Impact of enterococcal urinary tract infections in immunocompromised - neoplastic patients.

Infections in immunocompromised-neoplastic patients represent a severe complication. Among bacteria, Enterococcus species constitute a common causative pathogen of urinary tract infections (UTIs), especially among hospitalized patients with or without urinary tract carcinoma, related commonly to urinary tract abnormalities, urinary catheters or prolonged antibiotic treatment. Although enterococci have been considered more commonly as colonization bacteria in the intestine than virulent agents, they are frequently implicated in UTIs. The high incidence of enterococcal UTIs is associated with several risk factors including age, female gender, previous UTI, diabetes, pregnancy, immunosuppression due to cancer development and progression, renal transplantation and spinal cord injury. Clinical manifestations are usually absent or mild in enterococcal UTIs, which may also become an important source for both bacteremia and endocarditis. Over the last years, the prevalence of multidrug resistant enterococci, particularly vancomycin-resistant E. faecium and E. faecalis has significantly risen worldwide, associated with increased morbidity, limited treatment options and increased health-care costs. In this review, the current knowledge on enterococcal UTIs epidemiology and influence in the corresponding immunocompromised patients is highlighted.

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.

An Update on Sexual Transmission of Zika Virus.

Zika virus (ZIKV) is a single-stranded RNA virus belonging to the arthropod-borne flaviviruses (arboviruses) which are mainly transmitted by blood-sucking mosquitoes of the genus Aedes. ZIKV infection has been known to be rather asymptomatic or presented as febrile self-limited disease; however, during the last decade the manifestation of ZIKV infection has been associated with a variety of neuroimmunological disorders including Guillain⁻Barré syndrome, microcephaly and other central nervous system abnormalities. More recently, there is accumulating evidence about sexual transmission of ZIKV, a trait that has never been observed in any other mosquito-borne flavivirus before. This article reviews the latest information regarding the latter and emerging role of ZIKV, focusing on the consequences of ZIKV infection on the male reproductive system and the epidemiology of human-to-human sexual transmission.

Numerical Imbalances of Chromosome 7 in Oral Squamous Cell Carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is an aggressive neoplasm. Many chromosomal and gene alterations have been identified in OSCC, including structural and numerical changes. In this study, we implemented a molecular assay of chromosome 7 (Chr7) in order to investigate the level of its numerical instability in OSCC. MATERIALS AND METHODS: Using tissue microarray technology, 30 primary OSCCs were cored and re-embedded into one recipient block. Chromogenic in situ hybridization assay was performed based on Chr7 centromeric probedetection. RESULTS: Chr 7 numerical analysis detected polysomy (trisomy/ tetrasomy) in 4/30 (13.3%) of the examined tissue OSCC cores. Statistical significance was assessed correlating Chr7 numerical aberrations with stage (p=0.015), especially detected in cases not related to human papillomavirus (HPV) (p=0.01). CONCLUSION: Although Chr7 polysomy is a relatively rare gross genetic event in OSSC, it affects their biological behavior leading toa progressively aggressive phenotype (advanced stage). Furthermore, Chr7 polysomy is observed more frequently in non-viral (HPV) cases.

MRI in the histologic characterization of testicular neoplasms.

OBJECTIVE: The purpose of our study was to investigate the potential role of MRI in the preoperative characterization of the histologic type of testicular tumors and, more specifically, to differentiate seminomatous from nonseminomatous testicular neoplasms. MATERIALS AND METHODS: Twenty-one patients with histologically proven germ cell testicular tumors underwent MRI of the scrotum on a 1.5-T unit. T2- and T1-weighted sequences before and after i.v. administration of gadolinium chelate were performed. MRI studies were retrospectively reviewed by two radiologists and findings were correlated with the histopathologic diagnosis. An attempt was made to differentiate seminomatous from nonseminomatous testicular tumors on the basis of signal intensity and homogeneity of the lesions, presence of fibrovascular septa, tumor encapsulation, and patterns of contrast enhancement. Interobserver agreement was assessed using weighted kappa statistics. RESULTS: MRI findings correctly characterized 19 (91%) of 21 testicular neoplasms (nine seminomatous and 10 nonseminomatous testicular tumors), with excellent interobserver agreement. The presence of an intratesticular lesion of predominantly low signal intensity on T2-weighted images, with septa enhancing more than tumor tissue after contrast material administration, was more suggestive for the diagnosis of a seminoma. Tumors that were markedly heterogeneous both on unenhanced and contrast-enhanced images were indicative of a nonseminomatous neoplasm. CONCLUSION: Our study shows that MRI provides a credible preoperative differentiation of seminomatous from nonseminomatous testicular tumors, with excellent interobserver agreement.

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.

Penetration of antimicrobial agents into the prostate.

In the present review article, the penetration of antimicrobial agents into prostatic fluid and tissue was examined. Three major factors determining the diffusion and concentration of antimicrobial agents in prostatic fluid and tissue are the lipid solubility, dissociation constant (pKa) and protein binding. The normal pH of human prostatic fluid is 6.5-6.7, and it increases in chronic prostatitis, ranging from 7.0 to 8.3. A greater concentration of antimicrobial agents in the prostatic fluid occurs in the presence of a pH gradient across the membrane separating plasma from prostatic fluid. Of the available antimicrobial agents, beta-lactam drugs have a low pKa and poor lipid solubility, and thus penetrate poorly into prostatic fluid, expect for some cephalosporins, which achieve greater than or equal to the inhibitory concentration. Good to excellent penetration into prostatic fluid and tissue has been demonstrated with many antimicrobial agents, including tobramycin, netilmicin, tetracyclines, macrolides, quinolones, sulfonamides and nitrofurantoin.

Long-term evaluation of transurethral needle ablation of the prostate (TUNA) for treatment of symptomatic benign prostatic hyperplasia: clinical outcome up to five years from three centers.

OBJECTIVE: TUNA has been demonstrated to be a safe and effective therapy for BPH. However the major criticism, as with all alternative treatments for BPH, was the lack of long-term data. We present the clinical outcome of patients treated by TUNA and followed for 5 years. METHODS: 188 consecutive patients with symptomatic BPH treated with TUNA were followed for five years in three different centers. All patients were treated using the TUNA II or TUNA III catheters under local anesthesia only without general or spinal anesthesia. Baseline and 5-year follow-up evaluation included urinary peak flow, International Prostate Symptom Score (IPSS) and post-void residual urine (PVR). The number of patients requiring additional medical or surgical treatment was recorded. Statistics were performed using the t-test. RESULTS: At a mean follow-up of 63 months, mean urinary peak flow rate increased from 8.6 ml/s to 12.1 ml/s (p<0.01, t-test), IPSS and PVR decreased from 20.9 and 179 ml to 8.7 and 122 ml, respectively (both p<0.001, t-test). The percentage of patients who improved by at least 50% their peak uroflow and IPSS was 24% and 78% respectively. Mean prostate volume and PSA levels did not change significantly (53.9 cc vs. 53.8 cc and 3.3 vs. 3.6 ng/ml, respectively at 5 years, both p values > 0.05, t-test). Two patients died of unrelated comorbidities and 10 were lost for follow-up. Medical treatment was given to 12 patients (6.4%), a second TUNA performed in 7 patients (3.7%) and surgery indicated in 22/186 (11.1%). Overall 41/176 patients (188 at start, 2 deaths and 10 lost to follow-up) or 23.3% required additional treatment at 5 years follow-up following the original TUNA procedure. CONCLUSIONS: TUNA is effective and provides good long-term clinical improvement at 5-year follow-up. TUNA treatment stands the test of time at 5-year follow-up with low and acceptable failure rates. More than 75% of the patients do not need additional treatment for BPH on the long run.

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.

Assessment of in vivo chemotherapy-induced DNA damage in a p53-mutated rat tumor by micronuclei assay.

Production of DNA damage is the basis of cancer treatments such as chemo- and radiotherapy. Such treatments induce mitotic catastrophe, a form of cell death resulting from abnormal mitosis and leading to the formation of interphase cells with multiple micronuclei. In this study, we compared apoptosis induction and micronuclei formation to assess the DNA damage provoked in vivo by cytotoxic agents in established 9L rat gliosarcoma tumors expressing a mutated p53 gene. Results from TUNEL assays revealed the efficiency of local gamma-irradiation at the tumor site to induce apoptosis within 9L tumor mass. However, little or no apoptosis was detected after systemic (ip) injection of cisplatin (1 mg/kg). Interestingly, the micronuclei assays showed that not only gamma-irradiation but also cisplatin treatment led to an increase in the emergence of binucleated cells with micronuclei. Apoptosis induction and micronuclei emergence are thus not absolutely correlated. However, micronuclei assays, rarely performed on solid tumors, appear more sensitive than apoptosis assays in evaluating DNA damage linked to chemotherapy.

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.