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Glut(s) expression PC-3 cell line-derived xenograft model.

Clinical localization of primary tumors and sites of metastasis by PET is based on the enhanced cellular uptake of 2-deoxy-2-[18F]-fluoro-D-glucose (FDG). In prostate cancer, however, PET-FDG imaging has shown limited clinical applicability, suggesting that prostate cancer cells may utilize hexoses other than glucose, such as fructose, as the preferred energy source. Our previous studies suggested that prostate cancer cells overexpress fructose transporters, but not glucose transporters, compared with benign cells. Here, we focused on validating the functional expression of fructose transporters and determining whether fructose can modulate the biology of prostate cancer cells in vitro and in vivo. Fructose transporters, Glut5 and Glut9, were significantly upregulated in clinical specimens of prostate cancer when compared with their benign counterparts. Fructose levels in the serum of patients with prostate cancer were significantly higher than healthy subjects. Functional expression of fructose transporters was confirmed in prostate cancer cell lines. A detailed kinetic characterization indicated that Glut5 represents the main functional contributor in mediating fructose transport in prostate cancer cells. Fructose stimulated proliferation and invasion of prostate cancer cells in vitro. In addition, dietary fructose increased the growth of prostate cancer cell line–derived xenograft tumors and promoted prostate cancer cell proliferation in patient-derived xenografts. Gene set enrichment analysis confirmed that fructose stimulation enriched for proliferation-related pathways in prostate cancer cells. These results demonstrate that fructose promotes prostate cancer cell growth and aggressiveness in vitro and in vivo and may represent an alternative energy source for prostate cancer cells.Significance:This study identifies increased expression of fructose transporters in prostate cancer and demonstrates a role for fructose as a key metabolic substrate supporting prostate cancer cells, revealing potential therapeutic targets and biomarkers.

Biological/clinical parameters (patient age, PSA levels, Gleason score) and glucose and fructose levels in benign and PCa patients.

Background: Prostate cancer (PCa) represents one of the most frequent malignancies and the fifth leading cause of cancer death in adult men worldwide. PCa mortality rates have been declining in several Western countries; one of the possible reasons may be related to the application of prostate-specific antigen early detection policies. These early detection protocols increase PCa-specific patient survival; however, a high percentage of these cases corresponds to low-risk PCa that grows very slowly and is unlikely to metastasize to threaten survival. Many low-risk PCa patients receive aggressive therapies, such as radical prostatectomy and radiotherapy, that are costly for patients and/or health systems and generate side effects that affect the quality of life. An alternative to surgery and radiotherapy treatments for low-risk PCa is active surveillance (AS), a strategy based on close disease monitoring and intervention only if the disease progresses. However, proper identification of low-risk PCa patients at the time of diagnosis is essential for the effectiveness AS. The selection of AS candidates remains challenging; thus, effective prognostic biomarkers are needed. Summary: This review article addresses the characteristics of the current and emerging PCa prognostic biomarkers, including tests available for tissue, blood, and urine analyses, for the appropriate selection of PCa patients for AS. In addition, and based on published literature, we performed a selection of potential new biomarkers that can distinguish low-risk PCa. Key Messages: The literature search yielded four tissue-based tests, two blood-based tests, and six urine-based tests that can be used to determine PCa risk classification. However, most available tests are expensive; thus, cost-effective analyses are needed in order to obtain the approval of government agencies and to be financed by the health systems. Available prognostic urine tests have shown great progress over the last years, and they have the advantage of being minimally invasive; therefore, they may become a routine disease progression test for patients under AS. In addition, new research conducted in the last decade has shown promising biomarkers, including mRNA, miRNA, long noncoding RNA, and metabolites, that could improve existing tests or allow the development of new tools for AS patient selection.

Purpose Latin American reports on pheochromocytomas and paragangliomas (PPGLs) are scarce. Recent studies demonstrate changes in clinical presentation and management of these patients. Herein, we assessed the main characteristics of PPGL patients in our academic center over the past 4 decades. Methods Demographic, clinical, biochemical, and perioperative data from 105 PPGL patients were retrospectively and prospectively collected over the 1980–2019 period. Data were organized into 4 periods by decade. Results Age at diagnosis, gender, tumor size and percentage of bilaterality, percentage of paragangliomas, and metastases remained stable across the 4 decades. The proportion of genetic testing and incidentalomas increased in recent decades (all P < 0.001). Therefore, we compared PPGLs diagnosed as incidentalomas (36%) with those clinically suspected (64%). Incidentalomas had fewer adrenergic symptoms (38 vs. 62%; P < 0.001) and lower rates of hypertension (64% vs. 80%; P = 0.01) and hypertensive crisis (28% vs. 44%; P = 0.02); also, they had lower functionality (79% vs. 100%; P = 0.01) and lower catecholamines levels (8.4-fold vs. 12.5-fold above upper cutoffs; P = 0.04). Regarding management of all PPGLs over the decades, we observed significant increases in both perioperative doxazosin dose (P = 0.003) and laparoscopic approach rates (P < 0.001), along with a decrease in the length of hospital stays (P = 0.007). Conclusions We observed a change in the clinical presentation of PPGL in recent decades, with a marked increase in incidental cases and milder symptoms. The implementation of a multidisciplinary program for adrenal disorders in our institution has translated into more timely diagnoses, more genetic testing, and improvements in perioperative management.

Prostate cancer (PCa) is a multifocal neoplasm in which different cancer foci can be found within a single organ. This feature represents a technical difficulty when obtaining highly-enriched primary cultures of human prostate stroma cells (HPSCs), since their isolation involves enzymatic digestion of large pieces of tissue, resulting in an unknown proportion of benign- (BAF) and carcinoma-associated fibroblasts (CAF). Here we report an efficient tissue explant methodology to obtain highly-enriched populations of BAFs or CAFs from benign and malignant human prostate specimens, including needle biopsies. Also, we investigated whether different histological/pathological origins of the prostate tissue determine the activation of distinct transcription programs in HPSCs. Analysis of gene expression profiles revealed that CAFs exhibited a unique transcriptional program characterized by up-regulation of genes involved in proliferation, migration and cell adhesion. CAFs, but not BAFs, expressed typical activation markers such as α-smooth muscle actin, tenascin C and collagen 1 and stimulated tumor growth of PCa cells in vivo. Our study indicated that gene expression profile of HPSCs was determined mostly by the zone rather than the pathological state of the prostate tissue and that tissue explants from needle biopsies provide a valuable tool to obtain highly enriched primary cultures of HPSCs.

Objectives To establish the role of BCG instillations in the incidence and mortality of COVID-19. Patients and methods NMIBC patients in instillations with BCG (induction or maintenance) during 2019/2020 were included, establishing a COVID-19 group (with a diagnosis according to the national registry) and a control group (NO-COVID). The cumulative incidence (cases/total patients) and the case fatality rate (deaths/cases) were established, and compared with the national statistics for the same age group. T-test was used for continuous variables and Fisher's exact test for categorical variables. Results 175 patients were included. Eleven patients presented CIS (11/175, 6.3%), 84/175 (48.0%) Ta and 68/175 (38.9%) T1. Average number of instillations = 13.25 ± 7.4. One hundred sixty-seven patients (95.4%) had complete induction. Forty-three patients (cumulative incidence 24.6%) were diagnosed with COVID-19. There is no difference between COVID-19 and NO-COVID group in age, gender or proportion of maintenance completed. COVID-19 group fatality rate = 1/43 (2.3%). Accumulated Chilean incidence 70–79 years = 6.3%. Chilean fatality rate 70–79 years = 14%. Conclusions According to our results, patients with NMIBC submitted to instillations with BCG have a lower case-fatality rate than the national registry of patients between 70 and 79 years (2.3% vs. 14%, respectively). Intravesical BCG could decrease the mortality due to COVID-19, so instillation schemes should not be suspended in a pandemic.

Background Bladder tumors in pregnancy are extremely rare. No more than 50 cases have been published to date, including all histologic variants, and only three cases of bladder squamous cell carcinoma have been described. Case presentation We present a clinical case of a 31-year-old woman with bladder squamous cell carcinoma in the second trimester of pregnancy. After a C-section at 30 weeks, we performed radical cystectomy with extended bilateral lymphadenectomy, hysterectomy and right oophorectomy. The Studer neobladder technique was performed for urinary tract reconstruction. Definitive pathology showed invasive bladder squamous cell carcinoma, Grade 2, with microscopic infiltration of the perivesical fat, negative margins, and 3/28 lymph nodes with carcinoma (pT3aN2M0). The patient underwent 18 months of surveillance after radical cystectomy, without recurrence by PET-CT. Conclusions Bladder cancer in pregnant women is extremely rare but must be considered in those with recurrent gross hematuria and/or recurrent urinary tract infection. To our knowledge, this case involves the longest recurrence-free survival of a pregnant woman with squamous cell bladder cancer published thus far.

Objective: Latin American reports on pheochromocytomas and paragangliomas (PPGL) are scarce. Recent studies have shown changes in both clinical presentation and management of these patients. We aimed to assess the main characteristics of PPGL patients in a single academic center over the last four decades. Experimental design: Cohort study. Patients and methods: Demographic, clinical, biochemical, genetic and perioperative data from 105 PPGL patients were retrospectively and prospectively collected over the 1980–2019 period. Patients were categorized into four groups (14 patients in the 1st, 25 patients in the 2nd, 27 patients in the 3th and 39 patients in the 4th decade) according to the date of diagnosis. Results: The mean age at diagnosis was 46±19 years, and the tumor size was 5.3±2.2 cm, female gender was 63%, bilateral tumor of 15%, paragangliomas 9% and metastatic disease in 15%. The aforementioned parameters remained stable across the four decades. During the study period we observed significant increases in doxazosin dosing (2.7±2.6 mg vs. 8.0±4.5 p marked increase in incidental cases, which highlights the importance of early diagnosis and treatment.

Adrenal incidentalomas are common with a prevalence of 3-10% and in up to 30% of cases may have probable autonomous cortisol secretion. Hypercortisolism is associated with substantial cardiometabolic morbimortality and can physiologically decrease ACTH levels. Objective: To determine the sensitivity, specificity, and positive and negative predictive values of ACTH levels in evaluating autonomous cortisol secretion in a prospective cohort of incidentally discovered adrenal adenomas. Methods: We prospectively evaluated 224 consecutive adult subjects with incidentally discovered adrenal masses on computed tomography. Finally, 168 participants with radiographic adenoma criteria underwent systematic hormonal assessment, including measurements of morning cortisol and ACTH on day 1, and a 1 mg dexamethasone suppression test (DST) on day 2. Hypercortisolism was excluded if the DST was < 1.8 mcg/dL. Autonomous cortisol secretion was defined as a DST > 5.0 mcg/dL and DST levels of 1.8-5.0 mcg/dL were considered to be possibly autonomous hypercortisolism. We evaluated the correlation of ACTH levels with clinical, radiographic, and endocrine variables. In order to identify the most sensitive threshold value for diagnosing autonomous cortisol secretion, we determined ROC curves and negative likelihood ratio (NLR). Concordance of repeated ACTH was assessed using Bland Altman analysis. Results: The characteristics of the cohort were mean age 56 (+/- 11.8) years, 76% female, adenoma size 19 (+/- 7) mm, and 13% bilateral adenomas. Mean ACTH was 15 (+/- 11) pg/ml (range 5-72) and the mean DST was 2.2 (+/- 3.0) ug/dL (range 0.4-25.9). Fifty-four (32%) participants had a DST ≥1.8mcg/dL and 13 (8%) a DST≥5.0 mcg/dL. We found no correlation between ACTH levels and age, gender or body mass index. ACTH was inversely associated with adrenal adenoma diameter (r=-3.3 p=0.002) and volume (r=-2.9 p=0.008). There was an inverse association between ACTH and DST values (r=-3.1 p=0.01). In the subgroup of patients with a second ACTH measurement we found high concordance, with mean difference of 0.16+/-3.6 pg/ml (p=0.83). ROC analysis showed that an ACTH ≥20 pg/ml had a sensitivity of 98% to exclude hypercortisolism, with a negative predictive value of 97% and a negative likelihood ratio of 0.06. The only case with DST≥1.8 and ACTH≥20 had Cushing′s phenotype with both an adrenal adenoma and a pituitary ACTH-producing adenoma. Systematic evaluation of morning cortisol and ACTH allowed the detection of 5 cases of false negative low DST values due to the use of non-oral corticosteroids. Conclusion: In this cohort, an ACTH ≥20pg/ml excluded autonomous cortisol secretion with excellent sensitivity and negative predictive value, providing strong reassurance that there is no clinically relevant hypercortisolism. Therefore, subjects with a normal DST and ACTH ≥20pg/ml should be candidates for relaxed surveillance.

Lupus nephritis (LN) is one of the most serious manifestations of systemic lupus erythematosus (SLE). Based on studies showing the potential role of heme oxygenase-1 (HO-1), an enzyme that catalyzes the degradation of heme and has anti-inflammatory properties in SLE development, we decided to explore HO-1 in LN. Accordingly, we evaluated HO-1 levels and function in circulating and infiltrating monocytes and neutrophils of LN patients. HO-1 levels were assessed in peripheral monocytes of LN patients and controls by flow cytometry and immunofluorescence microscopy. Phagocytosis and the production of reactive oxygen species (ROS) were evaluated to determine the effect of HO-1 in monocyte function. In addition, renal biopsies with proliferative LN were used to identify HO-1 in infiltrating cells and renal tissue by immunofluorescence and immunohistochemistry. Biopsies of healthy controls (HC) and patients who underwent nephrectomy were included as controls. Circulating pro-inflammatory monocytes and activated neutrophils were increased in LN patients. HO-1 levels were decreased in all subsets of monocytes and in activated neutrophils. LN monocytes showed increased phagocytosis and higher production of ROS than those of HC. When HO-1 was induced, phagocytosis and ROS levels became similar to those of HC. HO-1 was mostly expressed in renal tubular epithelial cells (RTEC). Renal tissue of LN patients showed lower levels of HO-1 than HC, whereas infiltrating immune cells of LN showed lower levels of HO-1 than biopsies of patients who had renal surgery. HO-1 is decreased in circulating monocytes and activated neutrophils of LN patients. HO-1 levels modulate the phagocytosis of LN monocytes and ROS production. HO-1 expression in RTEC might be an attempt of self-protection from inflammation.

Activation of glucose transporter-1 (Glut-1) gene expression is a molecular feature of cancer cells that increases glucose uptake and metabolism. Increased glucose uptake is the basis for the clinical localization of primary tumors using positron emission tomography (PET) and 2-deoxy-2-[18F]-fluoro-D-glucose (FDG) as a radiotracer. However, previous studies have demonstrated that a considerable number of cancers, which include prostate cancer (CaP), express low to undetectable levels of Glut-1 and that FDG-PET has limited clinical applicability in CaP. This observation could be explained by a low metabolic activity of CaP cells that may be overcome using different hexoses, such as fructose, as the preferred energy source. However, these hypotheses have not been examined critically in CaP. This review article summarizes what is currently known about transport and metabolism of hexoses, and more specifically fructose, in CaP and provides experimental evidences indicating that CaP cells may have increased capacity to transport and metabolize fructose in vitro and in vivo. Moreover, this review highlights recent findings that allow better understanding of how metabolism of fructose may regulate cancer cell proliferation and how fructose uptake and metabolism, through the de novo lipogenesis pathway, may provide new opportunities for CaP early diagnosis, staging, and treatment.

IntroducciA³n: el objetivo de este estudio fue establecer una asociaciA³n entre diversas variables demogrAificas y epidemiolA³gicas con la agresividad del cAincer de prA³stata (CaP).MA©todos: pacientes diagnosticados con CaP respondieron una encuesta que incluye el nivel de educaciA³n, los factores de riesgo cardiovascular (FRCV), los antecedentes familiares (HF) de CaP, consumo de alcohol, tabaquismo y otros. Se utilizA³ anAilisis univariado y multivariado (AMV) para establecer si los factores mencionados anteriormente afectan las variables asociadas con la agresividad del CaP, como la edad al momento del diagnA³stico, el A­ndice de Gleason, los mAirgenes positivos (MP) y la metAistasis A³seas (MO), entre otras.Resultados: se incluyeron ciento setenta y dos hombres en el anAilisis. Los pacientes con HF fueron diagnosticados a edades mAis tempranas que los pacientes sin HF (55,73 vs 66,45 aA±os, p = 0,0001). Los pacientes que beben tienen un mayor nAomero de MP que los pacientes que no (15 vs 4 pacientes, p = 0,04). El AMV mostrA³ que los pacientes que consumen alcohol y los que fuman (activos o suspendidos) tuvieron un mayor riesgo de MP (OR = 4,45 y 4,1, IC 95% 1,16-17,07 y 1,14-14,72, respectivamente, ambos p

Introducción: Establecer un score genético utilizando los polimorfismos de nucleótido único (SNPs) del gen RNAsel y regiones cromosómicas 8q24 y 17q12-24 en combinación con el antígeno específico de la próstata (PSA) para predecir la agresividad del cáncer de próstata (CaP).Pacientes y métodos: hombres con CaP tratados con prostatectomía radical. Se analizaron variables clínicas y patológicas: edad al diagnóstico, PSA al diagnóstico, el volumen tumoral (TV) y extensión extracapsular (ECE) según el TNM (tumour, node and metástasis) (ECE ≥T3) y score de Gleason. Desarrollamos un modelo de puntaje genético usando regresión logística multivariable.Resultados: se incluyeron 86 pacientes sometidos a prostatectomía radical. Edad promedio fue de 62 ± 7,5 años. El promedio de PSA fue de 11,3 ± 10,6 ng/mL. Treinta y un pacientes (36%) tuvieron ECE. La mediana del TV fue de 3,8 cc. Un PSA ≥ 10 ng/mL se asoció con una mayor tasa de ECE (p 1 SNP tienen mayor riesgo de ECE que los pacientes con ≤ 1 SNP (42% vs. 10,5%, p = 0,01), y los pacientes con ≥ 3 SNP tienen más TV que los pacientes con

Introduccion: El cancer de prostata (CP) presenta una alta prevalencia. La radioterapia con intensidad modulada (IMRT) es una nueva tecnica con impacto poco conocido en la calidad de vida a largo plazo (CDVALP) de estos pacientes. El objetivo fue evaluar CDVALP en este grupo . Materiales y Metodo : Se incluyeron pacientes tratados entre 2000-2010, con mas de 1 ano de seguimiento. Se utilizo cuestionario EPIC, que fue completado directamente por el paciente. Se evaluaron dominios objetivos y subjetivos de habitos urinarios, intestinales, hormonales y sexuales. Estudio aprobado por el comite de etica. Resultados: Se analizaron 45 encuestas. La mediana de edad fue 75 anos (rango 55-90), seguimiento 4,4 anos (rango 1,5-8,5). Tasa respuesta promedio fue de 96,9%. La toxicidad moderada-importante objetiva para dominio urinario fue: escape urinario 8,8%, disuria 4,4%, incontinencia 4,4%, uso panales 2,2%, hematuria 6,6%. En lo subjetivo, la polaquiuria fue “un problema grande” en 6,7%. La toxicidad intestinal objetiva moderada-importante fue: frecuencia deposicion 8,9%, diarrea 4,4%, pujo 6,6%, incontinencia 4,4%, hematoquezia 0%. En el dominio hormonal: bochornos significativos 11,1%. En dominio sexual: compromiso importante del deseo 57,6%, ereccion 66,7%, orgasmo 55,6%, en globo 62,4%, Subjetivamente la disfuncion erectil se considero “un problema grande” en 31,1%. En globo, la disfuncion sexual subjetiva se considero importante en 24,4% y moderada en 17,8%. Conclusiones: La radioterapia con IMRT se asocia a buena CDVALP en dominios urinario, intestinal, hormonal. La alta toxicidad sexual podria estar asociada a la edad avanzada de los pacientes tratados con radioterapia.

Sex-related differences in the role of androgen have been reported in cardiovascular diseases and angiogenesis. Moreover, androgen receptor (AR) has been causally involved in the homeostasis of human prostate endothelial cells. However, levels of expression, functionality and biological role of AR in male- and female-derived human endothelial cells (ECs) remain poorly characterized. The objectives of this work were (1) to characterize the functional expression of AR in male- and female-derived human umbilical vein endothelial cell (HUVEC), and (2) to specifically analyze the biological effects of DHT, and the role of AR on these effects, in male-derived HUVECs (mHUVECs). Immunohistochemical analyses of tissue microarrays from benign human tissues confirmed expression of AR in ECs from several androgen-regulated and non-androgen-regulated human organs. Functional expression of AR was validated in vitro in male- and female-derived HUVECs using quantitative RT-PCR, immunoblotting and AR-mediated transcriptional activity assays. Our results indicated that functional expression of AR in male- and female-derived HUVECs was heterogeneous, but not sex dependent. In parallel, we analyzed in depth the biological effects of DHT, and the role of AR on these effects, on proliferation, survival and tube formation capacity in mHUVECs. Our results indicated that DHT did not affect mHUVEC survival; however, DHT stimulated mHUVEC proliferation and suppressed mHUVEC tube formation capacity. While the effect of DHT on proliferation was mediated through AR, the effect of DHT on tube formation did not depend on the presence of a functional AR, but rather depended on the ability of mHUVECs to further metabolize DHT. (1) Heterogeneous expression of AR in male- and female-derived HUVEC could define the presence of functionally different subpopulations of ECs that may be affected differentially by androgens, which could explain, at least in part, the pleiotropic effects of androgen on vascular biology, and (2) DHT, and metabolites of DHT, generally thought to represent progressively more hydrophilic products along the path to elimination, may have differential roles in modulating the biology of human ECs through AR-dependent and AR-independent mechanisms, respectively.

Androgen deprivation therapy (ADT) provides palliation for most patients with advanced prostate cancer (CaP); however, greater than 80% subsequently fail ADT. ADT has been indicated to induce an acute but transient destabilization of the prostate vasculature in animal models and humans. Human re-hydrated lyophilized platelets (hRL-P) were investigated as a prototype for therapeutic agents designed to target selectively the tumour-associated vasculature in CaP. The ability of hRL-P to bind the perturbed endothelial cells was tested using thrombin- and ADP-activated human umbilical vein endothelial cells (HUVEC), as well as primary xenografts of human prostate tissue undergoing acute vascular involution in response to ADT. hRL-P adhered to activated HUVEC in a dose-responsive manner. Systemically administered hRL-P, and hRL-P loaded with super-paramagnetic iron oxide (SPIO) nanoparticles, selectively targeted the ADT-damaged human microvasculature in primary xenografts of human prostate tissue. This study demonstrated that hRL-P pre-loaded with chemo-therapeutics or nanoparticles could provide a new paradigm for therapeutic modalities to prevent the rebound/increase in prostate vasculature after ADT, inhibiting the transition to castration-recurrent growth.

Objective To determine whether total testosterone and free testosterone levels predict disease reclassification in a cohort of men with prostate cancer (PCa) on active surveillance (AS). Patients and Methods Total testosterone and free testosterone concentrations were determined at the time the men began the AS protocol. Statistical analysis was performed using Student's t-test and a chi-squared test to compare groups. Odds ratios (ORs) with 95% confidence intervals (CIs) were obtained using univariate logistic regression. Receiver–operator characteristic curves were generated to determine the investigated testosterone thresholds. Kaplan–Meier curves were used to estimate time to disease reclassification. A Cox proportional hazard regression model was used for multivariate analysis. Results A total of 154 men were included in the AS cohort, of whom 54 (35%) progressed to active treatment. Men who had disease reclassification had significantly lower free testosterone levels than those who were not reclassified (0.75 vs 1.02 ng/dL, P = 0.03). Men with free testosterone levels

PURPOSE: This study aimed to evaluate the need for intraoperative ultrasound (IOUS) and recommendation for surgical approach in the resection of renal tumors through a survey of practicing urologists, with correlation to tumor imaging features and urologist practice pattern. MATERIALS AND METHODS: An institutional review board-approved retrospective review, compliant with the Health Insurance Portability and Accountability Act, of 44 renal tumors that underwent laparoscopic partial nephrectomy at the study institution was performed. The numeric component of the RENAL nephrometry score (radius [diameter], % exophytic, nearness [to collecting system/renal sinus], location) was calculated for each case using preoperative computed tomography/magnetic resonance imaging. Five anonymized images of each tumor were presented to 4 academic urologists with varying practice patterns. Reviewers independently scored each case for its need for IOUS, for recommendation of a surgical technique, and for the difficulty of the proposed surgery. RESULTS: The RENAL scores were as follows: RENAL 1 (low complexity, score 4-6; n = 19); RENAL 2 (moderate complexity, score 7-9; n = 23); RENAL 3 (high complexity, score 10-12; n = 2). The only RENAL score component significantly influencing need for IOUS was percentage exophytic (P = 0.00002). There was an inverse relationship between normalized and averaged need for IOUS and percentage exophytic (P < 0.0001). The predominant influence for recommendation of surgical method was the reviewer him/herself, with each reviewer's recommendations closely matching his/her practice pattern. Size and percentage exophytic represented the only tumor features significantly (P = 0.03) influencing surgical recommendation. CONCLUSIONS: There was a significant difference in the perceived need for IOUS and surgical recommendation when 4 academic urologists reviewed a series of renal masses requiring resection. Percentage exophytic correlated inversely with need for IOUS. Urologist's practice pattern and tumor size and percentage exophytic were most predictive of surgical recommendation.

Arteriovenous malformation (AVM) of the pancreas (AVMP) is uncommon and generally asymptomatic; therefore, few cases have so far been reported. The symptoms of AVMP include gastrointestinal bleeding, pain, and portal hypertension. Definitive diagnosis is confirmed by angiographic study, and surgery is the only effective treatment. We report a case of AVMP confirmed by computed tomography, magnetic resonance imaging, and angiographic study of the abdomen, in a patient who presented to us with epigastric pain. He underwent a pancreaticoduodenectomy, following which his symptoms resolved.

Androgen receptor (AR) is a ligand-inducible transcription factor, and a member of the steroid-thyroid-retinoid receptor superfamily, that mediates the biological effects of androgens in a wide range of physiological and pathological processes. AR expression was identified in vascular cells nearly 20 years ago, and recent research has shown that AR mediates a variety of actions of androgens in endothelial and vascular smooth muscle cells. In this mini-review, we review evidence indicating the importance of AR in human endothelial cell (HUVEC) homeostatic and pathogenic processes. Although a role for AR in the modulation of HUVEC biology is evident, the molecular mechanisms by which AR regulates HUVEC homeostasis and disease processes are not fully understood. Understanding these mechanisms could provide critical insights into the processes of pathogenesis of diseases ranging from cardiovascular disease to cancer that are major causes of human morbidity and mortality.

Objective: We evaluated the differences in pathologic findings and outcomes in patients undergoing radical retropubic prostatectomy (RRP) for localized prostate cancer diagnosed by either extended or non-extended prostate needle biopsy techniques. Patients and Methods: Two hundred and seventy eight men with the diagnosis of localized prostate cancer using needle biopsies who underwent RRP were evaluated. Two study groups were identified: the first consisted of 123 patients diagnosed with prostate cancer by the use of extended needle biopsies (10 or more biopsy cores), and the second group consisted of 155 patients diagnosed with cancer by non-extended needle biopsies (9 or less biopsy cores). Median time of follow-up was 45 and 50 months, respectively. Biopsy and RRP specimen characteristics and outcome were compared between the two groups. Results: Patients in the extended biopsy group had a median of 12 biopsy cores Interquartile range (IQR, 10–13; range, 10–16) with a mean of 2.7 cores positive for can...

Purpose: We examined the concordance of Gleason scores in prostate needle biopsy specimens and the corresponding radical retropubic prostatectomy specimens in a cohort of patients grouped according to the number of cores obtained during diagnostic needle biopsy.Materials and Methods: We reviewed clinical and pathological data on a cohort of 466 men diagnosed with localized prostate cancer by needle biopsies who underwent radical retropubic prostatectomy between January 1, 1990 and July 31, 2001. Two study groups were identified, including 126 patients diagnosed with prostate cancer by extended needle biopsies (10 or more cores) and 340 diagnosed with cancer by nonextended needle biopsies (9 or fewer cores). Mean age was 60 years and median prostate specific antigen was 5.8 ng./ml. The median number of cores in the extended and nonextended biopsy groups was 12 and 6, respectively. The concordance of Gleason score in the needle biopsy and prostatectomy specimens was compared and correlated with the number o...

Purpose: We investigated the relationship between prostate volume and cancer detection by needle biopsy, and determined the effect of an increased number of cores on the sampling error of needle biopsy on large prostate glands.Materials and Methods: The study cohort included 750 consecutive patients who underwent first time transrectal ultrasound guided prostate needle biopsy from January 1995 to August 2001. Prostate volumes were divided into quartiles (13 to 34, 34.1 to 45, 45.1 to 64 and 64.1 to 244 cc). Multivariate analysis controlling for age, prostate specific antigen (PSA) and biopsy indication was performed to determine the effect of the number of cores and prostate volume on prostate cancer detection.Results: Patients diagnosed with prostate cancer were older (p = 0.0035) and had higher PSA levels (p = 0.0002) than those with no cancer on biopsy. Decreasing cancer detection rates were seen with increasing prostate volume (p = 0.0074). The OR of detection for each additional core was 0.99...

To study the association between the polymorphisms Arg462Gln and Asp541Glu from the RNASEL gene (1q25), and the polymorphisms rs620861, rs1447295, rs6983267, rs7837328 from the chromosome 8q24 with the risk of presenting prostate cancer (PCa) and its clinical characteristics in a Hispanic (Chilean) population. The study was performed on 21 control patients and 83 patients diagnosed with PCa. Polymorphisms were analysed from blood samples through real-time PCR by using TaqMan probes, and the genetic analysis was performed with the SNPStats program. Also, a comparison was performed between clinical characteristics of PCa and the presence of the different polymorphism genotypes by using the Minitab software. There was a significant association between the genotype G/G from the polymorphism rs6983267 with an overall increased risk of PCa, in patients both with or without family history of PCa (OR = 4.47, 95% CI = 1.05–18.94, P = 0.034 and OR = 3.57, 95% CI = 0.96–13.35, P = 0.037, respectively). Regarding clinical parameters, patients carrying the genotype C/C from the polymorphism Asp541Glu had significantly higher prostate-specific antigen (PSA) levels than patients carrying the other genotypes (P = 0.034). Moreover, patients with the genotype G/G of rs6983267 had higher PSA levels (P = 0.024). The polymorphism rs6983267 from region 3 of the chromosome 8q24 appears to be a prominent risk factor for PCa and a biomarker for cancer aggressiveness in the group of patients who presented higher levels of PSA at the time of diagnosis.

This report presents our experience with T therapy in a cohort of T-deficient men on active surveillance (AS) for Gleason 3 + 3 and Gleason 3 + 4 prostate cancer (PCa). A retrospective chart review identified 28 men with T deficiency who underwent T therapy (T group) for at least 6 months while on AS for PCa. A comparison group of 96 men on AS for PCa with untreated T deficiency (no-T group) was identified at the same institution. The AS protocol followed a modified Epstein criteria and allowed inclusion of men with a single core of low-volume Gleason 3 + 4 PCa. Mean age was 59.5 and 61.3 years, and mean follow-up was 38.9 and 42.4 months for the T and no-T groups, respectively. Of all 28 men in the T group, 3 (10.7%) men developed an increase in Gleason score while on AS. Of 22 men in the T group with Gleason 3 + 3 disease, 7 (31.8%) men developed biopsy progression including 3 men (13.6%) who developed Gleason 3 + 4 PCa. Of 6 men with Gleason 3 + 4 disease at baseline, 2 (33.3%) men developed an increase in tumor volume, and none developed upgrading beyond Gleason 3 + 4. All 96 men in the no-T group had Gleason 3 + 3 disease at baseline and, 43 (44.7%) developed biopsy progression, including 9 men (9.38%) with upgrading to Gleason 7 (3 + 4). Biopsy progression rates were similar for both groups and historical controls. Biopsy progression in men on AS appears unaffected by T therapy over 3 years. Prospective placebo-controlled trials of T therapy in T-deficient men on AS should be considered given the symptomatic benefits experienced by treated men.

Robot-assisted partial nephrectomy (RAPN) is emerging as a viable minimally invasive surgical technique for small renal tumors. The warm ischemia time (WIT) during laparoscopic partial nephrectomy has been reduced using an early unclamping (EU) technique. We present our technique of EU technique in RAPN. From November 2009 to June 2010, 12 consecutive RAPNs were performed by a single surgeon (A.W.) using EU technique. The median operative time was 227 minutes (176-315); median WIT, 16 minutes (11-25). Median estimated blood loss was 150 mL (50-500) and length of stay 2 days. There were no intraoperative or postoperative complications. RAPN using EU technique is a safe and feasible option in experienced hands, allowing for a shorter WIT without increasing blood loss. This approach requires a highly skilled bedside assistant who is imminently familiar with the robotic system and advanced laparoscopic techniques.

Introduction: There is a paucity of realistic simulators for robot-assisted radical prostatectomy (RARP) despite the realization that they can shorten the well-known learning curve. Existi...

We evaluated whether the surgical approach during the implementation of a robotic kidney surgery program influenced perioperative and oncologic outcomes.We prospectively evaluated a single institution experience with minimally invasive partial nephrectomy between 2006 and 2010. The study cohort comprised 86 consecutively treated patients who underwent laparoscopic partial nephrectomy (LPN, N = 59) or robotic-assisted (RPN, N = 27) partial nephrectomy by a single surgeon.There was no difference between the LPN and RPN cohort in terms of gender, age, operative side, American Society of Anesthesiology score, or preoperative estimated glomerular filtration rate (eGFR). An early unclamping technique was used for 22 (82%) patients in the RPN cohort and 6 (10%) patients in the LPN cohort. (P0.001). Warm ischemia time was lower in the RPN cohort (mean 18.5 vs. 28.0 min, P =0.001) as result of majority undergoing early unclamping. There was no difference in operative time, estimated blood loss, length of stay, transfusion rate, positive surgical margin, or postoperative decrease in eGFR. There was no difference in mean eGFR decrease after early unclamping (16%) versus traditional clamping (22%); however, 11 (29%) patients had greater than 50% decrease in eGFR after traditional clamping versus 0 patients after early unclamping (P = 0.014).Patients undergoing RPN during implementation of a robotic kidney surgery program when compared with LPN appear to have equivalent perioperative outcomes and oncologic efficacy. RPN patients had surgery later in our minimally invasive partial nephrectomy experience, and these results may not be generalizable to laparoscopic and/or robotic naïve surgeons.

Las malformaciones arteriovenosas del páncreas (MAVP) son poco frecuentes y generalmente asintomáticas, por lo que existen escasos reportes en la literatura. Se pueden complicar con sangrado, dolor o hipertensión portal. El diagnóstico preciso se logra con la angiografía, que también puede ser usada como terapia inicial. El tratamiento definitivo es la cirugía. Se presenta el caso de un hombre de 35 años que consultó por dolor epigástrico intenso con escasa respuesta a analgésicos. El estudio con tomografía computada, resonancia y angiografía de abdomen mostró una MAVP. Se le realizó una pancreatoduodenectomía con desaparición de los síntomas en forma completa

We determined the relationship between age adjusted free T, and stage, grade and the biochemical-free survival rate in patients with surgically treated prostate cancer.A retrospective cohort study was done between 1995 and 2001 in 333 patients treated for clinically localized prostate cancer with radical retropubic prostatectomy by a single surgeon at our institution. The study cohort consisted of 279 patients (84%) who had free T levels available. Free T was assessed by single cutoff value of 1.5 ng/dl or less, as suggested by the assay manufacturer, or by age adjusted free T. The relationship of low free T as a single cutoff value and age adjusted reference ranges with clinical and pathological measures of disease progression were assessed using the Fisher exact and Wilcoxon rank sum tests with the outcome assessed by the log rank test.Using the assay manufacturer suggested single cutoff value of 1.5 ng/dl or less to define low free T 57% of patients with prostate cancer in the cohort were categorized as hypogonadal. However, using age adjusted free T reference ranges only 2.5% of patients with prostate cancer were categorized as hypogonadal, which is more logical and representative of clinically significant hypogonadism in the general population. Poorly differentiated prostate cancer was associated with low free T when measured by a single cutoff value of 1.5 ng/dl or less, or by age adjusted free T (p = 0.017 and 0.04, respectively).Low age adjusted free T as well as single cutoff free T correlates with poorly differentiated prostate cancer in surgically treated patients.

Carcinoma-associated fibroblasts (CAF) promote tumor progression of pre-neoplastic epithelial cells. To investigate the basis of this phenomenon, we compared the properties of fibroblasts cultured from normal human prostate (NHPF) to prostate CAF. NHPF and CAF were assayed for growth potential, cell death and proliferative capacity by measuring population doubling time, cell cycle distribution and capability to form colonies in soft agar. Resistance to genotoxic (UV radiation: 0-50 J/cm2) and chemotoxic (0-200 nM Taxol) agents were compared between CAF and NHPF by measuring cell viability and cell cycle analysis. Transforming growth factor beta1 (TGF-beta1) immunoreactivity was assessed in non-malignant and malignant prostatic tissue. No detectable differences were found when comparing CAF and NHPF with respect to population doubling time, cell cycle distribution and response to genotoxic and chemotoxic agents. The mean number of colonies in soft agar was 120.5 for CAF vs. 18.2 for NHPF (p < 0.05). Because TGF-beta1 and matrix metalloproteinase (MMP)-9 have been associated with growth of fibroblasts in soft agar and tumor promotion, we measured the expression of these factors in NHPF and CAF by ELISA. There was no difference in expression of MMP-9; however, TGF-beta1 was expressed in higher concentrations in CAF than in NHPF (p < 0.0014). Furthermore, TGF-beta1 expression was higher in the carcinoma-associated stroma of prostate cancer tissue than stroma of non-malignant prostatic tissue. Increased capability of CAF as compared to NHPF to form colonies in soft agar may be due to a higher expression of TGF-beta1 and correlates with the ability of CAF to promote malignant progression of prostate epithelial cells.

We examined the prognostic significance of clinical and pathological variables on outcome following radical retropubic prostatectomy (RRP) in a cohort of patients in the post-prostate specific antigen (PSA) era.We reviewed the clinical and pathological data on a cohort of 476 patients who underwent RRP for localized prostate cancer between January 1990 and July 2001 by 1 urologist (WCD). Median age, preoperative PSA and followup were 61 years, 5.8 ng/ml and 49 months, respectively. We used Cox proportional hazard modeling to evaluate the prognostic significance of clinical and pathological variables for cancer recurrence, defined as 2 successive PSA determinations 0.3 ng/ml or greater.Of the 476 patients 53 (11%) had recurrence. Estimated cancer nonprogression probability was 86% (95% CI 83 to 90) and 76% (95% CI 68 to 86) at 5 and 10 years, respectively. Two multivariate analyses were performed. The first analysis, using only preoperative indicators, found that the percent of biopsy cores positive for cancer and biopsy Gleason score were the best predictive indicators of recurrence. The second multivariate analysis, using preoperative and postoperative indicators, found that the percent of biopsy cores positive for cancer, RRP Gleason score and the combined pathological stage/margin status variable were the best predictive indicators of recurrence. PSA was not found to be an important predictor of recurrence on either multivariate analysis. Patients with a percent of biopsy cores in the upper half of the distribution (greater than 28% positive) were at significantly increased risk for recurrence compared with those in the lower half of the distribution (28% or less positive) (HR 3.86, p0.001).The percent of cores positive for cancer was a better predictor of cancer recurrence than PSA in this post-PSA era RRP series. In addition, surgical Gleason score and pathological stage/surgical margins were also independent predictors of cancer recurrence after RRP. These 3 predictors are displayed in a nomogram-type format to summarize estimated 5 and 10-year recurrence-free probabilities.

We investigated the relationship between prostate volume and cancer detection by needle biopsy, and determined the effect of an increased number of cores on the sampling error of needle biopsy on large prostate glands.The study cohort included 750 consecutive patients who underwent first time transrectal ultrasound guided prostate needle biopsy from January 1995 to August 2001. Prostate volumes were divided into quartiles (13 to 34, 34.1 to 45, 45.1 to 64 and 64.1 to 244 cc). Multivariate analysis controlling for age, prostate specific antigen (PSA) and biopsy indication was performed to determine the effect of the number of cores and prostate volume on prostate cancer detection.Patients diagnosed with prostate cancer were older (p = 0.0035) and had higher PSA levels (p = 0.0002) than those with no cancer on biopsy. Decreasing cancer detection rates were seen with increasing prostate volume (p = 0.0074). The OR of detection for each additional core was 0.99 (95% CI 0.93, 1.06), suggesting that increasing the number of biopsy cores did not increase the rate of prostate cancer detection. Multivariate analysis revealed that patients with larger prostates had the same, or possibly lower, cancer detection rate as the number of biopsy cores was increased. Patients with larger prostates were older (p0.0001), had higher PSA levels (p0.0001) and were even more likely to have undergone biopsy for increased PSA rather than abnormal digital rectal examination alone (p0.0001).Our study suggests that the lower cancer detection rate for men with large prostates may be due to a decrease in the use of increased serum PSA for prostate cancer detection in larger prostates in addition to other factors such as sampling error. Increased serum PSA levels in cases of larger prostates, although a risk factor for prostate cancer warranting biopsy, may also be due to nonmalignant sources such as benign prostatic hyperplasia.

We examined the concordance of Gleason scores in prostate needle biopsy specimens and the corresponding radical retropubic prostatectomy specimens in a cohort of patients grouped according to the number of cores obtained during diagnostic needle biopsy.We reviewed clinical and pathological data on a cohort of 466 men diagnosed with localized prostate cancer by needle biopsies who underwent radical retropubic prostatectomy between January 1, 1990 and July 31, 2001. Two study groups were identified, including 126 patients diagnosed with prostate cancer by extended needle biopsies (10 or more cores) and 340 diagnosed with cancer by nonextended needle biopsies (9 or fewer cores). Mean age was 60 years and median prostate specific antigen was 5.8 ng./ml. The median number of cores in the extended and nonextended biopsy groups was 12 and 6, respectively. The concordance of Gleason score in the needle biopsy and prostatectomy specimens was compared and correlated with the number of cores on needle biopsy.In the whole cohort 311 patients (67%) had identical Gleason scores on the needle biopsy and prostatectomy specimens, while 53 (11%) were over graded and 102 (22%) were under graded on needle biopsy. In patients who underwent extended needle biopsies the accuracy rate for Gleason scoring was 76% with 10% over and 14% under graded. The highest accuracy rates were in patients with 13, 14 and 16 cores (89%, 87% and 100%, respectively). No patients in the extended needle biopsy group had a discrepancy of more than 2 Gleason units in grade in the biopsy and surgical specimens. In those who underwent nonextended needle biopsies the accuracy rate for Gleason scoring was 63% with 12% over and 25% under graded. There were significantly different rates of accuracy (p = 0.008) and under grading (p = 0.01) in the 2 needle biopsy groups. Patients with a needle biopsy Gleason score of less than 7 had significantly higher concordance with the prostatectomy Gleason score when extended biopsies were done compared with nonextended biopsies (p = 0.001).Prostate cancer grading by extended needle biopsy is a better predictor of the final Gleason score than nonextended needle biopsy, as determined by radical prostatectomy histological evaluation. Therefore, extended prostate needle biopsy provides better guidance to determine the appropriate treatment in patients with prostate cancer.

Introduction: Although several pieces of data indicate a critical role of the carcinoma associated stroma (CAS) in the progression of prostate cancer (CaP), little is known about the specific mechanisms by which CAS contributes to the evolution of the castration-recurrent phenotype in locally advanced/metastatic CaP patients. The main challenge in this area has been the ability to obtain primary cultures of human prostate stroma cells (HPSCs) from locally advanced or metastatic CaP, because therapeutic surgery is not a feasible option for these patients. The aim of this study was to standardize a methodology to obtain primary cultures of HPSCs from from needle biopsies of the primary tumor of advanced CaP and to investigate whether HPSCs from different histological/pathological origins have distinct transcriptional programs. Material and Methods: Primary cultures of HPSCs were obtained from explants of needle biopsies from the peripheral zone of primary tumor of advanced/metastatic CaP patients (T3/T4) or from peripheral zone from patients without evidence of neoplasia (BAS). HPSCs were characterized using gene expression profile (Illumina), qPCR, immunocytochemistry and western blot. The phenotypic alterations were analyzed using the stroma cell markers calponin, vimentin, pro-collagen and α-smooth muscle actin. Migration and invasion assays using co-cultures of stroma-epithelium were utilize to evaluate the functional role of CAS. Results: Analysis of primary cultures of HPSCs from benign and locally advanced and/or metastatic CaP tissue explants revealed that CAS are a heterogeneous population of cells, typified by the increment of myofibroblasts/fibroblasts ratio and collagen production. The proliferation rate and doubling time was significantly higher in CAS compared to BAS. Analysis of gene expression profile revealed that CAS exhibited a unique transcriptional program, up-regulating genes involved in cell proliferation migration and cell adhesion. Furthermore, migration and invasion assays using co-cultures of stroma-epithelium demonstrated that HPSCs from CAS, but not BAS, contributed to the invasive potential of CaP cell lines. Discussion: Our studies demonstrated that CAS from the primary tumor of advanced/metastatic CaP patients was intrinsically different from the stroma associated to non-invasive CaP. Accordingly, primary cultures of HPSCs from primary tumors of metastatic patients provide an invaluable tool for modeling the effect of perturbation of the prostate tissue microenvironment during the progression of CaP. Citation Format: Javier Cerda-Infante, Paola F. Conejeros, Romina A. Coronado, Ignacio F. San Francisco, Gary J. Smith, Alejandro S. Godoy, Viviana P. Montecinos. Stromal primary cultures from advanced human prostate cancer obtained from needle biopsies revealed distinctive gene expression pattern and functionality. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 189. doi:10.1158/1538-7445.AM2014-189