Adherence to Mediterranean diet and risk of prostate cancer.

In Europe, countries following the traditional Mediterranean Diet (MeDi), particularly Southern European countries, have lower prostate cancer (PCa) incidence and mortality compared to other European regions. In the present study, we investigated the association between the MeDi and the relative risk of PCa and tumor aggressiveness in a Spanish population. Among individual score components, it has been found that subjects with PCa were less likely to consume olive oil as the main culinary fat, vegetables, fruits and fish than those without. However, these differences were not statistically significative. A high intake of fruit, vegetables and cooked tomato sauce Mediterranean style (sofrito) was related to less PCa aggressiveness. Results showed that there are no differences in the score of adherence to the Mediterranean dietary patterns between cases and controls, with mean values of 8.37 ± 1.80 and 8.25 ± 2.48, respectively. However, MeDi was associated with lower PCa agressiveness according to Gleason score. Hence, relations between Mediterranean dietary patterns and PCa are still inconclusive and merit further investigations. Further large-scale studies are required to clarify the effect of MeDi on prostate health, in order to establish the role of this diet in the prevention of PCa.

The influence of nutritional factors on prostate cancer incidence and aggressiveness.

There is an increasing evidence for a link between nutrition, lifestyle and prostate cancer (PCa) development and/or progression of disease. The objective of this study was to examine the association between dietary factors and PCa incidence and aggressiveness in a case-control study. After the analysis of the anatomic pathology, subjects were classified in patients with PCa (n = 157) and controls (n = 158). Clinical data including Gleason score, PSA values and biopsy results, were compiled. Frequencies of food consumption and sociodemographic data were also obtained. The results showed that physical activity was significantly higher in control (p < .022). It was also found that some nutritional habits offer a protective effect among studied subjects, like high nuts (p = .041) and fish (p = .041) intakes. Moreover, there was a significant reduction in risk (p = .029) in cases with a higher fruits and vegetables intakes. A decreased risk of aggressive PCa was associated with fruits, vegetables, legumes and fish intakes. However, these relationships were not statistically significant when data were adjusted for covariates. In conclusion, this study found an inverse association between PCa risk and the intake of fruits and vegetables, fish and nuts. The results suggested that a diet with higher intakes of these foods as Mediterranean diet may lower the risk of PCa in the studied population. As dietary factors are modifiable, identifying food groups or dietary patterns that modulate the risk of PCa and its aggressiveness can offer effective and practical strategies for its primary prevention.

Bioactive compounds of the Mediterranean diet and prostate cancer.

OBJECTIVE: The purpose of this review is to examine the evidence on the effects of bioactive constituents of the Mediterranean diet (MeDi) on prostate cancer (PCa) risk. METHODS: The search for articles came from extensive research in the following databases: PubMed, Scopus, and Web of Science. We used the search terms "Mediterranean diet," "lycopene," "vitamin E," "vitamin C," "Selenium," "resveratrol," "prostate cancer," and combinations, such as "lycopene and prostate cancer" or "resveratrol and prostate cancer." RESULTS: Numerous studies investigating the effect of various dietary nutrients on PCa have suggested that selenium is probably the most promising. Several studies reported reduced PCa risk associated with vitamin C and E intake, while other studies reported no association. Lycopene inhibits cell proliferation and inducts apoptosis, thus protecting against cancer. Also, it has been found in various in vivo and in vitro studies that resveratrol, inhibits PCa development. CONCLUSIONS: The high content of bioactive phytochemicals in the MeDi is of particular interest in the prevention of PCa. Further large-scale studies are required to clarify the effect of MeDi bioactive compounds on prostate health, in order to establish the role of this diet in the prevention of PCa.

Lifestyle and dietary factors in relation to prostate cancer risk.

The aim of the present study was to determine the association between the socio-demographic, lifestyle factors, and dietary habits with the risk of prostate cancer (PC) in a case-control study of Spanish men. None of the socio-demographic, lifestyle or dietetic variables was found predictors of PC risk. Body mass index was associated with an increased risk for aggressive PC and fruit consumption with lower Gleason scores, thus less aggressive cancers. Nonetheless, after applying Bonferroni correction, these variables were not still associated with PC aggressiveness. More adequately, powered epidemiological studies that measure the effect of lifestyle and dietary intake in PC risk and aggressiveness are warranted to further elucidate the role of these modifiable factors on PC etiology.

Biofabrication of a Tubular Model of Human Urothelial Mucosa Using Human Wharton Jelly Mesenchymal Stromal Cells.

Several models of bioartificial human urothelial mucosa (UM) have been described recently. In this study, we generated novel tubularized UM substitutes using alternative sources of cells. Nanostructured fibrin-agarose biomaterials containing fibroblasts isolated from the human ureter were used as stroma substitutes. Then, human Wharton jelly mesenchymal stromal cells (HWJSC) were used to generate an epithelial-like layer on top. Three differentiation media were used for 7 and 14 days. Results showed that the biofabrication methods used here succeeded in generating a tubular structure consisting of a stromal substitute with a stratified epithelial-like layer on top, especially using a medium containing epithelial growth and differentiation factors (EM), although differentiation was not complete. At the functional level, UM substitutes were able to synthesize collagen fibers, proteoglycans and glycosaminoglycans, although the levels of control UM were not reached ex vivo. Epithelial differentiation was partially achieved, especially with EM after 14 days of development, with expression of keratins 7, 8, and 13 and pancytokeratin, desmoplakin, tight-junction protein-1, and uroplakin 2, although at lower levels than controls. These results confirm the partial urothelial differentiative potential of HWJSC and suggest that the biofabrication methods explored here were able to generate a potential substitute of the human UM for future clinical use.

[Renal cell carcinoma with vena cava involvement: update and review of our series]. / Carcinoma de células renales con extensión a vena cava: puesta al día y revisión de nuestra casuística.

OBJECTIVE: To assess current management of renal cell carcinoma (RCC) extending into the inferior vena cava (IVC): staging, diagnosis, surgical approach, adjuvant therapy, prognostic factors and survival rate. MATERIALS AND METHODS: Nineteen cases of RCC extending into the IVC undergoing surgical resection from January 1988 to August 2008 were reviewed. TNM staging and Neves-Zincke grading of the tumor were also assessed. Surgical approach depended on thrombus level. RESULTS: With a perioperative mortality rate of 10.5% and a mean follow-up of 22.65 months (range 2-79), 5 patients are still alive, while 11 patients died from the disease, 1 from an unrelated cause, and 2 were lost to follow-up. Patients with metastatic disease received adjuvant treatment with immunotherapy or kinase inhibitors. Mean survival was 15.1 months. Significant differences were found in 3- and 5-year survival rates in patients staged as N0M0 as compared to all other stages (N+M0, N0M+, N+M+). No differences were found depending on thrombus level. CONCLUSIONS: RCC with thrombus in the IVC is a tumor with a high mortality rate. Surgery continues to be the best option, and requires adequate preoperative evaluation and the support of an experienced and well trained multidisciplinary team. Survival depends on disease extension.

Primary renal lymphoma: report of three new cases and literature review.

OBJECTIVES: We report the cases of three patients with primary renal lymphoma. Diagnosis and subsequent treatment are discussed. METHODS: The literature on the origin, epidemiology, clinical presentation, diagnosis, treatment and prognosis of primary renal lymphoma was reviewed. RESULTS: The first patient was diagnosed after radical nephrectomy and subsequently was given six cycles of CVP (cyclophosphamide, vincristine, prednisone). The diagnosis of the second patient was established by renal biopsy, and the patient received six cycles of CHOP (cyclophosphamide, adriamycin, vincristine and predisone). The last patient had a lymphoma, secondary to immunosuppression, in a transplanted kidney. In this case transplant nephrectomy sufficed to cure the patient's lymphoma. All patients had B-cell non-Hodgkin lymphoma (an extrarenal origin was ruled out by bone marrow biopsy), and were disease-free 15 months, 7 months, and 6.5 years after diagnosis, respectively. CONCLUSIONS: Primary renal lymphoma is rare. Diagnosis is established by renal biopsy, although it often presents as a mass simulating renal cell cancer and diagnosis is obtained after radical nephrectomy. Treatment consists of chemotherapy (CHOP). associated with rituximab.

Improving the genetic signature of prostate cancer, the somatic mutations.

BACKGROUND: Somatic mutations have been related to the highest incidence of metastatic disease and different treatment responses. The molecular cause of prostate cancer (PC) is still unclear; however, its progression involves alterations in oncogenes and tumor suppressor genes as well as somatic mutations such as the ones in PIK3CA gene. A high percentage of PC is considered sporadic, which means that the damage to the genes occurs by chance after birth (mainly somatic mutations will drive the cancer event). However, little is known about somatic mutations in PC development. MATERIALS AND METHODS: We evaluated prostate biopsies in the main somatic mutations genes (PIK3CA, TP53, EGFR, KIT, KRAS, PTEN, and BRAF) among individuals with PSA values>4ng/ml (n = 125), including affected and unaffected PC subjects. RESULTS: Mutations in KIT gene are related to aggressive PC: TNM stages II to III, Gleason score ≥ 7 and D'Amico risk (P = 0.037, 0.040, and 0.017). However, there are no statistical significant results when more than 3 somatic mutations are presented in the same individual. In relation to environmental factors (smoking, diet, alcohol intake, or workplace exposure) there are no significant differences in the effect of environmental exposure and the somatic mutation presence. The most prevalent mutations among patients with PC are c.1621A>C (rs3822214) in KIT, c.38G>C (rs112445441) in KRAS and c.733G>A (rs28934575) in TP53 genes. KRAS, KIT, and TP53 genes are the most prevalent ones in patients with PC. CONCLUSIONS: Somatic alterations predisposing to chromosomal rearrangements in PC remain largely undefined. We show that KIT, KRAS, and TP53 genes have a higher presence among patients with PC and that mutations in KIT gene are related to an aggressive PC. However, we did not find any environmental effect in somatic mutations among PC individuals.

Association between polymorphisms in sex hormones synthesis and metabolism and prostate cancer aggressiveness.

Novel biomarkers for prostate cancer (PCa) diagnosis and prognosis are necessary to improve the accuracy of current ones employed in clinic. We performed a retrospective study between the association of several polymorphisms in the main genes involved in the synthesis and metabolism of sex hormones and PCa risk and aggressiveness. A total of 311 Caucasian men (155 controls and 156 patients) were genotyped for 9 SNPs in AR, CYP17A1, LHCGR, ESR1 and ESR2 genes. Diagnostic PSA serum levels, Gleason score, tumor stage, D´Amico risk and data of clinical progression were obtained for patients at the moment of the diagnosis and after 54 months of follow-up. Chi-squared test were used for comparisons between clinical variables groups, logistic regression for clinical variables associations between SNPs; and Kaplan-Meier for the association between SNPs and time to biochemical progression. We found 5 variants (CYP17A1) rs743572, rs6162, rs6163; (LHCGR) rs2293275 and (ESR2) rs1256049 that were statistically significant according to clinical variables (PSA, D´Amico risk and T stage) on a case-case analysis. Moreover, the presence of A and G alleles in rs743572 and rs6162 respectively, increase the risk of higher PSA levels (>10 ng/µl). With respect to D´Amico risk rs743572 (AG-GG), rs6162 (AG-AA) and rs6163 (AC-AA) were associated with an increased risk; and last, AC and AA genotypes for rs6163 were associated with a shorter biochemical recurrence free survival (BRFS) in patients with radical prostatectomy. In multigene analysis, several variants in SNPs rs2293275, rs6152, rs1062577, rs6162, rs6163, rs1256049 and rs1004467 were described to be associated with a more aggressiveness in patients. However, none of the selected SNPs show significant values between patients and controls. In conclusion, this study identified inherited variants in genes CYP17A1, LHCGR and ESR2 related to more aggressiveness and/or a poor progression of the disease. According to this study, new promise PCa biomarkers for clinical management could be included in these previous SNPs.

A comprehensive study of circulating tumour cells at the moment of prostate cancer diagnosis: biological and clinical implications of EGFR, AR and SNPs.

Circulating tumor cells (CTCs) have been recently accepted as prognostic markers in metastatic prostate cancer (PCa). However, very few studies have analyzed their role in early-stage PCa. The aim of this research is to study the value of CTCs at the moment of PCa diagnosis and to identify different subpopulations of CTCs. Patients with PSA value > 4 ng/ml and clinical suspicion of PCa were included. Samples were collected immediately before prostatic biopsy. CTCs were isolated by immunomagnetic technique using a multi-CK specific antibody. Molecular expression of EGFR and AR in the tissue was analysed by real-time PCR. Up to eight different SNPs in patients' blood DNA were studied. In a total of 86 patients, the CTC detection rate was 18.6%. The sensitivity, specificity, positive and negative predictive values of CTCs to detect PCa was 14.2%, 78.4%, 31.2% and 57.4%, respectively. Up to 75% of CTC-positive patients were AR-negative. A direct association was found between the expression of AR in the prostatic tissue and the presence of CTCs in blood (p<0.05). We observed an inverse relation between the expression of EGFR in the tissue and the expression of AR in the CTCs. No significant association between SNPs and CTCs was found. The low detection rate of CTCs in early-stage PCa limits their role as a diagnostic marker. Nevertheless, we show that they may hide important prognostic information. Overexpression of AR in the prostate may facilitate cell dissemination.

[Evolution of urinary lithiasis composition in a Spanish health care area over the last four decades]. / Evolución de la composición de las litiasis urinarias en un área sanitaria española en las últimas cuatro décadas.

OBJECTIVE: To provide an updated epidemiological description of urinary lithiasis in a health area in the Western hemisphere over the past four decades. METHODS: 2704 urinary lithiases analysed in our institution between 1980 and 2015 were retrospectively reviewed. They were analyzed using polarized light microscopy, and in the case this method had questionable results we used X-ray diffraction. The variables collected were the lithiasis chemical composition (oxalates, phosphates, uric acid, infectious, cystine, mixed, other). Regarding the date of the analysis, the series of cases was grouped into four periods (1980-1989, 1990- 1999, 2000-2009, and 2010-2015), and also by sex and age of the patient. RESULTS: The mean age at diagnosis was 48.32 years (49.37 in men vs 46.53 in women, p=0.005). A male predominance was found (58.7%). Throughout the four decades, the involvement of women has progressively diminished compared to men. Of all the lithiases, the most frequent were those composed of oxalates (43.3%), followed by uric acid (16.9%) and infectious types (10.7%). The uric acid and oxalate lithiases were more common in men than in women (67.4% vs. 32.6% and 59.1% vs. 40.9%, respectively, p<0.001), while the lithiasis of infectious origin was more frequent in women than in men (56.3% vs. 43.7%, p<0.001). Throughout the time period, a trend of increasing oxalic lithiases and decreasing uric acid and phosphate lithiases was observed, as well as an increase of infectious lithiases over the past five years. CONCLUSIONS: In our setting, urinary lithiases appear more frequently in males at the end of the fourth decade of life. The most common lithiases are composed of oxalates, and their frequency has increased over time, while uric acid and phosphates lithiases have decreased.

Association between RNASEL, MSR1, and ELAC2 single nucleotide polymorphisms and gene expression in prostate cancer risk.

BACKGROUND: There is contradictory evidence of the effects that environmental factors-dietary habits (ingestion rates of red meat, soy products, fish, etc.) and work environment (exposure to metals, pesticides, several toxic products, etc.)-and KLK3, AR, RNASEL, MSR1, and ELAC2 expression patterns have on prostate cancer (PCa). In our study, we investigated the potential association between KLK3, AR, RNASEL, MSR1, and ELAC2 polymorphisms, expression patterns, exposure to environmental factors, and PCa in a Spanish cohort. Blood and fresh tissue samples were collected from 322 subjects with prostate-specific antigen (PSA)>4ng/ml to determine their genotypes (RNASEL, MSR1, and ELAC2) and assess messenger ribonucleic acid expression levels (by quantitative amplification testing). MAIN FINDINGS: Among clinical parameters, a 63.6% of patients with CC variants in rs11545302 (ELAC2) had PSA>20ng/ml (P = 0.008), and rs486907 (RNASEL), with 52.8% of patients with CT variants with Gleason score>7. Regarding TNM stage, patients with GG variants, rs4792311 (ELAC2) generally had stage 1 tumors. Genetic expression analysis revealed RNASEL (P = 0.007) was underexpressed in PCa tissue, whereas KLK3 (P = 0.041) was overexpressed. As to environmental factors, the intake of dried fruits (P = 0.036) and practice of sports (P = 0.024) revealed an effect in PCa. Moreover, environmental factors were observed to affect gene expression patterns. Thus, RNASEL (P = 0.018) and ELAC2 (P = 0.023) were found to be underexpressed in patients who ate processed foods frequently; MSR1 (P = 0.024) and AR (P = 0.004) were underexpressed in patients who did not practice sports; and KLK3 (P = 0.039; P = 0.046) underexpressed in patients exposed to dust and toxic products. CONCLUSIONS: This is the first study to analyze the correlation between RNASEL, MSR1, and ELAC2 genotypes and messenger ribonucleic acid expression in PCa. RNASEL and KLK3 show different expression patterns in normal vs. tumor tissue, which supports their reported relevance in human cancer. The results obtained confirm that RNASEL plays a crucial role in PCa. Environmental factors such as exercise, exposure to toxic agents, and intake of processed foods are associated with PCa.

Dormant Circulating Tumor Cells in Prostate Cancer: Therapeutic, Clinical and Biological Implications.

Circulating Tumor Cells (CTCs) are a valuable prognostic factor in several solid tumors. By understanding the biological characteristics of CTCs we could better understand the biology of metastasis. CTCs usually adopt a dormant state that is believed to be a strategy to survive in extreme conditions. To enter a dormant state, CTCs undergo numerous phenotypic, genetic and functional mutations that significantly affect the efficacy of the therapies used to kill dormant CTCs. Hence, understanding the biological events involved in the dormancy process of CTCs would allow the identification of new therapeutic targets. Some experimental studies or preclinical models have explored these biological events, as well as the molecular factors that contribute to the maintenance of and release from dormancy. However, few studies have assessed the effects of anticancer therapies on dormant cells. This study reviews current the data currently available on cell dormancy mechanisms in prostate cancer, with a special focus on the functional, genetic and phenotypic plasticity of CTCs and their potential implications in the clinical and therapeutic management of prostate cancer.

[Incidental finding of scrotal cystocele. Dumbbell sign]. / CRISTOCELE SCROTAL INCIDENTAL. SIGNO DE LA MANCUERNA.

We present the case of a 60-year-old male diagnosed with end stage renal disease due to polycystic kidney disease (urinary flow rate between 100-150mL/24h) in the study to enter renal transplantation waiting list. The patient complained of a right inguinoscrotal bulky mass, first noticed several years before. Physical examination suggested an irreducible inguinoscrotal hernia and surgical repair was offered before transplantation.

Prognostic role of genetic biomarkers in clinical progression of prostate cancer.

The aim of this study was to analyze the use of 12 single-nucleotide polymorphisms in genes ELAC2, RNASEL and MSR1 as biomarkers for prostate cancer (PCa) detection and progression, as well as perform a genetic classification of high-risk patients. A cohort of 451 men (235 patients and 216 controls) was studied. We calculated means of regression analysis using clinical values (stage, prostate-specific antigen, Gleason score and progression) in patients and controls at the basal stage and after a follow-up of 72 months. Significantly different allele frequencies between patients and controls were observed for rs1904577 and rs918 (MSR1 gene) and for rs17552022 and rs5030739 (ELAC2). We found evidence of increased risk for PCa in rs486907 and rs2127565 in variants AA and CC, respectively. In addition, rs627928 (TT-GT), rs486907 (AG) and rs3747531 (CG-CC) were associated with low tumor aggressiveness. Some had a weak linkage, such as rs1904577 and rs2127565, rs4792311 and rs17552022, and rs1904577 and rs918. Our study provides the proof-of-principle that some of the genetic variants (such as rs486907, rs627928 and rs2127565) in genes RNASEL, MSR1 and ELAC2 can be used as predictors of aggressiveness and progression of PCa. In the future, clinical use of these biomarkers, in combination with current ones, could potentially reduce the rate of unnecessary biopsies and specific treatments.

Right renal vein extension with cryopreserved external iliac artery allografts in living-donor kidney transplantations.

INTRODUCTION: A short right renal vein remains a challenge for renal transplant surgery, especially in the living donor. Our objective was to report on a new technique to solve this problem. TECHNICAL CONSIDERATIONS: We describe our experience with the use of cryopreserved iliac artery grafts for right renal vein extension. Two renal grafts from living donors with a short right renal vein were subjected to an extension with a cryopreserved external iliac artery allograft. There were no perioperative or postoperative complications. There were also no changes in ischemia times. The renal implantation was performed easily and conveniently using our standard technique. For the first and second procedures, at 3 and 3.5 years after surgery, respectively, both vascular grafts maintain good patency, and the renal function of both recipients is optimal. CONCLUSION: Tissue-banked cryopreserved cadaveric vessels can be a useful tool in renal transplant surgery. The use of a cryopreserved iliac artery for renal vein extension is a simple and effective new technique that can be added to the pool of surgical solutions for a short renal vein in living-donor kidney transplantation. To our knowledge, this is the first time that the use of such grafts for this purpose has been described.

[Intrathoracic ectopic kidney in an adult: case report and bibliographic review]. / Riñón ectópico intratorácico en un adulto: aportación de un caso y revisión de la literatura.

OBJECTIVE: We report the case of a 61-year-old male with the incidental diagnosis of intrathoracic renal ectopia during the workup study for a possible lung mass. METHODS: We performed a bibliographic review on the incidence, origin, clinical presentation and diagnosis of this type of renal ectopia. RESULTS: Chest x-ray showed a left posterior mediastinum mass. Bronchoscopy was performed showing signs of extrinsic compression with absence of neoplastic cells. CT scan revealed a left intrathoracic ectopic kidney with diaphragmatic hernia. CONCLUSIONS: Intrathoracic renal ectopia is a very unfrequent finding, often asymptomatic, frequently an incidental diagnosis that does not require treatment.

[Metachronic testicular tumor secondary to invasive bladder carcinoma]. / Tumor testicular metacronico secundario a carcinoma vesical infiltrante.

OBJECTIVE: To report a rare case of testicular metastasis secondary to an infiltrative transitional cell carcinoma years after radical surgery. CASE REPORT: 71-year-old male patient with history of infiltrative bladder tumor, status post radical cystoprostatectomy with urethrectomy. Seven years after surgery he presents with pain and swelling in the right testicle. Inguinal orchyectomy was carried out with the pathologic diagnosis of testicular metastasis of a high-grade transitional cell carcinoma. We perform a bibliographic review. RESULTS: The patient is disease-free twelve months after orchyectomy. CONCLUSIONS: Apart from leukemia and lymphoma, testicular metastases are extremely rare. The existence of testicular metastases means a metastatic dissemination to other organs, therefore chemotherapy could improve prognosis.

[Low flow priapism. Treatment by sapheno-cavernous shunt]. / Priapismo de bajo flujo. Tratamiento mediante shunt safeno-cavernoso.

OBJECTIVE: We report the clinical case of a 21-year-old male presenting with a 36 hour history of low flow priapism, its diagnosis and treatment. METHODS: We performed a bibliography review on the etiology, physiopathology, diagnosis and treatment options. RESULTS: The patient underwent unsuccessful punction-aspiration of intracavernous blood with phenylephrine injection and cavernous irrigation with saline solution. A covernous-spongiosum shunt was performed subsequently, firstly using the Winter technique and followed by the AlGorab technique with a final positive response. CONCLUSIONS: The performance of a sapheno-cavernous shunt is an effective treatment for the low flow priapism resistant to usual medical-surgical treatment.

[Metachronous adrenal metastasis in two patients undergoing radical nephrectomy for primary renal cell carcinoma]. / Metástasis suprarrenal metacrónica en 2 pacientes sometidos a nefrectomía radical por carcinoma de células renales primario.

OBJECTIVES: We report two exceptional cases of metachronous adrenal metastasis of renal cell carcinomas and perform a bibliographic review. After the evaluation of various features such as frequency, etiopathogenesis, diagnosis and follow-up of these patients we conclude that these metastases are rare, and they usually appear late in the evolution of patients with low stage renal cell carcinoma. RESULTS/CONCLUSIONS: Once reviewed the treatment and checked the absence of guidelines for the therapeutic management of these patients we propose surgery for the adrenal metastasis as well as adjuvant treatment with immunotherapy.