IntroductionBPH & prostate adenocarcinoma are the 2 majorneoplasms affecting the human prostate.The prostate is a complex organ consisting of epithelial,stromal, & muscular element.Anatomically the prostate gland is the shape of acompressed inverted cone, residing in the true pelvis.Arterial blood supply: inferior vesical+ middle rectal a.Venous drainage: Dorsal venous plexes
The normal prostate measures between 3-4cm at itswidest portion; it is 4-6cm in length & 2-3cm in thickness.Weight 17-25 gmIn the early 1970’s McNeal proposed a concept of zonalanatomy.According to this concept, the glandular portion of theprostate is composed of a large peripheral & a smallcentral zone, which together constitute about 95% of thegland.
The other 5% is formed by the transition zone which islocated just outside the urethra & is composed of theperiurethral glands, which presumably are responsiblefor all of the BPH.60-70% of prostatic CA occurs in the peripheral zone,10-20% in the transition zone, & 5-10% in the centralzone.
Benign Prostatic(hypertrohy (BPH
Incidence & EpidemiologyThe term BPH is a misnomer because the actualchange is a hyperplasia & not hypertrophy.The initiation of BPH may not be environmentalor genetically influenced.It is also suggested that the prevalence of BPHincreases with age in all male populations.
EtiologyThe etiology of BPH is unclear.Two factors necessary for BPH to occur are:(1) endocrine control (DHT)(2) agingThe relative roles of androgen & estrogen in inducingBPH, however , are complex & not completelyunderstood.
PathogenesisStromal – epithelial interaction normal 2:1, BPH 3 or 4:1 major change is connective tissueThe differential representation of the histologic components of BPH explains the potential responseviness to medical therapy
Pathophysiology Of SymptomsSymptoms of BPH:1( obstructive decrease in force & caliber of the stream: due to urethral compression is one of the early & constant features of BPH. Hesitancy: occurs because the detrusor takes a longer time to generate the initial increased pressure to overcome the urethral resistance. Intermittency: occurs because the detrusor is unable to sustain the increased pressure until the end of voiding. Terminal dribbling of urine & incomplete sense of bladder emptying
Pathophysiology Of Symptoms2( Irritative symptoms: Frequency: - Incomplete emptying during each void results in shorter intervals between voids. - The presence of enlarged prostate provokes the bladder to trigger a voiding response more frequently than in normal individuals, especially if the prostate is growing intravesically. Nocturia: normal cortical inhibitors are lessened and also because the normal urethral and sphincteric tone is reduced during sleep. urgency & dysuria: uncommon.
Pathophysiology Of Symptoms Obstructive symptoms are common with enlarged prostates. Predominance of irritative should suggest voiding dysfunction.
Pathophysiology Of SymptomsSystemic symptoms related to the UT:- Vesicoureteral reflux- Dilatation & hydronephrosis- Renal failure & symptoms of uremiaSymptoms unrelated to the UT:- hernias, hemorrhoids and vesical calculus- change in the caliber of bowl movementsSymptoms related to complications:- cystitis- pyelonephritis- bladder calculi- micro or gross hematuria.
Signs of BPHIf the disease is advanced & has resulted in renal failure. Signs of renal failure include elevated BP, rapid pulse &respiration, uremic fetor, pericarditis & pallor of nail beds.Abdominal examination may reveal palpable kidney orflank tenderness if there is hydronephrosis orpyelonephritis.A distended bladder may be noted on palpation orpercussion.
Signs of BPHRectal examination may reveal an enlarged prostate.The distinction between right & left lobes of the prostateis usually lost in BPH.Median sulcus always present.
Laboratory FindingsUrinalysis & microscopic examination: to R/O infectionor the presence of hematuria.serum U/E & creatinine: to provide baseline informationon renal function & metabolic status.Uroflowmetry: At a volume of 125-150ml, normalindividuals have average flow rates of 12ml/sec & peakflow close to 20ml/sec.Mild 11-15 ml/secModerate > 7 and < 10 ml/secSevere < 7ml/secResidual Urine: estimated by U/S or catheterizations.Volumes >150 ml are considered significant since theyconstitute approximately one-third of normal bladdervolume.
ImagingUltrasonography: In BPH, it is most useful for measuring bladder & prostate volume as well as residual urine. Estimation of prostatic size is important because most urologists prefer to perform TURP for glands under 100g. TRUS must be used as it is more accurate.IVP: For UTI & complications of BPH
TreatmentBecause BPH is not invariably progressive, the timing ofintervention for each patient is variable.Absolute indications for treatment include severeobstructive symptoms & renal insufficiency.Relative indications include moderate symptoms ofprostatism, recurrent UTI and hematuria.Until recently, surgery was the mainstay of therapy forBPH. In the last decade or so , there has been atremendous resurgence of interest in non surgicaltherapies.
Medical TreatmentObstruction secondary to BPH occurs becauseof 2 factors:a. Dynamic component: a result ofcontraction of smooth muscles of the prostate& prostatic urethra mediated mostly byadrenergic receptors.b. Mechanical component: related to thepresence of a mass which compresses &narrows the urethral lumen.
Alpha-1 adrenergic antagonists Ideally suited for the treatment of the dynamic component of BOO because they can selectively reduce resistance along the bladder outlet without impairing detrusor contractility. Example: - Tamsulosin 0.4mg OD - Alfuzosin XL 10mg OD - Doxazosin 4mg TID Indication: Prostate size < 40 gm S/E are related to their antihypertensive effects and include dizziness and lightheadedness, Tachycardia, palpitation, tiredness, weakness & nasal congestion. Retrograde ejaculation may occur due to relaxation of the bladder neck. Alpha blockers also have beneficial S/E including lowering of serum cholesterol & triglycerides.
alpha- reductase inhibitor 5Agents that selectively blockade androgens at theprostate cellular level are termed anti-androgens. the prostate normally requires conversion oftestosterone to dihydrotestosterone by the enzyme 5alpha-reductase.Proscar is an anti-androgen that blocks this enzyme.In long term clinical trials, proscar has been shown todecrease prostatic size & improve urine flow rates &symptoms of BPH.
alpha- reductase inhibitor 5Another approach to blocking androgen uptake byprostatic cells is to prevent androgen binding to nuclearandrogen receptors ( e.g. Flutamide).There are also anti-androgens that block both LH andnuclear androgen uptake.In BPH patients, this has been demonstrated to improveflow rates & voiding symptoms.Indication: Prostate size > 40 gmS/E include impotence, decreased libido & lowers serumPSA by approximately 50% within 6 months of use.
Conventional Surgical Therapy1) TURP The principles of TURP are to remove the obstructing adenomatous portion of the prostate via the urethra. Overall morbidity: 18%. Current mortality: 0.2%. One preventable complication is TUR syndrome Immediate complications: failure to void, post op. haemorrhage, clot retention, & UTI. Late complications: impotence, incontinence, uretheral stricture and retrograde ejaculation.
Conventional Surgical TherapyTUR syndrome Because irrigating fluid under pressure is used during resection, there is a certain amount of absorption via the venous sinuses. It results in hypervolemia & hyponatremia which leads to cerebral oedema & seizures. Other S/E include visual disturbance & hyperammonemia or hemolysis. The incidence is approximately 2%. Preventive measures include suprapubic drainage during TURP, continuous flow resectoscopes & diuretics.
Conventional Surgical Therapy2) TUIP It is indicated in patients with obstructive symptoms & normal or small prostates in whom TURP is considered excessive surgery to obtain relief of symptoms.
Conventional Surgical Therapy3) Open prostatectomy Open prostatectomy can be done either Tranvesical, perineal or Retropupic prostatectomy. In recent years the suprapubic & retropubic approaches for BPH have been limited to approximately 10% of patients. Indications for suprapubic prostatectomy are a gland size greater than 100g, cystolithotomy or diverticulum excision. Most post op complications are similar to TURP, however, wound infection & thromboembolism are additional complications.
Minimally Invasive Therapy1) Laser prostatectomy advantages over TURP: technical simplicity, lack of complications & shorter hospital stay. Laser energy works by thermal destruction of tissue. disadvantages: lack of tissue availability for pathologic examination, longer postop cathitarization time, more irritative voiding complain, & high costs
Minimally Invasive Therapy2) Transurethral needle ablation High frequency radio waves to cause thermal injury to the prostate.3) High-intensity focused Ultrasound
Minimally Invasive Therapy4) Prostate stents In recent years, metallic spirals & stents have been used as permanent indwelling prostheses . These stents may be placed endoscopically & under radiologic guidance.
Minimally Invasive Therapy5) Transurethral balloon dilatation It involves the use of non compliant balloons to dilate the prostate under pressure. This pressure is maintained for 15 min. The exact mechanism is unclear.6) Thermotherapy
Incidenceprostate cancers is the 2nd most common cause of cancer deaths inUSA.Autopsy studies demonstrate that there is an increasing incidencestarting around 30% in men at 50 increasing to 75% in men at 75years.USA (blacks) 137/100,000 per yearGermany 45/100,000 per yearKuwait 6.5/100,000 per year (1998-2002)Kuwait 12.8/100,000 per year (2002-2005)China <1/100,000 per year
Etiology* Genetic predisposition, racial origin. Autosomal dominant inheritance of rarely yet highly penetrant gene.* Hormonal influences.* Dietary & environmental factors.* Infectious agents.* Sexual habits, multiple sexual partner.* Idiopathic
PathogenesisMost prostate cancers are adenocarcinomas arisingfrom prostatic acinar cells.Prostate normally atrophies between the 5th & 7th decadesof life with some atypical and hyperplastic changes.Among dysplastic changes, prostatic intraepithelialneoplasia (PIN) considered premalignant lesion found in30% of patients with prostate cancers.70% of prostate cancers arise in the peripheral zone ofthe prostate; 15-20% arise in the central zone; 10-15%arise in the transition zone.Most prostate cancers are multicentric.
Grading of Prostatic CancerGleason grading system is the mostwidely used. It’s based on glandulardifferentiation:* Gleason Score 2-4 well differentiated 5-7 moderately differentiated 8-10 poorly differentiated
Stages of Prostatic Cancer
Pattern of ProgressionLocal Metastasis: Cancers arising in close proximity are prone to spread early to the urethra, periprostatic tissues, bladder and seminal vesicles. Spread to seminal vesicles indicates ominous prognosis with 50% of patients developing distant metastasis. Rectal invasion is rare, ? Due to the tough Denonvilliers’ fascia in between. Ureteral invasion by direct extension can occur but late, usually lymph node and distant metastasis present at this time.
Pattern of ProgressionDistant Metastasis Osseous metastases is most common form of hematogenous metastases and occur in 85% of patients dying from prostate cancer Frequent sites: lumbar spines, pelvis, proximal femur, thoracic spines, ribs, sternum and skull. Extension to the axial skeleton vai the Batson’s plexus of presacral veins which communicate with the pre & periprostatic venous complex.
Clinical FindingsSymptoms Most prostate cancers are discovered because of elevated PSA or with incidental finding on rectal examination. prostate cancers rarely cause symptoms but may present with bladder outlet obstruction, acute urinary retention, hematuria or incontinenceSigns irregular firm or hard prostatic nodule during rectal examination. Median sulcus is absent
Tumor MarkersProstate Specific Antigen (PSA) – Glycoprotein secreted in the cytoplasm of the prostatic cells and function normally in liquefaction of the semen, normal value in young adult 0-4 ng/dL. – PSA elevation is proportional to the size of the transitional zone. 1g of prostate cancer will ↑PSA by 0.3 ng/dL. – PSA production by the malignant cell depends on the degree of differentiation, well diff. gland will give more – Prostate cancer with poor differentiation have normal PSA
(Tumor Markers (PSA– PSA rises by 0.04 per year in individual without cancer upper limit of PSA for - 40-49 yrs is 2.5 ng/dL - 50-59 yrs is 3.5 ng/dL - 60-69 yrs is 4.5 ng/dL - 70-79 yrs is 6.5 ng/dL.– PSA density (PSA level/prostate volume( level between 0.1-0.15 associated with 15% incidence of cancer, level above 0.15 associated with 60%.– New studies showed two types of PSA, a. complex PSA associated with cancer b. free PSA goes with BPH.
Tumor MarkersOther Tumor Markers – DNA ploidy recently reported to be useful in predicting prognosis in prostate cancer. – Low grade tumors associated with diploidy and high grade tumors with aneuploidy. – Patients with deploid tumors do well with expectant therapy while those with aneuploidy do poorly.
Prostate BiopsyDiagnosis of prostate cancers is confirmed byneedle and core biopsy.Ultrasound guided systematic sampling of theprostate in 4 quadrants provides the mostaccurate information for staging and grading thecancer.
Imaging1) Trans-rectal U/S – Can identify 60% of cancers even if non-palpable. – By allowing precise placement of biopsy needle in various quadrants, adequate sampling achieved. – More accurate than DRE at detecting extra-capsular extension. – Allow biopsy of seminal vesicles which improve staging accuracy. – Disadvantage of TRUS include the inability to look at the pelvic lymph nodes.
Imaging2) CT: used only when extensive L.N. disease is suspected and it is based only on the size of the nodes thus false +ve and –ve are common.3) MRI: not useful because of the cost and the overlap in the appearance of benign & malignant processes, but its more accurate than TRUS for staging extracapsular extension and seminal vesicle involvement.4) Bone scanning: – most common way to assess systemic metastasis. – False +ve rate is less than 2%. – Diagnosis is confirmed by plain radiographs, thin section CT or MRI and bone biopsy
Management of Localized DiseaseThe current therapy of patients with low stage disease(stage T1 and T2( is radical prostatectomy &radiotherapy to the prostate.Treatment mortality is under 1%.For patients > 75 years of age, treatment is “watchfulwaiting”
Radical ProstatectomyRetropubic approach allow simultaneous access tothe prostate and the pelvic LN, but it is often associatedwith a greater amount of blood loss from the dorsal veincomplex.Perineal approach requires separate incision forpelvic LN, associated with minimal blood loss and it ispreferred for obese individuals.5 yrs disease free survival for Stage T1 is 92% and forstage T2 is 86%
Complication of Surgical TherapyIntra-operatively: – bleeding and injury to the obturator nerve, ureter or rectumPost-operatively:– DVT & PE.– Symptomatic pelvic lymphadenocele.– Wound infections & UTIThe long term : – Incontinence and impotence.
Radiation TherapyAll modern techniques use CT scans for accurate localizationof the prostate.Generally, prostate is subjected to 6800-7000 rads and thepelvic LNs are subjected to 4500-5000 rads.Total treatment duration is 6-7 weeks.5 yrs disease free survival rate for Stage T1 is 83% and forStage T2 is 72%.PSA level is useful for assessing the response to RTRising PSA or PSA level persistently more than 30 ng/dLindicate poor response to RT.
Complication of Radiation TherapyIntestinal sequelae: – Rectal bleeding, tenesmus, mucous discharge, diarrhea, fecal incontinence, intestinal obstruction and rectal strictures.Urological sequelae: – Frequency, dysurea, cystitis, hematuria and urethral strictureEdema of the extremities and impotence Majority of these complications are minor and persist less than 6 months
Neoadjuvant Hormonal TherapyLHRH agonists and antiandrogensStudies showed that hormonal therapy will not down-stage the cancer in patient with stage T3, however, inpatient with stage T2 the hormonal therapy will reducethe size and the incidence of positive margins
Manegment of patients with Margin-Positive Disease / Extracapsular Extension 60% of positive margins are at postlateral areas, 30% are posterior In stage T1 cancers, 40% of positive margins are anterior. Adjuvant radiation in these patients controls local recurrence but whether it reduces systemic recurrences is unclear. Adjuvant hormones & more recently intermittent adjuvant hormones appears to reduce PSA.
Management of locally extensive diseaseStage T3,T4 or C prostate cancer are advised to have radiation therapy. Surgery is not recommended.
Management of distant metastatic disease The standard treatment is androgen ablation therapy to lower serum testosterone. Methods of lowering testosterone include: (1) Bilateral subcapsular orchiectomy (2) LHRH agonist By downregulating pituitary LH production. (3) Estrogen e.g. diethylstilbestrol which create negative feedback to the pituitary. S/E include impotence, breast tenderness, & hot flushes
Prognostic Factors in Ca prostateStage 1&2 65 - 98% 5-yrs survival rate 3 60% 5-yrs survival rate 4 30% 5yrs survival rateGradeTumor Volume– < 0.5 ml → no capsular penetration– < 4 ml → less SV invasion & LN metastasis
NIH Consensus Conference on Prostatitis ((1995 Category I: Acute Bacterial Prostatitis = Acute infection of the prostate gland Category II: Chronic Bacterial Prostatitis = Recurrent infection of the prostate. Category III: Chronic Abacterial Prostatitis/CPPS: No demonstrable infection – Category IIIA: Inflammatory CPPS = WBCs in semen/EPS/VB3 – Category IIIB: Noninflammatory CPPS = No WBCs in semen/EPS/VB3 Category IV: Asymptomatic Inflammatory Prostatitis
Acute bacterial prostatitis Etiology• Is mainly caused by aerobic gram negative rods. (E-coli and Pseudomonas aerigenosa(• Common in people with “uptight personality” The possible routes of infection include:1( Ascent from the urethra.2( Reflux of infected urine into prostatic ducts that empty into the posterior urethra.3( Direct extension (lymphatogenous spread(: from the rectum. Ascending infection and reflux of infected urine into prostatic ducts are probably the most common routes of prostatic infection.
Leukocytic infiltration of stroma and glandular lumina during acute bacterial prostatitis
Acute bacterial prostatitisClinical FindingsA. Symptoms Acute febrile illness characterized by chills, low back and perineal pain, urinary urgency and frequency, nocturia, dysuria, and varying degrees of bladder outlet obstruction. Both myalgia and arthralgia are common.B. Signs Moderate or high grade fever. Rectal palpation: tender, swollen, indurated, boggy and warm to be touched. Since acute cystitis often accompanies acute bacterial prostatitis, the urine may be cloudy. Initial, terminal, or even total gross hematuria may be observed occasionally.
Acute bacterial prostatitisC. Laboratory Findings Voided urine usually shows significant pyuria, microscopic hematuria, and bacilluria. The prostatic expressate is purulent and yields the infecting pathogen in heavy growth on culture plates. Because massage of an acutely infected prostate is painful for the patient and can produce bactermia, prostatic massage is generally contraindicated. Except under anaesthesia and antibiotic cover.D. Instrumental ExaminationTransurethral instrumentation should be avoided during the acute stage of bacterial prostatitis.
Acute bacterial prostatitisComplications• Acute urinary retention.• Acute bacterial cystitis.• Acute pyelonephritis.• Unilateral or bilateral acute bacterial epididymitis.• bactermia with possible septic shock.1( Rarely meningitis, spread of infection via Batesan’s veinous plexus2( Prostate abcess
Acute bacterial prostatitisProstatic Abscess More recently, about 70% of prostatic abscesses have been caused by coliform bacteria, mostly E-coli. Although the pathogenesis remains unclear, most cases of prostatic abscesses are probably complications of acute bacterial prostatitis. The signs and symptoms of prostatic abscess can mimic those of bacterial prostatitis; Fluctuation is an important diagnostic clue. Once the diagnosis of prostatic abscess is made preferred treatment consists of surgical drainage combined with appropriate antimicrobial therapy. With proper diagnosis and therapy, the overall prognosis is good.
Acute bacterial prostatitisTreatment• Fluoroquinolone• Ciprofloxacin• Trimethoprim-sulfamethoxazole• Alternatively, initial therapy with Gentamicin or Amikacin or Tobraminycin, 3-5 mg/kg/d divided into 3 intravenous or intramuscular doses, plus ampicillen, 2 g intravenously every 6 hours, is recommended until the results of culture and sensitivity tests are known. Transurethral instrumentation is contraindicated during acute infection.
Acute bacterial prostatitisPrognosis• Unless the patient develops septicemia and septic shock, the prognosis generally is good with prompt and appropriate therapy.
Chronic Bacterial ProstatitisEtiology:Is a non acute infection of the prostate caused by one ormore specific bacteria.The possible routes of infection are the samein acute and chronic bacterial prostatitis.
Chronic Bacterial ProstatitisClinical FindingsA. Symptoms• Asymptomatic; most have varying degrees of irritative voiding dysfunction and low back or perineal pain and discomfort.• Occasionally, myalgia and arthralgia accompany the other symptoms.B. Signs• On rectal examination, the prostate may feel normal (rarely(, boggy, or very tender focally indurated.• Crepitation may be felt when large prostatic stones are present or if infection is due to gas forming organisms commenly seen in diabetic patients.• Secondary epididymitis sometimes is associated with chronic bacterial prostatitis.
Chronic Bacterial ProstatitisC. Laboratory findings• The Prostatic secretions obtained by prostatic massage typically show excessive numbers of inflammatory cells.• The presence of large numbers of lipid laden macrophages in prostatic fluid correlates particularly well with the presence of prostatic inflammation.D. X-Ray findings• normal unless there are complications (eg, prostatic calculi, prostatic enlargement, urethral stricture, renal infection(.E. Instrumental Examination• Cystoscopy and urethroscopy may reveal normal findings or erythema and edema of the prostatic urethra, with or without inflammatory polyps.
Chronic Bacterial ProstatitisComplications• Relapsing recurrent UTI.• Ascending bacterial infection of the upper urinary tract and bacterial epididymitis.• Bladder outlet obstruction.
Chronic Bacterial ProstatitisTreatmentGeneral Measures Symptoms can be relieved by the liberal use of hot sits baths. Irritative voiding discomfort and pain often respond to the use of anti-inflammatory agents ( eg, indomethacin, ibuprofen( and anticholinergic drugs.
Chronic Bacterial ProstatitisTreatmentSurgical Measures Radical prostatovesiculectomy is curative; unfortunately, the sequels of this operation ( sexual impotence and possible urinary incontinence( seldom make this a desirable choice. Transurethral prostatectomy can be curative provided all infective stones and tissues are successfully removed; unfortunately, this may be difficult to achieve, especially since the peripheral zone of the prostate usually contains the most foci of the infection.
Chronic Bacterial ProstatitisPrognosis Chronic bacterial prostatitis is difficult to cure permanently, but its symptoms and tendency to cause recurrent UTIs generally can be controlled by suppressive antimicrobial therapy.
Chronic Abacterial ProstatitisEtiology Is the most common of the prostatitis syndromes; its cause is unknown. There has been much speculations but little proof that chlamydial infection is responsible for many cases of apparent nonbacterial prostatitis. Like wise, there is little evidence that infection due to U urealyticum plays an important role in this prostatitis. Some researchers believe that non bacterial prostatitis is an autoimmune disease of the prostate.
Chronic Abacterial ProstatitisPathogenesis and Pathology The cause of the pathogenesis of nonbacterial prostatitis are unknown. The histopathologic findings are non specific and resemble those seen in chronic bacterial prostatitis.
Chronic Abacterial ProstatitisClinical Findings The signs and symptoms are similar except that documented UTI almost never occurs in former.Complications Non bacterial prostatitis causes no known organic complications
Chronic Abacterial ProstatitisTreatment• Antimicrobial therapy should be tried for at least 4 weeks.• Therapy must be directed toward control of the symptoms.• Symptomatic flare ups often respond to anti-inflammatory agents.• Like most patients with prostatodynia, most patients with non bacterial prostatitis respond favorably to therapy using an alpha blocking agent.• Most authorities agree that prostatectomy is not indicated.