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Purpose: To assess whether and to what extent irrigation fluid absorption occurs during laser vaporization (LV) of the prostate using the 180 W XPS™ GreenLight laser. Methods: This prospective investigation was performed in a tertiary care center with a consecutive series of patients undergoing 180 W LV of the prostate. Intraoperative irrigation was performed with isotonic saline containing 1 % ethanol. The volume of irrigation fluid absorption was calculated from periodically performed breath ethanol measurements during LV. Additionally, intraoperative changes in biochemical and hematological blood parameters were assessed. Results: Positive breath ethanol tests were detectable in 22 of 54 patients. The median absorption volume in these patients was 950 ml (range 208-4579 ml). Ten patients absorbed more than 2000 ml. Absorbers had smaller prostates, more capsular perforations and injuries to venous sinuses, and more total energy was applied with higher output power. Five patients had transient symptoms potentially related to fluid absorption. A significant drop in hemoglobin, hematocrit, venous pH and bicarbonate and an increase in chloride were detectable in the absorber group. These changes were significantly different in the non-absorber group. Conclusions: Absorption of irrigation fluid did occur in a relevant proportion of patients undergoing XPS™ GreenLight LV. High-volume absorption (≥2000 ml), which might be clinically relevant, was detectable in almost 20 % of all procedures. Absorption of saline irrigation fluid does not result in a classical TUR syndrome, but fluid and chloride overload can lead to serious complications, particularly in cardiovascular high-risk patients. Thus, patients with symptoms potentially related to fluid absorption should be monitored carefully. [ABSTRACT FROM AUTHOR]

The prostate gland is exquisitely sensitive to androgen receptor (AR) signaling. AR signaling is obligatory for prostate development and changes in AR levels, its ligands or shifts in AR mode of action are reflected in the physiology of the prostate. The AR is intimately linked to prostate cancer biology through the regulation of epithelial proliferation, suppression of apoptosis and the development of castration-resistant disease. Thus, AR is the primary therapeutic target in various prostate diseases such as BPH and cancer. Although some tumors lose AR expression, most retain the AR and have elevated levels and/or shifts in activity that are required for tumor progression and metastasis. New AR inhibitors currently in clinical trials with higher receptor affinity and specificity may improve prostate cancer patient outcome. Several events play an important role in initiation, primary tumor development and metastatic spread. Androgen receptor activity and promoter specificity change due to altered coregulator expression. Changes in epigenetic surveillance alter the AR cistrome. Both systemic and local inflammation increases with PCa progression affecting AR levels, activity, and requirement for ligand. Our current understanding of AR biology suggest that global androgen suppression may drive the development of castration-resistant disease and therefore the question remains: Does effective inhibition of AR activity mark the end of the road for PCa or only a sharp turn toward a different type of malignancy? [ABSTRACT FROM AUTHOR]

Objective: To report our unique approach for individualizing robotic prostate cancer surgery by risk stratification and sub classification of the periprostatic space into 4 distinct compartments, and thus performing 4 precise different grades of nerve sparing based on neurosurgical principles and to present updated potency and continence outcomes data of patients undergoing robotic-assisted laparoscopic prostatectomy (RALP) using our risk-stratified approach based on layers of periprostatic fascial dissection., Patients and Methods: (1) Between January 2005 and December 2010, 2,536 men underwent RALP by a single surgeon at our institution. (2) Included patients were those with ≥ 1-year follow-up and were preoperatively continent and potent, defined as having a SHIM questionnaire score of >21; thus, the final number of patient in the study cohort was 1,335. (3) Postoperative potency was defined as the ability to have successful intercourse (score of ≥ 4 on question 2 of the SHIM); continence was defined as the use of no pads per 24 h., Results: (1) The potency and continence for NS grades 1, 2, 3, and 4 were found to be 90.6, 76.2, 60.5, and 57.1 % (P < 0.001) and 98, 93.2, 90.1, and 88.9 % (P < 0.001), respectively. (2) The overall PSM rates for patients with NS grades 1, 2, 3, and 4 were 10.5, 7, 5.8, and 4.8 %, respectively (P = 0.064)., Conclusions: The study found a correlation between risk-stratified grades of NS technique and continence and potency. Patients with lesser grades of NS had higher rates of potency and continence.

Introduction: Despite the enthusiasm for an organ preserving approach to prostate cancer treatment, studies that support the supposition that this approach will offer patients the "Trifecta" of prostate cancer therapy are lacking., Methods: Review of published peer review literature using a combination of the terms "Focal", "Prostate Cancer", "Therapy", "Cryoablation", "HIFU", and "Clinical Trial"., Results: To date only three prospective clinical trials of subtotal prostate cryoablation and one of subtotal high-intensity focused ultrasound (HIFU) have been reported along with one retrospective review of patients treated in a subtotal manner with cryotherapy. In total, these reports present only 166 patients. All current strategies for focally ablative therapy for prostate cancer treatment have varied in their eligibility criteria and in the amount of tissue targeted for destruction and/or preservation., Conclusions: Very little is published on either the oncologic outcomes or quality-of-life outcomes following subtotal prostate ablation to justify its growing popularity with both patients and physicians. Significant research and clinical trials that examine patient selection, biopsy strategies, and ablative energies, along with oncologic efficacy and quality-of-life outcomes are needed. This article will review the current state of knowledge regarding subtotal prostate ablative strategies.

Treatment with alpha-adrenoceptor antagonists that reduce the tone of prostatic stromal and urethral smooth muscle has beneficial effects in patients with benign prostatic hyperplasia (BPH) and lower urinary tracts symptoms (LUTS) and has brought attention to regulatory mechanisms of smooth muscle contractility of the outflow region. The prostate, urethra and bladder neck are densely supplied by nitric oxide (NO)-synthase-containing nerves that cause relaxation upon activation. In various experimental models, altered function or activity of the NO/cGMP pathway of the bladder neck and urethra may be related to inappropriate or un-coordinated functions of the bladder outlet and detrusor, but causal connections between alterations in this signaling system, a dysfunctional bladder outlet, and the development of LUTS are not established for humans. The present review focuses on regulatory functions of smooth muscle contractility by the NO/cGMP-pathway in the bladder neck, urethra, and prostate. Disease-related alterations in the NO/cGMP-pathway, and putative options for pharmacological modification of this signaling pathway in the out-flow region are briefly discussed.

Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF alpha) are two closely related peptides that interact with cell-surface epidermal growth factor receptors (EGFR) to induce receptor tyrosine phosphorylation and activation of intracellular signal-transduction pathways. EGF appears to be the predominant EGF-related growth factor in the normal prostate and in benign prostatic hyperplasia (BPH). Evidence indicates that EGF and TGF alpha are important for maintainence of the structural and functional integrity of the benign prostatic epithelium. The EGF-related peptides are primarily localized to the secretory epithelium of the benign prostate, and their production and secretion is augmented by the presence of circulating androgens. EGFR are located in the basal/neuroendocrine (NE) compartment of the benign prostate and exhibit relatively androgen-independent expression. The EGF-related peptides and EGFR are also present in neoplastic prostatic tissues. There is currently no direct evidence to implicate EGFR activation in the pathogenesis of BPH. However, the EGF-related peptides appear to play a functional role in the growth of prostatic carcinoma cells, with TGF alpha being the predominant growth factor. Numerous investigators have demonstrated the functional significance of a TGF alpha/EGFR-mediated autocrine growth pathway in cultured prostatic carcinoma cells. Studies of cultured prostate cancer cells, but not normal epithelial cells, demonstrate constitutive activation of EGFR. Androgen-independent cancer cells exhibit more EGFR expression and phosphorylation than do androgen-responsive prostate cancer cells. Most studies indicate that EGFR do not play a functional role in androgen-stimulated growth of prostate cancer cells. Several studies have correlated EGFR expression with increased nuclear size and tumor dedifferentiation. Future studies should focus on determining both the prognostic significance of EGFR expression and whether manipulation of EGFR-mediated growth can be exploited for therapeutic benefit in human prostate cancer.

The insulin-like growth factor (IGF) system is involved in the regulation of cell growth. The system involves a network of molecules that includes the IGFs themselves (IGF-I and -II), IGF receptors (types I and II), IGF-binding proteins (IGFBP-1 through -6), and IGFBP proteases. Characterization of this complex system in the prostate has recently been initiated. Prostatic cell lines as well as primary cultures of prostatic epithelial and stromal cells have been analyzed for expression of IGFs, receptors, and IGFBPs. Prostatic epithelial cells and, quite likely, stromal cells as well respond to the mitogenic activity of IGFs via the type I IGF receptor. Prostatic stromal cells synthesize and secrete IGF-II; there is evidence that prostatic cell lines also synthesize IGFs, but this has not been confirmed in primary cultures of prostatic epithelial cells. Prostatic stromal and epithelial cells secrete a number of IGFBPs. The biological impact of some of these IGFBPs on the growth of prostatic cells has been examined, and proteolytic cleavage of IGFBP-3 by prostate-specific antigen (PSA) has been demonstrated. Aberrations in several elements of the IGF system have been observed in stromal cells derived from benign prostatic hyperplasia (BPH). The IGF system may therefore have a part in the etiology of BPH as well as in normal and malignant processes in the prostate.

Studies on the developing prostate and SV suggest that androgens act via mesenchymal AR to elicit synthesis and secretion of various autocrine and paracrine factors that regulate epithelial and stromal growth and differentiation. Clearly, the global regulation of epithelial growth and ductal branching morphogenesis is a complex multifactorial process involving the interplay of many diffusible factors (both positive and negative regulators), extracellular matrix molecules, cell-surface receptors for growth factors, receptors for extracellular matrix molecules, and matrix-degrading enzymes. Future progress will certainly be dependent upon the utilization of appropriate, biologically relevant models to examine the respective roles of various growth factors in the growth and development of androgen target organs.

This review focuses on the possible role of transforming growth factor-beta isoforms 1-3 (TGFbeta) in prostate cancer. TGFbeta1 appears to inhibit the cellular proliferation of normal prostate cells. Surprisingly, TGFbeta1 is overexpressed in prostate cancer. To help explain this apparent paradox, it has been revealed that with tumor progression, prostate cancer cells acquire reduced sensitivity to the growth-inhibitory effects of TGFbeta1. Aberrations of the TGFbeta1 signaling pathway at the prereceptor, receptor, or postreceptor level may lead to prostate cancer cell resistance to TGFbeta1 growth inhibition. Indirectly, elevated levels of TGFbeta1 may induce host effects that may be beneficial to prostate tumor growth by suppressing the immune system, promoting angiogenesis and extracellular matrix formation, and enhancing metastatic potential. Consequently, TGFbeta1 appears to be important in prostate carcinogenesis and tumorigenicity. TGFbeta2 and TGFbeta3 are only briefly presented as very little is known about their role in prostate cancer.

Members of the fibroblast growth factor (FGF) family are important growth-regulatory elements. Of the FGFs, keratinocyte growth factor (KGF) appears to have unique properties that implicate it as a paracrine factor in the prostate. Two KGF transcripts (approximately to 2.4 and 5.0 kb) encode a protein of approximately 22 kDa. In contrast to several other members of the FGF family, KGF has a signal peptide and is actively secreted. Cellular response to KGF is mediated by a specific receptor that is transcribed from an alternately spliced variant of the FGF type 2 receptor (FGFR-2). KGF transcripts have been detected in prostatic tissues and in stromal cells cultured from rat and human prostates as well as in a variety of stromal cells derived from other organs. Prostatic epithelial cells and numerous other types of epithelial cells are targets of KGF's mitogenic activity. Several factors involved in wound healing regulate the expression of KGF, but androgen regulation of KGF is of greatest relevance to the role of KGF in the prostate. Current efforts to localize and manipulate KGF activity in vivo should reveal the significance of KGF expression and function in the prostate and in other organs.

To identify the effect of orgasm on serum prostate-specific antigen (PSA) levels, a prospective trial before and after orgasm was performed in 14 healthy colleagues aged 32-62 years (mean, 44.4 years) with no evidence of prostatic disease. PSA determinations were performed on serum samples obtained before and after orgasm. Significant changes in PSA levels after orgasm were found (P = 0.002, analysis of variance). We conclude that the impact of orgasm on PSA levels should be taken into account when the latter are used for the detection of prostatic disease.