The prostate is a small gland placed right under the blatter, present just in men, that weighs about 20 g. It belongs to the genital system and its morphological and functional development depends on testosterone. It's formed by about thirty glandular units, each one with its own excretory duct toward the urethra. Cells with a secretory function are epithelial cells; the epithelial membrane is wrapped in tissue with muscle fibers also known as stroma. Glaundalar tissue and stroma are in turn wrapped in an external membrane called “capsule”. The prostate enlargening involves both the epithelium and the stroma.
The prostate fluid, appearing with a milky look, is full of enzymes and citric acid important for the survival and quality of the sperm; during the ejaculation it flows in the urethra and blends with the seminal fluid. The prostate fluid makes up for 70% of the seminal fluid.
The prostate is longways crossed, top to bottom, by the first portion of the urethra in which the prostate fluid flows in.
Benign prostatic hyperplesia (BPH)
Prostatic hypertropy, or prostatic hyperplesia, is the enlargement (volume increase) of the prostate. It's a benign pathology (BPH, benign prostatic hyperplesia) also known as benign enlargement of the prostate. The enlargement of the prostate squeezes the urethra, the canal through which urine gets expelled, with consequent urinary difficulties, urine stagnation in the bladder and need to urinate more often. In the long term the urine stagnation due to bladder obstruction (BOO, bladder outlet obstruction) may cause urine retention, renal insufficiency, recurring infections, hematuria (presence of blood in urine) and vesical cystolith. At bladder level, the prolonged obstruction of the urine outflow causes reduction of the functional volume of the bladder, bladder wall thickening with resulting minor extensibility and hyperactivity of the detrusor muscle because of the continuous stress it undergoes. The sensitivity increase of the detrusor muscle even for small urine volumes leads to some sort of instability of the muscle itself with resulting urination frequency increase and showing of the symptomps of the low urinary tracts (LUTS, Low urinary tract symptoms)
With advancing age, starting at the age of 35, the prostate tends to increase in volume, because of a process that may be considered physiological. We talk about prostatic hypertrophy when the gland's weight is higher than 20 g. Prostatic hypertrophy is common in men older than 50: 70% of men older than 70 shows hystological evidences of prostatic hypertrophy. In about 40% of all cases, prostatic hypertrophy evolves toward a full-blown urinary obstruction condition (prostatic hypertrophy is a progressive evolution disease). Prostatic hypertrophy is recorded as the second most diagnosed pathology in the Italian male poulation, after hypertension and before ischemic cardiomyopathy, dyslipidemias and diabetes and is characterized by low mortality rate, equal to 0,35 per 100.000 people (Pagliarulo et al. 2003; Levi et al., 2003).
The predominance of prostatic hypertrophy in male population varies according to adopted clinical criteria. Considering a prostate volume higher than 30 ml and a high IPSS scale score (internation prostatic simptomathology scale), the predominance of IPB in a population aged 55 to 74 is equal to 19%. If however these two criteria get added to a maximum urinary flow and a urinary residual volume post-urination > 50 ml, the predomaniance of IPB decreases to 4% (Merck Manual).
Prostate disorders may influence male sexual activity. About 15-20% of male infertility cases lead to a prostate inflammatory state. Low urinary tracts disorders (LUTS) may be indicative of prostatic hypertrophy: about half the patients affected by LUTS have been positevely diagnosed with IPB.
Benign prostatic hypertrophy does not eveolve into prostatic carcinoma. These two pathologies originate in different areas of the prostatic gland, may coexist but are not related one another. Prostatic hypertrophy affects the peripheral area of the gland (transitional area), while the tumor develops in the external side and affects the capsule that envelops the prostate (Kirk, 2006).
The symptomatology affecting low urinary tracts such as urinary difficulties, increased frequency in both day and night hours, urinary stimulus right after the end of one, are common in both prostatic hypertrophy and prostatic carcinoma. Usually prostatic carcinoma is asymptomatic in its initial stages, and becomes symptomatic in advanced stages. It's important to trace the reason that causes urinary disorders in order to a correctly intervention on the patient.
The cause that leads to benign prostatic hyperplesia are unknown. It is possible that the disease is associated to hormonal changes caused by aging. Testicles produce testosterone, the main male sexual hormone, that gets later converted into dihydrotestosterone (DHT) and estradiol (estrogen) in specific tissues. High levels of dihydrptestosterone may cause IPB. How and why the DHT increase causes IPB is still a debatable and studied topic.
The patient's history (anamnesis), a physical exam and an evaluation of the symptoms provide the basis for a benign prostatic hyperplesia diagnosis. The physical exam include a digital-rectal examination (DRE) while the symptoms evaluation is obtained through the use of a specific questionnaire known as IPSS (International Prostatic Symptoms score). The dosage in the bloodstream of the prostate specific antigen levels (PSA) in a patient affected by prostatic hyperplesia may help the urologist exlcude prostate cancer hints. PSA is a specifc enzyme produced by prostatic cells that has the job of dividing chemical bonds in the sperm and is important for male fertility. Even though it only gets produced by the prostate and, therefore, its increase unequivocally indicates the presence of a prostatic pathology, the PSA indiscrimnately increases in all prostatic diseases. PSA's level is also partly caused by the prostate's size. PSA is dosed in the bloodstream in nanograms per milliliter (ng/mL). A PSA value:
- 4 ng/mL or lower is normal,
- between 4 and 10 ng/mL is considered suspicious,
- between 10 and 35 is highly suspicious.
Most men with a PSA between 4 and 10 do not show prostate cancer, however there are cases of prostate cancer with normal levels of PSA (lower than 4). Very high PSA values strongly suggest the presence of a tumor.
Potential anomalies like IPB or prostate cancer may be found thanks to this exam. Urodynamic examinations, usually carried out in clinics, are used to measure the urine's volume and pressure inside the bladder and to evaluate the urinary flow. They are especially useful for the diagonisis of innate deficit of the urinary sphincter and cases of mixed incontinence caused by stress and urgency. These studies are especially useful, where suspected, in order to exclude that the symptomatology is caused by different conditions than IPB.
Uroflowmetry is a simple analysis for recording the urine flow, determining how completely and quickly the bladder gets empty and evaluating the obstruction. At full bladder patients urinate in a device that measures the quantity of urine, the time it takes for urination and the urine's flow. Patients with urgency or stress incontinence usually have a normal or increased flow, unless there is an obstruction. A reduced flow may indicate IPB. A pressure/flow study measures the pression in the bladder during urination and excludes that a slow flow may be caused by a condition different than IPB such as the inability of contraction of the total or partial bladder. This analysis requires the introduction of a small bladder catheter. The procedure is bothersome and may rarely cause urinary tract infections. Post-Void residual (RPM) measures the amount of urine left in the bladder after urination. The patients is invited to urinate immediately after the exam and the residual urine is calculated through medical ultrasound (non-invasive method) or through catheterization (invasive method). A RPM lower than 40 ml generally indicates the emptying of the bladder, while measures between 100 and 200 ml very often indicate the presence of an obstruction. Patient's anxiety and discomfort may influence the results so this study is not always reliable.
For the treatment of benign prostatic hyperplesia there are different options:
- Simple observation
Minimally invasive treatments
- Microwaves (TUMT)
- Other forms of thermotherapy
- Resection of the prostate by olmio laser (HoLEP)
- Simple Prostatectomy
- Transurethral incision of the prostate (TUIP)
There are several treatment options for patients affected by benign prostatic hyperpleasia according to the severity of the symptoms. If the symptoms do not bother too much it may be decided not to prescribe any therapy. If however the symptoms are severe enough, cause discomfort, interfere with daily activities and threaten the general health, treatment is recommended.
Patients with tolerable symptoms may choose to undergo just normal yearly routine exams that consist in rectal exploration, a hematic dosage of PSA and a suprapubic ultrasonography. Furthermore, through IPSS it is evaluated if the symptoms are getting worsening.
5-alpha-reductase inhibitors prevent the conversion of testosterone into dihydrotestosterone (DHT). In many cases, a period of treatment of at least 6 months is necessary for evaluating the effictiveness of the therapy. These medications are taken orally once a day. Patients shoud regularly consult their urologist to check potential side effects and evaluate the therapy's benefits. Side effects include libido reduction, erectile dysfunction, breast pain and enlargening (gynecomastia) and reduction of sperm count. Alpha-lytics act relaxing the smooth muscle of the bladder neck so increasing the urinary flow. They are taken orally once a day. Side effects may include headache, dizziness, hypotension, fatigue and generalized weakness.
Surgical treatment is an elective surgery and has the purpose of removing the enlarged part of the prostate that compresses the urethra. The urologist introduces a tool called resectoscope in the penis through the urethra to the prostate. The surgical indications are the following:
- blood in urine (hematuria),
- kidney damage caused by prostatic obstruction,
- recurrent infections,
- urinary inability (urinary retention),
- bladder stones,
- symptoms severity,
- high post-void residual.
Surgical treatment: TURP
Transurethral resection of the prostate (TURP) is to this day the best treatment (gold standard) to which the other treatments must be compared to. This procedure is usually performed under general or regional anesthesia and takes about 60-90 minutes. The urologist introduces a tool called resector in the penis through the urethra. The resectosope has an internal passage for a beam of light and is equipped with valves for an electric scalpel and liquid irrigation to remove prostate tissue and coagulate blood vessels. The urologist removes the obstructing tissue and the irrigation liquid transports it to the bladder. These residuals get removed at the end of the procedure through syringe aspiration. Patients usually stay in the hospital for about 3 days with a catheter in the bladder. Most patients can go back to their usual activities in a short period of time. During the convalescence it is recommended to:
- avoid lifting excessive weights and perform physical activities,
- drink a lot of water in order to wash the bladder,
- eat in a balanced way,
- use laxatives, if necessary, in case of constipation.
The patient is dismissed 3 days after the surgery with therapy indications based on antibiotics and heparin. Inflammatory and oxidative stress caused by the surgery should be treated with anti-inflmmatory medications that, however, as widely known, cause side effects that should not be underestimated especially for long term therapies. Therefore it is recommended the use of anti-inflammatory therapies with natural substances.
Blood in urine (hematuria) is common after surgery and usually persists even at the time of dismissal. Bleeding may also depend on excessive exertions. Some patients compain about ailments such as sensation of urgency with urination control difficulties. These inconveniences get better with time and tend to disappear but it is important to keep in mind that the more severe are the symptoms before the surgery the longer is the recovery period. At least 30% of the patients who undergo TURP complain about problems in their sexual function. The most common complication is retrograde ejaculation (“dry orgams”), which is caused by the removal of the muscle that closes the bladder neck during the ejaculation. Semen flows to the bladder rather than progressing toward the outside through the penis: this condition may cause infertility but does absolutely not interfere with sexual pleasure. Most patients who undergo TURP do not care for this inconvenience.
Prostatits mostly shows in men under the age of 50. Prostatitis is a prostatic gland inflammation, often accompanied by its swelling and pain. It is sometimes linked to urination difficulties. It must be noted that the symptoms caused by prostatits can also be transimitted to the anus, the perineal membrane, the penis, testicles, the groin and the inner thigh. According to the National Institutes of Health (NIH) there are four kinds of prostatitis:
- acute bacterial prostatitis,
- chronic bacterial prostatitis,
- chronic prostatits or chronic pelvic pain syndrome,
- asymptomatic inflammatory prostatitis.
Acute bacterial prostatitis is the least common of the four types of prostatitis and is also considered the most common to diagnose and efficiently cure. The therapy, decided by the response of the antiobiograms cultivation, is always accompanied by the administration of targeted antibiotics.
Chronic bacterial prostatitis is relatively rare and occurs when bacteria find a place on the prostate where they can survive. Men suffer from urinary tract infections, which may seem to go away but return with the same bacteria. The treatment usually requires the use of antimicrobical medications for a prolonged period of time. However antimicrobicals can't always eradicate this kind of prostatitis because of the difficulty for the antibiotic to soak the prostate with a bactericidal quantity.
Nonbacterial chronic prostatitis is the most common form of prostatitis, but is the hardest to cure. The appearance of its symptons doesn't appear in relation to anything specifically traceable and these may in time diminish and disappear for later reappearing without any previous sign. The specific characteristic is that in the urine, semen and urethral swab, the pathogenic bacteria cannot be isolated. Sometimes inflammatory cells can be found but other times they cannot. The treament usually happens through anti-inflammatory medications that however, as it's well known, cause side effects not to be underestimated especially for long term therapies. Therefore it is advised to undergo anti-inflammatory therapies with natural substances.
Chronic pelvic pain syndrome: the aforementioned nonbacterial chronic prostatits cannot be discerned from chronic pelvic pain syndrome. In the USA the acronym CPPS indicates that widely vast range of painful symptoms related or not related to urination or sexual problems. The clinical workers who handle “prostatits” catalogue, by now, in this syndrome 70-80% of the also called prostatitis patients. The disease, which may arise because of various reasons, is often a sequency of an actual previous prostatitis. But it may also be the consequence of proctological diseases (fistula, fissures, hemorrhoids), as well as being itself the cause. It may follow a long period of stress and psycho-physiological fatigue. It's based on the lingering of a prolonged spasm of the perineal muscle (levator ani), with a dramatic and usually consequent inflammation of the pudendal nerves. In this syndrome too, obviously, it won't be possible to detect the presence of patogenic bacteria, or if traceable, will just always be enterobacteria (E.Coli, Proteus, Klebsiella, Enterococcus, etc.) coming from the rectal ampulla of the same subject affected by the syndrome.
Asymptomatic prostatitis cannot be immediately diagnosed as the patient does not complain of any pain or annoyance, but shows the signs of inflammation or infection in the semen or in the prostatic secretions. This kind of prostatitis is usually diagnosed during the research for infertility causes or after the presence of a high PSA.
There are different kinds of cells in the prostate, each one that can change and become cancerous, but almost all diagnosed prostate tumors originate from the gland and are therefore called adenocarcinoma (like all tumors that originate from gland cells). Other than adenocarcinoma, rare cases of sarcoma, small cell carcinoma and transition cell carcinoma can be found in the prostate. Acording to the stage of the disease staging notation exams may be performed such as CT (Computerized tomography) or CAT scan. To verify the presence of potential bone metastasis bone scintigraphy is often used. The pathologist who analizes the tissue taken through the biopsy assigns the tumor the so called Gleason score, a number between 1 and 5 that indicates how the cancerous glands look is similar or different than that of normal glands: the more similar they are, the lower the Gleason score is. Tumors with a Gleason score lower or equal to 6 are considered low grade, those with a score equal to 7 are considered medium, whereas those between 8 and 10 are considered high score. These last ones present a higher risk of progressing and spread to other organs. Instead, in order to define the stage TNM system is usually applied to the tumor (T=tumor), where N indicates the lymph nodes status (N: 0 if untouched, 1 if damaged) and M the presence of metastasis (M: 0 if absent, 1 if present). For a complete characterization of the disease's stage the Gleason score and PSA level are also applied to these three parameters. The relation between these parameters (T, Gleason, PSA) allows to assign the disease three different risk classes: low, medium and high risk. Generally in case of low risk (which means a dieases that will unlikely spread and become metastasis) it is possible not to decide to surgically remove the gland but to just supervise the disorder's evolution. In its initial stages, prostate cancer is asymptomatic and is diagnosed after urological examination, which involves rectal exploration, or PSA control with blood sample. When the tumor mass grows it causes urinary symptoms: urinary difficulties (especially at the beginning) or the need to urinate often, pain while urinating, blood in urine or in semen, sensation of not being able to fully urinate. The aforementioned urinary symptoms are often tied to benign prostatic problems such as hypertrophy.
PSA, urinary symptoms, rectal exploration, prostate biopsy after diagnostic sonography.
In case of small and low risk tumors no surgical treatments are expected but frequent controls (PSA, rectal examination, biopsy), for all the others a radical removal surgery is performed and, if needed, radiotherapy.
Bladd cancer is the second most common tumor among those in urology and it mostly concerns males. Diagnosis show that about 80% of bladder tumors affects only the most superficial layers of the bladder walls. The other 20% of patients at the beginning present a disease that penetrates the deepest layers and the muscles, or the so called detrusor muscle, (T2), or it spreads outside the bladder (T3-T4). An important risk factor is cigarette smoking that increases by three the risk of developing bladder cancer. Also workers of certain industries are at risk, such as in the chemical, typographical, coloring, rubber, petroleum and leather industries. The most frequent first sign of bladder cancer presence is macroscopic hematuria (blood in urine visible to the naked eye), generally without any pain or urinary burning. Otherwise bladder cancer can appear with urinary burning and pollakiuria (urination frequency increase), symptoms that are similar to a urinary tracts infection. The best radiological exam is kidney and bladder ultrasonography. This examination may be followed by urinary cytology (a test aimed at searching for abnormal cells in urine) and urethrocystoscopy (endoscopic exam of the low urinary tracts. It allows for a direct vision of the urethra in all of its parts, neck and bladder walls in order to identify potential morphological anomalies). Urinary cytology, or the urine sample examination for the search for atypical cells, is especially useful in the diagnosis of high score tumors (G3 or Cis).
Surgical intervention: TURB
The acronym TURB means: Trans Urethral Resection of the Bladder. The surgery consists in the removal of one or more endovesical neoformations through an endoscopic tool (resector) that is inserted into the bladder via the urethra to get to the bladder. This tool is equipped with a small metallic handle through which electric current can pass that may be used at different intensity to cut or coagulate. Generally a locoregional (epidural or spinal) or general anaesthesia is performed. During the surgery the blatter gets stretched with an irrigating solution (glycine if using a monopolar electroscalpel or a physiological solution if using a biopolar tool). The material collected by the urologist is sent to the anatomic pathology where it gets tested in order to define the microscopic characteristics (typology, differentiation grade, wall infiltration stage). The duration of this operation varies according to the dimensions and number of neoformations. If the neoformation affects the urethral meatus this may also be included in the resection; this operation may require a later application of a double J urethral catheter. A bladder catheter is applied at the end of the surgery to which a system of continuous irrigation gets connected, called cystoclysis. This system's purpose is to keep the catheter accessible and to prevent the formation of coagulations in case of bleeding from the resected areas. Furthermore a precise hemostasis must be performed in order to avoid cystoclysis.
The cystoclysis duration is usually about 24 hours but may vary according to the resection and/or the presence of bleeding. In any case manual washing through the catheter may be neeeded to remove bladder clots, that cause retention and suprapubic pain. The bladder catheter is kept inside for a number of days according to the depth of the resection and the bleeding. In the first 24 hours, according to the specific directions of each case, a chemiotherapeutic substance may be instilled through the catheter in order to reduce the pathology's residuals. The patients is dismissed 3 days after the surgery with therapy directions based on antibiotics and heparin. Inflammatory and oxidative stress caused by the surgery may be treated with anti-inflammatory medications which, however as widely known, may cause side effects that should not be underestimated especially for long term therapy. It is therefore recommended the use of anti-inflammatory therapy with natural substances.
Typical complications, also uncommon, of this procedure are: fever, urinary tracts infections, deep vein thrombosis, pulminary embolisms, orchiepididymitis, electrolyte alterations caused by the reabsorption of the washing liquid (in case of glycine use), urinary retention, urethral meatus stenosis, vesicoureteral reflux, bladder perforations, ureteral stenosis. A post-surgery bleeding may rarely appear which requires a new coagulation by endoscopy. A bladder perforation may intentionally happen (deep bladder resection) or accidentally, for instance because of an eletric stimulation of a nerve close to the bladder, which causes a sudden movement of the patient's leg; this event generally only requires a surgical intervention to suture the bladder breach. Within a month from the surgical operation hematuria may happen (blood loss with urine) caused by the falling of endovesical eschars (scabs); the phenomenon generally ends spontaneously.
International prostate Symptom score (IPSS) at Urological Sciences Research Foundation. Retrieved November 2011. Patel SG, Cohen A, Weiner AB, Steinberg GD. Intravesical therapy for bladder cancer. Expert OpinPharmacother. 2015 Apr;16(6):889-901. Prasad AS. Zinc is an Antioxidant and Anti-Inflammatory Agent: Its Role in Human Health. Front Nutr. 2014;1:14. doi: 10.3389/fnut.2014.00014. eCollection 2014. Rassweiler J, Teber D, Kuntz R, Hofmann R. Complications of transurethral resection of the prostate (TURP)--incidence, management, and prevention. Eur Urol. 2006 Nov;50(5):969-79. Sánchez-Borges M, Caballero-Fonseca F, Capriles-Hulett A and González-Aveledo L. Hypersensitivity Reactions to Nonsteroidal Anti-Inflammatory Drugs: An Update. Pharmaceuticals 2010, 3, 10-18. Sciarra A, Di Silverio F, Salsiccia S, Autran Gomez AM, Gentilucci A, Gentile V. Inflammation and chronic prostatic disease: evidence for a link? Eur. Urol. 2007 Oct; 52(4): 964-72. Smith RD, Patel A. Transurethral resection of the prostate revisited and updated. CurrOpin Urol. 2011 Jan;21(1):36-41. doi: 10.1097/MOU.0b013e3283411455. Solomon DH. COX-2 selective inhibitors: Adverse cardiovascular effects: http://www.uptodate.com/contents/cox-2-selective-inhibitors-adverse-cardiovascular-effects. Solomon DH. Nonselective NSAIDs: Overview of adverse effects, 2015:http://www.uptodate.com/contents/nonselective-nsaids-overview-of-adverse-effects#H22. Walsh PC. Chemoprevention of prostate cancer. N Engl J Med. 2010; 362: 1237-38. Parsons JK. Benign Prostatic Hyperplasia and Male Lower Urinary Tract Symptoms: Epidemiology and Risk Factors. Curr Bladder Dysfunct Rep. 2010 Dec;5(4):212-218. Epub 2010 Sep 7. Wei JT, Calhoun E, Jacobsen SJ. Urologic diseases in america project: benign prostatic hyperplasia. J Urol. 2008 May;179(5 Suppl):S75-80. doi: 10.1016/j.juro.2008.03.141