Displaying all 8 publications

  1. Chan JY, Li H, Singh O, Mahajan A, Ramasamy S, Subramaniyan K, et al.
    Urol. Oncol., 2013 Nov;31(8):1553-60.
    PMID: 22561070 DOI: 10.1016/j.urolonc.2012.02.009
    OBJECTIVES: Recently, several genome-wide association studies have demonstrated a cumulative association of 5 polymorphic variants in chromosomes 8q24 and 17q with prostate cancer (CaP) risk in Caucasians, particularly those harboring aggressive clinicopathologic characteristics. The purpose of this study was to evaluate the influence of these variants on CaP susceptibility in Singaporean Asian men.
    MATERIALS AND METHODS: We performed a case-control study in 289 Chinese CaP patients and 412 healthy subjects (144 Chinese, 134 Malays, and 134 Indians), and examined the association of the 5 single nucleotide polymorphisms (SNPs) with CaP.
    RESULTS: In the healthy subjects, rs16901979 A-allele frequency was highest amongst Chinese (0.32) compared with Malays (0.13; P < 0.0001) or Indians (0.09; P < 0.0001); rs6983267 G-allele was highest in Indians (0.51) compared with Chinese (0.42; P = 0.041) or Malays (0.43; P = 0.077); whereas rs1859962 G-allele frequency was highest amongst Indians (0.56) compared with Chinese (0.40; P = 0.0002) or Malays (0.38; P < 0.0001). Individuals with the rs4430796 TT genotype were at increased CaP risk in the Chinese via a recessive model (odds ratios (OR) = 1.56, 95% CI = 1.04-2.33). Significant associations were observed for rs4430796 TT with Gleason scores of ≥ 7 (OR = 1.76, 95% CI = 1.14-2.73) and prostate-specific antigen (PSA) levels of ≥ 10 ng/ml at diagnosis (OR = 1.63, 95% CI = 1.01-2.63), as well as for rs6983267 GG with stage 3-4 CaPs (OR = 1.91, 95% CI = 1.01-3.61). A cumulative gene interaction influence on disease risk, which approximately doubled for individuals with at least 2 susceptibility genotypes, was also identified (OR = 2.18, 95% CI = 1.10-4.32).
    CONCLUSIONS: This exploratory analysis suggests that the 5 genetic variants previously described may contribute to prostate cancer risk in Singaporean men.
    KEYWORDS: Cancer; Ethnicity; Gleason; Pharmacogenetics; Polymorphism; Prostate
  2. Sothilingam S, Sundram M, Malek R, Sahabuddin RM
    Urol. Oncol., 2010;28(6):670-2.
    PMID: 21062649 DOI: 10.1016/j.urolonc.2009.12.014
    The incidence of prostate cancer in Malaysia is still low compared to the west. This may be due to a true low incidence or lower detection rates. Prostate Awareness Campaigns are held on a yearly basis to educate and encourage males over the age of 50 years to have their prostate examined. Such a campaign was organized in 2005 at the national level involving 12 district hospitals. A total of 2770 participants attended the campaign. 38.7% had no urinary symptoms and attended out of curiosity. Among the symptomatic patients, nocturia was the most bothersome in the majority. 84.6% of the participants also had some degree of erectile dysfunction based on the IIEF questionnaire. 10.4% of participants had a PSA > 4 ng/mL. Malay participants had the highest mean PSA level (2.32 ng/mL) and Indian participants the lowest (1.30 ng/mL). 408 participants were called back for biopsy but only 183 agreed to the biopsy. 30 cancers were detected. At present Malaysia will benefit most by continuing to conduct these awareness programmes to educate the public on prostate disease and hopefully in future patients will be less reluctant to have prostate biopsies taken when indicated.
  3. Teh GC
    Urol. Oncol., 2010 Nov-Dec;28(6):682-5.
    PMID: 21062652 DOI: 10.1016/j.urolonc.2010.03.017
    With maturing functional and oncologic outcomes data, open partial nephrectomy (OPN) has become the standard of care for T1a renal tumor. Laparoscopic approach can provide a speedier recovery with less blood loss and postoperative pain. Presuming adequate laparoscopic expertise, laparoscopic partial nephrectomy can provide equivalent oncologic outcome as for OPN albeit with higher urologic complications rate and longer warm ischemia time. With refinement of technique and use of robotic assistant, the shortcomings of laparoscopic approach can be further reduced. This article is a mini-review on the current status of laparoscopic approach to partial nephrectomy in the management of small renal mass.
  4. Fahmy O, Khairul-Asri MG, Schubert T, Renninger M, Kübler H, Stenzl A, et al.
    Urol. Oncol., 2018 02;36(2):54-59.
    PMID: 29196179 DOI: 10.1016/j.urolonc.2017.11.007
    PURPOSE: Currently, identified factors for urethral recurrence (UR) are based on individual reporting which has displayed controversy. In addition, risk of UR is one of the limiting factors to offer neobladder diversion during radical cystectomy (RC). We aim to systematically evaluate the incidence and risk factors of UR post-RC and its effect on survival.

    MATERIALS AND METHODS: A systematic online search was conducted according to PRISMA statement for publications reporting on UR after RC. From initial 802 results, 14 articles including 6169 patients were included finally after exclusion of ineligible studies.

    RESULTS: The incidence rate of UR was 4.4% (1.3%-13.7%). It was significantly lower with neobladder diversion (odds ratio = 0.44, 95% CI: 0.24-0.79, P = 0.006). Muscle invasion (hazard ratio = 1.18, 95% CI: 0.86-1.62, P = 0.31), carcinoma in situ (hazard ratio 0.97, 95% CI: 0.64-1.47, P = 0.88), prostatic stromal involvement (hazard ratio = 2.26, 95% CI: 0.01-627.75, P = 0.78), and prostatic urethral involvement (hazard ratio = 2.04, 95% CI: 0.20-20.80, P = 0.55) have no significant effect on UR. Men displayed tendency toward higher incidence of UR (odds ratio = 2.21, 95% CI: 0.96-5.06, P = 0.06). Absence of recurrence displayed tendency toward better disease specific survival, yet not significant (hazard ratio = 0.84, 95% CI: 0.66-1.08, P = 0.17). These results are limited by the retrospective nature of the included studies.

    CONCLUSION: Muscle invasion, carcinoma in situ and prostatic stromal or urethral involvement at time of RC have no significant effect on UR. Orthotopic neobladder is associated with a significant lower risk of UR after RC.

  5. Fahmy O, Khairul-Asri MG, Schubert T, Renninger M, Malek R, Kübler H, et al.
    Urol. Oncol., 2018 02;36(2):43-53.
    PMID: 29102254 DOI: 10.1016/j.urolonc.2017.10.002
    OBJECTIVE: This study aimed to comprehensively analyze the oncological long-term outcomes of trimodal therapy (TMT) and radical cystectomy (RC) for the treatment of muscle-invasive bladder cancer (BC) with or without neoadjuvant chemotherapy (NAC).

    PATIENTS AND METHODS: A systematic search was conducted according to the PRISMA guidelines for studies reporting on outcomes after TMT and RC. A total of 57 studies including 30,293 patients were included. The 10-year overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) rates for TMT and RC were assessed.

    RESULTS: The mean 10-year OS was 30.9% for TMT and 35.1% for RC (P = 0.32). The mean 10-year DSS was 50.9% for TMT and 57.8% for RC (P = 0.26). NAC was administered before therapy to 453 (13.3%) of 3,402 patients treated with TMT and 812 (3.0%) of 27,867 patients treated with RC (P<0.001). Complete response (CR) was achieved in 1,545 (75.3%) of 2,051 evaluable patients treated with TMT. A 5-year OS, DSS, and RFS after CR were 66.9%, 78.3%, and 52.5%, respectively. Downstaging after transurethral bladder tumor resection or NAC to stage ≤pT1 at RC was reported in 2,416 (29.1%) of 8,311 patients. NAC significantly increased the rate of pT0 from 20.2% to 34.3% (P = 0.007) in cT2 and from 3.8% to 23.9% (P<0.001) in cT3-4. A 5-year OS, DSS, and RFS in downstaged patients (≤pT1) at RC were 75.7%, 88.3%, and 75.8%, respectively.

    CONCLUSION: In this analysis, the survival outcomes of patients after TMT and RC for MIBC were comparable. Patients who experienced downstaging after NAC and RC exhibited improved survival compared to patients treated with RC only. Best survival outcomes after TMT are associated with CR to this approach.

  6. Poniah P, Mohd Zain S, Abdul Razack AH, Kuppusamy S, Karuppayah S, Sian Eng H, et al.
    Urol. Oncol., 2017 09;35(9):545.e1-545.e11.
    PMID: 28527622 DOI: 10.1016/j.urolonc.2017.04.017
    BACKGROUND: Two key issues in prostate cancer (PCa) that demand attention currently are the need for a more precise and minimally invasive screening test owing to the inaccuracy of prostate-specific antigen and differential diagnosis to distinguish advanced vs. indolent cancers. This continues to pose a tremendous challenge in diagnosis and prognosis of PCa and could potentially lead to overdiagnosis and overtreatment complications. Copy number variations (CNVs) in the human genome have been linked to various carcinomas including PCa. Detection of these variants may improve clinical treatment as well as an understanding of the pathobiology underlying this complex disease.

    METHODS: To this end, we undertook a pilot genome-wide CNV analysis approach in 36 subjects (18 patients with high-grade PCa and 18 controls that were matched by age and ethnicity) in search of more accurate biomarkers that could potentially explain susceptibility toward high-grade PCa. We conducted this study using the array comparative genomic hybridization technique. Array results were validated in 92 independent samples (46 high-grade PCa, 23 benign prostatic hyperplasia, and 23 healthy controls) using polymerase chain reaction-based copy number counting method.

    RESULTS: A total of 314 CNV regions were found to be unique to PCa subjects in this cohort (P<0.05). A log2 ratio-based copy number analysis revealed 5 putative rare or novel CNV loci or both associated with susceptibility to PCa. The CNV gain regions were 1q21.3, 15q15, 7p12.1, and a novel CNV in PCa 12q23.1, harboring ARNT, THBS1, SLC5A8, and DDC genes that are crucial in the p53 and cancer pathways. A CNV loss and deletion event was observed at 8p11.21, which contains the SFRP1 gene from the Wnt signaling pathway. Cross-comparison analysis with genes associated to PCa revealed significant CNVs involved in biological processes that elicit cancer pathogenesis via cytokine production and endothelial cell proliferation.

    CONCLUSION: In conclusion, we postulated that the CNVs identified in this study could provide an insight into the development of advanced PCa.

  7. Schubert T, Renninger M, Schmid MA, Hassan FN, Sokolakis I, Fahmy O, et al.
    Urol. Oncol., 2019 Sep 16.
    PMID: 31537484 DOI: 10.1016/j.urolonc.2019.08.013
    OBJECTIVES: To assess whether the presence and location of tumor-associated immune cell infiltrates (TAIC) on histological slides obtained from cystectomy specimens impacts on oncological outcomes of patients with bladder cancer (BC).

    MATERIAL AND METHODS: A total of 320 consecutive patients staged with cM0 bladder cancer underwent radical cystectomy (RC) between 2004 and 2013. The presence of TAIC (either located peritumorally [PIC] and/or intratumorally [IIC]) on histological slides was retrospectively assessed and correlated with outcomes. Kaplan-Meier analyses were used to estimate the impact of TAIC on recurrence-free (RFS), cancer-specific (CSS), and overall survival (OS). Multivariable Cox-regression analysis was carried out to evaluate risk factors of recurrence. The median follow-up was 37 months (IQR: 10-55).

    RESULTS: Of the 320 patients, 42 (13.1%) exhibited IIC, 141 (44.1%) PIC and 137 (42.8%) no TAIC in the cystectomy specimens. Absence of TAIC was associated with higher ECOG performance status (P = 0.042), histologically advanced tumor stage (≥pT3a; P < 0.001), lymph node tumor involvement (pN+; P = 0.022), positive soft tissue surgical margins (P = 0.006), lymphovascular invasion (P < 0.001), and elevated serum C-reactive protein levels (P < 0.001). The rate of never smokers was significantly higher in the IIC-group (64.3%) compared to the PIC-group (39.7%, P = 0.007) and those without TAIC (35.8%, P = 0.001). The 3-year RFS/CSS/OS was 73.9%/88.5%/76.7% for patients with IIC, 69.4%/85.2%/70.1% for PIC and 47.6%/68.5%/56.1% for patients without TAIC (P < 0.001/<0.001/0.001 for TAIC vs. no TAIC). In multivariable analysis, adjusted for all significant parameters of univariable analysis, histologically advanced tumor stage (P = 0.003), node-positive disease (P = 0.002), and the absence of TAIC (P = 0.035) were independent prognosticators for recurrence.

    CONCLUSIONS: In this analysis, the presence and location of TAIC in cystectomy specimens was a strong prognosticator for RFS after RC. This finding suggests that the capability of immune cells to migrate into the tumor at the time of RC is prognostically important in invasive bladder cancer.

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