recent studies have led to the development of a new ... · bilateral salpingectomy to the standard...

Type I tumors (low grade serous, low grade endometrioid, clear cell and mucinous carcinomas, and Brenner tumors) are generally indolent (but

chemoresistant!)and present in stage I (tumor confined to the ovary). They are characterized by specific mutations but rarely TP53 and are relatively stable

genetically.

Recent studies have led to the development of a new paradigm for the pathogenesis and origin of EOC, based on a dualistic model of carcinogenesis that divides EOC into 2 broad

categories designated types I and II.

Both type I and type II tumors develop from extraovarian tissue

that implants on the ovary. Both for LGSC and HGSC, the fallopian tube appears to be the source of the tumors

The mounting evidence that ovarian cancer does not develop in the ovary

and the lack of success of ovarian cancer screeningprovide a strong argument for directing efforts at prevention

Chan A, et al. Obstet Gynecol 2012

In women not at increased risk of ovarian cancer the disadvantages of prophylactic oophorectomy outweigh the

advantages up to the age of 65 years.

Reduction in the future risk of ovariancancer is the single most commonreason for normal ovaries to beremoved at the time of hysterectomy,particularly in the post-menopausalwomen

Over all, women with oophorectomy before 55 had about 8.5% excess mortality compared with ovarian conservation.

Women with oophorectomy before 59 had 4% excess mortality.

Parker WH, et al. Curr Opin Obstet Gynecol 2007

Parker WH, et al. Curr Opin Obstet Gynecol 2007

Harman H., et al. Climateric 2005

Nevertheless, the effects of salpingectomy on ovarian functions are still controversial. To the best of our knowledge, there are no strong

evidences on the effect of salpingectomy on surgical outcomes of a standard hysterectomy

It has been hypothesized that the destruction of the fallopian tube reduces the utero-ovarian arterial blood flow in the mesosalpinx, thereby leading to tissue damage to theovary. In addition, venous drainage may be compromised because venous plexuses arelocated near the arteries.

Cattanach JF, Milne BJ. Contraception 1988

However, given the dual ovarian blood supply, guaranteed both by infundibolopelvicvessels and from the ovarian branch of the uterine artery, and considering the additional anastomosis of these vessels at the tubal level, at the time of hysterectomy with salpingectomy, the whole infundibolopelvic blood volume, normally distributed between tubes and ovaries, becomes available to the ovaries.

Dietl J. Fertil Steril 2014

In order to validate a new preventive strategy, it is necessary to objectively asses

Assess the frequency of, and model the risk associated with STICs in both women at high risk and baseline risk for ovarian cancer and monitor gradual changes in the distribution of tumor histologies and patient history at diagnosis as a result of this initiative, and eventually determine if we have decreased

the number of ovarian cancers diagnosed per year.

in risk-reducing salpingectomy to ensure that these changes in surgical practice are both cost-

effective and safe to women

We retrospectively compared data of 79 patients who underwent TLH plus bilateral salpingectomy (group A),with

those of 79 women treated by standard TLH without adnexectomy (sTLH) (group B).

The goal of the study was to evaluate if ovarian function and surgical outcomes are modified by the addiction of

bilateral salpingectomy to the standard technique.

The data for these patients were compared with those of 79 women treated by standardTLH without adnexectomy, matched for uterine weight

Morelli M. et al. Gynecol Oncol 2013

A prior analysis conducted on our data demonstrated a post-operative AMH levels averagedecrease of 9% in women submitted to total laparoscopic hysterectomy with adnexalpreservation (standard procedure).

Assuming a 10% decrease with thisprocedure, and a maximal clinicallyacceptable decreasing for equivalence of15% in AMH levels in women aftersalpingectomy, a sample of at least 69patients per group would have given 95%power and a one-sided significance levelof 10%.

In our study, given a sample size of 79 patients in each group, power model resulted of 96.8%.

Nineteen patients (24%) submitted to TLH plus

salpingectomy in 2010, 22 (28%) in 2011 and 38 (48) in 2012

Venturella R. et al. Unpublished data!

Seventy-nine (100%) patients re-called to be submitted again to ovarian reserve evaluation in

2015

Eight (10.1%) women refused to participate to

the follow-up study

Seventy-one (89.9%) women accepted to participate and

were evaluated

Both women with and without menopausal symptoms have been analyzed. In ovulating women, ovarian reserve has been evaluated when early follicular phase has been confirmed by the presence of serum E2 level <60 pg/mL and P<1 ng/mL, in conjunction with ultrasound confirmation of the absence

of a dominant follicle >10mm in any of the ovaries.

The innovation introduced by our algorithm is that the final output is not a generic definition of good or poor ovarian reserve, like others tests already do.

Our test answers with a number, the patient’s OvAge.

Parameters Mean values±SD

Age at surgery (years) 45.85 ± 2.40

Age at follow-up (years) 49.61 ± 2.15

OvAge at follow-up (years) 49.34 ± 2.12

FSH at follow-up (mU/mL) 43.02 ± 19.92

AMH at follow-up (ng/mL) 0.12 ± 0.20

3D AFC at follow-up (n.) 1.91 ± 1.28

VI at follow-up (%) 2.80 ± 5.32

FI at follow-up (1-100) 19.37 ± 5.88

VFI at follow-up (1-100) 0.56 ± 1.12

Venturella R. et al. Unpublished data!

Recent evidence suggests that not only the fimbrial end of the tube but also the soft

tissues adjacent to the ovary in the mesosalpinx can give rise to neoplasms

According to this observation, simplesalpingectomy might not offer maximal

protection!

Objective: To study the effects of the radical excision of soft tissues adjacent to the ovary and fallopian tube on ovarian function and surgical outcomes in women undergoing laparoscopic bilateral prophylactic salpingectomy.

Design: Randomized-controlled trial (NCT02086370)

Setting: Magna Graecia University of Catanzaro

Patients: One-hundred-eighty-six women undergoing laparoscopic surgery for uterine myoma (n=143) or tubal surgical sterilization (n=43)between March 2014 and January 2015.

Main Outcome Measures: Ovarian reserve modification (Δ) prior to and post surgery was assessed as primary outcome. The operative time, variation of the haemoglobin level (ΔHb), postoperative hospital stay, postoperative return to normal activity, and complication rate were assessed as secondary outcomes.

Venturella R. et al. Under review on Fertil Steril 2015


Patients were randomly divided into two groups. In Group A (n=91), standard salpingectomywas performed. In Group B (n=95), the mesosalpinx was removed within the tubes.

Prior to and 3 months post surgery, AMH, FSH, 3D AFC, Vascular Index (VI), Flow Index (FI), Vascular-Flow Index (VFI) and OvAge were recorded for each patient.


Parameters Standard Salpingectomy

Group A (n.91)

Radical Salpingectomy

Group B (n.95)

p

Age (years) 41.16 ± 5.33 41.56 ± 5.45 0.61

Parity (children) 2.73 ± 1.1 2.60 ± 0.93 0.36

AMH (ng/mL) 0.93 ± 1.13 0.86 ± 1.01 0.65

FSH (mIU/mL) 12.97 ± 9.71 12.39 ± 7.88 0.66

E2 (pg/mL) 23.8±12.9 29.1±18.1 0.03

AFC (n) 7.80 ± 4.23 6.82 ± 4.68 0.14

VI (%) 0.97 ± 0.79 1.00 ± 0.98 0.43

FI (0-100) 31.28 ± 8.2 30.28 ± 9.07 0.79

VFI (0-100) 0.58 ± 0.48 0.55 ± 0.57 0.71

OvAge (years) 39.50 ± 5.43 40.13 ± 5.20 0.42

Baseline data

All data are expressed as mean and SD


Primary and secondary outcomes measures

Parameters Standard Salpingectomy

Group A (n.91)

Radical Salpingectomy

Group B (n.95)

p

Δ AMH (ng/mL) −0.09 ± 0.24 −0.07 ± 0.22 0.54

Δ FSH (mIU/ml) 0.47 ± 0.86 0.37 ± 0.84 0.40

Δ AFC (n) −0.33 ± 0.73 −0.26 ± 0.61 0.44

Δ VI (%) −0.10 ± 0.31 −0.11 ± 0.25 0.85

Δ FI (0-100) −0.74 ± 2.02 −0.61 ± 1.54 0.60

Δ VFI (0-100) −0.08 ± 0.23 −0.06 ± 0.21 0.61

Δ OvAge (years) 0.03 ± 0.12 0.04 ± 0.11 0.59

Operative time (min) 13.70 ± 5.70 15.01 ± 5.23 0.10

Δ Hb (g/dL) 1.52±0.79 1.35±0.83 0.17

Postoperative hospital stay (days) 2.07±0.70 2.14±0.66 0.48

Postoperative return to normal activity (days) 9.20±3.30 8.73±3.30 0.33

Complication rate (%) 0 0 -

All data are expressed as mean and SD


Even when the surgical excision includes the removal of the mesosalpinx, salpingectomy does

not damage the ovarian reserve. Moreover, radical salpingectomy with excision of the mesosalpinx did not alter blood loss, hospitalization stay, or return

to normal activities.

A demonstration of the absence of any detrimental effects of the radicalization of the currently practiced standard

technique for salpingectomy represents a new and important step in the long but exciting process that may

lead to one of the most important scientific revolutions in gynaecological surgery of the last few centuries.

The finding of equivalent outcomes in patients undergoing hysterectomy and salpingectomy, compared to hysterectomy alone, which was documented in the study by Morelli et al, is of general interest to the gynecology community, at this particular time,

because of recent changes in our understanding of the histogenesis of HGSC.

With regard to whether there are implications for subsequent ovarian function or an increased likelihood of complications, Morelli et al. have demonstrated that there are

no detectable complications of performing salpingectomy at the same time as hysterectomy, the data of which can be used immediately in counseling patients.

Parker W. Menopause 2014

Venturella R. et al. Eur J Canc Prev 2015 In Press

The objective of the study was to examine obstetrician-gynaecologists’ knowledge, opinions, and practice patterns relating to opportunistic

salpingectomy in the general population.

An anonymous electronic survey was sent to all Obstetrics and Gynaecology Residency Program

Directors, Full and Associate Professors, Delegates of FIGO, SIGO and AOGOI.

The survey was available online for completion between January 3 and July 2, 2014

More than two thousand colleagues invited to participate

A total of 479 surveys were returned

The largest survey published on the topic !!!


Residents3%

Hospital obstetricians and gynecologists

45%

Academic obstetricians and gynecologists

34%

Associate professors12%

Full professors6%

PRACTICE SETTING TYPOLOGY

Yes82%

No18%

Do you usually perform PBS in association with a hysterectomy without oophorectomy

for benign indications?


To reduce the risk of pelvic

pain ; 38

To reduce the risk of cancer ; 371

To reduce the risk of reoperation ; 29

To reduce the risk of hydrosalpinges ; 66

IF YES, WHY DO YOU PERFORM PBS?

It increases the risk of surgical

complications ; 19 It increases operative time; 14

It does not decrease the

risk of ovarian and peritoneal

cancers; 9

The risk of reoperation is the same regardless of

whether bilateral salpingectomy is performed ; 24

There is no benefit; 47

IF NO, WHY NOT?


No; 430

Yes; 47

Do you believe there are additional risks to performing PBS in addition to

hysterectomy or other form of tubal sterilization?

Yes, I was aware of the safety data

published about; 303

I have read the literature but I was not aware of the safety data published

about; 97

Yes, I have heard about

it at a conference ;

35

Yes, I was asked about by one or more patients ; 7

No, I had never heard of PBS; 21

It had happened before this survey to have information on the new and the possibility of

introducing PBS as a preventive measure?

Salpingectomy as a primary method of sterilization has notbeen considered routinely until the past few years.Interestingly, for individuals in whom sterilization fails, it hasbeen long been considered that bilateral salpingectomy isthe preferred method to ensure definitive treatment.

A recent case-control study over a 45-year period found that the risk of serous ovarian cancer after salpingectomy was reduced by more than 60% as compared with a group of

women who were either not sterilized or had a tubal interruption sterilization. Lessard-Anderson et al,. Gynecol Oncol 2013

The ideal BRCA carrier candidate for RRS would be: a premenopausal woman with a prior risk-reducing mastectomy desiring ovarian preservation for the medical and

cognitive benefits

The ideal trial to verify equivalence of salpingectomy (RRS) and salpingo-oophorectomy (PBSO) should include:• Salpingectomy once reproductive desire is accomplished (<40 ys)• CA125 and ETV every 6 months • Ovariectomy at 40 years with inspection for pathologic evidence of disease

If no evidence of ovarian cancer is found in the original cohort of RRS women equivalency trial of RSS to RRSO without the second surgery.

Anderson CK et al. Int J Gyn Cancer 2013

Anderson CK et al. Int J Gyn Cancer 2013

Salpingectomy can be considered at the completion of childbearing in women atincreased genetic risk of ovarian cancer who do not agree tosalpingooophorectomy. However, this is not a substitute for oophorectomy, whichshould still be performed as soon as the woman is willing to accept menopause,preferably by the age of 40 years. Women delaying or refusing risk-reducingoophorectomy will not receive the breast cancer risk reduction provided byoophorectomy.

RRSO between the ages of 35 and 40 years isrecommended for risk reduction in women at increasedgenetic risk of ovarian cancer. The age of RRSO may alsobe individualized according to the earliest age of onset inthe family and personal choices.

We are enrolling the first 80 patients who agree to implement PBS to LPS cholecystectomy (study group), starting from January 1, 2013. Other 80

patients who will ask us to undergo cholecystectomy without the addiction of PBS will constitute the control group

We are working with regional and national competent offices to develop a unique code for salpingectomy performed for OC risk

reduction.

To address specific genomic and transcriptomic risk pattern, different by BRCA mutation, in patients with HGSC

To validate already promising serum biomarkers and to try to address a

reliable cytological method to screen p53 positivity on tubal cells (both

obtained by cervicovaginal thin prep and by hysteroscopic collection)

recent studies have led to the development of a new ... · bilateral salpingectomy to the standard...

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