64 000 per yr in UK
Irreversible
Consider alternatives
Complications
EARLY
-Bleeding 3.6% (Philp)
-Bruising
-Wound D/C 1% (Philp)
-Wound infection 4%(Randall)
-Haematoma 1%
-Failure 0.36 (Philp) - 0.6% (early recanalisation, duplication, wrong structure)
LATE
-Chronic scrotal pain 13-16%
16% 1 yr, 13% 10 yrs
severe in 5%
(Stepping Hill: 460 pts in each group)
NB. Some evidence less if testicular end left open: (6% vs 2%, Moss, 1992, Contraception)
-Sperm granuloma 15-40%
-Non motile sperm (2-30%) 'special clearance' after 7mths/25 ejaculates <10000 NMS/ml
2% in Philp series from Oxford. 150 pts given special clearance, but only 51 followed up. 50/51 azoospermic, but no pregnancies attributable to vasectomy failure
-Failure 1/2500 Philp (recanalisation)
-CaP, testicular ca, IHD...no evidence in large trials
Need 2 clear SA before using as sole form of contraception at 12 &14 weeks OR 1 at 16 weeks
45% do not submit any samples (Chwala Urology 2004)
20 ejaculations probably needed (this is recommended in third world)
93% azoospermic by 20 weeks
SA Technique
Masturbation into a non-toxic container after 48hr abstinence; maintained at body temperature
Examine within 4hr
Assess within 1hr for persistent non-motile sperms
Germ cells, epithelial cells & leucocytes often seen in semen up to 16 weeks after vasectomy
Store between 20 & 40 °C and await liquefaction (within 4 hours)
Count 10 µl in a 20 µm chamber to allow sperm movement
Phase-contrast microscopy
If no sperms seen, centrifuge @ 3000g for 15 min and re-suspend in 100 µl autologous seminal plasma
Sivardeen, Annals RCS Eng 2001
75% of UK urologists send vas for histology.
95% request at least 2 semen samples.
Philp BJU 1984, from Oxford
16000 pts
1970-1983
Most diathermy, no fascial interposition
Vas not routinely sent
Semen analysis 4 and 41/2 months
Special clearance given if 2 consecutive semen analyses of under 10000 semen/ml, non motile, and >7 months post vasectomy. 2.2% in series
800 men sent questionnaire: 67% response rate
7.7% sought post op advice for pain
3.6% for bleeding
1% scrotal haematoma
Early failure 0.43%
12/69: vas not tied
57/69: early recanalisations (0.36%), 0.51% following ligation, and 0.28% after diathermy
6 late recanalisations (1 in 2000)
Failures lower in more experienced surgeons
Davies, Cranston et al, BJUI 1990, Oxford
6000pts
1980-85
2.5% men given special clearance (151)
Criteria as above
Follow up semen analysis after 3 yrs in 50
49/50 azoospermic, no attributable pregnancies
Vasectomy Reversal
1-3 per 1000 vasectomised men will request reversal (Swingl and Guess)
Testic biopsies show normal spermatogenesis up to 10yrs post vasectomy
NB Rx post vasectomy epididymal pain
Good prognostic indicators
· <8yrs since vasectomy
· Partner <40yo
· Fluid from epididymal end at time of reversal
Vasovasostomy/epididymovasostomy
2 layers
Use magnification - microscope a little better
Alternatives - ICSI, DI, Adoption
Tuesday, June 30, 2009
Friday, June 19, 2009
Physiology of Sperm production and Erection
Spermatogenesis
• germinal cells divide to become spermatogonia which divide to become spermatocytes
• Type A spermatocytes undergo meiosis to become secondary spermatocytes
• spermatocytes divide and give rise to mature cell lines (spermatids)
• spermatids (haploid) undergo a transformation into a spermatozoa
• There are six stages of seminiferous epithelium development
• 16 days required for a mature sperm to develop from early spermatogonia
• 72 days until ejaculation
• 1 spermatogonium becomes 215 spermatids
• testosterone and FSH are the hormones that are directed at the seminiferous tubule epithelium
• LH effects spermatogenesis indirectly in that it stimulates endogenous testosterone production
• The physical proximity of the Leydig cells to the seminiferous tubules and the elaboration by the Sertoli cells of androgen-binding protein, cause a high level of testosterone to be maintained in the microenvironment of the developing spermatozoa (i.e. 50X peripheral levels)
Epididymis: involved with maturation, storage and transport of spermatozoa.
• Testicular spermatozoa are non-motile
• Spermatozoa gain progressive motility and fertilizing ability after passing through the epididymis
• The epididymis consists of a fragile single convoluted tubule that is 5-6 meters in length. The epididymis is divided into the head, body, and tail
• Although epididymal transport time varies with age and sexual activity, the estimated transit time is four days.
• In epididymis, sperm develops the increased capacity for progressive motility and also acquire the ability to penetrate oocytes during fertilization
• The epididymis also serves as a reservoir or storage area for sperm
• The extragonadal sperm reservoir
• Is 440 million spermatozoa
• more than 50% of these are located in the tail of the epididymis.
• The sperm that are stored in the tail of the epididymis enter the vas deferens which is a muscular duct 30-35 cm in length
• The contents of the vas are propelled by peristaltic motion into the ejaculatory duct
• Sperm are then transported to the outside of the male reproductive tract by emission and ejaculation.
Erection:
Parasympathetic stimulation leads to penile erection (Eckhard, 1863, in the dog)
Sympathetic pathways important for detumescence and play a role in psychogenic erections (via inhibition of these pathways)
Reflex erection: afferent stimulation via S2-4, with efferent impulses via the same level sacral roots
Psychogenic erections: due to audiovisual, olfactory stimuli, or fantasy, and require the long tracts to be intact.
Afferent impulses via the dorsal penile nerves through pudendal nerves to dorsal roots of S2-4.
Upwards transmission via spinothalamic tracts to the thalamus and sensory cortex
Coordinated in medial pre-optic nucleus, contiguous with the hypothalamus
Efferent impulses via the medial forebrain bundle to the spinal cord. Parasympathetic fibres pass in intermediate lateral bundle and outflow through S2-4 in preganglionic pelvic nerves (nervi erigentes) to the pelvic plexus and then to the erectile tissue via the cavernous nerves
Sympathetic outflow from the spinal cord leads to flaccidity. Coordination in medial pre-optic nucleus, with outflow via T11-L4 via the hypogastric plexus, and thence to the pelvic plexus
Following spinal cord injuries higher than T9, erections can occur due to the reflex arc, and with lower lesions erections may occur as a result of efferent impulses through the thoracic sympathetic outflows, even though sympathetic stimulation normally leads to flaccidity (this is via a negative effect on the sympathetic outflow).
LMN pts unable to obtain a reflex erection, but 25% can get psychogenic erections
6 phases of erection (FFTFRD):
1: flaccid
contracted smooth muscle
2: filling
relaxation of arterial and cavernosal smooth muscle
3: tumescence
continued inflow
4: Full erection
compression of subtunical venous plexuses
decreased venous outflow via emissary veins
5: rigid erection
contraction of ischiocavernosus smooth muscle
6: detumescence
sympathetic stimulation and relaxation of ischiocavernosus smooth muscle
release of NA leads to stimulation of a1 receptors, an increase in intracellular calcium and contraction of cavernous smooth muscle
Ejaculation
Emission: sympathetic control (T10-L2)
Secretions from the seminal vesicles and prostate are deposited into the posterior urethra via contraction of epididymes and vasa and seminal vesicles
Bladder neck closure occurs under sympathetic nervous control.
Ejaculation: parasympathetic control (S2-4): the bladder neck tightens and the external sphincter relaxes with the semen being propelled through the urethra via rhythmic contractions of the perineal and bulbocavernosus and ischiocavernosus muscles.
The seminal vesicles provide 65% of volume fructose, prostaglandins and coagulating substrates.
A recognized function of the seminal plasma is its buffering effect on the acidic vaginal environment.
The coagulum formed by the ejaculated semen liquefies within 20 to 30 minutes as a result of prostatic proteolytic enzymes.
The prostate (30% volume) also adds zinc, phospholipids, spermine, and phosphatase to the seminal fluid.
The first portion of the ejaculate characteristically contains most of the spermatozoa and most of the prostatic secretions, while the second portion is composed primarily of seminal vesicle secretions and fewer spermatozoa.
• germinal cells divide to become spermatogonia which divide to become spermatocytes
• Type A spermatocytes undergo meiosis to become secondary spermatocytes
• spermatocytes divide and give rise to mature cell lines (spermatids)
• spermatids (haploid) undergo a transformation into a spermatozoa
• There are six stages of seminiferous epithelium development
• 16 days required for a mature sperm to develop from early spermatogonia
• 72 days until ejaculation
• 1 spermatogonium becomes 215 spermatids
• testosterone and FSH are the hormones that are directed at the seminiferous tubule epithelium
• LH effects spermatogenesis indirectly in that it stimulates endogenous testosterone production
• The physical proximity of the Leydig cells to the seminiferous tubules and the elaboration by the Sertoli cells of androgen-binding protein, cause a high level of testosterone to be maintained in the microenvironment of the developing spermatozoa (i.e. 50X peripheral levels)
Epididymis: involved with maturation, storage and transport of spermatozoa.
• Testicular spermatozoa are non-motile
• Spermatozoa gain progressive motility and fertilizing ability after passing through the epididymis
• The epididymis consists of a fragile single convoluted tubule that is 5-6 meters in length. The epididymis is divided into the head, body, and tail
• Although epididymal transport time varies with age and sexual activity, the estimated transit time is four days.
• In epididymis, sperm develops the increased capacity for progressive motility and also acquire the ability to penetrate oocytes during fertilization
• The epididymis also serves as a reservoir or storage area for sperm
• The extragonadal sperm reservoir
• Is 440 million spermatozoa
• more than 50% of these are located in the tail of the epididymis.
• The sperm that are stored in the tail of the epididymis enter the vas deferens which is a muscular duct 30-35 cm in length
• The contents of the vas are propelled by peristaltic motion into the ejaculatory duct
• Sperm are then transported to the outside of the male reproductive tract by emission and ejaculation.
Erection:
Parasympathetic stimulation leads to penile erection (Eckhard, 1863, in the dog)
Sympathetic pathways important for detumescence and play a role in psychogenic erections (via inhibition of these pathways)
Reflex erection: afferent stimulation via S2-4, with efferent impulses via the same level sacral roots
Psychogenic erections: due to audiovisual, olfactory stimuli, or fantasy, and require the long tracts to be intact.
Afferent impulses via the dorsal penile nerves through pudendal nerves to dorsal roots of S2-4.
Upwards transmission via spinothalamic tracts to the thalamus and sensory cortex
Coordinated in medial pre-optic nucleus, contiguous with the hypothalamus
Efferent impulses via the medial forebrain bundle to the spinal cord. Parasympathetic fibres pass in intermediate lateral bundle and outflow through S2-4 in preganglionic pelvic nerves (nervi erigentes) to the pelvic plexus and then to the erectile tissue via the cavernous nerves
Sympathetic outflow from the spinal cord leads to flaccidity. Coordination in medial pre-optic nucleus, with outflow via T11-L4 via the hypogastric plexus, and thence to the pelvic plexus
Following spinal cord injuries higher than T9, erections can occur due to the reflex arc, and with lower lesions erections may occur as a result of efferent impulses through the thoracic sympathetic outflows, even though sympathetic stimulation normally leads to flaccidity (this is via a negative effect on the sympathetic outflow).
LMN pts unable to obtain a reflex erection, but 25% can get psychogenic erections
6 phases of erection (FFTFRD):
1: flaccid
contracted smooth muscle
2: filling
relaxation of arterial and cavernosal smooth muscle
3: tumescence
continued inflow
4: Full erection
compression of subtunical venous plexuses
decreased venous outflow via emissary veins
5: rigid erection
contraction of ischiocavernosus smooth muscle
6: detumescence
sympathetic stimulation and relaxation of ischiocavernosus smooth muscle
release of NA leads to stimulation of a1 receptors, an increase in intracellular calcium and contraction of cavernous smooth muscle
Ejaculation
Emission: sympathetic control (T10-L2)
Secretions from the seminal vesicles and prostate are deposited into the posterior urethra via contraction of epididymes and vasa and seminal vesicles
Bladder neck closure occurs under sympathetic nervous control.
Ejaculation: parasympathetic control (S2-4): the bladder neck tightens and the external sphincter relaxes with the semen being propelled through the urethra via rhythmic contractions of the perineal and bulbocavernosus and ischiocavernosus muscles.
The seminal vesicles provide 65% of volume fructose, prostaglandins and coagulating substrates.
A recognized function of the seminal plasma is its buffering effect on the acidic vaginal environment.
The coagulum formed by the ejaculated semen liquefies within 20 to 30 minutes as a result of prostatic proteolytic enzymes.
The prostate (30% volume) also adds zinc, phospholipids, spermine, and phosphatase to the seminal fluid.
The first portion of the ejaculate characteristically contains most of the spermatozoa and most of the prostatic secretions, while the second portion is composed primarily of seminal vesicle secretions and fewer spermatozoa.
Saturday, June 13, 2009
What is Prostate?
The Prostate Gland and BPH. Basic Science
Function
Secretory
Produces 30% of the volume of seminal fluid
Provides nutrients for sperm
Proteases such as PSA (chymotrypsin) maintain semen fluidity by acting as an anticoagulant
Neutralises acidity of vagina
Antibiotic function of some secretions from the central zone.
Muscular pump
Smooth muscle surrounding the glands forces ejection of prostatic fluid to mix into seminal fluid during ejaculation
Development
Wk 7 male and female identical.
Mullerian ducts degenerate in male
Wolffian ducts differentiate - ejaculatory ducts, SV, vas and central zone of prostate
Wk 10-15 prostate derived from urogenital sinus (UGS) (peripheral zone)
Prostatic utricle is remnant of Mullerian or paramesonephric duct
3rd trimester gland quiescent till puberty
Structure
70% glandular / 30% fibromuscular
Zonal anatomy (McNeal 1968)
TZ - 5-10% glandular tissue
CZ - 25% glandular tissue structurally / immunohistochemically distinct from other zones.
Possibly originated from Wolffian duct
PZ - 70% glandular tissue
Derived from urogenital sinus
Transition zone BPH, 20% cancers
Central zone, 1-5% cancers
Peripheral Zone, 70% cancers
Blood supply: Inferior vesical and middle rectal arteries - branches of internal iliac artery
Venous drainage:
Prostatic venous plexus - sides & base of prostate
Located between capsule + fascial sheath
Drain to internal iliac veins
Communicate with vesical venous plexus, vertebral venous plexus
Innervation
Via cavernosal nerves which follow arterial supply
Parasympathetic fibres arise from pelvic splanchnic nerves S2, S3, & S4, promote secretions
Sympathetic fibres derived from inferior hypogastric plexuses, contraction of SM of capsule & stroma
Sphincters:
Rhabdosphincter (distal sphincter/urethral sphincter mechanism)
Three components: smooth muscle, then striated muscle, then periurethral component of levator ani (pubourethral sling)
Under conscious control
Signet ring shaped, deficient posteriorly
Bladder Neck
Both sexes, at bladder neck, cholinergic innervation, continence mechanism
Preprostatic sphincter
Males, supraverumontanal, adrenergic innervation, genital sphincter
Separate from rhabodosphincter
Smooth mucle, not under conscious control
Lymphatic drainage:
Lymph vessels terminate mainly in internal iliac and obturator lymph nodes
Some travel to external iliac lymph nodes & presacral nodes
Seminal vesicle
Pear shaped structure, 5cm long
Lies between fundus of bladder and rectum / (ureter enters bladder medial to tip of SV)
Provide majority of volume of seminal fluid, does not store sperm
Join vas deferens to form ejaculatory duct, opens posterior wall of prostatic urethra
Blood supply - sup / inf vesical arteries
Ejaculation
Emission of semen into urethra: peristalsis of vas / seminal vesicles, contraction of smooth muscle in prostate - sympathetic
Ejaculation clonic spasm bulbospongiosus muscles – parasympathetic
Sequence:
Bladder neck tightens
Emission of vasal ampullary sperm
Contraction of bulbospongiosus
Contraction of prostatic smooth muscle
Urethral sphincter mechanism overcome
Further contraction of prostate and seminal vesicle contraction
Seminal plasma
2ml seminal vesicle secretion, 0.5ml prostatic secretion, 0.1ml Cowper’s glands and glands of Littré
Role of seminal plasma
Optimise fertilisation
(ejaculated sperm v aspirated sperm)
protective effect
enhance motility and survival directly
Protective effect on urinary tract
biological esp. Zn, spermine, Ig
mechanical washing
Lubrication
Prostatic secretions
o Proteins: Acid phosphatase, PSA, Leucine aminopeptidase, Diamine oxidase, Β Glucuronidase, Plasminogen activator, Complement C3 and C4, transferrin, transferritin, Growth factors, annexin 1
o Non-proteins: Citrate (240-1300x conc elsewhere), Spermine, Spermidine, Putrescine, Zinc (high concentrations), Myoinositol, Cholesterol
o Functions: zinc for the structure of sperm chromatin and antibacterial. PSA for semen liquefaction. Cholesterol may stabilize sperm against temperature and environmental shock Citrate is important for electrochemical neutrality in combination with zinc and polyamines
Fructose
§ From seminal vesicles
§ Patients with congenital absence of seminal vesicles don’t have fructose in ejaculate [Barak 1994]
§ Concentration has some androgenic regulation but also depends on nutritional status and frequency of ejaculation
§ Provides anaerobic and aerobic energy source for sperm
§ Indirectly linked to forward sperm motility through prostasome function [Fabiani et al 1995]
Prostaglandins
§ Seminal vesicles are richest source in body (originally thought to be from prostate – hence the name) many types
§ Very potent pharmacological actions
§ Erection, ejaculation, sperm motility and transport
§ Effects on cervical mucus and vaginal secretions
Cell biology
Cellular organization is of a complex ductal system of epithelial cells embedded in a
stromal matrix
Epithelial: Exocrine and neuroendocrine cells
3 types: basal, luminal and neuroendocrine
Have different functions but are believed to originate from a common progenitor stem cell
Separated from stromal cells by the basement membrane
DHT formed mainly in these cells, and DHT then diffuses to stroma (where there are most of the androgen receptors)
Stromal nuclei produce growth factors, which then drive epithelial cells
Stroma: smooth muscle cells and fibroblasts
Has most of the androgen receptors
DHT diffuses from stromal cells, which produce growth factors, and these factors then work in an autocrine and paracrine fashion, stimulating epithelial cells
Cell type Function
Basal cells Proliferation
Luminal cells Secretion of prostatic fluid
Neuroendocrine Unknown - control growth and secretion?
Fibroblast Secrete growth factors (androgen dep)
Smooth muscle Contraction to eject prostatic fluid
Cellular organisation in the glandular prostate
Epithelial Cells
Neuroendocrine
Morphologically found in two forms
Open ended flask shaped cells with long extension towards the glandular lumen.
Closed cells without dendrite luminal extensions but with occasional horizontal processes.
Prostate has largest number of NE cells of any urogenital organ.
Function: Unknown but may play a role in the regulation of the normal growth and gland development (paracrine and autocrine) and may be important in the development of disease.
Basal cells
Spindle shaped, lying parallel to the basement membrane
Cigar shaped nuclei and high nucleus to cytoplasm ratio
81% of all proliferation occurs in the basal layer
Ratio of basal cells to luminal is 1:3 in normal and BPH tissue and 1:6 in hyperplastic situations
Major function: Proliferation
Includes stem cells
Luminal cells
Tall, columnar cells high in cytoplasm
Secretory cells contributing to the seminal fluid
PSA - Prostate specific antigen
PAP - Prostatic acid phosphatase
Only 1/10 the proliferative index of basal cells
Function - secretory - androgen dependent, as is survival
These cells most abundantly express the adrenoreceptor in BPH, cf basal cells
Cytokeratins:
Prostate: K5/14 basal cells and K8/18 in luminal cells
Stromal cells
Smooth muscle cells and fibroblasts
Little information about stromal cell types
Fibroblasts appear to initiate glandular growth and then differentiate into smooth muscle cells.
In cancer loss of muscle and gain of fibroblasts is associated with increased epithelial cell division
In culture a cell type called myofibroblasts appears and this may be an intermediate cell type
Both cell types express andrenoreceptors in BPH
98% of all α-adrenoreceptors in the prostate (90% α1 (60% α1a), 10% α2)
Stromal epithelial interaction theory
Interation between the stroma and the epithelium is important in growth and maintenance of the prostate
Reischauer suggested this first in 1925, and the theory was adopted by Cunha (1973)
Cunha showed that murine embryonic prostatic stroma could induce adult bladder epithelial cells to replicate and form prostate like glandular structures from the bladder cells. This effect does not occur in castrated animals, thus indicating the importance of androgens.
This interaction is thought to be the driving factor in the development of BPH, with androgens stimulating the local production of growth factors. These factors are responsible for the abnormal proliferation of the prostatic stroma and the appearance of micronodules and macronodules
Other Theories for BPH development
Embryonic reawakening: McNeal suggests that the initial abnormality in nodule genesis is a spontaneous reversion of a clone of stromal cells to the embryonic state
Oestrogen hypothesis: oestradiol modulates the action of androgens by altering the sensitivity of the prostate to androgens. A small increase in oestradiol concs results in an increased number of androgen receptors and prostate size. A large increase in oestradiol has the opposite effect. With aging, the oestrogen to androgen ratio increases, and these changes mimic those seen in BPH. Glandular BPH has been induced in castrated dogs by oestrogen and androgen administration (Walsh and Wilson, 1976)
Stem cell hypothesis: Isaacs and Coffey 1989. Number of stem cells, which is the rate limiting factor in prostate growth, slowly increases over time.
Growth Factors
FGF
IGF
TGFα all stimulatory (TGFα accounts for 20% of stimulatory factors)
EGF
TGFβ inhibitory
They all regulate the epithelial and mesenchymal interactions responsible for prostate development.
TGFβ inhibits prostate epithelial growth, but stimulates prostatic mesenchymal cells.
Following androgen withdrawal, there is decreased production of EGF, IGF and FGF, and an increase in expression of TGFβ1 and 2 receptors. This leads to prostatic involution.
Growth Factors in BPH:
bFGF stromal/epithelial autocrine/paracrine stimulatory
KGF stromal paracrine stimulatory
TGFβ1 stromal autocrine/paracrine inhibitory
TGFβ2 epithelial autocrine/paracrine inhibitory
IGF stromal paracrine stimulatory
In BPH there is no change in EGF, a large increase in FGF2, and keratinocyte growth factor and IGF appear.
Apoptosis and programmed cell death
Apoptosis is important in the development of BPH.
Activation of endonucleases occurs relatively early in the apoptotic pathway. This results from the hydrolysis of DNA, and the endonucleases are Ca2+/Mg2+ dependent.
Prostate stroma expresses α1a receptors, and pts treated with terazosin and doxasosin show induction of apoptosis, without affecting proliferation. Apoptitic index is higher in pts treated with an α blocker and proscar. Expression of TGFβ1 is increased with all therapies. However, α blocker treatment is not associated with a decrease in size of the prostate clinically.
BPH
LUTS
Urodynamic obstruction
BPE
LUTS, anatomical hyperplasia and urodynamic obstruction are interrelated.
Some pts have all three.
However, a large number have anatomical hyperplasia and urodynamic obstruction without LUTS.
Other have LUTS and urodynamic obstruction without anatomical hyperplasia, such as with bladder neck obstruction or a urethral stricture.
The last group have anatomical hyperplasia and symptoms of LUTS without urodynamic obstruction, and such pts may have a slow stream when voiding, but this is due to detrusor failure.
Anatomical hyperplasia
BPH consists of a mixture of glandular tissue and stromal components developing in a nodular fashion.
Glandular tissue that participates in BPH nodule formation is derived exclusively from branches of the few small ducts that join the urethra at or near its point of angulation at the base of the veru.
Nodules develop either in TZ or in periurethral stroma
Very different histologically: periurethral nodules are purely stromal in character or show only a few small glands. (TZ nodules are a proliferation of glandular (epithelial) tissue with a reduction in the relative amount of stroma ? correct)
In BPH stromal to glandular (epithelial) tissue is 5:1, while normally it is 2:1 in normal prostates
BPH has been described as primarily a stromal process
Causes obstruction in 2 ways
Static obstruction from increased tissue mass
Dynamic obstruction from contraction of the bladder neck, prostatic fibromuscular stroma and capsule
This sympathetic mediated obstruction may be responsible for upto 40% of bladder outflow obstruction
Natural History and Epidemiology
Initial development of BPH starts age 25-30 yrs, with a prevalence of 10% in that age range (data from autopsies involving 1075 prostates, Berry et al, J Urol 1984)
6th decade prevalence is >50%
by age 85, 90% affected
Data from Berry showed normal prostates weigh 20 +/- 6g in men 20-30 yrs, and remains constant throughout life
In pts with LUTS aged 60-80 yrs average weight is 40-50g
Risk factors and androgens
Age
Functioning testes leading to production of testosterone
BPH develops when test levels are on the decline
Role of androgens likely to be facilitative rather than causative
Intracellular androgens:
Testosterone metabolized to DHT, by 5 alpha reductase
Types 1 5a red (skin and liver) and type 2 (intraprostatic)
DHT: testosterone in prostate is 5:1
Both DHT and test bind to androgen receptors, DHT > testosterone, leading to greater subsequent intracellular changes of DNA activation and mRNA production
Males with 5a reductase def have no prostates
Androgen control:
Gene encoding 5a red enzyme type 1 found on Chr 5: expressed in nongenital skin and liver (inhibited by dutasteride)
Gene encoding 5a red enzyme type 2 found on Chr 2: expressed in prostate (stroma and basal epithelial cells) and genital skin (inhibited by finasteride and dutasteride)
Function
Secretory
Produces 30% of the volume of seminal fluid
Provides nutrients for sperm
Proteases such as PSA (chymotrypsin) maintain semen fluidity by acting as an anticoagulant
Neutralises acidity of vagina
Antibiotic function of some secretions from the central zone.
Muscular pump
Smooth muscle surrounding the glands forces ejection of prostatic fluid to mix into seminal fluid during ejaculation
Development
Wk 7 male and female identical.
Mullerian ducts degenerate in male
Wolffian ducts differentiate - ejaculatory ducts, SV, vas and central zone of prostate
Wk 10-15 prostate derived from urogenital sinus (UGS) (peripheral zone)
Prostatic utricle is remnant of Mullerian or paramesonephric duct
3rd trimester gland quiescent till puberty
Structure
70% glandular / 30% fibromuscular
Zonal anatomy (McNeal 1968)
TZ - 5-10% glandular tissue
CZ - 25% glandular tissue structurally / immunohistochemically distinct from other zones.
Possibly originated from Wolffian duct
PZ - 70% glandular tissue
Derived from urogenital sinus
Transition zone BPH, 20% cancers
Central zone, 1-5% cancers
Peripheral Zone, 70% cancers
Blood supply: Inferior vesical and middle rectal arteries - branches of internal iliac artery
Venous drainage:
Prostatic venous plexus - sides & base of prostate
Located between capsule + fascial sheath
Drain to internal iliac veins
Communicate with vesical venous plexus, vertebral venous plexus
Innervation
Via cavernosal nerves which follow arterial supply
Parasympathetic fibres arise from pelvic splanchnic nerves S2, S3, & S4, promote secretions
Sympathetic fibres derived from inferior hypogastric plexuses, contraction of SM of capsule & stroma
Sphincters:
Rhabdosphincter (distal sphincter/urethral sphincter mechanism)
Three components: smooth muscle, then striated muscle, then periurethral component of levator ani (pubourethral sling)
Under conscious control
Signet ring shaped, deficient posteriorly
Bladder Neck
Both sexes, at bladder neck, cholinergic innervation, continence mechanism
Preprostatic sphincter
Males, supraverumontanal, adrenergic innervation, genital sphincter
Separate from rhabodosphincter
Smooth mucle, not under conscious control
Lymphatic drainage:
Lymph vessels terminate mainly in internal iliac and obturator lymph nodes
Some travel to external iliac lymph nodes & presacral nodes
Seminal vesicle
Pear shaped structure, 5cm long
Lies between fundus of bladder and rectum / (ureter enters bladder medial to tip of SV)
Provide majority of volume of seminal fluid, does not store sperm
Join vas deferens to form ejaculatory duct, opens posterior wall of prostatic urethra
Blood supply - sup / inf vesical arteries
Ejaculation
Emission of semen into urethra: peristalsis of vas / seminal vesicles, contraction of smooth muscle in prostate - sympathetic
Ejaculation clonic spasm bulbospongiosus muscles – parasympathetic
Sequence:
Bladder neck tightens
Emission of vasal ampullary sperm
Contraction of bulbospongiosus
Contraction of prostatic smooth muscle
Urethral sphincter mechanism overcome
Further contraction of prostate and seminal vesicle contraction
Seminal plasma
2ml seminal vesicle secretion, 0.5ml prostatic secretion, 0.1ml Cowper’s glands and glands of Littré
Role of seminal plasma
Optimise fertilisation
(ejaculated sperm v aspirated sperm)
protective effect
enhance motility and survival directly
Protective effect on urinary tract
biological esp. Zn, spermine, Ig
mechanical washing
Lubrication
Prostatic secretions
o Proteins: Acid phosphatase, PSA, Leucine aminopeptidase, Diamine oxidase, Β Glucuronidase, Plasminogen activator, Complement C3 and C4, transferrin, transferritin, Growth factors, annexin 1
o Non-proteins: Citrate (240-1300x conc elsewhere), Spermine, Spermidine, Putrescine, Zinc (high concentrations), Myoinositol, Cholesterol
o Functions: zinc for the structure of sperm chromatin and antibacterial. PSA for semen liquefaction. Cholesterol may stabilize sperm against temperature and environmental shock Citrate is important for electrochemical neutrality in combination with zinc and polyamines
Fructose
§ From seminal vesicles
§ Patients with congenital absence of seminal vesicles don’t have fructose in ejaculate [Barak 1994]
§ Concentration has some androgenic regulation but also depends on nutritional status and frequency of ejaculation
§ Provides anaerobic and aerobic energy source for sperm
§ Indirectly linked to forward sperm motility through prostasome function [Fabiani et al 1995]
Prostaglandins
§ Seminal vesicles are richest source in body (originally thought to be from prostate – hence the name) many types
§ Very potent pharmacological actions
§ Erection, ejaculation, sperm motility and transport
§ Effects on cervical mucus and vaginal secretions
Cell biology
Cellular organization is of a complex ductal system of epithelial cells embedded in a
stromal matrix
Epithelial: Exocrine and neuroendocrine cells
3 types: basal, luminal and neuroendocrine
Have different functions but are believed to originate from a common progenitor stem cell
Separated from stromal cells by the basement membrane
DHT formed mainly in these cells, and DHT then diffuses to stroma (where there are most of the androgen receptors)
Stromal nuclei produce growth factors, which then drive epithelial cells
Stroma: smooth muscle cells and fibroblasts
Has most of the androgen receptors
DHT diffuses from stromal cells, which produce growth factors, and these factors then work in an autocrine and paracrine fashion, stimulating epithelial cells
Cell type Function
Basal cells Proliferation
Luminal cells Secretion of prostatic fluid
Neuroendocrine Unknown - control growth and secretion?
Fibroblast Secrete growth factors (androgen dep)
Smooth muscle Contraction to eject prostatic fluid
Cellular organisation in the glandular prostate
Epithelial Cells
Neuroendocrine
Morphologically found in two forms
Open ended flask shaped cells with long extension towards the glandular lumen.
Closed cells without dendrite luminal extensions but with occasional horizontal processes.
Prostate has largest number of NE cells of any urogenital organ.
Function: Unknown but may play a role in the regulation of the normal growth and gland development (paracrine and autocrine) and may be important in the development of disease.
Basal cells
Spindle shaped, lying parallel to the basement membrane
Cigar shaped nuclei and high nucleus to cytoplasm ratio
81% of all proliferation occurs in the basal layer
Ratio of basal cells to luminal is 1:3 in normal and BPH tissue and 1:6 in hyperplastic situations
Major function: Proliferation
Includes stem cells
Luminal cells
Tall, columnar cells high in cytoplasm
Secretory cells contributing to the seminal fluid
PSA - Prostate specific antigen
PAP - Prostatic acid phosphatase
Only 1/10 the proliferative index of basal cells
Function - secretory - androgen dependent, as is survival
These cells most abundantly express the adrenoreceptor in BPH, cf basal cells
Cytokeratins:
Prostate: K5/14 basal cells and K8/18 in luminal cells
Stromal cells
Smooth muscle cells and fibroblasts
Little information about stromal cell types
Fibroblasts appear to initiate glandular growth and then differentiate into smooth muscle cells.
In cancer loss of muscle and gain of fibroblasts is associated with increased epithelial cell division
In culture a cell type called myofibroblasts appears and this may be an intermediate cell type
Both cell types express andrenoreceptors in BPH
98% of all α-adrenoreceptors in the prostate (90% α1 (60% α1a), 10% α2)
Stromal epithelial interaction theory
Interation between the stroma and the epithelium is important in growth and maintenance of the prostate
Reischauer suggested this first in 1925, and the theory was adopted by Cunha (1973)
Cunha showed that murine embryonic prostatic stroma could induce adult bladder epithelial cells to replicate and form prostate like glandular structures from the bladder cells. This effect does not occur in castrated animals, thus indicating the importance of androgens.
This interaction is thought to be the driving factor in the development of BPH, with androgens stimulating the local production of growth factors. These factors are responsible for the abnormal proliferation of the prostatic stroma and the appearance of micronodules and macronodules
Other Theories for BPH development
Embryonic reawakening: McNeal suggests that the initial abnormality in nodule genesis is a spontaneous reversion of a clone of stromal cells to the embryonic state
Oestrogen hypothesis: oestradiol modulates the action of androgens by altering the sensitivity of the prostate to androgens. A small increase in oestradiol concs results in an increased number of androgen receptors and prostate size. A large increase in oestradiol has the opposite effect. With aging, the oestrogen to androgen ratio increases, and these changes mimic those seen in BPH. Glandular BPH has been induced in castrated dogs by oestrogen and androgen administration (Walsh and Wilson, 1976)
Stem cell hypothesis: Isaacs and Coffey 1989. Number of stem cells, which is the rate limiting factor in prostate growth, slowly increases over time.
Growth Factors
FGF
IGF
TGFα all stimulatory (TGFα accounts for 20% of stimulatory factors)
EGF
TGFβ inhibitory
They all regulate the epithelial and mesenchymal interactions responsible for prostate development.
TGFβ inhibits prostate epithelial growth, but stimulates prostatic mesenchymal cells.
Following androgen withdrawal, there is decreased production of EGF, IGF and FGF, and an increase in expression of TGFβ1 and 2 receptors. This leads to prostatic involution.
Growth Factors in BPH:
bFGF stromal/epithelial autocrine/paracrine stimulatory
KGF stromal paracrine stimulatory
TGFβ1 stromal autocrine/paracrine inhibitory
TGFβ2 epithelial autocrine/paracrine inhibitory
IGF stromal paracrine stimulatory
In BPH there is no change in EGF, a large increase in FGF2, and keratinocyte growth factor and IGF appear.
Apoptosis and programmed cell death
Apoptosis is important in the development of BPH.
Activation of endonucleases occurs relatively early in the apoptotic pathway. This results from the hydrolysis of DNA, and the endonucleases are Ca2+/Mg2+ dependent.
Prostate stroma expresses α1a receptors, and pts treated with terazosin and doxasosin show induction of apoptosis, without affecting proliferation. Apoptitic index is higher in pts treated with an α blocker and proscar. Expression of TGFβ1 is increased with all therapies. However, α blocker treatment is not associated with a decrease in size of the prostate clinically.
BPH
LUTS
Urodynamic obstruction
BPE
LUTS, anatomical hyperplasia and urodynamic obstruction are interrelated.
Some pts have all three.
However, a large number have anatomical hyperplasia and urodynamic obstruction without LUTS.
Other have LUTS and urodynamic obstruction without anatomical hyperplasia, such as with bladder neck obstruction or a urethral stricture.
The last group have anatomical hyperplasia and symptoms of LUTS without urodynamic obstruction, and such pts may have a slow stream when voiding, but this is due to detrusor failure.
Anatomical hyperplasia
BPH consists of a mixture of glandular tissue and stromal components developing in a nodular fashion.
Glandular tissue that participates in BPH nodule formation is derived exclusively from branches of the few small ducts that join the urethra at or near its point of angulation at the base of the veru.
Nodules develop either in TZ or in periurethral stroma
Very different histologically: periurethral nodules are purely stromal in character or show only a few small glands. (TZ nodules are a proliferation of glandular (epithelial) tissue with a reduction in the relative amount of stroma ? correct)
In BPH stromal to glandular (epithelial) tissue is 5:1, while normally it is 2:1 in normal prostates
BPH has been described as primarily a stromal process
Causes obstruction in 2 ways
Static obstruction from increased tissue mass
Dynamic obstruction from contraction of the bladder neck, prostatic fibromuscular stroma and capsule
This sympathetic mediated obstruction may be responsible for upto 40% of bladder outflow obstruction
Natural History and Epidemiology
Initial development of BPH starts age 25-30 yrs, with a prevalence of 10% in that age range (data from autopsies involving 1075 prostates, Berry et al, J Urol 1984)
6th decade prevalence is >50%
by age 85, 90% affected
Data from Berry showed normal prostates weigh 20 +/- 6g in men 20-30 yrs, and remains constant throughout life
In pts with LUTS aged 60-80 yrs average weight is 40-50g
Risk factors and androgens
Age
Functioning testes leading to production of testosterone
BPH develops when test levels are on the decline
Role of androgens likely to be facilitative rather than causative
Intracellular androgens:
Testosterone metabolized to DHT, by 5 alpha reductase
Types 1 5a red (skin and liver) and type 2 (intraprostatic)
DHT: testosterone in prostate is 5:1
Both DHT and test bind to androgen receptors, DHT > testosterone, leading to greater subsequent intracellular changes of DNA activation and mRNA production
Males with 5a reductase def have no prostates
Androgen control:
Gene encoding 5a red enzyme type 1 found on Chr 5: expressed in nongenital skin and liver (inhibited by dutasteride)
Gene encoding 5a red enzyme type 2 found on Chr 2: expressed in prostate (stroma and basal epithelial cells) and genital skin (inhibited by finasteride and dutasteride)
Friday, June 12, 2009
Lasers and Stents for the enlarged prostate
Lasers and stents
Lasers
•Light Amplification by the Stimulated Emmision of Radiation
•Flash-lamp with high intensity light bombards resonator cavity with photons
•Electrons excited, decay with emission of photon
•Cascade effect
•Photons leave resonator cavity as coherent laser beam
Principles
•Coherence, collimation and monochromaticity
•Differ with respect to wavelengths, power and mode of emission (pulsed or continuous)
Mechanism of Action
•Heat treatment
o 45-50ºC Desiccation
o 50-100°C Coagulation
o >100°C Carbonisation and Vapourisation
•Effect dependent on power of laser and length of time applied
•NB. Can be used if anti-coagulated or coagulation disorder
Laser types
•Nd:YAG (neodymium, yttrium, aluminium, garnet)
o 1064 nm wavelength
o absorption length in tissue of 0.5 to 1.75 cm, giving it excellent haemostatic properties
o VLAP uses the NF-YAG laser in a non contact mode using a side firing laser
o Contact laser ablation (CLAP) uses NDYAG via a sapphire tipped fibre. Direct contact between laser fibre and tissue causes tissue vaporisation at the point of contact
o CLAP and VLAP show similar improvements at 2 years in flow rates and SS, but at 4 yrs CLAP has a 23% reop rate. CLAP harder to learn, and has been abandoned
•KTP:YAG
o Beam from Nd-YAG passed through a potassium titanyl phosphate crystal (KTP) which doubled the frequency and halves the wavelength (532 nm)
o Good incisional and vaporization properties, with tissue penetration depth of 3mm
o Causes vaporization of tissue, and can result in an immediate TURP like channel
•Ho:YAG
o Wavelength of 2140 nm
o Penetration depth of only 0.4mm, with excellent incisional and haemostatic properties
o Laser ablation of prostate involves vaporization of prostate tissue using a side firing fibre
o Laser resection of the prostate divides the lobes into fragements small enough to irrigate from the bladder
o Laser enucleation of the prostate, whole lobes cut away, and then morcellated for removal
•Diode
o Wavelength of 830 nm
o Used for interestitial laser coagulation
o Coagulation necrosis occurs via a fibre inserted directly into interstitium of prostate
o Usually needs spinal or GA
Methods
Side-firing
TRUS guided Laser induced Prostatectomy (TULIP)
Visual laser ablation of the Prostate (VLAP)
Interstitial Laser Coagulation (ILC)
Ho laser resection of the prostate (HoLRP)
TULIP
‘Blind’
Side-firing Nd:YAG
Useless
Abandonded
Visual laser ablation of the Prostate (VLAP)
Mixture of coagulative necrosis and vapourisation
Nd:YAG laser(1064nm) at 40-90W for 60s
Quadrant / Sextant spot application technique via cystoscope
Tissue sloughs away
Results
85% have ³ 50% improvement in SS or Qmax
Significant reduction in BOO (80-95%)
No irrigation required
Best if gland < 50-60g
Not suitable if UTI / bacterial prostatitis
Complications
Prolonged catheterisation (3-4 weeks) & dysuria
Serious complications in 12%
Impotence 0%
Incontinence 0%
Urethral stricture 2%
Bladder neck contracture 4%
Ret ejaculation 22%
Retreatment rate 2%/year (Costello) – 8%/year (Puppo)
Interstitial Laser Coagulation (ILC)
Coagulation necrosis used to reduce prostate volume
Secondary atrophy & regression of prostate rather than sloughing
Nd:YAG or diode laser
Fibres placed into prostate tissue cystoscopically
1-2 fibres per 5-10ml prostate volume
Results and complications
Similar improvement in LUTS & BOO to TURP at 1 year follow-up (Muschter)
8% ILC subsequently required TURP
Mean catheterisation – 18 days
Complications
Ret ejaculation 12%
Stricture 5%
Impotence 0%
Incontinence 0%
Retreatment 3%/year for first year rising to 10%/year subsequently
Ho laser resection of the prostate (HoLRP)
Pulsed solid-state laser, l = 2140nm
Ho:YAG l is strongly absorbed by water
Zone of coagulative necrosis, 3-4mm, is adequate for haemostasis
Peak power causes intense vapourisation and precise cutting
550mm end-firing quartz fibre via continous flow resectoscope with normal saline irrigant
80W Ho:YAG laser
Results
Gilling et al (J Urol 1999; 162: 1640) Prospective RCT, TURP v’s HoLRP with 1 year follow-up
Similar improvements in SS, Qmax and PdetQmax
Complications
Dysuria 10%
Impotence 0%
Ret ejaculation 75-80%
4 yr follow up: J Urol 2004. Similar outcome to TURP with less morbidity
Stents
10-15% BPH patients unfit for surgery
AUA guidelines: only for use in unfit pts
A number of small studies using prostatic stents in unfit men with retention
Various materials used
Metallic alloys, bioresorbable, polyurethane, thermosensitive
Urolume
Self-expanding superalloy wire
Placed cystoscopically or US guided
Over a few weeks to a few months they become covered with normal transitional epithelium
Urolume North American Clinical Trial
13% required stent removal
Side effects
Urgency (67%), dysuria (50%), perineal pain (50%), persistent retention (10%), incontinence (<1%), haematuria, encrustation, occlusion,
TITAN Stent
Seamless titanium tubing
Expanded with non-compliant balloon
Placed cystoscopically with iv sedation & prostate block
Results inferior to Urolume
Lasers
•Light Amplification by the Stimulated Emmision of Radiation
•Flash-lamp with high intensity light bombards resonator cavity with photons
•Electrons excited, decay with emission of photon
•Cascade effect
•Photons leave resonator cavity as coherent laser beam
Principles
•Coherence, collimation and monochromaticity
•Differ with respect to wavelengths, power and mode of emission (pulsed or continuous)
Mechanism of Action
•Heat treatment
o 45-50ºC Desiccation
o 50-100°C Coagulation
o >100°C Carbonisation and Vapourisation
•Effect dependent on power of laser and length of time applied
•NB. Can be used if anti-coagulated or coagulation disorder
Laser types
•Nd:YAG (neodymium, yttrium, aluminium, garnet)
o 1064 nm wavelength
o absorption length in tissue of 0.5 to 1.75 cm, giving it excellent haemostatic properties
o VLAP uses the NF-YAG laser in a non contact mode using a side firing laser
o Contact laser ablation (CLAP) uses NDYAG via a sapphire tipped fibre. Direct contact between laser fibre and tissue causes tissue vaporisation at the point of contact
o CLAP and VLAP show similar improvements at 2 years in flow rates and SS, but at 4 yrs CLAP has a 23% reop rate. CLAP harder to learn, and has been abandoned
•KTP:YAG
o Beam from Nd-YAG passed through a potassium titanyl phosphate crystal (KTP) which doubled the frequency and halves the wavelength (532 nm)
o Good incisional and vaporization properties, with tissue penetration depth of 3mm
o Causes vaporization of tissue, and can result in an immediate TURP like channel
•Ho:YAG
o Wavelength of 2140 nm
o Penetration depth of only 0.4mm, with excellent incisional and haemostatic properties
o Laser ablation of prostate involves vaporization of prostate tissue using a side firing fibre
o Laser resection of the prostate divides the lobes into fragements small enough to irrigate from the bladder
o Laser enucleation of the prostate, whole lobes cut away, and then morcellated for removal
•Diode
o Wavelength of 830 nm
o Used for interestitial laser coagulation
o Coagulation necrosis occurs via a fibre inserted directly into interstitium of prostate
o Usually needs spinal or GA
Methods
Side-firing
TRUS guided Laser induced Prostatectomy (TULIP)
Visual laser ablation of the Prostate (VLAP)
Interstitial Laser Coagulation (ILC)
Ho laser resection of the prostate (HoLRP)
TULIP
‘Blind’
Side-firing Nd:YAG
Useless
Abandonded
Visual laser ablation of the Prostate (VLAP)
Mixture of coagulative necrosis and vapourisation
Nd:YAG laser(1064nm) at 40-90W for 60s
Quadrant / Sextant spot application technique via cystoscope
Tissue sloughs away
Results
85% have ³ 50% improvement in SS or Qmax
Significant reduction in BOO (80-95%)
No irrigation required
Best if gland < 50-60g
Not suitable if UTI / bacterial prostatitis
Complications
Prolonged catheterisation (3-4 weeks) & dysuria
Serious complications in 12%
Impotence 0%
Incontinence 0%
Urethral stricture 2%
Bladder neck contracture 4%
Ret ejaculation 22%
Retreatment rate 2%/year (Costello) – 8%/year (Puppo)
Interstitial Laser Coagulation (ILC)
Coagulation necrosis used to reduce prostate volume
Secondary atrophy & regression of prostate rather than sloughing
Nd:YAG or diode laser
Fibres placed into prostate tissue cystoscopically
1-2 fibres per 5-10ml prostate volume
Results and complications
Similar improvement in LUTS & BOO to TURP at 1 year follow-up (Muschter)
8% ILC subsequently required TURP
Mean catheterisation – 18 days
Complications
Ret ejaculation 12%
Stricture 5%
Impotence 0%
Incontinence 0%
Retreatment 3%/year for first year rising to 10%/year subsequently
Ho laser resection of the prostate (HoLRP)
Pulsed solid-state laser, l = 2140nm
Ho:YAG l is strongly absorbed by water
Zone of coagulative necrosis, 3-4mm, is adequate for haemostasis
Peak power causes intense vapourisation and precise cutting
550mm end-firing quartz fibre via continous flow resectoscope with normal saline irrigant
80W Ho:YAG laser
Results
Gilling et al (J Urol 1999; 162: 1640) Prospective RCT, TURP v’s HoLRP with 1 year follow-up
Similar improvements in SS, Qmax and PdetQmax
Complications
Dysuria 10%
Impotence 0%
Ret ejaculation 75-80%
4 yr follow up: J Urol 2004. Similar outcome to TURP with less morbidity
Stents
10-15% BPH patients unfit for surgery
AUA guidelines: only for use in unfit pts
A number of small studies using prostatic stents in unfit men with retention
Various materials used
Metallic alloys, bioresorbable, polyurethane, thermosensitive
Urolume
Self-expanding superalloy wire
Placed cystoscopically or US guided
Over a few weeks to a few months they become covered with normal transitional epithelium
Urolume North American Clinical Trial
13% required stent removal
Side effects
Urgency (67%), dysuria (50%), perineal pain (50%), persistent retention (10%), incontinence (<1%), haematuria, encrustation, occlusion,
TITAN Stent
Seamless titanium tubing
Expanded with non-compliant balloon
Placed cystoscopically with iv sedation & prostate block
Results inferior to Urolume
Sunday, June 7, 2009
Benign Prostatic Hyperplasia and Urodynamics
Facts:
BOO is present in 90% of men with larger prostates
(>80 ml), in those with small volumes (<40>15 ml/s only about 1/3 [3]. These data indicate that urine flow studies are not sufficient for the definitive
diagnosis of BOO (Abrams, BJUI 1995)
Obstructed patients do not always fare well with TURP (success rate: 79–93%) and conversely, unobstructed men do not always fail with success rates of 55–78% (Homma, BJUI 2001)
The EAU guidelines.
Who should have UDx prior to TURP?
(i) previous unsuccessful invasive treatment of LUTS;
(ii) elderly men (>80 years);
(iii) younger men (e.g. <50 years);
(iv) post-void residual volume >300 ml;
(v) suspicion
of neurogenic bladder dysfunction;
(vi) previous radical pelvic surgery
Previous unsuccessful invasive treatment
Nitti et al. have performed urodynamics studies in 50 consecutive patients referred because of persistent LUTS after prostatectomy. In this series, 62% of these men were urodynamically unobstructed, 22% were in the equivocal zone and only 16% were urodynamically obstructed; detrusor instability was present in 54%. Symptoms were unreliable in predicting urodynamic findings. These data clearly demonstrate that another deobstructing procedure (i.e. 2nd TURP) is unlikely solve the problem in this group of patients. Only pQs (urodynamics) can guide the appropriate treatment in these patients (Nitti, J Urol 1997)
Elderly patients
For two reasons, geriatric patients (>80 years) should undergo pQs prior prostatectomy. First of all, because morbidity of prostatectomy in this high age group is increased. Secondly, and equally important, is the fact that the ageing urinary bladder reveals a number of age related urodynamics changes in men [17,18]. Among these is a decrease of Qmax, an increase of post-void residual volume, a decline in bladder capacity and of bladder compliance. As a consequence
the percentage of patients without BOO despite a reduced Qmax of 10–15 ml/s and an interrnational Prostate Symptom Score (IPSS) exceeding 7 increases substantially in men older than 70 years and particularly above 80 years (Fig. 3) [17,18]. This observation is a strong argument for routine pQs in this high age group. The real predictive value of urodynamics on the outcome after surgery is also questionable. In a recent paper, van Venrooij (J Urol 2002) showed that in 32 unobstructed or equivocal patients, there was a 40% increase in mean effective capacity of the bladder after surgery which was correlated with the improvement
of symptoms. Furthermore, 50% of unstable bladders became stable after surgery, and this could not be predicted from urodynamics. Numerous studies show that more than 50% of
patients who would have been eliminated from surgery, according to PFS, are, in fact, improved after surgery.
This confirms that all symptoms in the presence of BPH do not correspond to obstruction, and that the latter may have different profiles on PFS. Patients with a weak detrusor should not be systematically eliminated from surgery. We should consider that the weaker the detrusor contraction is, the more important is the impact of an increase of urethral resistance. In such
patients, the relief of any degree of obstruction should improve micturition. There is an inherent limitation of PFS in detecting obstruction, when obstruction and a weak detrusor coexist, and a low detrusor pressure does not necessarily contraindicate prostatectomy. Operate on those who suffer failure with their conservative management. Some patients could benefit from minimally invasive therapies, but it has not yet been proven that urodynamics is able to differentiate
indications.
Urodynamics and success with TURP: Does obstruction make any difference to outcome.
No says Hakenberg et al: BJUI 2003
Variable
N
Age (yrs)
IPSS change
QOL
(improvements)
Pre Post
Ag Number
<15>40
46
72.5
9.5
5 1
AG# = Pdet at Qmax – 2(Qmax). >40 is obstrcucted, <20 is unobstructed, 20-40 equivocal
Outcome of TURP in pts with High Pressure Chronic Retention (Styles and Neal, J Urol 1991)
68 men with bladder outflow obstruction and chronic retention (residual urine greater than 300 ml.) Postoperatively, upper tract dilatation (present in 28 men preoperatively) resolved in all but 2 men and serum creatinine levels improved significantly. Irritative and obstructive symptom scores improved postoperatively (p less than 0.00006), although 17% of the men still had significant symptoms. Residual urine volumes decreased and flow rates improved (p less than 0.00006) 32% of the men still had a residual urine of greater than 200 ml.
BOO is present in 90% of men with larger prostates
(>80 ml), in those with small volumes (<40>15 ml/s only about 1/3 [3]. These data indicate that urine flow studies are not sufficient for the definitive
diagnosis of BOO (Abrams, BJUI 1995)
Obstructed patients do not always fare well with TURP (success rate: 79–93%) and conversely, unobstructed men do not always fail with success rates of 55–78% (Homma, BJUI 2001)
The EAU guidelines.
Who should have UDx prior to TURP?
(i) previous unsuccessful invasive treatment of LUTS;
(ii) elderly men (>80 years);
(iii) younger men (e.g. <50 years);
(iv) post-void residual volume >300 ml;
(v) suspicion
of neurogenic bladder dysfunction;
(vi) previous radical pelvic surgery
Previous unsuccessful invasive treatment
Nitti et al. have performed urodynamics studies in 50 consecutive patients referred because of persistent LUTS after prostatectomy. In this series, 62% of these men were urodynamically unobstructed, 22% were in the equivocal zone and only 16% were urodynamically obstructed; detrusor instability was present in 54%. Symptoms were unreliable in predicting urodynamic findings. These data clearly demonstrate that another deobstructing procedure (i.e. 2nd TURP) is unlikely solve the problem in this group of patients. Only pQs (urodynamics) can guide the appropriate treatment in these patients (Nitti, J Urol 1997)
Elderly patients
For two reasons, geriatric patients (>80 years) should undergo pQs prior prostatectomy. First of all, because morbidity of prostatectomy in this high age group is increased. Secondly, and equally important, is the fact that the ageing urinary bladder reveals a number of age related urodynamics changes in men [17,18]. Among these is a decrease of Qmax, an increase of post-void residual volume, a decline in bladder capacity and of bladder compliance. As a consequence
the percentage of patients without BOO despite a reduced Qmax of 10–15 ml/s and an interrnational Prostate Symptom Score (IPSS) exceeding 7 increases substantially in men older than 70 years and particularly above 80 years (Fig. 3) [17,18]. This observation is a strong argument for routine pQs in this high age group. The real predictive value of urodynamics on the outcome after surgery is also questionable. In a recent paper, van Venrooij (J Urol 2002) showed that in 32 unobstructed or equivocal patients, there was a 40% increase in mean effective capacity of the bladder after surgery which was correlated with the improvement
of symptoms. Furthermore, 50% of unstable bladders became stable after surgery, and this could not be predicted from urodynamics. Numerous studies show that more than 50% of
patients who would have been eliminated from surgery, according to PFS, are, in fact, improved after surgery.
This confirms that all symptoms in the presence of BPH do not correspond to obstruction, and that the latter may have different profiles on PFS. Patients with a weak detrusor should not be systematically eliminated from surgery. We should consider that the weaker the detrusor contraction is, the more important is the impact of an increase of urethral resistance. In such
patients, the relief of any degree of obstruction should improve micturition. There is an inherent limitation of PFS in detecting obstruction, when obstruction and a weak detrusor coexist, and a low detrusor pressure does not necessarily contraindicate prostatectomy. Operate on those who suffer failure with their conservative management. Some patients could benefit from minimally invasive therapies, but it has not yet been proven that urodynamics is able to differentiate
indications.
Urodynamics and success with TURP: Does obstruction make any difference to outcome.
No says Hakenberg et al: BJUI 2003
Variable
N
Age (yrs)
IPSS change
QOL
(improvements)
Pre Post
Ag Number
<15>40
46
72.5
9.5
5 1
AG# = Pdet at Qmax – 2(Qmax). >40 is obstrcucted, <20 is unobstructed, 20-40 equivocal
Outcome of TURP in pts with High Pressure Chronic Retention (Styles and Neal, J Urol 1991)
68 men with bladder outflow obstruction and chronic retention (residual urine greater than 300 ml.) Postoperatively, upper tract dilatation (present in 28 men preoperatively) resolved in all but 2 men and serum creatinine levels improved significantly. Irritative and obstructive symptom scores improved postoperatively (p less than 0.00006), although 17% of the men still had significant symptoms. Residual urine volumes decreased and flow rates improved (p less than 0.00006) 32% of the men still had a residual urine of greater than 200 ml.
Friday, June 5, 2009
Types of Penil prosthesis
1-Soft
2-Semi-rigid
3-Bendable metallic core
4-Interlocking segments
5-Inflatable- 1,2 & 3 part
1 Soft
Subrini
SSDA, Virilis
Rarely used in UK
Peyronnie's surgery
Augments natural erection by providing core bulk
2 Semi-rigid
Cheap
Simple
Reliable: No moving parts
Hard to conceal, ‘bendability’
Limited width
Erosion
Mentor Accuform
9.5 mm, 14-23 cm
11 mm, 16-25 cm
13 mm, 18-27 cm (hard to bend)
Bendability ~ 90 degrees
RTE 0-1 cm
AMS
600 series
9.5 mm & 11.5 mm width
650 series
11 mm & 13 mm width
Tip extenders, both ends
length 12-20 cm
Bendability ~110 degrees
AMS
Dura II
Interlocking PTFE segments with steel spring
10,12 mm
13 cm + tip extenders both ends
Bendability ~150 degrees
Inflatable
Concealment
‘Natural’
Rigidity
Expensive
Infection
Mechanical failure
Manual dexterity
Inflatable – 2 piece
AMS Ambicor
Combined cylinders + reservoir
Pump
limited fluid volume
Mentor Mark II
Inflatable-3 piece
AMS 700CX, CXM, CXR
Triple layer
Expands in width
Smallest 12 cm
AMS Ultrex
Expands in length and width
Antibiotic coating (inhibiZone)
Rifampicin & Minocycline
Inflatable-3 piece
Mentor Alpha 1, Titan & narrowbase
Smallest 10cm
Expands girth++
Oval
Bioflex
Lockout valve
Hydrophilic antibiotic adsorbant surface
2-Semi-rigid
3-Bendable metallic core
4-Interlocking segments
5-Inflatable- 1,2 & 3 part
1 Soft
Subrini
SSDA, Virilis
Rarely used in UK
Peyronnie's surgery
Augments natural erection by providing core bulk
2 Semi-rigid
Cheap
Simple
Reliable: No moving parts
Hard to conceal, ‘bendability’
Limited width
Erosion
Mentor Accuform
9.5 mm, 14-23 cm
11 mm, 16-25 cm
13 mm, 18-27 cm (hard to bend)
Bendability ~ 90 degrees
RTE 0-1 cm
AMS
600 series
9.5 mm & 11.5 mm width
650 series
11 mm & 13 mm width
Tip extenders, both ends
length 12-20 cm
Bendability ~110 degrees
AMS
Dura II
Interlocking PTFE segments with steel spring
10,12 mm
13 cm + tip extenders both ends
Bendability ~150 degrees
Inflatable
Concealment
‘Natural’
Rigidity
Expensive
Infection
Mechanical failure
Manual dexterity
Inflatable – 2 piece
AMS Ambicor
Combined cylinders + reservoir
Pump
limited fluid volume
Mentor Mark II
Inflatable-3 piece
AMS 700CX, CXM, CXR
Triple layer
Expands in width
Smallest 12 cm
AMS Ultrex
Expands in length and width
Antibiotic coating (inhibiZone)
Rifampicin & Minocycline
Inflatable-3 piece
Mentor Alpha 1, Titan & narrowbase
Smallest 10cm
Expands girth++
Oval
Bioflex
Lockout valve
Hydrophilic antibiotic adsorbant surface
Wednesday, June 3, 2009
Bladder cancer and BCG Immunotherapy
Bacillus Calmette-Guerin
First used 1921
Morales et. Al. 1976 (successful treatment in 7 of 9 patients of recurrent Ta and T1 tumours)
Live attenuated M.Bovis. (Freeze dried vaccine)
All derived from Pasteur Institute strain.
Connaught 81 mg or 180 * 10 8 CFU
Tice 12.5 mg or 2-8 *10 8 CFU
Pasteur
Frappier
Tokyo
Indications:
Mulitiple G2 pT1
G3 pTa / pT1, CIS
Monday, June 1, 2009
I am a lower pole calculus of 2 cm. My preferred treatment is:
Percutaneous nephrolothotomy
Why?
Lower pole study group (Albala, Clayman and et al, J Urol 2001):
122 pts, lower pole stone and symptoms, under 3cm, randomised to PCNL vs SWL, stratified by stone size
CLEARANCE RATES
LOWER Pole stone PCNL ESWL
1cm 100% 63%
1-2cm 92% 23% (but 56% by Lingman)
>2cm 85% 14%
SWL: stent for size >2.5 cm
PCNL: single stage procedure, used flexible endoscopy and fragmentation with laser, uss, lithoclast
Outcome: fragmentation to fragments less than 3mm
Clearance rate 11-20mm stones 23% vs 92% for SWL vs PCNL, 14% vs 100% for stones 21-30mm
No effect found from lower pole calyx anatomical factors
(cf Elbahnasy, where infundibulopelvic angle under 90°, length over 30mm and width <5mm all associated with poor clearance rates of stones using SWL)
Cost effectiveness to be stone free
Stones 11-19mm SWL 133% more than PCNL
Stones >20mm cost of SWL 411% greater than PCNL
No statistical difference in morbidity
Lower pole study group 2:
Ureteroscopy versus PCNL
1-2.5 cm lower pole stone
31% stone free in urs versus 76% for pcnl
Stone Ureteroscopy PCNL
1-2.5 31% 76%
Ureteroscopy versus ESWL for stone < 1cm (pearl, lower pole study 3 ) no diff between urs and eswl. (35% versus 50% statistically not significant) (Pearl Jurol 2005)
Stone Ureteroscopy ESWL
<1 cm 35% 50%
stones <10mm URS vs SWL, stones 11-25mm URS vs PCNL
• Why?
o Stone free rates 11-20mm 71%, >20mm 65% with URS (Grasso, 1999)
o All stones greater than 2cm clearance rate of 91% after second look procedure in pts with renal stones who were poor PCNL candidates (Grasso, J Urol 1998)
Why?
Lower pole study group (Albala, Clayman and et al, J Urol 2001):
122 pts, lower pole stone and symptoms, under 3cm, randomised to PCNL vs SWL, stratified by stone size
CLEARANCE RATES
LOWER Pole stone PCNL ESWL
1cm 100% 63%
1-2cm 92% 23% (but 56% by Lingman)
>2cm 85% 14%
SWL: stent for size >2.5 cm
PCNL: single stage procedure, used flexible endoscopy and fragmentation with laser, uss, lithoclast
Outcome: fragmentation to fragments less than 3mm
Clearance rate 11-20mm stones 23% vs 92% for SWL vs PCNL, 14% vs 100% for stones 21-30mm
No effect found from lower pole calyx anatomical factors
(cf Elbahnasy, where infundibulopelvic angle under 90°, length over 30mm and width <5mm all associated with poor clearance rates of stones using SWL)
Cost effectiveness to be stone free
Stones 11-19mm SWL 133% more than PCNL
Stones >20mm cost of SWL 411% greater than PCNL
No statistical difference in morbidity
Lower pole study group 2:
Ureteroscopy versus PCNL
1-2.5 cm lower pole stone
31% stone free in urs versus 76% for pcnl
Stone Ureteroscopy PCNL
1-2.5 31% 76%
Ureteroscopy versus ESWL for stone < 1cm (pearl, lower pole study 3 ) no diff between urs and eswl. (35% versus 50% statistically not significant) (Pearl Jurol 2005)
Stone Ureteroscopy ESWL
<1 cm 35% 50%
stones <10mm URS vs SWL, stones 11-25mm URS vs PCNL
• Why?
o Stone free rates 11-20mm 71%, >20mm 65% with URS (Grasso, 1999)
o All stones greater than 2cm clearance rate of 91% after second look procedure in pts with renal stones who were poor PCNL candidates (Grasso, J Urol 1998)
Male urethral Trauma
The important factors that need to be considered in the management of the Ijury in the Immediate settings include:
Mechanism of injury
Has the patient voided? Haematuria? Increase in swelling after voiding? (extravasation)
Examination
Signs of shock?
Perineum – extent of haematoma. Confined to perineum/penile shaft then Buck’s fascia intact. If more extensive then suggests rupture of Bucks fascia and will be confined by Colles fascia
Blood at urethral meatus?–present in 75% of anterior urethral trauma
PR – prostate should feel normal
Is bladder distended?
Investigation
Usual trauma investigations including bloods.
Injury may be contusion or laceration of the urethra.
Urethrography – if urethra intact this is a contusion injuries and the haematoma usually resolves without complication. May wish to prescribe analgesia and antibiotics as prone to infection. Patient should be encouraged to void.
If laceration then needs catheter either single attempt urethrally or through the abdomen- probably best done under GA in child.
Laceration injuries may allow extravasation of urine which can extend along penile shaft, and up abdo wall, extension limited by Colles fascia. This may become infected and require draiage.
Will need further assessment of urethra with urethrogram (up and down) in 4/52.
Most common problem is stricture formation at site of injury. The majority of which do not require surgical intervention.
Those that do require surgical intervention should have delayed repair >3/12 after injury.
Options include simple debridement and anastomosis if short stricture (<1cm). Longer strictures will require grafts or flaps to bridge deficiency.
What is urethrogram?
12/14ch catheter in fossa navicularis ( in the penile opening). 2mls in balloon to occlude urethra. 20 mls of undiluted contrast injected slowly and films taken at 30 degree oblique angle.
Mechanism of injury
Has the patient voided? Haematuria? Increase in swelling after voiding? (extravasation)
Examination
Signs of shock?
Perineum – extent of haematoma. Confined to perineum/penile shaft then Buck’s fascia intact. If more extensive then suggests rupture of Bucks fascia and will be confined by Colles fascia
Blood at urethral meatus?–present in 75% of anterior urethral trauma
PR – prostate should feel normal
Is bladder distended?
Investigation
Usual trauma investigations including bloods.
Injury may be contusion or laceration of the urethra.
Urethrography – if urethra intact this is a contusion injuries and the haematoma usually resolves without complication. May wish to prescribe analgesia and antibiotics as prone to infection. Patient should be encouraged to void.
If laceration then needs catheter either single attempt urethrally or through the abdomen- probably best done under GA in child.
Laceration injuries may allow extravasation of urine which can extend along penile shaft, and up abdo wall, extension limited by Colles fascia. This may become infected and require draiage.
Will need further assessment of urethra with urethrogram (up and down) in 4/52.
Most common problem is stricture formation at site of injury. The majority of which do not require surgical intervention.
Those that do require surgical intervention should have delayed repair >3/12 after injury.
Options include simple debridement and anastomosis if short stricture (<1cm). Longer strictures will require grafts or flaps to bridge deficiency.
What is urethrogram?
12/14ch catheter in fossa navicularis ( in the penile opening). 2mls in balloon to occlude urethra. 20 mls of undiluted contrast injected slowly and films taken at 30 degree oblique angle.
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