Men Disease... BPH

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Introduction

Prostate is the largest accessory male sexual gland that encircle the beginning of male urethra, located beneath the neck of the urinary bladder. It is weighing 20 g in adult male (the size of a chestnut). The gland secretes a milky thin fluid contains acid phosphatase amylase, citric acid, and fibrinolysin. Fibrinolysin liquefies coagulated semen after ejaculation. The prostatic fluid contributes to the formation of seminal fluid. (Gunasegaran, 2014)

Benign prostatic hyperplasia (BPH), one of the most prevalent diseases in elderly people, usually represent by low urinary tract symptoms (LUTS) that disturb the regular activities and sleep habits. The prevalence of BPH is depend on age, the development begins after 40 years of age. BPH prevalence at age of 60 years around 50% and reach 90% by 85 years old, also the disturbing symptom increase with the Increased age. LUTS are disturbing to many patients, the amount of disturb vary greatly between patients with the same severity of the symptoms. therefore, we should consider the patient lifestyle as well as his degree of disturbing symptom when choosing the proper management plan. There have been major improvements in the management choices available for BPH over the last decade. (AUA Practice Guidelines Committee ,2003).

We hope by the end of this review, we would be able to clarify some of the following objectives of this work, and they include: 

  • Microscopic structure of the prostate and its function

  • How to evaluate patient with BPH   

  • Outline the treatment options of BPH

Abstract:

Prostate is the largest accessory male sexual gland of reproductive system, located beneath the neck of the urinary bladder where it encircles the prostatic part of the urethra. The main function of the gland is to secrete a milky thin fluid contributes to the formation of seminal fluid. Histologically the prostate is made of parenchyma (30 to 50 tubuloalveolar glands arranged in three concentric layers) and a characteristic fibromuscular stroma.The prostatic parenchyma in adult is divided into four anatomically and clinically distinct zones. 

BPH occurs in transitional and periurethral zones mainly and lead to partial or total urethra obstruction. A widely accepted pathogenesis theory of BPH is related to the dihydrotestosterone (DHT) action. Once synthesized, DHT acts on the stromal cells as an autocrine agent and on the glandular epithelial cells as a paracrine hormone, causing them to proliferate.

Prostate:

Microscopic features

Stroma:

It is a fibromuscular stroma supports the parenchyma that consist of smooth muscle fibres with connective tissue fibres arranged in different directions. the smooth muscles contract during the ejaculation and secrete the prostatic fluid into the urethra.it contains a thin capsule that encircles the prostate gland. The lymphatics, blood vessels and nerves also present in the stroma. (Gunasegaran, 2014) (Kumar, 2013)

Parenchyma:

 The parenchyma composed of 30–50 tubuloalveolar glands.  These glands are arranged in three concentric layers: inner mucosal, intermediate submucosal and outer main glands.

 The mucosal glands are small tubular glands present in the inner zone and they open directly into the urethra. The submucosal and main glands are tubuloalveolar glands present in the intermediate zone and outer zone respectively. They open into the prostatic urethra by long ducts. The parenchyma is formed by large irregular prostatic alveoli with wide lumen. The epithelium varies depend on the activity, the inactive gland lined with simple cuboidal/columnar, and the active gland lined with pseudostratified epithelium.

The alveoli of the prostatic glands may show prostatic concretions (corpora amylacea) especially in older males appear as rounded eosinophilic bodies under the microscope. These are secreted substances that with time have become calcified. (Gunasegaran, 2014) (Kumar, 2013)

Ducts: As aforesaid previously, the submucosal and main glands open to the urethra by ducts. they are 12–20 ducts opening to the urethra. The ducts are lined with simple columnar epithelium which shift into transitional epithelium in the terminal portion. (Kumar, 2013)

The prostatic parenchyma in adult is divided into four anatomically and clinically distinct zones:

Peripheral zone:

involve 70 %of the glandular tissue of the prostate

It encloses the central zone and contain the posterior and lateral portion of the gland. prostatic carcinomas usually develop from the peripheral zone of the prostate gland. during digital examination of rectum, the peripheral zone can be palpable. also, this zone is the most suspectable to inflammation. (Ross & Pawlina, 2011)

Transitional zone: 

The transitional zone encloses the prostatic urethra; it constitutes about 5% of the glandular tissue of the prostate and include the mucosal glands. The parenchymal cells of this zone often undergo proliferation (hyperplasia) in elderly males and form nodular masses of epithelial cells. these nodules will squeeze the prostatic part of the urethra, leading to urination difficulties. The condition is called benign prostatic hyperplasia (BPH). (Ross & Pawlina, 2011)

Central zone:

the central zone encloses the ejaculatory ducts. It contains about 25% of the glandular tissue and is both carcinoma- and inflammatory-resistant. Cells in the central zone have characteristic morphological features comparison to the other zones (the cytoplasm slightly basophilic, and the nucleus is larger and displaced at different levels in adjacent cells). (Ross & Pawlina, 2011)

Periurethral zone:

the periurethral zone is consist of mucosal and submucosal glands. This zone can undergo pathological growth in later stages of BPH but mostly from the stromal elements. This development, coupled with the transitional zone glandular nodules, leads to increase the compression of the urethra and further urine retention in the bladder. (Ross & Pawlina, 2011)

Benign prostatic hyperplasia (BPH) :

Is a histological term that relates to proliferation of smooth muscle and epithelial cell within the transitional zone of prostate. The enlarged gland lead to the lower urinary tract symptoms through at least two ways (a) direct obstruction of bladder outlet (static portion) and (b) increase tone and resistance of smooth muscle (dynamic portion).

There are two figures: (a) gross pi

How to evaluate and diagnose:

Medical history of the patient:

 It is an important first step to exclude other causes that might represent the same urological symptom. also, to assess the severity of symptom and fitness for surgical procedure. (Edwards,2008)

Physical examination:

 Digital rectal examination can be done to assess the prostate volume and consistency (which usually harden in prostate cancer that require biopsy) symmetrically enlarged and the median sulcus is palpable. Abnormal sphincter tone indicates a neurological abnormality which can lead to urinary symptom. Cognitive or ambulatory impairment may exacerbate incontinence problems. (Edwards,2008)

Laboratory test:

A urinalysis should be done to scan for hematuria and urinary tract infection (UTI). As it can rule out (if was normal) non-BPH causes of the symptoms, such as bladder cancer, bladder stones, UTI, or urethral strictures.

Prostate-specific antigen (PSA) levels  measured in 2 specific case 1 those whom management plan will affected in presence of prostate cancer 2 Those for whom the PSA assessment can alter the way their voiding symptoms are handled (Males with high levels of PSA respond better to finasteride).males who at risk of bladder cancer should have Urine cytology test. (Edwards,2008)

management:

 Treatment options will differ according to severity of symptom and how it affects the quality of life.in males with mild symptoms (AUA Symptom Index score of 7 or less) or in those who do not perceive their symptoms as troublesome, the watchful waiting strategy is recommended.

Medical therapy: 

Can be used in those with mild to severe symptom affecting the quality of life.

Alpha blockers: it acts on smooth muscle of the prostate gland causing relaxation of it that relieve LUTS. some of these drugs (i.e. Doxazosin, terazosin, and prazosin) also act on vascular endothelium and decrease the blood pressure but should not depend on them alone as hypertension therapy as they less effective than the diuretic group. Tamsulosin and alfuzosin are more selective for prostatic smooth muscles.

5-α reductase inhibitors: the conversion of testosterone to dihydrotestosterone is blocked by finasteride and dutasteride (Avodart), which inhibits prostate development. When the volume of the prostate is 40 mL or greater, these agents appear to be most beneficial. The 5-alpha reductase inhibitors require around six months of therapy to achieve clinical benefit and do not give immediate symptom relief. In contrast to alpha blockers, 5-alpha reductase inhibitors can decrease the risk of acute urinary retention and surgical intervention after four years of treatment.  Finasteride side effects include diminished libido, ejaculatory dysfunction and erectile dysfunction. (AUA Practice Guidelines Committee ,2003).

Combination therapy: Suitable for those who suffer from prostate enlargement with the lower urinary tract symptom. (AUA Practice Guidelines Committee ,2003).

Alternative natural treatment:

Saw Palmetto: most the herbal agents used for BPH is Saw palmetto. this plant contains lauric acid and linoleic acid act as inhibitor 5-alpha-reductase types 1 and 2. there is conflict about its benefit, meta-analysis study in 2002 proved it had moderate improvement in symptoms. however updated study in 2010 that including other 9 trial proved no effect of saw palmetto on symptom. (Evans & Evans ,2011)

Stinging Nettle Root: Stinging nettle (Urtica dioica) is a plant found in Europe and Asia, and has several variant effects depending on the part of the plant being used. The root is used to enhance BPH symptoms while plant's stems and leaves are used as a diuretic, this agent reduce testosterone concentration by preventing it from binding to sex hormone binding globulin. it is effective in increase flow of urine at 120 mg twice daily. (Evans & Evans ,2011)

Beta-Sitosterols: Beta-sitosterols were used for BPH treatment and were studied. Popular sources include South African star grass, Hypoxis rooperi, as well as various groups of plants in the Pinus and Picea species. These agents inhibit the effects of androgens to decrease the size of the prostate. this plant improves the urinary symptom of prostatic enlargement with no effect on the size of prostate. The dosage of nonglucosidic beta-sitosterol used for the trials ranged from 60 mg to 195 mg daily. Gastrointestinal side effects were the most common complaint. (Evans & Evans ,2011)

Minimally Invasive Therapies: 

Transurethral Holmium Laser Resection/Enucleation:

It is new effective alternatives to transurethral prostate resection (TURP)and open prostatectomy with decreased risk of perioperative complication of TURP syndrome. Emerging evidence suggests that LASER therapies may play a role even in men with very large prostate (> 100 g). (McVary et al ,2011)

Transurethral Microwave Thermotherapy: No convincing evidence suggest that one device is better than another and it is partially efficient in relieving symptoms due to BPH. (McVary et al ,2011)

Transurethral Needle Ablation of the Prostate: uses radiofrequency energy to strip off periurethral tissue of the prostate. It is suitable for males with mild to moderate symptoms, and a volume of prostate below 60mL. (McVary et al ,2011)

Other Surgical procedure:

 Surgical Operation is the most invasive choice, and is suitable for moderate to severe symptom or if their complications associated with BPH.

Transurethral Incision of the Prostate TUIP:

Endoscopic technique only for the treatment of smaller prostates (≤30mL). it done as outpatient procedure with lower risk of ejaculatory dysfunction and a higher rate of secondary procedures. (AUA Practice Guidelines Committee ,2003).

Transurethral Resection of the Prostate TURP:

TURP was the most common procedure but the associated morbidities and long staying duration in hospital triggered the development of alternatives. also, a recent study found that within two years, two out of 30 TURP patients requires reoperation. Common complications involve ejaculatory dysfunction, urethral stricture, haemorrhage, and TURP syndrome (i.e., hyponatremia induced by the hypotonic irrigate absorption). (AUA Practice Guidelines Committee ,2003).

Conclusion:

Prostate is the largest accessory male sexual gland, located beneath the neck of the urinary bladder. The gland secretes a milky thin fluid fluid contributes to the formation of seminal fluid. Histologically the prostate is made of parenchyma (tubulo-alveolar glands) and a characteristic fibromuscular stroma. The prostate gland contains four major glandular regions; the peripheral zone, the central zone, transition zone and the periurethral zone, which differ histologically .

New pharmacotherapies and technologies that impacted treatment algorithms have emerged. LUTS / BPH Management continues to evolve. 

In the management of disturbing LUTS, it should consider the interactions of the prostate, urethra, bladder and bladder neck, and that symptoms may also from central nervous system. LUTS due to BPH has a marked impact on the quality of patient life but not life threatening. Previously the main goal of the treatment has been to relieve the irritating LUTS but lately, care has addressed disease progression prevention plan. This framework lists a number of important methods in management including alternative therapies, watchful waiting and minimally invasive procedure.

References:


  • AUA Practice Guidelines Committee. (2003). AUA guideline on management of benign prostatic hyperplasia (2003). Chapter 1: Diagnosis and treatment recommendations. The Journal of urology, 170(2), 530-547.           

  • Edwards, J. L. (2008). Diagnosis and management of benign prostatic hyperplasia. American family physician, 77(10), 1403.              

  • Evans, J. D., Pace, K., & Evans, E. W. (2011). Natural therapies used by adult men for the treatment of erectile dysfunction, benign prostatic hyperplasia, and for augmenting exercise performance. Journal of pharmacy practice, 24(3), 323-331.

  • Gunasegaran, J. P. (2014). Textbook of Histology and Practical guide. Elsevier Health Sciences

  • Kumar, B, (2013). Histology Text & Atlas, First Edition, pages (260-262).

  • McVary, K. T., Roehrborn, C. G., Avins, A. L., Barry, M. J., Bruskewitz, R. C., Donnell, R. F., ... & Ulchaker, J. C. (2011). Update on AUA guideline on the management of benign prostatic hyperplasia. The Journal of urology, 185(5), 1793-1803. 

  • Ross, M. H., & Pawlina, W. (2011). Histology a text and atlas 6th edition.



 



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