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Benign Prostatic Hyperplasia
Benign Prostatic Hyperplasia (BPH) also known as
nodular hyperplasia, benign prostatic hypertrophy or benign enlargement of the
prostate (BEP) refers to the increase in size of the prostate in middle-aged and elderly men. To be accurate, the process is one of hyperplasia
rather than hypertrophy, but the nomenclature is often interchangeable, even amongst urologists. It is characterized by hyperplasia of prostatic
stromal and epithelial cells, resulting in the formation of large, fairly discrete nodules in the periurethral region of the prostate. When
sufficiently large, the nodules compress the urethral canal to cause partial, or sometimes virtually complete, obstruction of the urethra which
interferes the normal flow of urine. It leads to symptoms of urinary hesitancy, frequent urination, increased risk of urinary tract infections and
urinary retention. Although prostate specific antigen levels may be elevated in these patients because of increased organ volume and inflammation
due to urinary tract infections, BPH is not considered to be a premalignant lesion.
Adenomatous prostatic growth is believed to begin at approximately age 30 years. An estimated 50% of men have histologic evidence of BPH by age 50
years and 75% by age 80 years. In 40-50% of these patients, BPH becomes clinically significant.
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Symptoms
Benign prostatic hyperplasia symptoms are classified as obstructive or irritative. Obstructive symptoms include hesitancy, intermittency, incomplete
voiding, weak urinary stream, and straining.
Irritative symptoms include frequency of urination, which is called nocturia when occurring at night time, and urgency (compelling need to void that
can not be deferred). These obstructive and irritative symptoms are evaluated using the International Prostate Symptom Score (IPSS) questionnaire,
designed to assess the severity of BPH.
BPH can be a progressive disease, especially if left untreated. Incomplete voiding results in stasis of bacteria in the bladder residue and an
increased risk of urinary tract infections. Urinary bladder stones, are formed from the crystallisation of salts in the residual urine. Urinary
retention, termed acute or chronic, is another form of progression. Acute urinary retention is the inability to void, while in chronic urinary
retention the residual urinary volume gradually increases, and the bladder distends. Some patients who suffer from chronic urinary retention may
eventually progress to renal failure, a condition termed obstructive uropathy.
Etiology
Androgens (testosterone and related hormones) are considered to play a permissive role in BPH by most experts. This means that androgens have to
be present for BPH to occur, but do not necessarily directly cause the condition. This is supported by the fact that castrated boys do not develop
BPH when they age, unlike intact men. Additionally, administering exogenous testosterone is not associated with a significant increase in the risk
of BPH symptoms. Dihydrotestosterone (DHT), a metabolite of testosterone is a critical mediator of prostatic growth. DHT is synthesized in the
prostate from circulating testosterone by the action of the enzyme 5α-reductase, type 2. This enzyme is localized principally in the stromal cells;
hence, these cells are the main site for the synthesis of DHT.
DHT can act in an autocrine fashion on the stromalie cells or in paracrine fashion by diffusing into nearby epithelial cells. In both of these cell
types, DHT binds to nuclear androgen receptors and signals the transcription of growth factors that are mitogenic to the epithelial and stromal
cells. DHT is 10 times more potent than testosterone because it dissociates from the androgen receptor more slowly. The importance of DHT in causing
nodular hyperplasia is supported by clinical observations in which an inhibitor of 5α-reductase is given to men with this condition. Therapy with
5α-reductase inhibitor markedly reduces the DHT content of the prostate and in turn reduces prostate volume and, in many cases, BPH symptoms.
There is growing evidence that estrogens play a role in the etiology of BPH. This is based on the fact that BPH occurs when men generally have elevated
estrogen levels and relatively reduced free testosterone levels, and when prostate tissue becomes more sensitive to estrogens and less responsive to
DHT. Cells taken from the prostates of men who have BPH have been shown to grow in response to high estradiol levels with low androgens present.
Estrogens may render cells more susceptible to the action of DHT.
On a microscopic level, BPH can be seen in the vast majority of men as they age, particularly over the age of 70 years, around the world. However,
rates of clinically significant, symptomatic BPH vary dramatically depending on lifestyle. Men who lead a western lifestyle have a much higher
incidence of symptomatic BPH than men who lead a traditional or rural lifestyle. This is confirmed by research in China showing that men in rural
areas have very low rates of clinical BPH, while men living in cities adopting a western lifestyle have a skyrocketing incidence of this condition,
though it is still below rates seen in the West.
Much work remains to be done to completely clarify the causes of BPH.
Diagnosis
Rectal examination (palpation of the prostate through the rectum) may reveal a markedly enlarged prostate, usually affecting the middle lobe.
Often, blood tests are performed to rule out prostatic malignancy: elevated prostate specific antigen (PSA) levels needs further investigations such
as reinterpretation of PSA results, in terms of PSA density and PSA free percentage, rectal examination and transrectal ultrasonography. These
combined measures can provide early cancer detection.
Ultrasound examination of the testicles, prostate and kidneys is often performed, again to rule out malignancy and hydronephrosis.
Epidemiology
The prostate gets larger in most men as they get older, and overall, 45% of men over the age of 46 can expect to suffer from the symptoms of BPH
if they survive 30 years. Incidence rates increase from 3 cases per 1000 man-years at age 45-49 years, to 38 cases per 1000 man-years by the age
of 75-79 years. Whereas prevalence rates are 2.7% for men aged 45-49, increasing to 24% by the age of 80 years.
For some men, the symptoms may be severe enough to require treatment.
Treatment
Lifestyle
Patients should decrease fluid intake before bedtime, moderate the consumption of alcohol and caffeine-containing products, and follow timed voiding
schedules.
Medications
Alpha blockers (α1-adrenergic receptor antagonists) provide symptomatic relief of BPH symptoms. Available drugs include doxazosin, terazosin,
alfuzosin and tamsulosin. Older drugs, phenoxybenzamine and prazosin are not recommended for treatment of BPH. Alpha-blockers relax smooth
muscle in the prostate and the bladder neck, and decrease the degree of blockage of urine flow. Alpha-blockers may cause ejaculation back into
the bladder (retrograde ejaculation).
The 5α-reductase inhibitors (finasteride and dutasteride) are another treatment option. This medication inhibits 5a-reductase, which in turn inhibits
production of DHT, a hormone responsible for enlarging the prostate. When used together with alpha blockers a reduction of BPH progression to acute
urinary retention and surgery has been noted in patients with larger prostates.
Though former research indicated the efficacy of Serenoa repens (saw palmetto) fruit extracts in alleviating mild-to-moderate BPH symptoms, a recent
double-blind study did not demonstrate any efficacy greater than that of a placebo for moderate-to-severe symptoms. Herbal medicines that have
research support in systematic reviews include beta-sitosterol from Hypoxis rooperi (African star grass) and pygeum (extracted from the bark of Prunus
africana), while there is less substantial support for the efficacy of Cucurbita pepo (pumpkin) seed and Urtica dioica (stinging nettle) root. At
least one double-blind trial has also supported the efficacy of rye flower pollen.
Sildenafil shows some symptomatic relief, suggesting a possible common etiology with erectile dysfunction.
Surgery
If medical treatment fails, transurethral resection of prostate (TURP) surgery may need to be performed. This involves removing (part of) the prostate
through the urethra. There are also a number of new methods for reducing the size of an enlarged prostate, some of which have not been around long
enough to fully establish their safety or side effects. These include various methods to destroy or remove part of the excess tissue while trying to
avoid damaging what's left. Transurethral electrovaporization of the prostate (TVP), laser TURP, visual laser ablation (VLAP), TransUrethral Microwave
ThermoTherapy (TUMT), TransUrethral Needle Ablation (TUNA), ethanol injection, and others are studied as alternatives.
Newer techniques involving lasers in urology have emerged in the last 5-10 years. Starting with the VLAP technique involving the Nd:YAG laser with
contact on the prostatic tissue. A similar technology called Photoselective Vaporization of the Prostate (PVP) with the GreenLight (KTP) laser have
emerged very recently. This procedure involves a high powered 80 Watt KTP laser with a 550 micrometre laser fiber inserted into the prostate. This
fiber has an internal reflection with a 70 degree deflecting angle. It is used to vaporize the tissue to the prostatic capsule. KTP lasers target
haemoglobin as the chromophore and typically have a penetration depth of 2.0mm (four times deeper than holmium).
Another procedure termed Holmium Laser Ablation of the Prostate (HoLAP) has also been gaining acceptance around the world. Like KTP the delivery
device for HoLAP procedures is a 550um disposable side-firing fiber that directs the beam from a high powered 100 Watt laser at a 70degree from the
fiber axis. The holmium wavelength is 2,140nm, which falls within the infrared portion of the spectrum and is invisible to the naked eye. Where KTP
relies on haemoglobin as a chromophore, water within the target tissue is the chromophore for Holmium lasers. The penetration depth of Holmium lasers
is <0.5mm avoiding complications associated with tissue necrosis often found with the deeper penetration and lower peak powers of KTP.
Both wavelengths, KTP and Holmium, ablate approximately one to two grams of tissue per minute.
(adapted from Wikipedia, the free encyclopedia http://en.wikipedia.org/wiki/Enlarged_prostate)
BPH Progression: Concept and Key Learning from MTOPS, ALTESS, COMBAT, and ALF-ONE
Authors: Roehrborn CG.
UT Southwestern Medical Center at Dallas, Dallas, TX 75390-9110, USA. claus.roehrborn@utsouthwestern.edu
Benign prostatic hyperplasia (BPH) represents a significant burden in ageing men due to frequently associated lower urinary tract symptoms (LUTS), which may impair quality of life. BPH is also a progressive disease, mainly characterized by a deterioration of LUTS over time, and in some patients by the occurrence of serious outcomes such as acute urinary retention (AUR) and need for BPH-related surgery. The goals of therapy for BPH are not only to improve bothersome LUTS but also to identify those patients at risk of unfavourable outcomes, to optimize their management. In selected patients, combination of an alpha(1)-blocker and a 5alpha-reductase inhibitor is the most effective form of BPH medical therapy to reduce the risk of clinical progression and relieve LUTS. Monotherapy also significantly reduces the risk of BPH clinical progression, mainly through a reduction of LUTS deterioration for alpha(1)-blockers while 5alpha-reductase inhibitors also reduce the risk of AUR and need for BPH-related surgery. Enlarged prostate and high serum prostate-specific antigen levels have been consistently found to be good clinical predictors of AUR and BPH-related surgery in longitudinal population-based studies and placebo arms of controlled studies. High post-void residual urine (PVR) is also associated with an increased risk of LUTS deterioration and should thus be reconsidered in practice as a predictor of BPH progression. Conversely, baseline LUTS severity and low peak flow rate, initially identified as predictors of unfavourable outcomes in community setting, behave paradoxically in controlled trials, probably as a consequence of strict inclusion criteria and subsequent regression to the mean and glass ceiling effects. Lastly, there is increasing evidence that dynamic variables, such as LUTS and PVR worsening, and lack of symptomatic improvement with alpha(1)-blockers are important predictors of future LUTS/BPH-related events, allowing better identification and management of patients at risk of BPH progression.
Journal: BJU Int. 2008 Mar;101 Suppl 3:17-21.
Adapted from PubMed; click here to access full journal article.
Medical Management of Benign Prostatic Hypertrophy
Authors: Nix JW, Carson CC.
Division of Urology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599-7235, USA.
Benign prostatic hyperplasia (BPH) is a common condition of the aging male. The bladder outlet obstruction caused by this condition occurs despite variations in prostate size. Symptoms of BPH include the irritative and obstructive voiding symptoms termed lower urinary tract symptoms (LUTS). While transurethral surgery has long been the gold standard for treatment of LUTS, medical treatment has emerged as the first line of treatment for those men who fail expectant or watchful waiting treatment. Medical options include: alpha blockers, 5alpha-reductase inhibitors and newly identified PDE 5 inhibitors, drugs for erectile dysfunction that have a relieving effect on the symptoms of LUTS. Newer prostate selective alpha blockers have replaced older nonselective agents as first choice in treatment of most men, especially those with smaller prostates and in whom preservation of sexual function is important. While tamsulosin has the effect of an ejaculation, alfuzosin preserves ejaculatory function. 5alpha-reductase inhibitors may decrease ejaculate volume, libido and sexual function. While this effect is frequently a self limited, it can be a compliance issue for many men. PDE 5 inhibitors, while effective in relieving LUTS symptoms, have not shown effectiveness in reducing post void residual volumes or increasing urinary flow rates.
Journal: Can J Urol. 2007 Dec;14 Suppl 1:53-7.
Adapted from PubMed; click here to access full journal article.
Cost-Effectiveness of Prostate Cancer Chemoprevention: A Quality of Life-Years Analysis
Authors: Svatek RS, Lee JJ, Roehrborn CG, Lippman SM, Lotan Y.
Department of Urology, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9110, USA.
BACKGROUND: The Prostate Cancer Prevention Trial (PCPT) demonstrated that finasteride reduces the prevalence of prostate cancer by 24.8% (risk reduction) but questions remain regarding the cost-effectiveness of widespread utilization. The purpose of the current analysis was to evaluate the cost-effectiveness of chemoprevention utilizing a quality-of-life adjustment. METHODS: A Markov decision analysis model with probabilistic sensitivity analysis was designed to determine the lifetime prostate health-related costs, beginning at age 50 years, for men treated with finasteride compared with placebo. Model assumptions were based on data from the PCPT; Surveillance, Epidemiology, and End-Results program; literature review of costs, utilities, and transition rates among various prostate cancer health states; and local institutional cost data. RESULTS: The quality-adjusted cost-effectiveness ratio for finasteride compared with men not receiving chemoprevention was $122,747 (in U.S.$) per quality-adjusted life-years saved (QALYs). If finasteride is assumed to not increase the incidence of high-grade tumors, the quality-adjusted cost-effectiveness ratio was $112,062 per QALYs. Sensitivity analysis found that chemoprevention of prostate cancer with an agent that has no effect on the prevalence of benign prostatic hyperplasia can render a cost-effectiveness ratio of <$50,000 per QALYs saved when applied to a high-risk population associated with a 25% risk reduction, and a cost of $30 per month. CONCLUSIONS: Finasteride is unlikely to be cost-effective when considering the impact on survival differences among treated versus untreated groups. However, chemoprevention may be cost-effective in high-risk populations when taking into consideration adjustments for the impact on quality of life.
Journal: Cancer. 2008 Mar 1;112(5):1058-65.
Adapted from PubMed; click here to access full journal article.
Injectables in the Prostate
Authors: Saemi AM, Plante MK.
Division of Urology, Department of Surgery, University of Vermont, Burlington, Vermont, USA.
PURPOSE OF REVIEW: Benign prostatic hyperplasia with associated symptoms and morbidity is increasingly common among aging men. Medical treatment of lower urinary tract symptoms is the mainstay of therapy with progressive disease requiring more invasive intervention. Transurethral resection of the prostate remains a widely applied gold standard therapy. Numerous minimally invasive surgical therapy options have arisen and subsequently faded over recent years. Those remaining in use are largely positioned between pharmacological treatment and transurethral resection of the prostate. Intraprostatic injection therapy, the oldest minimally invasive surgical therapy, has been investigated for over 100 years with renewed interest recently. This review will provide some history of intraprostatic injection for benign prostatic hyperplasia including the most recent reports using transperineal, transrectal and transurethral routes with different injectables. RECENT FINDINGS: For benign prostatic hyperplasia, transperineal and transurethral injection routes have received the most systematic evaluation. Intraprostatic injection of botulinum toxin type A has received much recent attention with regards to mechanism of action and efficacy. Anhydrous ethanol remains the most extensively studied injectable to date. SUMMARY: Injection therapy remains a very promising minimally invasive surgical therapy for benign prostatic hyperplasia with increased attention from the urologic community in recent years. Further experience both with systematic laboratory and clinical trials investigation will be necessary before widespread clinical adoption.
Journal: Curr Opin Urol. 2008 Jan;18(1):28-33.
Adapted from PubMed; click here to access full journal article.
Humoral Response Profiling Reveals Pathways to Prostate Cancer Progression
Authors: Taylor BS, Pal M, Yu J, Laxman B, Kalyana-Sundaram S, Zhao R, Menon A, Wei JT, Nesvizhskii AI, Ghosh D, Omenn GS, Lubman DM, Chinnaiyan AM, Sreekumar A.
Michigan Center for Translational Pathology, Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
There is considerable evidence for an association between prostate cancer development and inflammation, which results in autoantibody generation against tumor proteins. This immune system-driven amplification of the autoantibody response to intracellular antigens can serve as a sensitive tool to detect low abundance serum proteomic tumor markers for prostate cancer as well as provide insight into biological processes perturbed during cancer development. Here we examine serum humoral responses in a cohort of 34 patients with either benign prostatic hyperplasia or clinically localized prostate cancer (PCa). The experimental strategy couples multidimensional liquid-phase protein fractionation of localized and metastatic prostate cancer tissue lysates to protein microarrays and subsequent mass spectrometry. A supervised learning analysis of the humoral response arrays generated a parsimonious predictor having 78% sensitivity and 75% specificity in distinguishing PCa from benign prostatic hyperplasia in a cohort of American males with elevated prostate-specific antigen. Enrichment analysis of the PCa-specific humoral signature revealed large scale immune reprogramming mediated by STAT transcription factors and the generation of autoantibodies to enzymes involved in nitrogen metabolism. Meta-analysis of independent prostate cancer gene expression data validated the presence of STAT-induced immunomodulation. Concomitant validation of elevated levels of the nitrogen metabolism pathway was obtained by direct measurement of metabolic levels of glutamate and aspartate in prostate cancer tissues. Thus, in addition to functioning as markers in prostate cancer detection, humoral response profiles can serve as powerful tools revealing pathway dysregulation that might otherwise be suppressed by the complexity of the cancer proteome.
Journal: Mol Cell Proteomics. 2008 Mar;7(3):600-11. Epub 2007 Dec 11.
Adapted from PubMed; click here to access full journal article.
Characterizing TUNA ablative Treatments of the Prostate for Benign Hyperplasia with Gadolinium-Enhanced Magnetic Resonance Imaging
Authors: Mynderse LA, Larson B, Huidobro C, Meyer JJ, Busel D, Hanson DP, Larson T.
Department of Urology, Mayo Clinic, Rochester, Minnesota, USA.
BACKGROUND AND PURPOSE: Transurethral Needle Ablation of the prostate TUNA has been accepted as an office-based treatment for benign prostatic hyperplasia (BPH) for many years. Clinical outcomes have been reported, but the amount and location of the necrosis produced have yet to be characterized. The necrosis caused by TUNA was evaluated by gadolinium-enhanced magnetic resonance imaging (MRI) of the pelvis. PATIENTS AND METHODS: Twelve patients with BPH/lower urinary-tract symptoms underwent standard TUNA, and MRI scans with gadolinium enhancement were performed before and 1 week after treatment. The images were studied using Analyze software to quantify the amount of necrosis compared with the prostatic volume. Transverse, coronal, and sagittal images were obtained to identify the location of the necrosis. RESULTS: New gadolinium defects were seen in all patients after TUNA. The lesions coalesced into continuous areas of necrosis and correlated with the site of needle placement. The mean volume of necrosis was 6.84 cc and equated to 8.6% of the prostate volume. No lesions were found near the apex, urethra, or rectum; and none extended beyond the prostate capsule. CONCLUSIONS: Gadolinium-enhanced MRI demonstrates new vascular defects representing necrosis caused by TUNA of the prostate. This therapy for BPH produces necrotic lesions that can be placed strategically by the surgeon. The standard protocol produces lesions that coalesce to create larger lesions. This MRI study has characterized, for the first time, the heating pattern and intraprostatic necrosis of a complete TUNA procedure.
Journal: J Endourol. 2007 Nov;21(11):1361-6.
Adapted from PubMed; click here to access full journal article.
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Adapted from PubMed; click here to access full journal article.
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