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Metallothionein expression in carcinoma of the gallbladder.

AIMS: Metallothioneins (MT) are sulphur-rich, low molecular-weight, intracellular metal-binding proteins with a possible role in carcinogenesis of some human tumours. Metallothionein expression in gallbladder cancer has not been studied previously. METHODS AND RESULTS: Immunohistochemical expression of metallothionein was studied in 42 gallbladders (27 cases of carcinoma of the gallbladder, eight chronic cholecystitis and seven cases of normal gallbladder). Metallothionein expression was significantly higher in cases with carcinoma of the gallbladder (70.37%) as compared to chronic cholecystitis (25%) and normal gallbladders (0%). There was a trend suggestive of increasing MT expression with increasing histological dedifferentiation of carcinoma of the gallbladder. CONCLUSIONS: The increased expression of MT in cases of carcinoma of the gallbladder may represent an increased exposure to heavy metals, which are known carcinogens, and may have a role in gallbladder carcinogenesis. Metallothionein over-expression in carcinoma of the gallbladder may be relevant to the poor prognosis and chemoresistance seen in these cases.

Adult↗

Evidence that gallbladder epithelial mucin enhances cholesterol cholelithogenesis in MUC1 transgenic mice.

BACKGROUND & AIMS: The gel-forming mucins play an important role in the early stage of cholesterol gallstone formation. We investigated whether the gallbladder epithelial mucin encoded by mucin gene 1 (MUC1) influences susceptibility to gallstones. METHODS: Gallbladder motility and cholesterol absorption, gallstones and expression of the mucin genes in gallbladders, and secretion rates and compositions of biliary lipids were determined in male C57BL/6J mice transgenic for the human MUC1 gene (MUC1.Tg) and wild-type mice before (day 0, on chow) and at 4 weeks on a lithogenic diet containing 1% cholesterol and 0.5% cholic acid. RESULTS: On chow, expression levels of the gallbladder mucin genes were essentially similar between MUC1.Tg and wild-type mice. The lithogenic diet induced 3-fold higher expression levels of Muc1, Muc3, Muc4, Muc5ac, and Muc5b messenger RNA in MUC1.Tg mice compared with wild-type mice. Gallbladder cholesterol absorption and size were significantly greater in MUC1.Tg mice than in wild-type mice regardless of whether the chow or the lithogenic diet was fed. Gallbladder emptying in response to exogenously administered cholecystokinin-8 was significantly reduced in MUC1.Tg mice but not in wild-type mice. At 4 weeks on the lithogenic diet, mucin accumulation was found in all MUC1Tg mice and in 60% of wild-type mice. Consequently, these alterations greatly accelerated cholesterol crystallization and gallstone formation in MUC1.Tg mice. However, biliary lipid secretion rates and cholesterol saturation indices of gallbladder biles were comparable in MUC1.Tg and wild-type mice. CONCLUSIONS: Increased gallbladder epithelial MUC1 mucin enhances cholelithogenesis by promoting gallbladder cholesterol absorption and impairing gallbladder motility in mice.

Animals↗

Relationship of serum leptin concentration and other measures of adiposity with gallbladder disease.

Obesity increases the risk of gallstones, especially in women. Most gallbladder disease studies have used body mass index (BMI) as a measure of overall adiposity, although BMI does not distinguish between fat and lean body mass. Central adiposity may also increase gallstone risk, although this is less well studied. Leptin is a peptide whose serum concentration is highly correlated with total body fat mass. We examined the relationship of gallbladder disease with anthropometric measures and serum leptin concentration in a large, national, population-based study. A total of 13,962 adult participants in the Third National Health and Nutrition Examination Survey underwent gallbladder ultrasonography and anthropometric measurements of BMI, body circumferences, and skinfold thicknesses, and a random subgroup of 5,568 had measures of fasting serum leptin concentrations. Gallstone-associated gallbladder disease was defined as ultrasound-documented gallstones or evidence of cholecystectomy. When controlling for BMI and other gallbladder disease risk factors in multivariate analysis, a test for trend for increasing waist-to-hip circumference ratio and risk of gallbladder disease was statistically significant among women (P =.043) and men (P =.007). BMI remained strongly associated with gallbladder disease among women (P <.001), but was unrelated among men (P =.46). Leptin concentration was associated with gallbladder disease in both sexes (P <.001), but not after controlling for BMI and waist-to-hip circumference in either women (P =.29) or men (P =.65). In conclusion, waist-to-hip circumference ratio was related to gallbladder disease among women and men. Serum leptin concentration was not a better predictor of gallbladder disease than anthropometry.

Adipose Tissue↗

Studies on the mechanism of non-visualization of diseased human gallbladders during oral cholecystography.

Oral cholecystography is a well established method for studying the human gallbladder and radiological non-visualization of the gallbladder has been shown to correlate highly with the presence of disease. The exact mechanism by which diseased gallbladders fail to visualize is unclear, but may be due to a failure of the gallbladder to concentrate the luminal contents. Concentration of gallbladder contents is achieved by the reabsorption of water, the driving force for which is active sodium (Na+) absorption. Therefore Na+ transport was studied by measuring the flux of Na22 across isolated human gallbladder mucosa (obtained at cholecystectomy) and compared with the results of oral cholecystography and histological grading. In 27 gallbladders studied, 59% absorbed Na+, whilst the remainder secreted Na+. Comparison with histological grading showed that as gallbladders became more diseased they absorbed less Na+ and were more likely to secrete Na+. In addition, gallbladders that absorbed Na+ were significantly more likely to visualize on cholecystography than those that secreted Na+. These results indicate that some diseased human gallbladders secrete, rather than absorb, Na+ and suggest that the mechanism for radiological non-visualization is failure of fluid absorption and the development of active fluid secretion.

Cholecystography↗

Relationship of gallbladder contour, fasting volume and emptying to body size indices in normal subjects and patients with gallstones.

Fasting gallbladder volume and fasting gallbladder roundness index (ratio of anteroposterior diameter to gallbladder length) were estimated by ultrasonography in 182 normal subjects and 43 patients with gallstones and correlated to body size indices. In 20 of the normal subjects, gallbladder emptying was assessed and correlated to gallbladder roundness index. Gallstone patients had a larger fasting gallbladder volume as compared to normals (42 +/- 10 vs 22 +/- 7 (SD) ml, p < 0.001). Gallbladder fasting volume was found to be significantly related to roundness index (p < 0.001) and body surface area (p < 0.0001) in normals, but not in patients with cholelithiasis. Subjects with a roundness index > 0.3 showed a less-complete gallbladder emptying as compared to those with a roundness index < 0.3 (p < 0.01). It is concluded that increased body size, but not obesity alone, is associated with an increased gallbladder fasting volume, and that a rounder gallbladder tends to empty less completely.

Adult↗

Increases in plasma motilin follow each episode of gallbladder emptying during the interdigestive period, and changes in serum bile acid concentration correlate to plasma motilin.

BACKGROUND: The relationship between each single period of gallbladder emptying during the migrating motor complex (MMC) cycle and changes in concentration of plasma motilin and serum bile acids is unknown. METHODS: The variations in the concentration of plasma motilin and serum bile acids in relation to interdigestive gallbladder motility and the MMCs was studied in nine healthy male volunteers. A method combining biliary scintigraphy (99mTc-labelled dimethyl-iminodiacetic acid) and continuous pressure recording from the antroduodenal region was used. RESULTS: During 9 MMC cycles a total of 15 episodes of gallbladder emptying were observed with a median (range) duration of 25 min (15-45 min). Each episode of gallbladder emptying was followed by a steep increase in plasma motilin, reaching a median value of 30 pmol/l (13-43 pmol/l), corresponding to an increase of 18 pmol/l (4-33 pmol/l). The increase in plasma motilin started at the beginning of gallbladder emptying, but the peak value was not reached until a median of 20 min (10-45 min) later. Low plasma motilin concentrations were found between the emptying periods in cases with two or more emptying during the MMC cycle. The serum concentration of bile acids also showed a cyclic variation in relation to gallbladder motility. During periods of gallbladder emptying serum bile acid concentration had a median value of 1.78 mumol/l, as compared with a median value of 1.17 mumol/l during periods of gallbladder filling. This difference did not reach significance, however. In the pooled data from all subjects, a significant correlation (p < 0.01) between the serum concentration of bile acids and plasma concentration of motilin was found. CONCLUSION: Gallbladder emptying was followed by a steep increase in plasma motilin concentration, and in cases of two or more emptying periods during the MMC cycle the concentration decreased in between. The shape of the serum bile acid profile is dependent on the intestinal transport and absorption of bile acids, and the significance of the cyclic variation in serum concentration of bile acids in relation to plasma motilin, gallbladder motility, and MMC needs further investigation.

Adult↗

Gallbladder function and recurrent stones of the biliary tract in patients after endoscopic sphincterotomy.

BACKGROUND: Change in gallbladder function may occur in patients with an intact gallbladder after endoscopic sphincterotomy (EST). This study was designed to evaluate the factors influencing gallbladder filling after EST and the correlation between gallbladder function and stone recurrence. METHODS: Sixty Chinese patients with symptomatic choledocholithiasis and an intact gallbladder received EST to clear the bile ducts. They were further investigated with sphincter of Oddi manometry (SOM), quantitative cholescintigraphy (QC), and long-term clinical follow-up. RESULTS: Fifty-six of the 60 patients in the study group were confirmed to have a loss of sphincteric function by SOM. QC showed normal gallbladder filling in 35 of these patients and delayed or non-filling in 21 patients. A significantly higher incidence of normal gallbladder filling occurred in patients with juxtapapillary diverticulum than in those without (P < 0.02), but preexisting cholecystolithiasis had no effect on it. During the follow-up period (median, 32 months: range, 9-54 months) 10 of 56 patients developed recurrent choledocholithiasis. There was no correlation between the status of gallbladder filling, preexisting cholecystolithiasis, and recurrent stones, but 9 of the 10 patients with recurrent stones had a juxtapapillary diverticulum. Repeated endoscopic treatment was satisfactory in eight patients, and only two patients received cholecystectomy. CONCLUSIONS: EST does not alter gallbladder function in most patients. Juxtapapillary diverticulum may facilitate gallbladder filling after EST, but it is also a possible factor for recurrent choledocholithiasis.

Aged↗

Usefulness of intraductal ultrasonography in gallbladder disease.

This study was designed to compare intraductal ultrasonography of the gallbladder wall with histopathologic findings and to assess the clinical usefulness of this imaging method in gallbladder disease. Thirty-one gallbladder specimens were examined by intraductal ultrasonography retrospectively. The gallbladder is composed of three layers: an innermost hyperechoic layer, a middle hypoechoic layer, and an outermost hyperechoic layer. The second layer on ultrasonograms corresponds to the muscle layer plus the fibrous tissue of the superficial perimuscular connective tissue layer. In cases in which the thickness of the second layer was 500 microns or less, little fibrous tissue was seen and the second layer was approximately identical to the muscle layer on sonograms. Clinical study was performed on 22 gallbladders. The use of a guidewire through the papilla facilitated intraductal ultrasonographic examination. The intraductal sonographic probe could be inserted into the gallbladder fundus in 13 of 22 cases. In nine unsuccessful cases, technical difficulties were as follows: sharply angulated gallbladder (four cases), stenosis of the gallbladder (two cases), difficulty in transmitting power in the correct direction (three cases). With regard to the area visualized in 13 successful cases, in three cases the area visualized was 100%, in seven cases it was 75%, and three cases it was 50%. Intraductal ultrasonographic images could be obtained in 83.3% (10 of 12) of elevated lesions of the gallbladder. The indications for intraductal ultrasonography will be cases in which an abnormality was detected by transabdominal ultrasonography or other modalities in which the physician does not know whether or not to operate. In conclusion, we defined the intraductal sonographic images of gallbladder wall and clarified the clinical indications for use of this imaging method.

Gallbladder↗

Cholecystokinin prophylaxis of parenteral nutrition-induced gallbladder disease.

Recent studies indicate that long-term total parenteral nutrition (TPN) induces gallstone formation and acalculous cholecystitis in humans. Cholecystectomy is hazardous for these patients because they frequently have multiple medical problems and have undergone numerous abdominal operations. The present study was designed to develop a method to prevent TPN-induced gallbladder disease. The authors tested the hypothesis that a single daily intravenous infusion of cholecystokinin-octapeptide (CCK-OP) will prevent TPN-induced gallbladder stasis. Eleven prairie dogs received TPN for 10 days. Six of these animals were given a daily infusion of CCK-OP. Control animals were fed ad lib. Each animal's bile salt pool was labeled with intravenous 3H-cholic acid 16 hours prior to acute terminal experiments. The ratio of gallbladder to hepatic bile 3H-cholic acid specific activity (Rsa) provides an index of gallbladder stasis. A Rsa of less than 1.0 indicates gallbladder stasis. TPN animals had a Rsa of 0.54 +/- 0.13 (p less than 0.01 vs. controls), indicating stasis of bile in the gallbladder. Daily CCK-OP infusions resulted in a Rsa of 0.92 +/- 0.10 (p less than 0.05 vs. TPN without CCK-OP), indicating that TPN-induced gallbladder stasis is prevented by daily CCK-OP. Control animals had a Rsa of 1.03 +/- 0.06. The cholesterol saturation indices of gallbladder and hepatic bile were not increased by TPN or CCK-OP. These data indicate that 1) TPN induces gallbladder stasis but does not increase bile lithogenic index; and 2) daily injections of CCK-OP prevent TPN-induced gallbladder stasis.

Animals↗

Gallbladder carcinoma in the era of laparoscopic cholecystectomy.

OBJECTIVE: To assess the usefulness of laparoscopic cholecystectomy for unsuspected and suspected gallbladder carcinoma. DESIGN: Retrospective review with a mean follow-up of 27 months, ranging from 1 to 47 months. SETTING: University hospital and 8 affiliated hospitals. PATIENTS: Of 2616 laparoscopic cholecystectomies performed over 4 years, 24 gallbladder carcinomas were treated by laparoscopic cholecystectomy and retrospectively reviewed. RESULTS: The clinical course depended on the histopathologic depth of invasion of gallbladder carcinoma. All 6 cases of pathologic tumor (pT) stage in situ (pTis) gallbladder carcinoma and 2 cases of pT1 gallbladder carcinoma showed no invasion to the lymphatic, venous, or perineural spaces, and these 8 patients were all doing well from 2 to 19 months (mean, 11 months) after laparoscopic cholecystectomy. Sixteen cases of pT2 or pT3 gallbladder carcinoma invaded the subserosal layer or the liver, and 5 of the 16 patients were dead of liver dysfunction, abdominal wound recurrence, or liver metastasis 5 days and 7, 12, 15, and 18 months after operation, although additional resection of the liver bed with lymph node dissection was performed after laparoscopic cholecystectomy in 4 of these 5 patients. Abdominal wall recurrence in the absence of distant metastasis was present in 3 (19%) of the 16 patients with pT2 or pT3 gallbladder carcinoma due to inoculation of cancer cells in the abdominal stab wounds where the gallbladder or laparoscope was removed. CONCLUSIONS: Gallbladder carcinoma at the pTis or pT1 stage removed laparoscopically needs no other treatment. We recommend that the gallbladder be removed by vinyl bag and port sites be excised or washed with normal saline to prevent port site recurrence in patients with laparoscopic cholecystectomy for pT2 or pT3 carcinoma.

Adenocarcinoma↗

Monolayer and three-dimensional cell culture and living tissue culture of gallbladder epithelium.

Several models for preparing and isolating human and animal gallbladder epithelial cells, including low-grade gallbladder carcinoma cells, as well as proposed systems for culturing these isolated epithelial cells are reviewed here. Several reports concerning tissue culture of the gallbladder are also reviewed. The cell culture systems are divided into monolayer cell culture on collagen-coated or uncoated culture dishes or other culture substrate and three-dimensional cell culture in collagen gel. To prepare and isolate gallbladder epithelial cells, digestion of the gallbladder mucosa, abrasion of the mucosal epithelial cells, and excision of epithelial outgrowth of mucosal explants are applied. In monolayer cell culture, most of the specific biological features of isolated and cultured cells characteristic to the gallbladder are gradually lost after several passages, though quantitative and objective analyses of the pathophysiology of cultured cells and their secretory substances can be performed. Tissue culture using explants of the gallbladder has mainly been used for physiological studies of the gallbladder, such as investigating the transport of water and electrolytes. In this tissue culture system, quantitative assessment is difficult, though the original and specific biological and histological characteristics of the gallbladder are retained. Three-dimensional collagen gel culture could be an ideal model combining monolayer cell culture and tissue culture systems, and create controllable conditions or environments when several biologically active substances, such as growth factors, proinflammatory cytokines and adhesion molecules, are added to the culture medium. Advantages and shortcomings of individual cultivation models are discussed, and selecting the culture model most appropriate to the purpose of the study will facilitate investigations of the biology and pathogenetic mechanisms of gallbladder diseases such as cholelithiasis.

Animals↗

Structure, afferent innervation, and transmitter content of ganglia of the guinea pig gallbladder: relationship to the enteric nervous system.

Although a well-developed plexus of nerves and ganglia is known to be present in the wall of the gallbladder, little has previously been learned about the function or organization of this innervation. The current study was undertaken in order to evaluate the hypothesis that the ganglionated plexus of the gallbladder is analogous to elements of the enteric nervous system (ENS). The ganglionated plexus of the gallbladder was found to resemble closely the submucosal plexus of the small intestine in its organization into two irregular anastomosing and interwoven networks of ganglia, in the numbers of neurons per ganglion, and in the manifestation of histochemically demonstrable acetylcholinesterase activity in virtually all ganglion cells. In common with enteric ganglia, laminin immunoreactivity was observed to be excluded from the interiors of gallbladder ganglia, which were surrounded by a periganglionic laminin-immunoreactive sheath. As in the submucosal plexus, intrinsic substance P-, vasoactive intestinal polypeptide (VIP)-, and neuropeptide Y (NPY)-immunoreactive neurons were seen in the ganglionated plexus of the gallbladder. Extrinsic nerves in the gallbladder that degenerated following chemical sympathectomy with 6-hydroxydopamine (6-OHDA), and which contained NPY, tyrosine hydroxylase (TH), and dopamine-beta-hydroxylase (DBH) immunoreactivities, formed a perivascular plexus closely associated with blood vessels. Endogenous catecholamines could also be demonstrated in these perivascular nerves by aldehyde-induced histofluorescence. In addition to perivascular nerves, paravascular nerve bundles were observed that were loosely associated with vessels, did not degenerate following administration of 6-OHDA, and contained NPY immunoreactivity. Other paravascular nerves, probably visceral sensory axons, coexpressed substance P and calcitonin-gene-related peptide (CGRP) immunoreactivities. The ganglionated plexus of the gallbladder resembled enteric ganglia in having intrinsic 5-hydroxytryptamine (5-HT)-immunoreactive cells and highly varicose nerve fibers. The 5-HT-immunoreactive gallbladder axons were, like those of the gut, resistant to 6-OHDA, and separate from fibers that expressed TH immunoreactivity. Differences between the ganglionated plexus of the gallbladder and enteric ganglia of the small intestine included in the gallbladder are 1) the presence of TH-immunoreactive cells that contain an endogenous catecholamine, but not DBH; 2) DBH-immunoreactive neurons, some of which coexpress substance P immunoreactivity, but which contain neither a catecholamine nor TH immunoreactivity; 3) an apparent absence of CGRP-immunoreactive cell bodies.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholinesterase↗

Albumin absorption and protein secretion by the gallbladder in man and in the pig.

To study albumin absorption by the gallbladder in man, an in vitro model was first established in the pig and compared with in vivo function in the same species. Water and electrolyte transport and 125I-albumin absorption and protein secretion in vivo and in vitro were compared. Then similar in vitro studies were performed on human gallbladders obtained at surgery. The in vivo study in the pig was performed without disturbing the gallbladder except to tie a cannula in the cystic duct end. The in vitro model was identical in the pig and human gallbladders. Gallbladders were excised using a technique causing minimal injury and anoxia. They were oxygenated on both mucosal and serosal surfaces in a temperature-controlled environment. Luminal and external bath test solutions consisted of modified Ringers bicarbonate with added glucose; luminal solutions also contained 125I-albumin from different species, depending on the study. Active absorption of sodium and water occurred in both types of studies in the pig but in vivo absorption rates were considerably greater than in vitro rates. Albumin absorption in vivo was substantial; although present in vitro, the absorption of albumin was diminished relatively more than electrolyte transport rates. Protein secretion rates into the gallbladder were similar in vitro and in vivo. The results of studies in the human gallbladders in vitro were similar to the pig, except albumin absorption was greater. Some human gallbladders were obtained from control patients and some from patients with cholesterol gallstones. There were no significant differences between the two groups for any of the variables studied; however, the numbers were small and some control gallbladders were not normal gallbladders.

Absorption↗

Gallbladder emptying stimuli in obese and normal-weight subjects.

Gallbladder stasis may be an important factor in the pathogenesis of cholesterol-gallstone formation in some individuals. We investigated gallbladder function in a group of nondieting, gallstone-free, healthy subjects with normal (22 +/- 1 kg/m2) and high (36 +/- 1 kg/m2) body mass indexes. Fasting gallbladder volume (28.2 +/- 4.4 ml) and residual volume after maximal emptying (8.4 +/- 2.3 ml) in high-body-mass index subjects were not significantly different from those of normal-body-mass index subjects (20.5 +/- 2.5 ml and 4.2 +/- 1.3 ml, respectively). The percentage of gallbladder emptying (71% +/- 5%) and the rate of gallbladder emptying (-1.9 +/- 0.3 x 10(-2) min-1) in high-body-mass index subjects in response to a maximal emptying stimulus was similar to the percentage of emptying (78% +/- 6%) and rate of emptying (-2.3 +/- 0.6 x 10(-2) min-1) in normal-body-mass index subjects. A liquid meal containing less than 1 gm fat, 14 gm protein and 6 gm carbohydrate resulted in both a decreased rate of gallbladder emptying and an increased residual gallbladder emptying and an increased residual gallbladder volume in both groups. The addition of 10 or 20 gm (but not 4 gm) of fat to the liquid meal restored gallbladder emptying to the maximal-stimulus level. These results demonstrate that gallbladder emptying in response to a single liquid meal stimulus is not altered in obesity and that dose-response relationships to fat are similar in obese and normal-weight individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Hepatic bile versus gallbladder bile: a comparison of protein and lipid concentration and composition in cholesterol gallstone patients.

Many studies have demonstrated that gallbladder bile (but not hepatic bile) of animals or patients with cholesterol gallstones contains higher protein concentrations than does gallbladder bile of control patients without stones or with pigment stones. The underlying defect has not been elucidated. To establish whether there is net production or net absorption/degradation of protein by gallbladder epithelium for different classes of protein, paired samples of hepatic and gallbladder bile were obtained from fourteen patients with cholesterol gallstones during elective cholecystectomy. In these paired samples, lipid and protein composition were determined. To obtain the concentration ratio (CR) of protein and lipid, its concentration in the gallbladder was divided by the concentration determined in the paired hepatic bile sample. The CR of bile salts was used as a parameter for water absorption in the gallbladder. Of the biliary proteins that were determined only mucin, albumin, immunoglobulin (Ig) G, and aminopeptidase N appeared to increase in the gallbladder from another cause than water absorption. A strong correlation was found between mucin, albumin, and IgG. Haptoglobin, alpha1-acid glycoprotein, IgM, and IgA appeared to be absorbed by gallbladder epithelium in the majority of patients. In cholesterol gallstone patients, total protein concentration in gallbladder bile of cholesterol gallstone patients is increased when compared with hepatic bile. The increase in protein concentration cannot be explained for all bile samples solely by water absorption. In this study we show that the defect is largely caused by a selective increase in albumin, mucin, and IgG. All other proteins which were investigated are taken up by the gallbladder.

Bile↗

Incidentally discovered gallbladder cancer: role of cryotherapy.

BACKGROUND AND OBJECTIVES: Carcinoma of the gallbladder is the most common malignancy of the biliary tree. There is no standard surgical approach to the treatment of gallbladder cancer. Extended cholecystectomy with partial or complete hepatic lobectomy has resulted in high morbidity and poor long-term survival. This report describes cryotherapy of the gallbladder fossa as an alternative to liver resection in the treatment of gallbladder cancer. METHODS: A group of patients underwent cryotherapy to the gallbladder fossa for local control of gallbladder cancer. Portal lymph node dissection was performed at the same time and patients with positive lymph nodes received post-operative chemotherapy and radiation; negative node patients were observed. RESULTS: Seven patients underwent surgery. Gallbladder cancer had been incidentally found in all patients. Median hospital stay was 4 days. Five patients had positive nodes. Complications included biliary stricture, pleural effusion, congestive heart failure exacerbation, and pulmonary embolus. Mean disease-free survival for patients with T2 tumors was 11.7 months. Mean disease-free survival for patients with T3 tumors was 16.3 months. Mean disease-free survival for lymph node positive patients was 14.8 months compared to 13 months for node negative patients. No local recurrences have been detected in the gallbladder fossa. CONCLUSIONS: This study suggests cryotherapy to the gallbladder fossa done concomitantly with portal lymph node dissection may represent a safe and effective alternative to hepatic resection in the treatment of gallbladder cancer.

Adenocarcinoma↗

Association between false negative hepatobiliary scans and initial gallbladder visualization after 30 min.

We have reviewed the experience of our institution and the literature concerning the use of hepatobiliary scintigraphy for the diagnosis of acute cholecystitis. The aim of this study was to assess whether the hepatobiliary scintigraphic finding of initial gallbladder visualization within 30 min is a more reliable criterion for excluding acute cholecystitis than gallbladder visualization within 1 h after tracer injection. In our institution's consecutive series, 113 of 211 hepatobiliary studies had gallbladder visualization within 1 h. Gallbladder visualization time in this group had a log normal distribution, with gallbladder visualization occurring within 30 min in 107 of 113 (95%). Gallbladder visualization occurred between 31 and 60 min in only 6 (5%); nevertheless, our one false negative study came from this small subgroup of patient studies (P = 0.05). Review of the literature (1645 patients with iminodiacetic acid [99mTc-IDA] derivative studies) revealed 6 further timed false negative results with gallbladder visualization within 1 h. Of these studies, in 4 (67%) the gallbladder was visualized between 31 and 60 min and in only 2 before 30 min. One of these latter 2 patients had a rare anatomy. Analysis of the pooled institutional and literature data gave an estimated false negative rate of 21% if the gallbladder was visualized between 31 and 60 min. This was significantly higher (P less than 0.001) than the 0.5% false negative rate when the gallbladder was seen prior to 30 min, but similar to the false negative rate of 16% reported by Weissmann et al. for studies with initial visualization after 1 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Gallbladder carcinoma with biliary invasion: clinical analysis of the differences from nonbiliary invasion.

Gallbladder carcinoma is the most common malignancy of the biliary tract. Because of a lack of specific presentations, this condition frequently is diagnosed only at an advanced stage. The clinical difference between gallbladder carcinoma with and without biliary involvement remains uncertain. This study recruited all patients with gallbladder carcinoma treated at Chang Gung Memorial Hospital (Taoyuan, Taiwan) from 1987 to 2002. The sample included 120 patients aged 28 to 91 years (mean 65.5 +/- 12.3 years) (39 men, 81 women), whose medical records were reviewed retrospectively. Based on the 2002 newly revised TNM classification, 25, 38, 28, and 29 patients had stage I, II, III, and IV disease, respectively. After we excluded patients with stage I, the other patients were classified into two groups as follows: group I, gallbladder carcinoma with biliary invasion (n = 41); group II, carcinoma without biliary involvement (n = 54). The clinical presentations, laboratory data, operative methods, and outcome of these two groups were compared. The two groups did not differ in terms of age, sex distribution, cholelithiasis, and most clinical presentations. Chemistry laboratory data also identified patients in group I with significantly elevated liver function tests. Group II had a borderline tendency toward better curative resectability than group I (p = 0.09). Survival was significantly better for group I patients who underwent curative resection (n = 5) via cholecystectomy, partial hepatectomy, and bile duct resection than for those with noncurative resection (p < 0.05). However, long-term survival demonstrated that gallbladder carcinoma had the same poor prognosis in the two groups. In conclusion, gallbladder carcinoma with biliary invasion has been found to a more overt clinical presentation and abnormal laboratory data, which might alert clinicians to consider gallbladder carcinoma at an advanced stage or biliary invasion and examine the underlying disease. Generally, the outcome of gallbladder carcinoma is dismal, and radical curative resection combined with cholecystectomy, partial hepatectomy, and bile duct resection perhaps may offer good benefits for advanced gallbladder carcinoma. Furthermore, surgical resection should be performed whenever possible in patients with gallbladder carcinoma to increase life expectancy.

Adult↗