• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3315-3318
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• 2013

Gall bladder carcinoma is the most common cancer of biliary tree, characterized by rapid progression and a very high mortality rate. Detection at an early stage, however, is indicative of a very good prognosis and prolonged survival. The practice of histopathological examination of gall bladder specimens removed for clinically benign conditions and its usefulness has been a subject of controversy. The present prospective study was carried out over a period of four years in order to find out the incidence of unsuspected gallbladder carcinoma in cholecystectomy specimens received in our histopathology laboratory and to analyze their clinico-pathological features. A total of 4,115 cases were examined. Incidentally detected cases comprised 0.44%, which accounted for 72% of all gall bladder carcinomas detected. The majority were in an early, surgically resectable stage. From the results of this study we recommend that in India and other countries with relatively high incidences of gall bladder carcinoma, all cholecystectomy specimens should be submitted to histopathology laboratory, as this is the only means by which malignancies can be detected at an early, potentially curable stage.

• 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.

• 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

• Journal of Gastric Cancer
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• v.4 no.1
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• pp.1-6
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• 2004

Purpose: Despite numorous reports on the relationship between the level of carcinoembryonic antigen (CEA) in gall bladder bile and liver metastasis in colorectal cancer, no similar studies have been carried out for gastric carcinomas. We, therefore, undertook the present study to establish the relationship between the gall bladder bile CEA and liver metastasis as well as the post-operative survival rate in gastric carcinoma patients with curative resections. Materials and Methods: In 373 gastric cancer patients (252 males, 121 females, age $21\∼76$ years) operated on at Kosin University Hospital between 1989 1996, the CEA concentration in the gall bladder bile was determined during the operation and the value was related to the rates of post-operative survival and liver metastasis during follow-up period. Results: The overall rate of patient survival decreased gradually with increase in TNM stage. The 13-year postoperative survival rates for stages Ia, Ib, II, IIIa, and IIIb were $95.7\%,\;92.5\%,\;79.9\%,\;50.9\%,\;and\;43.3\$, respectively, and the 10-year survival rate for stage IV was $22.6\%$. The patients with a high ($\geq$10 ng/ml) biliary CEA showed a significantly lower rate of survival than those with a low (<10 ng/ml) biliary CEA. The 13-year cumulative survival rate was $55.4\%$ for the high CEA group and $76.5\%$ for the low CEA group (P<0.01). Also, the patients with a high biliary CEA showed a significantly higher rate ($11.5\%$) of liver metastasis than those with a low biliary CEA ($1.9\%$) (P<0.000). In patients with TNM stages (I and II), the CEA level did not affect the post-operative survival rates ($95.4\%\;and87.7\%$ in the high and low CEA groups, P>0.10), but in those with high TNM stages (III and IV), the survival rate was significantly lower in the high CEA group ($25.9\%$) than in the low CEA group ($57.8\%$) (P<0.05). Conclusion: These result suggest that the gall bladder bile CEA level obtained in an advanced-staged gastric cancer operation may be used in predicting the post-operational survival rate and in sorting out patients with a high risk for cancer recurrence, especially in the liver area.

• Journal of Life Science
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• v.21 no.3
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• pp.417-423
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• 2011

Thymosin ${\beta}4$ (TB-4) has been reported to play a key role in tumor growth, metastasis and angiogenesis. In addition, TB-4 induced the expression of vascular endothelial growth factor (VEGF) and stabilized the hypoxia-inducible factor (HIF)-$1{\alpha}$ in melanoma cells. Although the importance of thymosin ${\beta}4$ in angiogenesis and metastasis has been proven, there are few studies that show the expression patterns of TB-4, VEGF and HIF-$1{\alpha}$. This study was conducted to analyze the relationship among these proteins in various tumors. Using tissue microarray analysis, we investigated the expression patterns of TB-4, VEGF and HIF-$1{\alpha}$ in various tumors to identify the expression patterns and relationships of these proteins in certain tumors. TB-4 was highly expressed in osteosarcoma, colon adenocarcinoma, esophageal squamous cell carcinoma, kidney and urinary bladder transitional carcinoma, lung cancer, and liver cancer. HIF-$1{\alpha}$ was highly expressed in nasal cavity inverted papilloma, lung cancer, and esophageal squamous cell carcinoma. The expression patterns of TB-4 and HIF-$1{\alpha}$ were almost similar and co-localized. VEGF expression was high in the blood vessels in tumors, but usually not high in the tumors themselves. VEGF was moderately expressed in stomach cancer, liver angiosarcoma, gall bladder adenocarcinoma, and uterus endometrial adenocarcinoma. The expression patterns of VEGF shows similarities in certain tumors including stomach cancer, osteosarcoma, liposarcoma, lung cancer, liver cancer, gall bladder adenocarcinoma, esophageal squamous cell carcinoma, stomach cancer, colorectal carcinoma and renal cell carcinoma. These results suggest that the expression patterns of TB-4, HIF-$1{\alpha}$ and VEGF were co-localized and related to tumorigenesis and angiogenesis of certain tumors.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5647-5654
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• 2015

Gall bladder cancer (GBC) is a gastro-intestinal cancer with high prevalence among north Indian women. Platelet derived growth factor-B (PDGFB) and human epidermal growth factor receptor-2 (HER2) may play roles in the etiology of GBC through the inflammation-hyperplasia-dysplasia-carcinoma pathway. To study the association of PDGFB and HER2 polymorphisms with risk of GBC, 200 cases and 300 controls were considered. PDGFB +286A>G and +1135A>C polymorphisms were investigated with an amplification refractory mutation system and the HER2 $Ile^{655}Val$ polymorphism by restriction fragment length polymorphism. Significant risk associations for PDGFB +286 GG (OR=5.25) and PDGFB +1135 CC (OR=3.19) genotypes were observed for GBC. Gender wise stratification revealed susceptibility for recessive models of PDGFB +1135A>C (OR=3.00) and HER2 $Ile^{655}Val$ (OR=2.52) polymorphisms among female GBC cases. GBC cases with gall stones were predisposed to homozygous +286 GG and +1135 CC genotypes. Significant risk associations were found for ACIle (OR=1.48), GAVal (OR=1.70), GAIle (OR=2.00) haplotypes with GBC cases and GCIle haplotype with female GBC cases (OR=10.37, P=<0.0001). Pair-wise linkage disequilibrium revealed negative associations among variant alleles. On multi-dimensional reduction analysis, a three factor model revealed significant gene-gene interaction for PDGFB +286A>G, PDGFB +1135A>C and HER2 Ile165Val SNPs with GBC. Protein-protein interaction showed significant association of PDGFB and HER2 with the epidermal growth factor receptor signaling pathway.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.13
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• pp.5557-5563
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• 2015

Background: Cholelithiasis is associated in 54%-98% of patients with carcinoma of the gallbladder, and a high incidence among females suggests a role of female hormones in the etiology of the disease. Cytochrome $P450C17{\alpha}$ (CYP-17) is a key enzyme involved in estrogen metabolism and polymorphisms in CYP-17 are associated with altered serum levels of estrogens. Thus, we investigated whether the CYP-17 MspA1 gene polymorphism might impact on risk of gall bladder cancers or gallstones, as well as to determine if this gene polymorphism might be linked with estrogen serum levels and lipid profile among the North Indian gall bladder cancer or gallstone patients. Materials and Methods: CYP-17 gene polymorphisms (MspA1) were genotyped with PCR-RFLP in cancer patients (n=96), stone patients (n=102), cancer + stone patients (n=52) and age/sex matched control subjects (n= 256). Lipid profile was estimated using a commercial kit and serum estrogen was measured using ELISA. Results: The majority of the patients in all groups were females. The lipid profile and estrogen level were significantly higher among the study as compared to control groups. The frequency of mutant allele A2 of CYP17 MspA1 gene polymorphism was higher among cancer (OR=5.13, 95% CI+3.10-8.51, p=0.0001), stone (OR=5.69, 95%CI=3.46-9.37, p=0.0001) and cancer + stone (OR=3.54, 95%CI=1.90-6.60, p=0.0001) when compared with the control group. However there was no significant association between genotypes of CYP17 MspA1 gene polymorphism and circulating serum level of estrogen and lipid profile. Conclusions: A higher frequency of mutant genotype A1A2 as well as mutant allele A2 of CYP-17 gene polymorphism is significantly associated with risk of gallbladder cancer and stones. Elevated levels of estrogen and an altered lipid profile can be used as predictors ofgall bladder stones and cancer in post menopausal females in India.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.12 no.1
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• pp.142-147
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• 1990

Malignant oral tumors occurred in the oral cavity. They were thought to result from the other primary tumors through hematogenous metastasis. Primary tumors were unusually gall bladder tumor and pancreatic tumor. Biopsy was performed and these specimens were similar to those of the primary sites histologically and clinically. Diagnoses were adenocarcinomas metastatic from the primary tumors. They did not reveal the bony changes, only soft tissue masses.

• Radiation Oncology Journal
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• v.16 no.1
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• pp.43-49
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• 1998

Purpose : Carcinomas arising in the gall bladder(GB) or extrahepatic biliary ducts are uncommon and generally have a poor prognosis. The overall 5-year survival rates are less than $10\%$. Early experiences with the external radiation therapy demonstrated a good palliation with occasional long-term survival. The present report describes our experience over the past decade with irradiation of primary carcinomas of the gallbladder and extrahepatic biliary duct. Materials and Methods : From Feb. 1984 to Nov. 1995, thirty-three patients with carcinoma of the GB and extrahepatic biliary duct were treated with external beam radiotherapy with curative intent at our institution. All patients were treated with 4-MV linear accelerator and radiation dose ranged from 31.44Gy to 54.87Gy(median 44.25Gy), and three Patients received additional intraluminal brachytherapy(range, 25Gy to 30Gy). Twenty-seven Patients received postoperative radiation. Among 27 patients, Sixteen patients underwent radical operation with curative aim and the rest of the patients either had bypass surgery or biopsy alone. In seventeen patients, adjuvant chemotherapy was used and eleven patients were treated with 5-FU, mitomycin and leucovorin. Results : Median follow up period was 8.5 months(range 2-97 months). The overall 2-year and 5-year survival rates in all patients were $29.9\%$ and $13.3\%$ respectively. In patients with GB and extrahepatic biliary duct carcinomas, the 2-year survival rates were $34.5\%$ and $27.8\%$ respectively. Patients who underwent radical operation showed better 2-year survival rates than those who underwent palliative operation($43.8\%\;vs.\;20.7\%$), albeit statistically insignificant(p>0.05). The 2-year survival rates in Stage I and II were higher than in Stage III and IV with statistical significance(p<0.05). Patients with good performance status in the beginning showed significantly better survival rates than those with worse status(p<0.05). The 2-year survival rates in combined chemotherapy group and radiation group were $40.5\%$ and $22.0\%$ respectively. There was no statistical differences in two groups (p>0.05). Conclusion : The survival of patients with relatively lower stage and/or initial good performance was significantly superior to that of others. We found an statistically insignificant trend toward better survival in patients with radical operation and/or chemotherapy, More radical treatment strategies, such as total resection with intensive radiation and/or chemotherapy may offer a better chance for cure in selective patients with carcinoma of gall bladder and extrahepatic biliary ducts.

• 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.