Metastatic carcinoma of the gallbladder from renal cancer presenting as intraluminal polypoid mass

Summary We report a rare case of secondary involvement of the gallbladder by metastatic renal cell carcinoma. A 71-year-old man was diagnosed as having a polypoid mass within the gallbladder when he underwent right nephrectomy for a renal cell carcinoma. A preoperative diagnosis of simultaneous carcinoma of the gallbladder was made, and extended cholecystectomy with regional lymphadenectomy was performed five months after the initial operation.Postoperative histological examination of the polypoid mass within the gallbladder and a pancreatic mass excised during the second surgery revealed these resected tumors to be identical to the clear cell type of renal cell carcinoma. We feel that this case presents synchronous involvement of the gallbladder and pancreas by metastatic renal cell carcinoma of the right kidney.     

Effect of histone deacetylase inhibitor on proliferation of biliary tract cancer cell lines

AIM： To explore the effect of histone deacetylase inhibitor, trichostatin A （TSA） on the growth of biliary tract cancer cell lines （gallbladder carcinoma cell line and cholangiocarcinoma cell line） in vivo and in vitro, and to investigate the perspective of histone deacetylase inhibitor in its clinical application. METHODS： The survival rates of gallbladder carcinoma cell line （Mz-ChA-l cell line） and cholangiocarcinoma cell lines （QBC939, KMBC and OZ cell lines） treated with various doses of TSA were detected by methylthiazoy tetrazolium （MTT） assay. A nude mouse model of transplanted gallbladder carcinoma （Mz-ChA-l cell line） was successfully established, and changes in the growth of transplanted tumor after treated with TSA were measured. RESULTS： TSA could inhibit the proliferation of gallbladder carcinoma cell line （Mz-ChA-l cell line） and cholangiocarcinoma cell lines （QBC939, KMBC and OZ cell lines） in a dose-dependent manner. After the nude mouse model of transplanted gallbladder carcinoma （Mz- ChA-l cell line） was successfully established, the growth of cancer was inhibited in the model after treated with TSA. CONCLUSION： TSA can inhibit the growth of cholangiocarcinoma and gallbladder carcinoma cell lines in vitro and in vivo.     

Renal cell carcinoma with unusual metastasis to the gallbladder

Gallbladder involvement in patients with renal cell carcinoma (RCC) is extremely rare. We present a report of a 61-year-old man with a synchronous RCC metastasis to the gallbladder presenting as an intraluminal polypoid mass simulating primary gallbladder carcinoma. Enhanced abdominal computed tomography demonstrated a well-enhanced polypoid lesion in the gallbladder. Intraoperative rapid pathological examination of the gallbladder tumor showed clear cell-type cancerous cells. Microscopically, tumor cells of both the resected kidney and gallbladder had round uniform nuclei, clear cytoplasm, and well-defined cytoplasmic borders, forming alveolar patterns. Immunohistochemically, the tumor cells were negative for cytokeratin 7 (CK7) and carcinoembryonic antigen (CEA), which is usually positive in primary clear cell carcinoma of the gallbladder. Therefore, the final diagnosis was RCC with a synchronous gallbladder metastasis.     

Radical surgery for advanced pure squamous cell carcinoma of the gallbladder: report of a case

Squamous cell carcinoma (SCC) of the gallbladder is frequently detected at an advanced stage because of its tendency to infiltrate adjacent organs. In addition, more rapid growth of this type of carcinoma compared to that of adenocarcinoma, the most frequent subtype of gallbladder carcinoma, has been reported. Although it is not rare to find squamous cell carcinoma components in cases other than the usual adenocarcinoma of the gallbladder, these cases must be distinguished from those of pure squamous cell carcinoma, as diagnosed in the present case. Pure squamous cell carcinoma is characterized by a well-localized growth, no visceral metastasis, and a rarity or lack of lymph node metastasis, even when the tumor has grown to a large size locally. Prognosis of SCC of the gallbladder has generally been considered poor. Nevertheless, long-term survival after curative resection in patients with SCC of the gallbladder has been sporadically reported. We performed extended right hemihepatectomy with portal vein resection after portal vein embolization for a 55-year-old woman with advanced SCC of the gallbladder. The patient has not developed any signs of recurrence 40 months after the surgery. Although such radical surgery remains challenging, it may lead to a favorable outcome in selected patients with advanced SCC of the gallbladder.     

Asymptomatic metachronous metastatic renal cell adenocarcinoma to the gallbladder

Summary A case of asymptomatic metachronous metastatic unilateral renal cell adenocarcinoma to the gallbladder detected five years after resection of the primary renal neoplasm is reported here. The lesion was diagnosed by contrast enhancement of a gallbladder mass on abdominal computerized tomography scan and by color Doppler sonographic study of the gallbladder, both of which demonstrated the vascular supply to the intraluminal gallbladder mass. The biological behavior of renal cell adenocarcinoma is reviewed. Guidelines for the evaluation of intraluminal gallbladder masses are suggested.     

Endocrine cell carcinoma of the gallbladder with anomalous pancreaticobiliary ductal junction

We experienced a case of endocrine cell carcinoma of the gallbladder with anomalous pancreaticobiliary ductal junction. It is well known that anomalous pancreaticobiliary ductal junction has potentiality to cause gallbladder cancer and that most of the cases are papillary adenocarcinoma or well-differentiated adenocarcinoma. The direct relationship between endocrine cell carcinoma of the gallbladder and anomalous pancreaticobiliary ductal junction has not been elucidated.     

Expression of homeodomain protein CDX2 in gallbladder carcinomas

Purpose Caudal-related homeobox protein CDX2 plays an important role in the regulation of cell proliferation and differentiation of the intestinal epithelium. CDX2 is associated with intestinal metaplasia and carcinomas of the stomach, but the role of CDX2 in gallbladder carcinogenesis remains unknown.Methods We analyzed the expression of CDX2 and intestinal apomucin MUC2 in gallbladder cancer cell lines at the mRNA level by the RT-PCR method. We also investigated the expression of CDX2 and MUC2 in 68 primary gallbladder carcinomas by the immunohistochemical staining method and compared the expression of CDX2 with the clinicopathological factors in the gallbladder carcinoma cases.Results Expression of CDX2 and MUC2 was found in three of four gallbladder cancer cell lines at the mRNA level. In addition, we found that CDX2 was absent in the normal gallbladder epithelium, but the CDX2 protein was expressed in 25 of the 68 (36.8%) gallbladder carcinomas. Interestingly, in the tubular type gallbladder carcinomas, the frequency of CDX2 expression was much higher in the well-differentiated type than the moderately and poorly differentiated types, the difference being statistically significant (P<0.01). CDX2 expression showed a relationship with expression of MUC2 (P<0.04) in the gallbladder carcinomas. CDX2 was expressed in intestinal metaplasia and dysplasia, which are hypothesized to be premalignant conditions.Conclusion These results imply that CDX2 plays an important role in gallbladder carcinogenesis with intestinal differentiation.     

Cell kinetic studies on the gallbladder epithelium in patient with anomalous arrangement of pancreatobiliary duct

It is well known that the patients with anomalous arrangement of pancreatobiliary duct (AAPBD) are combined with biliary tract cancer. To clarify possible carcinogenesis of the gallbladder with AAPBD, DNA analysis of the gallbladder epithelium was performed in control (9 cases), AAPBD (26), gallbladder cancer confined in mucosa (10) and noncancerous epithelium around the gallbladder cancer (21). The mean values of DNA score, as already reported by us as an indicator of cell kinetics, were 12.1 (control), 27.2 (AAPBD, Type a), 13.3 (AAPBD, Type b), 14.8 (noncancerous epithelium around cancer) and 77.2 (gallbladder cancer confined in mucosa). The values of DNA score in the epithelium of AAPBD (Type a) showed significantly high level, which was next to that of cancer. Type a AAPBD may be supposed to have potential malignancy because of its accelerated cell cycle. But as Type b AAPBD without accelerated cell cycle combines cancer at least as often as Type a, further studies should be performed to reveal the relationship between cell cycle and malignancy.     

In primary sclerosing cholangitis,gallbladder polyps are frequently malignant

OBJECTIVE: The management of gallbladder polyps/masses in patients with primary sclerosing cholangitis (PSC) (i.e., cholecystectomy vs observation) remains problematic. Given the risk of biliary tract cancer in PSC in the face of the benign nature of most gallbladder polyps in the general population, our aim was to determine the prevalence of gallbladder cancer in PSC patients with a gallbladder mass who had undergone cholecystectomy. METHODS: The case records of all patients with PSC undergoing a cholecystectomy at the Mayo Clinic between 1977-1999 were reviewed. RESULTS: Of the 102 patients with PSC who underwent a cholecystectomy, 14 of 102 (13.7%) had a gallbladder mass. In the subset of patients with gallbladder masses, eight of 14 (57%) had adenocarcinomas (seven primary adenocarcinomas and one metastatic cholangiocarcinoma); the other six had benign masses (five adenomas and one cholesterol polyp). In those patients with benign masses, 33% had associated epithelial cell dysplasia; in patients with primary gallbladder cancers, 57% had associated dysplasia. The patients with primary gallbladder adenocarcinoma had a favorable outcome after cholecystectomy, with a 36-month survival of 66%. CONCLUSIONS: In conclusion, gallbladder neoplasms in PSC patients are malignant in approximately 40-60% of the cases. The presence of gallbladder epithelial cell dysplasia suggests a dysplasia-carcinoma sequence in PSC similar to that observed in ulcerative colitis. Consideration should be given to performing a cholecystectomy in PSC patients with gallbladder polyps. If a cholecystectomy is not performed, careful interval follow-up is warranted.     

Are industrial toxic substances a risk factor in gallbladder cancer?

Increased prevalence of gallbladder cancer has been related to specific occupations and suggests a possible professional exposure to carcinogens. The authors report the case of a 64-year-old woman who had a squamous cell carcinoma of the gallbladder with hepatic metastases, and professional exposure to trichloroethylene in a degreasing metal laboratory. Although trichlorothylene could not be assumed to be a true carcinogen for gallbladder cancer, this case underscores that epidemiologic studies taking into account professional exposure, in addition to the usual risk factors of gallbladder cancer, are requested, in order to detect a new patient group at risk for gallbladder cancer.     

Mucin-producing cells and endocrine cells of gallbladder epithelium in patients with uncomplicated cholelithiasis.

In this study we have investigated various morphofunctional features of gallbladder mucosa in patients with uncomplicated cholelithiasis. The histological changes, endocrine cell types and their distribution, and mucin-producing cells were characterized by immunocytochemistry and mucin histochemistry; moreover, we attempted to correlate these findings to the number and size of gallbladder stones and the type of bacteria present in the bile. Our results indicate that, despite similar clinical parameters, a wide range of histological changes can occur in the gallbladder mucosa of these patients. Moreover, the presence of certain endocrine and mucin-producing cell types in so-called "pyloric metaplasia" led us to hypothesize that this finding may be a trivial event in the gallbladder epithelium.     

Gallbladder carcinoma: the role of p53 protein overexpression and Ki-67 antigen expression as prognostic markers

BackgroundThe overexpression of p53 protein and the expression of Ki-67 antigen may affect the survival of patients with gallbladder carcinoma. This association has been tested in a series of 41 patients with relatively early carcinoma of the gallbladder.MethodsForty-one surgical specimens from patients with a postoperative histological diagnosis of gallbladder carcinoma were studied. All patients were operated by simple cholecystectomy only because the tumours were not advanced and/or their general condition was poor. Patients submitted to radical operations were excluded. p53 expression was calculated from nuclear staining according to the intensity and extent of positive cells, as graded on a scale from 1 to 3; a combined score of >3 was considered as overexpression. Ki-67 expression was calculated by the MIB-I index: the percentage of positively stained tumour cell nuclei out of the total tumour cells counted (n = 1000); >20% of stained cells was considered positive.ResultsTwenty-nine gallbladder carcinomas (71%) overexpressed p53 protein in the cell nuclei. No significant differences were found in relation to cell differentiation on the level of tumour infiltration through the gallbladder wall. Five-year survival of patients with gallbladder carcinoma overexpressing p53 was 17.2%, while survival of patients without p53 overexpression was 30% (not significant). Twenty-four cases (58.5%) were considered positive for the MIB-I index. There were no differences between the grade of cell differentiation and wall infiltration. Five-year survival of the patients with a MIB-I positive index was 9.2% as opposed to 27.7% for those with a negative index (not significant).Conclusionsp53 protein nuclear overexpression and Ki-67 protein expression in gallbladder carcinoma were not related to histological differentiation, level of gallbladder wall invasion or patient survival.     

细胞凋亡与细胞增殖在胆囊肿瘤形成中的作用

目的 探讨细胞凋亡和细胞增殖在胆囊肿瘤发生发展中的作用。 用原位末端标记法和免疫组织化学染色１、检测２４例胆囊癌和１６例胆囊腺瘤中的凋亡细胞数和ＰＣＮＡ及ｂｃｌ－２癌基因的表达情况。结果 胆囊腺癌中的凋亡细胞数明显低于胆囊癌;分化好的胆囊癌中的凋亡细胞数低于分化差的胆囊腺癌。ＰＣＮＡ和ｂｃｌ－２的阳性表达率在胆囊癌中明显高于胆囊腺瘤。结论胆囊癌不仅有较高的增殖能力,而且有很高的细胞凋亡率。细胞凋亡     

Identification and expansion of a unique stem cell population from adult mouse gallbladder

The identification of resident stem cells in the mouse gallbladder is, to date, unexplored. In addition, the relationship between adult gallbladder stem cells and intrahepatic bile duct (IHBD) cells is not well understood. The aim of this study was to isolate stem cells from an adult mouse gallbladder and determine whether they were unique, compared to IHBD cells. By limiting dilution analyses and index sorts, we found that an EpCAM(+) CD49f(hi) epithelial cell subpopulation from primary gallbladder is enriched in colony-forming cells, compared to EpCAM(+) CD49f(lo) cells. EpCAM(+) CD49f(hi) cells expressed cluster of differentiation (CD)29, CD133, and stem cell antigen-1, but were negative for lineage markers CD31, CD45, and F4/80. Using a novel feeder cell-culture system, we observed long-term (>passage 20) and clonal expansion of the EpCAM(+) CD49f(hi) cells in vitro. In a matrigel differentiation assay, EpCAM(+) CD49f(+) cells expanding in vitro underwent organotypic morphogenesis forming ductular structures and cysts. These structures are similar to, and recapitulate a transport function of, primary gallbladder. EpCAM(+) CD49f(+) cells also engraft into the subcutaneous space of recipient mice. We compared primary gallbladder and IHBD cells by flow cytometry and found phenotypic differences in the expression of CD49f, CD49e, CD81, CD26, CD54, and CD166. In addition, oligonucleotide microarrays showed that the expanded EpCAM(+) CD49f(+) gallbladder cells and IHBD cells exhibit differences related to lipid and drug metabolism. Notable genes that were different are cytochrome P450, glutathione S-transferase, Indian hedgehog, and solute carrier family genes. CONCLUSION: We have isolated an epithelial cell population from primary mouse gallbladder with stem cell characteristics and found it to be unique, compared to IHBD cells.     

Torsion of the gallbladder in a 3-year-old infant

A 3-year-old girl was admitted to hospital with complaints of severe upper abdominal pain and vomiting. On admission, a board-like rigidity in the right hypochondrium was noted, along with a high white blood cell count and a high C-reactive protein value. Abdominal ultrasonography (US) revealed a left-sided enlarged gallbladder with a thickened wall, without gallstones. Contrast-enhanced computed tomography (CT) demonstrated an enlarged gallbladder without enhancement effects and a cystic duct located on the right side of the gallbladder. The patient underwent an emergency operation following a diagnosis of torsion of the gallbladder. The gallbladder appeared gangrenous, and 180° clockwise torsion was found at the neck of the gallbladder. The gallbladder was straightened and then removed without difficulty because there was only slight inflammation around Calot’s triangle and the gallbladder was not fixed to the liver. Histopathological examination revealed an acute bleeding infarction of the gallbladder. The patient was discharged on the ninth day after surgery, without any complications. The present case suggested that abdominal US and contrast-enhanced CT examinations are helpful in making a correct diagnosis of torsion of the gallbladder even in an infant; in the event of this diagnosis, prompt cholecystectomy is necessary.     

Cardiac metastasis from squamous cell carcinoma of gallbladder

A 65-year-old woman was admitted to our hospital with the diagnosis of gallbladder tumor. Right extended hepatic lobectomy plus lymph node dissection of the hepatoduodenal ligament and left hepaticojejunostomy with Roux-en-Y reconstruction was performed in July, 1993. The gallbladder tumor was histologically proven to be squamous cell carcinoma. Seventeen months later, the patient experienced dyspnea and pitting edema of the lower legs and was admitted, in December 1994, with a diagnosis of heart failure. Despite intensive cardiac support, she died 12 days after the second admission. Autopsy revealed multiple cardiac tumors in the left and right ventricles, left atrium, left coronary artery, and left diaphragm. Histologically, these tumors were shown to be squamous cell carcinoma, considered to have metastasized from the primary gallbladder carcinoma. As neither local recurrence of the gallbladder carcinoma. As neither local recurrence of the gallbladder carcinoma nor any lymph node metastasis was found, the cardiac metastasis of the gallbladder carcinoma may have occurred via the hematogenous route. Although rare, this route of cardiac metastasis of gallbladder carcinoma may be an important aspect of distant metastasis, which should be monitored for during follow-up after resection of the primary tumor.     

A case of primary adenosquamous/squamous cell carcinoma of gallbladder directly invaded duodenum

A rare case of primary gallbladder carcinoma is reported. A 67 year-old woman was admitted to our hospital for treatment of suspected duodenal carcinoma. A series of radiographic examinations demonstrated a giant tumor involving the duodenum, gallbladder, pancreatic head, and transverse colon. These extensions made it difficult to identify the primary origin of the carcinoma. Pancreatoduodenectomy, cholecystectomy, and resection of the transverse colon were performed. Macroscopically, ulcerative lesions were seen in both the gallbladder and the duodenum. Microscopic examination revealed adenosquamous cell carcinoma of the gallbladder, invasive of the adjacent organs, including circumferential invasion of the second portion of the duodenum. The patient tolerated the operation well and was discharged 28 days post-operatively, but died of liver metastasis 4 months after surgery. Local invasion of the surrounding tissues is characteristic of adenosquamous/squamous cell carcinoma of the gallbladder. Although surgery for cure is deemed possible, the rapid growth rate of this type of tumor may cast doubt on the value of extensive radical surgery.     

Effects of aging on laboratory animals: I. Light and scanning electron microscopy of dog gallbladder

This study was begun in order to illustrate the changes that dog gallbladder undergo with age. Young (<8 weeks) and old (> 12 years) dogs were anesthetized, perfusion fixed and prepared for light and scanning electron microscopy. Observations with the light microscope suggested that gallbladder mucosa of young dogs was more folded and had few Rokitansky-Aschoff sinuses while the aging canine gallbladder mucosa appeared flattened and cystic. In addition, the gall-bladder lamina propria of old dogs exhibited increased numbers of lymphocytes and plasma cells, a less conspicuous vascular network, and lymph nodules. Few differences were noted in the muscular layer, the perimuscular connective tissue layer, and in the serosal layer between the young and old dogs. Scanning electron microscope observations of gallbladder mucosa tended to support the light microscopic data. The puppy gallbladder mucosa showed more folds and raised cell surfaces with the typical hobnail appearance while the aging canine gallbladder mucosa had few folds and considerable cellular flattening. These morphological findings suggest a reduced surface for absorption in the aging gallbladder.     

Culture of mouse gallbladder epithelial cells by microexplant culture on collagen gel]

We established a new culture method of mouse gallbladder epithelial cells. Explantation of a tiny fragment of the mouse gallbladder (microexplant) on the collagen gel allowed the epithelial cells to proliferate on the collagen gel for more than 4 weeks. The epithelial cells spread in a monolayer sheet from the microexplant and extended onto the surface of the collagen gel 0.31 +/- 0.02 mm per day. Whereas, contaminated stromal cells proliferated under the epithelial cell layer and into the collagen gel. At the peripheral zone of epithelial sheet, the shape of the epithelial cells was squamous, and the cells were frequently positive for BrdU immunostaining, indicating the high proliferative activity. In contrast, the cells in the central part of epithelial sheet were cuboidal or low columnar in shape and showed well cell-polarity and mucus-secretory activity similar to the gallbladder epithelia in vivo. It was indicated that the cultured epithelial cells in this system preserved the morphological and functional differentiation to the physiological gallbladder epithelia. This newly established culture method has the characteristics of both the organ and the cell culture, and might be useful for the morphological and functional studies of the gallbladder epithelia in vitro.     

细胞粘附分子在胆囊癌中表达的意义

研究胆囊癌组织中细胞粘附分子CEA和CD44v6蛋白表达的意义。用免疫组化法检测 44例胆囊癌组织中CEA和CD44v6蛋白的表达。 44例胆囊组织中CEA和CD44v6蛋白表达的阳性率分别为 75 %和 48% ;两者的表达与肿瘤浸润外膜和淋巴结转移均呈正相关 (P <0 0 5 ) ;胆囊癌组织中CEA和CD44v6蛋白呈协同表达 (P<0 0 5 )。CEA和CD44v6蛋白与胆囊癌的发展和淋巴结转移密切相关。