• Asian Pacific Journal of Cancer Prevention
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• v.15 no.24
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• pp.10813-10817
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• 2015

Background: Possible roles of nestin expression in terms of predicting intravesical BCG therapy response in T1 high grade bladder cancer patients were investigated. Materials and Methods: T1 high grade bladder cancer patients who were treated with intravesical BCG between 1990-2009 were included. Immunohistochemical staining for nestin expression was performed. Nestin(+) and nestin(-) patients were compared in terms of recurrence and progression rates. Results: Sixty-three patients were included and median follow-up time was twenty-five months. After staining; 33 patients (52.4%) were classified as nestin (+) and 30 (47.6%) as (-). Nestin (+) patients were more likely to recur compared to nestin (-) patients (60.6% vs. 30%, p<0.05). Progression rates were also higher in nestin (+) patients, although this result did not reach statistical significance (15.2 % vs. 10 %, p=0.710). Conclusions: Nestin expression, which seems effective in predicting recurrence, appears to have a potential role in the urothelial carcinoma tumorigenesis. Patients with high grade bladder cancer and positive nestin expression need close follow-up and might be informed about more tendency to recur. Further comprehensive studies including larger patient cohorts may clarify the role of nestin in bladder cancer.

• 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.15 no.21
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• pp.9137-9142
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• 2014

Background: To explore the expression of DcR3 protein and its clinicopathological significance in bladder urothelial carcinomas (BUC). Materials and Methods: Immunohistochemistry was performed to detect the expression of DcR3, caspase-3, Bcl-2, VEGF, Ki-67, PCNA and P53 in 166 BUC and 56 normal bladder tissues. Western blotting was used to detect the expression of DcR3 in the supernatants of cultured BUC cells. Results: Overexpression of DcR3 was found in BUC tissues and cell lines, with significant elevation as compared to normal bladder tissues (p<0.0001). Higher DcR3 expression was related to the status of invasion, lymph node metastasis and recurrence. Furthermore, DcR3 expression was negatively correlated with caspase-3 and positively associated with Bcl-2, VEGF, Ki-67 labeling index (LI), PCNA LI and P53 (all p<0.0001), respectively. Conclusions: DcR3 may play a crucial role as an oncogene in tumorigenesis, deterioration and progress of BUC via influencing related pathways of apoptosis, proliferation and angiogenesis. The detection of DcR3 protein in the formalinfixed and paraffin-embedded samples could assist to predict in prognosis of BUC patients.

• 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.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3223-3227
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• 2015

Objective: We evaluated the association of body mass index (BMI) with perioperative outcomes in patients who underwent laparoscopic or open radical nephroureterectomy. Materials and Methods: This retrospective single-center study included 113 patients who had been diagnosed with upper urinary tract cancer from January 1998 to June 2013 and were treated with laparoscopic nephroureterectomy (Lap group, n=60) or open nephroureterectomy (Open group, n=53). Laparoscopic nephroureterectomy was performed via a retroperitoneal approach following an open partial cystectomy. The two surgical groups were stratified into a normal-BMI group (<25) and a high-BMI group ($BMI{\geq}25$). The high-BMI group included 27 patients: 13 in the Lap group and 14 in the Open group. Results: Estimated blood loss (EBL) in the Lap group was much lower than that in the Open group irrespective of BMI (p<0.01). Operative time was significantly prolonged in normal-BMI patients in the Lap group compared to those in the Open group (p=0.03), but there was no difference in operative time between the Open and Lap groups among the high-BMI patients. Multivariate logistic regression analysis of the data for all the cohorts revealed that the open procedure was a significant risk factor for high EBL (p<0.0001, hazard ratio 8.02). Normal BMI was an independent predictor for low EBL (p=0.01, hazard ratio 0.25). There was no significant risk factor for operative time in multivariate analysis. There were no differences in blood transfusion rates or adverse event rates between the two surgical groups. Conclusions: Laparoscopic radical nephroureterectomy via a retroperitoneal approach can be safely performed with significantly reduced EBL even in obese patients with upper urinary tract cancer.

• Journal of the Korean Society of Radiology
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• v.81 no.3
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• pp.610-619
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• 2020

Purpose The study aimed to investigate the role of Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) in predicting incidental prostate cancer (PCa) or urothelial carcinoma (UCa) extension in urinary bladder (UB) cancer patients. Materials and Methods A total of 72 UB cancer patients who underwent radical cystoprostatectomy and 3 Tesla multiparametric MRI before surgery were enrolled. PI-RADS v2 ratings were assigned by two independent radiologists. All prostate specimens were examined by a single pathologist. We compared the multiparametric MRI findings rated using PI-RADS v2 with the pathologic data. Results Of the 72 UB cancer patients, 29 had incidental PCa (40.3%) and 20 showed UCa extension (27.8%), with an overlap for 3 patients. With a score of 4 as the cut-off value for predicting incidental PCa, the diagnostic accuracy was 65.3%, specificity was 90.7%, and positive predictive value (PPV) was 66.7%. The diagnostic accuracy for incidental UCa extension was 47.2%, specificity was 92.3%, and PPV was 83.3%. Conclusion Despite the low diagnostic accuracy, the PPV and specificity were relatively high. Therefore, PI-RADS v2 scores of 1, 2, or 3 may help exclude the probability of incidental PCa or UCa extension.

• Journal of the Korean Society of Radiology
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• v.82 no.5
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• pp.1033-1052
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• 2021

Bladder cancer is a relatively common cancer type, with a high recurrence rate, that can be often encountered in the imaging study. Accurate diagnosis and staging have a significant impact on determining treatment and evaluating prognosis. Bladder cancer has been evaluated by transurethral resection of bladder tumor for clinical staging and treatment, but it is often understaged when compared with final pathologic result by radical cystectomy. If the location, size, presence of muscle invasion, lymph node metastasis, distant metastasis, and presence of upper urinary tract cancer can be accurately diagnosed and evaluated in an imaging study, it can be treated and managed more appropriately. For an accurate diagnosis, radiologists who evaluate the images must be aware of the characteristics of bladder cancer as well as its types, imaging techniques, and limitations of imaging studies. Recent developments in MRI with functional imaging have improved the quality of bladder imaging and the evaluation of cancer. In addition, the Vesical Imaging Reporting and Data System was published to objectively assess the possibility for muscle invasion of cancer. Radiologists need to know the types of bladder cancer treatment and how to evaluate the changes after treatment. In this article, the characteristics of bladder urothelial carcinoma, various imaging studies, and findings are reviewed.

• BMB Reports
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• v.49 no.10
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• pp.578-583
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• 2016

Special AT-rich sequence binding protein 1 (SATB1) is a nuclear matrix-associated DNA-binding protein that functions as a chromatin organizer. SATB1 is highly expressed in aggressive breast cancer cells and promotes growth and metastasis by reprograming gene expression. Through genome-wide cross-examination of gene expression and histone methylation, we identified SATB1 target genes for which expression is associated with altered epigenetic marks. Among the identified genes, long noncoding RNA urothelial carcinoma-associated 1 (UCA1) was upregulated by SATB1 depletion. Upregulation of UCA1 coincided with increased H3K4 trimethylation (H3K4me3) levels and decreased H3K27 trimethylation (H3K27me3) levels. Our study showed that SATB1 binds to the upstream region of UCA1 in vivo, and that its promoter activity increases with SATB1 depletion. Furthermore, simultaneous depletion of SATB1 and UCA1 potentiated suppression of tumor growth and cell survival. Thus, SATB1 repressed the expression of oncogenic UCA1, suppressing growth and survival of breast cancer cells.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8293-8298
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• 2016

Background: Urinary stones are known predisposing factors for upper urinary tract carcinoma (UUTC) which are commonly detected at advanced stage with poor outcome because of rarity and lack of specific criteria for early detection. Aims and objectives: The main aim was to evaluate the impact of age, gender andstone characteristics on risk of developing UUTC in patients with chronic nephrolithiasis. We also discuss the role of aberrant angiogenesis (AA) and immunohistochemical expression of p53, p16INK4a, CK20 and Ki-67 in diagnosis of pelvicalyceal neoplastic (NL) and pre-neoplastic lesions (PNL) in these patients. Materials and Methods: Retrospective analysis of pelvicalyceal urothelial lesions from 88 nephrectomy specimens were carried out in a tertiary care centre from June 2012 to December 2014. Immunohistochemistry (IHC) was performed on 37 selected cases. Computed image analysis was performed to analyse aberrant angiogenesis. Results: All UUTC (5.7%) and metaplastic lesions were found to be associated with stones. Some 60% were pure squamous cell carcinoma and 40% were transitional cell carcinoma. Odd ratios for developing NL and PNL lesions in presence of renal stone, impacted stones, multiple and large stag horn stones were 9.39 (95% CI 1.15-76.39, p value 0.05), 6.28 (95% CI 1.59-24.85, p value 0.000) and 7.4 (95% CI, 2.29-23.94, p value 0.001) respectively. When patient age was ${\geq}55$, the odds ratio for developing NL was 3.43 (95% CI 1.19-9.88, p value 0.019). IHC analysis showed that mean Ki-67 indices were $3.15{\pm}3.63%$ for non-neoplastic lesions, $10.0{\pm}9.45%$ for PNL and $28.0{\pm}18.4%$ for NL. Sensitivity and specificity of CK20, p53, p16INK4a, AA were 76% and 95.9%; 100% and 27.5%; 100% and 26.5%; 92.3 % and 78.8% respectively. Conclusions: Age ${\geq}55years$, large stag horn stones, multiple stones and impacted stones are found to be associated with increased risk of NL and PNL in UUT. For flat lesions, a panel of markers, Ki 67 index >10 and presence of aberrant angiogenesis were more useful than individual markers.