• Korean Journal of Food Science and Technology
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• v.43 no.6
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• pp.659-674
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• 2011

Saccharin was reported to cause urinary bladder cancer in male rats when fed at high doses in a two-generation study, which led to a ban on the use of saccharin in Canada. However, no carcinogenic effect has been observed in other animal experiments conducted with mice, hamsters, or monkeys. Furthermore, numerous epidemiological studies have indicated that there was no relationship between saccharin consumption and the risk of bladder cancer in the human population. Sodium saccharin produces urothelial bladder tumors in rats by the formation of a urinary calcium phosphatecontaining precipitate, which is not relevant to humans because of critical interspecies difference in urine composition. Consequently, in 1999 IARC (International Agency for Research on Cancer) concluded that saccharin and its salts cannot be classified as to their carcinogenicity in humans. In 2010, the EPA (Environmental Protection Agency) of the United States removed saccharin from its list of hazardous substances. It is expected that the use of saccharin in foods might be expanded because saccharin is currently considered safe.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3773-3778
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• 2013

Increased oxidative stress and changes in DNA methylation are frequently detected in bladder cancer patients. We previously demonstrated a relationship between increased oxidative stress and hypomethylation of the transposable long-interspersed nuclear element-1 (LINE-1). Promoter hypermethylation of a tumor suppressor gene, runt-related transcription factor 3 (RUNX3), may also be associated with bladder cancer genesis. In this study, we investigated changes of DNA methylation in LINE-1 and RUNX3 promoter in a bladder cancer cell (UM-UC-3) under oxidative stress conditions, stimulated by challenge with $H_2O_2$ for 72 h. Cells were pretreated with an antioxidant, tocopheryl acetate for 1 h to attenuate oxidative stress. Methylation levels of LINE-1 and RUNX3 promoter were measured by combined bisulfite restriction analysis PCR and methylation-specific PCR, respectively. Levels of LINE-1 methylation were significantly decreased in $H_2O_2$-treated cells, and reestablished after pretreated with tocopheryl acetate. Methylation of RUNX3 promoter was significantly increased in cells exposed to $H_2O_2$. In tocopheryl acetate pretreated cells, it was markedly decreased. In conclusion, hypomethylation of LINE-1 and hypermethylation of RUNX3 promoter in bladder cancer cell line was experimentally induced by reactive oxygen species (ROS). The present findings support the hypothesis that oxidative stress promotes urothelial cell carcinogenesis through modulation of DNA methylation. Our data also imply that mechanistic pathways of ROS-induced alteration of DNA methylation in a repetitive DNA element and a gene promoter might differ.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1755-1758
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• 2016

Background: Anemia is the most common hematologic abnormality in bladder cancer (BC) patients. We evaluated the impact of preoperative anemia on oncologic outcomes in BC undergoing transurethral resection of a bladder tumor (TURBT) for the first time diagnosis. Materials and Methods: We retrospectively evaluated the data collected from 639 patients who underwent TURBT between January 2006 and September 2014 in our department. Of these patients, 320 qualified for inclusion in the study. The primary efficacy endpoint was the effect of preoperative anemia status on cancer-specific and overall survival. Independent t-test and chi-square analyses were performed to assess the effects of anemia on oncologic outcomes. Survival was estimated by using the Kaplan-Meier test. Results: There were 118 (36.9%) and 202 (63.1%) patients in the anemia (Group-1) and non-anemia groups (Group-2), respectively. The median follow-up duration was 68 months. Anemia was associated with decreased overall survival (p<0.001). Comparison between cancer-specific survival of two groups did not show any statistically significant difference (p=0.17). Conclusions: Preoperative anemia status of BC patients according to World Health Organization classification is associated with decreased overall survival, but not with cancer-specific survival. We think that preoperative hemoglobin levels should be considered in patient counseling and decision-making for additional therapy.

• The Korean Journal of Cytopathology
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• v.7 no.2
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• pp.192-196
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• 1996

The principal significance of the urothelial changes caused by polyomavirus activation is in an erroneous diagnosis of urothelial cancer; however, the clue to their benign nature is the smooth structureless nuclear configuration and the relative paucity of affected cells. Though virologic studies and electron microscopy are usually needed to firmly establish the diagnosis, cytology is the most readily available and rapid means of establishing a presumptive diagnosis of human polyomavirus infection. A urine specimen of a 24-year-old man with hemorrhagic cystitis beginning two months after bone marrow transplantation for acute myeloblastic leukemia(M2) was submitted for cytologic evaluation. Cytologic findings revealed a few inclusion-bearing epithelial cells intermingled with erythrocytes, neutrophils, lymphocytes, and macrophages. Most of the inclusion-bearing fells had large, round to ovoid nuclei almost completely filled with homogeneous dark, basophilic inclusion. The chromatin was clumped along the periphery and the cytoplasm was mostly degenerated. The other cells exhibited irregular inclusions attached to the nuclear membrane surrounded by an indistinct halo. These findings were consistent with polyomavirus infection.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.6
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• pp.2787-2793
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• 2016

Background: Urinary bladder cancer is a common malignancy in the West and ranks as the $7^{th}$ most common cancer in our region of Kashmir, India. FGFR3 mutations are frequent in superficial urothelial carcinoma (UC) differing from the RAS gene mutational pattern. The aim of this study was to analyze the frequency and association of FGFR3 and RAS gene mutations in UC cases. Materials and Methods: Paired tumor and adjacent normal tissue specimens of 65 consecutive UC patients were examined. DNA preparations were evaluated for the occurrence of FGFR3 and RAS gene mutations by PCR-SCCP and DNA sequencing. Results: Somatic point mutations of FGFR3 were identified in 32.3% (21 of 65). The pattern and distribution were significantly associated with low grade/stage (p<0.05). The overall mutations in exon 1 and 2 in all the forms of RAS genes aggregated to 21.5% and showed no association with any clinic-pathological parameters. In total, 53.8% (35 of 65) of the tumors studied had mutations in either a RAS or FGFR3 gene, but these were totally mutually exclusive in and none of the samples showed both the mutational events in mutually exclusive RAS and FGFR3. Conclusions: We conclude that RAS and FGFR3 mutations in UC are mutually exclusive and non-overlapping events which reflect activation of oncogenic pathways through different elements.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2303-2307
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• 2014

Background: Renal cancer is a serious public health problem which may be under reported and registered in our setup, since the Karachi cancer registry documented only 43 cases out of 4,268 incident cancer cases over 3 year duration. Therefore we aimed to determine the clinicopathologic characteristics of adult renal tumors in our setup. Materials and Methods: The study was conducted in histopathology department, Liaquat National Hospital and included total of 68 cases of adult renal tumors over 4 years. Detailed histopathologic characteristics of tumors were analyzed. Results: Mean age of patients was 56.4 (18-84) years. Renal cell carcinoma (RCC) was the most common cell type (78%) cases; followed by transitional/urothelial carcinoma (12.5%), leiomyosarcoma (4.7%), oncocytoma (1.6%), squamous cell carcinoma (1.6%) and high grade pleomorphic undifferentiated sarcoma (1.6%). Among 50 RCC cases; 62% were conventional/clear cell RCC (CCRCC) type followed by papillary RCC(PRCC), 24%; chromophobe RCC(CRCC), 6% and sarcomatoid RCC(SRCC), 8%. Mean tumor size for RCC was 7.2 cm. Most RCCs were intermediate to high grade (60% and 40% respectively). Capsular invasion, renal sinus invasion, adrenal gland involvement and renal vein invasion was seen in 40%, 18%, 2% and 10% of cases respectively. Conclusions: We found that RCC presents at an earlier age in our setup compared to Western populations. Tumor size was significantly larger and most of the tumors were of intermediate to high grade. This reflects late presentation of patients after disease progression which necessitates effective measures to be taken in primary care setup to diagnose this disease at an early stage.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2229-2234
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• 2012

Purpose: To assess efficacy of Ki67 combined with VEGF as a molecular grading model to predict outcomes with non-muscle invasive bladder cancer (NMIBC). Materials: 72 NMIBC patients who underwent transurethral resection (TUR) followed by routine intravesical instillations were retrospectively analyzed in this study. Univariate and multivariate analyses were performed to confirm the prognostic values of the Ki67 labeling index (LI) and VEGF scoring for tumor recurrence and progression. Results: The novel molecular grading model for NMIBC contained three molecular grades including mG1 (Ki67 $LI{\leq}25%$, VEGF $scoring{\leq}8$), mG2 (Ki67 LI>25%, VEGF $scoring{\leq}8$; or Ki67 $LI{\leq}25%$, VEGF scoring > 8), and mG3 (Ki67 LI > 25%, VEGF scoring > 8), which can indicate favorable, intermediate and poor prognosis, respectively. Conclusions: The described novel molecular grading model utilizing Ki67 LI and VEGF scoring is helpful to effectively and accurately predict outcomes and optimize personal therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3545-3549
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• 2016

Background: The incidence of bladder cancer is lower in Asian than in Western countries. However, the crude incidence and mortality of bladder cancer have recently increased in Japan because of the increased number of senior citizens. We have already reported risk factors for urothelial cancer in a large population-based cohort study in Japan (JACC study). However, we did not evaluate the cancer risk in the upper and lower urinary tract separately in our previous study. Materials and Methods: Here we evaluated the risk of cancer death in the upper and lower urinary tracts, separately, using the database of the JACC study. The analytic cohort included 46,395 males and 64,190 females aged 40 to 79 years old. The Cox proportional hazard model was used to determine hazard ratios and their 95% confidence intervals. Results: Current smoking increased the risk of both upper and lower urinary tract cancer deaths. A history of kidney disease was associated with an increased risk of bladder cancer death, even after controlling for age, sex and smoking status. Conclusions: The present study confirmed that current smoking increases the risk of both upper and lower urinary tract cancer deaths and indicated the possibility that a history of kidney disease may be a risk factor for bladder cancer death in the Japanese population.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6283-6286
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• 2014

In patients with microscopic hematuria there is a need for better identification of those who are at greater risk of harbouring bladder tumors. The RisikoCheck(C) questionnaire has a strong correlation with the presence of urothelial carcinoma (UC) of the bladder and in combination with other available tests may help identify patients who require detailed clinical investigations due to increased risk of presence of bladder tumors. This study aimed to evaluate the efficacy of RisikoCheck(C) questionnaire together with NMP-22(R) (BladderChek(R)) as a point-of-care urine test in predicting the presence of bladder tumors in patients presenting with microscopic hematuria as the sole finding. In this multi-institutional prospective evaluation of 303 consecutive patients without a history of urothelial carcinoma (UC), RisikoCheck(C) risk group assessment, urinary tract imaging and cystourethroscopy as well as urine cytology and Nuclear Matrix Protein-22 (NMP-22 BladderChek) testing were performed where available. The sensitivity, specificity, negative predictive value (NPV), and positive predictive values (PPV) for the risk adapted approach were calculated. All patients underwent cystoscopy, and tumors were detected in 18 (5.9%). Urine cytology and NMP-22 was positive for malignancy in 9 (3.2%) and 12 (7.5%) of patients, respectively. A total of 43 (14%) patients were in the high risk group according to the RisikoCheck(C) questionnaire. The sensitivity and specificity of the questionnaire in detecting a bladder tumor was 61.5 % and 84.0 % in the high risk group. In patients with either a positive NMP-22 test or high risk category RisikoCheck(C), 23.6% had bladder tumors with a corresponding sensitivity of 54.2% and specificity of 88.6%. If both tests were negative only 3.3% of the patients had bladder tumors. The results of our study suggest that the efficacy of diagnostic evaluation of patients with microscopic hematuria may be further enhanced by combining RisikoCheck(C) questionnaire with NMP-22.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2251-2255
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• 2014

Background: The aim of this study was to evaluate 10 years of false positive urine cytology records, along with follow-up histologic and cytologic data, to determine the significance of suspicious urine cytology findings. Materials and Methods: We retrospectively reviewed records of urine samples harvested between January 2002 and December 2012 from voided and catheterized urine from the bladder. Among the 21,283 urine samples obtained during this period, we located 1,090 eligible false positive findings for patients being evaluated for the purpose of confirming urothelial carcinoma (UC). These findings were divided into three categories: atypical, indeterminate, and suspicious of malignancy. Results: Of the 1,090 samples classified as false positive, 444 (40.7%) were categorized as atypical, 367 (33.7%) as indeterminate, and 279 (25.6%) as suspicious of malignancy. Patients with concomitant UC accounted for 105 (23.6%) of the atypical samples, 147 (40.1%) of the indeterminate samples, and 139 (49.8%) of the suspicious of malignancy samples (p<0.0001). The rate of subsequent diagnosis of UC during a 1-year follow-up period after harvesting of a sample with false positive urine cytology initially diagnosed as benign was significantly higher in the suspicious of malignancy category than in the other categories (p<0.001). The total numbers of UCs were 150 (33.8%) for atypical samples, 213 (58.0%) for indeterminate samples, and 199 (71.3%) for samples categorized as suspicious of malignancy. Conclusions: Urine cytology remains the most specific adjunctive method for the surveillance of UC. We demonstrated the clinical value of dividing false positive urine cytology findings into three categories, and our results may help clinicians better manage patients with suspicious findings.