell carcinoma.

The gallbladder is rarely the site of distant metastases and in most cases malignant melanoma is the primary tumor. We report a case of a 64-year-old man with a gallbladder metastasis secondary to a renal cell carcinoma. Renal cell carcinoma has a tendency toward metastatic disease, the most notable features of this tumor being its unusual pattern of metastatic disease. Pre-operative imaging studies are often futile in the differentiation between primary and secondary tumors of the gallbladder. Since primary tumors of the gallbladder often coexist with gallstones, a polypoid lesion in an acalculous gallbladder is more consistent with metastasis than a primary tumour. If feasible, surgical resection of the gallbladder is mandatory because it could guarantee better chances of survival for patients with metastatic renal carcinoma.

Carcinoma, Renal Cell↗

PubMed2000

Preoperative diagnosis of gallbladder torsion by magnetic resonance cholangiopancreatography.

The patient was a 78-year-old woman who was diagnosed as having gallbladder torsion preoperatively. This is the first reported case diagnosed by magnetic resonance cholangiopancreatography (MRCP). Signs and symptoms of this condition are often subtle. Radiologic evaluation by ultrasonography and computed tomography (CT) showed acute cholecystitis with stone. Drip-infusion cholangiography CT failed to outline the gallbladder, and distortion of the extrahepatic bile ducts and interruption of the cystic duct were observed. MRCP showed 1) a v-shaped distortion of the extrahepatic bile ducts due to traction by the cystic duct, 2) tapering and twisting interruption of the cystic duct, 3) a distended and enlarged gallbladder that was deviated to the midline of the abdomen, and 4) a difference in intensity between the gallbladder and the extrahepatic bile ducts and the cystic duct. A definitive diagnosis of gallbladder torsion (volvulus) was made by MRCP preoperatively. If treated surgically, gallbladder detorsion before cholecystectomy is a helpful technique to avoid bile duct injury. This condition should be suspected in elderly women with acute cholecystitis or acute abdominal pain of unknown origin, and MRCP may be very useful in making a definitive diagnosis.

Aged↗

PubMed1998

Dose-dependent inhibition of postprandial gallbladder motility and plasma hormone secretion during acute hyperglycemia.

BACKGROUND: Actual blood glucose concentrations influence gastrointestinal function. We investigated whether in healthy subjects the inhibitory effect of acute hyperglycemia on gallbladder motility is dose-dependent. METHODS: Seven healthy volunteers were studied on four separate occasions in random order during euglycemia and during hyperglycemic clamping, at 4 mmol/l, 8 mmol/l, 12 mmol/l, and 16 mmol/l, respectively. Gallbladder volumes (ultrasonography) and plasma hormone release were studied before and after ingestion of a meal. RESULTS: Postprandial gallbladder contraction was significantly (P < 0.05) and dose-dependently inhibited during the hyperglycemic experiments at 8, 12, and 16 mmol/l (56%+/-8%, 49%+/-8%, and 30%+/-5%, respectively) compared with euglycemia (68%+/-6%). Postprandial cholecystokinin release was significantly (P < 0.05) reduced compared with euglycemia only at a plasma glucose level of 16 mmol/l (116+/-28 versus 159+/-13 pmol x l(-1) x 120 min). Plasma pancreatic polypeptide secretion, as an indirect measure of vagal-cholinergic tone, was significantly (P < 0.05) and dose-dependently reduced during hyperglycemia at 8, 12, and 16 mmol/l. CONCLUSION: In healthy subjects acute hyperglycemia significantly and dose-dependently inhibits postprandial gallbladder motility. Future studies on gallbladder motility should take into account the influence of plasma glucose, because already at postprandial glucose levels gallbladder motility is reduced.

Adult↗

PubMed1998

Gallbladder volume and contractility in term and preterm neonates: normal values and clinical applications in ultrasonography.

The aim of this study was to establish the normal values and evaluate associated factors of gallbladder volume and contractility in term and preterm neonates by using ultrasonography. Sonographic measurement of gallbladder volume was performed by using the ellipsoid method in 50 preterm and 46 term infants. We collected data soon after delivery and at 6-h fasting, and at 3-h and 6-h fasting following regular milk feeding. Serial postprandial changes of gallbladder volume and contractility were collected at 15-min intervals for one hour. Gallbladder contraction index (C.I.) was determined as percentage decrement of postprandial size from initial size. Fasting gallbladder volume was larger in term group (p < 0.05). Term neonates more readily showed significant contraction (C.I. > 50%; p < 0.05). In preterm infants significant contraction was clearly observed at postconceptional age > 31 weeks or body weight > 1300 g. The presence of hepatobiliary diseases might be detected by evaluating serial changes of gallbladder volume and contractility under ultrasonography in the neonatal stage.

Gallbladder↗

PubMed1999

Gallbladder contraction in familial dysautonomia.

The impaired function of the autonomic nervous system in patients with familial dysautonomia (FD) is frequently associated with gastrointestinal dysfunction. This study sought to determine whether gallbladder contraction is also affected in these patients. Nine consecutive patients with FD were assessed by real-time ultrasonography for gallbladder volume and calculated percentage of gallbladder contraction before and 45-60 min after a 50 g fatty meal, and compared with nine healthy control patients, matched for age and gender. Gallbladder volume before the fatty meal was found to be larger in healthy controls than in FD patients (25.4+/-9.5 and 15.4+/-7.4 ml3, respectively; p = 0.024). No significant difference was demonstrated between the groups after the fatty meal (controls: 12.1+/-6.0; FD: 9.0+/-6.6 ml, respectively) and the calculated percentage of gallbladder contraction was similar in both groups (controls: 53.4+/-16.6; FD: 44.8+/-18.8%). These results indicate that gallbladder function in FD patients does not differ from the general population and preventive measures for gallstone formation are not required.

Abdominal Pain↗