• Asian Pacific Journal of Cancer Prevention
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• v.16 no.1
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• pp.363-365
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• 2015

Background: Kidney cancer is the third most frequent urologic cancer in Lebanon after prostate and bladder cancer, accounting for 1.5% of all diagnosed cancers. In this paper, we report the histologic characteristics and distribution of kidney cancer, never described in Lebanon or the Middle East. Materials and Methods: Pathology results of operated kidney cancer were collected during a two year period (2010-2011) from two different Lebanese hospitals (Hotel-Dieu de France University Hospital and Saint Joseph Hospital). A total of 124 reports were reviewed and analyzed according to WHO classification of 2009. Results: The 124 patients diagnosed with kidney cancer had a median age of 62.4 [18-86], 75% being men and 25% women. Some 71 % of the lesions were renal cell carcinoma (RCC), 25.8% had a urothelial histology, 1.6% were lymphomas and 1.6% were metastases to the kidney. Patients having RCC had a median age of 60.3 [18-85], 77.3% were men and 22.7% women. Of the RCCs, 59.1% were clear cell carcinoma, 22.7% papillary, 11.4% chromophobic, 3.4% rom the collecting ducts of Bellini and 3.4% were not otherwise classified. Conclusions: Histological distribution of Lebanese kidney cancer seems unusual when compared to the literature. The percentage of urothelial renal pelvis tumors is strikingly high. Moreover, clear cell carcinoma accounts for only 59.1% of RCCS in contrast to the 75% described elsewhere, while papillary carcinoma represents more than 22.7% compared to 10%.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1447-1451
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• 2014

Purpose: To compare histopathologic findings of patients who underwent transurethral resection of a bladder tumor (TUR-B) between groups with and without the metabolic syndrome. Materials and Methods: We retrospectively analyzed data of 535 patients who underwent TUR-B in our department between October 2005 and March 2011. All patients had primary urethelial cell carcinoma (UCB). Histologic stage, grade, the presence of hypertension, diabetes mellitus, body mass index (BMI), waist circumference, HDL and trigliseride levels were evaluated. The TNM classification was used, with Ta tumor accepted as lower stage and T1 and T2 tumors as higher stage bladder cancers. Also, the pathological grading adopted by the 2004 World Health Organization grading system were applied. Non-invasive papillary urothelial neoplasms of low malignant potential were regarded as low grade. Results: Among the total of 509 patients analyzed in our study, there were 439 males (86.2%) and 70 females (13.8%). Metabolic syndrome was significantly associated with high histologic grade, and high pathologic stage (p<0.001). Conclusions: The patients with metabolic syndrome were found to have statistically significant higher T stage and grade of bladder cancer. Further studies with more patients are needed to confirm our study.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2013-2020
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• 2014

Background: The aldehyde dehydrogenase 1 family member A1 (ALDH1A1) is one of the promising markers for identifying cancer stem cells in many cancer types, along with other markers including CD44. The aim of the present study was to evaluate the expression and clinical significance of putative cancer stem cell markers, CD44 and ALDH1A1, in a series of urothelial carcinomas of urinary bladder (UCUB) by tissue microarray (TMA). Materials and Methods: A total of 159 Urothelial Carcinomas (UC) including 96 (60%) low grade and 63 (40%) high grade carcinomas were immunohistochemically examined for the expression of CD44 and ALDH1A1. Correlations of the relative expression of these markers with clinicopathological parameters were also assessed. Results: High level expression of ALDH1A1 was found in 16% (25/159) of bladder UC which was significantly correlated with increased tumor size (p value=0.002), high grade (p value<0.001), pathologic stage (T1, p value=0.007 and T2, p value<0.001) and increased rate of recurrence (p value=0.013). A high level of CD44 expression was found in 43% (68/159) of cases, being positively correlated with histologic grade (p value=0.032) and recurrence (p value=0.039). Conclusions: Taken together, our results showed that ALDH1 was concurrently expressed in a fraction of CD44+ tumors and its expression correlated with poor prognosis in UCs. ALDH1A1 could be an ideal marker for targeted therapy of UCs in combination with conventional therapies, particularly in patients with high grade carcinomas. These findings indicate that cells expressing ALDH1A1 along with CD44 can be a potential therapeutic target in bladder carcinomas.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10401-10405
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• 2015

Background: Molecular prognostic markers have been under investigation for the last decade and no validated marker to date has been proven to be used in daily clinical practice for urinary bladder cancers. The aim of the present study is to evaluate the significance of HYAL-1 expression in prediction of recurrence and progression in pT1 urothelial carcinomas. Materials and Methods: Eighty-nine urothelial carcinoma cases staged as T1 according to 2004 WHO classification were studied. Representative sections from every case were stained immunohistochemically for HYAL-1 and scored between 0 and +3, according to staining density, and graded as low and high for the scores 0-1 and 2-3, respectively. Results: Of the 89 pT1 bladder cancer patients, HYAL-1 expression was high in 92.1% (82 patients; 72 patients +3 and 10 patients +2) and low in 7.9% (only 7 patients; 6 patients +1 and 1 patient 0) of the cases. Of the 89 patients, 38 (42.7%) had recurrence and 22 (24.7%) showed progression. HYAL-1 staining did not show significant characteristics for tumor grade, accompanying CIS, multiplicity, tumor size, age and sex. HYAL-1 expression did not have any prognostic value in estimating recurrence or progression. Conclusions: HYAL-1 expression was found to be high, but did not have any prognostic importance in T1 bladder urothelial carcinomas.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4057-4059
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• 2013

Background: Fluorescence in situ hybridization (FISH) testing may be useful to screen for bladder carcinoma or dysplasia by detecting aneuploidy chromosomes 3, 7, 17 and deletion of the chromosome 9p21 locus in urine specimens. This study aimed to assess the sensitivity, specificity, positive and negative predictive value of FISH in a multi-ethnic population in Asia. Materials and Methods: Patients with haematuria and/or past history of urothelial cancer on follow-up had their voided urine tested with FISH. Patients then underwent cystoscopy/ureteroscopy and any lesions seen were biopsied. The histopathological reports of the bladder or ureteroscopic mucosal biopsies were then compared with the FISH test results. Results: Two hundred sixty patients were recruited. The sensitivity and specificity of the FISH test was 89.2% and 83.4% respectively. The positive (PPV) and negative predictive values (NPV) were 47.1% and 97.9%. By excluding patients who had positive deletion of chromosome 9, the overall results of the screening test improved: sensitivity 84.6%; specificity 96.4%; PPV 75.9% and NPV 97.9%. Conclusions: UroVysion FISH has a high specificity of detecting urothelial cancer or dysplasia when deletion of chromosome 9 is excluded. Negative UroVysion FISH-tests may allow us to conserve health resources and minimize trauma by deferring cystoscopic or ureteroscopic examination.

• The Korean Journal of Urological Oncology
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• v.16 no.3
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• pp.89-96
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• 2018

Upper tract urothelial carcinoma (UTUC) has a relatively low prevalence rate of about 1.8 per 100,000 people. According to the recent literature, the development of diagnostic techniques has gradually increased the prevalence and diagnosis rate. In the past, when UTUC was diagnosed, more than 60% of the patients were diagnosed as locally advanced or metastatic cancer. However, since 2010, approximately 70% of the patients have been diagnosed as operable stage. Although radical nephroureterectomy is known as the basis of treatment for UTUC, overall survival is poor in patients with lymph node invasion. Especially, the finding that a localized UTUC is associated with a high risk of cancer metastasis in approximately 50% of patients suggests that these patients may not have sufficient treatment through surgery alone. The European Association of Urology and the National Comprehensive Cancer Network guideline 2017 suggested that postoperative adjuvant chemotherapy may be considered in patients with advanced UTUC beyond pT2. Also, recent meta-analyses have reported that cisplatin-based adjuvant chemotherapy can be expected to have a synergistic effect of overall survival and disease-free survival. However, many patients with UTUC undergo postoperative renal failure, which may result in failure to perform cisplatin-based adjuvant chemotherapy with adequate dose. For this reason, several researchers have suggested that it is beneficial to apply neoadjuvant chemotherapy when the preoperative renal function is maintained to a certain extent. But, neoadjuvant chemotherapy has not been used by many clinicians because of the lack of studies and the rarity of the disease. We are currently discussing the outcomes and prospects of perioperative chemotherapy.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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• pp.1539-1543
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• 2015

Background: Uroplakins have been widely investigated as potential markers in patients with bladder cancer because these proteins are specific to the urothelium. However, the role of uroplakin proteins in bladder cancer remains unknown. In this study, preoperative serum levels of uroplakin III were measured in patients with urothelial carcinoma of the urinary bladder and examined for possible association with clinicopathological features and clinical outcomes. Materials and Methods: This study included 52 bladder cancer patients at various stages and 28 healthy controls. Uroplakin III levels were detected in preoperative sera using an automated dot blot system and a micro-dot blot array. Results: There was a significant increase in serum uroplakin III levels in patients with bladder cancer as compared to healthy controls (p<0.05). In addition, serum uroplakin III levels were associated with muscle-invasive status, high grade and lymphovascular invasion (p<0.02). Log-rank tests indicated high serum uroplakin III to be significantly associated with cancer-specific mortality. Conclusions: Determination of serum uroplakin III level could be valuable for identifying patients with biologically aggressive bladder cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.1957-1962
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• 2012

Bladder cancer is a common malignancy worldwide. Despite the increased use of cisplatin-based combination therapy, the outcomes for patients with advanced disease remain poor. Recently, altered activation of the PI3K/Akt/mTOR pathway has been associated with reduced patient survival and advanced stage of bladder cancer, making its upstream or downstream components attractive targets for therapeutic intervention. In the present study, we showed that treatment with DTCM-glutaramide, a piperidine that targets PDK1, results in reduced proliferation, diminished cell migration and G1 arrest in 5637 and T24 bladder carcinoma cells. Conversely, no apoptosis, necrosis or autophagy were detected after treatment, suggesting that reduced cell numbers in vitro are a result of diminished proliferation rather than cell death. Furthermore previous exposure to 10 ${\mu}g/ml$ DTCM-glutarimide sensitized both cell lines to ionizing radiation. Although more studies are needed to corroborate our findings, our results indicate that PDK1 may be useful as a therapeutic target to prevent progression and abnormal tissue dissemination of urothelial carcinomas.

• 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.