Prophylactic Surgery in the High Risk Population

When considering prophylactic procedure in the high-risk population, the surgeon needs to be cognizant of the risk of an occult malignancy. The patient needs to have signed consent forms for additional procedures including hysterectomy and full surgical staging, since there is a 4% chance of detecting an occult malignancy at the time of the procedure.21,22 Prophylactic bilateral salpingo-oophorectomy can be performed by laparotomy or laparoscopy (minimally invasive surgery). A methodical survey of the abdomen, pelvis, and entire peritoneum should be performed. All ovarian tissue and as much fallopian tube as possible should be removed. Any suspicious area that is noted at the time of the procedure should be excised and submitted for frozen-section evaluation. If adhesions between the ovary and other peritoneal structures are present, they should be resected to ensure that all ovarian tissue has been removed. The infundibulopelvic ligament should be clamped and cut at least 2 cm proximal to the ovary to prevent leaving any ovarian tissue behind. Although the intramural portion of the fallopian tube is left behind after the bilateral salpingo-oophorectomy, there have no reports of malignant transformation in the tubal remnant after prophylactic surgery.23 See Figure 4-1.

A hysterectomy may be performed along with the bilateral salpingo-oophorectomy. The major disadvantage is that it converts a minor procedure into a major one with greater morbidity and requires admission to the hospital for postoper-

Figure 4-1. Prophylactic bilateral salpingo-oophorectomy. Manipulation of ovaries and tubes should be minimized. Infundibulopelvic vessels should be ligated approximately 2 cm proximal to the ovary. As much fallopian tube as possible should be excised. The pathology evaluation should include the entire specimen to rule out an occult malignancy. A, Laparoscopic view of the pelvis. Note location of uterus, left fallopian tube and ovary, left round ligament, and sigmoid colon. B, Divide broad ligament. C, Laparoscopic view of the left retroperitoneum. Note course of left ureter (1) on the medial leaf of the broad ligament. Left external iliac artery (2) is also visible. D, To mobilize the ureter away from the ovarian vessels, a defect is created between the left ureter (1) and the infundibulopelvic vessels (3).

Figure 4-1. Prophylactic bilateral salpingo-oophorectomy. Manipulation of ovaries and tubes should be minimized. Infundibulopelvic vessels should be ligated approximately 2 cm proximal to the ovary. As much fallopian tube as possible should be excised. The pathology evaluation should include the entire specimen to rule out an occult malignancy. A, Laparoscopic view of the pelvis. Note location of uterus, left fallopian tube and ovary, left round ligament, and sigmoid colon. B, Divide broad ligament. C, Laparoscopic view of the left retroperitoneum. Note course of left ureter (1) on the medial leaf of the broad ligament. Left external iliac artery (2) is also visible. D, To mobilize the ureter away from the ovarian vessels, a defect is created between the left ureter (1) and the infundibulopelvic vessels (3).

Cholecystectomy

ative care. Hysterectomy has been advocated as part of prophylactic surgery for several proposed benefits. Since the risk of endometrial carcinoma is no longer present, hormone replacement therapy with unopposed estrogen can be given to control menopausal symptoms. Normally, women with BRCA1 mutations may carry an increased risk of endometrial and fallopian tube cancer. Hysterectomy would address this risk. Finally, BRCA mutation carriers undergoing hysterectomy are not at an increased risk for endometrial cancer if they opt to use the selective estrogen-receptor modulator tamoxifen for chemoprophylaxis of breast cancer.

Several investigations have demonstrated an association between prophylactic bilateral salpingo-oophorectomy and a reduction in the risk of gynecologic cancers. Rebbeck and associates24 evaluated whether prophylactic bilateral salpingo-oophorectomy reduced the risk of cancers of the coelomic epithelium and breast in women who carry such mutations. A total of 551 women with disease-associated germline BRCA1 or BRCA2 gene mutations were identified from registries and studied for the occurrence of ovarian and breast cancer. The incidence of ovarian cancer was determined in 259 women who underwent prophylactic bilateral salpingo-oophorectomy and in 292 matched controls who did not undergo the procedure. In the subgroup of 241 women with no history of breast cancer or prophylactic mastectomy, the incidence of breast cancer was determined in 99 women who underwent prophylactic bilateral salpingo-oophorectomy and in 142 matched controls. The length of postoperative follow-up for both groups was at least 8 years. Six women (2.3%) who underwent prophylactic bilateral salpingo-oophorectomy were diagnosed with stage I ovarian cancer at the time of the procedure; two women (0.8%) were diagnosed with papillary serous peritoneal carcinoma 3.8 and 8.6 years after prophylactic bilateral salpingo-oophorectomy. Among the controls, 58 women (19.9%) were diagnosed with ovarian cancer after a mean follow-up of 8.8 years. With the exclusion of the six women whose cancer was diagnosed at surgery, prophylactic bilateral salpingo-oophorectomy significantly reduced the risk of coelomic epithelial cancer (hazard ratio 0.04; 95% CI, 0.01-0.16). Of 99 women who underwent prophylactic bilateral salpingo-oophorectomy and who were studied to determine the risk of breast cancer, breast cancer developed in 21 (21.2%) compared with 60 (42.3%) in the control group (hazard ratio 0.47; 95% CI, 0.29-0.77).

Similar results were obtained by Kauff and colleagues25 while prospectively comparing the effect of risk-reducing bilateral salpingo-oophorectomy with that of surveillance for ovarian cancer on the incidence of subsequent breast cancer and BRCA-related gynecologic cancers in women with BRCA mutations. A total of 170 women 35 years of age or older who had not undergone bilateral salpingo-oophorectomy chose to undergo either surveillance for ovarian cancer or prophylactic bilateral salpingo-oophorectomy. During a mean follow-up of 24.2 months, breast cancer was diagnosed in 3 of the 98 women who chose prophylactic bilateral salpingo-oophorectomy, and peritoneal cancer was diagnosed in 1 woman in this group. Among the 72 women who chose surveillance, breast cancer was diagnosed in 8, ovarian cancer in 4 and peritoneal cancer in 1. The time to breast cancer or BRCA--related gynecologic cancer was longer in the bilateral salpingo-oophorectomy group, with a hazard ratio for subsequent breast cancer or BRCA-related gynecologic cancer of 0.25 (95% CI, 0.08-0.74).

Rutter and colleagues26 tested 847 Israeli women with ovarian or primary peritoneal cancer for the three Ashkenazi founder mutations. BRCA1 mutations were noted in 187 subjects. A BRCA2 mutation was found in 64 patients. Noncarrier status was reported in 598 subjects. A total of 2396 control subjects were drawn from a population registry. A reduced risk of ovarian or primary peritoneal cancer was noted in women who underwent gynecologic surgery, with an odds ratio of 0.51 and a 95% CI of 0.32 to 0.81. The effect was greatest for bilateral oophorectomy with an odds ratio of 0.29 and a 95% CI of 0.12 to 0.73. Surgery that did not result in the removal of ovarian tissue (including hysterectomy and bilateral tubal ligation) was associated with a reduced risk of ovarian cancer with an odds ratio of 0.67 and a 95% CI of 0.38 to 1.18.

In view of the lack of screening methods for ovarian cancer and the lack of efficacy of current surveillance methods, it is recommended that BRCA1 or BRCA2 mutation carriers undergo prophylactic bilateral salpingo-oophorectomy after age 35 or once childbearing is completed. Gynecologic surgery such as hysterectomy and bilateral tubal ligation, which does not remove ovarian tissue, demonstrates a reduced risk of ovarian cancer in BRCA mutation carriers, but the 95% CI includes 1. Timing of the prophylactic bilateral salpingo-oophorectomy requires balancing the procedure-related consequences of surgical menopause and infertility against the risk of developing ovarian cancer. Removal of both tubes should be performed because of the increased risk of fallopian tube cancer. Despite the reduction in ovarian or fallopian tube cancer, women who undergo prophylactic bilateral salpingo-oophorectomy still have a small residual risk of developing primary peritoneal cancer27 (Tables 4-5 and 4-6).

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