4. PROSTATA
Anatomía
La glándula prostática es un órgano
sexual accesorio localizado por debajo
de la vejiga y las ampollas diferenciales
con salida hacia la uretra
Tiene forma cono invertido y tamaño a la
de una nuez pequeña, cerrada por una
cápsula fibrosa y rodea a la uretra
En la eyaculación produce un liquido
alcalino que es componente del semen
5. Anatomy of the prostate gland
Prostatic
urethra
Prostate
Ejaculatory duct
openings
External urethral
sphincter
Bladder
Kirby R et al (Eds) Adapted from
Textbook of BPH 1996
6. PROSTATA
Estructura
Se distinguen 4 regiones distintas originadas de
diferentes segmentos de la uretra prostática:
La zona ventral o anterior, carece de glándulas,
compuesta de tejido fibromuscular
El resto es tejido glandular (3 zonas):
– Zona periférica (70%): comprende la porción
lateral posterior de la próstata
– Zona central (25%): rodea a los cond. eyac.
– Zona transicional (5–10%):
Kirby R et al (Eds). Textbook of BPH 1996
7. Lateral section of a normal prostate
Transition zone
Anterior
fibromuscular
area
Peripheral zoneCentral zoneSeminal vesicle
Ejaculatory
ducts
Urethra
Bladder wall
10. HISTOLOGIA.
Los estudios de diferentes partes de la próstata
indican que:
La HPB se origina en el tejido glandular y en la
uretra pre-prostática.
El Cáncer Prostático se origina primariamente
en la zona periférica donde se aprecian muy a
menudo cambios inflamatorios.
Kirby R et al (Eds). Textbook of BPH 1996
11. Crecimiento Prostatico. H P B
CAUSAS:
Excesos de masturbaciòn,
Actividad sexual frecuente,
Presencia de enf. Venereas,
Pensamientos eròticos,
Equitaciòn, Ciclismo, Clima frìo
12. H P B. Factores
Edad
Tabaquismo
Obesidad
Cirrosis e Ingesta de
alcohol
Factores Familiares
Factores Raciales
Dieta
Vasectomia y Act. Sexual
13. Hiperplasia Prostàtica Benigna
La HPB es la neoplasia
benigna mas frecuente
en el hombre
Sus cambios patológicos
se encuentran en el 50%
de los hombres de la
quinta década y en 90%
de la novena
La etiología de HPB es
multifactorial. Es
requisito esencial
tener testículos y
edad
14. Crecimiento prostatico.
Mecanismo molecular
Los andrógenos y principalmente la DHT, son
los princ. reguladores del crecimiento y
actividad prostática vía cascada de
interacciones moleculares.
La testosterona libre se convierte dentro de la
célula en DHT que se une a los receptores
androgénicos (RA) del genoma nuclear.
Denis L et al. 4th International Consultation on BPH 1997
20. H P B. Cuadro Clìnico
PROSTATISMO.
Sindrome Miccional
Con Crecimiento ò Hiperplasia
Por Obstrucciòn
21. H P B Cuadro Clìnico
FALTA DE CORRELACIÒN ENTRE
VOLUMEN DE LA HIPERPLASIA
Y LA SEVERIDAD DE LOS
SINTOMAS
22. H P B. Cuadro Clìnico
PROBLEMAS EN ALMACENAMIENTO Y
LLENADO VESICAL. (sìntomas
irritativos): Nicturia, Frecuencia,
Urgencia con Incontinencia, Disuria.
PROBLEMAS DE VACIAMIENTO
VESICAL. (sìntomas obstructivos):
Dism. Fuerza del chorro, Retardo en
inicio de micciòn, Pujo, Chorro
Intermitente, Sensaciòn Vaciamiento
incompleto, Retencion urinaria.
24. Sintomatolgìa por HPB
30 20 10 0 10 20 30 40
Wet clothes
Irritability
Dysuria
Frequency
Weak stream
Incomplete emptying
Intermittency
Dribbling
Urgency
Straining
Hesitancy
Nocturia
Inicio Tres años
Symptom
Bother
Percentage of men Lee AJ et al. Eur Urol
1996; 30: 11–17
27. Prostata Crecida
The normal prostate is
triangular, becoming
rounder as BPH develops
and the transitional zone
expands
28. Prostata Crecida
Localizaciòn
Tìpica de la HPB
en la zona
trancisional.
Desplazamiento
de los lòbulos
central y
perifèrico
Urethra
Transitional
zone
Central zonePeripheral zone
29. Desarrollo de la HPB
Cambios en la Vejiga y
Complicaciones de
La HPB
30. Desarrollo de la HPB
La HPB se desarrolla en varios pasos:
Se induce la hiperplasia microscópica
Se desarrollan nódulos microscópicos
Inicia la manifestación clínica de HPB:
– crecimiento prostático
– obstrucción del cuello vesical
– sintomatología del tracto urinario inferior
31. Desarrollo de la HPB
Nódulos microscópicos de estroma empiezan a
crecer en la próstata alrededor de los 30-40
años de edad.
Este crecimiento ocurre alrededor de la zona
trancisional en el región periuretral
desarrollándose hiperplasia glandular.
Los nódulos varían en tamaño desde varios
mms. A cms.
Los nódulos continuaran creciendo.
Kirby R et al (Eds). Shared Care for Prostatic Diseases 1995
32. Desarrollo de HPB
Se comprime la capa mas externa de la
próstata
Se crea una cápsula ajustada y por lo
mismo se forman lóbulos.
El tamaño y posición de los lóbulos en
relación a la vejiga y la uretra, determinara
el tipo y la severidad de los síntomas del
tracto urinario inferior.
Ocurrirá una obstrucción urinaria si la
próstata crecida estrecha a la uretra.
Kirby R et al (Eds). Shared Care for Prostatic Diseases 1995
33. Vejiga e HPB
El lóbulo medio se
proyecta dentro de la
base de la vejiga
La uretra prostática se
estrecha
La pared vesical forma
trabéculas y
engrosamiento
34. Efectos de la Obstruccion Urinaria.
Cambios irreversibles y
engrosamiento de la
vejiga.
Sangrado (hematuria)
Diverticulos
Infecciones Urinarias
repetitivas.
Càlculos urinarios
Hidronefrosis (dilataciòn)
Daño renal
35. DAÑO RENAL
Puede ocurrir aùn
con minima
sintomatologìa y la
lesiòn renal no es
siempre reversible
36.
37. H P B Epidemiologìa
Focos de Crecimiento
prostatico: 25-30 años
25 % de varones de 40 años
presentan HPB y 100 % a los 80
Esto no significa presencia de
enfermedad clìnica.
38. PROSTATISMO.
Epidemiologìa
La enfermedad sintomatica se presenta
despues de los 50 años
Incidencia a los 55-64 años: 30%
Mas de 64 años: 55%
El numero de personas con prostatismo
aumentará en cerca del 45 % en los
siguientes 10 años y todavia mas a la
otra decada. (1999)
39. H P B
Causa significativa de
deterioro de calida de
vida en gente mayor
Quienes sufren de HPB
son renuentes a acudir al
médico. (envejec, normal)
40. Hallazgos de molestias por HPB en la
consulta mèdica
0 10 20 30
Weak stream
Incomplete bladder emptying
Dribbling
Intermittency
Straining
Urgency
Hesitancy
Nocturia twice or more
Grado Sintomatologìa consultada aL doctor
Finding symptom bothersome
9.4%
19.0%
4.1%
16.3%
4.5%
28.3%
4.1%
12.8%
4.7%
20.4%
6.3%
30.7%
6.0%
16.6%
4.2%
19.0%
Garraway WM et al.
Br J Gen Pract 1993; 43: 318–21
41. Prevalencia de sintomatologia
moderada a severa (I-PSS ≥8)
Includes both hospital/clinical-based and community-based studies
Community-based study (n=2,115) men aged 40–79 years
Denis L et al. 4th International Consultation on BPH 1997
Prevalence (%)
0
10
20
30
40
50
60
50–59 60–69 70–79
Age (years)
Asia USA Canada
29% 31%
15%
40%
36%
27%
56%
44%
31%
42. Prevalencia de Sintomas Severos
0 2 4 6 8 10 12 14 16 18
40-49
50-59
60-69
70-79
28% a los 70 años y 13% a los 40-49
43. Interferencia con las
actividadesPercentage of men in whom urinary symptoms affected living
activities at least some of the time
Avoids visits to theatre, cinema,
church etc
Avoid outdoor sports
Avoid places without toilets
Not getting enough sleep
Cannot drive for 2 hours
Limit fluid before bedtime
Limit fluid before travel
13.4%
29.9%
18.4%
34.7%
8.0%
21.0%
10.3%
27.1%
13.2%
32.4%
6.2%
12.8%
6.7%
15.1%
CON HPBSIN HPB
Garraway WM et al.
Br J Gen Pract 1993; 43: 318–21
44. HPB. Calidad de Vida
0.00
0.10
0.20
0.30
0.40
0.50
Degree of
bother
Degree of
interference
Degree of
worry
OGWB
scale
Sexual
worry
Sexual
satisfaction
No = 0
Leve = 1–7
Mod. A Severa = 8–35
Age adjusted means
(s.e.) on 0–1 scale
Girman CJ et al. Urology 1994; 44: 825–31
45.
46.
47.
48.
49.
50.
51.
52.
53.
54. Diagnostico
Historia Clìnica; Sintomas y
Severidad, Antecedentes trauma
uretral y herediatrios, Enf,
Neurològicas, Hàbitos, etc.
Determinaciòn del volumen
prostatico.
Examenes de laboratorio y
Gabinete
58. Determinación del Volúmen
Prostático
La exactitud del tacto digital
depende de la experiencia del
examinador
Es mas seguro el uso de USG
transrrectal para determinar
el volumen prostático
59. Volùmen Prostático
El examen digital sobrestima el
tamaño prostatico en prostatas de
mas de 30 ml.
El USG transrrectal y la resonancia
magnetica son invasivos y caros
El APE sérico es una medida util
60. H P B Diagnòstico
ANTIGENO PROSTATICO
ESPECIFICO
EXAMEN GENERAL DE
ORINA
QUIMICA SANGUINEA
61. TRATAMIENTO
BASADO EN LA INTENSIDAD DE LOS SINTOMAS Y LOS
CAMBIOS EN LA CALIDAD DE VIDA:
Sìntomas Leves: Expectante,
Revisiones periòdicas
Sintomas Moderados: Tx mèdico ò
quirùrgico.
Sìntomas Severos: Cirugìa
62. CANCER DE LA PROSTATA
PROBLEMA DE SALUD MUNDIAL.
AUMENTA PREVALENCIA CON LA
EDAD:
63. CANCER PROSTATICO
PRIMER LUGAR EN EEUU (8%) Y EN
MEXICO (25%) EN VARONES DE
CUALQUIER EDAD
EN LA POBLACION GENERAL: 11%
(TERCER LUGAR EN FRECUENCIA)
SEGUNDA CAUSA DE FALLECIMIENTOS
EN VARONES 50 AÑOS EN EEUU
(PRIMERO EN SUIZA)
INCIDENCIA: 50a : 30% 80a : 70%
90a: 90%
64. CANCER PROSTATICO
CUADRO CLINICO
ASINTOMATICO EN ETAPAS INCIPIENTES
HEMATURIA, SINTOMAS OBSTRUCTIVOS Ò
SINTOMATOLOGIA POR METASTASIS EN
ETAPAS AVANZADAS
66. CANCER PROSTATICO
Antigeno Prostàtico Especifico
MARCADOR ONCOLOGICO SECRETADO
POR PROSTATA EN SEMEN
DX INICIAL DEL CANCER Y
SEGUIMIENTO TX
ES ESPECIFICO PARA LA PROSTATA
MAS NO PARA CANCER
VALORA RIESGO DE CA. NO PRUEBA
DX
72. Numbers of TURPs per 1,000 men
≥50 years of age per year
5.55.9*United Kingdom†
6.89Germany
5.510Denmark
813*Canada (Alberta)
8.914France
5.815United States
19951989Country
†
Men 45 years and older
*1990 data
Denis L et al. 4th International Consultation on BPH 1997
73. Etiologia de la HPB
The molecular processes underlying the
development of BPH are not completely understood,
but androgens and age play a central role
Several hypotheses have been proposed to explain
the pathogenesis of BPH:
– dihydrotestosterone (DHT) hypothesis
– oestrogen–testosterone imbalance
– stromal–epithelial interactions
– reduced cell death
– stem cell theory
74. Aetiology of BPH – dihydrotestosterone
Dihydrotestosterone (DHT) is the main androgen
responsible for prostate growth
Two isoenzymes of
5α-reductase
have been identified
5α-reductase
inhibitors
suppress DHT
formation
Adapted from Kirby R et al (Eds).
Shared Care for Prostatic Diseases 1995
75. The stem cell concept
Kirby R et al (Eds). Shared Care for Prostatic Diseases 1995
76. HPB
La HPB en forma macroscopica es la de
nódulos de tamaño variable de color gris a
amarillento
Los nódulos se componen de musculo liso,
epitelio y tejido fibroso en cantidades variables
Varía la proporción de estroma a epitelio en la
HPB, lo que sugiere la determinación de
sintomatología en un paciente prostático
Kirby R et al (Eds). Textbook of BPH 1996
77. HPB. Fase Patológica
Inician cambios histologicos en la prostata por
una tranformació neoplastica de las células
prostaticas
Estas celulas se comportan como celulas
embriónicas
Los conductos prostáticos se organizan
formando nódulos de estroma y epitelio
glandular
78. HPB. Fase macrscópica
No todo el tejido hiperplasico progresa a la fase
macroscópica en estos pacientes
La prostata se engrosa haciéndose aparente la
sintomatología en algunos hombres
A medida que el tejido glandular crece la capa
externa se comprime, creandose una cápsula
dura que forza a la glandula a formar lobulos
El tipo y severidad de los síntomas dependerá
del tamaño y posición de los lobulos en
relación a la vejiga y la uretra
81. BPH tissue
The two layers of
epithelial cells, the
basal cells (A) and the
secretory cells (B), are
visible
Also note that the
secretory cells are tall
and columnar in
appearance
B
B
A
Stroma
H and E stain of BPH tissue (200x magnification)
82. BPH tissue
This shows extensive
infolding of the duct
This is typical of BPH
tissue and is caused by
the stroma pushing
against the duct
H and E stain of BPH tissue (100x magnification)
83. BPH tissue
This shows the
typical lobe-like
architecture of BPH
nodules and the
associated blood
vessels (A)
H and E stain of BPH tissue (40x magnification)
A
A
A
84. Bladder changes
Flow is maintained in the early phases of outflow
obstruction as hypertrophy of the detrusor muscle
allows an increase in detrusor pressure
As outflow obstruction progresses, smooth muscle
hypertrophy occurs, followed by connective tissue
infiltration and reduced parasympathetic innervation
Impaired emptying results, caused by decreased
compliance in the bladder wall and secondary
detrusor instability, due to the previous events
Ultimately these changes translate into the
persistent symptoms of frequency, urgency and
urge incontinence
85. Bladder changes
It has been postulated that increasing amounts
of extracellular matrix (ECM) components such
as collagen are deposited in the bladder,
leading to impaired emptying
ECM components are thought to be produced
by the detrusor smooth muscle in both the
normal and abnormal bladder
Alteration of ECM expression is thought to be a
predominant pathophysiological feature in long-
term obstruction
86. Bladder changes
Rabbit model of obstruction
Rapid increase
in bladder mass
Bladder
function
impairment
Smooth muscle
hypertrophy
1–2 weeks
Rapid and
full bladder
function
restoration
Partial
recovery
of bladder
function
Obstruction
removed
Obstruction
Initial period of
obstruction
removed
Compensated stage
Decompensated stage
Bladder mass
stabilises
Bladder emptying
80–90% less than
control
Rapid increase in
bladder mass
Progressive loss
of ability of
bladder to empty Kirby R et al (Eds). Textbook of BPH 1996
87. BPH – a progressive condition
Progression of BPH can be defined in a number of ways:
– increase in prostate volume
– worsening of LUTS, bother, interference with daily
activities and quality of life
– deterioration in urinary flow rate
– increased risk of acute urinary retention (AUR)
– increased risk of needing surgery
The risk of progression differs between patients
Stratification by baseline parameters can be used to
predict risk of progression and aid with management
decisions
88. Key studies supporting BPH as a
progressive condition
Cohort studies:
Arrighi et al (1990), n=1,057
Barry et al (1997), n=500
Lee et al (1996), n=217
Olmstead County study, n=2,115
Meigs et al (1999), n=51,529
Treatment studies:
Flanigan et al (1998), n=556
PLESS trial (n=3,040)
89. Smaller studies supporting BPH as a
progressive condition
Williams et al (1999), n=128
Cucchi et al (1994), n=34
Bosch et al (1994), n=502
Ball et al (1981), n=107
Birkhoff et al (1976), n=156
91. Development of BPH: Early
Bladder
Muscle
surrounding
upper prostate
BPH
Prostatic urethra
Prostate
tissue
Surgical
capsule
92. Development of BPH: Intermediate
BPH
Narrowed
prostatic urethra
Prostate
tissue
Surgical
capsule
93. Development of BPH: Late
BPH
Severely narrowed
prostatic urethra
Prostate
tissue
Surgical
capsule
94. Mean total prostate volume
by decade of life
50–59 60–69 >70
0
10
20
30
40
50
60
70
80
Volume (ml)
Age (years)
Roehrborn CG et al.
J Urol 2000; 163: 13–20
95. PLESS – patterns of prostate growth
(untreated BPH)
McConnell JD et al.
N Engl J Med 1998; 38: 557–63
Baseline
Years
Prostate volume (mean % change from baseline)
20
10
–20
0
–10
1 2 3 4
97. Patterns of prostate growth
Olmsted County study:
– mean overall annual growth was 0.6 ml
over a period of 3.5 yrs, ranging from 0.4 ml in men
aged 40–59 yrs to 1.2 ml in men aged 60–79 yrs
– seven-year follow-up showed an annual mean
increase in volume of 1.9%
PLESS trial:
– mean annual growth was 1.8 ml over a period of 4
years in placebo-treated patients, ranging from 1.45
ml in men aged 50–59 years to 2.4 ml in men aged 70–
79 years
Jacobsen SJ et al. J Urol 1999; 162: 1301–6
Rhodes T et al. J Urol 2000; 163 (4 Suppl): 249
Roehrborn CG et al. J Urol 2000; 163: 13–20
99. PSA as an indicator of prostate volume
Data from 2,270 patients with BPH show that:
– increases in PSA and age are associated
with increases in prostate volume, but the
relationship with PSA is independent
– a log-linear relationship between PSA and
prostate volume exists
Hochberg DA et al. Prostate 2000; 45: 315–9
103. Deterioration of urinary flow rate –
key studies
Cohort study:
Olmsted County study (n=2,115)
Treatment study:
PLESS trial (n=3,040)
McConnell JD et al. N Engl J Med 1998; 38: 557–63
Roberts RO et al. J Urol 2000; 163: 107–13
104. PLESS trial – Maximum flow rate
(untreated BPH)
McConnell JD et al. N Engl J Med 1998; 38: 557–63
Maximum urinary flow rate
(mean change from baseline)
1.0
0.0
0.5
Baseline
Years
1 2 3 4
105. Olmsted County Study – Peak urinary
flow rates by age
0
5
10
15
20
25
40–49 50–59 60–69 70–79
Baseline
+1 year
+2 years
+3 years
Peak flow rate
(ml/sec)
Age (years)
Roberts RO et al. J Urol 2000; 163: 107–13
107. Deterioration of urinary flow rate
Conclusions
Data from the Olmsted County study
demonstrate a deterioration in urinary flow
with age
In contrast, data from the PLESS trial do not
demonstrate a decrease in flow in placebo-
treated patients over a period of 4 years
The differences between urinary flow rates by
baseline PSA tertile in PLESS are significant;
therefore baseline PSA can aid prediction of
change in flow
McConnell JD et al. N Engl J Med 1998; 38: 557–63
Roehrborn CG et al. Urology 1999; 54: 662–9
Roberts RO et al. J Urol 2000; 163: 107–13
109. Deterioration of LUTS and QoL –
key studies
Cohort studies:
Lee et al (1996), n=217
Olmsted County study, n=2,115
UreEpik study,n=4,800
Treatment studies:
PLESS trial (n=3,040)
110. PLESS – IPSS overall (untreated BPH)
Baseline
Years
Quasi-AUA symptom score
(mean change from baseline)
0
–1
–2
–3
1 2 3 4
McConnell JD et al. N
Engl J Med 1998; 38: 557–63
111. Olmsted County Study – progression
of symptoms over 4 years
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
2.0
40–49 50–59 60–69 70–79 40–79
Age (years)
*
*
*
*p<0.001 versus baseline
Jacobsen SJ et al. J Urol 1996; 155: 595–600
Change in AUA symptom
index from baseline
113. PLESS – Bother score* (untreated BPH)
Mean change in
bother score
Year of follow up
1 2 3 4
-4
-3
-2
-1
0
PSA: 0–12 ng/ml
Bruskewitz R et al.
Urology 1999; 54: 670–8
0
*Extended response option version of the BII
114. PLESS – Bother score by PSA tertile
(untreated BPH)
30 1 2 4
Mean change
in bother score
PSA (ng/ml) 1.4–3.2
PSA (ng/ml) 3.3–12
PSA (ng/ml) 0.0–1.3
-3
-2
-1
0
-0.5
-1.5
-2.5
Serum PSA (ng/ml)
Bruskewitz R et al.
Urology 1999; 54: 670–8
115. The UrEpik Study – Percentage of men with
moderate to severe symptoms (IPSS 8–35)
Boyle P et al.
J Urol 2000; 163 (S4): 208
0
10
20
30
40
50
40–49 50–59 60–69 70–79
Age group
Percentage
Boxmeer (NL)
Birmingham (UK)
Auxerre (FR)
Seoul (KR)
116. The UrEpik Study – Health care visits
by age and IPSS for any reason
0
2
4
6
8
10
0–7 8–19 20–35
IPSS groups
12
14
40–49 years
50–59 years
60–69 years
70–79 years
Mean number of health care
visits per person/year
Boyle P et al. Eur Urol 2000; 37 (S2): 402
117. Deterioration of LUTS and QoL
Conclusions
Data from the Forth Valley study demonstrate
deterioration of symptoms and degree of bother
over 3 years, findings confirmed by the Olmsted
County and PLESS data
Data from PLESS demonstrate that men with
higher PSA levels are at greater risk of
progressive symptoms and increased bother
The UrEpik study demonstrates worse
symptoms in older men, which correlate with
increased numbers of health care visits
Lee AJ et al. Eur Urol 1996; 30: 11–17; Jacobsen SJ et al. J Urol 1996; 155: 595–600;
McConnell JD et al. N Engl J Med 1998; 38: 557–63; Roehrborn CG et al. Urology 1999; 54: 662–9
Bruskewitz R et al. Urology 1999; 54: 670–8; Boyle et al (2000)
119. Risk factors for AUR and need for
surgery – key studies
Cohort studies:
Arrighi et al (1990), n=1,057
Lee et al (1996), n=217
Olmsted County study, n=2,115
Meigs et al (1999), n=51,529
Treatment studies:
Flanigan et al (1998), n=556
PLESS trial (n=3,040)
120. Baseline Relative Confidence
variable risk intervals
Age (years)
40–49 Reference category
50–59 4.21.2–14.8
60–69 4.01.1–14.8
70–79 3.10.8–12.3
Symptom severity score
None/mild (≤7) Reference category
Moderate/severe (>7) 5.62.6–11.9
Olmsted County Study – baseline variables
and risk for treatment – I
Jacobsen SJ et al. J Urol 1999; 162: 1301–6
121. Bladder changes
The LUTS that accompany BPH can be exacerbated
by changes occurring in the bladder as a
consequence of obstruction of the urethra, which
can be dynamic, static, or a combination of both
Ultimately this can lead to a loss of bladder
compliance and involuntary detrusor contractions;
this leads to more severe urinary tract symptoms
In addition, obstruction causes the bladder to
undergo compensatory changes, and gross
anatomical, histological, cellular and molecular
alterations occur in the bladder wall
122. Olmsted County Study – baseline
variables and risk for treatment – II
Peak flow rate (ml/sec)
>12 Reference category
≤12 2.81.4–5.5
Prostate volume (ml)
≤30 Reference category
>30 2.31.1–4.7
Serum PSA (ng/ml)
≤1.4 Reference category
>1.4 2.11.1–4.2
Baseline Relative Confidence
variable risk intervals
Jacobsen SJ et al. J Urol 1999; 162: 1301–6
123. Need for surgery by baseline risk
factors (n=1,057)
0
5
10
15
20
25
30
35
40
0 1 2 3
Number of risk factors
Risk factors: Change in size & force of stream,
sensation of incomplete emptying, prostate
enlargement on DRE
% requiring prostatectomy
Arrighi HM et al. Prostate 1990; 16: 253–61
124. Outcome of BPH patients randomised
to watchful waiting versus TURP
% of WW patients crossing-over to TURP
30
25
20
15
10
5
0
0 1 2 3 4 5
Elective cross-overs
high bother
Elective cross-overs
low bother
Post-treatment failure
cross-overs high bother
Post-treatment failure
cross-overs low bother
Years of follow-up
Flanigan RC et al. J Urol 1998; 160: 12–17
125. Age (years)
40–49 Reference category
50–59 0.90.4–2.4
60–69 2.10.9–4.7
70–79 4.82.2–10.6
AUA Symptom Index
0–7 Reference category
>8 2.31.3–4.0
Peak flow rate (ml/sec)
>12 Reference category
≤12 2.11.2–3.8
Baseline Relative Confidence
variable risk intervals
Olmsted County Study – relative risk
of AUR by baseline factors
Jacobsen SJ et al. J Urol 1999; 162: 1301–6
126. Risk of AUR by baseline prostate
volume and serum PSA
(untreated patients over 2 years)
0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5
<40ml ≥40ml <1.4ng/ml ≥1.4ng/ml
Volume Serum PSA
% with retention
Marberger MJ et al. Eur Urol 2000; 38: 563–8
127. Incidence of AUR by age
0
2
4
6
8
10
12
14
16
45–49 50–59 60–69 70–79 80–83
No of AUR events per
1000-person years
Age (years) Meigs JB et al.
J Urol 1999; 162: 376–82
128. Incidence of AUR or surgery by PSA and
volume tertiles (untreated patients)
Baseline PSA tertiles (ng/ml)
0–1.3 1.4–3.2 3.3–12
Roehrborn CG et al. Urology 1999; 53: 473–80
Patients (%)
0
4
8
12
16
20
24
14–41 41–57 58–150
Baseline prostate volumes (ml)
129. Conclusions – I
Do outcome measures change over time in
patients with BPH?
There is consistent evidence from
methodologically robust studies for:
– increases in prostate volume
– worsening of lower urinary tract symptoms
(LUTS), bother, interference, and quality of life
– deterioration in urinary flow rate
– increased risk of acute urinary retention (AUR)
– increased need for surgery
130. Conclusions – II
Which risk factors have predictive value for
patients with a high risk of BPH progression?
There is strong evidence for:
– serum PSA
– age
Good evidence requiring confirmation for:
– prostate volume
Evidence exists for:
– baseline symptoms
– baseline maximum urinary flow
132. Clinical presentation
LUTS may be divided into two broad categories:
Storage symptoms (irritative symptoms) which
tend to have a greater influence in provoking
patients to seek medical advice
Voiding symptoms (obstructive symptoms) –
physicians tend to be more concerned about
these symptoms, which are more likely to result
in serious sequelae
133. Clinical presentation
BPH is by far the most common diagnosis in
men presenting with prostate problems
Physicians are primarily concerned with making
an accurate differential diagnosis, in particular
to exclude prostate cancer or to make an early
diagnosis
If left undiagnosed and untreated, BPH can
progress to complete blockage of the urethra
and acute urinary retention (AUR). This
necessitates hospitalisation and catheterisation
to remove accumulated urine, and often
subsequent surgery
135. Initial evaluation of LUTS
Medical history
IPSS questionnaire
Bolter score
Physical examination and digital rectal
examination
Urinalysis
Serum PSA
Voiding diary
Chatelain Ch et al. 5th International Consultation on BPH 2000
136. Medical history
A detailed medical history should be performed
to identify other causes of voiding dysfunction
and comorbidities that may complicate treatment.
The focus should be on:
The nature and duration of symptoms
Previous surgical procedures
General health issues
Medications taken by the patient
Fitness for possible surgical procedures
Chatelain Ch et al. 5th International Consultation on BPH 2000
137. Physical examination
An examination should be performed to assess:
– the suprapubic area to rule out bladder
distension
– overall motor and sensor function
A digital rectal examination (DRE) to evaluate
the anal sphincter tone and prostate gland with
regard to approximate size, consistency, shape
and abnormalities suggestive of prostate cancer
Chatelain Ch et al. 5th International Consultation on BPH 2000
138. Standard tests
Standard tests:
Urinalysis by dipstick and examination for
sediment following centrifugation
Serum prostate specific antigen (PSA)
Voiding diaries (frequency - volume chart),
especially where nocturia is the dominant
symptom
Chatelain Ch et al. 5th International Consultation on BPH 2000
139. Optional tests
Optional tests:
Flow rate recording
Residual urine
Pressure - flow studies
Transabdominal or transrectal ultrasound
Ultrasonography or intravenous urography of
the upper urinary tract
Endoscopy of the lower urinary tract
Chatelain Ch et al. 5th International Consultation on BPH 2000
140. Digital rectal examination (DRE)
Clinical parameters that can be assessed by DRE include:
Size: transverse, longitudinal and posterior protrusion
Consistency: slight pressure over the surface to detect
whether:
– smooth or elastic – normal
– hard or woody – may indicate cancer
– tender – suggests prostatitis
Mobility: attempts made to move the prostate up and
down to the sides. A malignant gland may be fixed to
adjacent tissue
Anatomical limits: finger used to try to reach lateral
and cranial borders – seminal vesicles should be
impalpable; induration of these suggests malignancy
Kirby R et al (Eds). Shared Care for Prostatic Diseases 1995
141. Urinalysis
Urinalysis by ‘dipstick’ or microscopic
examination of sediment will allow BPH to
be distinguished from UTI or bladder cancer
and should be performed in all men presenting
with LUTS
If positive, urine microscopy and culture should
be performed and further imaging and
evaluation of the renal tract considered
142. Uroflowmetry
This is a technique for electronically recording the
rate of urine flow and the volume of urine passed
during micturation
It is a simple, well used, useful, independent
measure, which is helpful in:
– distinguishing between BPH and urethral
strictures or prostatitis
– predicting which patients will benefit from
surgery
– identifying the need for invasive urodynamic
studies
– to help distinguish bladder problems from BPH
Most often used as a rough screening procedure, as
a way to assess treatment outcome, and as a
technique for monitoring the progression of disease
143. Uroflowmetry
The flowmeter device measures the quantity of fluid
passed per unit time
In addition, several different values can be
calculated
– voided volume: the total amount of urine voided
– max flow rate (Qmax): the fastest rate at which
urination occurs
– average flow rate = voided volume/flow time
– time to maximum flow: time between the onset of
micturation and when peak flow occurs
– flow time: the time over which measurable urine
flow occurs
144. Uroflowmetry
Qmax is the most useful uroflow measure used
and provides a good indication of whether a
patient is obstructed or not
Patients with a value:
– <10 ml/sec are generally considered
obstructed
– >15 ml/sec are judged unobstructed
– in the range of 10–15 ml/sec are equivocal
Accuracy is improved if the voided volume
exceeds 150 ml
146. Uroflowmetry: unobstructed
Voided volume Vcomp 158.0 ml
Average flow rate Qave 12.2 ml/s
Max flow rate Qmax 18.5 ml/s
Time to max flow TQmax 4.8 s
Flow time TQ 12.5 s
Voiding time T100 13.5 s
70-year-old man
Normal flow
trace
147. Uroflowmetry: obstructed
133.0 ml
2.7 ml/s
7.0 ml/s
6.2s
48.5s
68.0s
Voided volume V comp
Average flow rate Q ave
Max. flow rate Qmax
Time to max. flow TQ max
Flow time TQ
Voiding time T100
70-year-old man
Moderate obstruction
due to BPH
Reduced average and
peak flow
Prolonged duration
148. Uroflowmetry: urethral stricture
Voided volume Vcomp 567 ml
Average flow rate Qave 4.9 ml/s
Max. flow rate Qmax 5.5 ml/s
Time to max. flow TQmax 0.5 s
Flow time TQ 115.0 s
Voiding time T100 117.0 s 50-year-old man
Plateau-shaped trace
Similar Qmax and Qave
Long duration
Voiding time
149. Uroflowmetry: detrusor underactivity
Voided volume Vcomp 356ml
Average flow rate Qave 10.0ml/s
Max. flow rate Qmax 17.6ml/s
Time to max. flow TQmax 6.0s
Flow time TQ 34.0s
Voiding time T100 35.0s
50-year-old man
Symmetrical trace
Variable TQmax
150. Further tests
Further examination and tests can be performed if these
are considered appropriate, these are shown below:
Prostatic biopsy (if rectal exam
and/or PSA warrant it)
Transrectal ultrasound of the
prostate (to assess prostate volume
and reveal early neoplasia)
Bladder residual urine volume
(by transabdominal
untrasound)
Pressure/flow urodynamics (to
assess the degree of bladder outlet
obstruction and to identify any
detrusor impairment)
Uroflowmetry
(Assesses urinary flow rate)
Invasive testsNon-invasive tests
151. Post-void residual urine volume
(PVRV)
PVRV measurement is performed non-
invasively using transabdominal ultrasound
It can be useful in assisting with treatment
decisions but should not be used alone to
diagnose BPH
Patients found to have a large PVRV should
receive active treatment, otherwise they may be
more likely to develop AUR or fail conservative
therapy
152. Post-void residual urine volume
(PVRV)
PVRV measurement can also be useful for
monitoring improvement or worsening of BPH
in non-treated patients
Although an increased PVRV may be indicative
of obstruction, more than one measurement
should be made because variation has been
known to occur between voids
153. Urodynamics
These are the only means by which outflow
obstruction can be diagnosed
It is expensive and invasive, involving the
introduction of a small catheter, either urethrally
or suprapublically, to measure detrusor
pressure within the bladder (generated by the
contracting bladder muscle minus rectal
pressure)
It can can be used to distinguish outflow
obstruction from impaired detrusor contractility
It has been suggested that this technique
should be confined to patients for whom
surgery to relieve obstruction is being
considered
155. BPH - an increasing problem
Humanistic burden of BPH
156. Estimates of total costs of BPH surgical
treatment (1990)
2.918.6024.906Sweden
0.6756.7037.800France
5.579.9055.670Belgium
2.2842.4096.430England
3.72123.54459.600Japan
8.88259.602304.500United States
Cost per
capita ($)
Population
(million)
US dollars
(million)
Country
Cockett AK et al. 2nd International Consultation on BPH 1993
157. Level of negative well-being experienced
during the past month
<0.0012.214.2
Worry about urinary function
becoming worse
<0.0019.029.4
Embarrassed by urinary
function
<0.0120.928.3
Worried about sexual
function
<0.014.89.0
Worried about prostate
cancer
<0.0018.731.1
Worry/concern: urinary
function
<0.0510.514.0Bothered by nervousness
p value*
BPH absent
(%)
BPH present
(%)
Indices of general
well-being
Tsang KK & Garraway WM. Prostate 1993; 23: 1–7*Chi-square test
158. Effect of BPH on Quality of Life – SF-
36
Hunter DJW et al. Urology 1995; 45: 962–71
0
20
40
60
80
100
SF-36 domains
Physical
functioning
Physical
role
Bodily
pain
VitalityEmotional
role
Social
Function-
ing
Mental
health
General health
perception
Men 55–65 years, with moderate
and severe urinary symptoms
Healthy men 55–64 years
Mean scale scores
159. BASURA DE HPB
DE AQUÍ EN ADELANTE SON CUADROS DE
ARRIBA DESECHADOS PARA LA PLATICA DE
ENFERMEDADES DE LA PROSTATA
160.
161. 5 alpha-reductase enzymes
Occurs as two isoenzymes (type 1 and type 2),
which are hydrophobic proteins
Genital tissue
Seminal
vesicles
Liver
Non-genital skin
Scalp
Enzyme
location
Chromosome 2Chromosome 5
Gene
location
254 amino acids259 amino acidsSize
Type 2Type 1
Russell DW & Wilson JD. Ann Rev Biochem 1994; 63: 25–61
162. Hormones and prostate growth
Hormones play a key role in the development and
functional activity of the prostate with free non-protein-
bound testosterone (T) being the active moiety which
enters prostate target cells
The testes synthesise and secrete 30% of plasma
oestrogens, although a major proportion are also
formed from androsteredione and T by aromatisation
In a younger man, free T is approx 2%, which
decreases to 1.25% by the 8th decade. Total T is
approx 30–40% of a 25-year-old’s level
90–95% of T is produced by the Leydig cells of the
testes; T levels decrease with increasing age and a
decrease in the number of Leydig cells
Kirby R et al (Eds). Textbook of BPH 1996
163. Variability of prostate volume –
Determination by TRUS and MRI
The mean variability of TRUS determination has
been reported to be 1.3–3.4%
No studies have investigated the natural
variability of prostate volume, which may
explain some of the variability observed
Aarnink RG et al. B J Urol 1996; 78: 219–23
164. HISTOLOGIA
Se identifican dos diferentes compartimentos
histológicos: un estroma fibromuscular y un
epitelio acino-ductal.
Tienen numerosos tipos celulares.
Las células ductales se encuentran soportadas
por una matrix de estroma y secretan el liquido
prostático hacia la luz de los conductos.
165. HISTOLOGIA
La zonas central y periférica de la próstata son
diferentes histológicamente.
La zona central tiene mas epitelio con nódulos
glandulares mas grandes de contorno irregular.
La zona periférica tiene un abundante estroma
de trama mas holgado y haces musculares
ordenados al azar
En la zona trancisional predominan los haces
de músculo liso compactado.
Kirby R et al (Eds). Textbook of BPH 1996
166. Epitelio de la próstata.
Las células columnares secretoras revisten
todo el sistema de conductos acinares en cada
zona prostática.
Las células basales permanecen paralelas a la
membrana basal y separan de ella a las células
secretoras.
Las células basales se dividen para dar origen a
células maduras secretoras.
Kirby R et al (Eds). Textbook of BPH 1996
167. Epitelio de la prostata.
Las células secretoras producen los siguientes
componentes del semen:
– Ácido cítrico
– Fosfatasa ácida
– Fibrinolisina
– Antígeno prostático especifico
Kirby R et al (Eds). Textbook of BPH 1996
168. Endocrinologia
La DHT es el andrógeno intracelular activo
responsable de la morfogénesis de la próstata en el
feto.
En ratas, la enzima 5-alfa reductasa (5-AR) se
localiza en el epitelio basal desde el primer día de
gestación.
El epitelio lumninal aparece en el 5o. Y 10o. Días
después de la aparición de la 5-AR
El mesenquima periductal se diferencia en músculo
liso en el tercero a quinto días lo que indica que las
células pueden ser blancos importantes para la
morfogénesis.
Kirby R et al (Eds). Textbook of BPH 1996
170. Desarrollo
En el recién nacido la glándula es parecida a
una estructura de músculo liso.
Temprano aparecen cantidades mínimas de T
(30–60 dias posnatal), (requisito para el
crecimiento normal de la prostata debido a una
alteracion de las propiedades de las celulas
madres prostaticas. El numero de celulas
madres determina el tamano de la glandula.
Esta T impactara en el futuro crecimiento
anormal de la glándula.
Kirby R et al (Eds). Textbook of BPH 1996
171. Development of the prostate:
Formation of the kidney
Hindgut
Allantois
Cloaca
Mesonephric
tissue
Ureteric
bud
Mesonephric
gut
Mesonephric
blastema
Urorectal
septum
172. Development of the prostate:
Ascent of the kidney
Bladder
Gonad and remnants
of mesonephros
Phallus
Urogential
sinus
Metanephros
Ureter
Rectum
173. Development of the prostate:
Formation of the prostate
Seminal vesicle
Prostate and
membranous
urethra
Urachus
Penile
urethra
Prostate
gland
Ductus
deferens
Anorectal
canal
174. Palpación digital de la próstata
0 5 10 15 20 25 30 35
% underestimation
30-39ml
40-49ml
> 50ml
Prostate volume
Roehrborn CG et al. Urology 1997; 49: 548–57
178. Crecimiento prostatico
Testosterone (T) is the
principal androgen
secreted by the testis
T is converted to DHT
by the enzyme 5α-
reductase (5-AR)
DHT is the active
intracellular androgen
that has the major
androgenic effect
This provides the
scientific basis for
the advent of 5-AR
inhibitors for the
management of BPH
179. Epidemiology
The lack of widely accepted diagnostic criteria
has hindered the epidemiological study of BPH
Confusing terminology and the features
of BPH have made prevalence difficult to
determine accurately
In most cases prevalence is based on
histological autopsy findings or the clinical
relevance of lower urinary tract symptoms
180.
181.
182.
183. Mecanismo molecular.
El proceso de unión de la DHT al RA produce
dimerización en una proteína (hsp-90) y
complejo RA-DHT.
Este complejo induce a un segmento del DNA
del genoma, trascripción de genes andrógeno-
inducibles expresión de APE y otros factores
del crecimiento y estimulación en el
crecimiento y división de las células estromales
y epiteliales
Crecimiento prostático
Denis L et al. 4th International Consultation on BPH 1997
184. Receptores Androgenicos
La cantidad de receptores androgénicos refleja
el grado de actividad androgénica durantes el
desarrollo normal de caract. sexuales masc.
Después de la pubertad existe disminución en
la sensibilidad al estimulo androgénico en todo
tejido dependiente de ellos. En la próstata
queda alta .
Los RA de alta afinidad son numerosos en el
epitelio que en el estroma
Denis L et al. 4th International Consultation on BPH 1997
185. Receptores Androgénicos
La combinación de niveles consistentes de
DHT y la expresión continua de receptores
androgénicos produce crecimiento sostenido
de la próstata, como parte del proceso normal
del envejecimiento.
186. Hormonas y Crecimiento prostático
DHT es el andrógeno activo
Aunque los niveles de T disminuyen con la
edad, la DHT permanecen elevados
DHT (T) también se sintetizan en las glándulas
suprarrenales
Ciertos metabolitos de la DHT pueden provocar
efectos estrogénicos débiles
Kirby R et al (Eds). Textbook of BPH 1996
187. Factores de crecimiento prostático
Componentes epiteliales y del mesenquima
prostático expresan numerosos factores de
crecimiento:
– Estimuladores de los factores de crec:
epidérmico (EGF), de los fibroblastos (FGF),
parecido a la insulina (IGF) y el factor alfa
transformador (TGF-α)
– Inhibidores: factor beta transformador o
apoptosis (TGF-β)
188. Factores de Crecimiento y desarrollo
de la próstata
Numerosos factores de crecimiento y de receptores
están bajo la influencia androgénica debido a las
interacciones DHT/RA–DNA
Esto provoca una balance entre la liberación de
factores estimulantes y factores inhibitorios (TGF-
beta)
La castración es la forma mas florida de la
apoptosis (resultado de la expresión disminuida de
factores estimuladores y aumento de los inhibidores
La interacción de los factores de crecimiento
determina finalmente la cantidad de tejido glandular
y estromal en la HPB
189. Variability of prostate volume –
Determination by TRUS and MRI
In a phase III N American finasteride study, 86%
of the reported variability of MRI-measured
prostate volume was between-patient variability
In the same study, only 43% of patients had 2
consecutive determinations within ±10%
Jepsen JV et al. J Urol 1998; 160: 1689–94
190. The UrEpik study is a prospective, multinational, cross-
sectional, urology, epidemiological study in Europe and
Korea, funded by an unrestricted research grant from
GlaxoSmithKline
Primary aims:
Determine the impact of BPH-associated symptoms
on QoL of patients and their partners
Quantify economic and QoL burden of UI and MED
Enhance understanding of these disorders
The UrEpik Study – evaluating the
impact of BPH, MED and UI
Boyle P et al. J Epid Biostat 1998; 3: 179–87
191. The UrEpik Study – evaluating the
impact of BPH, MED and UI
Secondary aims:
Identify factors predicting medical consultation
Characterise co-morbid conditions
Define cultural factors affecting
knowledge/attitudes to urological conditions
Determine healthcare resources used
Reassess ability of I-PSS to identify patients
with BPH
Boyle P et al. J Epid Biostat 1998; 3: 179–87
192. BPH - an increasing problem
Economic burden of BPH
Editor's Notes
ESQUEMA DE UNA SECCION CORONAL DE LA PROSTATA
ESQUEMA DE UNA SECCION CORONAL DE LA PROSTATA
PROSTATA CRECIDA EN RESONANCIA MAGNETICA DONDE SE APRECIA MAS REDONDEADA A MEDIDA QUE LA HIPERPLASIA SE DESARROLLA Y SE EXPADE LA ZONA TRANCISIONAL
ESQUEMA DE SECCION TRANSVERSA DE LA PROSTATA CRECIDA: LOCALIZACION TIPICA DE LA HIPERPLASIA NODULAR TIPICA EN LA ZONA TRANCISIONAL. Y DESPLAZAMIENTO POSTERIOR DE LAS ZONAS PERIPEFERICA Y CENTRAL.
&lt;number&gt;
The LUTS that accompany BPH can be exacerbated by changes occurring in the bladder as a consequence of obstruction of the urethra, which can be dynamic, static, or a combination of both
Ultimately this can lead to a loss of bladder compliance and involuntary detrusor contractions; this leads to more severe urinary tract symptoms
In addition, obstruction causes the bladder to undergo compensatory changes, and gross anatomical, histological, cellular and molecular alterations occur in the bladder wall
The LUTS that accompany BPH can be exacerbated by changes occurring in the bladder as a consequence of obstruction of the urethra, which can be dynamic, static, or a combination of both
Ultimately this can lead to a loss of bladder compliance and involuntary detrusor contractions; this leads to more severe urinary tract symptoms
In addition, obstruction causes the bladder to undergo compensatory changes, and gross anatomical, histological, cellular and molecular alterations occur in the bladder wall
ANATOMIA ZONAL DE LA PROSTATA NORMAL EN IMAGENES POR RESONANCIA MAGNETICA. SE APRECIA LA ZONA TRANCISIONAL EN FORMA TRIANGULAR,