4D perfusion CT of prostate cancer for image-guided radiotherapy planning: A proof of concept study.

PURPOSE: Advanced forms of prostate cancer (PCa) radiotherapy with either external beam therapy or brachytherapy delivery techniques aim for a focal boost and thus require accurate lesion localization and lesion segmentation for subsequent treatment planning. This study prospectively evaluated dynamic contrast-enhanced computed tomography (DCE-CT) for the detection of prostate cancer lesions in the peripheral zone (PZ) using qualitative and quantitative image analysis compared to multiparametric magnet resonance imaging (mpMRI) of the prostate. METHODS: With local ethics committee approval, 14 patients (mean age, 67 years; range, 57-78 years; PSA, mean 8.1 ng/ml; range, 3.5-26.0) underwent DCE-CT, as well as mpMRI of the prostate, including standard T2, diffusion-weighted imaging (DWI), and DCE-MRI sequences followed by transrectal in-bore MRI-guided prostate biopsy. Maximum intensity projections (MIP) and DCE-CT perfusion parameters (CTP) were compared between healthy and malignant tissue. Two radiologists independently rated image quality and the tumor lesion delineation quality of PCa using a five-point ordinal scale. MIP and CTP were compared using visual grading characteristics (VGC) and receiver operating characteristics (ROC)/area under the curve (AUC) analysis. RESULTS: The PCa detection rate ranged between 57 to 79% for the two readers for DCE-CT and was 92% for DCE-MRI. DCE-CT perfusion parameters in PCa tissue in the PZ were significantly different compared to regular prostate tissue and benign lesions. Image quality and lesion visibility were comparable between DCE-CT and DCE-MRI (VGC: AUC 0.612 and 0.651, p>0.05). CONCLUSION: Our preliminary results suggest that it is feasible to use DCE-CT for identification and visualization, and subsequent segmentation for focal radiotherapy approaches to PCa.

Evaluation of ABO blood group as a prognostic marker in renal cell carcinoma (RCC).

OBJECTIVE: To evaluate ABO blood group as a prognostic marker in patients with renal cell carcinoma (RCC). PATIENTS AND METHODS: This retrospective study included 556 consecutive patients who underwent surgery for RCC at a single institution. The associations of ABO blood group with clinical and pathological variables were assessed using Kruskal-Wallis and chi-squared tests. The impact on overall survival (OS) and RCC-specific survival (RCC-SS) was analysed using univariable and multivariable Cox proportional hazards regression models. RESULTS: Blood group O was associated with the absence of lymph node metastases (P = 0.034) and the presence of bilateral RCC (P = 0.017). No associations with age, gender, body mass index, Charlson comorbidity index, T stage, M stage, grade and histological subtype were observed. In univariable and multivariable survival analysis, ABO blood group was not associated with OS and RCC-SS. CONCLUSIONS: In the present study, ABO blood group was not linked with RCC prognosis. Blood group O may be associated with the absence of lymph node metastases and the presence of bilateral RCC. External validation in larger cohorts is necessary.

Bladder outlet obstruction (BOO) in men with castration-resistant prostate cancer.

OBJECTIVE: To evaluate the frequency of bladder outlet obstruction (BOO) and detrusor overactivity (DO) in patients with castration-resistant prostate cancer (CRPC) and lower urinary tract symptoms (LUTS). PATIENTS AND METHODS: Our prospective urodynamics database was queried. Inclusion criteria were CRPC and an International Prostate Symptom Score (IPSS) ≥ 20. Exclusion criteria were previous local therapy to the prostate gland, known urethral stricture disease, and a neurological component of LUTS. Twenty-one patients were identified. Urodynamic findings were analysed and compared with those of a matched cohort of 42 patients with benign prostatic enlargement (BPE). RESULTS: The median age of patients in the CRPC group was 74 years, and the median prostate-specific antigen (PSA) level at the time of the urodynamic study was 90 ng/mL. According to the BOO index, three patients (14%) were obstructed, three were equivocally obstructed (14%) and 15 were unobstructed. DO was seen in 12 patients (57%). Compared with the BPE group, patients with CRPC had lower cystometric bladder capacities (P = 0.003), were less likely to have BOO (14 vs 43%, P = 0.009) and more likely to have DO (57 vs 29%, P = 0.028). CONCLUSIONS: This study generates the hypothesis that only a minority of CRPC patients with LUTS have BOO, and that more than half of patients have DO. LUTS in CRPC may therefore be seldom attributable to BOO, but are, at least in part, related to DO and reduced cystometric capacity. A urodynamic investigation may be necessary before palliative transurethral resection of the prostate to select appropriate candidates. Larger prospective studies are needed to confirm our findings.

Transperineal template-guided biopsy for diagnosis of prostate cancer in patients with at least two prior negative biopsies.

OBJECTIVE: To evaluate the prostate cancer (PCa) detection rate, PCa location, PCa significance and complications of a standardized 24-core template-guided transperineal biopsy (TPB) approach in patients with at least two negative transrectal biopsies. METHODS: We prospectively recruited 50 men who had at least two negative transrectal ultrasound-guided extended biopsies in the past 24 months, a prostate-specific antigen (PSA) < 20 ng/mL, a prostate volume < 100 mL, and life expectancy of at least 90 % at 10 years. All patients underwent a standardized 24-core template-guided TPB biopsy. The PCa detection rate, PCa location, PCa significance, and complications were recorded. RESULTS: Median age was 57.5 years and the median PSA level was 7.3 ng/ml. PCa was detected in 24 patients (48 %). The anterior zone was involved in 16 (32 %) PCa. Six PCa (25 %) were insignificant. Biopsy related complications occurred in 2 patients (4 %). CONCLUSIONS: A 24-core TPB is a safe procedure with a high PCa detection rate. Few of the detected PCa are clinically insignificant. Men with at least two negative transrectal biopsies may be counseled to undergo TPB.

A prospective evaluation of pain associated with stone passage, stents, and stent removal using a visual analog scale.

OBJECTIVE: To investigate the perception of colicky pain due to ureteral stones and double-J (DJ)-associated discomfort and to evaluate the role of clinical parameters that might influence the perception of pain. MATERIALS AND METHODS: From November 2011 to May 2012, 124 consecutive patients with colicky pain due to ureteral stones and ureteroscopic stone extraction underwent DJ stent placement. A visual analog scale (VAS) was used to assess the pain at ureteral colic, during indwelling DJ stent, and at DJ stent removal. The association of clinical data with pain scores was also analyzed. RESULTS: Pain perception at the time of colic did not vary according to sex (P = .804), age (P = .674), or DJ stent length (P = .389). Stone size (<4 mm) was a predictor of a high VAS score (P = .001). Patients with recurrent stone formation had significantly less pain at the time of colic (P = .004), and DJ stent removal (P = .004) than those with the first instance of stone formation. The clinical experience at cystoscopic DJ stent removal influenced pain perception (P <.001). CONCLUSION: Using a VAS for the evaluation of pain perception is a valid method for the objectification of subjective discomfort. The VAS is an easy to administer scale and provides accurate information on the patients' status. Additional studies with larger cohorts focusing on pain perception using the VAS and other validated questionnaires are recommended to produce more consistent data.

The protease activated receptor 1 gene variation IVSn -14 A>T is associated with distant metastasis and cancer specific survival in renal cell carcinoma.

PURPOSE: PAR-1 mediates angiogenesis and impacts the process of tumor growth and disease progression. We evaluated the associations of the gene variations PAR-1 IVSn -14 A>T (rs168753), -506 Ins/Del (rs11267092) and -1426 C>T (rs32934) with renal cell carcinoma pathology and cancer specific survival. MATERIALS AND METHODS: DNA was extracted from the peripheral blood leukocytes of 236 consecutive patients with renal cell carcinoma. Genotyping was done using restriction fragment length polymorphism analysis of polymerase chain reaction amplicons and sequencing. RESULTS: The IVSn -14 AA genotype was associated with a 3.13-fold increased risk of distant metastases (p = 0.015). In addition, cancer specific survival of patients with IVSn -14 AA was significantly worse than in those with AT/TT (HR 2.98, p = 0.019). The 1 and 4-year cancer specific survival rate for AA vs AT/TT was 89% vs 99% and 82% vs 92%, respectively. After adjusting for the stage, size, grade and necrosis (SSIGN) score on multivariable analysis, IVSn -14 AA was identified as an independent adverse prognostic factor (HR 2.72, p = 0.044). The variations -506 Ins/Del and -1426 C>T were not significantly associated with pathological factors or cancer specific survival. CONCLUSIONS: Results suggest that the AA genotype of the PAR-1 variation IVSn -14 A>T is associated with an increased risk of metastasis and poorer prognosis of renal cell carcinoma. Therefore, assessing the individual risk based on genotypes may be a helpful adjunct to identify subgroups at high risk for a poor clinical outcome.

Intravesical bacillus Calmette-Guérin instillation therapy for non-muscle-invasive bladder cancer following solid organ transplantation.

BACKGROUND: Solid organ recipients have a substantial risk of developing bladder cancer, with high-risk non-muscle-invasive bladder cancer (NMIBC) being the most frequent diagnosis. Theoretically, adjuvant bacillus Calmette-Guérin (BCG) therapy is contraindicated, but limited data indicate its feasibility. The objective of this study was to evaluate the safety and efficacy of BCG following solid organ transplantation. MATERIALS AND METHODS: We reviewed the data of four solid organ recipients who received adjuvant BCG for high-risk NMIBC at our institution. Additionally, individual data of 12 patients were extracted from case series and case reports, which were identified through a systematic review of the literature. A meta-analysis was performed. RESULTS: Fourteen patients (88 %) had received a kidney, one a heart, and one a liver transplant. The median time from transplantation to bladder cancer was 60.5 months. The regimen of immunosuppression was not modified in 12 patients (75 %). Forty-two percent of patients did not receive prophylactic antibiotics, and 70 % had no side effects. Ten patients (63 %) experienced recurrence after a median of 14 months. Progression to muscle-invasive or metastatic disease was observed in two patients (13 %). Four patients (25 %) underwent radical cystectomy, and two patients died of the disease. CONCLUSIONS: BCG therapy is a safe option for patients with high-risk NMIBC following solid organ transplantation. However, there is a substantial risk of recurrence and progression. Urologists and patients considering BCG therapy should be aware of this and may consider early cystectomy. There is no evidence to support the need for prophylactic antibiotics.

Validation of serum C-reactive protein (CRP) as an independent prognostic factor for disease-free survival in patients with localised renal cell carcinoma (RCC).

OBJECTIVE: To validate high-sensitivity C-reactive protein (hs-CRP) serum levels as an independent marker for disease-free survival (DFS) in clinically localised clear cell renal cell carcinoma (ccRCC). PATIENTS AND METHODS: In all, 403 consecutive patients with clinically localised (T1-3N0M0) ccRCC treated by radical or partial nephrectomy were enrolled. Preoperative serum levels of hs-CRP were evaluated as both a continuous and categorical variables. Associations with clinical (age, gender) and pathological variables (T classification, grade, tumour necrosis) were assessed with the chi-square and Kruskal-Wallis tests. Univariable and multivariable Cox proportional hazards models were fitted. The prognostic accuracy (PA) was assessed with Harrell's C-index. RESULTS: The mean hs-CRP level was 1.32 mg/dL. The hs-CRP levels were associated with T classification (P = 0.05), high-grade disease (P < 0.001) and tumour necrosis (P = 0.003). After a median follow-up of 43 months, 41 patients (10.1%) had developed disease recurrence. With each unit increase in hs-CRP levels, the risk of recurrence increased by 10% (hazard ratio 1.10, P = 0.015). The thresholds of 0.5 and 0.75 mg/dL showed the best discrimination for stratification of patients according to the probability of recurrence. These categorically coded hs-CRP levels were identified as independent prognostic factors in multivariable analyses (P < 0.001) and led to a significant increase in the PA of a multivariable base model containing the variables of the 'Stage, Size, Grade and Necrosis' (SSIGN) score. CONCLUSIONS: This study validates preoperative serum hs-CRP levels as independent prognostic factor after surgery for localised ccRCC. Hs-CRP may be included in standard prognostic modelling after surgery and may guide surveillance and inclusion in adjuvant clinical trials.

MNS16A tandem repeat minisatellite of human telomerase gene and prostate cancer susceptibility.

Telomere dysfunction is an early event in the development of prostate cancer and telomerase (TERT) activity is detectable in the majority of prostate cancers. Genetic variation in TERT and its regulatory elements may influence prostate carcinogenesis. MNS16A, a functional polymorphic tandem repeat minisatellite of TERT, has been studied in several malignancies. We determined MNS16A genotypes in an Austrian case-control study for the first time in the context of prostate cancer, comprising 1165 prostate cancer cases and 674 benign prostate hyperplasia controls with PCR. In addition to the five reported variable number of tandem repeats (VNTRs), we identified VNTR-212, a rare variant, for the first time in a European population. Multiple logistic regression analysis revealed no differences in genotype distribution between cases and controls. However, in stratified analysis, MNS16A VNTR-274 (OR = 0.25, 95% CI = 0.06-0.79, P = 0.016) and genotype 274/302 (OR = 0.13, 95% CI = 0.01-0.58, P = 0.005) were associated with a significantly decreased risk of prostate cancer in the age group >70 years. Our finding of a MNS16A genotype conferring a protective effect against prostate cancer in older men suggests a potential role of this polymorphism in prostate cancer susceptibility but demands to be validated in further studies.

The CASP8 -652 6N insertion/deletion promoter polymorphism is associated with renal cell carcinoma risk and metastasis.

PURPOSE: Caspase-8 is a key regulator of apoptosis. Its cancer cell antigen induced cell death activity is strongly impacted by the insertion/deletion promoter polymorphism CASP8 -652 6N ins/del (rs3834129). We studied the association of this polymorphism with renal cell carcinoma risk and pathology. MATERIALS AND METHODS: In this hospital based case-control study 500 Austrian patients were genotyped, including 250 with renal cell carcinoma, and 250 age and gender matched healthy controls. Polymerase chain reaction amplified genomic DNA was evaluated by restriction fragment length polymorphism analysis and automatic sequencing. We assessed associations with renal cell carcinoma risk and pathological factors, and performed a meta-analysis of the literature. RESULTS: The CASP8 -652 6N ins/del polymorphism was significantly linked to renal cell carcinoma (chi-square for trend = 9.50, p = 0.002). Compared with ins/ins, del/del was associated with a 57% decreased risk of the disease (OR 0.43, 95% CI 0.26-0.73, p = 0.002). Furthermore, del/del was associated with a lower risk of distant metastases (p <0.05) but not with T stage, N stage or grade. On meta-analysis the CASP8 -652 6N ins/del polymorphism was associated with renal cell carcinoma risk (p <0.001). CONCLUSIONS: The del/del genotype of the CASP8 -652 6N ins/del promoter polymorphism decreases the overall risk of renal cell carcinoma. It may be associated with a decreased risk of metastasis. Larger studies are warranted to validate our findings.

High-risk human papilloma virus infection of the foreskin in asymptomatic boys.

OBJECTIVE: To evaluate the prevalence and genotypes of high-risk human papilloma virus (HPV) infection of the foreskin in asymptomatic boys before first sexual intercourse. MATERIALS AND METHODS: We collected 50 consecutive foreskin specimens after radical circumcision. Indication for surgery was phimosis. High-risk HPV status was determined by real-time polymerase chain reaction for the genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59. Immunohistochemistry for p16(INK4a) was performed. RESULTS: The median age at the time of surgery was 5.5 years (range, 5 months-15 years). High-risk HPV was detected in 6 of 50 foreskins (12%). All positive samples showed HPV16. No association with age or grade of phimosis was observed. Two samples were focally positive for p16(INK4a), both of which were HPV-negative. CONCLUSION: In a significant proportion of boys, subclinical high-risk HPV infections are found in the foreskin, which could be a reservoir for HPV-associated diseases. Our study generates the hypothesis that nonsexual routes play significant roles in HPV transmission. Because the human foreskin represents a high-risk HPV reservoir, vaccination may be also advised in boys.

The value of transurethral bladder biopsy after intravesical bacillus Calmette-Guérin instillation therapy for nonmuscle invasive bladder cancer: a retrospective, single center study and cumulative analysis of the literature.

PURPOSE: We evaluated the need of routine transurethral biopsies after an induction course of intravesical bacillus Calmette-Guérin for high grade nonmuscle invasive bladder cancer. MATERIALS AND METHODS: This retrospective study included 180 patients with high grade nonmuscle invasive bladder cancer who underwent a 6-week induction course of bacillus Calmette-Guérin. Cystoscopic findings, urinary cytology and pathological results of transurethral biopsy were evaluated. For cumulative meta-analysis we systematically reviewed studies indexed in MEDLINE®, EMBASE® and Web of Science®. The records of 740 patients from a total of 7 studies were finally analyzed. RESULTS: Biopsy was positive in 58 patients (32%). Cystoscopy appeared normal in 75 patients (42%) and showed only erythema in 51 (28%) and tumor in 54 (30%), of whom 6 (8%), 11 (22%) and 41 (76%), respectively, showed positive findings at biopsy. The positive predictive value of erythema was 15% with negative cytology and 56% with positive cytology. The positive predictive value of a tumor with negative and positive cytology was 63% and 89%, respectively. A combination of negative cytology and normal cystoscopy was associated with a negative biopsy in 94% of cases. A total of 970 bladder biopsies were taken, of which 137 (14%) were positive, including 20 of 125 erythematous lesions (16%), 73 of 107 tumors (68%) and 44 of 738 normal-appearing areas (6%). Cumulative analysis findings were comparable. CONCLUSIONS: Routine transurethral bladder biopsies after a bacillus Calmette-Guérin induction course are not necessary. An individually approach is recommended, tailored from cystoscopic findings and cytology.

Sex hormone-binding globulin is an independent predictor of biochemical recurrence after radical prostatectomy.

PURPOSE: We studied the association of serum sex hormone levels with clinicopathological variables and biochemical recurrence in men with prostate cancer treated with radical prostatectomy. MATERIALS AND METHODS: We prospectively studied preoperative serum sex hormone-binding globulin, luteinizing hormone, follicle-stimulating hormone, and free and total testosterone in 372 patients undergoing radical prostatectomy. Biochemical recurrence was analyzed in 285 patients and defined as prostate specific antigen 0.2 ng/ml or higher at least 30 days after radical prostatectomy. Median followup was 43.6 months. RESULTS: Median sex hormone-binding globulin was 37.4 nmol/l, luteinizing hormone 4.1 mU/ml, follicle-stimulating hormone 5.9 mU/ml, and free and total testosterone 0.069 and 3.7 ng/ml, respectively. There was no significant association of sex hormone-binding globulin, luteinizing hormone, follicle-stimulating hormone or total testosterone with T and N stage, and margin status. Luteinizing hormone, follicle-stimulating hormone, and free and total testosterone were not associated with biochemical recurrence. In contrast, for each 10 U increase in sex hormone-binding globulin the risk of biochemical recurrence increased by 12% (p = 0.045). On multivariable analysis sex hormone-binding globulin achieved independent predictor status after adjusting for standard clinicopathological variables. After stepwise regression a model containing T and N stage, Gleason score, margin status, prostate weight and sex hormone-binding globulin improved the accuracy of a base model by 1.3% (79.0% vs 77.7%). CONCLUSIONS: Preoperative serum sex hormone-binding globulin is independently associated with biochemical recurrence after radical prostatectomy and increases the predictive accuracy of a standard multivariable model. Routine assessment of sex hormone-binding globulin sex hormone-binding globulin may be a helpful adjunct to identify patients who need early adjuvant therapy.

Multidetector computed tomography virtual cystoscopy: an effective diagnostic tool in patients with hematuria.

OBJECTIVE: To evaluate the efficacy and the potential use of multidetector computed tomography virtual cystoscopy (MDCT-VC) in patients with gross hematuria. METHODS: A total of 32 patients underwent MDCT-VC, cystoscopy, and a cytologic examination. The slice thickness of MDCT was 1 mm. Bladder distension was done with room air. The data were converted into 3-dimensional virtual reconstructive models. The data sets were reviewed independently by 2 experienced radiologists. Tumors confined to the mucosa, infiltrating the muscularis, and transmural tumors were distinguished. RESULTS: VC showed a sensitivity and specificity of 100%. The radiologic accuracy regarding T stage correlated in 87.5%. MDCT-VC identified 21 bladder lesions suspicious for bladder cancer in 18 patients. The histologic results showed 22 patients with bladder lesions, 18 were diagnosed with transitional cell carcinoma of the bladder, 3 had bladder endometriosis, and 1 had an infiltrating colon cancer. Four patients had concomitant carcinoma in situ lesions, which were not seen completely with MDCT-VC. However, cytology was positive in those cases. Ten patients did not have any tumor signs on VC and the subsequent conventional cystoscopy did not bring any change to the initial tumor-free diagnosis of VC. CONCLUSION: MDCT-VC combined with urine cytology is a good alternative to conventional cystoscopy for patients with painless gross hematuria. It should be used as a decision-making aid to identify patients who will benefit from additional cystoscopic examination. Future developments should focus on the visibility of sessile and carcinoma in situ lesions.

Age-specific PCA3 score reference values for diagnosis of prostate cancer.

PURPOSE: We evaluated the impact of age on PCA3 score and the utility of age-specific reference values in predicting initial prostate biopsy (pBx) outcomes. PATIENTS AND METHODS: This single-center, retrospective study included 205 men who underwent an initial 14-core TRUS-guided pBx due to PSA > 3.0 ng/ml or suspicious digital-rectal examination (DRE). PCA3 scores were measured with the Progensa assay. Linear regression models were fit to identify factors that impact PCA3 score and to determine age-specific reference values. Predictive accuracies of logistic regression models predicting presence of prostate cancer (PCa) were analyzed. RESULTS: The positive biopsy rate was 37%. In multivariable linear regression, age (P < 0.001), presence of PCa (P < 0.001), and multifocal HG-PIN (P = 0.012) were independent predictors of PCA3 score. Age showed the strongest impact on PCA3 score (T = 4.77). The upper 95% confidence interval of PCA3 score in each age category was defined as the age-specific limit. A PCA3-score over the age-specific limit (PCA3-age) was associated with an 4.17-fold increased odds of being diagnosed with PCa (P < 0.001). In multivariable logistic regression models predicting the presence of PCa, predictive accuracy of a base model (age, DRE, PSA, volume) increased from 69.6 to 75.4% (P = 0.037) by adding the continuous PCA3 score, to 73.9% (P = 0.098) with the 35 cutoff (PCA3-35) and to 77.1% (P = 0.008) with PCA3-age. CONCLUSIONS: PCA3 score increases with age, independent of PCa presence. Age-specific PCA3 score reference values are superior to PSA, continuous PCA3 score, and PCA3-35 in predicting initial pBx outcome. Therefore, an age-adjusted PCA3 score should be used for interpretation of the results.

Lower serum total testosterone is associated with lymph node metastases in a radical prostatectomy cohort study.

BACKGROUND: Data on testosterone levels of patients with prostate cancer of different grade and stage are inconsistent. We retrospectively investigated serum total testosterone of a radical prostatectomy cohort to further shed light on this problem. PATIENTS AND METHODS: The preoperative level of serum total testosterone of 217 patients (mean age: 65±5.8 years) undergoing radical prostatectomy between 1989 and 2002 was analyzed for possible associations with Gleason score (≤6 vs. <7 vs. 8-10) and tumor stage (pT2 vs. pT3 vs. N+) with adjustment for age, diabetes and obesity. Patients exhibiting prostate-specific antigen (PSA) levels of >10 ng/ml and biopsy Gleason scores of ≥7 were submitted to standard lymphadenectomy. RESULTS: The multivariate model revealed a significant effect of body mass index (BMI) (p=0.0003) and diabetes (p=0.002) on testosterone levels. Significantly lower testosterone levels were recorded in patients with nodal metastases (p<0.0001) compared to patients with non metastatic disease. No significant associations between testosterone, Gleason score and stage were found in patients with non- metastatic disease. CONCLUSION: Testosterone levels prior to radical prostatectomy were lower in patients with nodal involvement.

Insertion/deletion polymorphism of angiotensin I-converting enzyme gene is linked with chromophobe renal cell carcinoma.

OBJECTIVES: To study the putative significance of angiotensin I-converting enzyme (ACE) in renal cell carcinoma (RCC). Recent evidence has suggested that a 287-base pair insertion (I)/deletion (D) polymorphism (rs4646994) of the angiotensin I-converting enzyme (ACE) might be associated with cancer risk and progression. METHODS: The present case-control study accrued 383 subjects, including 210 with RCC and 173 age- and sex-matched healthy individuals without evidence or a history of cancer. Genomic DNA was extracted from the peripheral blood leukocytes. The ACE fragment containing the polymorphism was amplified using conventional polymerase chain reaction using specific primer pairs and subsequently genotyped using agarose gel electrophoresis. RESULTS: Overall, a DD genotype and D allele were more frequently noted in the patients with RCC than in the controls (P = .042 and P = .045, respectively), and resulted from a greater frequency of DD and D in chromophobe RCC (P = .023 and P = .020, respectively). In contrast, the genotype and allele distribution of the controls and patients with papillary or clear cell RCC was similar. The II genotype was not observed in any patient with chromophobe RCC. On multivariate logistic regression analysis, the ACE genotype was an independent risk factor for chromophobe RCC (P = .012). Neither the ACE genotypes or alleles were associated with the tumor stage or grade. CONCLUSIONS: The results of the present study have shown for the first time that the ACE insertion/deletion gene polymorphism rs4646994 might be linked with the development of chromophobe RCC. Neither the ACE genotypes nor the alleles were associated with RCC progression.

Renal cell carcinoma Fuhrman grade and histological subtype correlate with complete polymorphic deletion of glutathione S-transferase M1 gene.

PURPOSE: We outlined the putative significance of GST in renal cell carcinoma biology by investigating the influence of its deletion polymorphisms on renal cell carcinoma progression. MATERIALS AND METHODS: Genomic DNA was purified from peripheral blood leukocytes. GSTM1 and GSTT1 genes were polymerase chain reaction amplified and gene fragments were separated by agarose gel electrophoresis. Intact GSTM1 and GSTT1 alleles were identified by the presence of 230 and 480 bp fragments, respectively. Genotypes were associated with clinicopathological variables and survival. RESULTS: Of 147 patients with renal cell carcinoma 80 (54%) had the GSTM1 null and 27 (18%) had the GSTT1 null genotype. The GST genotype distribution did not differ significantly from that in 112 controls without renal cell carcinoma. However, the GSTM1 null genotype was associated with 60% lower odds of the papillary subtype (OR 0.40, 95% CI 0.18 to 0.92, p = 0.032), lower Fuhrman grade (chi-square 9.77, p = 0.008) and a lower risk of metastatic disease in patients with the clear cell subtype (chi-square 4.48, p = 0.034). Of patients with the clear cell subtype those with the GSTM1 null genotype had improved cancer specific survival (p = 0.0412). GSTT1 did not correlate with any pathological variable except age at renal cell carcinoma onset since patients with renal cell carcinoma and the GSTT1 null genotype were significantly younger than their counterparts (mean +/- SD age 58.5 +/- 14.2 vs 65.4 +/- 12.8 years, p = 0.016). CONCLUSIONS: GSTM1 deletion polymorphism impacts renal cell carcinoma histological subtype, Fuhrman grade and metastatic behavior while GSTT1 deletion leads to renal cell carcinoma onset at a younger age. In patients with clear cell renal cell carcinoma the GSTM1 null genotype may be associated with better prognosis.

Androgen deficiency symptoms in testicular cancer survivors are associated with sexual problems but not with serum testosterone or therapy.

OBJECTIVES: To investigate the association between androgen deficiency symptoms and sexual function, serum testosterone, and therapy in testicular cancer survivors (TCS). METHODS: A total of 83 patients treated for testicular cancer were investigated. All patients completed the International Index of Erectile Function-15 and the Aging Males Symptoms scale. Age, months of follow-up, treatment modality, and serum testosterone levels were measured. Scores for the erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction subdomains of the International Index of Erectile Function-15 were calculated. RESULTS: Overall, almost half (47.0%) of TCS experienced clinical symptoms of androgen deficiency, 28.9% had erectile dysfunction, and 25.3% had laboratory-proven hypogonadism. TCS with clinical symptoms of androgen deficiency were significantly older (median age 45.0 vs 37.5 years, P = .001) and had a longer follow-up (median follow-up 48.0 vs 39.5 months, P = .985, respectively) than TCS without symptoms. TCS with clinical symptoms had significantly lower scores for erectile function (P = .004), orgasmic function (P = .05), sexual desire (P = .001), intercourse satisfaction (P = .005), and overall satisfaction (P = .001) than those without symptoms. The aging males' symptoms correlated significantly with erectile dysfunction (r = -0.410, P = .001). In TCS with symptoms, age (r = -0.457, P = .003), but not treatment modalities (r = 0.223, P = .173) or testosterone levels (r = 0.205, P = .210), correlated with sexual function. CONCLUSIONS: Clinical symptoms of androgen deficiency were associated with sexual problems and increasing age, but not with serum testosterone or treatment.

Common genetic polymorphisms of AURKA and prostate cancer risk.

PURPOSE: AURKA is a centrosome-associated serine/threonine kinase involved in mitotic chromosomal segregation. The AURKA gene is located on chromosome 20q13, also known as HPC20 prostate cancer susceptibility locus. Therefore, we investigated in this Caucasian case-control study two single nucleotide polymorphisms (SNPs) of the AURKA gene, rs8173 located in the 3'-untranslated region (G1891C) and rs2273535 in exon 5 (Phe31Ile), and their association with prostate cancer risk. METHODS: DNA was extracted from peripheral blood of 824 prostate cancer patients and 1,081 control patients with benign prostatic hyperplasia (BPH). Genotypes were determined using 5'-nuclease TaqMan assays. Multiple logistic regressions were performed to calculate odds ratios (OR) and confidence intervals (CI) and to adjust for confounders. RESULTS: The odds ratios calculated relative to the wild-type were for the homozygous polymorphic genotypes 1.11 (95% CI = 0.70-1.76) for rs8173 and 1.32 (95% CI = 0.76-2.31) for rs2273535, respectively. Stratified analyses according to Gleason score showed also no statistically significant association for the investigated polymorphisms and prostate cancer risk. CONCLUSIONS: The two investigated SNPs in AURKA were not found to be associated with prostate cancer risk. Other common SNPs of AURKA should be investigated in further studies because of its location on a prostate cancer susceptibility locus.