Histologic Inflammatory Changes on the Prostatic Gland Due to Immunosuppression for Kidney Transplantation

OBJECTIVE To determine the incidence of type IV prostatitis in patients with kidney transplantation receiving an immunosuppression regimen and to compare it with that of a nonimmunosuppressed control group. METHODS We retrospectively reviewed 216 electronic charts of patients who had undergone surgical treatment for benign prostatic hyperplasia from August 2000 to January 2006. Of the 216 patients, 183 did not receive immunosuppressive therapy and were included in the control group (group 1). The other 33 patients had undergone kidney transplantation and were included in the study group (group 2). The patient data were accessed for age at surgery, International Prostate Symptom Score, prostate volume, preoperative serum prostate-specific antigen level, history of acute urinary retention, and surgical approach (open vs transurethral resection of prostate). Histologic findings from the surgical specimens were also recorded. RESULTS The mean age at surgery, mean serum prostate-specific antigen level, mean prostate volume, and mean International Prostate Symptom Score were not significantly different between both groups. However, histologic evidence of chronic prostatitis was obtained in 145 surgical specimens (78%) from group 1 and in just 3 specimens from group 2 (9%; P < .001). Moreover, nonimmunosuppressed patients had a 38.2 times greater risk of presenting with prostatitis than did the immunosuppressed patients. CONCLUSION Imunnosuppresion therapy in kidney transplantation has a protective factor in the prostatitis incidence. UROLOGY 79: 662-664, 2012. (C) 2012 Elsevier Inc.

Standard surgical treatment for benign prostatic hyperplasia is safe for patients over 75 years: Analysis of 100 cases from a high-volume urologic center

OBJECTIVES: In this study, we aimed to determine the complications of standard surgical treatments among patients over 75 years in a high-volume urologic center. METHODS: We analyzed 100 consecutive patients older than 75 years who had undergone transurethral prostatic resection of the prostate or open prostatectomy for treatment of benign prostatic hyperplasia from January 2008 to March 2010. We analyzed patient age, prostate volume, prostate-specific antigen level, international prostatic symptom score, quality of life score, urinary retention, co-morbidities, surgical technique and satisfaction with treatment. RESULTS: Median age was 79 years. Forty-eight patients had undergone transurethral prostatic resection of the prostate, and 52 had undergone open prostatectomy. The median International Prostatic Symptom Score was 20, the median prostate volume was 83 g, 51% were using an indwelling bladder catheter, and the median prostate-specific antigen level was 5.0 ng/ml. The most common comorbidities were hypertension, diabetes and coronary disease. After a median follow-up period of 17 months, most patients were satisfied. Complications were present in 20% of cases. The most common urological complication was urethral stenosis, followed by bladder neck sclerosis, urinary fistula, late macroscopic hematuria and persistent urinary incontinence. The most common clinical complication was myocardial infarction, followed by acute renal failure requiring dialysis. Incidental carcinoma of the prostate was present in 6% of cases. One case had urothelial bladder cancer. CONCLUSIONS: Standard surgical treatments for benign prostatic hyperplasia are safe and satisfactory among the elderly. Complications are infrequent, and urethral stenosis is the most common. No clinical variable is associated with the occurrence of complications.

Standard surgical treatment for benign prostatic hyperplasia is safe for patients over 75 years: analysis of 100 cases from a high-volume urologic center

OBJECTIVES: In this study, we aimed to determine the complications of standard surgical treatments among patients over 75 years in a high-volume urologic center. METHODS: We analyzed 100 consecutive patients older than 75 years who had undergone transurethral prostatic resection of the prostate or open prostatectomy for treatment of benign prostatic hyperplasia from January 2008 to March 2010. We analyzed patient age, prostate volume, prostate-specific antigen level, international prostatic symptom score, quality of life score, urinary retention, co-morbidities, surgical technique and satisfaction with treatment. RESULTS: Median age was 79 years. Forty-eight patients had undergone transurethral prostatic resection of the prostate, and 52 had undergone open prostatectomy. The median International Prostatic Symptom Score was 20, the median prostate volume was 83 g, 51% were using an indwelling bladder catheter, and the median prostatespecific antigen level was 5.0 ng/ml. The most common comorbidities were hypertension, diabetes and coronary disease. After a median follow-up period of 17 months, most patients were satisfied. Complications were present in 20% of cases. The most common urological complication was urethral stenosis, followed by bladder neck sclerosis, urinary fistula, late macroscopic hematuria and persistent urinary incontinence. The most common clinical complication was myocardial infarction, followed by acute renal failure requiring dialysis. Incidental carcinoma of the prostate was present in 6% of cases. One case had urothelial bladder cancer. CONCLUSIONS: Standard surgical treatments for benign prostatic hyperplasia are safe and satisfactory among the elderly. Complications are infrequent, and urethral stenosis is the most common. No clinical variable is associated with the occurrence of complications.

Prostate biopsy in patients with long-term use of indwelling bladder catheter: What is the rationale?

Objective: Acute urinary retention (AUR) is expected to occur in 2% to 39% men with benign prostatic hyperplasia. To date, no study has elucidated the effect of long-term use of indwelling bladder catheter on serum prostate specific antigen (PSA) levels and on the incidence of prostate cancer (CaP). The aim of the present study is to analyze the incidence of CaP in patients with long-term use of indwelling bladder catheter and determine some practice patterns on this issue. Materials and methods: The study comprised a retrospective analysis of data from 1,651 patients who had undergone transrectal ultrasound (TRUS)-guided prostate biopsy from July 2004 to June 2009. Among these patients, 198 (12%) were using an indwelling bladder catheter during the biopsy for at least 1 month. The incidence of CaP was recorded according to total PSA levels. Other variables such patient age, free/total PSA rate, PSA density, prostate volume, and duration of catheter use was also analyzed. Men with a digital rectal examination suspicious for cancer were not considered for analysis. Results: Median patient age was 71 years (37 to 89 years). Overall, 25% of patients presented a CaP diagnosis. CaP incidence according to the PSA levels was 0%, 18.9%, 24.5%, and 40.6% for patients with PSA <= 4.0, 4.1-10.0, 10.1-20.0, and >20.0 ng/ml, respectively. When prostate volume was analyzed together, we demonstrated that only 1 (2.4%) patient with PSA below 10.0 ng/ml and prostate volume >60 g had CaP. Median total PSA, PSA density, and prostate volume were statistically different between patients with and without CaP. Conclusions: Prostate biopsy should not be indicated for all patients with diagnosis of BPH and AUR who present an elevated PSA level. Patients with PSA below 10.0 ng/ml, and prostate volume >60 g should only undergo biopsy in selected cases. Patients with PSA >20.0 ng/ml and a prostate volume <= 60 g are at higher risk of CaP diagnosis. (C) 2012 Elsevier Inc. All rights reserved.

Surrogate endpoints for prostate cancer-specific mortality after radiotherapy and androgen suppression therapy in men with localised or locally advanced prostate cancer: an analysis of two randomised trials

Background Androgen suppression therapy and radiotherapy are used to treat locally advanced prostate cancer. 3 years of androgen suppression confers a small survival benefit compared with 6 months of therapy in this setting, but is associated with more toxic effects. Early identification of men in whom radiotherapy and 6 months of androgen suppression is insufficient for cure is important. Thus, we assessed whether prostate-specific antigen (PSA) values can act as an early surrogate for prostate cancer-specific mortality (PCSM). Methods We systematically reviewed randomised controlled trials that showed improved overall and prostate cancer-specific survival with radiotherapy and 6 months of androgen suppression compared with radio therapy alone and measured lowest PSA concentrations (PSA nadir) and those immediately after treatment (PSA end). We assessed a cohort of 734 men with localised or locally advanced prostate cancer from two eligible trials in the USA and Australasia that randomly allocated participants between Feb 2, 1996, and Dec 27, 2001. We used Prentice criteria to assess whether reported PSA nadir or PSA end concentrations of more than 0.5 ng/mL were surrogates for PCSM. Findings Men treated with radiotherapy and 6 months of androgen suppression in both trials were significantly less likely to have PSA end and PSA nadir values of more than 0.5 ng/mL than were those treated with radiotherapy alone (p<0.0001). Presence of candidate surrogates (ie, PSA end and PSA nadir values >0.5 ng/mL) alone and when assessed in conjunction with the randomised treatment group increased risk of PCSM in the US trial (PSA nadir p=0.0016; PSA end p=0.017) and Australasian trial (PSA nadir p<0.0001; PSA end p=0.0012). In both trials, the randomised treatment group was no longer associated with PCSM (p >= 0.20) when the candidate surrogates were included in the model. Therefore, both PSA metrics satisfied Prentice criteria for surrogacy. Interpretation After radiotherapy and 6 months of androgen suppression, men with PSA end values exceeding 0.5 ng/mL should be considered for long-term androgen suppression and those with localised or locally advanced prostate cancer with PSA nadir values exceeding 0.5 ng/mL should be considered for inclusion in randomised trials investigating the use of drugs that have extended survival in castration-resistant metastatic prostate cancer.

GREB1 tissue expression is associated with organ-confined prostate cancer

Objective: By reason of its heterogeneous behavior, it is difficult to determine the prognosis of many prostate cancer cases. Patients with the same clinicopathologic conditions may present varying clinical findings and rates of progression. We determined the role of new genes as potential molecular markers for prostate cancer prognosis. Materials and methods: We performed a microarray analysis of two pools of patients with prostate cancer divided according to their clinicopathologic characteristics. After that, we validated these results by testing the genes with most different expressions between the two pools using the quantitative real time polymerase chain reaction method. We analyzed gene expression in 33 patients with localized prostate cancer according to prostate specific antigen (PSA), pathologic stage, Gleason score, and biochemical recurrence. For statistical analysis we used the Mann-Whitney Test. Results: The microarray analysis revealed that 4,147 genes presented a different expression between the two pools. Among them, 3 genes, TMEFF2, GREB1, and THIL,, were at least 13-times overexpressed, and 1 gene, IGH3, which was at least 5times under-expressed in pool 1 (good prognosis) compared with pool 2 (bad prognosis), were selected for analysis. After the validation tests, GREB1 was significantly more overexpressed among patients with stage T2 compared with T3 (P = 0.020). The expressions of other 3 genes did not present significant differences according to the clinicopatholoOcal variables. Conclusions: Tissue expression of GREB1 is associated with organ-confined prostate cancer and may constitute a gene associated with a favorable prognosis. (C) 2012 Elsevier Inc. All rights reserved.

Expression of nonclassical molecule human leukocyte antigen-G in oral lesions

Introduction: Human leukocyte antigen (HLA)-G is a nonclassic class I molecule that acts as a modulator of immune responses, and the expression of these molecules in virus-infected cells has been associated with subversion of the immune response. Objective: In this study, we performed a cross-sectional study, systematically comparing the expression of the HLA-G in benign, premalignant, and malignant oral lesions and correlating it with the presence of high-risk and low-risk human papillomavirus (HPV) types. Specimens and Methods: Oral biopsies were collected from 51 patients and analyzed by immunohistochemistry using anti HLA-G antibody. Human papillomavirus detection and typing from oral biopsies were obtained by polymerase chain reaction using GP5+/GP6+ and specific primers. Results: The 51 biopsies were stratified into 3 groups according to lesion grade: oral benign lesions (oral hyperplasia and papilloma, n = 16), oral premalignant lesions (oral leukoplakia with dysplasia and lichen planus, n = 17), and malignant lesions (oral squamous cell carcinoma, n = 18). Human leukocyte antigen G overexpression was mainly observed in benign and premalignant oral lesions but was not related to HPV infection (P>.05). On the other hand, HPV DNA was detected in 24 (47%) oral lesions, mainly in benign and premalignant lesions, with the most frequent type detected being high-risk HPV type. Conclusion: The HLA-G molecule was expressed in a significant number of benign oral lesions and was not correlated with HPV infection or oral cancer. Crown Copyright (C) 2012 Published by Elsevier Inc. All rights reserved.

Lymphocyte transformation assay for C neoformans antigen is not reliable for detecting cellular impairment in patients with Neurocryptococcosis

Background: Cryptococcus neoformans causes meningitis and disseminated infection in healthy individuals, but more commonly in hosts with defective immune responses. Cell-mediated immunity is an important component of the immune response to a great variety of infections, including yeast infections. We aimed to evaluate a specific lymphocyte transformation assay to Cryptococcus neoformans in order to identify immunodeficiency associated to neurocryptococcosis (NCC) as primary cause of the mycosis. Methods: Healthy volunteers, poultry growers, and HIV-seronegative patients with neurocryptococcosis were tested for cellular immune response. Cryptococcal meningitis was diagnosed by India ink staining of cerebrospinal fluid and cryptococcal antigen test (Immunomycol-Inc, SP, Brazil). Isolated peripheral blood mononuclear cells were stimulated with C. neoformans antigen, C. albicans antigen, and pokeweed mitogen. The amount of H-3-thymidine incorporated was assessed, and the results were expressed as stimulation index (SI) and log SI, sensitivity, specificity, and cut-off value (receiver operating characteristics curve). We applied unpaired Student t tests to compare data and considered significant differences for p<0.05. Results: The lymphotoxin alpha showed a low capacity with all the stimuli for classifying patients as responders and non-responders. Lymphotoxin alpha stimulated by heated-killed antigen from patients with neurocryptococcosis was not affected by TCD4+ cell count, and the intensity of response did not correlate with the clinical evolution of neurocryptococcosis. Conclusion: Response to lymphocyte transformation assay should be analyzed based on a normal range and using more than one stimulator. The use of a cut-off value to classify patients with neurocryptococcosis is inadequate. Statistical analysis should be based on the log transformation of SI. A more purified antigen for evaluating specific response to C. neoformans is needed.

The impact of pretransplant donor-specific antibodies on graft outcome in renal transplantation: a six-year follow-up study

OBJECTIVE: The significance of pretransplant, donor-specific antibodies on long-term patient outcomes is a subject of debate. This study evaluated the impact and the presence or absence of donor-specific antibodies after kidney transplantation on short-and long-term graft outcomes. METHODS: We analyzed the frequency and dynamics of pretransplant donor-specific antibodies following renal transplantation from a randomized trial that was conducted from 2002 to 2004 and correlated these findings with patient outcomes through 2009. Transplants were performed against a complement-dependent T-and B-negative crossmatch. Pre- and posttransplant sera were available from 94 of the 118 patients (80%). Antibodies were detected using a solid-phase (Luminex (R)), single-bead assay, and all tests were performed simultaneously. RESULTS: Sixteen patients exhibited pretransplant donor-specific antibodies, but only 3 of these patients (19%) developed antibody-mediated rejection and 2 of them experienced early graft losses. Excluding these 2 losses, 6 of 14 patients exhibited donor-specific antibodies at the final follow-up exam, whereas 8 of these patients (57%) exhibited complete clearance of the donor-specific antibodies. Five other patients developed "de novo'' posttransplant donor-specific antibodies. Death-censored graft survival was similar in patients with pretransplant donor-specific and non-donor-specific antibodies after a mean follow-up period of 70 months. CONCLUSION: Pretransplant donor-specific antibodies with a negative complement-dependent cytotoxicity crossmatch are associated with a risk for the development of antibody-mediated rejection, although survival rates are similar when patients transpose the first months after receiving the graft. Our data also suggest that early posttransplant donor-specific antibody monitoring should increase knowledge of antibody dynamics and their impact on long-term graft outcome.

Involvement of TSSA (trypomastigote small surface antigen) in Trypanosoma cruzi invasion of mammalian cells

TSSA (trypomastigote small surface antigen) is a polymorphic mucin-like molecule displayed on the surface of Trypanosoma cruzi trypomastigote forms. To evaluate its functional properties, we undertook comparative biochemical and genetic approaches on isoforms present in parasite stocks from extant evolutionary lineages (CL Brener and Sylvio X-10). We show that CL Brener TSSA, but not the Sylvio X-10 counterpart, exhibits dose-dependent and saturable binding towards non-macrophagic cell lines. This binding triggers Ca2+-based signalling responses in the target cell while providing an anchor for the invading parasite. Accordingly, exogenous addition of either TSSA-derived peptides or specific antibodies significantly inhibits invasion of CL Brener, but not Sylvio X-10, trypomastigotes. Non-infective epimastigote forms, which do not express detectable levels of TSSA, were stably transfected with TSSA cDNA from either parasite stock. Although both transfectants produced a surface-associated mucin-like TSSA product, epimastigotes expressing CL Brener TSSA showed a similar to 2-fold increase in their attachment to mammalian cells. Overall, these findings indicate that CL Brener TSSA functions as a parasite adhesin, engaging surface receptor(s) and inducing signalling pathways on the host cell as a prerequisite for parasite internalization. More importantly, the contrasting functional features of TSSA isoforms provide one appealing mechanism underlying the differential infectivity of T. cruzi stocks.

Human Endogenous Retrovirus K(HML-2) Gag and Env specific T-cell responses are not detected in HTLV-I-infected subjects using standard peptide screening methods

Abstract Background An estimated 10–20 million individuals are infected with the retrovirus human T-cell leukemia virus type 1 (HTLV-1). While the majority of these individuals remain asymptomatic, 0.3-4% develop a neurodegenerative inflammatory disease, termed HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP results in the progressive demyelination of the central nervous system and is a differential diagnosis of multiple sclerosis (MS). The etiology of HAM/TSP is unclear, but evidence points to a role for CNS-inflitrating T-cells in pathogenesis. Recently, the HTLV-1-Tax protein has been shown to induce transcription of the human endogenous retrovirus (HERV) families W, H and K. Intriguingly, numerous studies have implicated these same HERV families in MS, though this association remains controversial. Results Here, we explore the hypothesis that HTLV-1-infection results in the induction of HERV antigen expression and the elicitation of HERV-specific T-cells responses which, in turn, may be reactive against neurons and other tissues. PBMC from 15 HTLV-1-infected subjects, 5 of whom presented with HAM/TSP, were comprehensively screened for T-cell responses to overlapping peptides spanning HERV-K(HML-2) Gag and Env. In addition, we screened for responses to peptides derived from diverse HERV families, selected based on predicted binding to predicted optimal epitopes. We observed a lack of responses to each of these peptide sets. Conclusions Thus, although the limited scope of our screening prevents us from conclusively disproving our hypothesis, the current study does not provide data supporting a role for HERV-specific T-cell responses in HTLV-1 associated immunopathology.

In vivo assessment of specific cytotoxic T lymphocyte killing

The direct killing of target cells by cytotoxic T lymphocytes (CTLs) plays a fundamental role in protective immunity to viral, bacterial, protozoan and fungi infections, as well as to tumor cells. In vivo cytotoxic assays take into account the interaction of target and effector cells in the context of the proper microenvironment making the analysis biologically more relevant than in vitro cytotoxic assays. Thus, the development, improvement and validation of in vivo methods are necessary in view of the importance of the results they may provide. We describe and discuss in this manuscript a method to evaluate in vivo specific cytotoxic T lymphocyte killing. We used as model system mice immunized with human recombinant replication-deficient adenovirus 5 (HAd5) containing different transgenes as the trigger of a CTL-mediated immune response. To these mice, we adoptively transferred syngeneic cells labeled with different vital fluorescent dyes. Donor cells were pulsed (target) or not (control non-target) with distinct CD8 T-cell epitopes, mixed in a 1:1 ratio and injected i.v. into immunized or non-immunized recipient mice. After 18-24h, spleen cells are collected and analysed by flow cytometry. A deviation from the 1:1 ratio of control and target cell populations indicates antigen specific lysis of target cells