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. 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.
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 screening provide a strong argument for directing efforts at prevention Chan A, et al. Obstet Gynecol 2012
Reduction in the future risk of ovarian cancer is the single most common reason for normal ovaries to be removed at the time of hysterectomy, particularly in the post-menopausal women Parker WH, et al. Curr Opin Obstet Gynecol 2007 In women not at increased risk of ovarian cancer the disadvantages of prophylactic oophorectomy outweigh the advantages up to the age of 65 years. Parker WH, et al. Curr Opin Obstet Gynecol 2007 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. 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 uteroovarian arterial blood flow in the mesosalpinx, thereby leading to tissue damage to the ovary. In addition, venous drainage may be compromised because venous plexuses are located near the arteries. Cattanach JF, Milne BJ. Contraception 1988 However, given the dual ovarian blood supply, guaranteed both by infundibolopelvic vessels 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 in risk-reducing salpingectomy to ensure that these changes in surgical practice are both costeffective and safe to women 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.
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 standard TLH 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 average decrease of 9% in women submitted to total laparoscopic hysterectomy with adnexal preservation (standard procedure). Assuming a 10% decrease with this procedure, and a maximal clinically acceptable decreasing for equivalence of 15% in AMH levels in women after salpingectomy, a sample of at least 69 patients per group would have given 95% power and a one-sided significance level of 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 Seventy-nine (100%) patients re-called to be submitted again to ovarian reserve evaluation in 2015 Seventy-one (89.9%) women accepted to participate and were evaluated Eight (10.1%) women refused to participate to the follow-up study 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 E 2 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. Venturella R. et al. Unpublished data!
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!
According to this observation, simple salpingectomy might not offer maximal protection! 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
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 salpingectomy was 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. Venturella R. et al. Under review on Fertil Steril 2015
Baseline data Parameters Standard Salpingectomy Radical Salpingectomy p Group A (n.91) Group B (n.95) 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 E 2 (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 All data are expressed as mean and SD Venturella R. et al. Under review on Fertil Steril 2015
Primary and secondary outcomes measures Parameters Standard Salpingectomy Radical Salpingectomy p Group A (n.91) Group B (n.95) 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 Venturella R. et al. Under review on Fertil Steril 2015
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. Venturella R. et al. Under review on Fertil Steril 2015
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
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!!! Venturella R. et al. Eur J Canc Prev 2015 In Press
PRACTICE SETTING TYPOLOGY Associate professors 12% Full professors 6% Residents 3% Do you usually perform PBS in association with a hysterectomy without oophorectomy for benign indications? No 18% Academic obstetricians and gynecologists 34% Hospital obstetricians and gynecologists 45% Yes 82% Venturella R. et al. Eur J Canc Prev 2015 In Press
IF YES, WHY DO YOU PERFORM PBS? IF NO, WHY NOT? To reduce the risk of hydrosalpinges ; 66 To reduce the risk of pelvic pain ; 38 There is no benefit; 47 It increases the risk of surgical complications ; 19 It increases operative time; 14 To reduce the risk of reoperation ; 29 To reduce the risk of cancer ; 371 Venturella R. et al. Eur J Canc Prev 2015 In Press The risk of reoperation is the same regardless of whether bilateral salpingectomy is performed ; 24 It does not decrease the risk of ovarian and peritoneal cancers; 9
Do you believe there are additional risks to performing PBS in addition to hysterectomy or other form of tubal sterilization? Yes; 47 It had happened before this survey to have information on the new and the possibility of introducing PBS as a preventive measure? 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 No; 430 Venturella R. et al. Eur J Canc Prev 2015 In Press I have read the literature but I was not aware of the safety data published about; 97 Yes, I was aware of the safety data published about; 303
Salpingectomy as a primary method of sterilization has not been considered routinely until the past few years. Interestingly, for individuals in whom sterilization fails, it has been long been considered that bilateral salpingectomy is the 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 salpingooophorectomy (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
RRSO between the ages of 35 and 40 years is recommended for risk reduction in women at increased genetic risk of ovarian cancer. The age of RRSO may also be individualized according to the earliest age of onset in the family and personal choices. Salpingectomy can be considered at the completion of childbearing in women at increased genetic risk of ovarian cancer who do not agree to salpingooophorectomy. However, this is not a substitute for oophorectomy, which should 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-reducing oophorectomy will not receive the breast cancer risk reduction provided by oophorectomy.
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)