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PubMed2001

Open versus laparoscopic cholecystectomy for gallbladder carcinoma.

Laparoscopic surgery has replaced conventional open cholecystectomy for benign gallbladder disease. A major concern is how to handle gallbladder cancer in the laparoscopic era, since there are numerous case reports of port site metastases from gallbladder cancer after laparoscopic cholecystectomy. There are also many experimental studies favoring the opinion that the laparoscopic technique implies a higher risk of spreading malignant disease. This opinion has gained wide acceptance despite little previous clinical effort to determine the risk of tumor dissemination and the lack of comparisons between open and laparoscopic surgery. This report is a short summary of our own studies and present knowledge with special respect to the clinical aspects of the development and incidence of abdominal wall metastases. Among 270 patients with verified gallbladder carcinoma in whom 210 had open surgery and 60 a laparoscopic cholecystectomy, 12 patients (6.5%) in the open cholecystectomy group and 9 (15%) in the laparoscopic group developed incisional metastases. Although the sparse clinical documentation does not unavoidably mean that laparoscopic cholecystectomy has an increased risk of disseminating tumor cells, we recommend open surgery in cases of known or suspected gallbladder carcinoma.

Abdominal Neoplasms↗

PubMed2003

Relaxant effect of omeprazole and lansoprazole in guinea pig gallbladder muscle strips in vitro.

BACKGROUND: The aim of this study was to investigate the role of omeprazole and lansoprazole, H(+)-K(+) ATPase inhibitors, in gallbladder smooth muscle contractility in vitro. METHODS: Gallbladder muscle strips obtained from guinea pigs were mounted in an organ bath. The responses of both precontracted strips and strips under basal tension to omeprazole and lansoprazole were determined. RESULTS: Spontaneous contractile activity was blocked following omeprazole and lansoprazole administration. The agents also caused concentration-dependent relaxation in carbachol- and KCl-precontracted gallbladder muscle strips. Pretreatment with atropine (1 microM), N(W)-nitro L-arginine methyl ester (L-NAME; 30 microM), indomethacin (10 microM), ammonium chloride (7.5 mM), sodium acetate (7.5 mM), tetraethylammonium chloride (0.5 mM), glibenclamide (1 micro M), 4-aminopyridine (0.1 mM), or clotrimazole did not inhibit this relaxation. Gallbladder strips were placed in high-concentrtion potassium (80 mM), calcium-free solution. The contraction produced with the addition of Ca(2+) (2.5 mM) was completely relaxed by omeprazole, lansoprazole, and nifedipine separately. CONCLUSIONS: These results demonstrate that omeprazole and lansoprazole have potent inhibitory effects on spontaneous contractions and cause dose-dependent relaxation in precontracted gallbladder smooth muscle strips of guinea pig in vitro. This effect could be due to blockade of the calcium channels.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2004

Hepatic artery pseudoaneurysm associated with cholecystitis that ruptured into the gallbladder.

Pseudoaneurysm of the hepatic artery due to cholecystitis may be very rare, and in our survey of the literature, the present case report is the first case of such a pseudoaneurysm. A 64-year-old woman presented with upper gastrointestinal bleeding and severe epigastric pain. Upper gastrointestinal tract endoscopy revealed blood coming out of the papilla of Vater. Color-Doppler ultrasound imaging showed a pulsatile wave pattern in an echogenic lesion inside the gallbladder. Contrast-enhanced computed tomography demonstrated a 3-cm pseudoaneurysm in the distended gallbladder. Angiography disclosed extravasation originating from the right hepatic artery. Emergency selective transcatheter arterial embolization was performed, with intravascular stainless steel microcoils, and complete occlusion of the pseudoaneurysm was achieved. The patient underwent cholecystectomy with resection of the extrahepatic bile duct and biliary reconstruction in a Roux-en-Y fashion. Macroscopically, the resected gallbladder contained clotted blood and multiple cholesterol stones. Microscopically, the mucosa of the gallbladder showed extensive necrosis and many inflammatory cells. The final diagnosis was pseudoaneurysm of the hepatic artery associated with calculous gangrenous cholecystitis. Although the mechanism of the pseudoaneurysm remains speculative, severe inflammatory reaction in the gallbladder may have infiltrated the liver parenchyma and may have eroded the wall of the hepatic artery, thus forming a pseudoaneurysm. Hemobilia is one of the important differential diagnoses when unexplained gastrointestinal bleeding is observed, especially in patients with hepatobiliary diseases.

Aneurysm, False↗

PubMed2005

Severe dysplasia of the gallbladder associated with occult pancreatobiliary reflux.

Pancreatobiliary reflux usually occurs in patients with pancreaticobiliary maljunction and can be associated with the occurrence of gallbladder carcinoma. We present the case of a patient with pancreatobiliary reflux despite having a normal pancreatobiliary junction (occult pancreatobiliary reflux; OPBR), in whom the resected gallbladder presented severe dysplasia. The patient, a 61-year-old woman, showed thickness of the gallbladder wall, detected by ultrasonography and computed temography (CT). Her biliary amylase level in the common bile duct was 103,000 IU/l, and in the gallbladder it was 153,500 IU/l, although endoscopic retrograde cholangiopancreatography revealed a normal pancreaticobiliary junction. Immunohistochemical staining showed many p53-positive nuclei in the dysplastic lesion, and about 50% of the dysplastic cells exhibited diffuse nuclear staining for Ki-67. In the present patient, early diagnosis of occult pancreatobiliary reflux led to early detection of a precancerous lesion of the gallbladder mucosa.

Abdominal Pain↗

PubMed2002

Diagnosis of pT2 gallbladder cancer by serial examinations with endoscopic ultrasound and angiography.

BACKGROUND: The prognosis of pT2 gallbladder cancer correlates with whether appropriate surgery for the spread of cancer has been performed. Therefore, accurate preoperative T staging is especially important. We carried out this study to evaluate the usefulness of serial examinations by endoscopic ultrasound (EUS) and angiography for the T staging of pT2 gallbladder cancer. METHODS: Forty-eight patients with gallbladder cancer who underwent both EUS and surgery between 1983 and 1998 were included in this study. The accuracy of serial examination by both EUS and angiography in T staging, based on previously established diagnostic criteria, was retrospectively evaluated. First, the presence or absence of subserosal tumor invasion was assessed by EUS alone. Second, in equivocal cases, the depth of tumor invasion was further evaluated by angiographic findings. RESULTS: Twenty-four patients were correctly diagnosed as having other than pT2 cancer by EUS alone. Angiographic findings were reviewed in 19 of the remaining patients, who had pT1, pT2, or a small number of pT3 lesions. The sensitivity, specificity, and overall accuracy in the T staging of pT2 gallbladder cancer was 81.8%, 90.6%, and 88.4%, respectively. CONCLUSIONS: Serial angiographic examination following adequate patient selection by EUS is effective and efficient for the diagnosis of pT2 gallbladder cancer.

Adult↗

PubMed2005

Prediction of prognosis in gallbladder carcinoma by mucin and p53 immunohistochemistry.

Mucin core proteins are known to be present in various organs and are specifically expressed with carcinogenesis and closely associated with the prognoses of various malignant tumors in the digestive tract such as colorectal cancer. The present study evaluated correlations between mucin and p53 expression and prognosis of gallbladder cancer using surgically resected tissue specimens from 26 patients with gallbladder carcinoma surgically treated at our hospital. Immunohistochemical staining was performed using MUC 1, MUC2, and p53 monoclonal antibody. The level of antigen expression in the lesion was classified into four stages: none(-), slight(+), moderate (++), and severe (+ + +). According to the UICC classification, histopathological grading, levels of T, N, and M factors, and tumor stages were compared with regard to the correlations with mucin and p53 expression. All cases were classified into two groups according to the results of mucin immunohistochemistry: group A (MUC1, > or = ++; and MUC2, < or = +) and group B (MUC1, < ++; or MUC2, > +). Postoperative survival periods were compared between the two groups and p53-positive and -negative groups. Neither histological grading nor T factor correlated with mucin or p53 expression, respectively. Moreover, neither N factor nor M factor correlated with mucin or p53 expression. Furthermore, stage grouping did not correlate with mucin or p53 expression. However, when the correlation between the postoperative survival period and mucin expression was evaluated, the mean postoperative surgical period was significantly shorter in Group A than in Group B (1.02 years in Group A vs 2.92 years in Group B; P = 0.016). There was no relationship between postoperative survival period and p53 positivity. Mucin expression was independent of various tumor growth factors and clearly reflected the prognosis of gallbladder cancer. Because the relative malignancy of gallbladder cancer could be evaluated by examining the level of glycoprotein expression in tumor tissue, mucin could be a more important marker than p53 for predicting prognosis in gallbladder carcinoma using surgically resected tissue specimens.

Aged↗

PubMed2003

Diabetes and hyperlipidemia correlate with gallbladder contractility in leptin-related murine obesity.

Obesity is associated with many comorbid conditions including diabetes, hyperlipidemia, and gallstones. However, the interaction among these modalities remains unclear. We recently demonstrated that both leptin-deficient and leptin-resistant obese mice have impaired biliary motility. These obese mice also are diabetic and hyperlipidemic. Therefore, we tested the hypothesis that serum glucose, insulin, cholesterol, and triglyceride levels would correlate with gallbladder contractility. Thirty-four lean control, 10 lean heterozygous leptin-deficient, 18 obese homozygous leptin-deficient, and 12 obese homozygous leptin-resistant mice were fed a nonlithogenic chow diet while nine lean control and nine obese homozygous leptin-deficient mice were fed a high-cholesterol diet for 4 weeks. In vitro gallbladder responses to cholecystokinin (CCK; 10(-8) mol/L), acetylcholine (ACh; 10(-5) mol/L), and neuropeptide Y (NPY; 10(-6) mol/L) were measured. Serum glucose, insulin, cholesterol, and triglyceride levels were measured from pooled serum from an additional 704 animals. Gallbladder responses were greatest for CCK, intermediate for ACh, and least for NPY. Serum glucose, insulin, cholesterol, and triglyceride levels and body weight all correlated similarly, negatively, and significantly (P<0.001) with gallbladder contractility. Hyperglycemia, insulin-resistance, hyperlipidemia, and body weight in obese mice with leptin dysfunction are associated with poor gallbladder contractility, which in turn may contribute to the association between obesity and gallstone formation.

Animals↗

PubMed1976

Papilloma of the gallbladder.

A case of papilloma of the gallbladder is reported. The gallbladder was associated with cholesterosis but not with stones. The causes of colicky pain in this case are discussed. Papillomas of the gallbladder exhibit no characteristic clinical picture; the symptoms are similar to those of any type of gallbladder disease. Papillomas of the gallbladder may be associated with malignant degeneration. Cholecystectomy is the treatment of choice.

Adult↗

PubMed1989

Operative therapy of gallbladder disease in patients with cystic fibrosis.

We retrospectively studied 20 patients with cystic fibrosis who underwent surgery for gallbladder disease from 1973 to 1986. A long delay between the onset of symptoms and the diagnosis was noted (mean 7.4 months). This delay was attributed to masking of the symptoms of biliary disease by the malabsorption and pulmonary symptoms seen in this patient population. There was a notable lack of common bile duct disease in our patients as well as in those reported in the literature. This may have been due to a combination of factors: the increased viscosity of the mucus, the small caliber of the gallbladder and ductal system, and the hypotonicity of the gallbladder. We do not recommend routine intraoperative cholangiography in patients with cystic fibrosis and gallbladder disease. Cystic fibrosis is a disease with progressive pulmonary deterioration. Cholecystectomy can be performed in these patients with relative safety if careful preoperative and postoperative care is provided. We recommend early operative intervention in the patient with gallbladder disease and cystic fibrosis.

Adolescent↗

PubMed1987

Effects of somatostatin on gallbladder emptying.

Because approximately 80% of reported patients with somatostatinomas have gallstones, this study was performed to determine the effects of exogenous somatostatin on gallbladder emptying responses to liquid and solid meals, direct cholinergic stimulation by bethanechol, indirect cholinergic stimulation by sham feeding, and intravenously administered octapeptide of cholecystokinin. Gallbladder emptying was quantitated using 99mTc-HIDA and a gamma-camera on line to a digital computer. Somatostatin, administered at a dosage of 7 micrograms/kg X h, prevented the gallbladder emptying responses to both test meals, sham feeding, and bethanechol. The maximal gallbladder emptying response to octapeptide of cholecystokinin at 5.0 ng/kg X min was reduced from 93.2% +/- 4.8% to 57.1% +/- 9.9% (p less than 0.01) and to octapeptide of cholecystokinin at 0.5 ng/kg X min from 91.3% +/- 5.3% to 14.8% +/- 4.2% (p less than 0.01). These findings suggest that somatostatin is a potent inhibitor of gallbladder emptying in humans. This may be an important factor in the development of gallstones in patients with somatostatinomas.

Adult↗

PubMed1989

Effect of dietary cholesterol on phosphatidylcholines and phosphatidylethanolamines in bile and gallbladder mucosa in the prairie dog.

Humans with cholesterol gallstones have been reported to have alterations in the molecular species of phospholipids in bile. Both decreases in phospholipids with linoleic acid and increases in those with arachidonic acid have been found. The purpose of this study was to investigate the effect of a lithogenic diet (0.34% cholesterol) on the relative abundance of individual molecular species of phospholipids in the biliary tract of the prairie dog. In hepatic bile, cholesterol feeding resulted in increases in phospholipid species containing arachidonate and decreases in the major species containing its precursor, linoleate. In gallbladder bile of both control and cholesterol-fed animals, phospholipid species containing linoleate were significantly less abundant than in hepatic bile, suggesting that linoleoyl species were selectively absorbed by the gallbladder epithelium. This apparent uptake was significantly increased by cholesterol feeding. Phosphatidylcholines and phosphatidylethanolamines containing arachidonate were also significantly increased in the gallbladder mucosa of the cholesterol-fed animals. These increases in arachidonate-containing phospholipids in the gallbladder mucosa may contribute to the increase in gallbladder prostaglandin synthesis that precedes gallstone formation in this animal model.

Animals↗

PubMed1993

Inositol trisphosphate restores impaired human gallbladder motility associated with cholesterol stones.

BACKGROUND: Gallbladder motility is impaired in specimens with cholesterol stones but normal with pigment stones. METHODS: Muscle cells obtained from 19 human gallbladders with cholesterol stones and 11 with pigment stones were enzymatically digested and contracted with cholecystokinin octapeptide (CCK-8), acetylcholine, and KCl. RESULTS: Muscle cells from pigment stones had a greater contraction than cells from cholesterol stones. CCK-8-induced contraction was unaffected by calcium-free media but was blocked by strontium. Potassium-evoked contraction was blocked by a calcium-free media and unaffected by strontium. Inositol triphosphate (IP-3)-induced contraction was similar to the contraction caused by CCK-8 in permeable cells from pigment stones but was greater than the response to CCK-8 in cells from cholesterol stones. CONCLUSIONS: Muscle cells from gallbladders with cholesterol stones contract less than cells from gallbladders with pigment stones; CCK-8-induced contraction only uses stored calcium; and IP-3 causes contractions of equal magnitude in cells from gallbladders with cholesterol and pigment stones. These abnormalities could result from an impaired receptor activation of the mechanism for IP-3 generation and release of stored calcium.

Acetylcholine↗

PubMed1993

Projections of nerve cells from the duodenum to the sphincter of Oddi and gallbladder of the Australian possum.

BACKGROUND: This study investigated the existence of direct neural connections between the duodenum and the biliary tract in the Australian possum. METHODS: Retrogradely transported neuronal dyes, Fast Blue and Dil, were injected into the wall of the gallbladder and the sphincter of Oddi. The duodenum, biliary tract, and sympathetic and sensory ganglia were examined for the presence of labeled cell bodies. RESULTS: Two to 3 weeks after gallbladder injection, labeled nerve cell bodies were found in the myenteric plexus of the proximal duodenum but were rare in the duodenum distal to the sphincter of Oddi. No neurons were found in the submucous plexus. Labeled nerve cells were also found in the sphincter of Oddi. After injection of the sphincter, labeled neurons were in both the submucous and myenteric plexuses of the duodenum, on either side. Approximately one third of labeled myenteric neurons were immunoreactive for enkephalin. Labeled cell bodies were also in the coeliaco-mesenteric, nodose, and dorsal root ganglia after both gallbladder and sphincter injection. After a myotomy on the proximal duodenum, no neurons were labeled on the pyloric side of the lesion by subsequent sphincter injection of dye. CONCLUSIONS: Direct neural pathways connect the duodenum with the gallbladder and the sphincter of Oddi, and the sphincter with the gallbladder; this implies that enteric nerve circuits participate in coordinating duodenal and biliary functions.

Animals↗

PubMed1994

Adenovirus-mediated transfer of human lipase complementary DNA to the gallbladder.

BACKGROUND/AIMS: Despite many improvements in current therapy, exocrine pancreatic insufficiency remains a significant problem in cystic fibrosis. To establish a new therapy for exocrine pancreatic insufficiency, the feasibility of transferring the human pancreatic lipase complementary DNA to the gallbladder as a possible target using a recombinant adenovirus vector was evaluated. METHODS: The adenovirus vector AdCMV. Lip was constructed using the cytomegalovirus immediate early promoter to drive the human pancreatic lipase complementary DNA. In vitro infection of the human gallbladder epithelial cell line HS-181 and ex vivo infection of the sheep gallbladder with AdRSV. beta-gal (an adenovirus vector containing the Escherichia coli lacZ [(beta-galactosidase] gene) or AdCMV. Lip were evaluated. RESULTS: The supernatant from AdCMV. Lip-infected HS-181 showed the secretion of active lipase for at least 2 weeks in vitro. The epithelium of gallbladder infected with AdRSV.beta-gal ex vivo showed the expression of the beta-galactosidase. The fluid from the gallbladder lumen infected with AdCMV. Lip showed the increased lipase activity. CONCLUSIONS: These observations show that an adenovirus vector can transfer a human pancreatic enzyme in vitro and ex vivo, suggesting the feasibility of in vivo gene therapy for exocrine pancreatic insufficiency in cystic fibrosis.

Adenoviridae↗

PubMed1995

Postprandial gallbladder motor function: refilling and turnover of bile in health and in cholelithiasis.

BACKGROUND & AIMS: Impaired gallbladder emptying is implicated in gallstone disease. Ultrasonography and scintigraphy have shown conflicting results because the former is influenced by postprandial refilling, whereas the latter is not influenced by refilling. The aim of this study was to measure postprandial refilling and turnover of bile by combining the two techniques. METHODS: Simultaneous scintigraphy and ultrasonography were used in 14 patients with gallstones and 11 healthy controls. Measurements were performed while the patients were fasting and at 10-minute intervals after a standard meal for 90 minutes, and the measurements were used to calculate postprandial refilling, turnover of bile (in milliliters), and turnover index. RESULTS: Ultrasonography and scintigraphy provided different gallbladder emptying patterns. Compared with controls, patients with gallstones had impaired emptying by both scintigraphy (P < 0.0001) and ultrasonography (P < 0.01). Postprandial refilling and turnover were both reduced between 60 and 90 minutes (P < 0.05), and the turnover index was markedly reduced (1.8 vs. 3.5; P < 0.001). CONCLUSIONS: Simultaneous scintigraphy and ultrasonography provide a new model of gallbladder motor function showing that refilling begins immediately postprandially. In healthy controls, the gallbladder postprandially handles up to six times its basal volume within a period of 90 minutes, but this turnover of bile is markedly reduced in cholelithiasis causing a reduced washout effect of the gallbladder contents, including cholesterol crystals.

Analysis of Variance↗

PubMed1992

Duodenal acidification and intra-arterial injection of CCK8 increase gallbladder motility in the rainbow trout, Oncorhynchus mykiss.

A sensitive method for in vivo measurement of intra-gallbladder pressure in free swimming rainbow trout (Oncorhynchus mykiss) is described. The method gives information on changes in gallbladder pressure after either instillation of liquids into the duodenum or infusion/injection of agents into the circulatory system. Blood samples can also be taken. Duodenal acidification is a potent initiating factor for gallbladder motility in the rainbow trout. Intra-arterially injected sulfated octapeptide of cholecystokinin is also a potent excitatory agent for activating the gallbladder. Acidification of the upper intestine causes release of cholecystokinin, which affects gallbladder motility in trout as in mammals.

Animals↗

PubMed1992

Septate gallbladder with cholelithiasis: a cause of chronic abdominal pain in a 6-year-old child.

This report describes the case of a 6-year-old girl with septate gallbladder and cholelithiasis without cholecystitis, an uncommon condition associated with chronic abdominal pain. The absence of smooth muscle components within the gallbladder septae supports an embryogenic abnormality that may have occurred early during the maturation of the gallbladder lumen. In concert with other predisposing factors, the septa may have induced gallstones and, thus, the patient's symptoms. Although rare, gallbladder abnormalities may cause abdominal pain in children and should be included in the differential diagnosis. Early ultrasound should be obtained as part of a workup if gallbladder abnormalities are suspected. Elective cholecystectomy is curative.

Abdominal Pain↗

PubMed1985

Effect of estrogen on rabbit gallbladder prostaglandin biosynthesis.

Male and female gallbladder prostaglandin biosynthesis was compared by radiochromatographic analysis of microsomal membrane fractions. Normal female rabbit gallbladder total prostaglandin activity was 10-fold higher than the normal male rabbit gallbladder total prostaglandin activity. The normal male rabbit extracts produced PGF2 alpha and PGE2 as the major arachidonic acid metabolites. The normal female rabbit extracts synthesized PGI2 and PGE2 (20-fold higher activity than the normal male) as the major arachidonic acid metabolites present. The effect of estrogen was studied by comparing prostaglandin activity in ovariectomized female rabbits given high-dose estrogen, low-dose estrogen, and no estrogen. The zero estrogen group prostaglandin activity was 5-fold lower than the normal female group. Treatment with low- or high-dose estrogen restored the gallbladder prostaglandin activity to the level of the normal rabbit gallbladder prostaglandin activity.

Animals↗