Risk-reducing salpingectomy during surgery for benign indications

Ovarian cancer is the most deadly gynecologic malignancy in the United States, with 14,270 deaths expected in 2014 (CA Cancer J. Clin. 2014;64:9-29 ). The 5-year overall survival remains less than 50%. Difficulties in treatment arise due to its aggressive nature, coupled with vague symptomatology and no effective screening test. Advanced-stage disease at the time of diagnosis is an unfortunate hallmark.

Traditional teaching about the pathogenesis of ovarian cancers has been that a metaplastic change in the mesothelial ovarian surface leads to their de novo development. Under this paradigm, 70% of serous tumors were ovarian, 17% peritoneal, and 13% tubal in origin. However, a major change occurred when BRCA carriers began having risk-reducing bilateral salpingo-oophorectomies (BSO). Sequential histologic sections of the adnexa found occult malignancy in 30% of fallopian tubes, but similar lesions were not present within the ovary (Am. J. Surg. Pathol. 1020;34:1407-16). Could these cancers in the fallopian tube be the precursor lesion and then seed or spread to the ovarian surface?

Molecular and genetic analysis of these serous tubal intraepithelial carcinoma (STIC) cells found p53 mutations that were identical to those in concurrent “ovarian” tumors. STICs have been identified in 70% of nonhereditary forms of serous ovarian cancer. Under this paradigm of STIC as tubal in origin, only 28% of serous tumors were ovarian and 64% were of tubal origin (Am. J. Surg. Pathol. 2007;31:161-9).

This paradigm shift elicited new hypotheses about the etiology of endometrioid and clear cell types of ovarian cancer. Rather than metaplasia of the surface epithelium, endometrioid and clear cell tumors may result from retrograde menstruation, with the fallopian tube acting as a conduit for cells to gain access to the peritoneal cavity and the ovarian surface. This hypothesis provides a mechanism for the 34% reduction in ovarian cancer with bilateral tubal ligation (Hum. Reprod. Update 2011;17:55-67). Interestingly, in a large collaborative pooled analysis, the risk reduction of tubal ligation was greatest for endometrioid and clear cell subtypes (Int. J. Epidemiol. 2013;42:579-89).

Given the mounting evidence of fallopian tube involvement in the development of ovarian cancers, there are new primary prevention considerations. After 5 or more years of oral contraceptive use, a 50% reduction in the relative risk of ovarian cancer has been reported (Ann. Epidemiol. 2011;21:188-96). Bilateral salpingo-oophorectomy provides a greater than 50% risk reduction even in the highest-risk BRCA-positive population. However, results from the Nurses’ Health Study suggest that while there are fewer cancers in a low-risk population following BSO, it comes with an increase in all-cause mortality, predominately due to negative cardiovascular effects. With these issues in mind, is it time to consider incorporating prophylactic bilateral salpingectomy in benign gynecologic surgery (Obstet. Gynecol. 2013;121:709-16)?

While salpingectomy at the time of hysterectomy for benign conditions or for sterilization is becoming more common, there are concerns about premature loss of ovarian function secondary to compromise of ovarian blood supply. However, amassing data demonstrates preserved ovarian function. A retrospective study comparing total laparoscopic hysterectomy (TLH) to TLH with bilateral salpingectomy found no difference in markers of ovarian function (anti-Müllerian hormone, FSH, antral follicle count, mean ovarian diameters) up to 3 months postoperatively (Gynecol. Oncol. 2013;129:448-51). In a randomized controlled trial, 30 women were 1:1 randomized to TLH vs. TLH with salpingectomy. There was no change in anti-Müllerian hormone levels (at 3 months), operative time, or estimated blood loss (Fertil. Steril. 2013;100:1704-8). While there are concerns about the paucity of long-term follow-up data, these initial studies are encouraging. Additionally, a large retrospective study of 540 BRCA-negative patients found no difference in surgical outcomes with salpingectomy (estimated blood loss, hospital stay), and furthermore, the study found that removal of the tubes significantly reduces the risk of developing subsequent benign adnexal lesions by nearly 50% (J. Cancer Res. Clin. Oncol. 2014;140:859-65).

Though salpingectomy removes tubal re-anastomosis as an option in cases of “tubal ligation regret,” wisely choosing candidates can minimize this risk. Women less than 30 years old are at highest risk for regret, and the decision for salpingectomy in these patients should be made with caution and extensive counseling. Yet recently, emerging thought leaders in family planning have called for removal to be routinely considered (Obstet. Gynecol. 2014;124:596-9).

Surgical technique involves electrosurgery or suture ligation just inferior to the fallopian tube, ligating the fallopian branches of the ovarian and utero-ovarian arteries while avoiding unnecessary involvement of ovarian branches within the mesosalpinx. Since the fimbria are thought to be the site of origin for many serous carcinomas, removing the fimbrial portion of the tube is crucial.

Ovarian cancer remains the most deadly gynecologic malignancy. Efforts to find effective screening methods have not yet delivered. Pathologic data confirms that over half of “ovarian” cancers are actually of tubal origin, and we should consider risk-reducing salpingectomy in the low-risk population. The Society of Gynecologic Oncology in their November 2013 Clinical Practice Statement stated, “For women at average risk of ovarian cancer, risk-reducing salpingectomy should also be discussed and considered with patients at the time of abdominal or pelvic surgery, hysterectomy or in lieu of tubal ligation [once childbearing is complete].”

Dr. Pierce is a third-year resident in the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill. Dr. Clarke-Pearson is the chair and the Robert A. Ross Distinguished Professor of Obstetrics and Gynecology, and a professor in the division of gynecologic oncology at the university. Dr. Pierce and Dr. Clarke-Pearson said that they had no relevant financial disclosures.

Ovarian cancer is the most deadly gynecologic malignancy in the United States, with 14,270 deaths expected in 2014 (CA Cancer J. Clin. 2014;64:9-29 ). The 5-year overall survival remains less than 50%. Difficulties in treatment arise due to its aggressive nature, coupled with vague symptomatology and no effective screening test. Advanced-stage disease at the time of diagnosis is an unfortunate hallmark.

Traditional teaching about the pathogenesis of ovarian cancers has been that a metaplastic change in the mesothelial ovarian surface leads to their de novo development. Under this paradigm, 70% of serous tumors were ovarian, 17% peritoneal, and 13% tubal in origin. However, a major change occurred when BRCA carriers began having risk-reducing bilateral salpingo-oophorectomies (BSO). Sequential histologic sections of the adnexa found occult malignancy in 30% of fallopian tubes, but similar lesions were not present within the ovary (Am. J. Surg. Pathol. 1020;34:1407-16). Could these cancers in the fallopian tube be the precursor lesion and then seed or spread to the ovarian surface?

Molecular and genetic analysis of these serous tubal intraepithelial carcinoma (STIC) cells found p53 mutations that were identical to those in concurrent “ovarian” tumors. STICs have been identified in 70% of nonhereditary forms of serous ovarian cancer. Under this paradigm of STIC as tubal in origin, only 28% of serous tumors were ovarian and 64% were of tubal origin (Am. J. Surg. Pathol. 2007;31:161-9).

This paradigm shift elicited new hypotheses about the etiology of endometrioid and clear cell types of ovarian cancer. Rather than metaplasia of the surface epithelium, endometrioid and clear cell tumors may result from retrograde menstruation, with the fallopian tube acting as a conduit for cells to gain access to the peritoneal cavity and the ovarian surface. This hypothesis provides a mechanism for the 34% reduction in ovarian cancer with bilateral tubal ligation (Hum. Reprod. Update 2011;17:55-67). Interestingly, in a large collaborative pooled analysis, the risk reduction of tubal ligation was greatest for endometrioid and clear cell subtypes (Int. J. Epidemiol. 2013;42:579-89).

Given the mounting evidence of fallopian tube involvement in the development of ovarian cancers, there are new primary prevention considerations. After 5 or more years of oral contraceptive use, a 50% reduction in the relative risk of ovarian cancer has been reported (Ann. Epidemiol. 2011;21:188-96). Bilateral salpingo-oophorectomy provides a greater than 50% risk reduction even in the highest-risk BRCA-positive population. However, results from the Nurses’ Health Study suggest that while there are fewer cancers in a low-risk population following BSO, it comes with an increase in all-cause mortality, predominately due to negative cardiovascular effects. With these issues in mind, is it time to consider incorporating prophylactic bilateral salpingectomy in benign gynecologic surgery (Obstet. Gynecol. 2013;121:709-16)?

While salpingectomy at the time of hysterectomy for benign conditions or for sterilization is becoming more common, there are concerns about premature loss of ovarian function secondary to compromise of ovarian blood supply. However, amassing data demonstrates preserved ovarian function. A retrospective study comparing total laparoscopic hysterectomy (TLH) to TLH with bilateral salpingectomy found no difference in markers of ovarian function (anti-Müllerian hormone, FSH, antral follicle count, mean ovarian diameters) up to 3 months postoperatively (Gynecol. Oncol. 2013;129:448-51). In a randomized controlled trial, 30 women were 1:1 randomized to TLH vs. TLH with salpingectomy. There was no change in anti-Müllerian hormone levels (at 3 months), operative time, or estimated blood loss (Fertil. Steril. 2013;100:1704-8). While there are concerns about the paucity of long-term follow-up data, these initial studies are encouraging. Additionally, a large retrospective study of 540 BRCA-negative patients found no difference in surgical outcomes with salpingectomy (estimated blood loss, hospital stay), and furthermore, the study found that removal of the tubes significantly reduces the risk of developing subsequent benign adnexal lesions by nearly 50% (J. Cancer Res. Clin. Oncol. 2014;140:859-65).

Though salpingectomy removes tubal re-anastomosis as an option in cases of “tubal ligation regret,” wisely choosing candidates can minimize this risk. Women less than 30 years old are at highest risk for regret, and the decision for salpingectomy in these patients should be made with caution and extensive counseling. Yet recently, emerging thought leaders in family planning have called for removal to be routinely considered (Obstet. Gynecol. 2014;124:596-9).

Surgical technique involves electrosurgery or suture ligation just inferior to the fallopian tube, ligating the fallopian branches of the ovarian and utero-ovarian arteries while avoiding unnecessary involvement of ovarian branches within the mesosalpinx. Since the fimbria are thought to be the site of origin for many serous carcinomas, removing the fimbrial portion of the tube is crucial.

Ovarian cancer remains the most deadly gynecologic malignancy. Efforts to find effective screening methods have not yet delivered. Pathologic data confirms that over half of “ovarian” cancers are actually of tubal origin, and we should consider risk-reducing salpingectomy in the low-risk population. The Society of Gynecologic Oncology in their November 2013 Clinical Practice Statement stated, “For women at average risk of ovarian cancer, risk-reducing salpingectomy should also be discussed and considered with patients at the time of abdominal or pelvic surgery, hysterectomy or in lieu of tubal ligation [once childbearing is complete].”

Dr. Pierce is a third-year resident in the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill. Dr. Clarke-Pearson is the chair and the Robert A. Ross Distinguished Professor of Obstetrics and Gynecology, and a professor in the division of gynecologic oncology at the university. Dr. Pierce and Dr. Clarke-Pearson said that they had no relevant financial disclosures.

Ovarian cancer is the most deadly gynecologic malignancy in the United States, with 14,270 deaths expected in 2014 (CA Cancer J. Clin. 2014;64:9-29 ). The 5-year overall survival remains less than 50%. Difficulties in treatment arise due to its aggressive nature, coupled with vague symptomatology and no effective screening test. Advanced-stage disease at the time of diagnosis is an unfortunate hallmark.

Traditional teaching about the pathogenesis of ovarian cancers has been that a metaplastic change in the mesothelial ovarian surface leads to their de novo development. Under this paradigm, 70% of serous tumors were ovarian, 17% peritoneal, and 13% tubal in origin. However, a major change occurred when BRCA carriers began having risk-reducing bilateral salpingo-oophorectomies (BSO). Sequential histologic sections of the adnexa found occult malignancy in 30% of fallopian tubes, but similar lesions were not present within the ovary (Am. J. Surg. Pathol. 1020;34:1407-16). Could these cancers in the fallopian tube be the precursor lesion and then seed or spread to the ovarian surface?

Molecular and genetic analysis of these serous tubal intraepithelial carcinoma (STIC) cells found p53 mutations that were identical to those in concurrent “ovarian” tumors. STICs have been identified in 70% of nonhereditary forms of serous ovarian cancer. Under this paradigm of STIC as tubal in origin, only 28% of serous tumors were ovarian and 64% were of tubal origin (Am. J. Surg. Pathol. 2007;31:161-9).

This paradigm shift elicited new hypotheses about the etiology of endometrioid and clear cell types of ovarian cancer. Rather than metaplasia of the surface epithelium, endometrioid and clear cell tumors may result from retrograde menstruation, with the fallopian tube acting as a conduit for cells to gain access to the peritoneal cavity and the ovarian surface. This hypothesis provides a mechanism for the 34% reduction in ovarian cancer with bilateral tubal ligation (Hum. Reprod. Update 2011;17:55-67). Interestingly, in a large collaborative pooled analysis, the risk reduction of tubal ligation was greatest for endometrioid and clear cell subtypes (Int. J. Epidemiol. 2013;42:579-89).

Given the mounting evidence of fallopian tube involvement in the development of ovarian cancers, there are new primary prevention considerations. After 5 or more years of oral contraceptive use, a 50% reduction in the relative risk of ovarian cancer has been reported (Ann. Epidemiol. 2011;21:188-96). Bilateral salpingo-oophorectomy provides a greater than 50% risk reduction even in the highest-risk BRCA-positive population. However, results from the Nurses’ Health Study suggest that while there are fewer cancers in a low-risk population following BSO, it comes with an increase in all-cause mortality, predominately due to negative cardiovascular effects. With these issues in mind, is it time to consider incorporating prophylactic bilateral salpingectomy in benign gynecologic surgery (Obstet. Gynecol. 2013;121:709-16)?

While salpingectomy at the time of hysterectomy for benign conditions or for sterilization is becoming more common, there are concerns about premature loss of ovarian function secondary to compromise of ovarian blood supply. However, amassing data demonstrates preserved ovarian function. A retrospective study comparing total laparoscopic hysterectomy (TLH) to TLH with bilateral salpingectomy found no difference in markers of ovarian function (anti-Müllerian hormone, FSH, antral follicle count, mean ovarian diameters) up to 3 months postoperatively (Gynecol. Oncol. 2013;129:448-51). In a randomized controlled trial, 30 women were 1:1 randomized to TLH vs. TLH with salpingectomy. There was no change in anti-Müllerian hormone levels (at 3 months), operative time, or estimated blood loss (Fertil. Steril. 2013;100:1704-8). While there are concerns about the paucity of long-term follow-up data, these initial studies are encouraging. Additionally, a large retrospective study of 540 BRCA-negative patients found no difference in surgical outcomes with salpingectomy (estimated blood loss, hospital stay), and furthermore, the study found that removal of the tubes significantly reduces the risk of developing subsequent benign adnexal lesions by nearly 50% (J. Cancer Res. Clin. Oncol. 2014;140:859-65).

Though salpingectomy removes tubal re-anastomosis as an option in cases of “tubal ligation regret,” wisely choosing candidates can minimize this risk. Women less than 30 years old are at highest risk for regret, and the decision for salpingectomy in these patients should be made with caution and extensive counseling. Yet recently, emerging thought leaders in family planning have called for removal to be routinely considered (Obstet. Gynecol. 2014;124:596-9).

Surgical technique involves electrosurgery or suture ligation just inferior to the fallopian tube, ligating the fallopian branches of the ovarian and utero-ovarian arteries while avoiding unnecessary involvement of ovarian branches within the mesosalpinx. Since the fimbria are thought to be the site of origin for many serous carcinomas, removing the fimbrial portion of the tube is crucial.

Ovarian cancer remains the most deadly gynecologic malignancy. Efforts to find effective screening methods have not yet delivered. Pathologic data confirms that over half of “ovarian” cancers are actually of tubal origin, and we should consider risk-reducing salpingectomy in the low-risk population. The Society of Gynecologic Oncology in their November 2013 Clinical Practice Statement stated, “For women at average risk of ovarian cancer, risk-reducing salpingectomy should also be discussed and considered with patients at the time of abdominal or pelvic surgery, hysterectomy or in lieu of tubal ligation [once childbearing is complete].”

Dr. Pierce is a third-year resident in the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill. Dr. Clarke-Pearson is the chair and the Robert A. Ross Distinguished Professor of Obstetrics and Gynecology, and a professor in the division of gynecologic oncology at the university. Dr. Pierce and Dr. Clarke-Pearson said that they had no relevant financial disclosures.