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Should we still perform tubal ligation instead of salpingectomy at the time of female sterilization?
P a lo m a L o b o A b a s c a l Hospital Universitario Infanta Sofía. San Sebastián de los Reyes, Madrid. Spain. Universidad Europea. Madrid. Spain
Disclosures
• N o c o n f l i c t o f in t e r e s t r e g a r d in g t h e c o n t e n t s o f t h i s le c t u r e
Female sterilization prevalence
• Female sterilization is the most commonmethod of contraception worldwide,used by 19 percent of all women ages
15 to 49 years who are married or in arelationship union.
• Reliance on female sterilization is highest
in Asia (23.4 %) and Latin America andthe Caribbean (26%), and lowest inAfrica (1.7%) and Europe (3.8%).
Tubal sterilization failure rate. The CREST study
• Cumulative 10-year probability of pregnancy depends on • Sterilization Technique (parcial salpingectomy, silicone rings, bipolar coagulation…)• Age of the patient • Time from the procedure
Age-dependent
Dependent on remaining years of potential fertility
CONCLUSIONS:• Although tubal sterilization is highly effective, the risk of sterilization failure is higher than generally reported. • The risk persists for years after the procedure and varies by method of tubal occlusion and age.
Salpingectomy as primary method of sterilization
U n t il th e p a s t fe w y e a rs s a lp in g e c to m y w a s re s e rv e d fo r in d iv id u a ls in w h o m s te r i l iz a t io n fa ils
a n d it h a s b e e n c o n s id e re d th e p re fe r re d m e th o d to e n s u re d e f in it iv e t re a tm e n t .
A shift in the paradigm of ovarian cancer
p 5 3
s ig n a tu re
S T IC
S e e d in g
o f c e l ls
2
For many epithelial malignancies the cell origin is well defined (colon, cervical cancer…)
This is not the case for ovarian epithelial cancer Many theories have been proposed to understand the cells of origin and the mechanisms of carcinogenesis.
Traditionally epithelial ovarian cancer has been assumed to arise from the epithelial surface of the ovary ( coelomic epithelium)
Incessant ovulation hypothesis proposed by Fathalla in1971
Epithelial ovarian cancerW h a t d id w e k n o w ?
Müllerian metaplasia of the coelomic epithelium
Dysplasiaand
Cancer
Higher risk in PCOS patients
Lower risk with pregnancy, breast feeding and COC use.
The gonadotropin hypothesis: overstimulation of ovarian surface epithelium by FSH and LH leads to proliferation and risk of malignant transformation.
Lower risk with pregnancy, breast feeding and COC use.
Coelomic epithelialdamage
Inflammation DNA damage
Ovulation Follicular rupture
Higher risk in PCOS, nulliparous, and postmenopausal women.
Development of Cortical inclusion
cysts(CICs)
Epithelial ovarian cancerW h a t d id w e k n o w ?
These and other theories have been proposed to understand how coelomic epithelium undergo metaplasia and dysplasia
• Benign ovarian cystadenomas can progress into a borderline tumor and later to a low grade malignancy.• Endometriosis is linked to endometrioid and clear cell cancers
• The progression from low grade to high grade serous carcinomas is extremely rare.
High grade serous carcinoma represents 70%
of epithelial ovarian cancers
Usually diagnosed at an advanced stage
(III, IV)
High mortality
Traditional theories do not explain the pathogenesis of High grade serous carcinoma
Tubal origin of ovarian high grade serous carcinoma
PiekJMJ, J Pathol 2001;195:451-59
Prophylactic tubal removal in BRCA 1 carriers or women who belong to families
with high risk of ovarian cancer development.
STIC “serous tubal intraepithelial carcinoma”
Epithelial stratification Nuclear atypia
Active proliferation
P53 signature:Nuclear enlargement
P53 mutationLack of cilia
After close examination of tubal segments these hyperplastic and dysplastic lesion resembled high-grade serous ovarian cancer without invasion.
S h i f t in g t h e p a r a d ig m
Tubal epithelial cells from the fimbria are dislodged
and implant on the denuded surface of the ovary resulting in the formation of an
inclusion cyst.
Ovulation: the ovarian surface ruptures with
expulsion and transfer of the oocyte to the fimbria.
Anatomical close relationship of fallopian tube with the ovary at
the time of ovulation
T h e O r ig in a n d P a t h o g e n e s is o f E p it h e l ia l O v a r ia n C a n c e r
A P r o p o s e d U n if y in g T h e o r y : S e r o u s c a r c in o m a .
Low grade serous carcinoma:
Mutation KRAS/BRAF/ERRB2From an inclusion cyst
Often develops from a serous borderline tumor which arises from a serous cystadenoma.
High grade serous carcinoma:
Mutation TP53From an inclusion cyst
High grade serous carcinoma: Direct dissemination or shedding of STIC “serous tubal intraephitelial carcinoma”cells onto the ovarian
surface.
Kurman Rj. Am J Surg Pathol 2010; 34:433-443.
Serous tumors very sim ilar to
fallopian tube epithelium
T h e O r ig in a n d P a t h o g e n e s is o f E p it h e l ia l O v a r ia n C a n c e r
A Proposed Unifying Theory: Endom etrioid and clear cell carcinom a.
Kurman Rj. Am J Surg Pathol 2010; 34:433-443.
Endometrial tissue by a process of retrograde
menstruation implants on the ovarian surface to form an
endometrioid cyst from which a LG endometrioid or clear cell carcinoma can develop.
Endometrioid and clear cells tumors
very similar to
endometrium
3
Expanded dualistic model of ovarian carcinogenesis
Kurman RJ. Am J Pathol 2016, 186: 733-747
Low grade Slow growing
Borderline precursors
High gradeEvolve rapidly
No precursors in the ovary
Why salpingectomy for sterilization?Evidences
• 60-75% of high grade serous ovarian carcinomas are associated with tubal intraephitelial carcinoma (STIC).
Bilateral tubal interruption confers some protection towards developing ovarian cancer. • Effects on ovarian vascularization that may affect its function • Acts as mechanical barriers against • Ascending vaginal carcinogens • Ascending proximal tubal and endometrial cells.
CibulaD. Acta ObstetGynecol Scand2011;90:559-63.
The precursor lesions arelocated in the distal portion
of the fallopian tube.
Jones PM. Frontiers in Oncology. 2013 | Volume 3 | Article 217
Salpingectomyshould confer
more protection
T u b a l l ig a t io n a n d r is k o f o v a r ia n c a n c e r
Review and meta-analysis
Cibula D. Hum Reprod 2011;17:55-67.
34%
Protection persist 10-14 years after the procedureConfirmed for Endometrioid and serous cancer
T u b a l l ig a t io n a n d r i s k o f o v a r ia n c a n c e r
Pooled analysis of case-control studies
Sieh W. Int Journal of Epidemiol. 2013;42:579-589.
The magnitude of risk reduction was significantly greater for endometrioid and clear cell cancers than for HGSC.
These data support the theory that these cancers originate from exfoliated endometrial cells. Conversely, HGSC appear to arise predominantly in the distal tube.
Therefore, to substantially reduce the risk of invasive serous cancer, the distal tube must be ablated or removed.
52%48%
19%
Salpingectomy for ovariancancer preventionRecom m endations
• When counseling women about laparoscopic sterilization methods, clinicians can communicate that bilateral salpingectomy can be consider a method that provides effective contraception.
• Prophylactic salpingectomy may offer clinicians the opportunity to prevent ovarian cancer in their patients.
• Randomized controlled trials are needed support the validity of this approach to reduce the incidence of ovarian cancer.
ACOG Committee Opinion 620-January 2015.
L o w r is k
p o p u la t io n
“The approach to sterilization should not be influenced by the theoretical benefit of salpingectomy”
Salpingectomy and ovarian cancerrisk reduction
• Population-based cohort study in Sweden.• 251.465 women with previous surgery on benign indication (sterilization, salpingectomy, hysterectomy, and bilateral salpingo-
oophorectomy [BSO], hysterectomy) compared with the unexposed population (n = 5.449.119) between 1973 and 2009.
• Data were analyzed with Cox regression models.
• The effects of one-and two-sided salpingectomy were considered in a sub-analysis.
35%
28%
Results:
• There was a statistically significantly lower risk for ovarian cancer among women with previous salpingectomy(HR = 0.65, 95% CI = 0.52 to 0.81) when compared with the unexposed population.
• There was a statistically significant risk reductions among women with previous sterilization(HR = 0.72, 95% CI = 0.64 to 0.81). • Bilateral salpingectomy was associated with a 50% decrease in risk of ovarian cancercompared with the unilateral procedure (HR =
0.35, 95% CI = 0.17 to 0.73, and 0.71, 95% CI = 0.56 to 0.91, respectively).
50%
Conclusion:
• Salpingectomy on benign indication is associated with reduced risk of ovarian cancer. • These data support the hypothesis that a substantial fraction of ovarian cancer arises in the fallopian tube. • These data suggest that removal of the fallopian tubes by itself, or concomitantly with other benign
surgery, is an effective measure to reduce ovarian cancer risk in the general population.
Falconer H. JNCI 2015;107(2): dju410
4
Salpingectomy…only for ovarian cancer prevention?
• Bilateral salpingectomy provide the best immediate and long-term contraceptive efficacy b e st im m e d ia te
The differences in pregnancy risk
after tubal interruption or salpingectomy
The risk of operative and perioperative
complications of the different techniques
The potential complications of
tubal interruption and salpingectomy
The impact over the ovarian reserve
of the different techniques
• W e should explain to wom en
Complications of tubal interruption
• F is t u la o r r e c a n n u la t io n U n in t e n d e d p r e g n a n c y
• H id r o s a lp in x C o n s u lt a t io n s , in t e r v e n t io n s
• E c t o p ic p r e g n a n c y in t h e t u b a l r e m n a n t
• The 10-year cumulative probability of ectopic pregnancy for all methods of tubal sterilization combined was 7.3 per 1000 procedures.• The cumulative probability varied substantially according to the method of sterilizationand the woman’s age at the time of sterilization. • Women sterilized by bipolar tubal coagulation before the age of 30 yearshad a probability of ectopic pregnancy that was 27 timesas high
as that among women of similar age who underwent postpartum partial salpingectomy.
Peterson HB.N Engl J Med 1997;336:762-7
Impact of extent of excision in ovarian reserve
Methods: Patients were randomly divided into two groups. In group A (n=91), standard salpingectomy was performed. In group B (n = 95), the mesosalpinx was removed within the tubes. Prior to and 3 months after surgery, antimullerian hormone (AMH), FSH, three-dimensional antral follicle count (AFC), vascular index (VI), flow index (FI), vascular-flow index (VFI), and OvAge were recorded for each patient.
Results: No significant difference was observed between groups for ∆AMH, ∆FSH, ∆AFC, ∆VI, ∆FI, ∆VFI, and ∆OvAge. Moreover, the groups were similar for operative time, ∆Hb, postoperative hospital stay, postoperative return to normal activity, and complication rate. Conclusions: Even when the surgical excision includes the removal of the mesosalpinx, salpingectomy does not damage the ovarian reserve. Moreover, wide salpingectomy with excision of the mesosalpinx did not alter blood loss, hospitalization stay, or returnto normal activities.
Venturella R. Fertil&Steril 2015;104:1332-9.
R is k a n d c o m p lic a t io n o f s a lp in g e c to m y v e rs u s tu b a l l ig a t io n
• Tubal sterilization cohort: Salpingectomy v tubal ligation • Additional surgical time: 10 minutes • No differences in blood loos
• Length of hospital stay • Hospital readmission
• Salpingectomy: open versus laparoscopic approach • Additional surgical time: 14 minutes • Significantly more blood transfusions• Longer length of hospital stay ( 3 days; 70% postpartum)• Higher hospital readmission
McAlpine JN. AJOG 2014;210:471. e1-e11.
The opportunistic salpingectomy do not increase the risk of operative/perioperative complications
and appears both feasible and safe.
n=15. 288 n=2.492
Salpingectomy for permanent contraception
The question should not be focused only on ovarian cancer prevention; rather, the more important questionshould be:
• Why we are not offering women a chance for near 100% efficacy by removing the Fallopian tube completely for sterilization?
To avoid surgical risks?• Salpingectomy is safe and feasible and do not confer higher surgical risk compared with tubal interruption
To avoid risk of regret?• The younger the woman, the more likely she will regret choosing a permanent form of contraception.• For women who are not certain, LARC methods offer equal to or greater efficacy than tubal interruption
procedures and women should be counseled more carefully about LARC rather than a less effective sterilization method that also has a risk of ectopic and ectopic pregnancy.
Creinin MD. Obstet & Gynecol 2014;124:596-9
Why we are not offering women a chance for near 100% efficacy by removing the Fallopian tube completely for sterilization?
Do we have reasons for changing our practice?
Operative time
Perioperative complications
No option for tubal reversal
Effect on ovarian reserve
Ovarian cancer risk reduction
Lower failure rate
5
Do we have reasons for changing our practice?
Operative time
Perioperative complications
Effect on ovarian reserve Ovarian cancer risk reduction
Lower failure rate
Yes wehave!!
Tubal sterilization Recom m endations ( to take hom e)
• For women undergoing surgical sterilization, all options for sterilization should be discussed, includingcomplete salpingectomy, and wemust communicate that sterilization by salpingectomy• It is not reversible• Has higher efficacy than tubal interruption• According to the actual evidence may confer greater protection against most subtypes of ovarian cancerincluding High grade serous carcinomas
• The available data regarding minimal added surgical time and risk of morbidity should be share with thewomen.
• Opportunistic salpingectomy for permanent sterilization should be offered both in cases of interval tubal
sterilization and at the time of cesarean section.
Thank you very much for your attention!!Köszönöm szépen!!