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PubMed1999

Mucosal cell proliferation activity of the gallbladder in children with anomalous arrangement of the pancreaticobiliary duct.

Anomalous arrangement of the pancreaticobiliary duct (AAPBD) is an anatomical maljunction of the bile duct and the pancreatic duct that is frequently associated with gallbladder carcinoma. In patients with AAPBD, it has been postulated that pancreatic juice regurgitates into the biliary tree, and the mixture of refluxed pancreatic juice and stagnant bile juice acts as an irritant factor to the biliary tract epithelium, leading to chronic inflammation and metaplasia. Eventually these mucosal changes may progress to invasive carcinoma. We reviewed clinicopathologic studies on epithelial changes of the gallbladder in patients with AAPBD to clarify the implications relevant to carcinogenesis. Conventional histological studies have shown that the most characteristic change observed in the gallbladder of children with this anomaly was epithelial hyperplasia. Furthermore, the incidence of mucosal hyperplasia was significantly increased in the gallbladder of children in whom the pancreatic duct joined the common bile duct (P-C type) compared with the incidence in children in whom the common bile duct joined the pancreatic duct (C-P type). In addition, cell kinetic studies have demonstrated increased cellular proliferative activity of the gallbladder in children with AAPBD. Cell proliferative activity was significantly elevated in children with the P-C type of AAPBD compared with that in children with the C-P type of anomaly. In conclusion, AAPBD may yield increased cell proliferation in the gallbladder of patients with this anomaly in early childhood, resulting in epithelial hyperplasia. Although it remains unknown which agents are responsible for promoting the activation of cellular function, it seems that bile acids and refluxed pancreatic proteases are likely play a role in such promotion. Further investigations are needed to elucidate the mechanism of increased cellular function.

Adenocarcinoma↗

PubMed1999

Gallbladder torsion: case report and review of 245 cases reported in the Japanese literature.

We report here a case of torsion of the gallbladder in a 73-year-old woman. The patient was admitted to our hospital with right hypochondralgia. Ultrasonography and computed tomography demonstrated a distended gallbladder, with a multilayered wall, which contained no stones. Since the symptoms did not respond to antibiotics, laparotomy was performed. The gallbladder was found to be twisted around its pedicle and to be gangrenous. Cholecystectomy was performed, and the patient had an uneventful postoperative course. We also reviewed 245 cases reported in the Japanese literature. The clinical features of gallbladder torsion, which include low frequency of fever and jaundice, poor response to antibiotic therapy, and acute onset of abdominal pain, may be helpful in the differential diagnosis from acute cholecystitis. Moreover, a highly suggestive sign of gallbladder torsion observed by ultrasonography or computed tomography is a markedly enlarged "floating" gallbladder with a continuous hypoechoic line indicating edematous change in the wall.

Abdomen, Acute↗

PubMed2000

Relation between K-ras codon 12 mutation and p53 protein overexpression in gallbladder cancer and biliary ductal epithelia in patients with pancreaticobiliary maljunction.

It is well known that the incidence of biliary cancer is higher in patients with pancreaticobiliary maljunction (PBM) than in individuals without PBM. However, the relationship between PBM and the carcinogenesis remains unclear. The purpose of the present study was to examine histopathologic changes in the mucosa of the gallbladder and bile duct in patients with PBM, and to investigate K-ras oncogene mutation and overexpression of p53 protein in the mucosa. We examined 47 surgical specimens of gallbladder and 36 surgical specimens of bile duct obtained from 48 patients with PBM. The 48 patients were divided into three age groups: group A (0-3 years), group B (4-39 years), and group C (40 years or more). Investigation of K-ras mutation and overexpression of p53 protein was performed using an enriched polymerase chain reaction (PCR) and enzyme-linked mini-sequence assay (ELMA), and by the streptavidin-biotin (SAB) method, using DO-7 antibodies, respectively. Hyperplastic changes in the gallbladder mucosa were observed in patients in the three groups. However, metaplastic or dysplastic changes were observed in the mucosa of only groups B and C. K-ras gene mutation in the gallbladder mucosa was found in 18.8% of the hyperplastic mucosae in group B and in 20% in group C. The mutation was found in 33.3% of lesions with metaplastic change associated with hyperplastic changes and in 25% of lesions with dysplastic changes in group C. No mutation was observed in the non-cancerous mucosae of gallbladders and bile ducts without congenital dilatation of the bile duct. Overexpression of p53 protein was observed only in carcinoma of the gallbladder; in seven of nine advanced carcinomas and in two of three carcinomas in situ. We concluded that the mucosal epithelia of the biliary system in patients with PBM showed a high frequency of gene mutations and the carcinogenesis appeared in involve a multistage process of mutation in the K-ras gene and the p53 suppressor gene.

Adolescent↗

PubMed2001

Present status of the diagnosis and treatment of gallbladder carcinoma.

Because early carcinoma of the gallbladder causes no specific signs or symptoms, most patients with this disease are diagnosed with advanced-stage tumors. High-resolution ultrasonography and a low index of suspicion for polypoid masses or asymmetric gallbladder thickening represent the best method of early detection. Despite regular preoperative gallbladder imaging, many cancers are only detected intraoperatively or incidentally on pathologic examination. All known or suspected gallbladder cancers should be definitively treated with a laparotomy, not laparoscopic surgery. For early gallbladder cancers (Tis and T1 cancers), simple cholecystectomy is adequate therapy. More advanced-stage carcinomas without distant metastases should routinely be managed with a radical cholecystectomy, which includes partial hepatectomy and regional lymphadenectomy. Any adherent organs should be resected en bloc with the cancer. Pancreatoduodenectomy has been performed in several Japanese centers, but is rarely performed in the West for locally advanced gallbladder cancers. Most patients who undergo curative resection will develop recurrent disease, but there is currently no proven effective adjuvant therapy.

Biopsy↗

PubMed2001

Spontaneous necrosis of gallbladder carcinoma in patient with pancreaticobiliary maljunction.

While gallbladder carcinoma is occasionally associated with pancreaticobiliary maljunction, spontaneous necrosis of carcinoma is extremely rare. We herein present a case of spontaneous necrosis of gallbladder carcinoma associated with direct invasion of viable cancer cell nests to the muscularis propria and subserosal layer located beneath the primary nodules. A 65-year-old Japanese man was admitted to a local hospital, complaining of repeated discomfort in the right hypochondrium. Ultrasonography and computed tomography scanning revealed cholecystitis associated with gallstones. Cholecystectomy was performed, and operative cholangiography demonstrated pancreaticobiliary maljunction. The resected gallbladder showed multiple mixed stones filled with necrotic debris and bile sludge. Scrutiny of the mucosal surface revealed multiple small necrotic nodules in the fundus, which were histologically confirmed to be necrotic remnants of a cancerous glandular structure. Small nests of papillary adenocarcinoma were found beneath the nodules in the muscularis propria and in the venous structure located in the connective tissues next to the divided margin of the gallbladder bed. Resection of S4a and S5 of the liver and resection of the extrahepatic bile duct was then performed to remove the remaining cancerous tissues and/or micrometastasis in the liver and bile duct. The biliary tree was reconstructed with a hepaticoduodenostomy. No cancer nests or any precancerous lesions were found in the additionally resected specimens. This case indicates a unique morphological feature of gallbladder carcinoma associated with pancreaticobiliary maljunction, which provides some insight into the pathogenesis of spontaneous necrosis of gallbladder carcinoma.

Adenocarcinoma, Papillary↗

PubMed2003

Small-cell carcinoma manifesting systemic lymphadenopathy combined with adenocarcinoma in the gallbladder: aggressiveness and sensitivity to chemotherapy.

Small-cell carcinoma of the gallbladder is a very rare tumor. In this report, we describe a patient with small-cell carcinoma combined with adenocarcinoma in the gallbladder. The patient was a 70-year-old man, who clinically manifested systemic lymphadenopathy. An incisional biopsy of Virchow's lymph node revealed small-cell carcinoma. Abdominal computed tomography (CT) showed massive multiple paraaortic lymph node swelling and a round mass in the gallbladder, although chest CT did not show any abnormal masses in the lung. After two courses of chemotherapy (PVP therapy; cisplatin [CDDP], 80 mg/m(2), day 1, intravenous injection; and etoposide [VP-16], 50 mg/m(2), every day, per oral intake; given every 3 weeks) were performed, the systemic lymphadenopathy had completely diminished and only the gallbladder tumor remained on clinical examinations. Endoscopic retrograde cholangiopancreatography (ERCP) revealed nodular tumors in the gallbladder fundus. Cholecystectomy with partial resection of the liver was performed. Pathological examination revealed small-cell carcinoma combined with adenocarcinoma of the gallbladder. We discuss the characteristics and the treatment of this rare tumor.

Adenocarcinoma↗

PubMed2005

Microsatellite instability in preneoplastic and neoplastic lesions of the gallbladder.

BACKGROUND: Gallbladder cancer is very common in Chile and is the leading cause of cancer deaths in women aged over 40 years. However, there is limited information about the molecular changes involved in its pathogenesis. Microsatellite analysis was performed using polymerase chain reaction (PCR)-based assays to identify genetic loci that were altered in neoplastic and preneoplastic conditions of early and advanced gallbladder cancer. Our findings were then correlated with clinicopathological variables and survival time. METHODS: We selected 59 surgical specimens of gallbladder adenocarcinomas (29 early cancers and 30 advanced cancers) and 22 surgical specimens from patients with chronic cholecystitis from a high-risk area for gallbladder cancer (Temuco, Chile). Laser capture microdissection (LCM) was used to harvest tumor cells and preneoplastic lesions. Microsatellite analysis was performed using 13 different markers. The tumors and preneoplastic lesions were also examined with immunohistochemistry for hMLH1, hMSH2, and hMSH6. RESULTS: We found that 10% (6/59) of gallbladder cancers showed high-frequency microsatellite instability (MSI-H), with identical proportions in both early and advanced cancers. In premalignant lesions adjacent to the six MSI-H tumors, we detected instability in two of six examples of intestinal metaplasia (33%) and five of six examples of dysplasia (83%). All MSI-H cases showed an altered pattern with the antibodies studied. MSI status was not associated with survival or other clinicopathological features. No MSI or immunohistochemical alterations were found in the chronic cholecystitis group. CONCLUSIONS: Microsatellite instability was observed in equal proportions in early and late cancers, and it was also found in premalignant lesions, indicating that inactivation of mismatch repair genes occurs early in gallbladder carcinogenesis.

Adenocarcinoma↗

PubMed2006

Gallbladder carcinoma with osteoclast-like giant cells.

Extraskeletal tumors containing multinucleated, osteoclast-like giant cells (OGCs) are uncommon. These neoplasms are most frequently reported in the breast and pancreas. Recently, some authors have suggested that carcinomas containing OGCs may represent a distinct clinicopathological entity with a more favorable prognosis. Occurrence in the gallbladder is extremely rare, with only one previous case. We report here on an additional case of gallbladder carcinoma with an infiltrate of OGCs. A 72-year-old woman presented with postprandial abdominal pain and was found to have a mass in the body of the gallbladder with direct liver invasion. Histological examination showed an adenosquamous carcinoma with an infiltrate of benign OGCs. Immunohistochemical analysis demonstrated that the giant cells were of histiocytic origin. The patient survived for 6 years without evidence of recurrence. This case adds to a small body of literature on gallbladder carcinoma with OGCs. Further studies are required to clearly define the prognostic significance of these giant cells in gallbladder cancer and the differences between adenosquamous carcinoma with OGCs and other gallbladder carcinomas (such as adenocarcinoma and squamous cell carcinoma) with those cells.

Aged↗

PubMed1999

Posttraumatic intra-gallbladder hemorrhage in a patient with liver cirrhosis.

We report a case of intra-gallbladder hemorrhage secondary to blunt abdominal trauma in a patient with liver cirrhosis. A 58-year-old man was admitted to a local hospital with persistent right upper quadrant abdominal pain. Anemia was detected, and computed tomography (CT) revealed a high-density mass in the gallbladder lumen. He was transferred to our hospital because a gallbladder tumor was suspected. He had a history of habitual alcohol abuse and had sustained blunt abdominal trauma in the right upper quadrant 29 days before admission to our hospital (4 days before to the admission local hospital). The intra-gallbladder high-density mass depicted on the CT scan, observed as non-shadowing low-level echoes, was deemed to represent a blood clot on ultrasonography (US) performed 31 days after the trauma. US-guided percutaneous transhepatic gallbladder aspiration and cholecystography confirmed the presence of an old blood clot in the lumen. Because of the patient's persistent pain, a cholecystectomy was performed. The distended gallbladder was filled with old clotted blood.

Cholecystography↗

PubMed2003

Ciliated foregut cyst of the gallbladder: report of a case.

We report the rare case of a gallbladder cyst arising from the foregut remnants. A 36-year-old woman was referred to our hospital after screening ultrasonography (US) detected a tumor in the gallbladder. On admission, she was well and her blood analyses were all normal. US showed a cystic mass with internal high-echoic lesions, and computed tomography (CT) demonstrated a protruding tumor with slight enhancement in the gallbladder. Angiography provided no additional information; however, sequential CT-arteriography (CTA) clearly demonstrated that this tumor was a cystic lesion. Surgical exploration was performed, first because of the difficulty in establishing a definite diagnosis, and also because the patient wanted the tumor removed. The resected specimen contained a unilocular cystic tumor that looked like a submucosal tumor. Histologically, the wall of the cyst was lined by ciliated stratified columnar epithelium with interspersed goblet cells and underlying smooth muscle fibers. The mass was finally diagnosed as a congenital ciliated foregut cyst of the gallbladder. Cysts of the gallbladder are uncommon and the majority are acquired. To our knowledge, this represents only the fourth report of a ciliated foregut cyst of the gallbladder in the literature. Although rare, an awareness of this entity could allow a preoperative diagnosis to be made, whereby surgical exploration may be avoided. CT-A is a very useful diagnostic tool, especially when the nature of the tumor presents a difficult differential diagnosis.

Adult↗

PubMed2005

Height and body mass index in relation to colorectal and gallbladder cancer in two million Norwegian men and women.

OBJECTIVES: The present study aimed at exploring the relations between BMI and stature and colorectal and gallbladder cancer in a huge Norwegian cohort with measured height and weight. MATERIAL AND METHODS: Height and weight were measured in two million Norwegian men and women aged 20-74 during 1963-2001. During follow-up, 47,117 colorectal and 1715 gallbladder cancer cases were registered. Relative risks (RRs) of colorectal and gallbladder cancer were estimated using Cox proportional hazards regression. RESULTS: The risk of colon cancer increased with increasing BMI in men; the RR of colon cancer per unit increase in BMI was 1.04 (95% CI: 1.04-1.05). For mucinous colorectal adenocarcinomas, the risk increased to a larger extent with increasing BMI in both sexes. The RR of colorectal cancer associated with 10 cm increase in height was 1.14 (95% CI: 1.11-1.16) in men and 1.17 (95% CI: 1.14-1.20) in women. The risk of gallbladder cancer increased with increasing BMI in women; the overall RR associated with one unit increase in BMI was 1.06 (95% CI: 1.04-1.07). There was no association between height and gallbladder cancer in either sex. CONCLUSION: The risk of colon cancer increased with increasing BMI in men, and the risk of gallbladder cancer increased with increasing BMI in women. In both sexes, the risk of colon cancer increased with increasing height.

Adenocarcinoma, Mucinous↗

PubMed1997

Isolation and long-term culture of gallbladder epithelial cells from wild-type and CF mice.

Mice with targeted disruption of the cftr gene show pathophysiologic changes in the gallbladder, which correlate with hepatobiliary disease seen in cystic fibrosis patients. As gallbladder epithelium secretes mucin, and as this epithelium consists of a relatively homogenous cell type, study of CFTR function in these cells would be beneficial to delineate the complex cellular functions of this protein. The size and anatomic location of the murine gallbladder makes such studies difficult in vivo. Therefore, the need exists for in vitro models of gallbladder epithelium. We describe a method to isolate and culture murine gallbladder epithelium from wild-type and CF mice. Cells were grown in a monolayer on porous inserts over a feeder layer of fibroblasts. These nontransformed cells can be successively passaged and maintain a well-differentiated epithelial cell phenotype as shown by morphologic criteria, characterized by polarized columnar epithelial cells with prominent microvilli and intercellular junctions. Organotypic cultures showed columnar cells simulating in vivo morphology. This culture system should be valuable in delineating cellular processes relating to CFTR in gallbladder epithelium.

Animals↗

PubMed1976

Primary carcinoma of the gallbladder. The role of adjunctive therapy in its treatment.

Of forty-three patients with carcinoma of the gallbladder discovered ih a twenty-five year period (during which 10,349 patients were diagnosed as having cholelithiasis), eighteen patients (42 per cent) had no obvious tumor outside of the gallbladder at the time of operation, nineteen patients (44 per cent) had local spread of the disease, and six patients (14 per cent) had abdominal carcinomatosis or distant metastasis. In the twenty-one patients who underwent surgical therapy for cure of their disease, the five year survival rate was 33 per cent. The more extensive surgical procedures (other than cholecystectomy alone) did not significantly increase survival. Neither the duration of the symptoms nor the pathologic type of the tumor altered the eventual outcome. No patients with tumor outside the gallbladder at the time of operation survived longer than two years. Compared to those who did not receive it, the fifteen patients treated postoperatively with adjunctive therapy (radiation therapy or chemotherapy or both) lived longer and also were significantly better palliated when tumor outside of the gallbladder was found at the time of operation. From these findings, the routine use of adjunctive therapy is recommended in all patients with disease outside of the gallbladder and serious consideration should be given to its use in all patients found to have carcinoma of the gallbladder.

Adenocarcinoma↗

PubMed1982

Stasis before gallstone formation: altered gallbladder compliance or cystic duct resistance?

Gallbladder stasis occurs before gallstone formation and provides the link between the hepatic secretion of supersaturated bile and cholesterol cholelithiasis. We recently observed that cystic duct resistance increases while sphincter of Oddi resistance is unchanged in the presence of lithogenic bile without gallstones. Whether alterations in gallbladder function also lead to gallbladder stasis has been unclear. Therefore, we tested the hypothesis that before gallstone formation, stasis results from increased cystic duct resistance and altered gallbladder compliance. Adult, male prairie dogs were fed either a trace cholesterol (control) or a 0.4 percent cholesterol-enriched diet. Cystic duct resistance increased but gallbladder compliance was unchanged before gallstone formation. A significant correlation (p less than 0.001) was found between the lithogenic index and cystic duct resistance in pregallstone animals. We conclude that increased resistance to flow across the cystic duct, and not altered gallbladder compliance, is etiologically related to bile stasis, an important event in gallstone formation.

Animals↗

PubMed1992

Subclinical gallbladder carcinoma.

Clinicopathologic features of 31 patients with subclinical gallbladder carcinoma were reviewed in an attempt to determine the parameters for a course of therapy. Subclinical gallbladder carcinoma was defined as a gallbladder carcinoma that was first diagnosed microscopically by surgical pathologists. Of 31 patients, there were 26 women and 5 men, ranging in age from 54 to 84 years (mean age: 68 years). All 31 patients had undergone cholecystectomy for presumed benign gallbladder conditions. The 31 gallbladder carcinomas consisted of 6 carcinomas limited to the mucosa or the muscle coat (m or pm) and 25 carcinomas extending into the subserosal layer with surgical margins free of malignant cells in 14 (ss ew [-]) and affected by malignant cells in 11 (ss ew [+]). Cumulative 1-year, 3-year, and 5-year survival rates of six patients with m or pm carcinoma were 100% (p less than 0.001, versus ss ew [+] at 1 year), 100% (p less than 0.05, versus ss ew [-] at 3 years), and 100% (p less than 0.05, versus ss ew [-] at 5 years) compared with 91% (p less than 0.01, versus ss ew [+] at 1 year), 65%, and 65% of 14 with ss ew (-) carcinoma and 43%, 0%, and 0% of 11 with ss ew (+) carcinoma. Thirteen of the 31 patients died of local recurrence and/or liver metastasis. Univariate logrank analysis of 10 prognostic factors showed that depth of invasion, venous invasion, and surgical margin were prognostic factors. Multivariate Cox-regression analysis of these three profound factors demonstrated that surgical margin and depth of invasion were independent variables. These results showed that m or pm subclinical gallbladder carcinoma does not necessarily require an additional operation, whereas ss ew (-) and ss ew (+) carcinomas necessitate additional resection and adjuvant treatment.

Aged↗

PubMed1986

Regulation of gallbladder cholesterol concentration in the hamster. Role of hepatic cholesterol level.

The goal of this investigation was to determine how alterations in hepatic cholesterol metabolism influence the cholesterol content of gallbladder bile in hamsters. Although the rate of hepatic cholesterol synthesis was varied over 600-fold, there was no direct relationship between the rate of cholesterol synthesis and the cholesterol content of gallbladder bile. However, expansion of the hepatic cholesterol pool by 42-fold resulted in an 11-fold increase in gallbladder bile cholesterol. Examination of four subfractions of the hepatic cholesterol pool revealed that the cholesterol content of gallbladder bile was most consistently correlated with the free cholesterol level in both hepatic tissue and hepatic microsomes from all experimental groups. In most groups of animals in which gallbladder bile cholesterol was increased, plasma lipoprotein cholesterol levels were also increased. It was concluded that in hamsters, under these experimental conditions, changes in the cholesterol content of gallbladder bile were directly related to alterations in cholesterol content of the liver and most closely related to alterations in the free cholesterol content of that tissue.

Animals↗

PubMed1989

The effect of loxiglumide (CR-1505) on basal and bombesin-stimulated gallbladder volume in man.

This study was undertaken in 5 normal subjects to determine the role of cholecystokinin (CCK) in the regulation of basal gallbladder volume and gallbladder contraction stimulated by infusion of bombesin. Administration of the CCK-receptor antagonist, loxiglumide (CR-1505), led to doubling of the gallbladder volume (increase 104 +/- 26%; P less than 0.05) and reduced the bombesin-stimulated gallbladder contraction from 69 +/- 17 to 19 +/- 17% (P less than 0.05). The findings provide evidence suggesting that CCK plays an important role in the regulation of basal gallbladder tone and in mediating the gallbladder contraction induced by the administration of bombesin.

Adult↗

PubMed1985

Association of gallbladder carcinoma and anomalous pancreaticobiliary ductal union.

A total of 96 patients with gallbladder carcinoma in whom direct cholangiography clearly opacified the pancreaticobiliary ductal union and the common channel, and 65 patients with an anomalous union of these two duct systems at a distance greater than 15 mm from the papilla of Vater (normally less than 4.6 +/- 2.2 mm, mean +/- SD) were studied. It was found that this anomalous ductal union occurred in 16.7% of the patients with gallbladder carcinoma in comparison with an incidence of 2.8% among 641 consecutive patients with various hepatobiliary and pancreatic diseases studied by endoscopic retrograde cholangiopancreatography who did not have gallbladder carcinoma. It was also found that gallbladder carcinoma occurred in 24.6% of the 65 cases of anomalous ductal union in comparison with a 1.9% incidence of this cancer among 635 consecutive patients similarly studied and found to have normal ductal union (p less than 0.001). Thus, a close etiologic association was suggested between this anomaly in the terminal segment of the biliary tract and gallbladder carcinoma. Of the 65 patients with anomalous ductal union, 50 had the so-called congenital cystic dilatation of the common bile duct and 15 did not. Five of the 50 (10%) and 11 of the 15 (73.3%) had gallbladder carcinoma (p less than 0.01), and this carcinoma seems to be related to anomalous ductal union rather than to cystic dilatation of the common bile duct. As a tumorigenic factor in this anomaly, regurgitation of pancreatic juice has been stressed.

Adult↗