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Professional land marks
-
Use of Holmium Laser in Urology
- Endourology
- Pediatric urology
- Reconstructive urology
- Uro Oncology
- Andrology
- Urogynecology (Female urology)
- Neurogenic bladder
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Urogenital problems in elderly
Learning Objectives
With the advancing age and subsequent to that the changes in the Urinary Tract cause
many problems in Elderly males. These problems in this module have been categorized
under the following heads:
Benign hyperplasia of Prostate (BPH)
Carcinoma Prostate
Urinary Tract Infections
Urinary Incontinence
Benign hyperplasia of Prostate (BPH)
Incidence: At the age of 45 years: 50%of men will have histological evidence of
BPH. Clinical evidence of BPH may be found in 14% of men between 40 to 49 years
and 40%of men between 70 to 79 years.
Pathology: Hyperplasia of Transitional zone of prostate which increases in size
to cause obstruction and/or irritation of bladder outlet. Initially bladder muscle
hypertrophies to push out urine, but eventually fails and results in urinary retention.
Clinical Presentation:
Enlarged Prostate may present as-
(a) Irritative urinary symptoms
- Frequency
- Dysuria
- Urgency i.e. difficulty in postponing urination.
- Nocturia
- Precipitancy i.e. Failure to control the outburst of urine.
(b) Obstructive symptoms
- Hesitancy i.e. Difficulty in starting the act of urination.
- Poor stream, broken stream
- Need to strain to pass urine
- Sense of incomplete evacuation of urine
- Prolonged urination
(c) Complications of BPH
- Retention of urine
- Overflow incontinence
- Hematuria
- Urinary tract infection
- Compromised renal function
Approach to a patient with suspected BPH
(a) History : Exclude other causes of
obstructed urination-
- Obvious neurogenic bladder
- Stricture urethra, in which the flow of urine improves on straining
- Vesical calculus, in which there is a very good flow at times but it suddenly stops
and results in severe pain.
- Carcinoma prostate, history of low backache painful skeletal metastasis
(b) Examination :
- Palpation of abdomen for distended bladder, hydronephrotic kidneys, any other mass.
- Digital rectal examination of prostate, which reveals smooth surface, Firm consistency
and absence of any nodularity.
(c) Investigations:
- Microscopic analysis of urine for pyuria and if indicated culture
- Ultrasonogram to evaluate kidneys, urinary bladder, size and Echo texture of prostate,
residual urine after voiding.
- Uroflometry.If available, this is a simple test to ascertain the degree. The degree
of obstruction caused by prostatic enlargement. The Patient is asked to pass urine
in computerized container and the rate of flow of urine is measured. The following
are the Indications for active intervention:
1. Peak flow rate less than 15 ml per second
2. Average flow rate less than 10 ml per second.
- Transrectal ultrasound may be done to further evaluate the echo texture of prostate.
A majority of malignant lesions would appear as hypo echoic areas.
Treatment of BPH
After adequate evaluation, one can generally classify patients of BPH into three
categories:
-
Primarily irritative BPh which includes patients with adequate uroflowrates
and insignificant post void residual urine. These patients can be managed successfully
by oral medication.
-
Borderline obstruction, in which uroflometry reveals peak flowrate is around
10 ml per second and post void residual urine is between 50 to 100 ml. These Patients
may be put on medical management with an understanding that They may require to
under go surgical intervention at a later date and need to be followed very closely.
- Severe obstruction, as evident on uroflometry, episodes of retention, sonographic
evidence of bilateral hydronephrosis.
Size of prostate is not related to severity of the symptoms.
Treatment options in BPH :
(a) Oral medication
- Alpha-adrenergic antagonists (e.g., terazosin). Bladder neck has
circular smooth muscle fibers which constitute internal or involuntary sphincter.
These are innervated by adrenergic fibers rich in alpha-receptors. Drugs blocking
these receptors are expected to increase the outflow of urine from bladder by relaxing
the smooth muscle fibers of bladder neck. A variety of alpha adrenergic antagonists
have been studied. The selective alpha one blockers which spare alpha two receptors
result in much lower incidence of side effects like postural hypotension, nasal
congestion and light headedness. Terazosin demonstrates some of these side effects
and therefore concomitant anti hypertensive treatment may need to be revised. However
newer agents like Tamsulosin and Alfuzosin are devoid of these side effects. The
once daily recommended oral dose of Tamsulosin is 0.4 mg and that of Alfuzosin is
10mg.
- 5 alpha reductase inhibitors: 5 alpha reductase is the enzyme which
is necessary for conversion of Testosterone molecule to it's active metabolite Diydrotestosterone
(DHT). Depriving BPH tissue of DHT support causes reduction in size of the prostate
gland thereby improving urinary flow rates. It takes around 12 weeks of regular
treatment before any sonographic evidence of reduction in the size of the prostate
can be demonstrated. These drugs are well tolerated and have been shown to be safe
over long periods of followup.
- Finasteride in the oral once daily dose of 5 mg has been studied
for more than 10 years with improvements in flowrates without significant side effects.
- Dutasteride is a newer molecule which has been shown to inhibit
both isoforms of the enzyme and hence is more potent as well as faster acting. Dutasteride
has been recommended in the dose of 0.5mg per day a single oral dose.
(b) Minimally invasive options
- Prostatic stent : A prostatic stent is a self-retaining expandable
flexi metallic device which can be positioned in the prostatic urethra to keep it
open. It is passed under cystoscopic vision in operating room under mild sedation
and local anaesthesia. Advantages of this procedure include avoidance of spinal
or general anaesthesia, short operating time, low risk of water intoxication. Thus
it can be useful in cases of obstructive BPH who may not be medically fit enough
to undergo anesthesia. Disadvantages of this procedure include poor tolerance of
the stent by the patient, as it may be associated with dysuria, terminal hematuria,
and frequent urination. Migration of stent is also a possibility. Other problems
in Indian scenario are prohibitive cost (Rs.20, 000 per stent) and limited availability.
Overall it is a poor alternative to an indwelling catheter.
- Transurethral needle ablation of prostate (TUNA) : Along a urethral
catheter, metallic needles are inserted into prostate and radio frequency energy
is delivered to the adenoma. This causes rise in the temperature of the localized
area which then degenerates and shrinks. Multiple sites along the prostatic urethra
are treated in this manner expecting to overcome urethral obstruction. Advantages
include all those of avoidance of major anesthesia. Disadvantages include unpredictable
long-term results and multiple sessions of treatment.
(c) Surgical options
- Trans urethral resection of prostate (TURP): This is the gold standard
of surgical treatment of prostate. Indications: Obstruction causing retention of
urine retention.
Advantages:
- resection of adenoma can be done through urethral passage;
- resected specimen is available for histopathological examination.3. mechanical clearing
of urinary passage is achieved.
Disadvantages:
- Technically demanding procedure.
- Steep learning curve.
- Morbidity associated with the procedure, e.g. complications.
Complications of TURP:
(i) Intra operative:
- Primary hemorrhage needing abandoning of procedure.
- Water intoxication, causing cerebral edema and death. In experienced hands using
latest equipment and irrigation fluids the risk of this serious complication is
around 0.5%. However, patients with Compromised renal and cardiac function run a
higher chance of this syndrome called TURP syndrome.
(ii) Immediate post operative:
- Reactionary hemorrhage. This occurs after approximately7days of surgery .It may
be treated by conservative means and transfusions if required. Occasionally cystoscopic
evacuation of clots may be required.
- Retention of urine. It may occur due to presence if clots, retained prostates chips
or inadequate operation.
- Infection. Presents as dysuria, fever, epididymo orchitis , secondary hemorrhage
- Incontinence of urine. Incidence 0.5%. If external sphincter is divided by mistake
Trans urethral laser prostatectomy. Endoscopic procedure done using Holmium laser
contact fiber.
Advantages:
- Very minimal blood loss,
- Short hospital stay,
- advisable in high-risk patients.
Disadvantages:
- High cost of equipment,
- Long operative time,
- Results yet to be standardized.
Laser Prostatectomy
It has been over two decades that various forms of laser generators have been used
to ablate the obstructing prostatic adenoma. However in last 5 years two such modalities
have gained stability while others have largely failed to survive.
a. Holmium Laser enucleation of Prostate (HOLEP). This involves
high power (100 watts) laser energy generated using Holmium Yag medium to be delivered
through an end firing contact probe. By moving this probe all around the adenoma
it can be enucleated and dropped into the urinary bladder, where it could be morcellated
and sucked out piecemeal. The probe works like the finger of a surgeon performing
open prostatectomy.
Advantages:
- Almost blood less surgery, minimal blood loss
- Excellent vision through the telescope as there is no bleeding
- Normal saline may be used as irrigant
- Short catheter period; less than 24 hours
- Quick recovery
- Early return to work
- Very low incidence of stricture urethra and reactionary haemorrhage
- Advisable in patients with coagulation disorder
Disadvantages:
- High cost of equipment
- Recurring cost of fibre
- Steep learning curve
b. Photoselective Vaporisation of Prostrate (PVP) Using KTP laser
This involves vaporization of prostrate tissue using a side firing laser beam generated
by KTP laser. Since the laser frequency happens to fall in the green light zone,
it is selectively absorbed by the red color. Therefore it coagulates all blood vessels
and bleeding surfaces. It vaporizes the obstructing adenoma and therefore is effective
in making the patient catheter free quickly. However it is too slow a process and
a large residual adenoma still says behind.
Advantages:
- It makes a patient rapidly catheter free with minimum morbidity
- It can be done under sedation and local anesthesia in very sick patients
Disadvantages:
- Cost is much higher than holmium laser as the fibre is not reusable
- Tissue is not available for histopathology
- Should not be performed on infected prostate and residual prostate tissue may continue
to produce symptoms.
Trans urethral electrovaporisation of prostate
In order to overcome the disadvantage of bleeding in TURP, the loop electrode has
been modified into a ceramic roller electrode called Vapotrode. contact of this
electrode on the prostatic surface causes charring and dessication of tissues in
addition to vaporization of superficial layers. If done properly, there is minimal
blood loss and good vision is preserved throughout the procedure.
Advantages:
- Minimal blood loss.
- Less hospital stay
- Less risk of water intoxication.
Disadvantages:
- No material available for histopathology.
- Depth of tissue charing and thermal damage may not be always controllable leading
to mishaps e.g. damage to sphincter.
Open prostatectomy
Indications:
- Very large gland i.e. more than 120 grams.
- in patients with high risk of water intoxication e.g. poor cardiac ejection fraction,
chronic renal failure
Techniques:
- Trans vesical (Freyer‘s)
- Retropubic (Millin‘s)
Advantages: May be done where sophisticated equipment is not available.
Disadvantages:
- Prolonged hospital stay.
- Blood loss may necessitate transfusion.
Carcinoma Prostate
Incidence: In autopsy series histological evidence of foci of Adenocarcinoma
may be found up to 67% of men above the age of 80 years
Pathology: Malignant change involves the peripheral zone of prostate which is fortunately
easily felt on digital rectal examination. Histologically, 95%of these are Adenocarcinoma.Other
varieties include Transitional cell carcinoma, Sarcoma and Melanoma. Adenocarcinoma
spreads along the neurovascular bundles on either side and settles in pelvic lymph
nodes, i.e. obturator, internal iliac, external iliac and para aortic
Hematogenous metastasis occurs into bones e.g. lumbar spine, pelvic bones, femur
humerus, ribs etc. Hepatic, pulmonary and intra cranial metastasis signify grave
prognosis.
Clinical presentation
- Incidental: Upon routine histological examination of prostatectomy specimen, foci
of Adenocarcinoma may be found.
- Asymptomatic i.e. picked up on routine screening.
- Presenting as lower urinary symptoms and picked up on digital rectal examination
- Symptomatic due to distant metastasis e.g. painful skeletal deposits of tumor
Diagnosis
Digital rectal examination (DRE) : A good clinician should be able
to pickup and differentiate nodular hard prostate from smooth, firm benign prostate.
Sensitivity of DRE to pickup Ca prostate is around 80%i.e.only about 20% of tumors
would be missed on this simple examination. However the specificity of DRE is only
50% i.e. 50% of the nodules thus picked up would turn out to be lesions other than
malignancy. Deseases mimicking malignancy include granulomatous prostatitis, prostatic
calcifications and occasionally calculus impacted in prostatic urethra. Abdominal
Ultrasound (USG): this is a useful investigation to study the gross morphology of
prostate. In addition, it gives information regarding status of kidneys, any lymph
nodes and residual urine after voiding.
Trans Rectal Ultrasound (TRUS): Finer details of echo texture of
prostate can be readily made out by TRUS. Around 40% of the malignant foci are hypoechoic,
30% are hyper echoic and rest are isoechoic. Pericapsular invasion by the tumor
is important in planning the treatment and is best-identified by TRUS.
Prostate Specific Antigen (PSA): It is a protein normally present
in prostate cells. Serum levels of PSA are related to prostatic volume. In adenocarcinoma
prostate, the level of PSA is raised and corresponds to the tumor load. However,
PSA levels may also be found high in prostatitis and after instrumentation of urinary
tract. Even DRE is expected to raise the serumPSA levels transiently. On the other
hand PSA values may be within normal range in the presence of small foci of adenocarcinoma.
Therefore, PSA is not to be used for the primary diagnosis of malignancy. It is
used as a screening modality in addition to DRE and TRUS. The main role of PSA is
in following already diagnosed case of adenocarcinoma prostate and assessing the
response to treatment or relapse.
Trans rectal biopsy of prostate: Trucut Needle biopsy of prostate
is the investigation to clinch the diagnosis of adenocarcinoma prostate. If a nodule
is felt on DRE then digitally guided biopsy may be performed. Sometimes TRUS guided
biopsy may be required if the nodule is better seen on TRUS than felt by the finger.
Histological examination of biopsy specimen reveals tumor grade, a measure of tumor
aggressiveness. A common grading system adopted is called Gleason scoring.
Staging
Once the diagnosis of Ca prostate (CaP) is established, staging is required for
planning further treatment. Following is usual plan of staging investigations: TRUS
gives information regarding local spread and differentiates extra capsular disease
from localized intra prostatic disease.
Contrast enhanced CT scan of abdomen would identify intra abdominal lymphadenopathy
and any metastasis in liver. However it is not a sensitive modality to pickup small
pelvic lymph nodes.
X-ray chest PA view should be done in all cases to look for any pulmonary metastasis.
Skeletal survey should be done with radionucleide labelled MDP bone scan. Hot spots
signify areas of increased vascularity and suggest metastatic deposits. However
inflammatory lesions would also appear, as hotspots and conventional radiography
of the concerned region must be done in case of doubt. Metastatic deposits appear
as osteoblastic (osteo sclerotic) lesions on conventional X ray studies.
TNM Staging system of CaP
Primary tumor
TX minimum requirements to assess the primary tumor cannot be met.
T0 No tumor present
T1 No palpable tumor
T2a Palpable tumor less than 1.5 cm
T2b Palpable tumor more than 1.5 cm
T3 Palpable tumor extending into or beyond the capsule
T4 Tumor involving surrounding pelvic structures.
Nodal involvement
Nx Minimum requirements to assess the pelvic lymph nodes cannot be met.
N0 No involvement of regional lymph nodes
N1 Involvement of single homolateral lymph node.
N2 Involvement of bilateral contra lateral or multiple regional lymphnodes.
N3 pelvic lymph node mass fixed to parieties
Distant metastasis
Mx Minimum requirements to assess distant metastasis cannot be met.
M0 No distant metastasis.
M1 Distant metastasis present.
At the time of diagnosis upto40% of cases have distant metastasis
Treatment
A. Localised CaP
- Observation : In elderly men with localized CaP, the progression
may be so slow that they are hardly inconvenienced by the disease. These men may
be put on a surveillance regime and periodic PSA, DRE and TRUS may be al that is
needed. Many of these people would die due to unrelated illness with their disease
rather than die of it.
- Radical Prostatectomy : The treatment of choice in otherwise healthy
relatively young men with localised CaP. However upon histological examination of
excised specimen 30 to40% may show extra prostatic spread missed on preoperative
staging procedures. Complications of this procedure include incontinence in almost
all patients in immediate postoperative period which improves in about85 to 90 %
over6month period. Another significant complication is impotence which is permanent
and occurs in up to 90% of cases. Operative mortality in most series is around 1%.
- Radiotherapy :Locally advanced disease may be treated with radiotherapy.6000
to7000 rads is administered spread over 6to7weeks duration. The field of radiotherapy
includes prostate and surrounding pelvic tissues along with lymph nodes in an inverted
Y field. Good tumor control is achieved in most cases but needle biopsy done several
years later still shows viable tumor cells in most cases. Side effects of radiotherapy
include radiation cystitis, enteritis and proctitis. In order to avoid these side
effects, interstitial radiotherapy using surgically implanted radioactive iodine
seeds has been given.
Advanced CaP
1.Endocrine manipulation:Prostatic epithelial cells demonstrate apoptosis i.e. spontaneous
cell death, in the absence of androgens. The aim of endocrine manipulation is to
cut off the supply of testosterone to prostatic cells. This can be done
by -
- Surgical casteration. Bilateral orchidectomy may be performed under
local anesthesia as a day care procedure. Immediate fall of serum testosterone levels
is achieved to negligible levels. Other benefits include low non-recurring cost
without the problem of patient compliance.
- Medical manipulation.
- Anti androgens e.g. Futamide is a non-steroidal competitive inhibitor of testosterone
at the target cell. It is given in a dose of 100mg three times a day.
- LHRH analogues e.g.Leuprolide is used to prevent the production of testosterone
from Leydig cells of testes by suppressing the release of LH from pituitary gland
It is available is a depot preparation administered every three weeks subcutaneously.
The above two compounds can be used in combination as Complete Androgen Blockage
as an alternative to surgical casteration. High cost of treatment and poor patient
compliance makes medical treatment less popular than orchidectomy in India. Results
of hormonal manipulation
Initially there is a good response to treatment but after a variable period, which
depends upon the tumor grade and load, there is a flare of disease and is called
‘escaped desease ‘or‘hormone refractory disease‘. Not much can be done at this stage.
Second line drugs like Ketoconazole may be tried in the dose of 400mg three times
a day. Painful bony metastasis may require palliative radiotherapy. Several chemotherapeutic
agents have been used with very little benefit. Those which have been tried include
Cyclophosphamide, DTIC, Estramustine and Streptozocin.
Urinary Tract Infections
Incidence of bacteriuria (urine culture positive for bacteria) increases with age.
Above 65 years of age, 20%females and 10% males will have bacteriuria. Bacteriology:
The most common organism isolated are E.Coli, Klebsiella and Proteus. Less commonly
isolated organism include Enterococci, coagulase negative Staphylococci and group‘B‘
Streptococci. In young females, vaginal flora consists of lactobacilli which prohibit
the growth of uropathogens. In postmenopausal state, colonization if vagina by gram-negative
uropathogens increases on slightest opportunity. These then invade the vulnerable
urothelial lining of urethra and bladder. In males, increasing prostate size and
residual urine may be triggering factors for initiation and perpetuation of infection.
Co-morbid conditions predisposing to urinary infections:
1. Diabetes Mellitus
2. Neuropathic bladder
3. Poor local hygiene e.g. unclean perineum, use of diapers.
4. Instrumentation of urinary tract.
Symptoms of urinary tract infection (UTI)
- Lower tract symptoms:
(i) Dysuria
(ii) Frequency
(iii) Urgency
(iv) Hematuria
- Systemic symptoms:
(i) Fever (ii) Confusion
(iii) Anorexia
(iv) Vomiting
(v) Pain abdomen
Diagnosis
- Urine analysis:Microscopic examination for pyuria. Special care
must be taken to obtain a clean catch midstream sample.
- Bacteriological culture:To diagnose UTI, 10^5 colony forming units
(CFU) per ml of unspun urine must be demonstrated. However in a frank symptomatic
patient even 10^3CFUper ml may be sufficient to diagnose UTI.
- Ultrasound of abdomen must be performed to screen the urinary organs to exclude
any morphological problem, calculus disease, post void residual urine.
Treatment
Appropriate antimicrobial as per the culture report may be given. Special problems
encountered in elderly include:
- Low tolerance to medication
- Poor compliance
- Higher incidence of compromised renal function needing appropriate dose adjustment.
- Interactions with concomitant drug therapy
- Controversies regarding asymptomatic bacteriuria.
Urinary Incontinence
Incontinence may be defined as an involuntary loss of urine through intact urinary
tract.
Prevalence of incontinence in population above 65 years of age is about 12%in females
and 7%in males.
Types of incontinence
(a) Urge incontinence :It is defined as uncontrollable desire to
pass urine. It occurs in cases of hyperactive detrussor (bladder muscle). The
various causes include
- Early prostatism
- UTI
- Senile strophic urethro trigonitis
- Detrussor hyper reflexia as in various intra cranial lesions e.g. Parkinsonism,
CVA, Senile dementia, acute confusional states etc.
(b) Stress incontinence : Genuine stress incontinence occurs in
females due to sagging of perineal floor muscles and consequent lowering of bladder
neck Some degree of stress incontinence is usual in healthy adult women But if it
is severe enough to interfere in day to day activity then it requires to be treated
surgically.
(3) Overflow incontinence occurs when the bladder is unable to empty and is persistently
filled with urine to its capacity. Any further production of urine would overflow
without notice. Usually it is associated with severe back pressure changes in the
kidneys in the form of hydro urethro nephrosis. Renal function may be compromised
in long standing cases. Various causes of overflow incontinence include:
- BPH
- Ca Prostate
- Stricture urethra
- Vesical calculus
- Hypotonic detrussor (e.g. due to spinal injury, autonomic neuropathy, DM etc.)
Management of incontinence
Investigations:
- urine microscopic and culture to exclude infection.
- USG to evaluate full bladder volume and residual urine
- Detailed uro dynamic evaluation.
Treatment:
(1) Appropriate treatment of infection with anti microbial.
(2) Bladder sedatives:
- Anticholinergic agents are used to reduce the frequency and strength
of Detrusor muscle contractions. The latest of these is Tolterodine which is highly
selective anticholinergic agency specific to detrusor muscle and has very little
effect on the muscuraine receptors in the salivary glands. Therefore the incidence
of dry mouth is much less with this agent as compared to earlier agents like oxybutinine.
Tolterodine is also available as a sustained release formulation where by the oral
dosage frequency has been reduced to convenient once a day. While oxybutine has
been recommended as 2.5 or 5 mg two to three times a day, Tolterodine is recommended
as 2 mg twice a day or as sustained release formulation 4 mg once a day. There may
be a feeling of abdominal distension and constipation as a side effect of these
medications.
- Smooth muscle relaxants : Flavoxate hydrochloride has a specific
effect on the smooth muscle of urinary bladder and causes reduction in the force
of contraction in addition to its anticholinergic action. This is used as 100 mg
three times a day and is used as a useful adjunct in acute cystitis with severe
urgency. It is a well tolerated molecule with few side effects, which include nausea,
vomiting dry mouth, nervousness, vertigo, headache, blurred vision and tachycardia.
- Antidepressants:
(i) Impramine :Apart from elevating the mood in elderly it causes
reduction in bladder pressure by relaxing the detrusor muscle. Also the adrenergic
activity helps to maintain the sphincter tone thus reducing the episodes or urge
precipitancy. However the side effects include increase blood pressure, dry mouth,
tachcardia, palpitation, constipation, impotence, difficulty in accommodation of
vision and retention or urine. The dose recommended is 25 mg three times a day.
It should be cautiously used in cases of coronary heart disease, CVA and history
of convulsions.
(ii) Duloxetine : This is another antidepressant which acts by
inhibiting sertonin receptors. It acts on Onuf's nucleus situated in the sacral
spinal cord in addition to having intracranial action. Elderly patients with stress
incontinence may be helped by this drug. The usual dose is 20 t0 30 mg twice a day.
Side effects include dryness of mouth, insomnia, fatigue, constipation, dizziness
and sweating. It should be used very cautiously in patients with renal failure or
chronic liver disease. There is also a risk of precipitating narrow angle glaucoma.
(3) Collection Appliances e.g. Pads, Catheters, etc.
(4) Intermittent self-catheterization
Further Reading
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- Kozlowski IN, JT. Carcinoma of the prostate. In: Gillenwater JY, Grayhack JT, Howards
SS, Duckett JW (eds). Adult and Ped Urol, 2nd ed. St Louis: Mosby Year Books 1991;1277-393.
- Epstein J, Walsh PC, Carmichael M, Brendler CB. Pathologic and clinical findings
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- Veterans Administration Co-operative Urological Research Group. Treatment and survival
of patients with cancer of the prostate. Surg Gynecol Obstet 1967;124:1011-7.
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J Steroid Biochem 1985;23:833-841.
- Taylor CD, Elson P, Trump DZ. Importance of continued testicular suppression in
hormone refractory prostate cancer. J Clin Oncol 1993;137:1-10.
- Boscia JA, Kaye D. Asymptomatic bacteruria in the elderly. Infect Dis Clin North
Am 1994;1:893-905.
- Childs SJ, Egan RJ. Bacteruria and urinary infections in the elderly. Urol Clin
North Am 1996;23(1):43-54.
- Schaeffer AJ. Infections and inflammations of the genitourinary tract. In: Walsh
PC, Retik AB, Vaughan ED Jr, Wein AJ (eds). Campbell’s Urology, 7th ed. Philadelphia:
WB Saunders 1998;601-3.
- Debruyne F, Barkin J, van Eryzz P, et al. Efficacy and safety of long-term treatment
with the dual 5 alpha-reductase inhibitor dutasteride in men with symptomatic benign
prostatic hyperplasia. Eur Urol. 2004 Oct;46(4):488-94
- Clans G Rehrborm. The Clinical Benefits of Dutasteride. Treatment for LUTS and BPH.
Reviews in Urology, vol 6, suppl 9
- Landis JR, Kaplan S, Swift S, Veisi E. Effiecacy of antimuscarinic therapy for overactive
bladder with varying degree of incontinence severity. J Urol 2004; 191:752-756.
- Norton PA, Zinner NR, Yalcin I et al. duloxetine versus placebo for the treatment
of women with stress urinary incontinence. Am J Obstretric Gynecol 2002; 187: 40-8.
- Wong DT, Bymastu FP, Mayle DA, et al. A new inhibitor of serotonin and norepinephrine
uptake. Neuropsychopharmacology 1993;8:23-33.
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