Bilateral salpingectomy: An opportunity to reduce cancer risk

February 16, 2017

The data, say the authors, support counseling post-reproductive women undergoing hysterectomy about the risks and benefits of retaining their fallopian tubes.

None of the authors has a conflict of interest to report in respect to the content of this article.

 

Here we outline the rationale and data supporting a policy of performing bilateral salpingectomy (BS) at the time of benign gynecologic intra-abdominal surgery in post-reproductive-age women, including a proposal to use BS to replace other methods of tubal sterilization.

In 2011, The Society of Gynecological Oncology of Canada issued a statement recommending that “physicians discuss the risks and benefits of bilateral salpingectomy with patients undergoing hysterectomy or requesting permanent, irreversible sterilization.”1 This practice statement reflects robust histological, immunohistochemical and molecular evidence that most high-grade serous epithelial ovarian cancers (HGSC) in BRCA1/2 + women-and in many women with sporadic, non-hereditary pelvic serous carcinomas-actually originate from the distal portion of the fallopian tube.

Illustration by Alex Baker, DNA Illustrations, Inc.Experience with risk-reducing salpingo-oophorectomies in healthy carriers of BRCA mutations revealed that a significant percentage (5%-10%) had pre-existing distal tubal precursor or serous tubal intraepithelial carcinoma (STIC) lesions, mostly in association with p53 mutations.2 Subsequently, analysis of fallopian tube histology slides from cases of women diagnosed with sporadic, non-hereditary ovarian serous carcinoma revealed STIC lesions in up to 50% to 60% of these cases.3

This paradigm shift is provocative on several levels. It challenges existing concepts about the origin of epithelial ovarian cancer and in so doing provides novel opportunities for prevention of ovarian cancer in both high-risk women and for women in the general population.

It also raises two questions: (1) Is there any additional risk to incorporating BS into other gynecologic surgeries? and (2) what are the consequences of the remaining ovaries?

 

 

 

Risks of BS at time of hysterectomy

Ghezzi et al. studied women with benign disease undergoing total laparoscopic hysterectomy (TLH) with BS versus historic controls who underwent TLH alone.4 They found no significant differences in estimated blood loss, operative time, or intraoperative complications, but did note a statistically significant reduced risk of short-term (1-30 days) febrile morbidity in the salpingectomy group. They attributed this lower risk of infection, at least in part, to the role of salpingectomy in prevention of tubo-ovarian abscesses, which were seen in 2 women in the control group. 

Morelli et al. published a retrospective case control study comparing premenopausal women after hysterectomy either without (2008–2010) or with salpingectomy (2010–2012).5 There were no differences between groups in operative time, postoperative length of stay, time to return to normal activity, surgical complication rates, or ultrasonic or hormonal markers of ovarian function.

Also read: Should salpingetomy be standard care at time of bilateral tubal ligation?

However, the largest study confirming the perioperative safety of BS comes from the innovative work being done by the Ovarian Cancer Research Program of British Columbia.6 These investigators initiated an educational campaign directed at all gynecologists in British Columbia about the role of the fallopian tube in ovarian cancer and they encouraged their physicians to consider BS: (1) at the time of hysterectomy, even when the ovaries were being preserved, and (2) for permanent sterilization in place of tubal ligation. Their data included hysterectomy and tubal ligations performed (2008-2011) in almost 44,000 women before and after the educational ovarian cancer prevention campaign. They showed a significant uptake in BS procedures, with minimal additional operative time and no significant differences in perioperative complications. They concluded: “Fundamental for this initiative to continue, we are assured that this surgical intervention is safe and achievable.”6

Does BS alone affect ovarian function?

Dar at al. studied women undergoing ovarian stimulation for in vitro fertilization (IVF) before and after salpingectomy for ectopic pregnancy, using each woman as her own control and evaluating the operated versus non-operated sides.7 They found no significant differences in peak estradiol levels, gonadotropin requirements, oocytes retrieved from operated versus non-operated sides, fertilization rates or embryo quality.

Lass et al. compared IVF cycles in women in whom unilateral salpingectomy for ectopic pregnancy had been performed versus women with unexplained or male factor infertility.8 There was equivalence in total numbers of follicles on sonogram, total number of oocytes retrieved, peak estradiol levels, and pregnancy rates between the 2 groups.

Does BS at time of hysterectomy affect ovarian function?

Sezik et al. performed a randomized trial of total abdominal hysterectomy +/- salpingectomy in premenopausal women with regular menses and a normal basal follicle-stimulating hormone (FSH) level.9 They found no significant differences in postoperative FSH, estradiol levels, or ovarian volumes, although they did find that ovarian blood flow parameters improved in both groups after surgery. Therefore, it would appear that at the time of hysterectomy we are not adding significant risk by including BS, but by omitting it we are incurring significant lifetime risk of tubal pathology.

Broadening the discussion from cancer prevention, it is important to assess the benign pathologic potential of the fallopian tube. Left in situ it can develop infection or hydrosalpinx, contribute to ovarian or tubal torsion, and is the site for ectopic pregnancy, especially after tubal sterilization.

 

 

Tubal sterilization failures

In a landmark 1996 publication, Peterson et al prospectively enrolled 10,865 women undergoing tubal sterilization at academic medical centers across the nation, and followed them for 8 to 14 years after their surgery.10 This study revealed an unexpectedly high long-term failure rate after tubal sterilization (overall 18.5 per 1000 women-years or nearly 2%). There were major differences in failure rates between commonly performed sterilization techniques. Failure rates were also much greater in younger women and reached over 5% (per 1000 women-years) for women aged < 27 undergoing bipolar cautery procedures. Despite the notoriety of this report, its findings have failed to influence the day-to-day practice of most physicians.

Tubal ligation failures often result in ectopic pregnancies. These failures most often arise from fistula formation at the proximal scar site, allowing egress of sperm into the peritoneal cavity, where they may successfully encounter and fertilize an oocyte within the distal segment of the fallopian tube.

The world literature contains only 3 case reports of sterilization failure following BS (all were intrauterine pregnancies). Because the distal end of the fallopian tube is the location for most ectopic pregnancies after sterilization failure and would be absent after BS, virtually all ectopic pregnancies after sterilization failure would be prevented by performing complete bilateral salpingectomy instead of tubal ligation.

Finally, while tubal ligation may block retrograde passage of endometrial cells associated with clear cell and endometrioid cell ovarian cancers, it will not protect against HGSC that originates in the distal fallopian tube.

Summary

Recent recognition that many high-grade serous epithelial carcinomas of the ovary arise from precursor lesions in the distal fallopian tube requires an urgent reassessment of our thinking about the post-reproductive fallopian tube. That tube serves no physiological role and provides no benefit to women in whom it is retained (unlike the ovary, preservation of which may reduce mortality). The residual tube remains a possible site of infection, is at risk for torsion, may undergo malignant transformation in BRCA1/2+ carriers and in low-risk women alike, and is also the most likely site for ectopic pregnancy after sterilization failure.

BS removes the conduit responsible for the retrograde passage of endometrial glands (which reduces the risk of endometriosis–associated clear cell and endometrioid ovarian cancers) along with removing the distal tube where the STIC lesions seem to typically arise.

More: Techniques for salpingectomy at time of hysterectomy

Recent data from a Danish study of more than 13,000 ovarian cancer cases confirm that BS reduces the risk of epithelial ovarian cancer by 42% (OR 0.58).11 Removal at the time of hysterectomy or tubal sterilization adds minimal risk to a planned intra-abdominal surgical procedure and has the potential to greatly reduce the occurrence of our most deadly gynecologic malignancy.

Applying the number needed to treat of 100 to the more than 700,000 sterilization procedures performed every year in the United States alone would yield 7000 fewer ovarian cancers annually, a nearly one-third reduction.

We suggest that all women who are undergoing gynecologic surgery after having completed childbearing be counseled about the lack of benefit and possible harm from retaining the post-reproductive fallopian tube. BS should be recommended to all women undergoing hysterectomy (regardless of whether oophorectomy is planned) and it should be offered preferentially to women desiring permanent female sterilization in place of less effective alternatives (bipolar cautery, Pomeroy partial salpingectomy, etc.).

We believe data support the relative safety of these measures, and in the absence of effective screening, these simple changes in surgical practice could have a significant impact in the prevention of ovarian cancer.

While this is indeed a paradigm shift, perhaps ob/gyns should be asking themselves: “Why keep an organ with no ongoing physiological role when it can be safely removed at the time of planned surgery, and leaving it in situ places the woman at risk for a potentially preventable cancer?”

 

 

 

References

1. The Society of Gynecologic Oncology of Canada. GOC statement regarding salpingectomy and ovarian cancer prevention. September 15, 2011.

2. Tone AA, Salvador S, Finlayson SJ, Tinker AV, et al. The role of the fallopian tube in ovarian cancer. Clin Adv Hematol Oncol 2012;10(5):296-306.

3. Kindelberger DW, Lee Y, Miron A. Hirsch MS, et al. Intraepithelial carcinoma of the fimbria and pelvic serous carcinoma: evidence for a causal relationship. Am J Surg Pathol 2007;31(2):161-169.

4. Ghezzi F, Cromi A, Siesto G, Bergamini V, et al. Infectious morbidity after total laparoscopic hysterectomy: Does concomitant salpingectomy make a difference? BJOG 2009:116:589-593.

5. Morelli M, Venturella R, Mocciaro R, Di Cello A, et al. Prophylactic salpingectomy in premenopausal low-risk women for ovarian cancer: Primum non nocere. Gynecol Oncol. 2013;129:448-451.

6. McAlpine JN, Hanley GE, Woo MM, Tone AA, et al. Opportunistic salpingectomy : uptake, risks,and complications of a regional initiative for ovarian cancer prevention. Am J Obstet Gynecol. 2014;210:471 e1-11.

7. Dar P, Sachs GS, Strassburger D, Bukovsky I, Arieli S. Ovarian function before and after salpingectomy in artificial reproductive technology patients. Hum Reprod. 2000;15(1):142-144.

8. Lass A, Ellenbogen A, Croucher C, Trew G, et al. Effect of salpingectomy on ovarian response ot superovulation in an in vitro fertilization-embryo transfer program. Fert Steril. 1998;70(6):1035-1038.

9. Sezik M, Ozkaya O, Demir F, Sezik HT, Kaya H. Total salpingectomy during abdominal hysterectomy: Effects on ovarian reserve and ovarian stromal blood flow. J Obstet Gynaecol Res. 2007;33(6):863-869.

10. Peterson HB, Xia Z, Hughes JM, Wilcox LS, et al, for the US Collaborative Review of Sterilization Working Group. The risk of pregnancy after tubal sterilization: Findings from the US Collaborative Review of Sterilization. Am J Obstet Gynecol. 1996;174(4):1161-1170.

11. Madsen C, Baandrup L, Dehlendorff C, Kjaer SK. Tubal ligation and salpingectomy and the risk of epithelial ovarian cancer and borderline ovarian tumors: a nationwide case-control study. Acta Obstet Gynecol Scand. 2015;94(1):86-94.