• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2511-2514
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• 2012

Objective: To evaluate the prognostic factors of gallbladder carcinoma. Methods: Presentation, operative data, complications, and survival outcome were examined for 132 gallbladder carcinoma patients who underwent gallbladder surgery in our unit during 2002-2007, and follow-up results were obtained from every patient for univariate and multivariate survival analysis. Results: The univariate analysis showed that gallbladder lesion history, tumor cell differentiation, Nevin staging, preoperative lymph node metastasis and the surgical approach significantly correlated with the prognosis of the patients (p<0.05). The results of the multivariate analysis (Cox regression) showed that gallbladder lesion history, Nevin staging and the surgical approach were independent predicators with relative risks of 6.9, 4.4, 2.8, respectively (p=0.002, 0.003, 0.008). Conclusion: Gallbladder lesion history, Nevin staging and the surgical approach are independent prognostic factors for gallbladder carcinoma, a rapidly fatal disease. Therefore, early diagnosis, anti-infective therapy and radical surgery are greatly needed to improve the prognosis of gallbladder carcinoma.

• Journal of Yeungnam Medical Science
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• v.23 no.2
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• pp.152-161
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• 2006

Carcinoma of the gallbladder is an uncommon but highly malignant tumor with a poor five year survival rate. Early detection is very important for successful treatment because this tumor is very hard to cure in cases where it has advanced beyond the reach of surgical treatment. The purpose of this review was to evaluate risk factors for carcinoma of the gallbladder and determine the best management approach.. Solitary polys, more than one cm are considered to be predisposing factors for gallbladder carcinoma when they are found to be echopenic, sessile, and with a high cell density. Anomalous union of the pacreato-biliary duct(AUPBD) without a choledochal cyst is also considered to increase risk for gallbladder carcinoma. A polyps size of more than one cm and an AUPBD are indications for prophylactic cholecystectomy. The presence of gallstones is a well-established risk factor for the development of gallbladder carcinoma; risk appears to correlate with the stone size and the duration of chronic cholecystitis. Metaplastic changes of the gallbladder epithelium present with chronic cholecystitis and may indicate a premalignant lesion. Abnormal forms of cholecystitis such as xanthogranulomatous or a porcelain gallbladder also have malignant potential; cholecystoenteric fistula as well as bacterial infection of the gallbladder(typhoid, helicobacter species) also has malignant potential. In this review, the risk factors associated with carcinoma of the gallbladder are summarized with special attention to gallstones, polyps, AUPBD, and chronic inflammation.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2185-2190
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• 2013

Gallbladder carcinoma, the most frequent malignant neoplasm of the biliary tract system, has always been considered to feature late clinical presentation and diagnosis, limited treatment options and an extremely poor prognosis. In recent years, while the incidence of gallbladder cancer has appeared to be on the increase, the available treatment methods have not greatly improved survival of the affected patients. Thus, exploring new therapeutic targets for this devastating disease is an urgent matter at present. Epidemical studies have demonstrated that the incidence of gallbladder carcinoma exhibits a distinct gender bias, affecting females two to three times more than males, pointing to crucial roles of estrogen. It is well known that estrogen acts on target tissues by binding to estrogen receptors (ERs), which are mainly divided into three subtypes, $ER{\alpha}$, $ER{\beta}$ and $ER{\gamma}$. $ER{\alpha}$ and $ER{\beta}$ appear to have overlapping but also unique even opposite biological effects. As important pathogenic mediators, ERs have been considered to relate to several kinds of tumors. In gallbladder carcinoma tissue, ERs have been shown to be positively expressed, and ERs expression levels are associated with differentiation and prognosis of this cancer. Nevertheless, the exact mechanisms of estrogen inducing growth of gallbladder carcinoma remain poorly understood. On the base of the current investigations, we deduce that estrogen participates in promotion of gallbladder carcinoma by influencing the formation of gallstones, stimulating angiogenesis, and promoting abnormal proliferation. Since ERs mediate the carcinogenic actions of estrogen in gallbladder, and therapy targeting ERs may provide new directions for gallbladder carcinoma. Therefore, it should be stressed that ERs are potential therapeutic targets for gallbladder carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.2711-2715
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• 2013

Background: Cancer of the gallbladder is a relatively rare neoplasm with a poor prognosis. The exact mechanisms of its genesis are not known and very little information is available on molecular events leading to labeling this as an orphan cancer. Materials and Methods: In this prospective case control study we evaluated the expression of p16, pRb and cyclin D1 by immunohistochemistry to study the G1-S cell-cycle check point and its possible role in gallbladder carcinogenesis. A total of 25 patients with gallbladder carcinoma (group I), 25 with cholelithiasis (group II) and 10 normal controls. were enrolled Results: Cyclin D1 expression was seen in 10 (40%) patients each with carcinoma and cholelithiasis while only in 2 (20%) of the normal gallbladders but differences were not statistically significant (p value=0.488). p16 was expressed in 12% patients of carcinoma of the gallbladder and 28% of cholelithiasis, however this difference was not statistically significant (p value=0.095). Retinoblastoma protein was found to be expressed in 50% of normal gallbladders and 6 (24%) of carcinoma and 8 (32%) of gallstones. The present study failed to demonstrate any conclusive role of cyclin D1/RB/ p16 pathway in carcinoma of the gallbladder. Conclusions: The positive relation observed between tumor metastasis and cyclinD1 expression and p16 with nodal metastasis suggested that higher cyclin D1/p16 expression may act as a predictive biomarker for aggressive behavior of gallbladder malignancies.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3747-3752
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• 2014

Background: Gallbladder carcinoma (GBC) is the most common carcinoma of the biliary system. Among its research models, orthotopic xenograft models, important research tools, have been rarely reported in the literature however. Aim: To explore establishment of an orthotopic xenograft model and to evaluate the advantage and disadvantage as compared with other models. Materials and Methods: Subcutaneous xenograft and orthotopic xenograft models of gallbladder carcinoma in nude mice were established and compared with human gallbladder carcinomas. Results: For the orthotopic xenograft model and clinical gallbladder carcinomas, the lymph node metastatic rates were 69.2% and 53.3% (p>0.05); ascites generation rates, 38.5% and 11.7%(p<0.05); liver invasive rates, 100% and 61.7%(p<0.05); and lymphatic vessel densities (LVD), $10.4{\pm}3.02$ and $8.77{\pm}2.92$ (p>0.05), respectively. In the subcutaneous xenograft model, no evidence of ascites generation, lymph node metastasis and liver metastasis were found, and its LVD was lower ($4.56{\pm}1.53$, p<0.05). Conclusions: Compared with the subcutaneous xenograft model, the orthotopic xenograft model better simulates clinical gallbladder carcinoma in terms of metastasis and invasion, which may be attributed to the difference in microenvironment and LVD.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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• pp.1535-1538
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• 2015

Background: The objectives of the study were to: 1) determine the frequency of incidental malignancy in unsuspected/grossly normal looking gall bladders; 2) determine the frequency of malignancy in suspected/grossly abnormal looking gall bladders. Materials and Methods: This prospective, cross sectional study was carried out at a tertiary care hospital in Pakistan, during a four year period (Jan 2009-dec2012). All the cholecystectomy cases performed for gallstone diseases were examined initially by a surgeon and later on by a pathologist for macroscopic abnormalities and accordingly assigned to one of the three categories i.e. grossly normal, suspicious, abnormal/malignant. Frequency of incidental carcinoma in these categories was observed after receiving the final histopathology report. Results: A total of 426 patients underwent cholecystectomy for cholelithiasis, with a 1:4 male: female ratio. Mean age of the patients was 45 years with a range of 17-80 years. The frequency of incidental gallbladder carcinoma was found to be 0.70 %(n=3). All the cases of gallbladder carcinoma were associated with some macroscopic abnormality. Not a single case of incidental carcinoma gallbladder was diagnosed in 383 'macroscopically normal looking' gallbladders. Conclusions: Incidental finding of gall bladder cancer was not observed in any of macroscopically normal looking gall bladders and all the cases reported as carcinoma gallbladder had some gross abnormality that made them suspicious. We suggest histopathologic examination of only those gall bladders with some gross abnormality.

• Journal of Physiology & Pathology in Korean Medicine
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• v.27 no.1
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• pp.136-138
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• 2013

Carcinosarcoma of gallbladder is a rare malignant tumor characterized by malignant epithelial and malignant mesenchymal components. Its pathogenesis is unknown and most of carcinosarcomas of gallbladder are associated with poor survival because the disease presents at an advanced stage. A 69-year-old man presented with right upper quadrant pain. The preoperative diagnosis was gallbladder cancer, and thus, curative radical cholecystectomy was performed. Pathologic examination of the surgical specimen revealed that the tumor was composed of carcinomatous components with adenocarcinoma and squamous cell carcinoma, and sarcomatous components with spindle cell sarcoma and chondrosarcoma, which was consistent with a diagnosis of primary carcinosarcoma of the gallbladder. The tumor was found to extend to the pericholecystic fat and no metastasis in regional lymph nodes.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5613-5617
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• 2012

Gallbladder carcinoma (GBC) is the commonest cancer of the biliary tree and the most frequent cause of death from biliary malignancies. The incidence of GBC shows prominent geographic, age, race, and gender-related differences and is 4-7 times higher in patients with gallstones. This prompted us to study the clinicopathological aspects of the disease and the incidence of gallstones in gallbladder carcinoma patients, in this part of India. In this, combined retrospective (Jan 2004-March 2010) and prospective study (April 2010-Dec 2011) of eight years, 198 patients of gallbladder carcinoma (50 males and 148 females), (range 28-82 years; mean 55 years) were studied. Most of the patients were poor and presented with abdominal pain and mass, with abnormal lab parameters. Gallstones were present in 86% of patients. Surgical exploration was performed in 130, with gallbladder resection in 60 (including 7 incidental GBC). Adenocarcinoma (87.7%) was the commonest histological type. The study indicates that GBC is common in our scenario. It is a disease of elderly females, has a strong association with gallstones and every cholecystectomy specimen should be examined histopathologically.

• Journal of Digestive Cancer Research
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• v.4 no.2
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• pp.83-87
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• 2016

Till now, two distinct epithelial lesions, dysplasia and adenoma, are currently recognized as premalignant stages of gallbladder (GB) carcinogenesis. In these two carcinogenesis pathways, GB stones and polyps are regarded as one of the most important risk factors of GB carcinoma respectively. Although there still remain controversies for the indication of prophylactic cholecystectomy for GB stones and polyps due to lack of high-level evidence, the present review demonstrated that patients who have GB stones with more than 3 cm size, chronic typhoid carriers, porcelain GB, or anomalous pancreaticobiliary ductal union and patients with more than 1 cm sized GB polyp would be recommended prophylactic cholecystectomy.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.2923-2928
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• 2015

Background: Gallbladder carcinoma (GBC) has been stated as an Indian disease, with the highest number of cases being reported from certain districts of northeast India, which has an ethnically distinct population. Unfortunately there are no scientific reports on the underlying molecular mechanisms associated with the pathogenesis of the disease from this region. Aim: The present study evaluated the role of differential expression of human telomerase reverse transcriptase (hTERT) in the development of gall bladder anomalies. Materials and Methods: Blood and tissue samples were collected from patients undergoing routine surgical resection for clinically proven cases of gallbladder disease {cholelithiasis (CL, n=50), cholecystitis (CS, n=40) and GBC (n=30) along with adjacent histopathologically proved non-neoplastic controls (n=15)} with informed consent. Whole blood was also collected from age and sex matched healthy controls (n=25) for comparative analysis. Differential hTERT mRNA expression was evaluated by semi-quantitative rt-PCR and real-time PCR based analysis using ${\beta}$-actin as an internal control. Evaluation of differential hTERT protein expression was studied by Western blot analysis and immunoflourescence. Statistical analysis for differential expression and co-relation was performed by SPSSv13.0 software. Results: Gallbladder anomalies were mostly prevalent in females. The hTERT mRNA and protein expression increased gradiently from normal