Vercellini [Sola lettura] - Bollettino Emilia Romagna

DOLORE PELVICO CRONICO – RIMINI 2011
CPP ED ENDOMETRIOSI:
NUOVE PROSPETTIVE DI
DIAGNOSI E TERAPIA
Paolo Vercellini & Maria Pina Frattaruolo
Department of Obstetrics and Gynecology
Università degli Studi di Milano
Milan, Italy
CPP ED ENDOMETRIOSI: NUOVE PROSPETTIVE DI
DIAGNOSI E TERAPIA
- La laparoscopia è il “gold standard” per la
diagnosi di endometriosi
- La laparoscopia è un’indagine invasiva
invasiva,, che richiede
ospedalizzazione,, anestesia generale,
ospedalizzazione
generale, è associata a
morbilità ed è costosa
- La diagnosi non invasiva è indicata tra le priorità nella
ricerca sull’endometriosi
Rogers et al., 2009
CPP ED ENDOMETRIOSI: NUOVE PROSPETTIVE DI
DIAGNOSI E TERAPIA
Ecografia transvaginale nella diagnosi non invasiva di
endometriosi ovarica
ovarica:: dati della letteratura,
letteratura, 1993 – 2009
SENSIBILITA’:
84 - 100 %
SPECIFICITA’:
90 - 100 %
Moore et al., 2002
Garcia Velasco, 2009
Savelli, 2009
CPP ED ENDOMETRIOSI: NUOVE PROSPETTIVE DI
DIAGNOSI E TERAPIA
Diagnostic accuracy of transvaginal ultrasound for
non--invasive diagnosis of bowel endometriosis:
non
a systematic review and metameta-analysis
Pooled estimates
SENSITIVITY:
91 %
SPECIFICITY:
98 %
PPV:
98 %
NPV:
95 %
Hudelist et al., Ultrasound Obstet
Obstet.. Gynecol
Gynecol.. 2011
CPP ED ENDOMETRIOSI: NUOVE PROSPETTIVE DI
DIAGNOSI E TERAPIA
Diagnostic accuracy of transvaginal sonography
for bladder endometriosis
PPV :
100 %
NPV :
98 %
LR+ :
75.50
LR-- :
LR
0.75
Hudelist et al., Ultrasound Obstet
Obstet.. Gynecol
Gynecol.. 2011
CPP ED ENDOMETRIOSI: NUOVE PROSPETTIVE DI
DIAGNOSI E TERAPIA
Gli impianti peritoneali superficiali
sono l’unica forma di endometriosi
non identificabile con modalità
diagnostiche non invasive
CPP ED ENDOMETRIOSI: NUOVE PROSPETTIVE DI
DIAGNOSI E TERAPIA
Test diagnostico:
si applica a pazienti che si rivolgono al
medico a causa dei sintomi
Test di screening:
si applica ad individui asintomatici a rischio
di patologia
CPP ED ENDOMETRIOSI: NUOVE PROSPETTIVE DI
DIAGNOSI E TERAPIA
Applicazione di un test diagnostico
non invasivo per endometriosi:
endometriosi:
- infertilità
- dolore pelvico cronico
Overview of RCTs comparing laparoscopic ablation of lesions with no surgery
in infertile women with minimal or mild endometriosis
Source, year
Pre g n a n cie s/ To t a l
Exp e rim e n t a l g ro u p
C o n t ro l g ro u p
O R (95% , C I)
N o su rg e ry b e t t e r
A b la t io n o f le sio n b e t t e r
M a rco u x et al., 1997
63/ 172
37/ 169
2.06 (1.28, 3.33)
Pa ra z z in i et al., 1999
12/ 47
13/ 54
0.75 (0.30, 1.85)
C o m m o n o d d s ra t io
0.01
1.65 (1.06, 2.58)
0.1
0.5
1
2.0
10.0
100.0
O d d s Ra t io
Diamonds represent odds ratio of conception and horizontal lines 95% CI. BreslowBreslow-Day test
for heterogeneity:
heterogeneity: X2 = 13.24, P = 0.42. Data from Al
Al--Inany et al. (2000).
Vercellini et al., Hum. Reprod
Reprod.. 2009
CPP ED ENDOMETRIOSI: NUOVE PROSPETTIVE DI
DIAGNOSI E TERAPIA
Effect of surgery for stage II-IV endometriosis:
controlled studies
Author, year
Absolute benefit increase
(pain recurrence rate)
Sutton et al., 1997
37%
Abbott et al., 2004
48%
Jarrel et al., 2005
==
CPP ED ENDOMETRIOSI: NUOVE PROSPETTIVE DI
DIAGNOSI E TERAPIA
In letteratura vi è confusione tra il concetto di
“time--to“time
to-diagnosis” e “time“time-toto-laparoscopy”
La laparoscopia non è indispensabile per
diagnosi e trattamento
Kennedy S., Fertil
Fertil.. Steril
Steril.. 2006
CPP ED ENDOMETRIOSI: NUOVE PROSPETTIVE DI
DIAGNOSI E TERAPIA
The availability of a reliable nonnon-invasive test to detect
endometriosis would help to avoid worthless diagnostic
laparoscopies
Catenacci et al., 2009
HOWEVER
The availability of a simple test able to detect endometriosis
is expected to boost the demand for the test, and the ultimate
effect would be to increase the number of women who are
diagnosed with the disease
Somigliana et al., 2010
CPP ED ENDOMETRIOSI: NUOVE PROSPETTIVE DI
DIAGNOSI E TERAPIA
There is a very real possibility that a
non--invasive diagnostic test aimed at
non
detecting endometriosis in a very
specific symptomatic population may,
in fact, become a screening test
Somigliana et al., 2010
Somigliana et al., Hum. Reprod
Reprod..
2010
CPP ED ENDOMETRIOSI: NUOVE PROSPETTIVE DI
DIAGNOSI E TERAPIA
Disease mongering is the promotion of sickness that
widens the boundary definition of illness in order to
grow markets for those who sell and deliver
treatments
It is a process that turns healthy people into patients,
causes iatrogenic harm (both physical and
psychological), and wastes precious resources
Moynihan et al., 2008
CPP ED ENDOMETRIOSI: NUOVE PROSPETTIVE DI
DIAGNOSI E TERAPIA
Experimental drugs and proposed future therapeutic schemes for endometriosis
(literature data 19871987-2010)
Vercellini et al., Hum. Reprod
Reprod.. 2010
CPP ED ENDOMETRIOSI: NUOVE PROSPETTIVE DI
DIAGNOSI E TERAPIA
Aromatase inhibitors: pharmacological extravagance
-
During the reproductive period aromatase inhibitors
stimulate ovarian function
-
In premenopausal women, these compounds must be used
together with other drugs
-
When these combined regimens are used for
endometriosis, it is impossible to assess how much of the
effect on pain is related to which of the two medications
CPP ED ENDOMETRIOSI: NUOVE PROSPETTIVE DI
DIAGNOSI E TERAPIA
“ The general principles that should guide
medical management of endometriosis are not
different from those applicable to other chronic
inflammatory disorders: achievement of long
phases of disease remission is the reasonable
goal, and reappearance of symptoms at drug
discontinuation must not be considered as a
demonstration of inefficacy of therapy”
Effect of OCs and progestins as assessed in controlled trials on the treatment of symptomatic
endometriosis (literature data, 19901990-2010)
Vercellini et al., Hum. Reprod
Reprod.. 2010
Main results of individual studies included in systematic review of medical treatments for
rectovaginal endometriosis
Vercellini et al., Hum. Reprod
Reprod.. 2009
RESULTS OF STUDIES COMPARING CONSERVATIVE SURGERY FOR
OVARIAN ENDOMETRIOMAS WITH OR WITHOUT POSTOPERATIVE
LONG--TERM ORAL CONTRACEPTIVE USE
LONG
Horizontal lines indicate 95
95%
%CIs
CIs;; boxes show the studystudy-specific weight;
weight; rhombi represent combined effect
sizes;; dashed line indicates the overall estimate.
sizes
estimate.
Cost of 12 months of continuous medical treatment of rectovaginal endometriosis; Italy, 2009
Vercellini et al., Hum. Reprod
Reprod.. 2009
CPP ED ENDOMETRIOSI: NUOVE PROSPETTIVE DI
DIAGNOSI E TERAPIA
Scientific glasnost
- Outcome selection
- Placebo
Placebo--controlled design
- Monophasic OCs taken continuously or low
low--dose NETA
as the reference comparator
- Satisfaction with treatment vs pain relief
- Duration of study
- Intention
Intention--toto-treat analysis
CPP ED ENDOMETRIOSI: NUOVE PROSPETTIVE DI
DIAGNOSI E TERAPIA
Too soon, too late, too often, to seldom?
As beneficial as early diagnosis may be, without
careful analysis of the potential many factors
that may contribute to her pain, it may also send
the patient down a trail of endless,
inappropriate, and irreversible treatment
Steege J.F., Fertil
Fertil.. Steril
Steril.. 2006
CPP ED ENDOMETRIOSI: NUOVE PROSPETTIVE DI
DIAGNOSI E TERAPIA
Surgery for Endometriosis
Obviously, the skill of the surgeon is relevant to
the final outcome, but even the most talented
surgeon should think before recommending
surgery,“Why
surgery,“
Why do I do what I do?”
Garcia--Velasco & Arici
Garcia
Arici,, Fertil
Fertil.. Steril
Steril.. 2004
CPP ED ENDOMETRIOSI: NUOVE PROSPETTIVE DI
DIAGNOSI E TERAPIA
SURGICAL PROCEDURES AND THEIR COST ESTIMATES
AMONG WOMEN WITH NEWLY DIAGNOSED
ENDOMETRIOSIS: A US DATABASE STUDY
- Over 65% of patients had endometriosis
endometriosis--related surgical
procedures,, including hysterectomy,
procedures
hysterectomy, within 1 year of being
diagnosed with endometriosis
- The cost of surgical procedures related to endometriosis
places a significant financial burden on the healtcare system
Fuldeare et al., J. Med. Econ. 2011
CPP ED ENDOMETRIOSI: NUOVE PROSPETTIVE DI
DIGNOSI E TERAPIA
ORAL CONTRACEPTIVE
AND THE “ENDOMETRIOSIS DOMINO EFFECT”
Projection studies are urgently needed in order to
evaluate the impact of two different healthcare
models for women with endometriosis
endometriosis,, one based
mainly on longlong-term management with OCs and
progestins,, and the other based mainly on surgical
progestins
procedures targeted at lesion elimination
Vercellini et al., Hum. Reprod
Reprod.. 2011