Screening for prostate cancer: moving forward in the molecular era.

Prostate specific antigen (PSA) is the most widely known screening test to detect prostate cancer (PCa). However, PSA testing has been recently put under the microscope mainly due to its weak correlation with prostate malignancy. In several clinical trials the PSA-screening validity for the diagnosis of PCa was evaluated. PSA lacks the ability to define the progression potential of the disease usually resulting in overdiagnosis and overtreatment of patients. Therefore, the development of new "multivariate" prediction models for PCa that would combine the PSA screening marker (and probably PSA metrics) with better biomarkers and imaging techniques has become an evolving field. New screening tests and/or methods with increased specificity could reduce the number of men undergoing prostate biopsy - thus alleviating patients from the anxiety and the distress experienced by an unnecessary (negative) biopsy- and minimizes the healthcare cost. Herein, we reviewed the information on PSA and other novel tests that can assist in diagnosing clinically meaningful prostate cancer.

Effective treatment of neurogenic detrusor overactivity in multiple sclerosis patients using desmopressin and mirabegron.

INTRODUCTION: Multiple sclerosis (MS) is the commonest progressive neurological disease affecting young people. With advancing disease, management of neurogenic detrusor overactivity (NDO) based on antimuscarinics may prove inadequate and if based on botulinum toxin, may necessitate clean intermittent self-catheterization. The aim of the study was to evaluate the effectiveness of combined mirabegron and desmopressin administration in the treatment of NDO in patients with MS. MATERIALS AND METHODS: Sixty patients diagnosed with MS and NDO were evaluated. All had received treatment with solifenacin 10 mg/daily for 3 months and were displeased with the results. Patients were divided in four groups. In Group A (n = 15) patients continued receiving solifenacin 10 mg/daily; in Group B (n = 15) patients received mirabegron 50 mg/daily; in Group C (n = 15) patients received desmopressin 120 mcg/daily and in Group D (n = 15) patients received mirabegron 50 mg/daily and desmopressin 120 mcg/daily. All patients were assessed with a 3 day bladder diary at the beginning and at the end of the treatment. RESULTS: All patients in Groups A, B and C did not demonstrate statistically significant changes at the end of the treatment period in their 3 day bladder diary and in the presence of urinary infections. In Group D, a statistically significant improvement was noted in the mean change from baseline to end of treatment in micturition episodes (3.5 +/- 0.4 micturition/24h), in urgency episodes (2.3 +/- 0.2) and mean number of urinary incontinence (1.0 +/- 0.2 episodes/24h). CONCLUSIONS: Treatment with mirabegron and desmopressin revealed both effectiveness and safety in patients with NDO and MS.

Magnetization transfer imaging of normal and abnormal testis: preliminary results.

OBJECTIVES: The aim was to determine the magnetization transfer ratio (MTR) of normal testes, possible variations with age and to assess the feasibility of MTR in characterizing various testicular lesions. METHODS: Eighty-six men were included. A three-dimensional gradient-echo MT sequence was performed, with/without an on-resonance binomial prepulse. MTR was calculated as: (SIo-SIm)/(SIo) × 100 %, where SIm and SIo refers to signal intensities with and without the saturation pulse, respectively. Subjects were classified as: group 1, 20-39 years; group 2, 40-65 years; and group 3, older than 65 years of age. Analysis of variance (ANOVA) followed by the least significant difference test was used to assess variations of MTR with age. Comparison between the MTR of normal testis, malignant and benign testicular lesions was performed using independent-samples t testing. RESULTS: ANOVA revealed differences of MTR between age groups (F = 7.51, P = 0.001). Significant differences between groups 1, 2 (P = 0.011) and 1, 3 (P < 0.001) were found, but not between 2, 3 (P = 0.082). The MTR (in percent) of testicular carcinomas was 55.0 ± 3.2, significantly higher than that of benign lesions (50.3 ± 4.0, P = 0.02) and of normal testes (47.4 ± 2.2, P < 0.001). CONCLUSIONS: MTR of normal testes decreases with age. MTR might be helpful in the diagnostic work-up of testicular lesions. KEY POINTS: MTR of normal testes shows age-related changes. Testicular carcinomas have high MTR values. MTR may be useful in the diagnostic work-up of testicular lesions.

Omental metastases from uveal melanoma-An interesting intraoperative omental pattern appearance.

Uveal melanomas represent approximately 5% of all human melanomas. Omental metastases are often diagnosed as secondary metastatic sites and only a few cases have been described as the first single manifestation of distant metastasis. In this case image, we illustrate the interesting appearance of the metastatic localization of metastatic uveal melanoma.

Perirenal fat invasion on renal cell carcinoma: evaluation with multidetector computed tomography-multivariate analysis.

OBJECTIVE: The objective of this study was to assess the accuracy of multidetector computed tomography (CT) in diagnosing perinephric (PN) and/or renal sinus (RS) fat invasion in patients with renal cell carcinoma (RCC), with reference to the CT findings predictive for the diagnosis of invasion. METHODS: This was a retrospective study of 48 RCCs. Examinations were performed on a 16-row CT scanner, including unenhanced and 3-phase contrast-enhanced CT scanning. Unenhanced transverse images and multiplanar reformations of each contrast-enhanced CT phase were evaluated. The predictive value of CT findings in diagnosing PN and/or RS fat invasion was determined using multivariate logistic regression analysis. RESULTS: The CT findings that were most predictive for the diagnosis of PN fat invasion were the presence of contrast-enhancing nodules in the PN fat and tumoral margins. Invasion of the pelvicaliceal system was the most significant predictor in the diagnosis of RS fat invasion. CONCLUSIONS: Multidetector CT provides satisfactory results in detecting PN and/or RS fat invasion in RCC.

Urinary Bladder Carcinoma Demonstrated on Bone Scintigraphy and SPECT/CT Images.

Bone scintigraphy with Tc-99m-diphosphonate analogs are widely used in staging, restaging, and monitoring the therapy effectiveness of various cancer types. Bone-seeking agents are excreted through urination, resulting in the visualization of either anatomical abnormalities or pathological conditions of the kidneys and bladder. We present a case of a 63-year-old man with urinary bladder carcinoma depicted on whole body planar and single-photon emission computed tomography/computed tomography images.

Accurate Characterization of Bladder Cancer Cells with Intraoperative Flow Cytometry.

Bladder cancer represents a major health issue. Transurethral resection is the first line treatment and an accurate assessment of tumor margins might warrant complete tumor removal. Genomic instability and proliferative potential are common hallmarks of cancer cells. We have previously demonstrated the utility of intraoperative flow cytometry (iFC), a next-generation margin evaluation methodology for assessment of DNA content, in the detection of several types of malignancy. In the current study we investigated the possible value of iFC in the characterization of bladder cancer during surgery. Samples from a population of 52 people with urothelial cancer were included in the study. The total time for iFC evaluation is 3-5 min per sample and included a two-step analysis, including DNA-index and Tumor-index calculation. First, DNA-index calculation revealed 24 hyperploid and one hypoploid tumor. Second, cell cycle analysis and Tumor-index calculation revealed that tumor samples are distinguished from normal cells based on their significantly higher proliferative potential. The standard for iFC evaluation was pathology assessment and revealed that our protocol exhibits an accuracy of 98% in defining the presence of cancer cells in a given sample. Our results support the further assessment of iFC value towards its use as a novel malignancy evaluation tool in transurethral resections.

Impact of total PSA and percent free PSA in the differentiation of prostate disease: a retrospective comparative study implicating neoplastic and non-neoplastic entities.

PURPOSE: To evaluate the potential of prostate cancer detection on the basis of prostate-specific antigen (PSA)-level and percent free PSA (% fPSA) according to the outcome of prostate needle biopsy. METHODS: This was a retrospective study of 1040 patients that underwent a prostate biopsy in the Urologic Clinic of the University Hospital of Ioannina, Greece. The patients underwent needle biopsy after abnormal finding in digital rectal examination (DRE). Tissue samples were extracted using a 12-core TRUS-GB. The patients were divided into four groups according to the biopsy outcome. Total serum and free PSA were measured. RESULTS: The mean PSA concentration of cancer versus noncancer groups was significantly higher (p<0.05). The positive predictive value (PPV) of PSA for serum concentration >10 ng/ml was 47% while the negative predictive value (NPV) in patients with PSA levels <4 ng/ml was 81%. The diagnostic accuracy of % fPSA for patients with PSA level between 4-10 ng/ml was 0.651 (95% CI, 0.549-0.754) (p<0.05). A statistically significant difference in mean PSA concentration was recorded between prostate cancers classified as grade 2 (3+4=7) and 3 (4+3=7) and grade 4 (8) and 5 (9-10) (p<0.05). CONCLUSIONS: Though informative and suggestive, PSA and % fPSA are not definitive for cancer or non-cancer determination. The differentiation of PSA level between tumours classified as grade 2 (3+4=7) and grade 3 (4+3=7) could support the determination of treatment by backing pathologist's interpretation of the histological diagnosis.

Curcumin Acts as a Chemosensitizer for Leiomyosarcoma Cells In Vitro But Fails to Mediate Antioxidant Enzyme Activity in Cisplatin-Induced Experimental Nephrotoxicity in Rats.

Background. Cisplatin (cis-diamminedichloroplatinum) is a widely used chemotherapeutic agent for the treatment of various cancers. Although it represents an effective regimen, its application is accompanied by side effects to normal tissues, especially to the kidneys. Cisplatin generates free radicals and impairs the function of antioxidant enzymes. Modulation of cisplatin-induced oxidative stress by specific antioxidant molecules represents an attractive approach to minimize side effects. Methods. We studied the ability of curcumin to sensitize leiomyosarcoma (LMS) cells to cisplatin. Assays for cell proliferation, mitochondrial function, induction of apoptosis, and cell cycle arrest were performed using various concentrations of cisplatin and a concentration of curcumin that caused a nonsignificant reduction in cell viability. Moreover, the effect of curcumin was examined against cisplatin-induced experimental nephrotoxicity. Renal injury was assessed by measuring serum creatinine, blood urea nitrogen (BUN), and the kidney's relative weight. Oxidative stress was measured by means of enzymatic activities of superoxide dismutase and glutathione peroxidase in the rats' blood and malondialdehyde levels in rats' urine. Results. In our study, we found that curcumin sensitizes LMS cells to cisplatin by enhancing apoptosis and impairing mitochondrial function. In an in vivo model of cisplatin-induced experimental nephrotoxicity, intraperitoneal administration of curcumin failed to preserve blood's antioxidant enzyme activity and decrease lipid peroxidation. Nevertheless, curcumin was able to protect nephrons' histology from cisplatin's toxic effect. Conclusion. Our results showed that curcumin can act as chemosensitizer, but its role as an adjunctive cisplatin-induced oxidative stress inhibitor requires further dose-finding studies to maximize the effectiveness of chemotherapy.

Hormonal regulation of spermatogenesis and spermiogenesis.

Normal testicular function is dependent upon hormones acting through endocrine and paracrine pathways both in vivo and in vitro. Sertoli cells provide factors necessary for the successful progression of spermatogonia into spermatozoa. Sertoli cells have receptors for follicle stimulating hormone (FSH) and testosterone which are the main hormonal regulators of spermatogenesis. Hormones such as testosterone, FSH and luteinizing hormone (LH) are known to influence the germ cell fate. Their removal induces germ cell apoptosis. Proteins of the Bcl-2 family provide one signaling pathway which appears to be essential for male germ cell homeostasis. In addition to paracrine signals, germ cells also depend upon signals derived from Sertoli by direct membrane contact. Somatostatin is a regulatory peptide playing a role in the regulation of the proliferation of the male gametes. Activin A, follistatin and FSH play a role in germ cell maturation during the period when gonocytes resume mitosis to form the spermatogonial stem cells and differentiating germ cell populations. In vitro cultures systems have provided evidence that spermatogonia in advance stage of differentiation have specific regulatory mechanisms that control their fate. This review article provides an overview of the literature concerning the hormonal pathways regulating spermatogenesis.

Fibroepithelial polyp of distal ureter with periodic prolapse into bladder.

Ureteric fibroepithelial polyp is a rare disease; it is of mesodermal origin and exhibits benign characteristics. Hydronephrosis occurs in rare cases, and it is generally accepted that it may result in an obstruction without causing alterations of renal function. In many cases it is difficult to differentiate from transitional cell carcinomas. Nowadays, endoscopic evaluation is the means of treatment and management. In our case study we report a patient with a long fibroepithelial polyp of the distal ureter prolapsing into the bladder in a periodic pattern. Cystoscopy revealed that movement of the polyp was moving forward and backward in the right ureteric orifice. Cold-cut biopsy established the diagnosis. The patient underwent ureteroscopic excision and remains asymptomatic a year later.

Penile erection during transurethral surgery.

Intraoperative penile erection during endoscopic surgery, although an infrequent occurrence, is a troublesome complication and a challenge to the urologist. It is difficult to perform the procedure during penile erection, because various complications may occur. The etiology is unclear, and a number of pharmacological remedies have been discussed in the literature. Herein, we describe the treatment and outcomes for 3 patients with intraoperative penile erection and provide a brief review of the associated literature. Intraoperative penile erection is a rare event during transurethral procedures, with a frequency of approximately 0.1% in our institution. To our knowledge, no generally accepted protocols for the prevention or treatment of this phenomenon have been reported in the literature. We recommend intracorporeal injection of 250 microg of phenylephrine: detumescence occurred rapidly in all patients after a single injection. The mode of administration is simple, and no complications have been reported.

Genetic and epigenetic risks of intracytoplasmic sperm injection method.

Pregnancies achieved by assisted reproduction technologies, particularly by intracytoplasmic sperm injection (ICSI) procedures, are susceptible to genetic risks inherent to the male population treated with ICSI and additional risks inherent to this innovative procedure. The documented, as well as the theoretical, risks are discussed in the present review study. These risks mainly represent that consequences of the genetic abnormalities underlying male subfertility (or infertility) and might become stimulators for the development of novel approaches and applications in the treatment of infertility. In addition, risks with a polygenic background appearing at birth as congenital anomalies and other theoretical or stochastic risks are discussed. Recent data suggest that assisted reproductive technology might also affect epigenetic characteristics of the male gamete, the female gamete, or might have an impact on early embryogenesis. It might be also associated with an increased risk for genomic imprinting abnormalities.

The role of apparent diffusion coefficient values in detecting testicular intraepithelial neoplasia: preliminary results.

INTRODUCTION: The aim of this study is to improve detection of testicular intraepithelial neoplasia (TIN) by measurement of apparent diffusion coefficient (ADC) values. MATERIALS AND METHODS: Fifty-six MRI examinations of the scrotum, including 26 histologically proven testicular germ cell neoplasms were retrospectively evaluated. DWI was performed using a single shot, multi-slice spin-echo planar diffusion pulse sequence and b-values of 0 and 900 s mm(-2). ADC measurements were classified into three groups according to their location: group 1 (n=19), non-tumoral part, adjacent to testicular carcinoma, where the possible location of TIN was; group 2 (n=26), testicular carcinoma; and group 3 (n=60), normal testicular parenchyma. Analysis of variance (ANOVA) followed by post hoc analysis (Dunnett T3) was used for statistical purposes. RESULTS: The mean±s.d. of ADC values (×10(-3) mm(2)/s) of different groups were: group 1, 1.08±0.20; group 2, 0.72±0.27; and group 3, 1.11±0.14. ANOVA revealed differences of mean ADC between groups (F=38.859, P<0.001). Post hoc analysis showed differences between groups 2 and 3 (P<0.001), groups 2 and 1 (P<0.001), but not between groups 3 and 1 (P=0.87). CONCLUSIONS: Based on our preliminary results, ADC values do not provide a reliable differentiation between TIN and testicular carcinoma or normal testicular parenchyma.

The role of N-acetyltransferase-2 and glutathione S-transferase on the risk and aggressiveness of bladder cancer.

N-acetyltransferase-2 (NAT-2) and Glutathione-S-transferase M1 and T1 (GSTM1 and GSTT1) polymorphism have been implicated in the detoxification of urothelial carcinogens, such as arylamines and polycyclic aromatic hydrocarbons. The results of epidemiological studies examining the role of NAT-2, GSTM1 and GSTT1 genotypes on the risk factors for bladder cancer were controversial, although suggesting that there may be an increased risk of the disease associated with these genotypes. The aim of the present study was to examine the independent effect and a possible interaction of NAT-2, GSTM1 and GSTT1 genotypes on the risk of bladder carcinogenesis, in the frame of a case-control study. We also investigated the possible association of specific genotype combinations with more aggressive disease in terms of tumor grading and local staging at the time of initial diagnosis. Between August 1996 and May 1998, 89 newly-diagnosed bladder cancer patients (transitional cell type) and 147 controls were included in the study. All patients were selected at the time of first diagnosis, done in the Department of Urology at the University Hospital of Ioannina, in north-western Greece. GSTM1 and NAT-2 deficient genotypes were found to be independently associated with the risk of bladder cancer (odds ratios 2.87 and 2.64, respectively). The GSTT1 genotype did not present any significant association with bladder cancer risk. We did not find a significant interaction between genotypes. These results could be explained by the independent activity of the two enzymes. Studies that will simultaneously examine the role of several genetic and environmental factors involved in bladder carcinogenesis are needed to give a global picture for the risk factors of bladder cancer and their potential interaction.

Cytokine effects on cell viability and death of prostate carcinoma cells.

We analyzed the effects of IL-13, IFN- γ , and IL-1 ß on cell viability and death of LNCaP and PC-3 cells and major signaling pathways involved in these effects. Significant increase of LNCaP cell death (apoptotic and necrotic) and increased levels of active caspase 3 were observed in cells treated with inhibitors of ERK 1/2 (UO126) and p38 (SB203580) prior to IL-1 ß treatment in comparison to cells treated with UO126, SB203580, or IL-1 ß alone. Significant increase of LNCaP but not PC-3 cell death was detected after treatment with LY-294002 (inhibitor of phosphatidylinositol 3-kinase). No significant increase of LNCaP and PC-3 cell death was observed after treatment with SP600125 (inhibitor of JNK), SB203580 (inhibitor of p38), UO126 (inhibitor of ERK 1/2), or BAY 11-7082 (inhibitor of NF- κ B). Reduced c-FLIPL expression was observed in LNCaP cells treated with LY-294002. The significant potentiation of LNCaP cell death by inhibition of ERK 1/2, p38, and PI3-K pathways may provide a rationale for therapeutic approach in androgen-dependent prostate cancer.

Penis auto-amputation and chasm of the lower abdominal wall due to advanced penile carcinoma: a case report.

INTRODUCTION: Penile cancer is uncommon. When penile cancer is left untreated, at an advanced stage it can have tragic consequences for the patient. CASE PRESENTATION: Our case report does not concern a new manifestation of penile cancer, but an interesting presentation with clinical significance that emphasizes the need to diagnose and treat penile cancer early. It is an unusual case of a neglected penile cancer in a 57-year-old Greek man that led to auto-amputation of the penis and a large chasm in the lower abdominal wall. The clinical staging was T4N3M0 and our patient was treated with a bilateral cutaneous ureterostomy, chemotherapy and radiotherapy. Our patient died 18 months after his first admission in our clinic. CONCLUSIONS: Emphasis must be placed on early diagnosis and treatment of penile cancer, so further development of the disease can be prevented.

Combined use of antisense oligonucleotides and chemotherapeutics in the treatment of refractory prostate cancer.

Throughout the past six decades, our understanding of cancer of the prostate and the treatment of the disease using endocrine therapy has been centred on the classical investigations of Charles Huggins, which established that tumor tissue of the prostate as well as the normal tissue of the gland retained some degree of androgen dependence. Attention must now be focussed on the 20-40% of patients who are resistant to endocrine therapy. These patients are non-responders to conventional endocrine treatment after 3 to 6 months, quickly progress and die of the disease. In terms of molecular endocrinology related to the progressive stage of the disease, it would be expected that the cancer is being driven by the uncontrolled action of growth factors. Experiments combining oligonucleotide treatment with cytotoxic chemotherapeutic agents demonstrated a marked increase in the sensitivity of the prostate cancer cells. Results indicate that despite the presence of Bcl-x pre-mRNA in a number of cell types, the effects of modification of its splicing by antisense oligonucleotides vary depending on the expression profile of the treated cells. The transition from androgen-dependent to androgen non-dependent prostate cancer is accompanied by a number of molecular genetic changes, including overexpression of the Bcl-2 gene. Overexpression of Bcl-2 protein decreases the pro-apoptotic response to such cellular insults as irradiation, chemotherapy, and androgen withdrawal. The future looks promising and this kind of treatment offers a novel approach to alternative therapeutic options for advanced prostate cancer. Although numerous chemotherapeutic regimens have been evaluated for patients with hormone-refractory prostate cancer, none has improved survival.

Monotherapy in advanced prostate cancer: an overview.

Prostate cancer is the second leading malignancy in men associated with an enormous research interest in all aspects of the disease. It is well recognized that the regulation of prostatic growth is a complicated biological process. Further more the androgenic dependence of the advanced prostate cancer is well know and in the last 50 years significant progresses regarding the principle of deprivation of androgens for the treatment of the disease occured. Prostate cancer is now diagnosed in earlier stages and treatment results in increased potential for cure or extension of overall survival. Unfortunately, every treatment for prostate cancer has adverse effects with negative impact in health-related quality of life. Surgical or pharmacological castration has a significant negative impact on quality of life in patients with prostate cancer (loss of sexuality, osteoporosis, and loss of muscle mass, e.g.). Antiandrogen monotherapy is considered to be a treatment in well-informed patients who wish to remain sexually active, can be administered orally, and is well tolerated by patients with prostate cancer. This review is focused on antiandrogen monotherapy in the treatment of advanced prostate cancer.

Orbital metastasis from prostatic carcinoma.

A rare case of orbital metastasis from carcinoma of the prostate in a 76-year-old man who presented with pain in his left eye, mild proptosis and reduced visual acuity is reported. Cranial CT scanning demonstrated large bone metastases in the left orbit. The patient underwent orbital evisceration. The histopathological studies that were based on the morphological and immunohistochemical findings confirmed the histological diagnosis of orbital metastasis arising from prostatic carcinoma with neuroendocrine features.